Organophosphorus Chemistry

Organophosphorus Chemistry Volume I 0 A Specialist Periodical Report Organophosphorus Chemistry Volume 10 A Review...

Author: D. W. Hutchinson | S. Trippett

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Organophosphorus Chemistry

Volume I 0

A Specialist Periodical Report

Organophosphorus Chemistry Volume 10

A Review of the Literature published between July 1977 and June 1978

Senior Reporters

D. W. Hutchinson, Department of Chemistry and Molecular Sciences, University of Warwick

S. Trippett, Department of Chemistry, University of Leicester Reporters

D. W. Allen, Shemeld Cify Polytechnic R. S. Edmundson, Universify of Bradford J . B. Hobbs, The Cify Universify, London R. Keat, Universify of Glasgow

J . A. Miller, University of Dundee

D. J. H. Smith, Universify of Leicesfer J . C. T e bby, North Staffordshire College of Technology, Stoke-on- Trent

B. J . Walker, Queen's University of Belfast

The Chemical Society Burlington House, London W I V OBN

British Library Cataloguing in publication Data Organophosphorus chemistry.(Chemical Society. Specialist periodical reports). VOl. 10 1. Organophosphorus compounds I. Hutchinson, David 11. Trippett, Stuart 111. Series 547’.07 QD412.Pl 73-268317 ISBN 0-85186-096-6 ISSN 0306-0713

Copyright 0 1979 The Chemical Society All Rights Reserved No part of this book may be reproduced or transmitted in any form or by any means - graphic, electronic, including photocopying, recording, taping or information storage and retrieval systems - without written permissionfrom The Chenzical Society Printed in Great Britain by Adlard and Son Ltd Bartholomew Press, Dorking

Foreword

The volume of publication in organophosphorus chemistry continues to rise, leading inevitably to greater selectivity on the part of Reporters. Perhaps the most interesting development in the year under review was the observation, in solution, of the first stable hydroxyphosphorane, a type of molecule long postulated as intermediatesin many substitutions at four-co-ordinatephosphorus. Other particularly active areas included the study of silyloxy-phosphites and -phosphonates, a-halogenoalkylphosphonates, and allenic phosphonic acids and their derivatives. The synthesis of, and structural studies on, derivatives and metabolites of the anti-tumour drug cyslophosphamide have continued to attract attention, and interesting observations have been made on two-coordinate pn-pn-bonded phosphorus compounds, including new routes to threeco-ordinatepn-pn compounds. Expansion in the use of physical methods in organophosphorus chemistry has continued. Of particular note is the application of n.m.r. spectroscopy to the study of the stereochemistry of enzyme-catalysed phosphoryl transfer using chiral phosphates and thiophosphates. The discovery of an oligonucleotide containing 2’-5’ phosphodiester links in rabbit reticulocytes and in cells that have been treated with interferon should stimulate interest in the involvement of unusual nucleoside phosphates in control mechanisms in cells. From Volume 12 this series will be under new management, and an opportunity for change will arise. One of us (DWH) would welcome comments and suggestions.

D.W.H. S.T.

Corrigendum Readers should note that in the Contents list pages ix and xi have unfortunately been transposed.

Contents Chapter 1 Phosphines and Phosphonium Salts By D. W.Allen 1 Phosphines Preparation From Halogenophosphines and Organometallic Reagents From Metallated Phosphines By Addition of P-H to Unsaturated Compounds By Reduction Miscellaneous Reactions Nucleophilic Attack at Carbon Nucleophilic Attack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous

2 Phosphonium Salts Preparation Reactions Alkaline Hydrolysis Additions to Unsaturated Phosphonium Salts Miscellaneous

1

1 1 1 3 6 7 8 10 10 12 15 17 20 20 22 22 23 24

3 Phospholes

27

4 Phosphorins

30

Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippett 1 Introduction 2 Structure and Bonding 3 Acyclic Systems 4 Four-membered Rings 5 Five-membered Rings Phospholans 1,2-Oxaphospholans 1,2-Oxaphospholens 1,3,2-Dioxaphospholans 1,3,2-Dioxaphospholens Nitrogen-containing Rings

33 33

34 36 36 39 39 40 40 41 42 43

Contents

viii 6 Six-membered Rings

47

7 Higher-membered Rings

49

8 Six-co-ordinate Species

50

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller

52

1 Introduction

52

2 Halogenophosphines Preparation Reactions with Alkenes and Related Compounds Reactions with Carbonyl Compounds and their Derivatives Reactions with Hydroxy-groups Reactions with Amines and Derivatives Miscellaneous Aspects Silylphosphines and Related Compounds

52

3 Halogenophosphoranes Preparation By Addition of Halogen to Phosphorus(m) By Insertion of Phosphorus(II1) into other Halogen Compounds with c----O Compounds By Reactions of Phosphorus(~~r) By Exchange Reactions of Phosphoranes From Arsenic(1v) Compounds Reactions of Halogenophosphoranes Miscellaneous

67

Chapter 4 Phosphine Oxides and Sulphides By J, A. Miller

52 53 57 59 63 63 65

67 67 68 69 69 71 71 74

75

1 Introduction

75

2 Preparation via Alkenes via Carbonyl Compounds via Phosphorus(1v) Chlorides P-P Compounds uia P(0) Anions

75 75 76 78 80 80

Miscellaneous Syntheses 3 Reactions Reactions at the P=X Group Reactions of the Side-chain

82

4 Structural and Physical Properties

91

82 85

Contents

ix

Chapter 5 Tervalent Phosphorus Acids By B. J. Walker

95

1 Phosphorous Acid and its Derivatives Nucleophilic Reactions Attack on Saturated Carbon Attack on Unsaturated Carbon Attack on Nitrogen Attack on Oxygen Attack on Halogen Electrophilic Reactions Rearrangements Cyclic Esters of Phosphorous Acid Miscellaneous Reactions

95 95 95 96 104 105 107 107 112 113 116

2 Phosphonous and Phosphinous Acids and their Derivatives

118

Chapter 6 Quinquevalent Phosphorus Acids By R. S. Edmundson

120

1 Synthetic Methods General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives

120 120 121 127

2 Reactions General Reactions of Phosphoric Acid and its Derivatives Reactions of Phosphonic and Phosphinic Acids and their Derivatives

133 133 134

3 Structure

150

143

Chapter 7 Phosphates and Phosphonates of Biochemical Interest 151 By D. W. Hutchinson 1 Introduction

151

2 Coenzymes and Cofactors Nicotinamide Nucleotides Pyridoxal Phosphate 0ther Cofactors

152 152 153 154

3 Sugar Phosphates

156

4 Phospholipids

159

Contents

X

5 Phosphonates

160

6 Oxidative Phosphorylation

160

7 Enzymology Enzyme Mechanisms Phosphoproteins Protein Purification

162 162 165 166

8 Other Compounds of Biochemical Interest

166

Chapter 8 Nucleotides and Nucleic Acids By J. B. Hobbs

169

1 Introduction

169

2 Mononucleotides Chemical Synthesis Cyclic Nucleotides Affinity Chromatography

169 169 173 177

3 PolyphospFtes Chemical Synthesis AffinityLabelling

179 179 187

4 Oligo- and Poly-nucleotides Chemical Synthesis Enzymatic Synthesis Sequencing Other Studies

190 190 196 198 200

5 Analytical Techniques and Physical Methods

200

Chapter 9 Ylides and Related Compounds By D. J. H. Smith

204

Preparation and Structure Reactions Aldehydes Ketones Miscellaneous

204 204 206 206 212 214

2 Reactions of Phosphonate Anions

218

1 MethylenephosphoraneS

xi

Contents 3 Selected Applications in Synthesis Pheromones Prostaglandins Carbohydrates Car0ten0ids Non-benzenoid Aromatic Compounds

Chapter 10 Phosphazenes By R. Keat

225 225 226 226 227 230

232

1 Introduction

232

2 Synthesis of Acyclic Phosphazenes From Amines and Phosphorus(v) Halides From Azides and Phosphorus(1n) Compounds Other Methods

232 232 234 236

3 Properties of Acyclic Phosphazenes Halogeno-derivatives Amino-, Alkoxy-, Alkyl-, and Aryl-derivatives

237 237 238

4 Synthesis of Cyclic Phosphazenes

245

5 Properties of Cyclic Phosphazenes Halogeno-derivatives Amino-derivatives Alkoxy- and Aryloxy-derivatives Alkyl and Aryl Derivatives

247 247 249 253 253

6 Polymeric Phosphazenes

255

7 Phosphazenes as Fire Retardants

257

8 Molecular Structures of Phosphazenes that have been determined by X-Ray Diffraction Methods

258

Chapter 11 Physical Methods

262

By J. C. Tebby 1 Nuclear Magnetic Resonance Spectroscopy Biological Applications Chemical Shifts and Shielding Effects Phosphorus-31 Sp of PI1 Compounds 8p of PIII Compounds Sp of PIV Compounds Sp of P V Compounds

262 262 263 263 263 263 265 265

Contents

xii Carbon-13 Fluorine-19 Oxygen-17 and Nitrogen-15 and -14 Hydrogen-1 Equilibria and Shift Reagents Pseudorotation Restricted Rotation Inversion, Configuration, and Medium Effects Spin-Spin Coupling JPP JP~'o and J P ~ ~ N JPC

JPH JPC~H JPXCH

Double-resonance, Relaxation, C.I.D.N.P., and N.Q.R. Studies

266 267 267 267 267 269 270 271 272 272 273 273 275 275 275 276

2 Electron Spin Resonance Spectroscopy

276

3 Vibrational and Rotational Spectroscopy Band Assignments Stereochemistry Bonding Microwave Spectra

278 278 278 279 280

4 Electronic Spectroscopy Absorption Photoelectron

280 280 281

5 Diffraction X-Ray Electron

28 1 281 285

6 Dipole Moments, Conductance, and Polarography

286

7 Mass Spectrometry

288

8 pKa and Thermochemical Studies

289

9 Chromatography G.1.c. T.1.c. Paper Chromatography Column Chromatography

290 290 291 291 291

Author I ndex

292

Abbreviations*

AIBN DAD DBN DBU DCC DEAE DMF DMSO g.1.c. HMPT h.p.1.c. PEI QAE TDAP TFAA THF TPS t.1.c.

bisazoisobutyronitrile diethyl azodicarboxylate 1,5-diazabicyclo[4.3.O]non-5-ene 1,5-diazabicyclo[5.4.0]undec-5-ene dicyclohexylcarbodi-imide diethylaminoethyl dimethylformamide dimethyl sulphoxide gas-liquid chromatography hexamethylphosphortriamide high-performance liquid chromatography polyethyleneimine quaternary aminoethyl tris(dimethy1amino)phosphine trifluoroacetic acid tetrahydrofuran tri-isopropylbenzenesulphonylchloride thin-layer chromatography

* Abbreviations used in chapters 7 and 8 are those recommended by the IUPACIUB Commission on Biochemical Nomenclature. These have been published in the BiochemicaIJournall978,171,1and 1970,120,449

Abbreviations*

AIBN DAD DBN DBU DCC DEAE DMF DMSO g.1.c. HMPT h.p.1.c. PEI QAE TDAP TFAA THF TPS t.1.c.

bisazoisobutyronitrile diethyl azodicarboxylate 1,5-diazabicyclo[4.3.O]non-5-ene 1,5-diazabicyclo[5.4.0]undec-5-ene dicyclohexylcarbodi-imide diethylaminoethyl dimethylformamide dimethyl sulphoxide gas-liquid chromatography hexamethylphosphortriamide high-performance liquid chromatography polyethyleneimine quaternary aminoethyl tris(dimethy1amino)phosphine trifluoroacetic acid tetrahydrofuran tri-isopropylbenzenesulphonylchloride thin-layer chromatography

* Abbreviations used in chapters 7 and 8 are those recommended by the IUPACIUB Commission on Biochemical Nomenclature. These have been published in the BiochemicaIJournall978,171,1and 1970,120,449

Phosphines and Phosphonium Salts ~

~~

BY

~

D. W. ALLEN

1 Phosphines Preparation.-From Halogenophosphines and Organometallic Reagents. Improved procedures for the isolation of pure tris(2,3,5,6-tetramethylphenyl)phosphine (1) from the reaction of phosphorus trichloride with the duryl Grignard reagent have been described.l The cis- and trans-isomers of the 1,4-dirnethylphosphorinane system (2) have been isolated from the reaction of methylphosphonous dichloride with the Grignard reagent derived from 1,5-dibromo-3-methylpentane.2 The Grignard procedure has also been applied in the synthesis of a range of phosphines bearing chiral alkyl substituent~,~ and in the synthesis of o-carboxyarylphosphines, e.g. (3), the 2-oxazoline system being employed as the carboxyprotecting group.4 As part of a study of the transmission of electronic effects in triarylphosphines by l9F n.m.r., a number of new substituted triarylphosphines (4) have been prepared by the action of appropriate Grignard or organolithium reagents on p-fluorophenyldichlorophosphine. ti A range of optically active phosphines, e.g. Me

\M:

M e /3

ife

(3) A. I. Bokanov, P. Yu. Ivanov, N. A. Rozanel'skaya, and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 702. 2 L. D. Quin and S. 0. Lee, J. Org. Chem., 1978, 43, 1424. a R. Lazzaroni, S. Barsanti, and P. Salvadori, Chimica e Industria, 1977,59,456 (Chem. Abs., 1978, 88, 6979). 4 R. Luckenbach and K . Lorenz, 2. Naturforsch., 1977, 32b, 1038. 5 S. I. Pombrik, V. F. Ivanov, A. S. Peregudov, D. N. Kravtsov, A. A. Fedorov, and E. 1. Fedin, J. Organometallic Chem., 1978, 153, 319.

1


2

( 5 ) and (6), have been prepared by ortha-lithiation of chiral aralkylamines followed by treatment with cldorodiphenylphosphine.6 r ortho-Lithiation steps are also involved in the preparation of the o-hydroxyphenylphosphine (7) from phenol, the phenolic OH being protected as the methoxymethyl ether,s and in the synthesis of a range of dimethoxyphenylphosphines, e.g. (8). The reaction of (8; R=Ph) with boron tribromide at -78 "C, followed by treatment with acetic acid at 20 "C, leads to the diacetoxyphosphine (9).9 The new bulky ligand (10) has been prepared from the reaction of chlorodi-tbutylphosphine with phenylalkynyl-lithium.l o Preliminary details have been given of the preparation of a range of new chelating ligands (11) from the reactions of 1,2-dilithiobenzene with bis(dialky1amino)chlorophosphines. The aminophosphine (1 1 ; R = Me,N) undergoes solvolysis in methanol or ethanol to give (1 1 ; R = Me0 or EtO) respectively.ll Treatment of bis(dich1orophosphino)methane with methyl-lithium gives the diphosphine (12).12 Sequential treatment of phenyldichlorophosphine with a dialkylcadmium followed by a second organometallic reagent gives a direct route to the chiral phosphines (13).13 A route to the phosphinodiacetic acid (14) has been described, involving the reaction of phenyldichlorophosphine with the Reformatsky reagent derived from ethyl bromoacetate. l4 Stereospecifically generated vinylcuprates

(4) X = nz-Me, p-Me, p-NMe,, or p-C1

Me2PCH,PMe,

PhC= CPB u t2 (10) 6

7

(11) R = Me,N, Et,N, OEt, or OMe

(1 2)

K. Yamamoto, A. Tomita, and 3. Tsuji, Chem. Letters, 1978, 3. W. R. Cullen and E.-Shan Yeh, J. Organornetallic Chem., 1977, 139, C13.

* T. B. Rauchfuss, Inorg. Chem., 1977,16,2966.

H. D. Empsall, P. N. Heys, and B. L. Shaw, J. C . S . Dalton, 1978,257. H. D. Empsall, E, M. Hyde, E. Mentzer, and B. L. Shaw, J. C . S. Dalton, 1977, 2285. 11 3. H. Meiners and J. G. Verkade, J. Coordination Chem., 1977, 7 , 131. l2 M. Fild, J. Heinze, and W. Kruger, Chem.-Ztg., 1977, 101, 259. l3 D. Jore, D. Guillerm, and W. Chodkiewicz, J. Organornetallic Chem., 1978, 149, C7. 14 J. PodlahovB, CON.Czech. Chem. Comm., 1977, 43, 57. lo

Phosphines and Phosphonium Salts

3

react with chlorodiphenylphosphine to form the corresponding alkenylphosphines (15).16 Polymers bearing diphenylphosphino substituents (1 6) have been prepared by direct phosphination of a precursor polymer and also by polymerisation of the phosphine monomer (1 7). l6 From Metallated Phusphines. The reactions of diorganophosphides with organic halides have been examined by 31P CIDNP and by product analysis. These reactions proceed in part by a radical mechanism and in part by a competing non-radical mechanism, the preferred route depending on the nature of the organic group, the halide, and the substituents bound to phosphorus. There is no evidence for radical participation in the reactions of dialkylphosphides with aryl halides or of diarylphosphides with alkyl halides.l7 The reaction of metallophosphide reagents with alkyl halides or tosylates continues to be a favoured route for the synthesis of chiral phosphines of interest in connection with their use (in the form of rhodium complexes) as catalysts for asymmetric hydrogenation reactions. The reaction of sodium methylphenylphosphide with menthyl or neomenthyl chlorides gives mixtures of epimeric neomenthyl- or menthyl-phosphines respectively, thus providing the first examples of phosphines which are chiral both at phosphorus and carbon. l8 The reaction of lithium diphenylphosphide with alkyl tosylates has been employed in the synthesis of the new, chiral, chelating diphosphines (1 8)1° and (19).20Polymer-bound chiral diphosphines, e.g. (20), have been similarly 22

PhP

/cH2CozH

\

CH,CO,H

(13) R' = Me or PhCH, R' = Me, PhCH,, or o-tolyl

15 16 17

1s

19 20 21 22

(14)

RIRZC=CHPPh,

(15) R', R2 = H, alkyl, or aryl

H. Westmijze, J. Meijer, and P. Vermeer, Rec. Trav. chim., 1977, 96, 194. A. J. Naaktgeboren, R. J. M. Nolte, and W. Drenth, Rec. Trav. chim., 1978, 97, 112. B. W. Bangerter, R. P. Beatty, J. K. Kouba, and S. S. Wreford, J . Org. Chem., 1977, 42, 3247. C. Fisher and H. S. Mosher, Tetrahedron Letters, 1977, 2487. G. Descotes, D. Lafont, and D . Sinou, J. Organometallic Chem., 1978,150, C14. M. D. Fryzuk and B. Bosnich, J. Amer. Chem. SOC.,1977,99, 6262. N.Takaishi, H.Imai, C. A. Bertelo, and J. K. Stille, J . Amer. Chem. Soc., 1978,100, 264. T. Masuda and J. K. Stille, J. Amer. Chem. SOC.,1978, 100, 268.


4

><x ~--fC;pHp~,

Ph,P

PPh,

(MeCCO,CH,CHiOH

Ph,P

0.92

\

Tertiary phosphines of types (21) and (22) have also been prepared, using metallophosphide reagents. The silyl groups permit attachment of the phosphines to inorganic supports, and the related rhodium complexes function as heterogenised homogeneous hydrogenation c a t a l y s t ~24. ~A~series ~ of chloromethylated phenylchlorosilanes and related polyphenylsiloxane polymers have been phosphinated, using lithium diorganophosphide reagents, to give silicon-based polymer-supported phosphines which are also active in the form of rhodium complexes as hydrogenation catalysts.25 The diphosphine (23) (the product of catalytic dehydrogenation of 1,6-bisdiphenylphosphinohexane) has been prepared by the reaction of lithium diphenylphosphide and 1,6 - dichloro - trans - hex - 3 - ene.26 Diorganophosphide reagents have also been employed in the synthesis of a range of trans-spanning chelating diphosphines (24). In the course of this work, it was noted that whereas both triphenylphosphine and tris(m-toly1)phosphine undergo cleavage on treatment with sodium in liquid ammonia to form the sodium diarylphosphide, corresponding treatment of tris(m-trifluoromethyIpheny1)phosphine leads only Improved procedures have been desto partial recovery of starting

(EtO),Si(CH,),P(Ph)R (21) R = Ph or menthyl

H

(22)

,CH,CH,PPh,

\

QPP4

Ph,PCH;CH, /c=c\H (23)

23 24 25

26 27

(24) R = Ph, tfZ-tolyl, /I-McOC,H,, nz-CF,C,H,, C6HI1, or But

(25)

M. Capka, Synth. React. Inorg. Metal-Org. Chem,, 1977, 7 , 347; M. Capka, Coll. Czech. Chem. Comm., 1977,42, 3410. M. Cernf, Coll. Czech. Chem. Comm., 1977, 42, 3069. M. Bartholin, J. Conan, and A. Guyot, J. Mol. Catalysis, 1977, 2, 307. P. W. Clark, J. Orgnnometallic Chem., 1977, 137, 235. P. N. Kapoor and L. M. Venanzi, Helv. Chim. Acta, 1977,60,2824.


5

cribed for the synthesis of pyridyldiphenylphosphines,e.g. (25)rrom the reactions of 2-or 4-halogenopyridines with lithium diphenylphosphide.28 The reagent (26), obtained from methyldiphenylphosphine and n-butyllithium, undergoes transmetallation on treatment with copper(1) chloride to form (27), which is stable in THF, and which undergoes substitution reactions with both aryl and alkyl halides to form, e.g., (28).29 Dialkylmethylphosphines are metallated on carbon by t-butyl-lithium to give (29),which react with monohalogenophosphines or phosphite esters to give the diphosphines (30)or the multidentate phosphines (31) respe~tively.~~ No evidence of attack on halogen was observed in the reactions of diphenylphosphide reagents with 2-chlorobutadienes, which give rise to the phosphines (32) and (33). These reactions appear to be the first examples of the conjugate addition of phosphide anions leading to s N 2 ’ Interest in the use of dimetallodiphosphide reagents for the synthesis of - ~ O the new systems heterocyclic phosphines continues at a high l e ~ e l . ~ ~Among described by Baudler’s group is the P,B heterocycle (34).3aIssleib’s group have described a route to the 1,5-diphosphabicyclo[3.3.0]octanesystem (35), which is remarkably stable towards both nucleophilic and electrophilic reagent^.'^ The diphosphide (36) is a key intermediate in the synthesis of a number of macrocyclic pho~phines.~~

G. R. Newkome and D. C. Harger, J. Org. Chem., 1978, 43, 947. T. Kauffmann and R. Joussen, Chem. Ber., 1977,110, 3930. 30 H. H. Karsch and H. Schmidbaur, 2. Nuturforsch., 1977, 32b, 762. 31 M. Arthurs, S. M. Nelson, and B. J. Walker, Tetrahedron Letters, 1978, 1153. 92 M. Baudler, A. Marx, and J. Hahn, 2.Naturforsch., 1978, 33b, 355. 33 M. Baudler and B. Carlsohn, 2. Naturforsch., 1977, 32b, 1490. 34 M. Baudler, C. Pinner, C. Gruner, J. Hellmann, M. Schwamborn, and B. Kloth, Z. Naturforsch., 1977, 32b, 1244. 35 M. Baudler, E. Tolls, E. Cleff, B. Kloth, and D. Koch, Z. anorg. Chem., 1977, 435, 21. 36 M. Baudler, B. Carlsohn, D. Koch, and P. K. Medda, Chem. Ber., 1978, 111, 1210. 37 M. Baudler, D. Koch, and B. Carlsohn, Chem. Ber., 1978, 111, 1217. 38 K. Issleib, A. Balszuweit, and P. Thorausch, Z. anorg. Chem., 1977,437, 5. 39 K. Issleib, F. Krech, and E. Lapp, Synth. React. Inorg. Metal-Org. Chem., 1977, 7 , 253. 40 K. rssleib and P. Thorausch, Phosphorus and Sulfur, 1978, 4, 137. 4 1 E. P. Kyba, C. W. Hudson, M. J. McPhaul, and A. M. John, J. Amer. Chem. SOC.,1977, 99, 8053; R. E. Davis, C. W. Hudson, and E. P. Kyba, ibid; 1978,100, 3642. 28

29

6


(35)

(34)

A number of reactions of lithium bis(trimethylsily1)phosphide with organic halides have been described.42The reagent (37), obtained by the action of methyllithium on tris(trimethylgermyl)phosphine, reacts with 1,Zdibromoethane via attack on halogen to form the diphosphine (38) and ethylene.43 By Addition of P-H to Unsaturated Compounds. Secondary phosphines undergo stereospecific addition at room temperature to the triple bond of phosphinoacetylenes co-ordinated to palladium or platinum in cis-square-planar complexes to form related complexes (39) of rigid, unsymmetrical, cis-olefinicdiphosphines, which can be freed from the metal complex by treatment with cyanide Secondary phosphines have also been added to a range of azo-compounds to form the phosphinohydrazones (40),46 and the carboxyalkylphosphines (41) add to the hydrazone or phenylhydrazone of benzaldehyde to form the heterocyclic phosphines (42).** The thermal addition of phenylphosphine to fluorinated olefins to give fluoroalkyl secondary phosphines has also been rep~rted.~' (Me,Ge),PLi

+

(Me,Ge),P-P(GeMe,),

BrCH,CH,Br

(37)

Cl,~,

/ \

+

LiBr

(3 8) Ph

P (Ph),C =C R' n,n\nrr

C1

+ CH,=CH2

P(Ph),C-CR' '6

cl\

/

PL$H

/ \

C1

(39)

P-CR' R2R3

11

M = Pd or Pt R' = CF3, But, or Ph RZ, R3 = Ph, Et, or CH,CH,CN

PhCH=NNHRa,

(40)

42 43

R:PN(R2)NHR3 C,H, PHCH(R')CO,H R* = Bu or Ph (41) R' = H or Me R2, R3 = Ph or CO,R

* PhPvNNHR2

H*Ph (42)

R2 = H or Ph

G. Fritz and W. Holderich, 2. anorg. Chem., 1977,431, 61, 63, and 76. H. Schumann, L. Rosch, and W. Schmidt-Fritsche,J . Organontetallic Chem., 1977, 140, c21.

D. K. Johnson and A. J. Carty, J.C.S. Chem. Comm., 1977, 903. 46 K. H. Linke and W. Brandt, 2.anorg. Chem., 1977,423, 119. 413 H. Oehme, E. Leissring, and A. Zschunke, Phosphorus and Sulfur, 1978,4, 59. 42 R. N. Haszeldine, D. R. Taylor, and E. W. White, J. Fluorine Chem., 1977, 10, 27. 44


7

Base-catalysed addition of primary phosphines to a range of dialkynyl compounds has led to the heterocyclic phosphines (43) and (44).48Diphenylphosphine undergoes base-catalysed addition to a range of vinysulphonyl derivatives to form the b-sulphonylalkylphosphines(45). 4 9 By Reduction. Lithium aluminium hydride has been used to reduce (46) to the tetraphosphine (47), which was subsequently alkylated [in the form of its nickel(I1) complex] to give the macrocyclic tetraphosphine (48). 6 o The o-aminophenylphosphine (49) has been obtained by reduction of the corresponding oxide, using either diphenylsilane or methylpolysiloxane in diphenyl ether.61 A number of new unsymmetrical chelating diphosphines have been obtained by reduction of the monosulphides (50), using hexachlorodisilane

R’

R’

c3 (43) R1 = Ph, p-tolyl, or p-Me,NC,H,

(44) R* = Ph, p-tolpl, or p-hIe,NC,H,

R2 = Me, Ph, But, C,H,,,

X = B u f P , Me&

or P h S i

1-naphthyl, or y-MeOC,H, P&PCHCH,S0,R2

I

(45)

R‘ R’ = H or Ph R2 = NR,, F, or Et

(47)

s II

Ph,PCH,PR’R2

(49) 48

49

60

(50)

R’ = Me, Pri, or Ph R2 = Me, Et, or Pri

G. Markl, H. Baier, and R. Liebl, Synthesis, 1977, 842. K. Issleib and K. Zimmermann, 2. anorg. Chem., 1977, 436, 20. T. A. DelDonno and W. Rosen, J. Amer. Chem. SOC.,1977,99, 8051. M. K. Cooper and J. M. Downes, Inorg. Chem., 1978,17, 880.

(48)

8


or Sodium naphthenide is the preferred reagent for the reduction of triphenylphosphine sulphide.63 New procedures for the reduction of phosphine oxides include treatment with dialkylaluminium hydridesK4or conversion into the dichlorophosphorane followed by reduction either with hydrogen under pressure in the absence of a catalystS6or with a mixture of ethanethiol and triethylamine in benzene.66 Miscellaneous.The reaction of 2,6-diacetylpyridine with the phosphinoamines (51) in the presence of cadmium(r1) or silver@ perchlorates gives rise to complexes of macrocyclic phosphines (52).67 A range of N-acyl chelating diphosphines (53)58-60 and (54)61 have been prepared by acylation of precursor aminodiphosphines. By appropriate choice of the N-acyl group, the achiral (54) [as the rhodium@ complex] can be incorporated at a specific site in a protein, the tertiary structure of which provides the chirality required for subsequent use as a catalyst for enantioselectivereduction.6aAnother approach to chiral diphosphine Iigands involves the reaction of hydrochlorides of optically active amino-acid esters with chlorodiphenylphosphine in the presence of base to give (55).63 The new, sterically hindered, phosphinoesters (56) have been prepared by the reaction of di-t-butylphosphine and the appropriate bromo-ester, the intermediate phosphonium salts being deprotonated with sodium acetate.64Several routes to

H,N(CH,),P(Ph)(CH,),, P(Ph)(CHJ,NII, (51)

iz

= 2 or 3

,PPh,

fi

:c: Ph

Ph,P /\/PPh2 RCON

CH,PPh,

Ph,P

\

P',h (CH,),, (5 2 )

N3

\ NCH (R)CO,Me /

(5 3) ( 5 4) ( 5 5 ) R = H, Me, CH,Ph, or Pri S. 0. Grim and J. D. Mitchell, Znorg. Chern., 1977, 16, 1770. G. A. Olah and D. Hehemann, J. Org. Chem., 1977,42,2190. D. B. Malpass and G. S. Yeargin, Ger. Offen. 2 714 721 (Chem. Abs., 1978, 88, 89 842). 65 M. Masaki and N. Kakeya, Angew. Chem. Internat. Edn., 1977, 16, 552. s6 M. Masaki, K. Fukui, and J. Kita, Japan. Kokai 77 151 126 (Chem. Abs., 1978,88,105 569). 6' J. de 0. Cabral, M. F. Cabral, M. G. B. Drew, S. M. Nelson, and A. Rodgers, Znorg. Chim. 62 53 5*

6*

SQ 6o

81 g2

63 64

Acta, 1977,25, L77. K. Achiwa, Tetrahedron Letters, 1978, 1475. K. Achiwa and T. Soga, Tetrahedron Letters, 1978, 1 1 19. K. Achiwa, Tetrahedron Letters, 1977, 3735. M. E. Wilson, R. G. NUZZO, and G. M. Whitesides, J. Amer. Chem. SOC.,1978,100,2269. M. E. Wilson and G . M. Whitesides, J. Amer. Chem. Soc., 1978, 100, 306. P. W. Lednor, W. Beck, H. G Fick, and H. Zippel, Chem. Ber., 1978, 111, 615. H. D. Empsall, E. M. Hyde, D. Pawson, and B. L. Shaw, J.C.S. Dalton, 1977, 1292.


9

a-dialkylaminomethylphosphines(57) have been described; these compounds react with acetyl chloride to form acetylphosphines.s6A new, high-yield, route to chloromethyldiphenylphosphinehas been developed; this compound reacts with cyclopentadienylsodium to give a mixture of cyclopentadienylmethyldiphenylphosphines (58), which polymerize rapidly at ordinary temperatures.66

BufP(CH,),, COzEt ( 5 6 ) IZ = 1-3

R,PCH,NMe, H 2

(5 7)

( 5 8)

A new approach to the synthesis of compounds containing the C-P double bond (phospha-alkenes) and the C=P triple bond (phospha-alkynes) has been described. Slow passage of trifluoromethylphosphine vapour over solid potassium hydroxide at room temperature yields the new, linear, reactive triatomic molecule FC-P, in very high yield. If the flow rate is increased, the intermediate F2C==PH (previously characterized during pyrolysis experiments on trifluoromethylphosphine) is dete~ted.~' Full details of synthetic routes to the cyclic keto-phosphines (59) have now appeared.68psgThese compounds react with hydrazoic acid to form the ringexpanded systems The reactions of halogenophosphines with chiral alcohols or secondary amines in the presence of base have given a wide range of chiral phosphines, e.g. (61),70 which have applications in homogeneous catalysis.70-73 The chiral phosphines (62) have been prepared in order to investigate the effects of the aryl substituents on the activity of related rhodium complexes as asymmetric hydrogenation Full experimental details of the synthesis of the chiral diphosphine (63) have now appeared.

R (59) R = Me or Ph 65 66 67

68

69 70

71 72

73

74 75

K. Kellner, B. Seidel, and A. Tzschach, J. Organometallic Chem., 1978, 149, 167. C. Charrier and F. Mathey, Tetrahedron Letters, 1978, 2407. H. W. Kroto, J. F. Nixon, N. P. C. Simmons, and N . P. C. Westwood, J. Amer. Chem. SOC., 1978,100,446. K. A. Petrov, V. A. Chauzov, and N . Yu. Mal'kevich, Zhur. obshchei Khim., 1977, 47, 2516 (Chem. Abs., 1978,88, 89 768). Y. Segall, K.Alkabets, and I. Granoth, J. Chern. Res. ( S ) , 1977, 310; J. Chem. Res. ( M ) , 1977, 3541. W. K.Cullen and Y. Sugi, Tetrahedron Letters, 1978, 1635. G. Pracejus and H. Pracejus, Tetrahedron Letters, 1977, 3497. H. Brunner and J. Doppelberger, Chem. Ber., 1978, 111, 673. M. Fiorini, M. Giongo, F. Marcati, and W. Marconi, Ger. Offen. 2 718 533 (Chem. A h . , 1978, 88, 136 978). L. Horner and B. Schlotthauer, Phosphorus and Sulfur, 1974, 4, 155. B. D. Vineyard, W. S. Knowles, M. J. Sabacky, G. L. Bachman, and D. J. Weinkauff, J. Amer. Chem. SOC.,1977, 99, 5946.


10 Me

I

I

H

Ph ,

X

OPPh,

(62)

(61)

Ph,,

\

(6 3)

R = Pr” or Pr’

X = O-NH,, o - N M ~ , , o-OMe, or p-OhIe

The reaction of chlorodimethylphosphine with lithium bis(trimethylsily1)amide gives the silylamino-phosphine (64), which is also formed in the reaction of dimethyl(trimethylsily1)phosphine with trimethylsilyl azide.76Compared to the P-C bond, the stability of the P-E bond (E=Si, Ge, Sn, or Pb) in ‘organoelement-phosphines’is low, thereby facilitating scrambling reactions and making the isolation of chiral ‘organoelement-phosphines’difficult.However, by linking t-butyl groups to phosphorus, a range of stable, chiral, organoelement-phosphines (65) has been prepared.77The cyclotriphosphines (66) have been prepared by the reaction of bis(phenyltrimethylsily1)biphosphine with dichlorophosphines.78 Procedures for the silylation of hydroxyalkylphosphineshave been reported. Reactions.-Nucleophilic Attack at Carbon. It has been known for some time that triphenylphosphine reacts with the triphenylcarboniumion to form two isomeric phosphonium ions (67) and (68), the nature of the product depending on conditions and the nature of the anion. These have now received detailed spectroscopic study, which confirms the suggested structures. In solution in hot acetonitrile, (67) is yellow, indicating free-radical dissociation. In the presence of Lewis bases in acetonitrile solution, (67) is isomerized to (68), which is colourless, and a mechanism for this process has been suggested. The ion (67) is immediately decomposed by water to a mixture of triphenylphosphine and triphenylmethanol. In contrast, the ion (68) is much more resistant to hydrolysis.81 79t

PhP -PPh .Me2P-N(SiMeJZ

(64)

Me,MP(Bu‘)Ph

( 6 5 ) M = Si, Ge, Sn, or Pb

\P/

R (66) R = Me, Et, or Ph

f

Ph,C-PPh,

76

77 78

79 80

81

J. C. Wilburn and R. H. Neilson, Inorg. Chem., 1977, 16, 2519. H. Schumann and R. Fischer, J. Chem. Res. ( S ) , 1977,272; J. Chem. Res. (M), 1977, 3101. M. Baudler, B. Carlsohn, B. Kloth, and D. Koch, Z . anorg. Chem., 1977, 432, 67. E. S. Kozlov, V. I. Tovstenko, and L. N. Markovskii, J . Gen. Chem. (U.S.S.R.), 1977, 47, 869. R. K. Valetdinov, S. I. Zaripov, E. P. Lebedev, R. Kh. Shakirova, V. M. D’yakov, and N. M. Kudyakov, Zhur. obshchei Khim., 1977, 47, 2213 (Chem. Abs., 1978, 88, 37 897). G. Bidan and M. Genies, Tetrahedron Letters, 1978, 2499.

11


Nucleophilic attack by tertiary phosphines occurs at the co-ordinated cyclobutadiene system of the complex (69) to form the related phosphonium salts (70). 82 Further studies of the addition of tertiary phosphines to isocyanates and isothiocyanates, to form the zwitterionic adducts (71)83and (72)84respectively, have appeared. A recently published thesis contains a useful review of kinetic studies of the quaternization of phosphines.86 Rate data for the quaternization of tri-nbutylphosphine and triphenylphosphine with iodomethane, ethyl bromoacetate, andp-nitrobenzyl bromide in various solvents have been compared with those for the quaternization of related amines.86The rates of quaternization of a series of phosphinoacetic acid derivatives (73) with iodoethane have been studied, and the rate data correlated with the ionization potentials of the phosphorus lone pair.87 Triphenylphosphine and tri-n-butylphosphine react with dibrornotrimethylantimony(v), via attack at carbon, to form the salts (74).88Triphenylphosphine reacts with the stable sulphonium ylides (75) to form the salts (76).8g9Do The aminodiphosphines (77) react with two moles of dimethyl acetylenedicarboxylate to form the stable heterocyclic ylides (78). 91 Triphenylphosphine

+

A-

R,P-C,-NX

X = FSOz or C,F9S0, R = Ph or Me,N

(71)

Ph,PCII,X

(72) It1

(73) X = CO,H, COLTt, CONII,,

CONMc?, o r ('N 82

83 84

86

87 88 8g 90

91

Pli2kIT,X I'

I

1:t

A. Efraty, S. S. Sandhu, Jr., R. Bystrek, and D. Z. Denney, Znorg. Chem., 1977, 16, 2522. H. W. Roesky and G. Sidiropoulos, Chem. Ber., 1977, 110, 3703. E. S. Batyeva, E. N. Ofitserov, and A. N. Pudovik, Zhur. obshchei Khim., 1977, 47, 559 (Chem. Abs., 1977,87, 39 598). G. L. Keldsen, Ph.D. Thesis, University of Massachusetts, 1977. (Univ. Microfilms, Order

NO.77-15 86

R = Ph or PhCO

104).

F. Qukmeneur, B. Bariou, and M. Kerfanto, Compt. rend., 1977, 285, C, 155. 0. Dahl and L. Henriksen, Acta Chem. Scand. (B), 1977, 31, 427. G. E. Graves and J. R. van Wazer, J. Inorg. Nuclear Chem., 1977, 39, 1101. B. A. Arbuzov, Yu. V. Belkin, N. A. Polezhaeva, and T. V. Yudina, Zzvest. Akad. Nauk. S.S.S.R.,Ser. khim., 1977, 2086 (Chem. Abs., 1978, 88, 37 893). Yu. V. Belkin, N. A. Polezhaeva, and B. A. Arbuzov, Izuest. Akad. Nauk. S.S.S.R., Ser. khirn., 1977, 2617 (Chem. Abs., 1978, 88, 121 305). W. Zeiss and H. Henjes, Chem. Ber., 1978, 111, 1655.


12 0

(74) R = Ph or Bu

0

(75) R = hle or PIiCIl,

;.m

MeOzC

R,P-N-P Me

R

2 M eO,CC-CCO,Zle

C0,Me

co,hlt:

M~ 0

R?P\ N /PR, R;I e

(77) R = Me or Ph

(76)

(78)

+

Ph ,PC(Ph)=NNPh

C1-

I PhC=NNfIPli (79)

forms the salt (79) with two moles of diphenylnitrilimine in the presence of

Nucleophilic Attack at Halogen. Following their elucidation of the course of the reactions which occur in the triphenylphosphine-carbon tetrachloride system, Appel and his co-workers have now described procedures for the synthesis of the salts (80)--(82) from the reactions of triphenylphosphine and carbon tetrachloride in various molar ratios, and in different solvent systems.93 Trichloromethyltriphenylphosphonium chloride (80) is not only the first isolable intermediate in the reactions of the triphenylphosphine-carbon tetrachloride system, but is now a readily accessible starting material for the synthesis of P-C ylides whose preparation is difficult. The reaction of the salt (80) with chlorodiphenylphosphine gives the salt (83), which is dechlorinated by trisdimethylaminophosphine to give the carbodiphosphorane (84). This is thermally unstable, and on heating forms the heterocyclic system (85), which is devoid of ylidic properties. This is claimed to be the first four-membered P-C compound having partly endocyclic double 95

Under carefully chosen conditions, tertiary alkylphosphines react with carbon tetrachloride to give the chloromethine-bridged phosphonium salts (86).96

(83) 93

98 94

95 96

I. N. Zhmurova and V. G. Yurchenko, J . Gen. Chem. (U.S.S.R.), 1977,47,927. R. Appel and W. Morbach, Synthesis, 1977, 699. R. Appel, F. Knoll, and H.-D. Wihler, Angew. Chem. Internat. Edn., 1977, 16, 402. R. Appel and H.-D. Wihler, Chem. Ber., 1978, 111, 2054. R. Appel and H.-F. Scholer, Chem. Ber., 1978,111,2056.

Phosphines and Phosphonium Salts [ R~R2Pr=-=C(C1)==PR2R~]+ C1'

(86)

13 R:PCHR;

(87)

R' = Et or Bu

RZ = Et, B u y or Ph

cx,

R' = Et or Ph R2 = CO,Et, SO,Ph, or SO,CF,

RlP(X)=CRZ

X = C1 or Br

(88)

Phosphines having acidic hydrogens adjacent to phosphorus (87) react with carbon tetrahalides to form the ylides (S8).97 Applications of phosphine-carbon tetrahalide and related phosphine-halogen reagents in synthesis continue to appear. The triphenylphosphine-carbon tetrachloride and trisdimethylaminophosphine-carbon tetrachloride systems have found further uses in carbohydrate c h e m i ~ t r y . ~ A * -new ~ ~ ~method for the preparation of peptides uia the simultaneous action of triphenylphosphine and hexachloroethane on N-protected amino-acids and amino-acid esters has been reported. This procedure can also be conveniently applied using a polymeric phosphine resin, which can be easily regenerated by treatment with phosgene.lo2 As an alternative to the triphenylphosphine-carbon tetrachloride system, the use of the triphenylphosphine-hexachloroacetone combination has been described for the regio- and stereo-selectiveconversion of allylic alcohols into the corresponding chlorides. This reagent allows easier isolation of low-boiling products than does triphenylphosphine-carbon tetrachloride. Studies with optically active alcohols show that the reaction proceeds with predominant inversion of configuration, as is usually found in this type of reaction.lo3 A copolymer of divinylbenzene, styrene, and styryldiphenylphosphine has been used to effect the chlorination of alcohols in carbon tetrachloride s01ution.~~* The reaction of several isomeric benzobicyclo-octadienylalcohols and dibenzobicyclononatrienyl alcohols with the triphenylphosphine-carbon tetrachloride reagent demonstrates that these alcohol to chloride transformations are all much more complex than originally believed. Products from these and related deuteriumlabelled alcohols show that direct displacements, displacements with WagnerMeerwein rearrangement, and displacement with allylic rearrangement all O C C U T . ~The ~ ~ usual inversion of configuration at hydroxylic carbon does not occur in the reactions of the 13C-labelledalcohol (89) with various phosphine-

M~SCH,?H~OII (89)

RP

R = Ph, Pri, or n-CJ,,

Me SCH,6H2C1

+ Me SdH,CH $1

0. I . Kolodyazhnyi, Zhur. obshchei Khim., 1977, 47, 2159 (Chem. Abs., 1978, 8,121 297). R. Boigegrain and B. Castro, J. Carbohydrates, Nucleosides, Nucleotides, 1976, 3, 335. 99 Y.Chapleur, B. Castro, and B. Gross, Tetrahedron, 1977, 33, 1609. 100 Y. Chapleur, B. Castro, and B. Gross, Tetrahedron, 1977, 33, 1615. 101 I. Pinter, J. Kovacs, and A. Messmer, Magyar Kkm. Folydirat, 1977, 83,231 (Chem. Abs., 1977, 87, 136 185). 102 R . Appel and L. Willms, Chem. Ber., 1977, 110, 3209. 103 R. M. Magid, 0. S. Fruchey, and W. L. Johnson, Tetrahedron Letters, 1977, 2999. 104 D . C. Sherrington, D. J. Craig, J. Dagleish, G. Domin, J. Taylor, and G. V. Meehan, European Polymer J., 1977, 13, 73. 105 S. J. Christol, R. M. Strom, and D. P. Stull, J . Org. Chem., 1978, 43, 1150. 97

9s

14


carbon tetrachloride reagents, which result in the formation of a mixture of labelled products, via the l-methylthiiranium ion.lo6 Triphenylphosphine has been used as a selective dechlorinating agent in the conversion of the fluorochloro-ester (90) into (91).lo7 The direct reactions of the polymethylene diphosphines (92) with molecular fluorine have been shown to occur under controlled conditions in fluorotrichloromethane, with formation of the diphosphoranes (93).lo8 Following earlier work on the reactions of triphenylphosphine with various a-halogeno-rn-cyanobenzyl phenyl sulphones, rate data for corresponding reactions involving nucleophilic attack of phosphine on the halogen of a-halogeno-pyridylmethylphenyl sulphones (94) have been reported.lo9 The reaction of triphenylphosphine with tellurium tetrachloride results in the formation of tellurium and dichlorotriphenylphosphorane.110 A combination of triphenylphosphine with iodine and sodium iodide has been used to effect a very mild deoxygenation of sulphoxides.ll1 The combination of triphenylphosphine with thiocyanogen reacts smoothly with alcohols to give the corresponding thiocyanates, presumably via the phosphonium intermediate (95). This reagent also reacts with indoles or pyrroles to give nuclear cyano-substituted products,112 and converts secondary amines into 1,l-disubstituted thioureas.l13 Ptl

P

F,C(CI)CF (CI)CF,C F(CI)CF,CO,E t 4 F,C =CFC F,CF(CI)CF,CO,E t

(90)

lo6D.

(91)

C. Billington and B. T. Golding, J.C.S. Chem. Comm., 1978, 208. Johncock, Synthesis, 1977, 551. lo*I. Ruppert and V. Bastian, Angew. Chem. Internat. Edn., 1977, 16, 718. log B. B. Jarvis and B. A. Marien, J . Org. Chem., 1977, 42, 2676. 110 F. J. Berry, N. Gunduz, M. Roshani, and B. C. Smith, Commun. Fac. Sci. Univ. Ankara, Ser. B, 1975, 22B, 21 (Chem. Abs., 1977, 87, 135 615). ll1 G. A. Olah, B. G. B. Gupta, and S. C. Narang, Synthesis, 1978, 137. 1 1 2 Y. Tamura, T. Kawasaki, M. Adachi, M. Tanio, and Y . Kita, Tetrahedron Letters, 1977, 4417. 113 Y . Tamura, M. Adachi, T. Kawasaki, and Y . Kita, Tetrahedron Letters, 1978, 1753. lo7P.

15

Phosphines and Phosphonium Salts R-OH

Ph P(SCN)

b=L

+

[Ph,P-O--K

SCN] --+ R-SCN

+ Ph,PO

(95)

Nucleophilic Attack at Other Atoms. Further applications of the triphenylphosphine-diethyl azodicarboxylate (DAD) combination in synthesis have appeared. The inversion of configuration accompanying substitution reactions mediated by this reagent has been utilized in a synthesis of e p i c h ~ l e s t e r o l . ~ ~ ~ Similarly, a combination of triphenylphosphine, diethyl azodicarboxylate, and azide or iodide ions effects replacement of the 3’-hydroxy-group in the nucleosides (96) by azide or iodine, the substitution proceeding with inversion of configuration at the 3’-carbon.llS The triphenylphosphine-dimethyl mesoxalate (DMM) combination can also be used to promote esterification. The reaction proceeds with inversion of configuration at the alkoxy carbon as for related reactions involving DAD, and a mechanism involving initial formation of the betaine (97) has been proposed. Unlike the Ph,P-DAD reagent, Ph3P-DMM does not act as a dehydration reagent for the formation of phthalimido-derivatives of alcohols.116 A detailed study of the mechanism of oxidation of tertiary phosphines catalysed by platinum(o) complexes has appeared. Contrary to earlier suggestions, the reaction does not involve direct transfer of oxygen from a PtO-0, complex to the phosphine. Instead, the role of the phosphine is to effect displacement of co-ordinated peroxide by nucleophilic attack on the metal. The free peroxide ion 0

0

OH

OH ,CO,Me

0-

I,Cope

Ph,P-C

I

A rCOJ 1 f

P1l3P-C

‘C0,hle

c‘

ArCOi O,M e

(97)

Ph,P=O

+

ArCOzR

f-

Ph,iOR ArCO;

+ H’

‘C0,Me

115

L.P.L. Piacenza, J. Org. Chem., 1977, 42,3778. H.Loibner and E. Zbiral, Annulen, 1978, 78.

116

0. Achmatowicz, Jr. and G. Grynkiewicz, Tetrahedron Letters, 1977. 3 179.

114

16

OrganophosphorusChemistry

then oxidizes other phosphine molecules present in The kinetics of oxidation of tertiary phosphines using t-butyl hydroperoxide have been studied. The rate of the reaction decreases as the substituents at phosphorus become increasingly electron-withdrawing. A Hammett plot of the rate data for a range of para-substituted arylphosphines is consistent with there being little development of positive charge at phosphorus in the transition state.ll* Sulphur dioxide reacts with trimethylphosphine to form a mixture of the phosphine oxide and sulphide, and with primary and secondary phosphines it gives rise to the most fully oxidized phosphorus acid that can be formed without cleavage of P-C bonds. Thus diphenylphosphine forms diphenylphosphinic acid (together with some tetraphenyldiphosphine disulphide) and phenylphosphine forms phenylphosphonic acid.llg The transfer of selenium from tertiary phosphine selenides to tertiary phosphines is fast on the n.m.r. time-scale at elevated temperatures, and is concentration-dependent, resembling the analogous process with tellurium rather than that with sulphur, which proceeds much more The cyclopolyphosphine(98) reacts with sulphur to yield either the monosulphide (99) or the disulphide (loo), depending on the mole ratio of PhP to S.121 Deoxygenation of nitrobenzene by tri-n-butylphosphine in the presence of primary or secondary alcohols gives 2-alkoxy-3H-azepines (101) in good yield.122 The diazo-ester (102) reacts with triphenylphosphine to give the pyrimido[4,5-c]pyridazine system (103). 23 Treatment of steroidal ccp-azido-alkyl alcohols wit6 triphenylphosphine gives Tris(trifluoromethy1)phosphine reacts with a route to steroid perfluoro-(2,4-dimethyl-3-oxa-2,4-diazapentane) to give the phosphines (104).125

117

118 119

lZ1 122

123 124 125

A. Sen and J. Halpern, J. Amer. Chem. SOC.,1977, 99, 8337. J. I. Schulman, J. Org. Chem., 1977, 42, 3970. S. Chan and H. Goldwhite, Phosphorus and Sulfiir, 1978, 4, 33. D. H. Brown, R. J. Cross, and R. Keat, J.C.S. Chem. Comm., 1977, 708. M. Baudler, J. Vesper, B. Kloth, D. Koch, and H. Sandmann, 2. anorg. Chem., 1977,431, 39. M. Masaki, K. Fukui, and J. Kita, Bull. Chem. SOC.Japan, 1977, 50, 2013. T. Miyamoto, Y. Kimura, J. Matsumoto, and S . Minami, Chem. andPharm. Bull. (Japan), 1978, 26, 14. M. Huebner and K. Ponsold, East Ger. P. 123 327 (Chem. Abs., 1977, 87, 168 264). H. G. Ang and W. S . Lien, J . Fluorine Chem., 1978, 11, 419.


(104) n

= 1 or 2

17

(106)

(105)

The compound (105) reacts with triphenylphosphine to produce the stable free radical (106). l a 6 The stereochemical course of oxidation of tertiary phosphines by hydroxylamine derivatives depends on the nature of the oxidizing agent and on the conditions. Thus, e.g., methylphenyl-n-propylphosphineis oxidized with almost complete retention of configuration at phosphorus by treatment with hydroxylamine hydrochloride, whereas racemization results with free hydroxylamine in the presence of pyridine. It has been suggested that, under acidic conditions, direct nucleophilic attack on oxygen occurs, resulting in retention. Under neutral or basic conditions, attack at nitrogen occurs to form the aminophosphonium salt (107), which is then hydrolysed via the hydroxyphosphorane (108). Pseudorotation of the latter results in loss of stereo~pecificity.~~~ Miscellaneous. Treatment of the phosphine (109) with concentrated acid gives the cyclic phosphonium salt (1 lo), which is converted into the phosphino-aldehyde (111) at pH 8 in aqueous solution. Simple acid hydrolysis of (109) does not give (1 11). As expected, (1 11) shows both tertiary phosphine and carbonyl reactivity, and also exhibits keto-enol tautomerism. Stereospecificreductions of the keto-phosphine (1 12) by NaH2Al(OC2H40Me)z and LiAIH(OBut), give the pseudo-axial and pseudo-equatorial alcohols (1 13) respectively. The pseudo-equatorialalcohol undergoes a very rapid intramolecular transfer of oxygen from carbon to phosphorus to form the cyclic oxide (114).12B Various reactions, both at the phosphorus and also at the carbonyl group, of p-diphenylphosphinobenzaldehyde have also been

(107)

Ph,PCH,CH(OEt),

.

conc.

+

Ph,P

-

( 109)

+

(111)

/

Ho' 126

rHC; 2c1- J=+Ph,PCH,CHO

\cI:

(110)

M. Ballester, J. Riera, and C. Rovira, AnaZes de Quim., 1976, 72, 489 (Chem. Abs., 1977, 87, 151 794).

127 128 1Z9

130

W. J. Stec and A. Okruszek, J. Chem. Res. (S),1977, 142. M. Sokolov and K. Issleib, Z . Chem., 1977, 17, 365. I. Granoth, Y. Segall, and H. Leader, J.C.S. Perlcin I , 1978, 465. I. N. Zhmurova, V. G. Yurchenko, R. I. Yurchenko, and T. V. Savenko, Zhur. obshchei Khim., 1977,47, 2207 (Chem. Abs., 1978, 88, 50 971).


18

R1

0

ye

(i) NaH,AI(OC,H,OMe), or (ii) LiHAI(OBu'),

Me

_Me _

(114)-

(113) (i) R' = OH, R2 = H or (ii) R' = H, R2 = OH

(112)

The reaction of diphenylphosphine with the oxirans (115) gives the p-hydroxyalkyl-phosphine oxides (116).131 Secondary phosphines also cleave the Sic2 ring of hexamethylsiliran to form the silylphosphines (117).132The thiiran (1 18) reacts with tertiary phosphines to form the furan (119).133 A cautionary note has appeared concerning the assignment of the configuration of cyclic phosphines from n.m.r. studies carried out in CDC13. Thus it has been found that the cis-1-alkyl(or aryl)-2,5-dimethyl-3-phospholens (120) isomerize to the trans-isomers (121) in this solvent, but not in CD2C12,CD3CN, or C6D6.134 Primary or secondary amines react with the fluorinated phosphine (122) to give mixtures of aminophosphines. The reactions are believed to proceed via an intermediate 'phospha-alkene' (123). 136 0 Ph,PCRIRZCRIRZOH

R2

RZ

R,PSiMe,CMe,C€IMe, (117)

(116)

(115) R' = H or CN RZ = H or Ph R3P

PhCO

(PhCO),C= C (COPh),

\

COPh

Me

Me

CDC'3

p

!

p

I

(120) R = alkyl or aryl

(121)

A. N. Pudovik, G. V. Romanov, and V. M. Pozhidaev, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1978, 473 (Chem. Abs., 1978, 88, 190 977). 132 W. Holderich and D. Seyferth, J . Organometallic Chem., 1978, 153, 299. 138 B. A. Arbuzov, N. A. Polezhaeva, and M. N. Agafonov, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1977, 1399 (Chem. Abs., 1977, 87, 117 734). 134 P. J. Hammond and C. D. Hall, Phosphorus and Sulfur, 1977, 3, 351. lai5R. N. Haszeldine, D. R. Taylor, and E. W. White, J. Fluorine Chem., 1978, 11, 441. 131

19

The rate of solvolysis of a series of climethylaniinophosphines depends on the An e.p.r. study of the ability of the solvent to protonate the a1niiiopho~phine.l~~ reduction and cleavage of triphenylphosphine by alkali metals in ether solvents shows that the reactions involve the initial formation of a radical anion, Ph,P-*M+. A radical anion derived from tetraphenyldiphosphine is also 0 b s e r ~ e d . Silyll ~ ~ and germyl-phosphines add to the carbonyl group of benzoyltrimethylsilanes. In the phospholan series (124), this results in ring expansion to form a mixture of the diastereoisomers (125).13* Procedures for the resolution of racernic tertiary phosphines using chiral palladium(rr) complexes have been developed The importance of the steric effects of phosphine ligands in organsmetal!ic chemistry and in homogeneous catalysis has been reviewed,140and an improved procedure for estimating the size of phosphorus ligands in metal coniplexes has appeared. 141Dehydrogenation of tricy~lohexylphosphine~~~ and cleavage of a P-C bond in tri-t-butylphosp l i i r ~ ehave l ~ ~ been noted in their reactions with rhodium and iridium complexes. The 1-cyano-1-hydroxyalkylphosphines (12S), formed from the reactions of secondary phosphines with acyl cyanides, are isomerized into the tertiary phosphine oxides (127) when heated for a short time in the absence of a c a t a 1 y ~ t . l ~ ~

(1 25)

L. Lafaille, F. Mathis, and J. Barrans, Compt. rend., 1977, 285, C, 575. R. Nasirov, S. P. Solodovnikov, and M. I. Kabachnik, B d . Acad. Sci. U.S.S.R. (Div. Chem. Sci.), 1976, 25, 2230. 138 C. Couret, J. Satg6, and J.-P. Picard, J . Orgnnonietnllic Cf2~m., 1977, 141, 35. 139 K. Tani, L. D. Brown, J. Ahmed, J. A. Ibers, M. Yokota, A. Nakarnura, and S. Otsuka, J . Amer. Cfzenz. SOC.,1977, 99, 7876. 140 C. A. Tolnian, Chem. Rev., 1977, 77,313. 141 A. lrnmirzi and A. Musco, Inorg. Chim. A d a , 1977, 25, L41. 142 S. Hietkamp, D. J. Stufkens, and K. Vrieze, J. Organometallic Cltem., 1978, 152, 347. 143 R. G. Goel, R. G. Montemayor, and W. 0. Ogini, J. Amer. Chem. Soc., 1978, 100, 3629. 14* A. N. Pudovik, G. V. Romanov, and V. M. Pozhidaev, J . Geii. Cliern. (U.S.S.R.), 1977, 47, 653.

136

137

2

0rganoph osphor us Chemistry

20

2 Phosphonium Salts Preparation.-A number of routes to a-alkylated vinylphosphonium salts have been described. However, all lack generality, and the problems associated with the synthesis of such salts have still not been s01ved.l~~ The azo-alkenylphosphonium salts (128), prepared by quaternization of triphenylphosphine with t-butyl phenylhydrazonochloroacetates,are a new type of phosphonium salt, and are useful intermediates in the synthesis of azo-alkenes via the Wittig Triphenylphosphonium tetrafluoroborate is a useful reagent for the conversion of thio-dienes into y-thioallylphosphonium salts, e.g. (129).14' The protected formylphosphonium acetals (130) have been prepared by treatment of a tertiary phosphine with an orthoformate and an acetyl halide.14*The reactions of the stabilized ylides (131) with tropylium tetrafluoroborate give the salts (132).149 Cyclization of the phosphine (133) with phenacyl bromide gives the phosphoniacyclohexadienesystem (134).150 (i) Ph,P, 140-160°C (ii) HCIO,

HBF,

Ph3P

C,H,

'

+

Ph,PH BF,'

+

GPh, BFJ

Ph$-CHCOR

\

+Ph,&--CHCOR

(131) R = Ph, OMe, or OEt

(130) X = 0 or S R', R2 = Et, Buy or Ph

6 (132)

145 146 147 148 149

150

J. M. McIntosh and R. S. Steevensz, Canad. J . Chem., 1977,55,2442 P . Dalla Croce and A. Zaniboni, Synthesis, 1977, 552. D. A. Clark and P. L. Fuchs, Synthesis, 1977, 628. B. Costisella and H. Gross,J. prakt. Chem., 1978, 320, 128. G. Cavicchio, M. D'Antonio, G. Gaudiano, V. Marchetti, and P. P. Ponti, Tetrahedron Letters, 1977, 3493. M. S. Chattha, J. Chem. and Eng. Data, 1978,23, 95.

21

Phosphinw and Phosphonium Salts

The salts (135) undergo intramolecular cyclization on heating in 115% polyphosphoric acid to give the benzophosphepinium salts (1 36).161 A procedure has been developed for the synthesis of the cage phosphonium salt (137), which cannot be obtained simply by quaternization of the parent triazaphospha-adamantane with iodomethane.162The salts (138), obtained by quaternization of triphenylphosphine with N-(2-bromoethyl)phthalimidesYhave been found to have antileukaemic Compounds of the type (139), believed to be intermediates in the Arbuzov reaction, have been isolated and characterized from the reactions of appropriate PI11 esters with methyl trifluoromethanesulphonate. 6 4 The reactions of tertiary phosphines with the chloroacetyl derivatives (140) have given a range of functionalized phosphonium salts (141).166-167 Quaternization of tri-n-butyl- and triphenyl-phosphinewith 2-halogeno-2-methyl-but-3-ynes gives mixtures of phosphonium salts containing allenic, acetylenic, and conjugated double bonds.16* Ph,

,Ph (i) 115Y I'PA, 200*C (ii) H20 (iii) KPI-(,

(139) R', R2 = Et, Ph, OMe, OY OPh ClCH,COZ

R3P

(140) 2 = NHCONH,, OC,H,Cl, or NR,

151

+ R,kH,COZ C1' (141)

G. D. Macdonell, K. D. Berlin, S. E. Ealick, and D. Van Der Helm, Phosphorus and

Sulfur, 1978, 4, 187. E. Fluck and H.-J. Weissgraeber, Chem.-Ztg., 1977, 101, 304. R.J. Dubois, C.-C. Lin, and J. A. Beisler, J. Medicin. Chem., 1978, 21, 303. K. S. Colle and E. S . Lewis, J . Org. Chem., 1978, 43, 571. V. N. Kushnir, M. I. Shevchuk, and A. V. Dombrovskii, Zhur. obshchei Khim., 1977,47, 1715 (Chem. Abs., 1977, 87, 152 324). 156 N. B. Petrina, B. A. Kaskin, and N. N. Mel'nikov, Zhur. obshchei Khim., 1977, 47, 1027 (Chem. Abs., 1977, 87, 135 630). N. B. Petrina, B. A. Khaskin, N. N. Mel'nikov, S. F. Dymova, and N. N. Tuturina, J . Gem Clrem. (U.S.S.R.), 1977, 47, 946. 158 M. Zh. Ovakimyan, R. K. Lulukyan, and M. H. Indzhikyan, Armyan. khim. Zhur., 1977, 30, 320 (Chem. Abs., 1977, 87, 135 641).

152 153 154

22


Reactions.-Alkaline Hydrolysis. A comprehensive review of studies of the alkaline hydrolysis of phosphonium salts is available in thesis form.85 Hydrolysis of (+)-benzylethylmethylphenylphosphonium iodide (via the corresponding ylide) in a low-polarity medium gives the racemic ethylmethylphenylphosphine oxide, in contrast to the inversion of configuration that accompanies alkaline hydrolysis of the salt in highly aqueous media. It has been concluded that a decrease in the polarity of the medium increases the lifetimes of the intermediate five-co-ordinatephosphoranes, which are thereby permitted to undergo extensive pseudorotation, which results in eventual racemization in the product. The inversion of configuration noted in hydrolyses in highly aqueous media is due to the short lifetimes of the intermediate phosphoranes; these inhibit pseudorotation and block the reaction pathways that lead to products with retention of configuration.lS9 The steric courses of alkaline hydrolysis of the cis- and trans-isomers of the 4-t-butyl-substituted phosphorinanium salts (142; R = But) have been compared with those of the related 4-methyl-substituted system (142; R = Me).lsoWhen the reactions are carried out under homogeneous conditions, complete inversion of configuration at phosphorus is observed, whereas under heterogeneous conditions, small amounts of retention products are observed, as reported earlierlsl for the 4-methyl system, for which l*O-labellingstudies had established that the latter steric course involved attack of hydroxide on alkoxy-carbon. These authors are now convinced that attack on carbon in the 4-methyl salts [and also in the fivemembered ring system (143)] could have been obviated by homogeneous treatment with base. They have also re-examined homogeneous versus heterogeneous hydrolysis of the isomeric benzylphosphorinanium salts (144). In this case, the choice of conditions does not influence the nature of the products. Kinetic studies of the hydrolysis of the isomeric salts (142; R = But) have shown that both cisand trans-isomers react at a similar rate, indicating that the t-butyl group is not having any significant steric effect. Consistent with earlier studies of the steric course of alkaline hydrolysis of phospholanium salts, it has now been shown that the geometrically isomeric salts (145) and (146) undergo hydrolysis with cleavage of the benzyl group, with retention of configuration at phosphorus.lG2

A. Schnell and J. C. Tebby, J.C.S. Perkin I, 1977, 1883. K. L. Marsi and J. L. Jasperse, J. Org. Chem., 1978, 43, 760. 1 6 1 K. L. Marsi, J. Org. Cliem., 1975, 40, 1779. 162 H. Tomioka, K. Sugiura, S. Takata, Y. Hirano, and Y . Izawa, J . Org. Chem.,1977, 42, 3070. 159

160

23


ph‘

‘-CH,Ph

ph‘

“CH2Ph

The 3-heteroarylphosphonium salts (147) undergo alkaline hydrolysis with preferential loss of the benzyl group, indicating that the latter is better able to support the forming carbanionic centre than are the 3-heteroaryl groups. Studies of the rate of hydrolysis of related methylphosponium salts (148) indicate that the 3-heteroaryl substituents are much less strongly electron-withdrawing than the 2-isomers. Also reported in the same paper is a study of the course of decomposition of phosphonium betaines (149) derived from the reactions of tri-3-heteroarylphosphines with styrene oxide. That from tri-3-furylphosphine decomposes to form the related phosphine oxide and styrene, whereas the 3-thienyl analogue gives rise to the vinylphosphine oxide (150) and the rearranged phosphine oxide (151) uia the hydrolysis of an intermediate vinylphosphonium Treatment of the salts (152) with aqueous ammonia gives the phosphines (1 53), but the corresponding hydrolysis with aqueous sodium hydroxide is complicated by secondary reactions of the phosphines with other by-products.ls4 The salts (154) undergo hydrolysis to form a complex mixture of products arising from attack of hydroxide both at phosphorus and the alkoxyvinyl group.lSs Additions to Unsaturated Phosphonium Salts. Full details have appeared of the addition of various nucleophilic reagents to the diallylphosphonium salts (1 55) to give, via the corresponding divinyl salts (156), the heterocyclic systems (157).lea

0

(RO,CNHCHJ,I: ci- Nl 1401I (152)

163 164 165

106

0

i-

+

(RO,CNHCH,),P (153)

R:PC(OR2)=CH,

Br‘

(154) R‘ = Bu or Ph R2 = Et or Bu

D. W. Allen and B. G. Hutley, J.C.S. Perkin I , 1978, 675. A. W. Frank and G . L. Drake, jun., J. Org. Chem., 1977,42, 4040. A. M. Torgomyan, R. A. Khachatryan, M. Zh. Ovakimyan, and M. G . Indzhikyan, Armyan. khim. Zhur., 1977, 30, 596 (Chem. Abs., 1978, 88, 23 059). S. Samaan, Chem. Ber., 1978, 111, 579.

24

R2 R1\$ ,CH ,C =CH,

R2

I

R!,,CH=CCH,

x/ \

Ph

-


CH,C=CHR3

I

Ph/

R2 (155) R' = Me, CH,Ph, But, or Ph R2 = H or Me R3 = H or Ph

R1

\CH=CCH2R3

X-

ph/ q y C H 2 R 3 R2

I

R2 (156)

A~HI

x-z \;

(157) Y = 0, S, or NR

The latter have been shown to act as phase-transfer catalysts in the Finkelstein and Kolbe reactions.ls7 Addition of sulphonium ylides to the 2-acylvinylphosphonium salts (1 58) yields the substituted-cyclopropyl-phosphonium salts (1 59) as a mixture of stereoisomeric species. These undergo alkaline hydrolysis to form triphenylphosphine oxide and a mixture of isomeric cyclopropanes, in which the cis-form predominates.16* A range of nucleophilic species have been added to the allenylphosphonium salt (160), to form mainly the substituted allylphosphonium salts (161). In some cases, these isomerize to the substituted vinylphosphonium salts (162) under the reaction conditions.lsQ Miscellaneous. A number of studies of electrochemicalreduction of phosphonium salts have appeared. The course of electrolysis of a range of alkyl- and cycloalkyltriphenylphosphonium salts has been shown to depend on temperature, applied potential, the nature of the electrode material, and the nature of the supporting electrolyte.17* The polarographic reduction of various trans-l,2-ethylenediphosphonium salts (163) in both protic and aprotic solvents has been studied. Stable radical cations result from the first, reversible, one-electron stage of the reduction in aprotic media. In protic media, three reduction waves are observed. The first wave is associated with a two-electron cleavage of a P-C bond to form phosphine Br-

Ph&CH=CHY

(158) Y = COPh, COMe, COEt, COPri, COzMe, o r CN Ph,GCH=C=CHPh

Br-

f

Me,$-eHX X = COPh, CO,Et, or CN

aI'h,kH,C=CIIPh

-' ~ 1 Ph,;

I-I (159)

Br- +Ph,;CH=CCII,Ph

I

(160) Nu = C5HION,PhjP, OPr, or SBu

Br-

x

Nu (161)

Br-

I NU

(162)

167

S. Samaan and F. Rolla, Phosphorus and Sulfur, 1978,4, 145.

168

F. Hammerschmidt and E. Zbiral, Annalen, 1977, 1026. Zh. A . Aklyan, R. A. Khachatryan, F. S. Kinoyan, and M. G. Indzhikyan, Armyan. khim.Zhur., 1977,30, 582 (Chem. Abs., 1978,88, 6993). L. Homer and J . Roder, Annalen, 1977, 2067.

169 l70


25

and a vinylphosphonium salt, the latter being subsequently reduced to ethylene and phosphine. The third wave arises from reduction of the p h 0 ~ p h i n e . lThe ~~ 1,4-diphosphoniacyclohexa-2,5-dienesalts (1 64) also give stable one-electronreduction products in dimethylformamide. E.s.r. studies of these radical cations indicate that there is significant conjugative interaction by the quadrivalent phosphorus atom.172 A two-step mechanism for the formation of active esters of hydroxybenzotriazole in the reaction of carboxylate ions on the peptide-coupling reagent BOP (165) is indicated by 180-labelling The BOP reagent has been used to achieve the synthesis of phenyl esters of amino-acids in high yield, giving a method superior to that employing carbodi-imide.174 Methyltriphenoxyphosphonium trifluoromethanesulphonate (1 66) has been used to synthesize a variety of compound types, including ethers, esters, nitriles, and diols. The reaction of (166) with hydroxylamine hydrochloride in methyl cyanide gives a reagent capable of reducing cyclohexene to cyclohexane. It is thought that a di-imide intermediate is involved, arising from the phosphonium ion (167).176A further report of the application of the ‘peoc’ salts (168) as protecting groups in peptide synthesis in homogeneous aqueous solution has appeared.176 The furanosyloxyphosphonium salts (1 69) react with silver tosylate to give labile tosyl glycosides with retention of configuration, whereas reaction with aryl

R‘ \+/R’

(1’64) R’ = Et, PhCH,, or aryl RZ = H, Me, Et, But, CJI,,, or Ph X = C1 or Br

(Me,N),PO

171

E. A. Berdnikov, F. R. Tantasheva, V. I. Morozov, A. V. Il’yasov, and A. A. Vafina, Bull. Acad. Sci. U.S.S.R.,Diu. Chem. Sci.,1977, 26, 731. D. Rieke, R. A. Copenhafer, C . K. White, A. Aguiar, J. C . Williams, jun., and M. S. Chattha, J. Amer. Chem. SOC.,1977, 99, 6656. B. Castro, J.-R. Dormoy, G. Evin, and C. Selve, J. Chem. Res. ( S ) , 1977, 812; J. Chem. Res. ( M ) , 1977, 2118. B. Castro, G.Evin, C. Selve, and R. Seyer, Synthesis, 1977, 413. E.S. Lewis, B. J. Walker, and L. M. Ziurys, J.C.S. Chem. Comm., 1978,424. H. Kunz, Angew. Chem. Internat. Edn., 1978, 17, 67.

172R. 173 174 175 176

0rganophosphorus Chemistry

26

ON1I, +/

(PhO),P,

CI-

K1R2R3kIl,C1120COClC1-

thiols gives 1,2-cis-thioglycosides in an s N 2 process, with inversion of configuration.17' Pyridine N-oxides react with phenylethynyltriphenylphosphonium bromide to give the betaines (170), which on sublimation at 200 "C give mixtures of phenylalkynylpyridines.l7* An unexpected reaction of the methylenebisphosphonium salt (171) is its rearrangement to the carbodiphosphorane (172) on deprotonation. The biphosphorane (173) is not f 0 ~ m e d . l ~ ~

R. A. Boigegrain, F. Chrktien, B. Castro, and B. Gross, J . Chem. Res. (9,1978, 8 5 ; J . Chem. Res. ( M ) , 1978, 1229. 178 N. Morita and S. I. Miller, J. Org. Chem., 1977, 42, 4245. A. Wohlleben and H. Schmidbaur, Angew. Chem. Znternar. Edn., 1977, 16,417.

177

27 slP n.m.r. studies show that, in solutions of phosphonium halides in organic solvents such as dichloromethane or methyl cyanide, there is no formation or intermediate halogenophosphoranes via P-halogen bonding. lSoSome 31P studies have also shown that zwitterionic phosphonium betaine intermediates can be detected in the Wittig reaction, provided that the negative charge at oxygen is reduced by binding to Li+ or by resonance delocalization into an adjacent carbonyl group.lS1 The phosphonium salt (174) decomposes when an attempt is made to recrystallize it, forming the diphosphine (175),lBa Thermal decomposition of the saIt (176) is reported to give mainly n-bromobutane and tri-n-butylphosphine oxide, together with smaller amounts of vinyl bromide and acetyl bromide. It has been suggested that the reaction proceeds uia an intermediate oxyphosphorane.lS3Mass spectral studies of the thermolysis of the salts (177) indicate that the reaction involves the stepwise loss of methyl bromide followed by carbon dioxide.lS4 Phosphines and Phosphoniurn Salts

3 Phospholes The compounds obtained from the reactions of methylhydrazones of methyl or primary alkyl ketones and phosphorus trichloride have been shown to be the ionic azaphosphole systems (178), and not the isomeric 3-chlorodiazaphospholines (179). X-Ray studies show that the ring system of (178) is planar, and that bond lengths are consistent with 6n-delocalization, which favours the ionic form.lS6 Reductive eliminations from tetraco-ordinate to dico-ordinate phosphorus were formerly known only for phosphabenzenes. This pathway has now been employed in the synthesis of the 1,2,4,3-triazaphosphoIe system (18O).ls6 4.

A

A

v

v

(PhNHCH,),P C1’ + PhN

B u , k H (OBu)CH,Br Br(176)

(178) R = H or Me

p-P

NPh

Ph3kH(R)C0,Me Br‘ (177) R = alkyl

(179)

L. V. Nesterov, N. A. Aleksandrova, I. D. Temyachev, A. A. Musina, and R. G. Gainullina, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1161. lS1M. Schlosser, H. B. Tuong, and C. Tarchini, Chimia (Switz.), 1977, 31,219. A. W. Frank and G. L. Drake, Jr., J. Org. Chem., 1977, 42, 4125. A. M. Torgomyan, M. Zh. Ovakimyan, and M. G. Indzhikyan, Armyan. khim. Zhur., 1977,30,439 (Chem. Abs., 1977, 87, 135 657). 184 F. Sanchez-Ferrando and A. Virgil;, Anales de Quim., 1977, 73, 1059. 185 P. Friedrich, G. Huttner, J. Luber, and A. Schmidpeter, Chem. Ber., 1978, 111, 1558. A. Schmidpeter, J. Luber, and H. Tautz, Angew Chem. Internat. Edn., 1977, 16, 546. 180


28

/===Y

Ph

Ph

N, ,NMe

-HC1:

P‘

c1’

I

‘S(CH,),SH

-

r y P\/ NwNMe s’ ‘s Me I

The 1,2,3-diazaphosphole (181) reacts with phenylhydrazine to give (182;

R = H). The related system (182; R = Ph) has been shown to react with bromine to give (183); this reaction proceeds via addition of bromine to the P-C bond of (182; R=Ph).18’ The phosphine (184) condenses with imido-ester hydrochlorides to form the 1,3-benzazaph0spholes (185). A new route to the phosphindole system has been described. The sulphide derived from the phosphole (186) undergoes spontaneous dimerization to the Diels-Alder adduct (187), which on heating forms the phosphindole sulphide (188). As yet, this has not been desulphurized to the parent p h o s p h i n d ~ l e . ~ ~ ~ Certain phosphole sulphides have been shown to undergo reduction on treatment with Fe,(CO),, with the formation of phosphole iron carbonyl complexes, in which both the phosphorus and the n-system of the ring may be linked to the metal.1goA full account of the synthesis and properties of phosphaferrocenes, e.g. (189), has now appeared,lD1following the preliminary communication noted

(1 84)

(185) R = H, Me, or Ph

PhP-S

187

1B8 1g9 19O 191

R. G. Bobkova, N. P. Ignatova, N. I. Shvetsov-Shilovskaya, N. N. Mel’nikov V. V. Negrebetskii, L. Ya. Bogel’fer, S.F. Dymova, and A. F. Vasil’ev, J. Gen. Chem. (U.S.S.R.), 1977, 47, 527. K. Issleib, R. Vollmer, H. Oehme, and H. Meyer, Tetrahedron Lerrers, 1978, 441. D. G . Holah, A. N. Hughes, and D. Kleemola, J . Heterocyclic Chem., 1977, 14,705. F. Mathey and G . Muller, J . Organometallic Chern., 1977, 136,241. F. Mathey, J . Organometallic Chem., 1977, 139, 77.

Phosphines and Phosphoniunz Salts

29

E‘e

in last year’s Report. The n-phospholyl anion (190) seems to be very similar to the n-cyclopentadienyl anion in terms of its properties as a ligand.la2 The possible aromatic nature of the phosphole system would be expected to affect the availability of the phosphorus lone pair for donation to a transition metal. From a survey of the complexes of a series of simple phospholes (191) with nickel(ir), palladium(Ir), and platinum(I1) halides, it has been concluded that nickel(@ is only able to form complexes with phospholes that are only weakly aromatic in the pyramidal ground state, and not with those which have a higher degree of lone pair-diene interaction in this state. It would seem that only simple phospholes with alkyl substituents at phosphorus, and no ring substituents, are resistant to complex formation with nickel@). Whether this means that such 1-alkylphospholesare more aromatic than others is debatable. It may only mean that the phosphorus lone pair is not the HOMO in these In a similar vein, a comparison of the electronic spectra of tetrahedral nickel@)complexes of 5-phenyldibenzophosphole (192) and triphenylphosphine shows, surprisingly, that the former appears to be the better donor towards the metal ion. Clearly, in the dibenzophosphole system, there is very little delocalization of the lone pair. The above result may be a consequence of the reduced steric bulk of (192) compared to triphenylphosphine as a result of two benzene rings being linked together, the smaller ligand therefore approaching closer to the metal and causing a greater interaction with the metal Also relevant to the issue of phosphole aromaticity is an X-ray structural study of the dibenzophospholium salt (193), in which the endocyclicangle at phosphorus is shown to be only 93.9 ’. It is suggested that this low value is consistent with the presence of considerable bond-angle strain at phosphorus, which is relieved either on dealkylation to form the parent phosphole or on the formation of a phosphorane following nucleophilic attack at phosphorus. The introduction of bond-angle strain when phospholes and their benzologues are quaternized could

R2 (191) K’ = 11 or Me K2 = Ph or BU lQ2 193 194

Q p Q-pPh

(1 92)

Ph/

‘ C H 2 0 B r

Br-

(193)

A. Breque and F. Mathey, J . Organometallic Chem., 1978, 144, C9. D. G. Holah, A. N. Hughes, B. C. Hui, and P.-K. Tse, J. Heterocyclic Chem., 1978,15, 89. D. W. Allen and D. Hogarth, Phosphorus and Sulfur, 1977, 3, 381.

30


well be responsible for the reduced nucleophilic reactivity of these systems, rather than considerations of possible delocalization of lone pairs.lSS Following an earlier report that the bond-angle-strained phospholium ylide (194) undergoes smooth decomposition on heating at 175 "C in diphenyl ether to form (195), it has now been shown that this reaction proceeds via an intramolecular rearrangement and extrusion mechanism, and not by initial elimination of phosphole oxide to form the highly strained acenaphthyne system.lg6 It has been shown that pentaphenylphosphole reacts with nitrilimines to form the azornethylenephosphoranes (196), which do not undergo further cyclization involving the double bonds of the phosphole ~ysfen1.l~~ 4 Phosphorins

The chemistry of il:3-phosphabenzene(197) has been reviewed, along with that of other A3-heterobenzenes.In the review, it was noted that phosphabenzene does not react with strong protic acids or with iodomethane, and the low basicity was attributed to the bond-angle constraints imposed by the ring system, which do not permit the necessary changes in geometry at phosphorus on protonation or quaternization.lg8 Ph

T Ph

+ RIco~N-fiRz

h:Q:p

Ph

lQ5 lg6 197

l98

R* = O E ~or Me R2 = aryl

Ph

---+ p h o p h

Ph'

P \C-N=NR2

I

COR' (196)

D. W. Allen, I. W. Nowell, A. C. Oades, and P. E. Walker, J.C.S. Perkin I, 1978, 98. J. I. G. Cadogan, A. G. Rowley, and N. H. Wilson, Annalen, 1978, 74. N. P. Ivanova, V. N. Chistokletov, L. A. Tamm, and A. A. Petrov,J. Gen. Chem. (U.S.S.R.), 1977, 47, 696. A. J. Ashe, 111, Accounts Chem. Res., 1978, 11, 153.

Pltosphines and Phosphonium Salts

31

i=> (197)

(198)

(199)

However, a study of the relative basicities of 4-cyclohexyl-A3-phosphorin (1 98) and a series of para-substituted triarylphosphines (with regard to their ability to form hydrogen bonds to p-trifluoromethylphenol) shows that, while the phosphorin is a much weaker base than the corresponding pyridine, nevertheless it is more basic than tripheny1pho~phine.l~~ The lone pair at phosphorus is also available for donation to a transition The ‘phosphaphenol’ (199) has been prepared. It has phenolic character, but is very sensitive to acids and bases, readily undergoing ring-opening reactions.201 With the intention of generating P=C bonds by a novel approach, the DielsAlder reaction between the A3-phosphanaphthalene(200) and hexafluorobut-2yne has been studied, in the hope that the adduct (201) would be stable. However, (201) is thermally unstable, and decomposes to give the naphthalene (202) and a polymer, possibly from [MeC-PI, arising from a retro-Diels-Alder reaction.202 Cyclization of bisdiphenylphosphinomethane with 1,3-dibromo-2-hydroxypropane gives the cyclic salt (203), which, after conversion into the perchlorate and treatment with phosphoric acid followed by aqueous sodium carbonate, forms the salt (204). Treatment of the latter with aqueous sodium hydroxide does not, however, result in the bis-A6-phosphorin(205), but instead gives rise to a mixture of ring-opened phosphine oxide hydrolysis products.2 0 3

I

OEI (203) 199 200

201 202

203

H. P. Hopkins, H. S. Rhee, C. T. Sears, K. C. Nainan, and W. H. Thompson, Inorg. Chem., 1977. 16, 2884. K. C. Nainan and C. T. Sears, J. Organometollic Chem., 1978, 148, C31. G. Mgrkl, G. Adolin, F. Kees, and G . Zander, Tetrahedron Letters, 1977, 3445. T, C. Klebach, L. A. M. Turkenburg, and F. Bickelhaupt, Tetrahedron Letters, 1978, 1099. T. A. Mastryukova, G. K. Genkina, R. M. Kalyanova, T. M. Shcherbina, P. V. Petrovskii, and M. I. Kabachnik, Zhur. obshchei Khim., 1978,48,263 (Chem. Abs., 1978,88,190 983).

32


Photolysis of the 'diphosphabarralene' (206) gives the 1 ,4-A3-diphosphabenzene (207) and subsequently a diphosphabenzvalenederivative (208).204 The diphosphabenzene (207) also reacts with carbon tetrachloride, via attack on chlorine by the tervalent phosphorus, to form the bicyclic system (209).205

204

Y.Kobayashi, S. Fujino, H. Hamana, I. Kumadaki, and Y.Hanzawa, J . Amer. Chem. SOC., 1977,99, 8511.

Y.

loS Kobayashi, I.

Kumadaki, H. Hamana. and S. Fujino, Tetrahedron Letters, 1977, 3057.

3

6 f

Quinquecovalent Phosphorus Compounds BY S. TRLPPETT

1 Introduction

Pride of place this year must go to the preparation of the first stable hydroxyphosphorane (2) by the action of dry hydrogen chloride on the silyloxyphosphorane (l).l In solution the hydroxyphosphorane is in equilibrium with the phosphate (4),equilibration being slow on the n.m.r. time-scale below 10 “C in acetonitrile. With diazomethane, (2) gives the methoxyphosphorane (3). A similar hydroxyphosphorane (6) has been obtained2from POCl, and the hydroxyacid (5) in the presence of pyridine and from the pH-phosphorane (7) by oxidation with DMSO in DNF. (6)was isolated as the salts with DMF or with triethylamine.

OPCI, + 2

CO,H

I

PkCOH

\

OH

(5)

F. Ramirez, M. Nowakowski, and J. F. Marecek, J . Amer. Chem. Soc., 1977, 99, 4515. A.. Munoz, B. Garrigues, and M. Koenig, J.C.S. Chem. Comm., 1978, 219.

33

34


Equally intriguing is the detection of PH-phosphoranes such as (9) in the alcoholysis of phosphoramiditesq3No detectable amount of (9) is formed from the product phosphite (10) and methanol, and (9) may be formed as shown in (8). 2 Structure and Bonding Ab initio calculations on intramolecular rearrangements in H2PF3have been r e p ~ r t e d Calculations .~ on the loss of a hydrogen molecule from PH5 show that the lowest energy path is via a transition state involving considerable stretching of one apical bond, with slight contraction of one equatorial bond, and leading to loss of the hydrogens originally attached by these bonds.5 The synchronous, symmetry-allowed, process involves loss of two equatorial hydrogens.s CNDQ/2calculations have shown the importance of upp lone-pair orientations in determining the energies of the various rotamers of the phosphorane (11).7In the alkaline hydrolysis of the dimethyl phosphate anion, the rotamer of the intermediate phosphorane that results from the lowest energy transition state for attack of HO- is not the one that leads to the lowest energy transition state for loss of MeO-.8 Therefore, if stereoelectronic control is to influence the overall rate of the hydrolysis, rotation about the equatorial ester bond must occur in the intermediate. X-Ray analysis has revealed geometry varying between trigonal-bipyramidal , ~ R = C1),l0 (13),11 and square-pyramidal in the phosphoranes (12; R = P ~ I )(12; (14),12 (15),13 (16),14 (17),15 and (18).16 Another analysis of the distortions of cyclic phosphoranes from ideal trigonal-bipyramidal geometry has appeared.17 The inclusion of a term that measures the effect of electron-pairrepulsion modified by ligand electronegativity for the two sets of bonds around phosphorus in a molecular mechanics programme leads to good agreement between predicted and found geometry in a range of acyclic and cyclic phosphoranes.18 The reversal, in the phosphorane (17), in the normal relative apicophilicity of oxygen and nitrogen is presumably associated with the involvement of the M. T. Boisdon, C . Malavaud, F. Mathis, and J. Barrans, Tetrahedron Letters, 1977, 3501 ; L. Lafaille, F. Mathis, and J. Barrans, Compt. rend., 1977, 285, C, 575. 4 A. Strich, Inorg. Chem., 1978, 17, 942. 5 J. M. Howell, J. Amer. Chem. SOC., 1977, 99, 7447. 6 R. Hoffmann, J. M. Howell, and E. L. Muetterties, J. Amer. Chem. SOC., 1972, 94, 3047. 7 D. G. Gorenstein, B. A. Luxon, J. B. Findlay, and R. Momi, J. Amer. Chem. SOC., 1977, 99, 4170. 8 D. G. Gorenstein, B. A. Luxon, and J. B. Findlay, J. Amer. Chem. SOC.,1977, 99, 8048. 9 R. K. Brown and R. R. Holmes, J. Amer. Chem. SOC., 1977, 99, 3326. 10 R. K. Brown and R . R. Holmes, Inorg. Chem., 1977,16, 2294. 11 J. R. Devillers and R. R. Holmes, J. Amer. Chem. SOC., 1977, 99, 3332. 12 P. Narayanan, H. M. Berman, F. Ramirez, J. F. Marecek, Y.Chan, and V. A. V. Prasad, J . Amer. Chem. SOC.,1977, 99, 3336. 13 J. S. Szobota and R. R. Holmes, Inorg. Chem., 1977,16,2299. 14 V. G. Andrianov, A. E. Kalinin, and Yu. T. Struchkov, Zhur. strukt. Khim., 1977, 18, 310 (Chem. Abs., 1977, 87, 6 s 252). 15 E. P. Kyba and D. C . Alexander, J.C.S. Chem. Comm., 1977,934. 16 G. M. L. Cragg, B. Davidowitz, G. V. Fazakerley, L. R. Nassimbeni, and R. J. Haines, J.C.S. Chem. Comm., 1978, 510. 17 R. R. Holmes and J. A. Deiters, J. Amer. Chem. Soc., 1977, 99, 3318. 18 J. A. Deiters, J. C . Galluci, T. E. Clark, and R. R. Holmes, J. Amer. Chem. SOC.,1977,99, 5461. 3

QuinquecovalentPhosphorus Compounds

ro>PN M e,

+

35

0'

?? H

0-P'

1 O' Me

MeOH

pM* (10)

+

MeOH

Me0 (8)

s

OMe

PbC-CHN,

PhPC12 + 2

0

f

Ph,P

O--PHPh P' h Ph (17)

I

COMe "

I

phP.[oq +

"

MeCO (19)

36


p-electrons on nitrogen in n-bonding. The complex phosphorane (18) is probably formed by rearrangement of the phosphonite (19). R. R. Holmes has developed a model which allows the estimation of the relative stabilities of the various trigonal-bipyramidal and square-pyramidal isomers of a phosphorane and thus may be used to predict the free energies of activation for Berry pseudorotations.l 9These agree well with experimental values over a wide range of phosphoranes. The model incorporates apicophilicity scales spanning 10 kcal mol-l and is based on ligand electronegativity and both ring-strain and steric terms.

3 Acyclic Systems The and Cavell have extended their studies of the stable conformations of (trifluoromethy1)phosphoranes to include the phosphoranes Me(CF,),PX, 2 o Me(CF3)2PX2,21 and Me2(CF3)2PX,22 where X = F , C1, OMe, SMe, or NMe,. An unexpected feature of the 19F n.m.r. spectra of the phosphoranes Me(CF,),P(OMe), and Me,(CF,),PSMe is the loss of fluorine equivalence at very low temperatures. Thus the latter shows an [AB,],P pattern at - 110 "C. Apical and equatorial trifluoromethyl groups can also be distinguished on the basis of their different ' J P l 3 C coupling constants.23 The heat of hydrolysis of (EtO),P has been dete~mined.~~ From this, and on the basis of various assumptions, the free energies of formation in aqueous solution of the species (EtO)nP(OH)5-nhave been calculated. Among other acyclic phosphoranes described are (20),25(21),,* (22),,' (23),28 (24),29and the crystalline (25).,O The variable-temperature lH, l9F, and 31P n.m.r. spectra of (22) were reported. At room temperature the lH and leFn.m.r. spectra of (24) show separate signals for the two alkoxy-groups; these coalesce at about 45 "C. 4 Four-membered Rings Fluorodimethylphosphine and hexafluoroacetone give the phosphoranes (26), (27), and (28), all with X = F, in equal amounts.S1Chlorodimethylphosphine and hexafluoroacetone give only (27; X=C1).32 This rearranges at 100 "C to give (28; X = Cl), probably via the ylide (29), as the ketone can be detected by laF R. R. Holmes, J. Amer. Chem. SOC.,1978, 100, 433. K. I. T h e and R. G. Cavell, Inorg. Chem., 1977, 16, 2887. K. I. The and R. G. Cavell, Znorg. Chem., 1977, 16, 1463. 22 K. I. The and R. G. Cavell, Znorg. Chem., 1978, 17, 355. R. G. Cavell, J. A. Gibson, and K. I. The, J. Amer. Chem. SOC.,1977, 99, 7841. 24 J. P. Guthrie, J. Amer. Chem. SOC., 1977, 99,3991. 26 D. D. Poulin, C. Demay, and J. G. Riess, Inorg. Chem., 1977, 16, 2278. 26 G. Bauer and G. Hagele, Angew. Chem. Internat. Edn., 1977, 16, 477. 27 S. C. Peake, M. J. C. Hewson, 0. Schlak, R. Schmutzler, R. K. Harris, and M. I. M. Wazeer, Phosphorus and Sulfur, 1978, 4, 67. 28 I. Ruppert and V. Bastian, Angew. Chem. Internat. Edn., 1977, 16, 718. 29 G.-V. Roschenthaler, Z. Naturforsch., 1978, 33b, 3 11. D. A. Bowman, D. B. Denney, and D. Z. Denney, Phosphorus and Sulfur, 1978,4, 229. *l G.-V. Roschenthaler, 2. Naturforsch., 1978, 33b, 131. 33 J. A. Gibson, G.-V. Roschenthaler, K. Sauerbrey, and R. Schmutzler, Chem. Ber., 1977, 110, 3214.

l9 2o 21

Quinquecovalent Phosphorus Compounds

+ 2Me,SiOR

PhPF,

--?

37 PhPF2(OR),

+

2Me,SiF

(20)

R = CW2CCI,, CH,CI-ICb, CHMeCN, or CH,CF, F2

X

r,mPF(Ohre),

(21) X = C1, R r , or I Ph,PF,(Cl I,),, Pl~J%,

PhCH,NMePF4 ,,R,,

(23)

(22) R = Me or Ph n = 0, 1, or 2

-

Me2PH + (CF,),CO

Me,PF[OCH(CF,),],

IZ

= 1--4

+ (Me,P), + Me,P(O)OCH(CF,),

(24) PhP(OR),

+

2PhSOR

PhP(OR), (25) R = Me,CCH, or c-C&

CH, (27; X = Cl)

loo"c

*

II

MePOCH(CF,), + (CF3),C0

-

(28; X

f

C1)

Cl (2%

n.m.r. spectroscopy during the rearrangement. With SbF3the chlorophosphorane (27; X = Cl) gives (27; X = F), which rearranges to (28; X = F) at 170 "C. Detailed n.m.r. studies have appeared on the phosphoranes produced from (Me2P)2and hexafluoroacetone, which include (28 ;X = F).33 Cyclic iminophosphoranes, e.g. (30), and ketones3*or isocyanates 36 are in equilibrium in solution with the bicyclic phosphoranes (31). A range of biphosphoranes (32) has been obtained from acyl hydrazides, as shown.86 35s

33 35

36

J. A. Gibson, G.-V. Roschenthaler, and V. Wray, J.C.S. Dalton, 1977, 1492. A. Schmidpeter and T. von Criegern, Angew. Chem. Interat. Edn., 1978, 17, 55. A. Schmidpeter and T. von Criegern, J.C.S. Chem. Comm., 1978, 470. A. Schmidpeter, J. Luber, and T. von Criegern, Z.Naturforsch., 1977, 32b, 845.

38

Organophosphorus Chemistry R’P=N Me02cuPh,

+

0 - 1 1 ~ 3

-

R2R3C0

R\l

‘/P--N

C0,Me

(30) R1 = Me or P h

MR,02cWPh2 C0,Me

R Z , R 3= Me, Ph, CF, or RN=

X,POCI or X,PCI, or X,PSCl

(3 1) R 0-N I / X,P-N

I

I

y-px,I

X = Cl, Me, Ph, or NMe,

Me (Me3Si)2N\

R‘

/”

PR~R~, Me3SdP\N/ SiMe,

(33) R’ = alkyl or SiMe, R’, R3 = Me, Ph, or NMe,

I

(Me,Si),N 15N ’P‘ \P(NMe,), Me,% N// \N/ SiMe,

(34)

Details have appeared of the preparation and properties of the diazadiphosphetidines (33).37 The temperature dependence of the n.m.r. spectra of the 16N-labelled phosphorane (34) suggested dissociation, as shown, at higher temperatures, and this was confirmed by exchange reactions.38The diazadiphosphetidines (35) were obtained from o-azido-phenols and phosphorochloridites, including the catechyl ester, in the presence of base.3s 97

38

39

M. Halstenberg and R. Appel, Chem. Ber., 1978, 111, 1815. R. Appel, M. Halstenberg, and F. Knoll, 2.Naturforsch., 1977, 32b, 1030. N. A. Tikhonina, V. A. Gilyarov, and M. I. Kabachnik, Zhur. obshchei Khim., 1978, 48, 44 (Chern. Abs., 1978, 88, 170 042).


39

5 Five-membered Rings Phospho1ans.-Careful control of the reaction conditions allowed the preparation of the spirophosphorane (36)."O Its lH and 13Cn.m.r. spectra are unchanged at - 105 "C. Variable-temperature n.m.r. studies show that at - 50 "C the fivemembered ring occupies an apical-equatorial position in the phosphorane (37), with the methoxy-group apical.41 With The phosphorane (39) was formed on heating the ylide (38) in acetyl chloride it gave the phosphonium salt (40).The ylide (41) derived from this salt gave, with non-enolisable ketones, the bicyclic phosphoranes (42) (Scheme 1). Me

Ph,P=C=C(OEt),

c1-

i_,

(38)

OEt (39) Iii

(41) (42) Reagents: i, reflux, in toluene;

ij,

MeCOCl; iii, NaN(SiMe&; iv, RIRZCO

Scheme 1

40

42

H. Schmidbaur, P. Holl, and F. H. Kohler, Angew. Chem. Internat. Edn., 1977, 16, 722. H. Schmidbaur and P. Holl, 2.Naturforsch., 1978, 33b, 489. H. J. Bestmann, K. Roth, and R. W. Saalfrank, Angew. Chem. Internat. Edn., 1977,16,877.

40


The products from the hydrolysis, alcoholysis, and acetolysis of the phosphoranes (43)have again been assigned the structures (44).43 l,%Oxaphospholans.-Oxiran and the ylide (45) gave the phosphorane (46).44 The ylide (48), formed from the phosphorane (47) and butyl-lithium, gave trans-olefins with aldehydes.45 1,2-Oxaphospholens.-A full account has appeared of the very stable bicyclic phosphoranes (49), including examples where R1R2 = 2,2’-biphen~lylene.~~ The spirophosphorane (50) was synthesized as shown, using an intramolecular

43

44 45 46

N. A. Kurshova, N. A. Razumova, A. A. Petrov, and K. A. V’yunov, J. Gen. Chem. (U.S.S.R.), 1976,46, 1693. H. Schmidbaur and P. Holl, Z . Naturforsch., 1978, 33b, 572. W. G. Salmond, M. A. Barta, and J. L. Havens, J. Org. Chem., 1978,43, 790. D. Hellwinkel and W. Krapp, Chem. Ber., 1978, 111, 13.


41

Cannizzaro reaction. Isomeric spirophosphoranes, e.g. (51), are formed from crotonaldehyde and cyclic arylpho~phonites.~~ The 1 :1 adduct (52) from trimethyl phosphite and methyl vinyl ketone reacts exothermally with chlorotrimethylsilane to give the phosphonate (53) quantitatively. * 1,3,2-Dioxaphospholans.-Tripheny lphosphi ne and the trans-1,2-dioxetan (54) gave the phosphorane (55).49 At 50 "Cthis gave phosphine oxide and cis-stilbene epoxide. A number of phosphoranes, e.g. (56), have been prepared from cyclic esters derived from a-hydroxy-acids.6 o Spin-labelled phosphoranes, among them

R = Ph, OPr, or NMe,

(56)

47

N. A. Razumova, Yu. Yu. Samitov, V. V. Vasil'ev, A. Kh. Voznesenskaya, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.),1977, 47, 289; V. V. Vasil'ev, N. A. Razumova, V. I. Zakharov, and M. P. Gruk, Zhur. obshchei Khim., 1977, 47, 2485 (Chem. Abs., 1978,88,

48

D. A. Evans, K. M. Hurst, L. K. Truesdale, and J. M. Takacs, Tetrahedron Letters, 1977,

105 231). 2495. 49

50

P. D. Bartlett, M. E. Landis, and M. J. Shapiro, J . Org. Chem., 1977, 42, 1661. A. Munoz, B. Garrigues, and R. Wolf, Phosphorus and Suvur, 1978, 4, 47.

42


(57), containing one or more 4-oxy-l-oxyl-2,2,6,6-tetramethylpiperidine residues

have been d e s ~ r i b e d . ~ ~ 1,3,2-Dioxaphospholens.-In the presence of less than one equivalent of fluorosulphonic acid in dichloromethane, the phosphorane (58) and the enol-phosphonium salt (59) are in equilibrium.6aAt - 100 "C this is slow on the n.m.r. time-scale. The signals in the lH n.m.r. spectrum due to the vinyl methyls of (58) and (59) coalesce at -80°C and those due to the methoxy-groups coalesce at - 50 "C.Above 0 "Cthe enol-phosphonium salt isomerizes to the keto-form. More phosphorane intermediates in Arbuzov-typereactions have been detected by low-temperature 31Pn.m.r. spectroscopy, among them (GO)53 and (61).64The

61 52

53

54

W. Storzer and G.-V. Roschenthaler, Z , Naturforsch., 1978, 33b, 305. M. M. C. F. Castelijns, P. Schipper, and H. M. Buck, J.C.S. Chem. Comm., 1978, 382. J. Michalski, J. Mikolajczak, M. Pakulski, and A. Skowronska, Phosphorus and Suljiur, 1978, 4, 233. D. B. Denney, D. Z. Denney, and G. DiMiele, Phosphorus and Sulfur, 1978,4. 125.


43

phosphoranes (60) derived from ( + )-2-octanol decompose above - 40 "C to give 2-halogeno-octanes with inversion of configuration at carbon. The intermediate (61) is in slow equilibrium with the phosphonium salt (62). Nitrogen-containing Rings.-Spirophosphoranes (63), containing a 1,3,2-0xazaphospholidine ring derived from cr-amino-acids, have been prepared as shown in Scheme 2.66More examples of bicyclic phosphoranes of the general structure (64) have been described, among them (66) and (67) (Scheme 3), derived from a mixture of dl- and meso-forms of the amino-diol (65).56Schmidpeter has outlined two general routes to bicyclic phosphoranes analogous to (64); firstly the addition of the phosphites (68) to activated olefins such as (69)67and secondly the use of o-heterodienyl-phenols(70), among them the azo-compound (71) and the imine

Reagents: i, PhPC12; ii, (PhCO)2

Scheme 2

H. Lavayssiere, G. Dousse, and J. SatgB, J. Organometallic Chem., 1977, 137, C37. D. Houalla, F. H. Osman, M. Sanchez, and R. Wolf, Tetrahedron Letters, 1977, 3041. s7 A. Schmidpeter, J. H. Weinmaier, and E. Glaser, Angew. Chem. Internat. Edn., 1977, 16, 55

56

549.

44


Reagents: i, (Me2N)sP ;

(67) PhOH; iii, PhOPC12, EtaN; iv, o-chloranil

Scheme 3

i >P-x

+

N Z

Y/I

Z=CorN Y = C, N, or 0

- rix


45

(73).58,5 9 These are either treated with chloro-phosphines in the presence of base 58 or added to the triazaphosphole (72) to give phosphoranes such as (74).sB The phosphonamidite ( 7 3 , with thiols, gave the PH-phosphoranes (76) and, possibly, the thio-esters (77).60 The position of the equilibrium between the phosphine-imines (78) and the phosphoranes (79) has been studied by n.m.r. At low temperaspectroscopy at different temperatures and in different tures, solutions of the species with R1=But or Ph3C and R2=Ph show two separate high-field 31Presonances, presumably due to the isomers (80) and (81). The methoxyphosphorane (82) has been synthesized as shown.62 The hindered phosphorane (83) is stable at pH 13.2 in aqueous dioxan at 100°C for 6 h, but undergoes ready acid-catalysed hydrolysis to give the phosphinic amide (84).63Similar hydrolysis of the trimethoxyphosphorane (85) gives the ring-retained acid (86), probably via the initial ring-opened amide (87).

+

N'

I

R'

58

59 60

63

A. Schmidpeter and J. H. Weinmaier, Angew. Chem. Internat. Edn., 1977, 16, 865. A. Schmidpeter, M. Junius, J. H. Weinmaier, J. Barrans, and Y. Charbonnel,2.Naturforsch., 1977,32b, 841. S. A. Terent'eva, M. A. Pudovik, and A. N. Pudovik, Bull. Acad. Sci. U.S.S.R., 1977, 26, 199. H. B. Stegmann, R. Haller, and K. Schemer, Chem. Ber., 1977,110, 3817. J. 1. G. Cadogan, N. J. Stewart, and N. J. Tweddle, J.C.S. Chem. Comm., 1978, 182. J. I. G. Cadogan, D. S. B. Grace, and P. K. G. Hodgson, J. Chem. Res. (S), 1978, 63.

46


Ph,POMe

Ph,POMe

NP(O)Ph, Ar

OMe

(8 3)

(84) 94%

Ar

Ar

(85)

(86)

I I

4I

Ar= 0

---+

'N P(O)!OMe),

Ar

(87)

Ar

0

..bMe Me

Quinquecoualent Phosphorus Compounds

47

Addition of dimethyl phenylphosphonite to the nitro-olefin (88) gave the phosphorane (89) q~antitatively.~~ More stable analogues (91) were obtained from the nitro-stilbenes (90), and displayed the expected isomerism.66 Benzhydroxamicacid and PCI, in molar ratios of 1:2 or 2 :1 gave mixtures of the phosphoranes (93) and (94), whereas a ratio of 3 :1 gave the six-co-ordinate species (92).6 6 With SbF,, (94) gave the corresponding fluorophosphorane. The PH-phosphorane (95) was obtained from benzhydroxamic acid and PCl,. The amino-thiol (96) and PCI, gave the chlorophosphorane (97).67 Deselenation of the heterocycle (98) with trimethyl phosphite gave the azathiaphospholidine (99), which decomposed at room temperature. 6 Six-membered Rings Variable-temperature n.m.r. studies show that, at - 90 "C, the six-membered ring in the phosphorane (100) occupies an apical-equatorial position, with the methoxy-group apical.41Among other phosphoranes having the phosphorus in a six-membered ring are (101),69(102),50and (103),70obtained as shown. Structure (104) has been given to the product from triethyl phosphite and maleic anhydride.71

R~(oR~),

64 65 66

67 68 69 70

71

R, D. Gareev, G. M. Loginova, and A. N. Pudovik, J . Gen. Chem. (U.S.S.R.),1976, 46, 1843. J. 1. G. Cadogan, R. A. North, and A. G . Rowley, J. Chem. Res. (S), 1978, 1 . E. Fluck and M. Vargas, 2. anorg. Chem., 1977, 437, 53. V. P. Kukhar, T. N . Kasheva, and A. Ya. Ul'chenko, J. Gen. Chem. (U.S.S.R.),1977, 47, 436. K. Burger and R. Ottlinger, Synthesis, 1978, 44. L. B. Littlefield and G. 0. Doak, Phosphorus and SulJirr, 1977, 3, 35. B. A. Arbuzov, Yu. Yu. Samitov, Yu. M. Mareev, and V. S. Vinogradova, Zzoest. Akad. Nauk S.S.S.R., Ser. khim., 1977, 2000 (Chem. Abs., 1978, 88, 23 055). N. D. Kazakova, Ts. A. Lyubman, and S. R. Rafikov, Zzoest. Akad. Naitk Kazakh S.S.R., Ser. khim., 1977, 27, 75 (Chem. Abs., 1977, 87, 201 653).

48


(97)

(96)

Ph

+JJ

Me3Si0

+

- &JQ ph\;/F 0 ’ ‘ 0

OSiMe, Ph2PF.3

(101)

49

Quinquecoz~alerit Phosphorus Compounds 0

+

7 Higher-membered Rings 1,ZDioxan added to the phosphetan (105) to give the seven-membered phosphorane (106).7aThe value of AG* for equivalence of the methyl groups in the lH n.m.r. spectrum of (106) is 13.5 kcal mol-l. 31PN.m.r. evidence was presented for the formation of unstable seven-membered phosphoranes from 1,Zdioxan and trimethyl phosphite or methyl o-phenylene phosphite. Adducts (107) are described from cycloheptane-1,Zdione or cyclo-octane-1,Zdione and trialkyl phosphites.73

72

73

N. J. De’ath and D. B. Denney, Phosphorus and Suvur, 1977, 3, 51. R. Neidlein and W. Friedrich, Arch. Pharm., 1977,310,622 (Chem. Abs., 1978,88,37 704).

50


The bis-silyl ether (108), with trifluorodiphenylphosphorane,gave the fluorophosphorane (log), and with PF, it gave a crude spirophosphorane (110), whose 19Fn.m.r. spectrum was consistent with the fluorine occupying an apical position in a trigonal-bipyramidal 8 Six-co-ordinate Species The remarkable six-co-ordinate species (112) are formed from the phosphorane (111) and COz, CS2, or COS (two isomers) in ether at room ternperat~re.~~ The structure of (112; X = 0)was established by X-ray analysis. The six-co-ordinate PH-compound (114) is in equilibrium in solution both with the phosphite (113) and phenol and with (115) and 8-hydroxyquinoline,the positions of the equilibria varying with the Details have appeared of the formation of the tris-(o-phenylenedioxy)phosphate anion from an excess of catechol and PCl,.78 The salt (116) has been obtained as shown.?' The PH-anion (118) is formed exothermically from the phosphonite (117) in the presence of diethylamine but not of triethylamine.78On heating, the diethylammonium salt of (118) gives the spirophosphorane (119) and hydrogen. Ph

Me,SiO

OSiMe,

(543

f

(108)

74

75 76

77 78

Ph,PF,

K. 1. The, L. V. Griend, W. A. Whitla, and R. G. Cavell, J. Amer. Chem. SOC.,1977, 99, 7379. C. Bui Cong, A. Munoz, M. Koenig, and R. Wolf, Tetrahedron Letters, 1977, 2297. J. Gloede, H. Gross, and G. Engelhardt, J. prakt. Chem., 1977, 319, 188. A. Kh. Voznesenskaya, N. A. Razumova, A. A. Petrov, and 0. G. Sheptienko, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1316. M. A. Pudovik, S. A. Terent'eva, N. P. Anoshina, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.).1977, 47, 1133.

Quiuquecovalent Phosphorus Compounds

Me(CF3),PNMe, (111)

+

CX,

51

C-NMe,

X = O o r S (-112)

aQ>p”o. 0

3

?

J

Halogenophosphines and Related Compounds BY J. A. MILLER

1 Introduction This year's literature has been notable for the attention given to the reactions of halogenophosphines with alkenes. Thus some new synthetic applications have been presented, while other studies have resulted in an improved understanding of these I eactions. The main interest in halogenophosphoraneshas been preparative, with the highlight perhaps being the preparation of arsenic pentachloride for the first time. 2 Halogenophosphines Preparation-Considerable improvements in the methylation of the phosphorus trichloride-aluminium chloride complex have been reported1 Thus dichloro(methy1)phosphine (1) is available in SO% yield, using a potentially more convenient procedure than that described last year." Organocadmium reagents have been advocated for the preparation of monochlorophosphines, provided that pyridine is used in the work-up. This procedure leads to chloro(methy1)phenylphosphine (2) in 72 o/,yield. An organo-aluminium intermediate is involved in a related reaction, which produces the new bisphosphine (3). (i) AlCI, (ii) Me1

I3'

(iii) distil from KCI and Fe

2PhPC4

ti) Me,Cd (ii) pyridine

*

hiePC& 70-80%

PhP(C1)Me

72%

The preparation of iodophosphines has been further described in the Russian literature. In general, the method involves halogen exchange, using lithium 1 2

3 4

M. Soroka, Synthesis, 1977, 450. F. W. Parrett and M. S. Sun, Synth. React. Inorg. Metal-Org. Chem., 1976, 6, 115. D. Jore, D. Guillerm, and W. Chodkiewicz, J. Organometallic Chem., 1978, 149, 6 7 . Z . S. Novikova, A. A. Parishchenko, and I. F. Lutsenko, J. Gea. Chem. (U.S.S.R.), 1977, 47, 707.

52

Halogenophosplzines and Related Compounds

53

iodide in non-polar solvents, and the iodophosphines (4),5 (5),6 and (6)' have been prepared by this route. Other preparations include those of the pseudohalogen derivatives (7)8 and (Q9 via silver salts. The phosphine derivatives (9) and (10) have been prepared from bromodifluorophosphine by reaction with Group IV derivativesof sulphur1O and seleniumll respectively.

I,PCH,

P hCH,PI,

R,NPI,

Reactions with AIkenes and Related Compounds.-Renewed interest has been shown in the reactions between alkenes and complexes of chlorophosphines with aluminium halides. Much of the new work has yielded new types of phosphine oxides, and these are described in detail in Chapter 4. The other dominant theme has been mechanistic, and this is discussed below. The question of the nature of the species formed from chlorophosphines and aluminium trichloride has been answered in an admirably concise paper from Quin's group.12 It is now clear (from 31Pn.m.r. studies)12 that the favoured adducts from dichloro- and monochloro-phosphines are molecular 1 :1 and 2: 1 complexes with aluminium chloride, and that ionic species are therefore unlikely reaction intermediates. Since phosphorus trichloride does not show any reaction with aluminium chloride, it is argued that the effect of the latter is to assist in the removal of chloride as the alkene interacts with the formerla (see Scheme 1). Other mechanistic work has been concerned with the way in which the C-P bond is made in these reactions, and with the rearrangements which may occur thereafter. Thus, trapping of the chlorophosphine-aluminium chloride complex(es) by electrophilic attack on an alkene gives carbonium ions, which may be 5

T. V. Kovaleva, I. T. Rozhdestvenskaya, and N. G. Feshchenko, J. Gen. Chem. (U.S.S.R.),

6

N. G. Feshchenko, E. A. Mel'nichuk, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1977,

1977,47, 294. 47, 924. Zh. K. Gorbatenko and N. G. Feshchenko, J. Gen. Clzeni. (U.S.S.R.), 1977, 47, 1752. 8 R. J. Dimand and R. P. Pinnell, J. Inorg. Nuclear Chern., 1977, 39, 1455. 9 S. Cradock, E. A. V. Ebsworth, M. L. McConneII, D. W. H. Rankin, and M. R. Todd, J.C.S. Dalton, 1977, 1925. 1') G. N. Bockerman and R. W. Parry, J. Fluorine Chem., 1976, 7 , 1. 11 D. E. J. Arnold, E. R. Cromie, and D. W. H. Rankin, J.C.S. Dalton, 1977, 1999. 18 C. Symmes and L. D. Quin, J. Org. Chem., 1978, 43, 1250. 7

54


prone to rearrangement, as shown for the suggested pathways to (11) and (12) (Scheme 2),13 to (13) (Scheme 3),14 and to (14) (Scheme 4).16 Rn

R,,PCI,-n

Rn(Cl)2-n$ AlC&

+ AlCl,

ti

= 1 or 2

C1,

-n

I

P AICI,

’.”, products

n = oli, ii

2 : 1 complex

products Reagents: i, alkene; ii, H2O; iii, RlaPC13-n

Scheme 1

‘Ph ((R’R= ’ph=o P h ow y (11) 5% R 5% I

f i p , pP h

I

R’ = Ph when R2 = CH=CH, R’ = CH=CH, when R2 = M e

SC& A Alc&

I

C1 c1

(12) 25% Reagents: i, PhPCla-AICla; ii, aq. NaHC03

Scheme 2

Me

P’

c1

a-pinene

v

I

Cl

v

25%

Me P’

I

CI Scheme 3 13 14

15

M. Rotem and Y. Kashman, Tetrahedron Letters, 1978, 63. E. Vilkas, M. Vilkas, D. Joniaux, and C . Pascard-Billy, J.C.S. Chem. Comm.,1978, 125. A. Rudi and Y . Kashman, Tetrahedron Letters, 1978, 2209.

Halogenophosphines and Related Compounds

55 i i ,

i ,

R+H2

Mi

:u”’

RMe

Y

R

I

P’-CI

Ph

45% MQ . ee OH ‘Ph

(14) Reagents: i, PhPClz.AIC13; ii, RMeC=CH2; iii, aq. NaHCOs Scheme 4

However, there have been further examples, from the work of Kashman’s group, in which a redox process appears to be occurring, as in the formation of (15)13 and (16).16 These results are probably related to the formation of (17) from tetramethylethylene, reported recently by Crews.l8 An attractive rationalization12 of this set of results is that the presence of additional water is the key, since it will generate hydrogen chloride under the reaction conditions. This will then protonate the alkene, producing a carbonium ion, which is subsequently trapped by the PII1chloride (see Scheme 5). Such a rationalization seems to be the best available at present, and is given further substance by the demonstration that (18),12and not (17),18 is the structure of the tetramethylethylene product. This apparently trivial alteration removes the need for a redox step in the reactions leading to (17), and a similar view would seem to be appropriate in the formation of (15) and (16). 0

lLJ-y:o%

PhP

(i) PhPBr, .AIBr,(H,O) (ii) aq. NaHCO,

I

Me

OH (15)

0 (i) PhPCl, AICI,(H,O) a

Me2C= CH,

(ii) aq. NaHCO,

*

II

Me,CPPh

I C1

50%

(16)

Me

\

’

Me

l6

c=c

/Me

PhPC1, * AICI,(H,O)

‘Me

P. Crews, J Org. Chem., 1975, 40, 1170.

*

Me,CCHMe,

I

PhPCl * AICI, (17)

Me,CCHMe,

I

PhP’Cl, ZlCl, (18)

56


Reagents: i, HCI, AlC13; ii, RPCh; iii, HzO

Scheme 5

The related reactions of 1,3-dieneshave been further described, and a work-up using methanol has been shown to facilitate the isolation of pure A2-phospholen oxides (1 9) or A3-pliospliolen oxides (20) from reactions of is0prene.l' The formation of isomers (at phosphorus) in the reactions of 1,4-dimethylbuta1,3-dienehas been ascribedl8 to quinquecovalent species intervening between the salt intermediates (isomerically homogeneous) and the final oxides (21) and (22).

(i) AIC!, (ii) MeOH (iii) distil (iv) crystallize " ~

(J /\

0

$.

PhPBr,

Ph

AlBr, c

/-\

Ph

Br

(21) (two geometric isomers) (one isomer)

(22) (two geometric isomers)

l7

K. Moedritzer and R. E. Miller, Syrzth. React. Inorg. Metal-Org. Chenz., 1978, CS,167

18

L. D. Quin and R. C . Stocks, Pliosplzorus and Sulfur, 1977, 3, 151.


57

The complexities of the perchloryl-fluoride-catalysedaddition of halogenophosphines to alkenes have been ascribed to radical processes.1DThe first example of uncatalysed addition of phosphorus trichloride to methoxyacetylenes appears to be both regio- and stereo-specific,20as shown for (23). Direct formation of triphenylphosphinefrom phosphorus trichloride is a very inefficient process, but this has been overcome in a neat one-pot reaction which proceeds via triphenylphosphine sulphide (24). 21 Chlorodiphenylphosphine has been converted into the phosphine (25).22

MeOC=CR

+ PC1,

c_)

c4pxc1

R OMe (23) R = Me 82% R = Et 50%

PbPCI + CH,(CO,Et),

Et3N:

P h K H (CO,Et), (25)

Reactions with Carbonyl Compounds and their Derivatives.-Hexafluoroacetone has once again been a rewarding substance for those interested in structure and mechanism in halogenophosphine chemistry. Thus dimethyl(fluoro)phosphine (26) gives three products on treatment with hexafluoroacetone, and their structures [(27), (28), and (29)] have been rationalized, as in Scheme 6.23 Chloro(dirnethyl)pho~phine,~~ like chloro(diphenyl)phosphineYZ6 reacts with hexafluoroacetone to give a 1,4,2-dioxaphospholan. On heating to 100"C, the initial product (30) rearranges to (3l), and hexafluoroacetone is temporarily regene~ated.~~ The ylide (32) is to be the other intermediate formed from (30), and the sequence is outlined in Scheme 7. Hexafluoroacetone reacts with tetrafluorodiphosphine to produce (33) in good yield.1° Phosphorus trichloride has been shown to form unique dienol phosphites (34) on treatment with p-diketones or their analogues in the presence of base.26 19

S. V. Fridland, N. V. Dmitrieva, and R.A. Salakhutdinov,J. Gen. Chem. (U.S.S.R.), 1976, 46, 2536.

20 21

22

M. A. Kazankova, A. R. Sheffer, E. A. Besolova, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1535. G.A. Olah and D. Hehemann, J. Org. Chem., 1977,42, 2190. L. A. Ripina, R. A. Loktionova, and Yu. G.Gololobov, J. Gen. Chem. (U.S.S.R.), 1976, 46, 2561.

23

24

G.-V. Roschenthaler, 2. Nuchrforsch., 1978, 33b, 131, J. A. Gibson, G.-V. Roschenthaler, K. Sauerbrey, and R. Schmutzler, Chem. Ber., 1977, 110, 3214.

25 26

R. K. Oram and S. Trippett, J.C.S. Perkin I, 1975, 1300. G. M. L. Cragg, B. Davidowitz, R. G. F. Giles, and R. J. Haines, J.C.S. Chem. Comm., 1977,569.


58

F

0

Me,PF

ll I + F3CCCF3 + Me,;OC

F

-

,cF3

A

\

F

F

0

Me,PCl

I1

+ F,CCCF,

0- C -CF3

Me. (F$)zCHO

I I >P-C& 1

0

+--

Me

II 1 (CF,)C + H,C==POCH(CF,), 1

c1

c1 (32)

(31)

Scheme 7 0

I1 (F3C),C + FzPPFz

PF,

I

(F,C),COPF2

(33)

80%

c1

6

I I Me,T-C-CF, i


59

Typical carbonyl-addition reactions of chloro(dipheny1)phosphine yield the oxides (35) and (36).27 The products of the reactions of chloro(diethy1)phosphine with cyclic ketones depend on the ring size of the ketone, as shown for the oxides (37) and (38).28 Scheme 8 illustrates the suggested2*pathway to (37), although it seems to the present author that this view takes little account of the evidence of the past few years, that 2:l adducts are intermediates in such reactions (compare with Scheme 6). Ethylphosphonous chloride (39) has been shown to be an intermediate in the well-explored reaction of acrylic acid with dichloro(ethyl)phosphine.29 The unusual mixed anhydride (40) has been made by exchange with the related oxo-germadioxolan (41).30 Phosphorus tribromide in DMF has been used in a convenient preparation of 2-bromo-4-methylquinoline (42) from the 2-methoxyanalogue.3f Cl

I

Reactions With Hydroxy-groups.-Stereochemical aspects of the reactions of propargyl alcohols with halogenophosphines have been given further attention. For example, the chiral alcohol (43) yields a chiral phosphonate (44)as shown, and this is taken as evidence for a concerted [3,2]sigmatropic rearrangement pathway.32The preferred approach of acetylide ion to the carbonyl of (45) has been deduced from the geometry of the oxides (46).a3 27

28 29

30

81 32

33

A. I. Razumov, P. A. Gurevich, S. Kh. Nurtdinov, S. A. Muslimov, and L. M. Tyl’nova, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1301. S. Kh. Nurtdinov, N. M Ismagilova, T. V. Zykova, R. A. Salakhutdinov, and V. S. Tsivunin, J. Gen. Chern. (U.S.S.R.), 1977, 47, 1 158. T. Kh. Gazizov, A. P. Pashinkin, V. A. Kharlamov, V. I. Kovalenko, and A. N. Pudovik, J. Gen. G e m . (U.S.S.R.), 1977, 47, 1129. H. Lavayssiere, G. Dousse, and J. Satge, J. Organometallic Chem., 1977, 137, C37. T.Yajima and K. Munakata, Chem. Letters, 1977, 891. R. S. Macomber, J. Amer. Chem. Soc., 1977, 99, 3072. J.-P. Battioni and W. Chodkiewicz, Bull. SOC.chim. France, 1977, 320.


60

II Et2PCl + R,C

c1

0

0 __L

[Et,P-O-CR2]fC1‘

_+

ll I Et,P-CR,

(37) R, = -(CH2)4-

(38) R, = -(CHz)sScheme 8 0

EtPC1,

+

_.)

H2C=C€K02H

II EtPH + CH,=CHCOCl I C1 (39)

0

I_)

I1 I c1

EtPCH,CH,COCI

pw<x;

Me,Ge(NEt,),

0

4-

RCH (0II)C02H (41)

(40)


61

The reactions of activated 1,4-diols, such as (47), with tetraiododiphosphine have been shown to give low yields of very complex mixtures.34The reaction mechanism34and scope35have been discussed. Intermediateshave been identified in the formation of trialkyl phosphites (48) from phosphorus trichloride. 3 6 Various reactions of chlorophosphines with ambident nucleophiles have been studied, and found to result in cyclic compounds, as shown for (49) and (50),37 (51),38 and (52).39A more spectacular example leads to the bicyclic phosphorane (53),*O presumably the result of nucleophilic substitution at phosphorus, then [4,l]cycloaddition to the azopyridine unit in the intermediate. The aliphatic nitro-compounds (54)41and (55)42show quite different reactivity towards phosphorus trichloride. Thus, in the presence of pyridine, nitroalkanes are converted, in one pot, into nitriles, possibly via a p h ~ s p h o r a n e .In ~ ~the absence of pyridine, the nitro-group of (54) is inert to phosphorus trichloride, and a standard acetal cleavage occurs.41

OH

1.9%

0.5%

(47) PCI,

+

ROH -+

ROPCI,

H

(RO),;’

C1‘

‘Cl

34

(RO),PCl

+

HCI

* (RO),P (48)

R. Dyllick-Brenzinger,J. F. M. Oth, C. B. Chapleo, and A. S. Dreiding, Helv. Chim. A d a , 1977,60, 1404.

35

36

37 38

H. Suzuki and T. Fuchita, Nippon Kagaku Kaishi, 1977, 1679. T. Kh. Gazizov, V. A. Kharlamov, A. P. Pashinkin, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1977,47, 1137. E. Fluck and M. Vargas, 2. anorg. Chem., 1977, 437, 58. V. I?. Shishkin, G. V. Sitanova, Yu. M. Yukhno, and B. I. No, J. Gen. Chem. (U.S.S.R.), 1977, 47, 208.

39 40 41 42

M. A. Pudovik, S. A. Terent’eva, N. P. Anoshina, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1133. A. Schmidpeter and J. H. Weinmeier, Angew. Chem. Znternat. Edn., 1977, 16, 865. M. B. Gazizov, V. S. Tsivunin, L. P. Ostanina, and F. I. Shaikhutdinova, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1747. P. Wehrli and B. Schaer, J. Org. Chem., 1977, 42, 3958.


62 HOCH,CH,C

fioR

HNH

+ PCI,

Et3Nb

RO'

Pl\PCI

+ QN

//

OE t

PCI,

50%

I + CH3CHOCHN02 1 Me

Me

I

CH,CH(Cl)OEt + C1,POCHN02

76%

(5 4)

RCH,NO, (55)

+ PCI, + RCH2N-0

I I/ 0-P I c'1 c1

RCSN

Halogenophosphines and Related Compounds 63 Reactions with Amines and Derivatives-Hexamethyldisilazane (56) reacts as In contrast, (57) reacts with dichloroshown with chloro(dipheny1)pho~phine.~~ phosphines to give ~yclotetra(~~-phosphazanes) (58).44 The authors clearly expected a phosphetidine from this reaction, and they present extensive spectral and X-ray evidence for (58).44 This compound has been reported p r e v i o ~ s l y , ~ ~ for R=Me, but there is not full agreement on physical data. Lithium amides displace halogen from phosphorus to give the aminophosphines (59)46 and (60).47The analogous reaction of tris(trimethylsily1)amine (61) with the chlorophosphine (62) can be explosive.4 6 The products of the reaction of primary or tertiary dichloroamines (63) with phosphorus trichloride are tetrachlorophosphoranes (a), isolated at low temperature~.~~ Above 0 "C these lose chlorine to give phosphazenes (n= 1) or . ~ ~ work clarifies an earlier study of this reaction.49 dimers ( T Z = ~ ) This Miscellaneous Aspects.-Diphosphine monosulphides (65) have been prepared as ~ h o w nO .Reactions ~ of various phosphorus-containing ambident nucleophiles with chlorophosphines may lead to new P-P bonds, as in (66), or to P--0-P bonds, as in (67).51The thermodynamic and kinetic factors controlling these reactions have been discu~sed.~l The reaction of phosphorus trifluoride with sulphenyl fluorides leads to phosphoranes (68).52 Cyclohexyldichlorophosphine (69) is converted into its sulphide quantitatively if tin@) chloride is used as the The mechanism of copolymerization of styrene with dichoro(pheny1)p h o ~ p h i n eand ~ ~ the effect of chlorophosphines on the polymerization of methyl methacrylate have been Ph,PCl + (Me,Si),NH --+ HN(PPhJ, + ClSiMe, (5 6) 5 8% Me

RP RPC4 + (Me,Si),Nhle ( 5 7)

43 44

45 46

47 48

4U 60

51 62

53 54

55

R = Me or Et ____I_)

/N-Pe

I MeN 'P-NMe R

NMe

I

/

PR

50%

(5 8) F. T. Wang, J. Najdzionek, K. L. Leneker, H. Wasserman, and D. M. Braitsch, Synth React. Znorg. Metal-Org. Chem., 1978, C8, 119. W. Zeiss, W. Schwarz, and H. Hess, Angew. Chem. Znternat. Edn., 1977, 16, 407. U. Wannagat and H. Autzen, 2. anorg. Chem., 1976,420, 119. R. H. Neilson, R. C. Lee, and A. H. Cowley, Znorg. Chem., 1977, 16, 1455. G.-V. Roschenthaler and R. Starke, Synthesis, 1977, 580. V. A. Covenya and A. M. Pinchuk, J . Gen. Chem. (U.S.S.R.), 1976, 46, 2557. K. A. Petrov, A. A. Neimysheva, G. V. Dotsev, and A. G. Verich, Zhw. obshchei Khim., 1961, 31, 1361. V. L. FOSS,Yu. A. Veits, P. L. Kukhmisterov, V. A. Solodenko, and I. F. Lutsenko, J . Gen. Chem. (U.S.S.R.), 1977, 47, 437. C. Glidewell, J. Organometallic Chem., 1977, 142, 171. W. Gombler, 2. anorg. Chem., 1978, 439, 207. T. G. Al'zoba and S . I. Suminov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1810. S.R.Rafikov, N. D. Kazakova, and L. B. Iriskina, Vysokomol. Soedineniya, 1978,20B, 183. H. Uemura, T. Taninaka, and Y. Minoura, J . Polymer, Sci., Polymer Chem. Edn., 1978 16, 41.


64 R

' + X2PY

Me,SiN

'Li

.__+

hle,SiN(R)PX, (5 9 )

(X=Y=F or X = CF,,Y = C1)

-Li

t PCl,

-+ (60)

(Me,Si),N

+

(61) RNCI,

+ PCI,

(CF,),PCl

---+

EXPLOSION

(62) RN(Cl)PCI,

>O"C

+ Cl,

n = l o r 2

(64)

(63)

(CI,PNR),

r-

60-90% S

R',PS-

-I-RZ,PCl

II * R',PPRZ, (65)

X

RSF

+ PF,

X

R = CF or FCH

HO

RSPF, 4RSH (68)

+

P(O)F,

65


Spectroscopic studies reported during the year include low-frequency vibrational spectra for (70)9 and n.q.r. studies on iodophosphines.56 Electrondiffraction data on the phosphines (71) have appea~ed.~' EtnPC1, -,, (71) n = 1 or 2

F2PX (70) X = -CN,-NCO, -NCS, or - W S e

Silylphosphines and Related Compounds.-The phosphine (72)6* and the diphosphine (73)59have been synthesized as shown, The stannylene (74) is the first of its type to be made, and it exists in solution as a dimer of great stability. 31Pand IlgSn n.m.r. data were used to assign structure ( 7 9 , in preference to (76) or (77), to the dimer.60 t-Butyl(pheny1)trimetliylsilylphosphine(78) has been prepared, and from it the germylphosphine (79) has been synthesized.61 The t-butyl group seems to enhance the stability of (78) and (79), by inhibiting exchange reactions. The inversion barrier in (79) has been found to be fairly high (AG*=19.7 kcal mo1-1).61 The 31P n.m.r. shifts have been discussed for the related Group IV phosphines (80),62 Becker's work on silylated acylphosphines continues. Thus tris(trimethy1sily1)phosphine (81) reacts with pivaloyl chloride to give (82),63 providing an analogy with previous work using bis(trimethyl~i1yl)phosphines.~~ The phosphaalkene (82) reacts with methanol, to give a stable enol (83).65 The enol derivative (84) is formed as shown, although in the case where R = Ph, the acylarsine (85) is stable at room temperature.66 A study has been made of the insertion reactions of the silyl ketone (86).67 These have resulted in the synthesis of a range of new phosphines (87)-(89). Si2F,

+ PF, 5 (F,Si),P (7 2)

But2P K'

56

57 58 69

+

Et,P- SnC1,

__f

{(Buf2P),Sn), (74) 40%

H. Terao, T. Okuda, and H. Negita, Bull. Chem. SOC.Japan, 1978,51, 710. V. A. Naumova, L. L. Tuzova, and N. M. Zaripov, Zhur. strukt. Khim., 1977,18,67. K. G . Sharp, J.C.S. Chem. Comm., 1977, 564. H. Schumann, L. Roesch, and W. Schmid-Fritsche, J. Organometallic Chent., 1977, 140,

c21. W.-W. D u Mont and H.-J. Kroth, Angew. Chem. Internat. Edn., 1977, 16, 792, 81 H. Schumann and R. Fisher, J. Chem. Res. (S), 1977, 272. 62 H. Schumann and H.-J. Kroth, 2. Naturforsch., 1977, 32b, 513. e3 G. Becker, 2. anorg. Chern., 1977, 430, 66. 64 G. Becker, Z . anorg. Chem., 1977, 423, 242. 8 5 G. Becker and H. P Beck, 2. anorg. Chem., 1977, 430, 77. 66 G . Becker and G. Gutekunst, Angew. Chem. Internat. Edn., 1977, 16,463. 67 C. Couret, J. Satgk, and J. P. Picard, J . Organometallic Chem., 1977, 141, 35. 60


66 But But ‘P/ But2PSn/ ‘SnPBu‘, P‘’

/\

But

But

(B ut,P),Sn=Sn

(75)

But\

Ph/

(]5uf2P),SnSnPB ut

(PBu f2)

(76)

(77)

/But PC1 + Me,SiCl

+

Mg

+

+ MgC4

Me,SiP

‘Ph

(Me3E1nPR3-n

(80) E = Si or Ge R = Butor Ph

0

(Me,Si),P

II + Me,CCCl

-1OOC

0

I1

(Me,Si),PCCMe,

f

Me,SiCl

(81) 0

I

MeOSiMe, + Me,CC

II

,OSiMe,

MeOH f--

Me,SiP=C

p/‘\CMe,

‘CMe,

(83) RAs(SiMe3,

0 I1

+ Me,CCCl

(82) ,OSiMe,

/SiMe, --+

RAs

-+

‘CCMe,

It 0 (85)

RAs--C ‘CMe,

(84)


67

/PE4 PhCOSiMe,

\

0

II

,

PhCSiMe,

Et,PGeMe,

PEt,

I

PhCOSiMe,

(89) (diast ereoisomer s)

3 Halogenophosphoranes Preparation.-Much preparative work has appeared in the past year, and the following subsections have been sequenced according to the co-ordination level of the phosphorus in the starting material. By Addition of Halogen to Phosphorus(n1).A small piece of history has been rewritten by Seppelt, who has prepared arsenic pentachloride (90)for the first time.68This paper recounts the efforts of Liebig and Wohler (in 1834) to prepare (W),and describes the successful use of chlorine as a solvent for the photolytic generation of (90),68which is metastable.

Other halogenation reactions are outlined in Scheme 9.6g- - 7 3 The phosphoranes (91) have been used in the preparation of the acyclic pentaoxyphosphorane.70 The phosphorane (92) is of interest because its analogues (93)show an increased tendency to form phosphonium salts as n ranges from 3 (phosphorane-salt equilibrium) to 1 (salt only in Another interesting aspect of this paper7ais the n.m.r. evidence for TBP structures for (92), and its support for an apicophilicity order based on aI-values, and not on electronegativity. 68

69

70

71 72

K Seppelt, 2.anorg. Chem., 1977, 434, 5. I. Ruppert and V. Bastian, Angew. Chem. Znternat. Edn., 1977, 16, 718. D. Dakternieks, G.-V. Roschenthaler, and R. Schmutzler, J. Fluorine Chem., 1978,11, 387. K. I. The and R. G . Cavell, Znorg. Chem., 1977,16, 1463. R. G. Cavell, J. A. Gibson, and K. I. The, J. Amer. Chem. Soc., 1977,99, 7841.


68 Ph,P(CH,),PR,

+ F2

__f

Ph2PF2(CH,),,PF2R2 R = Me or Ph

-

hIeP(CF,), + C1, -+ MePC1,(CF3), FP(CF3>2+ Br,

(Ref. 69)

(Ref. 71)

FBr,P(CF,),

(Ref. 72)

(92)

Reagents: i, LiOCH(CF3)z

Scheme 9

+

ClNEt,

- 5ooc

___3.

c1

(94)

It fio\D40

f

EtCl

By Insertion of Phosphorus(Ir1) into other Halogen Compounds. The phosphorane (94) has been detected as an intermediate in the conversion of phosphites into phosphor amid ate^.^^ From n.m.r. evidence, it seems that the salt (95) is also present in solution. This sequence forms an interesting contrast with that in which (64) is an intermediate4*(see Section 2). New phosphoranes (96)74 and (68)52 have been prepared. A convenient and efficient general preparation of dichlorophosphoranesfrom hexachloroethane (97) has much to commend it.76A related reaction uses carbon tetrachloride as the 73

74 75

D. B. Denney, D. Z. Denney, and G. Dimiele, Phosphorus and S~dfur,1978, 4, 125. G. Bauer and G. Hiigele, Angew. Chem. Iriternat. Edn., 1977, 16, 477. R. Appel and H. Scholer, Chem. Ber., 1977,110,2382.


69

halogen source and yields the dichlorides (98). 7 6 Methyltetrachlorophosphorane has also been used as a halogen source, as in the preparation of (99). By Reactions of Phosphorus(1Ir) with G O Compounds. The preparation of the phosphoranes (26)-(3 1) from hexaflu~roacetone~~~ 2 4 has been described in Section 2. By Exchange Reactions of Phosphoranes. Silicon derivatives continue to be used to convert simple halogenophosphoranes into more complex structures, as shown in Scheme 10.7 8 -81 Phosphorus pentachloride has been converted into the phosphoranes (100)s2 and (101).37Alkyls of Group IV metals have been used in the synthesis of the methylphosphoranes (102)'l and (103).83

+ F

F

(96) R,P

+ Cl,CCCI,

--+

(97)

X = F, C1, Br, or I

R,PCI, + Cl,C=CCl, 78-93%

R 3Me,PR

+ CCl,

Me,P(R)CI,

F,+

0,

,NPh P

MePC14

-+

+

I

.R

I

Me,tC(Cl)=PMe,

)=p:

0, ,NPh

I Ph

P

82

R. Appel, R. Milker, and 1. Ruppert, Chem. Ber., 1977, 110, 2385. A. Schmidpeter, J. Luber, H. Riedl, and M. Volz, Phosphorus and Surfur, 1977, 3, 171 L. B. Littlefield and G . 0. Doak, Phosphorus and Sulfur, 1977, 3, 35. D. D. Poulin, C. Demay, and J. G. Riess, Inorg. Chem., 1977, 16, 2278. S. C. Peake, M. J. C. Hewson, 0. Schlak, R. Schmutzler, R. K. Harris, and M. 1. M. Wazir, Phosphorus and Sulfur, 1978, 4, 67. M. Volkholz, 0. Stelzer, and R. Schmutzler, Chem. Ber., 1978, 111, 890. V. P. Kukhar, T. N. Kasheva, and A. Ya. Ul'chenko, J. Gen. Chem. (U.S.S.R.), 1977,47,

83

436. R. G. Cave11 and K. I. The, Inorg. Chem., 1978, 17, 355.

'6

77 78

79 80

81

70

Organophosphorus Cheniistry Ph

Me\Si/Me

'0

\;/

'0

'0

F

Ph

0 ' (Ref. 78)

-

R'PF, + 2Me,SiOR2

R'PF,(OR2),

(Ref. 79)

86% if R' = CH,CHCI, 90% if R' = CH,CF,

PhCH,

\

NSiMe,

/

Me

+ RnPFS -,,

(Ref. 80)

+

n = 0, 1, or 2 R = Me or Ph

(Ref. 81)

PCI,

+

2

[ (INHMe - [ qn I

benzene leflux*

SH

PCl, + PhC-0

(100)

Ph

I

PCIS-Zn

HN-OH

(101)

iz

= 1 or 2

Halogeriophosphines and Related Compounds hle,Sn t F3P(CF,),

71 hlePF2(CF,), (102)

hle,Pb I- Cl,P(CF,),

--+

Me,PCI(CF,),

(103)

From Arsenic(rv) Compounds. An improved route to difluoro(tripheny1)arsorane (104) has been reported, and conductivity data have been rationalized by suggesting that there exists some arsonium salt c h a r a ~ t e rThe . ~ ~stability of the arsoranes (105) towards water has been suggested to determine their ease of preparation from the

-

HI: + Ph,As=O

Ph,AsF,

I1CI t R,As=O

_.)

(104)

R,AsCL, (105)

Reactions of Halogenophosphoranes.-Ph osphine dihalides continue to be valued in geneial organic synthesis. A particularly impressive example is provided by the chlorination reactions of the alcohols (106), (107), and (108) with dichloro(triphenyl)phosphorane, generated in situ from hexachloroacetone.88 The retention of alkene geometry, together with the low levels of allylic rearrangement or racemization, are attractive features of these reactions. Extensive product analyses have been reported for the reactions of some bridged alcohols, e.g. (109) and (1 lo), with dichloro(triphenyl)phosphorane.8 The authors deduce that several different pathways may be operating in these reaction^.^' Progress has been made in the field of peptide synthesis, using dichloro(tripheny1)phosphorane generated from hexachloroethane (97).88 The major problem of racemization has largely been overcome in several cases, and the method has been applied to an immobilized Ph,P-system, as in Scheme 1l.8e Iminophosphoranes (1 1 1) may be prepared as shown. 7 6 The bis(thiocyanato)phosphorane (112) has been made,89and used in the preparation of alkyl thiocyanates (1 13)89and of thioureas (1 14).90 0

ii

Phg + Cl,ccccl,

99%

CH,OH

U C H 2 O H (1071 84 85

-

98% WCHZCi

G. S. Harris, I. M. Mack, and J. S. McKechnie, J. Fluorine Chem., 1978, 11, 481. B. E. Abalonin, Yu. F. Gatilov, and Z. M. Izmailova, J. Gen. Chem. (U.S.S.R.), 1977,47, 569.

87 88

89

R. M. Magid, 0. S. Fruchey, and W. L. Johnson, Tetrahedron Letters, 1977, 2999. S. J. Cristol, R. M. Strom, and D. P. Stull, J. Org. Chem., 1978, 43, 1150. R. Appel and L. Willms, Chem. Ber., 1977, 110, 3209. Y . Tamura, T. Kawasaki, M. Adachi, M. Tanio, and Y . Kita, Tetrahedron Letters, 1977, 4417.

90

Y.Tamura, M. Adachi, T Kawasaki, and Y . Kita, Tetrahedron Letters, 1978, 1753.

72


y c1

OH (108) (W-(-)

94%

mclWCl (90%retention)

Ph3p+CC4*

b

OH (10%

major product (80%)

%

Ph,P + ccl,

\

b %\ l

\

/

/

\

(110)

FYI-

major product (75%)

R2 R2 R'NHCHC0,H + H,NCHC0,R3

(> 90%)

R'NHCHCONHCHC0,R3 RZ R2 HSiCl,

Scheme 11

R,P + HN(SiMe3, + C13CCCl, --+ R,P=NSiMe,

+

R3iNHz C1-

(111)

Ph,P

+

(SCN),

- 40°C

/

RSCN

48-10070

(113)

if R is primary a:kyI

Ph,P(SCN),

H,NCNR, (114)

60-100%


73

Dichlorophosphoranes (1 15) may be reduced by hydrogen gas.91 An efficient deoxygenation of sulphoxides to sulphides (116) may well occur via a diiodophosphorane.O * Treatment of the fluorophosphoranes (1 17) with amines leads to very complex mixtures, and not to simple exchange The reactions of phosphorus pentachloride with urea (118) are very complex.04 Additional reactions of phosphorus pentachloride with enolphosphates (1 19)eB and with a-methylstyrene (120)96have been described.

R,PCl,

+

H,

3

R3P.HC1

+ HCl

(115) Ph3P

+ I, + R,SO

* R2S

70-95%

(116) HnPFs - n

(117) n = 1 or 2

0

H,C

II II PhCCH,PCI,

80%

+ 0

II

PhC(Me)=CHPC&

91 92

93 94

95 96

10%

M. Masaki and N. Kakeya, Angew. Chem. Internat. Edn., 1977, 16, 552. G. A. Olah, B. G. B. Gupta, and S. C. Narang, Synthesis, 1978, 137. A. H. Cowley, P. J. Wisian, and M. Sanchez, Inorg. Chem., 1977,16, 1451. L. Riesel and M. Henkel, Z . anorg. Chem., 1977,435,268. V. G. Rozinov, V. E. Kolbina, V. 1. Glukhikh, and Yu. A. Klimov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1746. V. V. Rybkina, V. G. Rozinov, V. I. Glukhikh, and L. A. Larionova, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1524.

74


Miscellaneous.-A paper by Strichg7is the only sign of what was once a major industry in the world of theoretical chemistry. This paper describes an ab initio SCF MO study of the intramolecular rearrangement modes for trifluoro,~~ of a sequence phosphorane (121 ;Y = H). The multi-step M , - p a t h ~ a yconsisting of BPR steps, has been found to have the lowest barrier height (9.1 k 0.5 kcal mol-l). The same pathway has been used to rationalize the change in heights across the series Y = F < CF, < CI < Br < H < Me? Ph- NMe,.9 Modes of rearrangement in the anions (122) have been The solvent dependence of the n.m.r. shift of (123) has been ascribed to variable degrees of ionization, according to the dielectric constant of each solvent.lOO

A. Strich. Znorg. Chem., 1978, 17, 942. J. I. Musher, J Amer. Chem. SOC.,1972, 94, 5662. g9 J. I. Musher, Phosphorus and Sulfur, 1977, 3, 247. lo0 V. I. Dmitriev, L. M. Sergienko, G. V. Ratovskii, B. V. Timokhin, and V. I. Glukhikh, J. Gen. Chern. (U.S.S.R.), 1977, 47, 1526. 97

98

Phosphine Oxides and Sulphides BY J. A. MILLER

1 Introduction There has been a big increase in synthetic work in the phosphine oxide field, and two stimulae are apparent behind this trend. The first is the interest in new phosphorus heterocycles which may be of value to the pharmaceutical industry. The second is the potential usefulness of phosphine oxide handles in general organic synthesis. It will be seen that the subdivision of this chapter into ‘preparation’ and ‘reaction’ sections is rather arbitrary, since several of the more interesting structures have been prepared from simpler phosphine oxides.

2 Preparation Many phosphine oxides are included in a review of fused polycyclic phosphorus heterocycles. Via A1kenes.-The diene-chlorophosphine cycloaddition has been exploited very elegantly to provide a route to medium-ring phosphine oxides. Typically, oxides of structure (1) have been prepared, and treatment with acid gives the internal aldol product (2).2 Imp1oved quenching conditions, using methanol, have been reported to give the oxides (3) and (4), and the problems of separate preparations of these have

0 n=4 heat (R = OH) 01:

HC(R = Me)

(1) n = 2, 3, or 4 1 2

S. D. Venkataramu, G. D. Macdonell, W. R. Purdum, M. El-Deek, and K. D. Berlin, Chem. Reo., 1977, 77, 121. L. D. Quin and E. C. Middlemas, J . Amer. Chem. SOC.,1977,99, 8370.

75


76

been les~ened.~ The related oxides (5) and (6) are formed as diastereoisomeric mixtures, and this has been ascribed to pseudorotation of quinquecovalent intermediates (Scheme l).*

(3)

(4)

(6)

(5) Reagents: i, PhPClz; ii, MeOH; iii, PhPBrz; iv, Mg; v, Cla; vi, HzO

Scheme 1

The oxides (7)-(12) have been prepared, as shown in Scheme Z5-' Once again it is clear that the product type depends on reaction conditions, and on alkene structure, due largely to the facility for rearrangement via carbonium intermediates. Mechanistic details of some of these reactions appear in Chapter 3. Via Carbony1 Compounds.-Incorporation of phosphorus as the heteroatom into sugar-like structures has been achieved for the oxides (13) and (14).8The method essentially involves generation of the free aldehyde form of the sugar precursors in situ, trapping with a secondary phosphine oxide, and then acetylation of the. a-hydroxyphosphine oxide thus formed. 0

I

PhP- CHMe H

c

(ii) AGO, pyridine

OAc

4

*

K. Moedritzer and R. E. Miller, Synth. React. Inorg. Metal-Org. Chem., 1978, C8, 167. L. D. Quin and R. C. Stocks, Phosphorus and Surfitr, 1977, 3, 151. E. Vilkas, M. Vilkas, D. Joniaux, and C. Pascard-Billy, J.C.S. Chem. Comm.,1978, 125. M. Rotem and Y. Kashman, Tetrahedron Letters, 1978, 63. A. Rudi and Y. Kashman, Tetrahedron Letters, 1978, 2209. M. Yamashita, Y. Nakatsukasa, M. Yoshikane, H. Yoshida, T. Ogata, and S. Inokawa, Carbuhyrlrate Res., 1977,59, C12.

Phosphine Oxides and Subhides

77

Me

ii, iii

Me

(8) 20%

(9) 25%

Ph

PhP

OH (11) 60%

E,ii

y-/\

Ph

0

Reagents: i, MePCla, AlCla; ii, PhC1z .AICIa; iii, HC0a2-(aq.); iv, PhPBra -AIBra(HzO doped)

Scheme 2

O\\ (3) AGO, (i) aq.pyridine IICl

=

,Ph

*O ' *\*A. (14)

A series of acyl anion equivalents has been prepared by Evans' group, and the oxides (15) are among the e x a r n p l e ~Both . ~ ~ ~have ~ @)-geometry, and this has

Q

D. A. Evans, K. M. Hurst, L. K. Truesdale. and J. M. Takacs, Tetmhedron Letters, 1977, 2495. D. A. Evans, K. M. Hurst, and J. M. Takacs, J . Amer. Chern. SOC.,1978, 100, 3467.

78


been rationalized by suggesting that the phosphorane (16) is an intermediate.gl10 The nearly exclusive formation of only one diastereoisomer of the oxides (17) has been ascribed to similar factors.ll The oxides (17) are surprisingly stable, and the formation of the less stable (kinetic) isomer is believed to be determined by the relative stability of the diastereoisomeric phosphorane intermediates (1 8).11 Michler’s ketone (19) reacts with the anion of diethylphosphine oxide to form the oxide (20).12 This type of reductive addition to an electron-rich carbonyl group has been observed previo~s1y.l~ An even more puzzling redox process is that leading to the oxide (21), and its phosphinate isomer (22), isolated by Pudovik’s group.l* The oxides (23),16 (24), and (25)16 have been prepared as shown. Other aspects of these reactions are discussed in Chapter 3. Via Phosphsrus(1v) Chlorides.-Displacement of chloride by various types of carbanion continues to be useful in synthesis,17-I9 as illustrated in the selected examples (Scheme 3). The oxide (26)17 has been resolved, while the dienylphosphonates (27)18 may be of value in general synthesis.

Ph,PO M e

1 R

(16 )

= Me

100%

0

PhCHO + MeOPFh,

AcOH

F+

___f

OMe

11 12

P&PCHOCHOAc

I I

Ph Ph

J. A. Miller and D. Stewart, J.C.S. Pcrkin I , 1977, 2416. N. N. Rychkov, A. G . Shemya-Tenkov, A. I. Bokanov, and B. I . Stepanov, J . Gen. Chem. (U.S.S.R.), 1977, 47, 2026. 13 R. S. Davidson, R. A. Sheldon, and S . Trippett, J . Chem. SOC. ( C ) , 1967, 1547. 14 A. N. Pudovik, G. U. Romanov, and V. M. Pozhidaev, J. Gen. Chem. (U.S.S.R.),1977,47, 1745. 1 5 A. 1. Razumov, P. A. Gurevich, S. Kh. Nurtdinov, S . A. Muslimov, and L. M . Tyl’nova, J. Gen. Chern. (U.S.S.R.), 1977, 47, 1301. l 6 S. Kh. Nurtdinov, N. M. Isrnagilova, T. V. Zykova, R. A. Salakhutdinov, and V. S. Tsivunin, J . Gen. Chern. (U.S.S.R.), 1977, 47, 1158. 1 7 R. Luckenbach and K. Lorenz, Z. Naturforsch., 1977, 32b, 1038. N. G. Kuzina, L. N. Mashlyakovskii, M. B. Simanovich, and B. I. Ionin, J. Gen. Chern. (U.S.S.R.), 1977, 47, 1537. A. R. Acharekar, V. N. Gogte, and B. D. Tilak, Indian J. Chem., Sect. B., 1977, 15, 408.

Phosphine Oxides and Sulphides

79

(20) 46%

(1 9 )

c1 c1 0 0

O

+

PbPH

*:?:

c1 c1

c1

O

P b ! G O H

c1

+ P h . &G

I

c1

c1c1

c1

c1 c1

(21) 46%

(22) 37% 0

li

CH(Cl)PPh, PhpcI + H

=c

Et,PCI + 0

(CH,),

H (23) 71%

0

'

Or

*

and/or Et2P (24)

(25)

n = 0, 65%

n = 1, 55%

0

0 H2C=CH-C(R')=CHPC4

II

'"

+.

HzC=CH-C(R')=CHPR22 (27) R' = R' = Me R1 = H, R2 = Me

ll

35% 20%

(28) Reagents: i, PhCHzP(0)ClEt; ii, HC1; iii, NaOH; iv, R2MgX;v, BuLi (excess); vi, EtOP(0)Clz

Scheme 3


80

P-P Compounds via P(0) Anions.-The group led by Foss and Lutsenko have continued their study of the phosphorus(II1)-phosphorus(1v) isomerizations. O - 2 2 The preparations are generally displacement reactions, as shown in Scheme 4, and the product type depends upon the ligands R1, R2, and X, and upon the reaction conditions. Electron donation from the group R1is believed to be the most important single factor enhancing the oxide stability.

X

X

I1 R1,P- + RZ,PCl (X = 0 or S)

It

I1

R',PPRZ,

x x

= s; R' = B2= primary alkyl stable = 0;R' = R2 = NMe, stable (20 "C)

R',PXPR22

X = S; R' = R2 = But stable X = 0; R' = R2 = OMe stable Scheme 4

In systems where the ligands R1and R2 are different, the stable arrangement has the P=O group with a phosphonate structure, i.e. structure (29) is preferred. The thermodynamics and structure assignments in such systems have been discussed. 0

II R,PP(OMe),

0

* R,POP(OMe),

II

R,PP(OMe), (29)

Miscellaneous Syntheses.-A number of routine preparations are illustrated by compounds (30),26(31),26 and (32) and (33).27 The ratio of isomers (30) is controlled by the t-butyl group. 2 6 P-Halogeno-ethers are notoriously poor alkylating agents, and forcing conditions lead to the bis-oxide (33), believed to be formed as shown. Dimethyl selenoxide (34) looks like being the reagent of choice for the exchange of oxygen for other ligands at phosphorus(1v) centres.28This process is highly stereoselective, although the absolute stereochemistry varies from acyclic systems (- 100% inversion) to cyclic systems (phosphorinans retain stereoV. L. FOSS, V. A. Solodenko, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1976,46,2280. V. L. FOSS, Yu. A. Veits, P. L. Kukhmisterov, V. A. Solodenko, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1977, 47, 437. 22 V. L. Foss, Yu. A. Veits, N. V. Lukashev, Yu. E. Tsvetkov, and I. F. Lutsenko, J . Gen. Chem. (U.S.S.R.), 1977, 47, 439. 2 3 V. L. FOSS, Yu. A. Veits, and I. F. Lutsenko, Phosphorics and Sulfur, 1977, 3, 299. 24 C. Glidewell, J. Organometallic Chem., 1977, 142, 171. 25 J.-P. Battioni and W. Chodkiewicz, Bull. SOC.chim. France, 1977, 320. 26 G. D.Macdonell, K. D. Berlin, S. E. Ealick, and D. Van der Helm, Phosphorus and Sulfur, 1978, 4, 187. 27 N. G. Osipenko and E. N. Tsvetkov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 2390. 28 M. Mikolajczyk and J. Luczak, J. Org. Chem., 1978, 43, 2132. 20

21


81 0-PPb

Ph 0

0

It BqP'

M+

CICH,CH,OMe

II

Bu,PCH,CH,OMe (32) 18% when M

(33) 78%

chemistry). The same reagent (34) will donate oxygen to phosphorus(rr1) species stereospecifically,2sas shown in Scheme 5. Me,Se(O) (34)

R,P=X

(X = S or

Se)

: R,P=O

MeMO)

: (34)

RQ

(inverted in acyclic series)

Scheme 5

S

NSiMe,

II ll Me,P-PMe,

s o

11 I1

-%Me,P-PMe,

-% Me,PPMe, + Me,POPMe, + Me,POPMe,

(35)

II II

0 s

II I1

s s

The diphosphine derivative (35) has been prepared and found to disproportionate at high temperature^.^^ The disulphide (36) has been shown to have 29

R. Appel and R.Milker, Chem. Ber., 1977, 110,3201.


82

trans-geometry.30Standard oxidation procedures have been used to prepare the oxides (37)31and (38).32 0

(38)

3 Reactions Reaction at the P=X Group.-The spectacular work of Hellwinkel's group has been published in detail,33and provides many examples of intramolecular addition to the P-0 group, to produce bicyclo-, spiro-, and spirobicyclophosphoranes: see Scheme 6 Extensive physical data are provided on the phosphorane products.

/--OR &-p"p'

-0 EtOH + H+ (R = THP) Heat(RnH) or

LOR

-0

(i) KOH,heat

IHht

0 Scheme 6 J. D. Lee, J. Organometallic Chem., 1977, 137, 193. a1 G. R. Newkome and D. C. Hager, J. Org. Chem., 1978,43,947. sa E. S. Kozlov, V. I. Tovstenko, and L. N. Markovskii, J . Gen. Chem. (U.S.S.R.), 1977, 47, 869. s3

D. Hellwinkel and W. Krapp, Chem. Ber., 1978, 111, 13.

Pliosphine Oxides and Sulpliides

83

Hydrolysis reactions of tris(heteroary1)phosphine oxides (39) have been studied, and rate constants are found to be related to the heteroatom, i.e. X = 0 > S > NMe. 3 4 Interconversion of phosphorus(1v) derivatives via selenoxides has been reported for dibenzyl selenoxide (40),36and for dimethyl selenoxide (34)28 (see also Section 2). The exchange of selenium36 and of between phosphorus(1v) and phosphorus(Ir1) centres has been investigated. For the general structure (41), the rate falls in going from n = 2 to n = 1, and also falls across the series X = Te > Se+ S.36

(PhCH,),SeO

+

R3P=Se

d

R3P=0

90%

(40)

x II

x

I1

PhP(CH,),PPh,

+ R3P --+

R3P=X

(41)

Details have appeared of the reactions of tosyl azide or of tosyl isocyanate or analogues with phosphines or phosphine The overall stereochemistry (at phosphorus) depends on the acyclic or cyclic nature of the starting oxide. This is rationalized by the different sequences outlined in Scheme 7, in which the Me,CI I

0

II

MeCH

I

R', = Me,(:-

OCNTs

IQ',PR2 L

R' = alkyl OCNTs

Retained configuration Scheme 7 34

35 36

37 38

39

D. W. Allen, B. G. Hutley, and M. T. J. Mellor, J.C.S. Perkin I f , 1977, 1705. K. Sakaki and S . Oae, Chem. Letters, 1977, 1003. D. H. Brown, R. J. Cross, and R. Keat, J.C.S. Chem. Comm., 1977, 708. D. H. Brown, R. J. Cross, and D. Millington, J. Organometallic Chem., 1977, 125, 219. C . R. Hall and D. J. H. Smith, J.C.S. Perkin 11, 1977, 1373. C. R. Hall, D. J. H. Smith, and P. Watts, J.C.S. Perkin 11, 1977, 1379.

4

84


stereochemistry of the phosphetan series is controlled by the stability of the spirophosphorane (hence only 1:1 adduct), and by Ra being the only favourable pivot for pseudorotation in the spirophosphorane (42). Phosphorus pentasulphide reacts with the phosphine oxide (43) as shown.*O Triphenylphosphine sulphide (44) is an intermediate in a potentially useful preparation of triphenylpho~phine.~~ Gaseous reagents may be used to deoxygenate oxides (45) in two

Me&ph

l lP&> 0"C

M

e

A

+""h I I

OH

+

0 +

s

AIC1,

>-

Ph 'Ph

14%

35%

(4 3)

Pcl,

s//

s/ \ Ph Ph

OR 'Ph

1

PhT

% :a& ;"

~

(44) 71%

Ph,P

89%

0

I1

RQ + C4 + CO

--+

RQCI,

-% RJ' +

HC1

(45)

Deoxygenation of arsine oxides (46) to give arsenic(v) dihalides has been the s ~ Chapter ~ ~ ~ ~3). Other reactions46- 4 8 of arsenic(1v) subject of two s t ~ d i e (see compounds are presented in Scheme 8, but they do not seem to add much to previous work. The reactions of a range of arsine oxides (46) with n-butyl iodide have been studied by kinetics. Thus AS* is approximately 50cal deg-l mol-l, and the reaction is faster in polar solvents, and is held to be of sN2 type.4g R,As=O

+ BuI

+

__*.

R,AsOBu I'

(46)

4a

F. Mathey, Tetrahedron Letters, 1978, 133. G. A. Olah and D. Hehemann, J. Org. Chem., 1977,42,2190. M. Masaki and N. Kakeya, Angew. Chem. Internat. Edn., 1977, 16, 552. G. S. Harris, I. M. Mack, and J. S. McKechnie, J. Fluorine Chem., 1978, 11, 481. B. E. Abalonin, Yu. F. Gatilov, and Z. M. Izmailova, J, Gen. Chem. (U.S.S.R.), 1977, 47,

46

L. B. lonov,A. P. Korovyakov, and S. S. Molodtsov, J. Gen. Chem. (U.S.S.R.), 1976, 46,

40 41

569.

2441. It3

B. E. Abalonin, Yu. F. Gatilov, and G. 1. Vasilenko, J. Gen. Chem. (U.S.S.R.), 1978, 46, 2608.

47

B. E.Abalonin, Yu. F. Gatilov, and G. I. Vasilenko, J . Gen. Chem. (U.S.S.R.), 1976, 46, 2611.

T. Kauffmann, R. Joussen, and A. Woltermann, Angew. Chem. Internat. Edn., 1977, 16, 709. 4Q

B. D. Chcrnokal'skii and L. A. Vorob'eva, J . Gen. Chem. (U.S.S.R.), 1977, 47, 969.

Phosphine Oxides and Sirlphides R&=O

I EtAs=S

I

R~AsX,

R = Ph, X = F or R = alkyl, X = C1

(46)

Ph

85

HX

0

11 + ClCOMe

(Ref.43) (Ref. 44)

Ph

25OC I__)

I 1 Me

EtAbC0,Me C1'

Me

(Ref. 45)

Et

Me

\

\

Ph/AsSCo2Me

+

Ph/AsSCo2Me

5 3%

42%

S

II

R*,AsR2 + 2R3COCl -+

0

I1 P&AsCH,R

R',As(C4)R2

11 /E PkAsCH

(Refs. 4 6 , 4 7 )

E

0

i,ii

+ (RT0)S

iii-v --+

I

RCH-N

(Ref.48)

R ' Reagents: i, base; ii, electrophile E; iii, LiAlHd; iv, Br2; v, nucleophile N

Scheme 8

Reactions of the Side-chain.-Pudovik and co-workers have published an extensive kinetic study of the reactions of azido-arenes (47) with l-alkynylphosphoryl compounds (48).6 O These are regiospecific, and in the propl-ynyl series (48; R=Me) the order of reactivity is X=Ph>Et>OEt.60 The authors interpret this, and other substituent effects, in terms of a concerted four-centre process.ti

Cycloaddition of vinyl(dipheny1)phosphine oxide to diazomethane is also regiospecific, and the initial product has been converted into a l-carbamoyl50

N. G. Khusainova, Z. A. Bredikhina, E. A. Berdnikov, A. I. Konovalov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1339.

86


A2-pyrazoline(49).51 Details have appealed of the formation of the regiomeric 3H-pyrazoles (50) and (51) from phenyldiaz~methane.~~ The 3H-pyrazoles rearrange on heating, to give 1H-pyrazoles. 0\c/NHAr

0

I1

N-NH

P\PCH=-CH,

N-N

1

ArN=C=O

+ H,C-~N

(49)

The Regitz group has also described, in detail, the trapping of photolysis products of a-diazoalkylphosphine (52). Thus the intermediates are carbene-like, and are shown to be trapped by benzophenone to give (53), or to dimerize to give (54) and (55).S3 Heterocyclic nitrones, such as (56), undergo 1,3-dipolar addition reactions with stabilized ylides, to give enamines.6 4 Ph Ph

I1 P&PC(N,)COPh

0\p-7

7 ]

0

0

dimerization

-% PhP-GCPh

(5 2)

p

Phl'

0

Ph

0 P j0 -\/ Ph Ph (54)

o>f$Ph

f

Ph O X Ph 0 (5 3)

Ph

51

52

63 54

J. Gloede, K. H. Schand, and H. Gross, 2. Chem., 1978, 18, 18. H. Heydt and M. Regitz, Annalen, 1977, 1766. M. Regitz, W. Illger, and G . Maas, Chem. Ber., 1978, 111, 705. S. Zbaida and E. Breuer. Tetrahedron. 1978. 34. 1241.


( 5 6)

87

‘0

+

+

0

ll Ph,P -6 H R

0

I1

PbP-0-

(R = CN or C0,Et)

An investigation into the conjugate addition reactions of vinyldiphenylphosphine oxide (57) has revealedss an inconsistent pattern: see Scheme 9. The corresponding sulphide does add methoxide ion.s6 The oxide (58) has now been postulated as a likely intermediate on the pathway to the fluoranthene (59).s6An alternative intermolecular process is ruled out, because of the failure of a crossover experiment with 1,2,5-tri-Cp-tolyl)phosphole(60). s6 a-Phenylthioalkylphosphineoxides (61) have been prepared as shown, and used in Wittig-Horner reactions to produce vinyl sulphides (62). This sequence has few limitations in reactions with aldehydes, but steric problems arise for ketones. Since the sulphides (62) may be regarded as ketone precursors, the anions of (61) are acyl-anion equivalent^.^^ Much of the earlier work on diphenylphosphinoyl migration has been summarized in a paper which pays particular attention to the structural limitations 0

0

ll PbPC I1(Br)CH,OH

.

ii . _+

I1

Ph,PCH(OH)CH,OMe

58%

X

1

I1

(57)

(

PhjCHI2 96%

(

--% p J c H 2 cH2J2

Ph,PCH=CH,

\

79%

Ph2PCH,C H,OM e 93%

(X = 0 unless stated)

Reagents: i, N-bromoacetamide; ii, MeO-; iii, HO-; iv, HOOScheme 9 55

57

S. R. Postle and G. H. Whitham, J.C.S. Perkin I , 1977, 2084. J. I. G. Cadogan, A. G. Rowley, and N. H. Wilson, Annalen, 1978, 74. J. I. Grayson and S. Warren, J.C.S. Perkin I, 1977, 2263.


88

Ar 0 /

+

of the rearrangement. The resultant allylic oxides (63) generally undergo Wittig-Horner reaction at the a-carbon, although there are ex~eptions.~~ The oxide (64) has been synthesi~ed.~~ A rare example of ylide methylation on phosphoryl oxygen leads to the phosphorane (65).s0 0

II Ph,PC H (R')C H, R2

(i) base (ii) >C=O 9-

(iii) H'

I R'CH=C--R1

,c=o ' >->i,€iR2

(i) base

-C-PPh (ii)

/

R'

(63) 5*

59 60

A. H. Davidson, C. Earnshaw, J. I. Grayson, and S. Warren, J.C.S. Perkin I, 1977, 1452. A. I. Razumov, P. A. Gurevich, S. A. Muslimov, and V. G. Usacheva, J . Gen. Chem. (U.S.S.R.), 1976, 46, 2279. 0.I. Kolodyazhnyi, J. Gen. Chem. (U.S.S.R.), 1976, 46, 2285.

Phosphine Oxides and Srr@hides

89 0

II

- o---j/::t

+ Ph,PCH,CO,Et 0 I1

‘

H

N

H (64) 40%

0

OMe

Acetyldiphenylphosphine oxide (66) has succumbed again, this time to the Arbusov route.61It has been shown to be a potent acylating agent, and a study of its methanolysis reveals the ease of dissociation of the initial product, the bisoxide (67). On storage, (66) dimerizes to give (68):61see Scheme 10. 0 AcCl + PhPOMe -+- MeCl

I1

f

Ph,PAc

0

ll

PkPH + MeOAc

\

Scheme 10

The oxides (69) have been prepared chiral,s2 and are found to be stable [compare (66)]. Cram’s Rule has been used to explain the preferred mode of Grignard addition to (69; R = Ph), provided that the P=O and C-0 groups are kept cisoid.62As indicated in Scheme 11, the initial reaction product is predominantly erythro- (kinetic control), but warming in the presence of acetophenone gives the threo-isomer (thermodynamiccontrol). Confirmatory evidence for the facile reversal of C=O addition comes from reactions of (70).62 Work in the phosphorin-10-one 5-oxide field continues, with steric considerations prominent in Granoth’s papers:6s$64 see Scheme 12 for a selection. In view of these results, the failure of (71; R = Me or Ph) to undergo Grignard reactions 61 62

6s 64

J. A. Miller and D. Stewart, J.C.S. Perkin I, 1977, 1898. S. Musierowicz and W. T. W. Waszkuc, Phosphorus and Suljiur, 1977, 3, 345. Y. Segall, R. Alkabets, and I. Granoth, J. Chem. Res. ( S ) , 1977, 3541. I. Granoth, Y. Segall, and H. Leader, J.C.S. Perkin I , 1978, 465.


90 0

Et,

0

0

II I1

i, ii R=Phf

“P-C-R Ph‘

Ef.\,ll Ph‘p-c”

(69) R = Me or Ph

OH

I

,Me ’Ph

erythro- (85%)

erythro- (70%) + threo- (30%) Reagents: i, MeMgI; ii, H20; iii, heat, PhCOMe

Scheme 11

Me

\

ref. 63 i-iii

i

ref. 65

no reaction Reagents: i, MeMgI; ii, CFsC02H; iii, LiAlH4; iv, HNs; v, PhMgBr or PhCHzMgCl

Scheme 12 (part)

Phosphine Oxides and $&hides

91

?H no reaction

I

Me

I

0

Me

Me

Reagents: vi, NaH2Al(OCaH40Me)a; vii, LiA1H(OBut)3

Scheme 12 (cont.)

at the C=O group is s~rprising.~~ The phosphine oxides (72)--(74) have been prepared.* 0 Ph2!CH,0

'

(72) -50%

0

ll Ph2PCH2Cl

It

Ph,P

+

Licp

0 P & H , oI

[CpFe(CO),I,

: B i' 49

4 Structural and Physical Properties

Crystal structures have been reported on compounds (75),67 (76),68 and (77).6@ K. A. Petrov, V. A. Chauzov, and N. Yu. Mal'kevich, J. Gen. Chem. (U.S.S.R.), 1977,47, 2299. C. Charrier and F. Mathey, Tetrahedron Letters, 1978, 2407. 67 S. Hoehne, H. Leseicki, H.-D. Ebert, E. Lindner, and J. Straehle, 2. Naturforsch., 1977, 32b, 707. 68 K. A. Kerr, P. M. Boorman, B. S. Misener, and J. G. Van-Roode, Canad. J. Chem., 1977, 55, 3081. 139 Z . Galdecki, M. L. Glowka, J. Michalski, A, Okruszek, and W. J. Stec, Acta. Cryst., 1977, B33,2322. 65

66

92


Electron-diffraction O and liquid-crystal n.m.r. 71 studies of the trimethylphosphine derivatives (78) have been presented. Vibrational spectra for the and for the oxides (81)74 have appeared. disulphides (79)72and The 13Cn.m.r. spectra of tertiary phosphine sulphides (82)76and of l-methylphosphorinan l-oxides and l-sulphides (83)76 have been described. The lH n.m.r. spectrum of 1-methyl-A3-phospholen1-oxide (84) is much more complex than previous data would suggest. The tervalent phosphorus structure (85) has been confirmed by a combination of n.m.r. and m.c.d. studies.78 Electron-impact studies on the oxides (86) have revealed ring-cleavage and rearrangement p r o c e ~ s e s .A~ ~range of species have been identified in 6oCo y-irradiated solutions of the triphenylphosphine and triphenylarsine derivatives (87).*O 0

CF, 0

Me

II I II PbP-CHOPPh,

//P=S

\

Pr "-P=Se

/

Ph (75)

(76)

(7 7) 7) ( x a P = o

Me,P =X

(78) X = 0,S, or Se

(79) R = Me (80) R = Et, Prn, or Bun

(81)

0

R,P =S (83) X = 0 or S

(82)

R' or R2 = Me

/ \ Me

0

(84)

0

Ph,M=X (86) n = 1, 2, or 3

70 71 73 73 74 75 76 77 78 79

(87) M = P or As when X = 0 M = P when X = S or S e

E. J. Jacob and S . Samdal, J. Amer. Chem. Soc., 1977,99, 5656. J. P. Albrand, A. Cogne, and J. B. Robert, Chem. Phys. Letters, 1977, 48, 524. G. P. McQuillan and I. A. Oxton, Spectrochim. Acta, 1977, 33A, 233. G. P. McQuillan and I. A. Oxton, Spectrochim. Acta, 1978, MA, 33. J. M. Casper and E. E. Remsen, Spectrochim. Acra, 1978, MA,1. S. R. Postle, Phosphorus and SuVur, 1977, 3, 269. L. D. Quin and S . 0. Lee, J. Org. Chem., 1978,43, 1424. K. Moedritzer and P. A. Berger, J. Org. Chem., 1977,42,2023. J . Wirlishie and P. Dagnac, Rev. Chim. rninkrale, 1977, 14, 355. C. W. Koch, D . H. Eargle, and G. L. Kenyon, Org. Mass. Spectrometry, 1977, 12, 624. G . W. Eastland and M. C. R. Symons, J.C.S. Perkin I t , 1977, 833.

93


Measurements of the basicity of the oxides (88) and (89; n = 2) reveal little difference between them, and suggest that constraint into a bicyclic system is, of itself, not important to basicity.81 However, the oxide (89; n = l ) is much less basic, and the authors ascribe this to angle strain, which might be expected to increase the s-character of the phosphorus lone-pair. Extensive study has been made of the nature of the complexes of tertiary phosphines and hydrogen halides.saThese are distillable 1 :1 complexes and have been assigned a protontransfer structure The molecular structure of (90; R=Ph) has been and the protonation of tris(trimethylsily1)methylphosphine oxide (38) in solution has been reported.84 The remainder of this year's literature centres on the related fields of acid extractants and metal extractants, in which phosphine oxides have become pre-eminent in recent years. In the former category, tri-n-octylphosphine oxide (91) has been used to extract hydrogen halidess6 and carboxylic acid^.^^^^^ Extraction of perchloric acid by the bis-oxides (92) in halocarbon solvents has been described.88 The oxide (91) has also been used to extract a range of metal ions.89--06 Other phosphine derivatives which have found application are the oxide (93), derived from pyruvic the oxides (94)98and (95),g9and the bisphosphine derivative (96).loo

R,P=O (88) R = Me or Bun

(89) n = 1 or 2

D. S. Milbrath, J. G. Verkade, G. L. Kenyon, and D. H. Eargle, J. Amer. Chem. SOC.,1978, 100, 3167. V. V. Malovik, V. Ya. Semenii, V. N. Zavatskii, I. E. Boldeskul, N. N. Kalibabchuk, and E. V. Ryl'tsev, J. Gen. Chem. (U.S.S.R.), 1977, 47, 933. as H. J. Haupt, F. Huber, C. Kreuger, H. Preut, and D. Thierbach, 2. anorg Chem., 1977, 436, 229. 84 N. K. Skvortsov, B. I. Ionin, and V. 0. Reikhsfel'd, J. Gen. Chem. (U.S.S.R.), 1977,47, 655. 85 M. Niitsu and T. Sekine, Bull. Chem. SOC. Japan, 1977, 50, 1015. 06 M. Konstantinova, S. Mareva, and N. Iordanov, A w l y t . Chim. Acta, 1977, 90, 185. a7 M. Niitsu and T . Sekine, Bull. Chem. SOC.Japan, 1978, 51, 705. 88 A. M. Rozen, Z. I. Nikolotova, N. A. Kartasheva, and A. S . Bol'shakova,Zhur. neorg. Khim., 1978, 23, 761. 89 T. Yanagi, H. Mukai, and M. Shinagawa, Bunseki Kagaku, 1977,26, 313. 90 M. Konstantinova, Analyt. Chim. Acta, 1977, 90, 185. 91 V. K. Manchanda, K. Chander, N. P. Singh, and G. M. Nair, J. Inorg. Nuclear Chem., 1977,39, 1039. 92 R. Murai, S. Iwahori, and T. Sekine, Bull. Chem. SOC.Japan, 1977, 50, 1315. 93 T. Sekine, S. Iwahori, S. Johnson, and R. Murai, J. Inorg. Nuclear Chem., 1977,39,1092. 94 F. T. Bunus, V. C. Domocos, and P . Dumitrescu, J. Inorg. Nuclear Chem., 1978,40,117. Q5 G. J. De-Jong and U. A. Brinkman, 2.analyt. Chem., 1978,289,358. 96 T . Sekine, R. Murai, K. Takahashi, and S . Iwahori, Bull. Chem. SOC.Japan, 1977,50,3415. 97 A. K. Miftakhova, L.Dozsa, and M. T. Beck, Acta Chim. Acad. Sci. Hung., 1977,92,379. 9s G . Anderegg, 2.Naturforsch., 1977, 32b, 547. 99 P. I. Artyukhin, M. S. Sukhov, B. M.Shavinskii, and Z. N. Mironova, Izvest. Sibirsk. Otdel. Akad. Nauk. S.S.S.R.,1977, 84. 100 V. G. Dashevskii, A. P. Baranov, T. Ya. Medved, and M. I. Kabachnik, Teor. i eksp. Khim., 1977,13, 340. 81

82

94


Equilibrium and structural studies have also been reported on metal salt complexes of simple oxides1O1rl O 2 and ~ u l p h i d e s ~and ~ ~of , ~some ~ * bis-phosphine derivatives.lo5 R, $OH.

- -x-

(Me,SiC HJ3 P= 0

(90) X = halogen

(38)

0

(n-C& ,),P=O

(92)

(91)

0

OH

II 1 ByP-CCO,H I iie (93)

0

It It R,PCH,CH,PR,

[

“I

(HO),PCH, ,P=O

(94) 0

(ROCH,), P-0 (95)

lo1

102 103 104 105

0

II II Me,PCH,PM e, (9 6)

J. G. Du-Preez,B. J. Gellatly, and M. L. Gibson, J.C.S.Dalton, 1977, 1062. C. Perchard. J. Angenault, and J. C. Couturier, Spectrochim. Acru, 1977, 33A, 793. S. S. Sandhu and T. Singh, Indian J. Chem., 1977, ISA, 829. S. S. Sandhu and T. Singh, Indian J. Chem., 1977, 15A, 831. S. S. Sandhu and T. Singh, J. Inorg. Nuclear Chem., 1977,39, 1086.

c

Y

Tervalent Phosphorus Acids BY B.

J. WALKER

1 Phosphorous Acid and its Derivatives Nucleophilic Reactions.-Attack on Saturated Carbon. Among numerous reports of the Arbusov reaction are the syntheses of 1,3-di(oxoalkoxyphospha)cycloalkanes (1)l and of halogenofluoromethylphosyhonates(2). The Arbusov reaction gives a variety of products (Scheme 1), of l-bromo-4,4-diethoxybut-2-yne depending on the reaction condition^.^

A general method of preparation for alkoxy-phosphonium salts (3) (the assumed intermediates in the Arbusov reaction) is provided4 by methylation of the corresponding PII1compound with methyl triflate, and these salts are @leO),P

+ BrCH,C=CCH(OEt),

Scheme 1 1 2

3 4

2. S. Novikova, A. A. Prishchenko, and 1. F. Lutsenko, Zhur. obshchei Khim., 1977,47,2636

(Chem. Abs., 1978,88, 89 769). D. J. Burton and R. M. Flynn, J. Fluorine Chem., 1977, 10,329. A. J. Rudinskas, T. L. Hullar, and R. L. Salvador, J. Org. Chem., 1977, 42, 2771. K. S. Colle and E. S. Lewis, J. Org. Chem., 1978, 43, 571.

95

96


relatively stable owing to the low nucleophilicityof the trifluoromethylsulphonate anion;6 the addition of iodide caused rapid decomposition. The salts (3) were also shown to react very rapidly with trimethyl phosphite, and it seems certain that this reaction is a major contributor to the methyl-iodide-catalysedconversion of trimethyl phosphite into phosphonate. R'R'POMe + MeSO,CF,

ct

R1R2i(OMe)MeCF,SO;

(Y

(MeO),P

/ II R1R2PMe+ Me1

II

o

0

R'R'PMe + (MeO),sMe

Attack on Unsaturated Carbon. Numerous reports of the addition of tervalent phosphorus to nitroalkenes have Although simple addition products, e.g. (4), are usually formed, various other reactions also take place, as exemplified by the products from 2-nitro-styrenes (5).7 Further reports of stable oxazaphosphole (6) formation from 1,2-diaryl-l-nitroalkeneshave appeared.* 0

II

(R'O),PCHRZCH,NO, (4)

0

ArCH=CHNO,

+ PbPOR

_.+

II ArCH=CHPPh,

0

0

I1 II + P€+PCHArCH,PPh, + RON0

(5) 0-

Ar CH-CPhNO,

6

E. S. Lewis, B. J. Walker, and N. L. Ziurys, J.C.S. Chem. Comm., 1978,424.

6

e.g. N. M. Vafina and I. M. Shermergorn, Zhur. obshchei Khim., 1977, 47, 2391 (Chem. A h . , 1978,88,23 069); E. A. Borisova, R. D. Gareev, and I. M. Shermergorn, ibid., p. 2622 (Chem. A h . , 1978,88, 89 784); R. D. Gareev, G. M. Loginova, and A. N. Pudovik, ibid., p. 2676 (Chem. Abs., 1978,88,105 472); R. D. Gareev, G. M. Loginova, A. G. Abul'khanov, and A. N. Pudovik, ibid., 1978, 48, 269 (Chem. Abs., 1978, 88, 190 984); R. D. Gareev, A. G. Abul'khanov, and A. N. Pudovik, ibid., p. 276 (Chem. Abs., 1978,88,190 985). H. Teichmann, W. Thierf'elder, E. Schafer, and A. Weigt, Tetrahedron Letters, 1977, 2889. J. I. G. Cadogan, R. A. North, and A. G. Rowley, J. Chem. Res. ( S ) , 1978, 1 ; ( M ) , 1978,

7

*

0178.

Tervalent Phosphorus A cids

97

o-(Methy1eneamino)phenyl phosphites react with a variety of activated double and triple bonds to give apparent [3 21 cycloaddition products (7).# However, rather than an intermediate (8), the authors prefer a mechanism involving initial addition of phosphorus to the multiple bond. A rare example of a stable fiveco-ordinate intermediate (9) in an Arbusov reaction is provided by the reaction of trimethyl phosphite with 1-halogeno-pentafluorocyclobutenes,’* although further heating does lead to the phosphonate. 2-Imidazolidinyl-phosphonates (10) are the reaction products from secondary phosphitesand ethylenetetramines.ll Arylphosphonates have been prepared by the reaction of secondary and tertiary phosphites with activated aryl halides l2 and with unactivated aryl halides, through photostimulation l3 (see also Chapter 11) or catalysis by metal

+

Q 0, + , N - ~ H R ~

P

OR‘

0

A. Schmidpeter, J. H. Weinmaier, and E. Glaser, Angew. Chem. Internat. Edn., 1977, 16, 549.

G. Bauer and G. Hagele, Angew Chem. Internat. Edn., 1977, 16, 477. J. Hocker and R. Merten, Annulen, 1978, 16. L. N. Markovski, G. G. Furin, Yu. G. Shermolovich, and G. G. Yakobson, Izuest. Akad. Nauk S.S.S.R. Ser. khim., 1977, 2839 (Chem. Abs., 1978,88, 105 470). S. Hoz and J. F. Bunnett, J. Amer. Chem. SOC.,1977, 99, 4690; J. F. Bunnett and R. P. Traber, J. Org. Chem., 1978,43, 1867; J. F. Bunnett and S. J. Shafer, ibid., pp. 1873, 1877.


98

i011s.l~ Related phosphonates, e.g. (1l), can be prepared from heteroaromatic cations under mild conditions.16 Successful dimerization of 1-methylpyridinium ion to 1,l'-dimethyl-4,4'bipyridyldi-ium (14) after oxidation has been accomplished by treatment with various secondary phosphite and phosphinite esters.ls Good evidence of (12) is presented for the mechanism shown. A similar coupling of l-methylpyridinium4carboxylate to give (13) also takes place1' The acid-catalysed addition of triethyl phosphite l8 to aldehydes, ketones, diketones, and ketens and the reaction of dialkyl phosphites with cc-diketones l9 have been investigated, The related Abramov reaction of 2,3 :5,6-di-O-isopropylidene-a-D-mannofuranose (15 ) ultimately leads to the 1,2A6-oxaphosphorinan (16) through intramolecular transesterification.20In the absence of strong acids,

X'

(11) Y =

0

II

14

16 16 17

18 19 20

8

8Me

Me

Me

NR, 0,or S. Me

Me

Me

V. P. Kukhar and E. I. Sagina, Zhur. obshchei Khim., 1977,47,1662 (Chem. Abs., 1977,87, 135 666). K. Akiba, K. Ishikawa, and N. Inamoto, Synthesis, 1977, 862. J. G . Carey and J. R. Case, J.C.S. Perkin I, 1977, 2429. J. G . Carey and J. R. Case, J.C.S. Perkin I, 1977, 2431. T. Kh. Gazizov, A. M. Kibardin, V. A. Kharlamov, A. A. Karelov, and A. N. Pudovik, Zhur. obshchei Khim., 1977,47, 2465 (Chem. Abs., 1978,88, 89 766). M. M. Sidky, F. M. Soliman, and A. A. El-Kateb, Indian J. Chem., 1976,14B, 961. J. Thiein, M. Gunther, H. Paulsen, and J. Kopf, Chem. Ber., 1977,110, 3190.

99

Tervalent Phosphorus Acids

phosphinites do not normally react with unactivated benzaldehydes; however, methyl diphenylphosphinite and benzaldehyde in the presence of carboxylic acids are reported to form the adduct (17) almost entirely in one diastereomeric form (see Scheme 2).21

OR'

R'OPPh, PhCHO

?Me

/R~=oM~

BbP-CHPh

/I 0-CH(OC0R')Ph i

0 0 lC/HPh

f)

(17) Reagents: i, R2COzH; ii, PhCHO

Scheme 2

Extensive interest has been shown in the synthesis of 1-siloxyphosphonates, R1=OR), since these compounds can act as equivalents of carbonyl anions. The addition of silyl esters of phosphorus(1n) acids to carbonyl compounds provides a convenient route to these compounds, and with ab-unsaturated ketones either 1,2- (19) or 1,4-addition products (20) can be obtained, depending on the substituents on phosphorus and the conditions used.22In a similar reaction with silyl esters of phosphonous acid, 1-hydroxyalkyl-phosphinates (21) are formed.23 An alternative synthesisfor 1-siloxybenzylphosphonates (22) is provided by the reaction of phosphites with silyl phenyl

e.g. (18;

0 OSiMe,

II I

/ RWCO

R1,POSMe,

R',P-CR2R3

!1@ 0 OSiMe,

ii I

RiP--CRJCH=CHR*

(19) 0

II

+

OSiMe,

I

R',PCHRZCH=CR3 (20) 21 22

23 24

J. A. Miller and D. Stewart, J.C.S. Perkin I , 1977, 2416. T. Hata, A. Hashizume, M. Nakajima, and M. Sekine, Tetrahedron Letters, 1978, 363; D. A. Evans, K. M. Hurst, L. K. Truesdale, and J. M. Takacs, ibid., 1977, 2495; D. A. Evans, K. M. Hurst, and J. M. Takacs, J. Amer. Chem. Soc., 1978,100,3467; M. Sekine, I. Yamamoto, A. Hashizume, and T. Hata, Chem. Letters 1977, 485. T. Hata, H. Mori, and M. Sekine, Chem. Letters, 1977, 1431. A. Sekiguchi, M. Ikeno, and W. Ando, Bull. Chem. SOC.Japan, 1978, 51, 337.


100

HP(OSiMe3),

R’COR’

HO PhNH, EtOH

*

0

I II

R‘RZC-P’

0-

H ‘

0 PhCOSiMe,

II

+ (RO),P -+ (RO),PCHPh

I

OSiMe,

(22)

The reactions of trialkyl phosphites with cycloalkanethiones or cycloalkanedithiols give mixtures of l-alkylthio- (23) and 1-mercapto-cycloalkylphosphonic esters (24).2sThe proposed mechanism involves concerted cyclic migration of an alkyl group or a proton.

The addition of tervalent phosphorus esters to or&unsaturatedketones continues to be investigated, although in general the products remain the same, i.e. phosphonates (25) 28 or phosphoranes (26),27depending on the carbonyl compound. Oxaphospholens (27) are formed on treatment of furandiones with triethyl phosphite28even when the aryl group carries a 2-nitro substituent; in related systems 2 9 this has led to the formation of pyridine derivatives via deoxygenation and nitrene insertion. The previously unknown lN-1,2,3-diazaphosphole(28) is formed in the reaction of azoalkeneswith trimethyl (but not triethyl) phosphite.30 The usual reports of addition of secondary phosphites to Schiff bases have appeared.31 Variations include reactions with aldazines, to give (1 -aminoalkyl)phosphonic acids (29) after hydrolysi~,~~ and the synthesis of optically pure S. Yoneda, T. Kawase, and Z. Yoshida, J. Org. Chem., 1978,43, 1980. M. M. Sidky, F. M. Soliman, and R. Shabana, Austral. J . Chem., 1976,31, 139. B. A. Arbuzov, Yu. Yu. Samitov, Yu. M. Mareev and V. S. Vinogradova, Izvest. Akad. Nauk S.S.S.R.,Ser. khim., 1977, 2000 (Chem. Abs., 1978, 88, 23 055). 28 H. Zimmer, W. W. Hilstrom, J. C. Schmidt, P. D. Seemuth, and R. Vogeli, J. Org. Chem., 1978,43, 1541. 29 T. Kametani, T. Yamanaka, F. F. Ebenito, and K. Nyu, Heterocycles, 1974, 2, 209. 8o G. Baccolini and P. E. Todesco, Tetrahedron Letters, 1978, 2313. *l A. N. Pudovik, I. V. Konovalova, M. G. Zimin, T. A. Dvoinishnikova, and V. M. Pozhidaev, Zhur. obshchei Khim., 1977, 47, 1694 (Chem. Abs., 1977, 87, 152322); R. Gancarz and J. S. Wieczorek, Synthesis, 1977, 625. 32 J. Rachon and C. Wasielewski, Tetrahedron Letters, 1978, 1609. 25 26 27


H,C=CHCHO

101

+ MeOP Me

0 '

OMe (26)

R PhCHZCRNzNPh

NMe

+ (MeO),P + p h c > N p h D

I1

HP(OEt),

ArCH==-N-N=CHAr

0 R',C=NRz

II

ArCH(NH,)P(OEtj, +

I

HNP(O)(OEt),

0

II

+ (HO),PH

0 ti -. Ar$X€P(OEt),

0

0

I1

-+

R',C(NH,)P(OH),

-t R1,CHNHRZ

102


(1 -aminoalkyl)-phosphonic acids through the use of an optically active Schiff base.33The reactions of phosphorous acid with imines and enamines have been throughly investigated.Whether the predicted (l-aminoalky1)phosphonic acid (30) is formed or reduction to the corresponding amine takes place depends on the imine Enamines are invariably reduced to the amine, and in the presence of alcohols monoalkyl phosphates are also formed (presumably via trimetaphosphate). (l-Aminoalky1)-phosphonic acids can also be prepared by variations of the Mannich reaction,35for example the reactions of alkyl carbamates36 or substituted ureas 3 7 with aldehydes and phosphites give (l-aminoalky1)phosphonates (31). Reinvestigation of the report38 of a Mannich reaction of benzylamine, ketones, and phosphorous acid shows it to be incorrect, and the products originally designated as (1 -aminoalky1)-phosphonic acids have now been shown to be benzylammonium 0 (R’O)3P + R2CH0

+

XCONH,

I1

__f

(R’O),PCHR2

I

NHCOX (31) X = NHPh or OR3

Halogenoacyl-furans react with trialkyi phosphites to give a mixture of However, tris(trimethylsily1)phosphite Perkow (32) and Arbusov (33) reacts with a-halogeno-ketones to give l-siloxyphosphonates ( 3 9 , although Perkow and Arbusov products are formed in reactions with ketones containing electron-withdrawing groups.41The results offer supporting evidence for (34) as an intermediate in the Perkow and Arbusov reactions. Tris(dimethy1amino)phosphine reacts with isocyanates and isothiocyanates43 to give the zwitterions (36) and (37) respectively. Similar reactions with trimethyl phosphite give rearranged products, for example (38) is formed from isocyanates. The reaction of methyl diphenylphosphinite with acetyl chloride provides the first truly effective route to acetyldiphenylphosphine oxide (39) and allows a comprehensive study of its r e a ~ t i v i t y .Perhaps ~~ surprisingly, acetoxydiphenylphosphine (40) is in equilibrium with the rearranged oxide (39). Acylphosphonic acids (41) (isolated as their mono-anilinium salts) have been prepared by the 33

34 35 36

37 88

39 40

41 42

43

44

T. Glowiak, W. Sawka-Dobrowolska, J. Kowalik, P. Mastalerz, M. Soroka, and J. Zon, Tetrahedron Letters, 1977, 3965. D. Redmore, J. Org. Chem., 1978, 43, 992. J. Lukszo and R. Tyka, Synthesis, 1977, 239. J. Oleksyszyn and R. Tyka, Tetrahedron Letters, 1977, 2823. J. W. Huber 111 and M. Middlebrooks, Synthesis, 1977, 883. W. Szczepaniak and J. Siepak, Roczniki Chem., 1973, 47, 929. D. Redmore, J. Org. Chem., 1978, 43, 996. S. Andreae and H. Seeboth, 2. Chem., 1978, 18, 17. M. Sekine, K. Okimoto, and T. Hata, J. Amer. Chem. Suc., 1978, 100, 1001. H. W. Roesky and G. Sidiropoulos, Chem. Ber., 1977, 110, 3703. E. S. Batyeva, E. N. Ofitserov, and A. N. Pudovik, Zhur. obshchei Khim., 1977, 47, 559 (Chem. Abs., 1977,87, 39 598). J. A. Miller and D. Stewart, J.C.S. Perkin I, 1977, 1898.

Tervalent Phoshporus Acids 103 reaction of tris(trimethylsily1) phosphite with acyl chlorides followed by solvol y ~ i sPhosphites .~~ react with or-chloroacyl chlorides to give l-phosphonato-enol phosphates (42), which on treatment with strong base give the synthetically useful allylic anions (43), as shown in Scheme 3.46

X

I

X

R'R2CCOR3

RS (34)

+

iM el),

I iI

(Me,SiO),P

(Me,N),P

OSihfe,

11 +R'R2C- C-P(0S

-

RN=C=X

0

(35) +

0

(Me,N),PC-N---R

II

-:1

X

(MeO),PCONMeR

(36) X = 0

(37)

x=s

0 PhPOMe + MeCOCl

II

-10°C ___f

PhpCOMe (33)

11 PhPCl

(Me,SiO),P

-k

MeC0,Na

+ R'COCl

-

PhP-0-COMe (40)

0

ll

0

II

(Me,SIO),PCOR'

HOPCOR' R'OH

A-

PhA1-1, (41) 45 46

M. Sekine and T. Hata, J.C.S. Chem. Comm., 1978, 285. H. Ahlbrecht, B. Konig, and H. Simon, Tetrahedron Letters, 1978, 1191.

104


M eCHClCOC1

+ (RO)J'

-

0

0

I1

MeCH-C

P--p(o

R)2

\

-L

(OR),

O=P(OR),

/

(42)

O

Me3SiCH2CH=C

I1

\

0=P(OR),

O ,

-P

O , -- --- -- - - H,C-CH-C

ll

-P(0 R 1,

(43) iii1

0

II

\

O-P(OR),

O=P(OR),

I I O=P(OR),

H,C=CH-C-Me

Reagents: i, BuLi, in THF, at

-78 "C;ii, MesSiCl; iii, Me I Scheme 3

Attack on Nitrogen. The reaction of methyl diphenylphosphinite with o-azidophenol or with o-aminophenol and N-chlorodi-isopropylamineprovides routes to 2,3-dihydro-l,3,2-benzoxazaphosph(v)oles (44).47A similar reaction between o-azidophenyl benzoate and hexamethylphosphortriamide gives the 1,3,2benzoxazaphosphole (45).

MeOPPh, CINPr',

~

y HN-P' 7 . m I'Ph OMe

47

J. I. G. Cadogan, N. J. Stewart, and N. J. Tweddle, J.C.S. Chern. Comrn., 1978, 182.


105

Attack on Oxygen. a-Keto-acids can be reduced to a-hydroxy-acids in good yield by trialkyl p h o ~ p h i t e s .The ~ ~ suggested mechanism involves attack at carbonyl oxygen followed by proton transfer to give (46). The authors suggest that ethylenephenyl phosphite forms the phosphorane (47) at this stage, while acyclic phosphites undergo an Arbusov-type rearrangement; however, hydrolysis gives identical products in each case.

11

NaOH, IH,O

RTH(OH)CO,H

+

H3P0,

NaOH

a

CrI ;p-o\

pho

,CHR2

O h 0 (47)

Attempts to generate a carbene from nickel meso-formyloctaethylporphyrin by reaction with triethyl phosphite gave instead the meso-trans-propenyl derivative (48).49 The suggested route, involving a Horner reaction of diethyl ethylphosphonate, seems unlikely since olefinations of this type normally require carbanion-stabilizingsubstituents.

RCHO

(EtO) P

=R

RCH=CHMe (48)

Et

48

49

T. Saegusa, S. Kobayashi, Y.Kimura, and T. Yokoyama, J. Org. Chem., 1977, 42,2797. D. P. Arnold, A. W. Johnson, and M. Mahendron, J.C.S. Perkin I, 1978,366.


106

Tris(dimethy1amino)phosphine reacts with amide oximes (49) to give a variety of products. Initial formation of the unstable intermediate (50) has been suggested, and 31PCIDNP effects, in certain cases, indicate some contribution from free 61 A complication to the now standard desulphurization or deselenization route to tetrathia- and tetraselena-fulvalenes has been reported. 63 Treatment of (51) with phosphites can lead to scrambling of sulphur and selenium in one ring of the product, e.g. (52). The unsymmetricalnature of (52) indicates a step-wisereaction, with Se/S scrambling in the initially formed adduct with phosphite. Of course, no such problems exist for (53), and normal conversion into tetrathiafulvalene (54) occurs,63although with aliphatic phosphite esters the yield of (54) is low, because there is a competing Arbusov reaction to give (55). It is mechanistically significant that the condensation products (57) and (58) are obtained from the reaction of triethyl phosphite with the thione (56) in the presence of an excess of thiacyclohexan-4-one.6 4 Mild oxidation and decarboxylation of (58) gives the n-donor (59), which forms semiconducting salts with 7,7,8,8-tetracyanoquinodimethane (Scheme 4).

(53) R2 50

51 52

53 54

f

CN, Ph, or C0,R3

L. Lopez and J. Barrans, J.C.S. Perkin I , 1977, 1806. B. J. Walker in ‘Organophosphorus Chemistry’, ed. S . Trippett (Specialist Periodical Reports), The Chemical Society, London, 1978, Vol. 9, p. 91. E. M. Engler, V. V. Patel, and R . R. Schumaker, J.C.S. Chem. Comm., 1977, 835. S. Yoneda, T. Kawase, M. Inaba, and Z . Yoshida, J. Org. Chem., 1978,43, 595. D. J. Sandman, A. P. Fisher, T. J. Holmes, and A. J. Epstein, J.C.S. Chem. Comm., 1977, 687.


(56)

107

X = C0,Me

(57)

0

+

(5 9)

(58)

Reagents: i, (R0)aP; ii, 0G

O ;iii, LiBr, HMPT

c1

CI

Scheme 4

Attack on HaZogen. The long saga of the Perkow reaction mechanism (apparently put to rest) is resurrected in a recent The suggestion that an initial slow reaction involving attack at halogen, probably to give an enolatehalogenophosphonium ion-pair (60), is the common first step in the formation of both Arbusov and Perkow products from a-bromo- and cc-iodo-acetoyhenonesappears to be justified by the kinetic data presented.

(MeO),P + XCH,COAr

I_)

(MeO),;-X

HZC, -?C-Ar

.y

0

(60)

Electrophilic Reactions.-A variety of optically active aminophosphines, e.g. (61), and amino-diphosphines, chiral at carbon, have been prepared and used as ligands for asymmetric hydrogenation catalysts.6 6

Bridged 1,3,2A3, 4i13-diazadiphosphetidines(63) have been prepared from 2,4dichloro-1,3,2i13,4A3-diazadiphosphetidine(62) and diamines or diols.5 7 However, when a choice of reaction with P-Cl or Si-Cl bonds exists, as in the 1,3-diaza-2-phospha-4-silacyclobutane(64), the final product (65) or (66) depends on the amine substituents.s8The subtleties of substituent effects in this type of reaction are well illustrated by two recent attempts at the synthesis of 1,3,2,455

L. Toke, I. Petriehazy, and G. Szakal, J. Chem. Res.(S), 1978, 155. Pracejus and H. Pracejus, Tetrahedron Letters, 1977, 3497. Keat and D. G. Thompson, Angew. Chem. Internat. Edn., 1977, 16, 797. U. Klingebiel, P. Werner, and A. Meller, Chem. Ber., 1977, 110, 2905.

513 G. 57 R. 58

108


diazadiphosphetidine. The reactions of chloro-phosphines with sodium bis(trimethylsily1)amide give 1,3,2,4-diazadiphosphetidines(67) (stereospecifically cis);6ghowever, the reactions of alkyl-dichlorophosphines and heptamethyldisilazane give instead cyclotetra(A3-phosphazanes)(68).60In the latter case the eight-membered ring structure was confirmed by X-ray crystallography. The geometrical isomers of cyclodiphosph(Ir1)azanes (69) have been separated and, in one example, their structures assigned.61In view of the stereospecificformation of cis-l,3,2,4-diazadiphosphetidines(67)69 it is interesting that cis-(69) is thermodynamically favoured and trans-(69) kinetically. A distinct difference in reaction rate between cis- and traw(69) was noted in a variety of reactions.

-

But

/”\

C I P y

But

C1

ANSiMe, Me,SiN

PC1

+ HX(CH,),XH n = 2 o r 3 X = 0 or NMe

R’R*NH

Me,SiN

NSiMe, or Me,SiN

/\

‘s ’i /\

(64)

(65)

‘si/

c1

N R’Rz /p\

c1 c1

\Si/NSiMe3

c1 Cl

2(R,N),PCl + 2NaN(SiMe3),

-

/p\

R’R’N

/ \Cl (66)

SiMe, P

”\

(67)

4RPCI, + 4MeN(SiMe& --+

Me R ,N--p, RP’ ‘NMe

I

I

MeN,

R XP/N\PX ‘N’

(68) 60

6o

R

(69) X = NMe, or OMe

W. Zeiss, C. Feldt; J. Weis, and G . Dunkel, Chem. Ber., 1978, 111, 1180. W. Zeiss, W. Schwarz, and H. Hess, Angew. Chem. Internat. Edn., 1977, 16, 407. R. Keat, A. N. Keith, A. Macphee, K. W. Muir, and D. G. Thompson, J.C.S. Chem. Comm. 1978, 372.


109

Two-co-ordinate phosphorus compounds have been reviewed.62Complexes of the dico-ordinate phosphorus cation (70) are formed in the reaction of 2fluoro-l,3-dimethyl-l,3,2-diazaphospholidine with a variety of anionic transitionmetal compounds.6 3 The product of the reaction of t-butyliminodi(isopropy1)aminophosphine (71;R1=Pri, R2=But) with tertiary butyl azide, first allocated the novel imino-bridged structure (73),64is now thought to be monocyclic on the basis of an X-ray crystal structure of the analogous product (72).66 Although postulated as an intermediate in the reaction of the amino-iminophosphine (74) with diazomethane, no trico-ordinate A6 phosphorus compound containing a phosphorus-carbon double bond has yet been isolated. However, Niecke and his co-workers now report that compounds (75) can be obtained as thermally stable liquids from similar reactions with substituted diazoalkanes. Secondary amino-phosphines (77) generally prefer the iminophosphorane form (78); however, a remarkably stable example of (77;R=SiMe,) has now been prepared by treatment of imino-aminophosphine (76) with dimethylaminob~rane.~'

R',N-P=NRz

+

RzN3

(7 1)

W"'PNR12 N". R2

(72) R' = SlMe,; R2 = But R',N

+

R',N-P=NR' (74) R* = SiMe,

H3B+NHMez

+ R,N-P-NR (76)

62

63 64

65

66 67

MeRTN,

-+

Ra = Me, e t , Pri, or But

R'N

H

% R,N-P-N€IR (77)

\

'P=CR~Mg / (75 1

H R,N--P=NR H (78)

N. I. Shvetsov-Shilovskii, R. G. Bobkova, N. P. Ignatova, and N. N. Mel'nikov, Rum. Chem. Rev., 1977, 46, 514. R. W. Light and R. T. Paine, J. Amer. Chem. SOC.,1978, 100,2230. E. Niecke and H. G. Schafer, Angew. Chem. Internat. Edn., 1977, 16,783. S. Pohe, E. Niecke, and H. G. Schafer, Angew. Chem. Internat. Edn., 1978, 17, 136. E. Niecke and D. A. Wildbredt, Angew. Chem. Internat. Edn., 1978, 17, 199. E. Niecke and C. Ringel, Angew. Chem. Internat. Edn., 1977, 16, 486.


110

1,2,4,3A3-Triazaphosphole (80) has been prepared by reductive elimination from the 1,2,4,3A6-triazaphospholedimer (79) with propane-1,3-dithi01.~~ This type of reaction was previously unknown outside phosphabenzenes. Although (80) does not normally undergo uncatalysed oxidative addition reactions, it does react with 2-heterodienyl-phenols to give tricyclic phosphoranes (81). 8B The synthesis of various diazaphospholes, including (82; R = H), by reduction of acetyldiazaphospholewith phenylhydrazinehas been investigated.70 Bromination of (82; R=Ph) takes place at the 4-position to give (83; R=Ph), as with the previously reported Friedel-Crafts reaction. 71 The spectral properties and an X-ray crystal structure of 1,2,3A2-diazaphospholiumchloride (84) have been rep~rted.?~

MeN/N\)P \ h

+

/N=CMe2 MeNH

Schmidpeter, J. Luber, and H. Tautz, Angew. Chem. Znternat. Edn., 1977, 16, 546. Schmidpeter, M. Junius, J. H. Weinmaier, J. Barrans, and Y . Charbonnel, 2.Naturforsch., 1977, 32b, 841. 70 R. G . Bobkova, N. P. Ignatova, N. I. Shvetsov-Shilovskii, N. N. Mel’nikov, V. V. Negrebetskii, L. Y. Bogel’fer, S. F. Dymova, and A. F. Vasil’ev, Zhur. obshchei Kliim., 1977, 47, 576 (Chem. Abs., 1977,87, 23 400). 7 1 B. J. Walker in ref. 51, p. 92. 7 2 P. Friedrich, G. Hiittner, J. Luber, and A. Schmidpeter, Chem. Ber., 1978, 111, 1558. 68 A. 139 A.


111

Language difficultiesto some extent obscure the interesting results contained in a recent study of the alcoholysis of amino-ph~sphines.~~ Good n.m.r. evidence is presented for the intermediate formation of the phosphorane (86) in the reaction of the amino-l,3,2-dioxaphospholan(85) with methanol to give, ultimately, the phosphite (87). The phosphorane (86) is not observed in solutions of phosphite in methanol and amine, which supports (86) as a true intermediate and leads the authors to suggest the mechanism shown (Scheme 5). A similar mechanism has been suggested (Scheme 6) for the uncatalysed transesterification of alkyl phosphinates (88) which takes place rapidly at room temperature, even with tertiary alcohols (although not with phenols).74Phosphate, phosphonate,

M\" M e

J

OMe

Me Me

H

0

I1

MeOPH,

_I

/OH MeOP H '

+ ROW

_.OR

H 1' OH

(88) M

I

i=t MeO-P'

11

eo -

0

MeOPOH

L M %

[HP-01

ROH

Ii

-----+ ROPH,

+ McOH

(89) Scheme 6

73 74

M. T. Boisdon, C. Malavaud, F. Mathis, and J. Barraus, Tetrahedron Letters, 1977, 3501. M. J. Gallagher and H. Honegger, J.C.S. Chem. Conzm., 1978, 54.

112


and substituted phosphinate esters do not react under similar conditions. The basecatalysed reaction of (88), to give the same products, probably involves a phosphenite intermediate (89). Evidence for alkyl phosphenite intermediates (90) in the reaction of alkyl phosphinates with base and tetracyclone to give dialkyl phosphonates is provided by the isolation of t-butyl alkyl phosphonate from reactions carried out in the presence of tertiary butyl alcohol (Scheme 7).76 0

I1

(ROIPH,

L

ROP-H

+-+

II 0

ROPH

I

0-

I

[ROP-01

+

phP: H

(90)

0

Reagents: i, Et3N; ii, ‘ ’ 6 0 ; iii, ButOH; iv, ROH Ph Ph

Scheme 7

Rearrangements.-Phosphite complexes of the type (91) undergo methyl transfer, seemingly by an intermolecular reaction, to give phosphonate complexes.7 6 Phosphorus(m) amides react with propargyl alcohol to give enamine phosphonates (92),” presumably by the mechanism shown.

Q+- -

Me&* 4 \ T O OC P(OMe), (91) I3 = Sb or As M = Mo 01 W

75

76 77

Me,E-’/

.M.

OC

(To P(OMe),

//

0

C. J. R. Fookes, M. J. Gallagher, and H. Honegger, J.C.S. Chem. Comm., 1978, 324. W. Malisch and R. Janta, Angew. Chem. Internat. Edn., 1978, 17, 211. Yu. A. Kondratev, 0. N. Emel’yanova, K. D. Shvetsova-Shilovskaya, V. V. Negrebetskii, and S. F. Dymova, Zhur. obshchei. Khim., 1977,47,2707 (Chem. Abs., 1978, 88, 105 475).

113

Tervalenf Phosphorus Acids R’R2PNR3, + HC=CCH,OH

-+ R1R2g=/&\~~,

c-d + -

HC@

1

0 R3,NII

R32NH

R’R*P- CII

C =CH,

Me

R’ (93)

‘N’m r -

(94)

cis-l,3-Dimethyl-2,4-di-t-butyl-2-telluro-l,3,216,413-diazadiphosphetidine (94), prepared from the diazadiphosphetidine (93), acts as a fluxional redox system through tellurium site e~change.’~ Cyclic Esters of Phosphorous Acid.-Various thymidine nucleoside 3’,5’-cyclic phosphoramidites and phosphites have been synthesized. The previously reported 8o reaction of furanosides with hexaethylphosphortriamide to give bicyclic phosphites, e.g. (99, has been further investigated.81Not surprisingly, the formation of a bicyclic phosphite depends on the cis-orientation of the 3- and 4-substituents on the furanoside ring. HOCH, I

/O-CH2 I

The cyclic phosphite (96),rather than the hoped for acyclic phosphite (98), is the product of the reaction of phosphorus trichloride with 2-hydroxyacetophenone in the presence of basees2However, a similar reaction with dichlorophenylphosphine gives the tricyclic phosphorane (97), the structure of which was determined by X-ray analysis. 78 79 80

81 82

0. J. Scherer and G. Schnable, Angew. Chem. Internat. Edn., 1977, 16, 486. G. S. Bajwa and W. G . Bentrude, Tetrahedron Letters, 1978, 421. E. Ye. Nifant’ev, M. P. Koroteev, Z. K. Zhane, A. A. Borisenko, and N. K. Kochetkov, Carbohydrate Res., 1976, 47, 221. E. Ye. Nifant’ev, M. P. Koroteev, Z. K. Zhane, A. A. Borisenko, and N. K. Kochetkov, Tetrahedron Letters, 1977, 4125. G . M. L. Cragg, B. Davidowitz, G . V. Fazakerley, L. R. Nassimbeni, and R. J. Haines, J.C.S. Chem. Comm., 1978, 510.

Organophosphorus Chemisrry

114

aoH Et,N PCI, *

COMe

PhPCI,

IEhN

(97)

(9 8)

The radical Arbusovreactionsof cis- and trans-five-(99) and six-memberedcyclic phosphites (101)with phenyl and dimethylaminoradicals have been inve~tigated.~~ The reactions are highly stereoselective, with inversion at phosphorus (Scheme 8), and in the case of the six-membered ring the trans-isomer reacts about 8 times faster than the cis. The authors suggest that the formally pentaco-ordinate phosphoranyl radical intermediates, e.g. (103), undergo p-scission to product faster than they undergo pseudorotation.

trans- (99)

cis- (100)

cis-(99)

X = Ph4

z

b

frans-(lOO)

or -NMe,

Scheme 8

(103) 83

W. G. Bentrude, W. D. Alley, N. A. Johnson, M. Murakami, K. Nishikida, and H. W. Tan, J. Amer. Cliem. SOC.,1977, 99, 4383.

115

T'rvalent Phosphorus Acids

The eight-membered cyclic phosphonite (104) and the corresponding sulphide have been prepared and their n.Iz1.r. spectra studied in details4(see Chapter 11). Like similar ring systems, (104) dimerizes on standing in benzene solution to give very low yields of two isomeric dimers that have been characterized as their sulphides. N.m.r. investigations of complexes of alkali-metal cations with I, lO-dio~a-4,7-diaza-ll-phosphacycloundecanes (105) show that, of the metals studied, lithium was most strongly bound.s6 A variety of the so-called phosphatianes (107) have been prepared from the parent compound (106), itself prepared in low yield from tris(2-hydroxyethy1)amine.86In certain cases, n.m.1. studies suggest a tricyclic structure (108), with a transannular N-+P bond.

MeP(NMe),

3.

(105) R = Me or Et

(107) Y = 0, S, Se, BH,, or (OC),W

(108) Y = H+ or Ph$+

J. P. Dutasta and J. B. Robert, J. Amer. Chem. SOC., 1978, 100, 1925. s5 J. Grandjean, P. Laszlo, J. P. Picavet, and H. Silwa, Tetrahedron Letters, 1978, 1861. g 6 D. S. Milbrath and J. G. Verkade, J. Amer. Chem. SOC.,1977,99, 6607.

84

5


116

Miscellaneous Reactions.-Trialkyl phosphites have been obtained directly from white phosphorus by reaction with alkoxide and carbon tetrachl~ride.~~ The principle involved, nucleophilic ring-opening of P4 and trapping of the anion by attack on halogen (Scheme 9), suggests that the method may offer a general route to a range of phosphorus(u1) compounds.

RO

\

RO P‘

(RO),P

RO-etc. f-- f-

P-

-P/

c1

a,/

Scheme 9

Sodium dicyanophosphide (109), stabilized as a crown ether complex, has been prepared for the first time by the reaction of tricyanophosphine with sodium dialkyl phosphites.8 8 Dialkyl phosphite anions react with chlorophenylphosphines entirely through nucleophilic phosphorus, to give, for example, (1

PhPC!, + 2(RO),PG0

PI

PhP P(OR),

Trialkyl phosphites are thought to act as bases in their reactions with dithioacetates to give isomeric vinyl thioketones (Scheme A rhodium complex of the carbohydrate diphosphinite (111) has been used as an asymmetric hydrogenation catalyst to prepare optically active a-amino-acids

88 89

C. Brown, R. F. Hudson, G. A. Wartew, and H. Coates, J.C.S. Chem. Comm., 1978, 7. A. Schmidpeter and F. Zwaschka, Angew. Chem. Ifiternat. Edn., 1977, 16, 704. C. Glidewell, J. Organometallic Chem., 1977, 142, 171. Z. Yoshida, S. Yoneda, T. Kawase, and M. Inaba, Tetrahedron Letters, 1978, 1285.


117

Me

RS’

CH

z\c/

I

SR

II

S-

S

k+ H‘

Me

H’

S

\ /

C=CH-CSR

R S‘

ll

E and Z

Scheme 10

in up to 80 % enantiomeric excess.g1Lindner and his co-workers have prepared a series of complexes of transition metals with secondary phosphine oxides,g2*gs s ~ l p h i d e s and , ~ ~ selenides 9 4 which are co-ordinated through either heteroatom. In the compound (1 12) the SH group can be modified in a variety of ways without decomposition of the complex.g5

91 92 93

94 95

W. R. Cullen and Y . Sugi, Tetrahedron Letters, 1978, 1635. E. Lindner and B. Schilling, Chem. Ber., 1977, 110, 3266. E. Lindner and B. Schilling, Chem. Ber., 1977, 110, 3889. E. Lindner and B. Schilling, Chem. Ber., 1977, 110, 3725. E. Lindner, K. W. Rodatz, and J. P. Gumz, Chem. Ber., 1978, 111, 125.

118

Organophosphorus Chemistry Et,N

L@nP( SH)Me,

b2(112) k~>

[L,MnPMe,S]-

*.

RCO),O

[ L,MnPMe,S],

L,MnP(SCOR)Me,

L,MnP(SMe)Me,

A variety of trinuclear sandwich complexes, e.g. (1 13), of dialkyl phosphonates have been prepared.9*

2

2 Phosphonous and Phosphinous Acids and their Derivatives The formation of methyl phosphinate, (MeO)P(O)H,, in the reaction of trimethyl orthoformate with phosphinic acid has now been shown to be accompanied by a variety of other The authors present a comprehensive mechanistic scheme and suggest that the results can only be interpreted by a substantial contribution from the phosphorus(m) tautomer in phosphinic acid and its esters. Trimethylsilyl dimethylphosphinite (114) has been synthesized and its chemistry inve~tigated.~~ Although a variety of 1,3,2A6-dioxaphospholans(1 15) were prepared from (114), attempts to synthesize hydroxyphosphoranes were unsuccessful.

0

II + Me,NSiMe,

Me,PH

B6 97

Q8

-

Me,POSiMe, (1 14)

(115)

X = OSiMe,, F, C1, NMe,, N, or OMe

W, KlBui and K. Dehnicke, Chem. Eer., 1978, 111, 451. M. J. Gallagher and H. Honegger, Tetrahedron Letters, 1977, 2987. M. Volkholz, 0.Stebzer, and R. Schmutzler, Chem. Ber., 1978, 111, 890.

119

Tervaleizt Phosphorus Acids

Optically active amino-phosphines (1 16) and phosphinites (1 17) have been prepared by standard methods and used in the resolution of chiral metal c o n i p l e ~ e sA . ~variety ~ of optically active ethyl ethylphosphonamides(1 18) have been obtained from optically active ethyl ethylphosphonite by reaction with amines and carbon tefrachloride.lo0

R*,P-N

/

R2

\ ( p e

\-'H. Ph

99

H. Brunner and J. Doppelberger, Chem. Ber., 1978, 111, 673. A. Buina, M. A. Giniyatullina, I. A. Nuretdinov, and F. G. Sibgatullina, Zzuest. Akad. Nauk S.S.S.R., Ser. khim., 1977, 1437 (Chem. Abs., 1977, 87, 135 649).

loo N.

6 Q ui ng uevalent Phosphorus Acids BY

R. S. EDMUNDSON

Interest in the chemistry of the important anti-cancer drug cyclophosphamide and its derivatives and analogues, and in that of (1-aminoalkane)phosphonic acids, commented upon in last year's Report, has been maintained throughout this year. Elsewhere, there have been many applicationsof phosphoramidate chemistry to conventional organic synthesis, and in a mmber of cases, X-ray analysis has been used to confirm the structures of reaction products as well as to elucidate stereochemical features. As in previous years, the heading 'General' covers papers which describe work on phosphonic and/or phosphinic acid derivatives, as well as on phosphoric acid compounds. 1 Synthetic Methods General.-Reaction between aliphatic or aromatic nitriles R2CN and the sodium salts of dialkyl phosphites affords N-(dialkoxyphosphinomethy1)phosphoramidates (l).l 2,3,4,5-Tetrahydro-l,2,4,5,3-tetra-azaphosphorines (2) have been prepared from orthocarboxylic esters and phosphoric and phosphonic dihydrazides. Interaction of tris(dimethy1amino)phosphine and amidoximes yields one or more products, depending upon the temperature of reaction and upon the degree and nature of substitution in the amidoxime molecule. Presumably, the site of the initial reaction is at the amidoxime oxygen, which is then followed by rearrangement to the amidines (3), isolable if the reaction takes place at room temperature; at 80 "C, 1,3,5,2-triazaphosphorine2-oxides (4) or 2,l-benzazaphosphole 2-oxides (5) may also be i~olated.~

(2)

x

= 0 or

s

R' = Ph or FhQ M. G. Zimin, T. A. Dvoinishnikova, 1. V. Konovalova, and A. N. Pudsvik, Izvest. Akad. Maitk S.S.S.R., Ser. khim., 1978, 499 (Chem. Abs., 1978, 88, 190 978). J. P. Majoral, M. Revel, R. Kraemer, €I. Germa, and J. Navech, J. Heterocyclic Chem., 1977, 14, 749. L. Lopez and J. Barrans, J.C.S. Perkin I , 1977, 1806.

120

Qitinquei:alent Phosphorus Acids

(3)

121

(4)

A full paper on the synthesis of optically active dialkyl alkylphosphonothioates and -selenoates, trialkyl phosphoro-thioates and -selenoates, dialkyl methylphosphonates, and trialkyl phosphates by the stereospecific ring opening and covering work previously reported in of perhydro-l,3,2-oxazaphosphorines, preliminary form (see ‘Organophosphorus Chemistry’, Vol. 8, p. 103; Vol. 9, p. 114) has been published.* Phosphoric Acid and its Derivatives.-Current methods of phosphorylation have been reviewed. Phenyl4-nitrophenyl phosphates, prepared from the phosphorochloridate, lose the 4-nitrophenoxy-group when treated with thiocresol and triethylamine, a reaction forming the basis of a new phosphosylation technique. Di-t-butyl phosphorobromidate is probably a better 0-phosphorylating agent than the corresponding phosphorochloridate; the t-butyl groups are removable by trifluoroacetolysis. Two papers describe the phosphorylation of adamantols and related compounds by o-phenylene phosphorochloridate, the o-phenylene group being removed by initial ring opening with alkali followed by bromine water.* A convenient preparation of 2-methylthio-4H-l,3,2-benzodioxaphosphorinan 2-oxide from its thiono-isomer, by initial demethylation (using NN-dimethylcarbamic acid) and subsequent remethylation, and its use as a phosphorylating agent, have been described. L-Proline ethyl ester is the starting material in a sequence (Scheme 1) for the preparation of optically active phenyl dialkyl phosphates.loThe first alkyl group is introduced via the chloridate (6), and the products (8) are obtained by the acid-catalysed alcoholysis of the chromatographicallyseparated diastereoisomeric phosphoramidates (7). Yields of products vary considerably, depending on R, but the sequence is potentially valuable for other types of compounds, and may indeed prove more attractive, from the standpoint of practicality, than other methods currently being researched. Following last year’s report on the electrochemicalpreparation of (2,2-dichlorovinyl)phosphonates, Matschiner et al. have now described the preparation of 2,2-dichlorovinyl phosphates by the electrochemical reduction of 1,2,2,2-tetrachloroethyl phosphate esters.l1 D. B. Cooper, C . R. Hall, J. M. Harrison, and T. D. Inch, J.C.S. Perkin Z 1977, 1969. L. A. Slotin, Synthesis, 1977, 737. 6 C . 8.Reese and Yan Tak Yan Kim, J.C.S. Chem. Comm., 1977, 802. 7 T. Gajda and A. Zwierzak, S.vnthesis, 1977, 623; A. Gorecka, M. Leplawy, J. Zabrocki, and A. Zwierzak, Synthesis, 1978, 474. 8 W, Bohringer and PI. Vogt, Arch. Pharm., 1977, 310, 235, 894. M. Eto, M. Iio, H. Ohmura, and M. Eto, J. Fac. Agric., Kyushu Uniu., 1977, 22,25 (Chem. Abs., 1978, 88, 89 633); Agric. Biol. Chem., 1978, 42, 199 (Chem. Abs., 1978 88, 191 302). lo T. Koizumi, Y. Kobayashi, H. Armitani, and E. Yoshii, J . Org. Chem., 1977, 42, 3459. l1 H. Matschiner, F. Cotta, R. Voigtlaender, and H. Schilling, J.prakt. Chem., 1977,319,561. 5


122

O=P

pho/pT;

PhO’

(6)

‘OR1

(7)

Reagents: i, PhOP(0)Ch-pyridine; ii, RlOH (R1=Et or Bu); iii, R20H-H+ (R2=Me, Et, or Pr)

Scheme 1

A series of optically active naphthyl phosphorothionates, together with their (conventional) reactions, have been noted. l2 The 00s-tris(trimethyIsily1) phosphorothiolate (9) is also obtainable by conventional means. The corresponding phosphorothionate (10) yields the sulphenyl chloride (11) when ch10rinated.l~ (Me,SiO),P(O)SSiMe,

(Me,SiO),P=S

(9)

so cl,

(Me,SiO),P(O)SCI (11)

(10)

Mikolajczyk et al. have continued their studies on 1,3,2-dioxaphospholan 2-sulphidesYand have reported the preparation and separation of cis- and transisomers (the original paper should be consulted for revisions to the authors’ definitions of these terms in relation to the compounds under study) of the 2-sulphides from the 2-hydroxy-4,5-dimethyl-, the 2-chloro-4,5-dimethyl-, and the 2-hydroxy-4,5-diphenyl systems, utilizing the imidazolium and tetramethylammonium salts for the separation of the free thioic acids.14 Within the area of polythio-acid chemistry, a successive deprotonation and alkylation sequence commencing with NN’N”-triphenylphosphoric triamide (Scheme 2) leads to asymmetric phosphorotrithioate esters, e.g. (12).15 A pro-

(PhNH),PO

(PhNH),P,

H~

i, ii, iv+

PhNH-P

’ll/

SMe

SMe i, ii, v

Reagents: i, NaH; ii, CS2; iii, MeI; iv, PhCHzhalide; v, PriI

Scheme 2 l2 l3 l4

D. A. A. Akintoniwa, Tetrahedron, 1978, 34, 959. J. Chojnowski, M. Cypryk, W. Fortuniak, and J. Michalski, Synthesis, 1977, 683 M. Mikolajczyk and M. Witczak, J.C.S. Perkin I, 1977, 2213. K. Lesiak and W. J. Stec, Synthetic Comm.,1977, 7 , 339.

Quinquevalent Phosphorus Acids

123

cedure for the preparation of trialkyl phosphorotetrathioates, by heating together a dialkyl sulphide and phosphorus pentasulphide in sealed tubes at ca. 200 "C,has been patented.ls Aspects of the chemistry of phosphoroselenoic acids have been described in a series of papers by Russian authors. This work covers the formation of phosphorodiselenoate esters from selenophosphoryl chlorides (13) l7 and the unusual observation of the loss of sulphur when arylselenols are treated with thiophosphoryl chloride.l* SeSeSe-Phosphorotriselenoates(14) are obtainable conventionally from phosphoryl chloride and selenols. SeSeSe-Triphenyl phosphorotriselenothionate (15 ) loses sulphur in the presence of excess phenylselenol, and is also readily oxidized, losing sulphur, in the presence of atmospheric oxygen. Phenols and phosphorus pentaselenide fail to give 00-diary1 hydrogen phosphorodiselenoates,lgbut the potassium salts of these acids are obtainable from the corresponding phosphorochloridoselenoate and potassium hydrogen selenide.l9 Hydrolysis of 00-dialkyl Se-phenyl phosphorodiselenoates with alkali yields salts of the 00-dialkyl hydrogen phosphor~selenoate.~~ (RO),PCl + Se

PSCl,

+

-

(RO),P(Se)Cl

PhSeH+

(1 3)

PhSeH

1 (PhSe),P (PhSe)J?S

(RO),P(Se)SePh

+ 2PhSeH

+ Ph,Se2

I- H2S

(14)

Sosnovsky et al. have reported further on nitroxyl spin-labelled compounds.10 Within this study, these authors claim that phosphorodi-imidazolates are superior to phosphorodichloridates for reaction with mono- and for cyclization with di-functional compounds, leading to 1,3,2-0xazaphospholidines and perhydro-l,3,2-oxazaphosphorines respectively.21 Unlike the corresponding imidazole derivative, the enediol phosphoryl pyrrole (16) undergoes methanolysis with ring opening to give a mixture of the diastereoisomeric pyrrolides (17), acidolysis of which (see also ref. 110) affords an example of a new heterocyclic system, i.e. 7,8-dimethyl-5-methoxy-5-oxo-AS5-phospha-6-oxa-indolizine (18). a Hall and Inch have extended their studies on the stereospecificity of ring opening of 1,3,2-0xazaphospholidines to include the 2-amino-derivatives (19), 16

17 18 19 20

21 32

U.S.P., 4034024, 1977 (Chem. A h . , 1977, 87, 84 518). Ya. I. Kolodii, Ya. I. Mel'nik, N. I . Zemlyanskii, and V. V. Turkevich, Ukrain.Khim. Zhur. (Russ. Edn.), 1977, 43, 721 (Chem. Abs., 1977, 87, 134 280). N. I . Zemlyanskii, Ya. I. Kolodii, and Ya. I. Mel'nik, Zhur. obshchei Khim., 1977, 47, 62 (Chem. Abs., 1977, 87, 22 662). L. M. Dzidovskaya, N. I. Zemlyanskii, and Ya. I. Mel'nik, Zhur. obshchei Khim., 1977,47, 59 (Chem. Abs., 1977,87, 22 661). G . Sosnovsky and M. Konieczny, Synthesis, 1977, 618, 619. G. Sosnovsky and M. Konieczny, Z . Natrcrforsch., 1977, 32b, 1048. F. Ramirez, J. F. Marecek, and H. Okazaki, Tetrahedron Letters, 1977. 4179.

124

Organophosphorus Chemistry Me

Me

Me Me

0

'

H', OMe

Me0/&No

and have thereby been able to prepare optically active OS-dialkyl phosphoroamidothioates (20). These results afford a clear indication that, at least under the particular experimental conditions, ring opening by acid-catalysed fission of the endocyclic P--N bond is more important than fission of the exocyclic P-N bond. Alcohol-free acidolysis of (19; R1= R2= Me) gives, perhaps unusually, the oxazaphospholidine (21).23

Ephedrine continues to be a source of interesting compounds and reaction sequences. Perhaps the most interesting of this year's examples is the synthesis of the chiral CX6O, 17Q,l*O]phosphate ester of (S)-propane-l,2-diol (Scheme 3). 2 4 2-Chloro-l,3,2-oxazaphospholidine(22; R = C1) was allowed to react with (S)-propane-l,2-diol monobenzyl ether, a step proceeding with retention of configuration at phosphorus, and the resulting ether ester was acidolysed, when ring opening occurred. 1-(R)-[160,170,1sO]phospho-(S)-propane-l ,2-diol was finally obtained by hydrogenolysis. Stereochemical analysis of compound (23) presented an intriguing problem which was solved by a lengthy chemical sequence involving cyclization of (23), methylation, chromatographic separation of diastereoisomers, hydrolysis, and finally mass spectrometry. 23 24

C . R. Hall and T. D. Inch Tetrahedron Letters, 1977, 3761. S. J. Abbott, S. R. Jones, S . A. Weinman, and J. R. Knowles, J. Amer. Chem. SOC., 1978, 100,2558.

125


Me A (22; R = H t O CH2Ph) R = c1 0-

H

Me H+OCH,Ph \'

iii

Me

EtsN; ii, H3180+-TFAA; iii, H2-Pd/C

Scheme 3

Cyclophosphamide (24; R = H) has been obtained in optically active forms by hydrogenolysis of the separated diastereoisomeric N-a-phenylethyl derivatives,2 6 and by the desilylation, using cyclohexylammonium fluoride, of the separated N-a-naphthylphenylmethylsilylderivatives.26 A useful review of the chemistry of C-4-functionalized perhydro-1,3,2oxazaphosphorines related to cyclophosphamide has appeared.2 7 A metabolite, (25), of cyclophosphamide, has been synthesized by oxidation of 4-hydroxycyclo-

(24)

R = PhCHMe

(24; R = H) (-)-(S)-o-NpPhMeSiCI

(*)-(24; R = H)

*

7 (24;

R

= a-NpPhMeSi)

(-1-Sp-R s i (+)-Rp-Rsi 28

Ger. Offen. 2 644 905, 1977 (Chern. A h . , 1977, 87, 53 401). T. Kawashima, R. D. Kroshefsky, R. A. Kok, and J. G. Verkade, J. Org. Cliem., 1978,43,

27

A. Takamizawa, S. Matsumoto, T. Iwata, and I. Makino, Heterocycles, 1977, 7, 1091.

25

1111.


126 0 ,NH2 (ClCH,CH,),NP

I

\

‘OCH2CH2CH0 (25)

phosphamide with pyridinium chlorochromate, as well as by a more conventional route.28 0-3-Butenyl phosphoramidates (26) have proved to be useful synthetic precursors to derivatives (27) of isophosphamide.2 B More recently, the preparation of the perhydro-l,3,2-diazaphosphorines(28) and related compounds by routes similar to those summarized in Scheme 4 has been described.30Ozonolysis of 0-2-propenyl NN-di-(2-chloroethyl)phosphoramidic hydrazides in aqueous acetone yields dihydro-6H-l,3,4,2-oxadiazaphosphorine2-oxides, e.g. (29), whereas the acetyl derivative (30) affords a mixture of the two products (31) and (32).31 0

POCI,

NP/

i-iii __f

XN R

NHX

’

(26) R = alkylor X

R (27) R = H, akyl, or X

X = CH,CH,Cl Reagents: i, HO/\/\,

EtsN; ii, XNHR-HCl-Et3N; iii, XNHz qHCl-EtsN; ivy Os-HaOn

Scheme 4

28

29

A. Myles, C. Fenselau, and 0. M. Friedmann, Tetrahedron Letters, 1977, 2475. A. Takamizawa, S. Matsumoto, T. Iwata, and I. Makino, Chem. and Pharm. Bull. (Japan), 1977,25, 1877.

A. Takamizawa and S. Matsumoto, Chem. and Pharm. Bull. (Japan), 1978,26, 790. 31 A. Takamizawa, S. Matsumoto, T. Iwata, S. Sakai, and I. Makino, Chem. and Pharm. Bull. (Japan), 1977.25. 1582.

80


127

A usefully simple method for the synthesis of the 2-amino-l,3,2-diazaphospholidine (33) as a 1: 1 mixture of cis- and trans-isomers is very limited in its potential scope by the failure of other phosphoramides to Phosphoric diamides, as their disodium or dilithium derivatives, and malonyl chlorides react 2-oxides (34). 33 to give the perhydro-l,3,2-diazaphosphorine-4,6-dione Structural assignments have been made to the two possible N-phosphorylated 1-carboxymethyl-2-iminoimidazolidines.That isomer produced by enzymic phosphorylation of (35) is the ring-phosphorylated compound (36). The second isomer, (37), was obtained as its diphenyl ester, starting from SS-dimethyl N-diphenoxyphosphinyldithiocarbonimidate, in the sequence indicated.3 4 Phosphonic and Phosphinic Acids and their Derivatives.-The replacement of the vinylic hydrogens in styrenes when these are acted upon by PCl, has been known

HO

Me (33)

CH,CO,H

CH,CO,H (36)

(35)

0

II

(PhO),P-N=C(SMe),

+ H,N(CH,),NHCH,CO;

N$

\

o\ &N!i0Ph)2 CH,CO,H (37)

32 33 34

(i) HO4 (ii)AgNO,

I1

(P hO),P-N=C N 'H

I

(dH,),NHCH,CO;

P. R. Schenkenberg and C. R. Williams, J. Heterocyclic Chem., 1977, 14, 1071. Ger. Offen. 2 600 665, 1977 (Chem. A h . , 1977, 87, 168 102). G. E. Struve, G. Gazzola, and G. L. Kenyon, J. Org. Chem., 1977,42, 4035.

Na+

128


for some time. It has now been found that, for styrenes of the type (38), two products may be formed. Of these, (48) is possibly one of rearrangement. For (38 ; R = Et or Pr) the rearranged product is the major one, but only traces of such a compound are formed when R is Me.35 0

0

CB,R

11 PhC=CHPC12 I CH,R

(38)

(39)

PhC=CH2

I

PCI,

--+

+

I1

PhC-CH,PCL,

I1

CHR

(40)

A convenient synthesis of free arylphosphonic acids, utilizing an initial Arbuzov reaction involving tris(trimethylsily1)phosphite, has been announced in preliminary form and is outlined in Scheme 5.36 Treatment of the phosphonate esters (42) with methanolic aniline yields the acid (43) as its anilinium salt. Compound (42;R=Ph) reacts further with starting phosphite, and the product on similar treatment with methanolic aniline yields the hydroxydiphosphonic acid (44). (2-Oxoalkyl)phosphonic acid esters are obtainable by ring opening of diethyl (epoxyalky1)phosphonates(45).37 0

(Me,SiO),P

A

I1 (Me,SiQ),P-CR

(41)

0

II

(42)

0

0

II I1 -% RC-P(OH), (43)

R = Phb1)

Me,SiO

OH

I

PhC [ P(OSiMe,),],

II

--%Phd [P(Q)(QH), 1, (44)

0 Reagents: i, RCOC1; ii, MeOH

Scheme 5

(45)

95

36 17

R', R3 = alkyl; R2 = H or alkyl

V. V. Rybkina, V. G. Rozinov, V. I. Glukhikh, and L. A. Larionova, Zhur. obshchei Khim., 1977,47, 1663 (Chem. Abs., 1977, 87, 135 667). M. Sekine and T. Hata, J.C.S. Chem. Comm., 1978, 285. M. Baboulene and G. Sturz, Synthesis, 1978, 456.


129

Lack of space does not permit a complete listing of the many other papers describing developments and applications of well-established synthetic procedures, but the following may be mentioned. Improved yields of prop-l-enyland prop-1-ynyl-phosphonic esters, potential precursors in the synthesis of fosfomycin analogues, are obtained by the reactions shown in Scheme 6 . Both isomers of the alkenyl esters are obtained in very high yield, and also in a considerably higher degree of isomeric purity than has hitherto been achieved.38 0

H,C=CR'CH,Cl

0

I/

i .

R' = Pr'

11

+ II,C=CR'CH,F(OR2),

1

H,CC=CP(ORZ), [iii, iv

v R' = 11, R*= Me

Me

H

0 II

H

X

Me#p(oH)z H H

i(OMe),

0 Reagents: i, P(OR2)3; ii, aq. N a ~ C 0 3 ;iii, H2-Pd; iv, H30+; v, RhC13

Scheme 6

The reaction between di-isopropylidenefructofuranose and dialkyl hydrogen phosphonates results in ring expansion to give 1,2-0xaphosphorinans, presumably by way of linear (hydroxya1kyl)phosphonic esters and subsequent ring closure.39 Ethyl (2-diethoxy)phosphinylacrylate (46) can be isolated in very high yield if one uses the reactions shown in Scheme 7.40 The esters (47; R = aralkyl) of [2,2-dimethyl-3-(2-methyl-l -propenyl)cycIopropyl]phosphonicacid have been prepared from 2,5-dimethylhexa-2,4-dieneand dimethyl (diazomethy1)phosphonate; these compounds lack the insecticidal activity associated with the carboxylic acid analogue^.^^

It -

C0,Et

i, ii

P(O)(OEt),

A s e p h P(O)(OBt),

xt

P(O)(OEt),

(46) Reagents : i, NaH-THF; ii, PhSeBr; iii, H202-CH2Cla

Scheme 7 \

(47) H. L. Slates and N. L. Wendler, Chem. and Ind., 1978, 430. 39 J . Thiem, M. Gunther, H. Paulsen, and J. Kopf, Chem. Ber., 1977, 110, 3190. *O W. A. Kleschick and C. H. Heathcock, J. Org. Chem., 1978,43, 1256. I1 J. R. Reid and R. S . Marrner, J. Org. Chem., 1978, 43, 999.

38


130

Chlorination of the dialkyl esters of (2-chloro-3-methyl-1,3-butadienyl)phosphonic acid (48) results in cyclization to yield (49) and (50) in the proportions 4-5: 1, each compound being formed as a mixture of geometrical isomers.42

Further details of the synthesis of phospha-thiazolones and 4midazolones (51) have now appeared (Scheme 8),43 and examples of the isomeric system (52) have also been recorded (Scheme 9).44 The reaction between 3-phenylprop-2-yn-1-01and (pheny1dichloro)phosphine does not give the expected phenylphosphonite ester, but rather the allenic

cl+==c

/

N € K OAr

‘P(0)

N=CCIAr

i i , (51; X

i , (0Et)Ph

Y L

(51;

x

Ivx

(51;

CCl, (51) X = NH Reagents: i, PC15-POCls; ii, H2S-Et3N; iii, pyridine-PCla; iv, NHs; v, RNHz Scheme 8

c1

Arc

/

\NCH=CCI,

Reagents: i, (Et0)sP; ii, Cl2, heat; iii, Et3N

Scheme 9 4a 43

44

A . M. Shekhade, V. M. Ignat’ev, V. I. Zakharov, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1977,47, 720 (Chem. Abs., 1977, 87, 68 455). B. S . Drach and 0. P. Labanov, Zhur. obshchei Khirn., 1977, 47, 1994 (Chem. Abs., 1978, 88, 23 052); ibid., p. 2158 (Chem. Abs., 1978, 88, 23 053). B. S. Drach and V. A. Kovalev, Zhur. obshchei Khim., 1977,47,480 (Chem. Abs., 1977,87, 39 588).

Quinquevalent Phosphorus Acids 131 phosphinate (53), which, in boiling toluene, or even at room temperature, cyclizes to 4-oxo-4,5,8-triphenyl-3,4-A5-oxaphosphabicyclo[4.4.O]octa-5,8-diene (54),a structure that has been confirmed by X-ray analysis.45 Photolysis of the diazophosphonate (55) in the presence of aldehydes or ketones gives 1,3,4-A5-dioxaphosphorins(56) in a [4 2]cycloaddition step, presumably through the rearrangement of a phosphoryl carbene formed in situ. Compounds (56) are capable of epimerizing at the carbon atom between the ring oxygens by a process of heat-catalysed ring opening and closure. Of the two products isolated from such a reaction with acetaldehyde, that with the higher melting point has the (2)config~ration.~~

+

o\p PhC=CCH,OH

PhPCI, Et,N 5

,OCH,CrCPh

/ \ Ph 'CPh=C=CH2 (5 3)

0 Ph,P(O)-E-COPh

I

+ N*

(55)

-%

II

Ph,P(O)C-CPh

A

[

Ph

)=c RpRpYp > RpY, the second phosphate group may bind directly to the enzyme. Complexes of RNase A with 2’-deoxy-2’-fluorouridylyl(3’-5’)adenosine20and of C2‘p5‘A with RNase S21have been studied by n.m.r. and X-ray crystallography respectively. In each case the inhibitor is bound at the active site in an extended conformation, with no intramolecular interaction of the bases. In the former case the phosphodiester fragment appears to interact directly with His-119; in the latter, no contact is observed. A review on phosphonates as analogues of natural phosphates, which includes a useful section on phosphonate analogues of nucleotides, has appeared.2zWhen 3-(P-~-ribofuranosyl)adenine is treated with phosphoryl chloride and trimethyl phosphate, and subsequently hydrolysed, the main product is the corresponding nucleoside 5’-phosphate, but a by-product precipitates out which appears to be 3-(~-~-ribofuranosyl)adenine-9,5’(P)-cyc1icphosphonate (22), presumably arising by attack of N-9 of the adenine ring on the intermediate nucleoside-5’-phosphorodichloridate.23 Upon aqueous hydrolysis, (22) affords the corresponding 5‘phosphate, or, in concentrated ammonia, the phosphoramidate. Treatment of thymidine with 1-adamantylphosphonodichloridate in pyridine affords 5 ’ 4 thymidyl 1-adamantylphosphonochloridate (23) and the corresponding 3 ’ 4 thymidyl isomer, in addition to smaller quantities of condensed cyclic f011~1s.~~ On addition of trityl phosphonodichloridateto uridine in hot pyridine, uridine2’,3’-OO-tritylphosphonate (24) is obtained in low yield, together with some of the 5’-O-tritylated derivative.25 On treatment of the 2’,3’-00-isopropylidene derivatives of adenosine or uridine with alkyl phosphonochloridates and triethylamine, and removal of the protecting group, the corresponding phosphonate 5’-nucleosidyl esters (25) are obtained in moderate yield.26 Cyclic Nuc1eotides.-On treatment of 8-quinolyl nucleoside-5‘-phosphates (26) with cupric chloride in pyridine, good yields of the corresponding nucleoside If phosphoric or pyrophosphoric acid is 3’,5’-cyclic phosphates are added before addition of cupric chloride, the corresponding 5’-di- or tri-

* R = purine, l9 20

21 22

23 24

25

36 27

Y = pyrimidine.

M. D. White, S. Bauer, and Y . Lapidot, Niicleic Acids Res., 1977, 4, 3029. 1. V. Antonov, A. Z. Gurevich, S. M. Dudkin, M. Ya. Karpeisky, V. G.Sakharovsky, and G. I. Yakovlev, Ellropean J. Biockern., 1978, 87, 45. S. Y. Wodak, M. Y. Liu, and H. W. Wyckoff, J. Mol. Biol., 1977, 116, 855. R. Engel, Chern. Rev., 1977, 77, 349. J. T. Uchic, Tetrnhedron Letters, 1977, 3775. S. Ya. Mel’nik, I. D. Shingarova, 1. V. Yartseva, and M. N. Preobrazhenskaya, Bio-org Khim.,1977, 3, 1034 (Chern. A h . , 1978, 88, 7273). I. D. Shingarova, S. Ya. Mel’nik, I. V. Yartseva, A. A. Borisenko, and M. N. Preobrazhenskaya, Bio-org. Khim.,1977, 3, 1641 (Clzern. Abs., 1978, 88, 105 705). Yu. V. Khropov, N. N. Gulyaev, and E. S. Severin, Biokliimiyn, 1977,42,1742(Chem.Abs., 1978, 88, 38 102). H. Takaku, M. Kato, and T. Hata, Chem. Letters, 1978, 681.

174

Organophosphorus Chemistry 0

i

Vhy

Cl-P-0-

OH

HO OH 0

HO-

II

RcH2y-oY/ HO

HO OH

(24)

(25) R = C1, BrCH,, or CICH,CONH B = Ade or Ura

phosphates are obtained.28 The starting materials (26) may be prepared by condensing 8-quinolyl phosphate and the desired nucleoside, using triphenylphosphine and 2,2’-dipyridyl diselenide. A more conventional method of preparing nucleoside 3,Y-cyclic phosphates is cyclization of the nucleoside 5’-phosphate using DCC, as exemplified by the preparation of cyclic CMP.29The cyclic nucleotides may be acylated directly to form base- and sugar-acylated deri~afives.~~, 30 Cyclic AMP may be monodansylated at pH 10, using dansyl chloride, with attack occurring at the 2’position.31A large number of nucleotides and nucleotide components appear to undergo this, or a similar, reaction. It is difficult to prepare CAMP derivatives which are substituted at the 2-position directly from CAMP. However, treatment with chloroacetaldehyde affords the 1,N6-etheno-derivative(see above), which readily undergoes alkaline hydro-

HO R (26) B = Ura,Cyt,Ade, or Gua; R = OH B = Thy; R = H 28 29

30

31

I

HO

‘0

OH

(27)

H. Takaku, T. Konishi, and T. Hata, Chem. Letters, 1977, 655. W. Wierenga and J. A. Woltersom, J. Carbohydrates Nucleosides Nucleotides, 1977,4, 189. G. Cantarelli, M. Carissimi, P. Gentili, and F. Ravenna, Farmaco, Ed. Sci., 1977, 32, 827 (Chem. Abs., 1978,88, 121 632). H. Wada. H. Nakamura, and K. Miyatake, J. Carbohydrates Nucleosides Nucleotides, 1977, 4,231 ; H. Nakamura, H. Wada, E. Sato, and Y. Kanaoka, ibid., p. 421.

175

Nucleotides and Nucleic Acids

lysis, affording 3-/3-~-(3’,5’-cyclicphospho)ribofuranosyl-4-amino-5-(imidazol2-y1)imidazole (27), which may then be condensed with suitable agents to afford 1,NG-etheno-2-substituted cAMP derivative^.^^ Finally, treatment with Nbrornosuccinirnide and alkali removes the etheno-group, affording the required derivatives. Spin-labelled derivatives of cAMP have been prepared by allowing piperidine- or pyrrolidine-derived nitroxyl species bearing spacer arms of varying length to react with 2-chloro- or 8-bromo-cAMP, or with 6-chloropurine riboside3’,5’-cyclic phosphate.33 The degree of immobilization of the spin label upon binding the analogue to the active site of rabbit muscle protein kinase has been used to derive information about the position of the adenine ring on the enzyme. Treatment of xylo-3’-amino-3’-deoxyadenosinewith phosphoryl chloride in triethyl phosphate, or with thiophosphoryl chloride in pyridine, leads directly to the corresponding cyclic phssphoramidates, (28) and (29) re~pectively.~~ Again, attack presuinably occurs initially at the 3’-amino-group, with subsequent cyclization.

(28) X = O (29)

x

=

s

The stereospecific synthesis of thymidine cyclic 3’-5’ (SIB) and (RP) phosphorotliioates has been The starting material, 2-chlorophenyl 5’-@monoinethoxytritylthymidine-3’-phosphoranilidate(30), had previously been obtained as stereoisomers and the P-enantiomers had been separated. The compound is detritylated with acetic acid and then cyclized with potassium t-butoxide in DMSO, a fully stereospecific ring-closure which affords (31); this is then treated with sodium hydride and carbon disulphide to give (32), a conversion which proceeds stereospecifically, with retention of configuration (Scheme 2). If it is

NMPh (3 1) MMTr = monsrnethoxytrityl Scheme 2

S (32)

N. Yarnaji, K. Suda, Y . Onoue, and M. Kato, Chem. and Pharm. Bull. (Japan), 1977, 25, 3239. 33 J. Iioppe, E. Rieke, and K. G. Wagner, European J. Biochem., 1978, 83,411. s4 M. Morr and R. Mengel, Chem. Ber., 1977,110, 3947. 35 W. S. Zielinksi and W. J. Stec, J. Amer. Chem, SOC.,1977, 99, 8365.

32

176


assumed that (31) and (32) exist in the chair conformation known to be found for the 1,3,2-dioxaphosphorinanylmoiety in cTMP, an absolute stereochemistry may be assigned to the stereoisomers, using 31P n.m.r. data from these and model compounds. These compounds may also be attainable by another route; treatment of thymidine with tris(dimethylamino)phosphine, followed by fast column chromatography, allows the separation of a single stereoisomer of (33), which on treatment with dinitrogen tetroxide in dichloromethane affords phosphoramidate (35) in a stereochemically retentive Treatment of (33) with methanol affords (34) in a 60:40 mixture of stereoisomers, and oxidation as before affords (36) in similar isomer ratio. The reaction of (33) with sulphur affords thiophosphoramidate (37), and treatment of (34) with methyl iodide gives methyl phosphonate (38), offering interesting scope for future work. By comparison with 31Pn.m.r. spectra of model compounds, the structure of the isolated diastereoisomer of (35) was assigned as shown, and the structure of (33) thus delineated also.

(33) X = Me,N (34) X = Me0

X

0

(35) (36) (37) (38)

X = Me,N, Y = 0 X = MeO, Y = 0 X = Me,N, Y = S X = Me, Y = 0

The fusion of the six-membered phosphate ring to the five-membered sugar ring in nucleosides imposes a rigid geometry on the latter, and thus a specific range of values for the coupling constant J1?-g,depending on whether the parent nucleoside has a- or P-configuration. It has therefore been proposed that if one wants to determine the anomeric configuration at C-1’ in a nucleoside, the 3’3’cyclic phosphate should be prepared and J1f-2rmeasured.37 The 2’-hydroxy-group seems to impose a different sugar conformation in a-anomers of nucleoside 3’3cyclic phosphates to that found in ~ - a n ~ r n e r sSome . ~ * previously anomalous results obtained in the 2’-deoxy series of nucleoside 3’,5’-cyclic phosphates have been resolved by specific deuteriation at the 2’-position to resolve the spectra, and by the use of shift reagents.39Crystal and solution studies on ara-cytidine-2‘,5’cyclic phosphate indicate that ring strain associated with the seven-membered 36

37 38

G. S. Bajwa and W. G. Bentrude, Tetrahedron Letters, 1978, 421. M. J. Robins and M. MacCoss, J . Amer. Chem. SOC.,1977, 99, 4654. M. MacCoss, F. S. Ezra, M. J. Robins, and S. S. Danyluk, J . Amer. Cliem. SOC.,1977,99, 7495.

39

M. J. Robins, M. MacCoss, and J. S. Wilson, J. Amer. Chem. SOC.,1977, 99, 4660.

177

"Ielcotic/es and Nucleic Acids

ring leads to much larger JPOCH coupling than that forecast from measurements on six-membered cyclophosphates, and warn against extrapolation of these parameters between systems.40 It has been reported that treatment of cAMP with ethylene oxide in aqueous solution for an extended period affords the corresponding P-(2-hydroxyethyl) ester (39) in moderate yield, apparently as a single stereoi~omer.~~ This anomalous finding, and much of the n.m.r. data reported, would be explained if this compound were in fact the (also electrically neutral) N1-hydroxyethyl species (40). Alkylation by epoxides tends to occur on the base rather than on the phosphodiester link,42and recent results from affinity chromatography (described below) tend to support this explanation. Treatment of cAMP with ethereal diazoalkanes affords the corresponding phospliotriesters (41) and (42) as diastereoisomericpairs that are separable by t.1.c. and assignable by 31Pn . ~ l l . r The . ~ ~ benzyl triesters (42) were able to penetrate rat glioma cells and induce morphological alteration characteristic of CAMP. On hydrolysis in H2180, (42; R=PhCHJ affords [180]benzyl alcohol but no label in the CAMP, indicating that there is C-0 bond The crystal structure of the benzyl ester of 2'-Q-acetyluridine-3',5'cyclic phosphate shows the pyrimidine to have syn conformation, with the benzyl group e q ~ a t o r i a lThis . ~ ~ is noteworthy: in cUMP, the anti-conformationis found.

OR O=P ' 1

0

0-

OH (40)

(39) R = CH,CH,OH (41) R = Me or Et (42) R = PhCH,, 2-N0,PhCH2, 4-NO2PhCH, , or 4-CH3PhCH,

Affinity Chromatography.-Lysine has been used as a spacer link for immobilizing the phosphate groups of nucleotides or oligonucleotides. For instance, lysine and AMP may be coupled using DCC to yield the nucleotidyl(P-+N)lysine, which is then immobilized on Sepharose 4B.46In another study, the y-phosphate groups of dATP and dTTP were esterified with 4-aminophenol and the amino-group was used to couple the nucleotide to Sepharo~e.~' The elution characteristics of ribonucleotide reductase from Escherichia coli bound to the derivatized Sepharose were then used to characterize two classes of allosteric effector sites on the 40

41 42 43 44

45 4~

47

W. Kung, R. E. Marsh, and M. Kainosho, J. Arner. Chem. Soc., 1977, 99, 5471. W. S. Zielinski, S. Hynie, and J. Smrt, Coll. Czech. Chem. Comm., 1978, 43, 1655. H. B. Gamper, A. S.-C. Tung, K. Straub, J. C. Bartholomew, and M. Calvin, Science, 1977, 197, 671. S. Engels and E.-J. Schlaeger, J. Medicin. Chem., 1977, 20, 907. J. Engels, 2. Nalurforsclz., 1977, 32b, 807. W. Depmeier, J. Engels, and K. H. Klaska, Acta Cryst., 1977, B33, 2436. B. Juodka, L. Liorancaite, R. Leimontaite, A. Malinauskas, J. Kulys, N. I. Sokolova, and Z. A. Sliabarova, Khim. prirod. Soedinenii, 1977, 435 (Chem. Abs., 1978, 88, 121 671). U. von Dobeln, Biochemistry, 1977,16, 4368.

178


enzyme. Similar immobilization of a nucleotide was used in another experiment, in which an inactive, but stable, semi-synthetic analogue of RNase S , containing 4-fluorohistidine instead of histidine, was bound to a column of uridine-5’(Sepharose-4-aminophenylphosphoryl)-2’(3’)-phosphate and the elution characteristics of known ribonuclease active-site ligands were examined.4 8 Methods of immobilizing nucleic acids on solid supports and applications have been critically summarized in a review letter.49 Straightforward non-specific coupling of tRNA to CNBr-Sepharose has been used for affinity purification of tRNA nucleotidyl transferase.60Single-stranded DNA has been inlmobilized by treatment with 4-diazobenzoic acid and subsequent coupling to aminoalkylaminoSepharose.61The bound material was functional in hybridization experiments. A new method for immobilization of nucleic acids consists of treating the polynucleotide with Sepharose 6B which has been activated with a bis-oxiran (e.g. butane-l,4-diol diglycidyl ether) for extended periods at slightly elevated temperatures (35 0C).52DNA, RNA, and poly(U) have reportedly been immobilized in this way. The coupled nucleic acid is treated with 0.01M sodium hydroxide for 5 days (no degradation of polyribonucleotides is mentioned) to destroy unreacted epoxy-groups, washed, and used for the purposes desired. DNA-Sepharose has been used for affinity purification of DNA polymerase I and RNA polymerase. The covalent linkage is reportedly very stable, particularly when cellulose is used as the matrix. The same method has been used to immobilize AMP, ADP and ATP,53 and evidence has been presented to show that alkylation initially occurs at N-1 of adenine, with subsequent Dimroth rearrangement to afford the N6-alkylated nucleotide (43). ATP and ADP that had been immobilized in this way were good substrates for hexokinase and pyruvate kinase, respectively. Adenosine and inosine may be condensed with ethyl laevulinate and the product then phosphorylated with phosphoryl chloride to afford After alkaline hydrolysis the carbonyl group is coupled to 6arninohexylagarose, using a water-soluble carbodi-imide, to give the immobilized nucleotide. If ADP is heated with hexamethylene di-isocyanate in HMPT at 70 “C, and subsequently treated with acid, N6-[N-(6-aminohexyl)carbamoyl]ADP is formed; in addition, the corresponding AMP and ATP derivatives are also obtained, in modest yields !55 This ostensibly curious reaction may be mediated by the formation of carbodi-imides in situ by other condensed products that resemble imidoyl phosphates and are capable of forming AS’ppppS‘A. Acid hydrolysis would then afford the products observed. The carbamoyl linkage is very stable. The 6-aminohexyl moiety may be coupled to CNBr-Sepharose or to activated soluble dextran, and the immobilized nucleotides may be used in membrane reactors or for affinity chromatography of kinases and dehydrogenases. H. C. Taylor and I. M. Chaiken, J. Biol. Chem., 1977, 252, 6991. H. Potuzak and P. D . G . Dean, F.E.B.S. Letters, 1978, 88, 161. 50 P. Schofield and K. R. Williams, J . Biol. Chem.. 1977, 252, 5584. 51 H. W. Dickerman, T. J. Ryan, A. I. Bass, and N. K. Chatterjee, Arch. Biochem. Biophys.,

48

49

62

53

54 55

1978,186,218. H. Potuzak and P. D. G . Dean, Nucleic Acids Res., 1978, 5, 297. C. W. Fuller and H. J. Bright, J . Biol. Chem., 1977, 252, 6631. H. Rosemeyer and F. Seela, Carbohydrate Res., 1978, 62, 155. Y. Yamazaki, H. Maeda, and H. Suzuki, European J . Biochem., 1977, 77, 511.

179

Nuckotides and Nucleic Acids

8-(6-Aminohexyl)-aminoguanylic acid has been prepared by treatment of 8bromoguanylic acid with 1,6-diaminohexane, immobilized on CNBr-Sepharose and used for affinity chromatography of inosinic acid dehydr~genase.~~ Treatment of AMP with diphenyl phosphorochloridate, followed by N-trifluoroacetylleucinol, and subsequent de-acylation, affords (49, which has been immobilized AMP, and used for afinity chromatography of aminoacyl-tRNA syntheta~es.~~ AD?, AT?, and (45) hdve been immobilized by attack of diazotized $-aminobenzainidoalkyl-Sepharose at (2-8 of the adenine ring;57,5 8 AMP 5 8 and CAMP^^ 6o bound to Sepharose via 1,2-dian-ninoethylB0 or 1 , 2 - d i a m i n o h e ~ y l ~ ~ ~ ~ ~ spacers introduced at C-8 by amination of the 8-bromo-compounds; (45)57 and CAM? Go immobilized via diarninoalkyl spacers introduced at C-6 by amination of the corresponding 6-chloropurine c ~ r n p o u n d s or , ~ at ~ ~C-2 ~ ~ by attack on 2-chl0ro-cAMP.~~ Species (45),57AMP,58ADP, and ATP58, have also been 9

NIICH,CH(OH)(CH,),Me I

0 0

Rib -5 ’-ql (43)

t~ =

x

H3C CH,CH,CO,Et (44) B = Ade or Ino

1-3

HO QH (45)

immobilized by oxidation with periodate followed by condensation with adipoyldihydrazo-Sepharose,and GDP by the same oxidation and condensation with aminohexyl-Sepharose.6 For the individual uses to which these matrixbound analogues have been put, the reader is referred to the original papers. 3 Polyphospliates Chemical Synthesis.--One of the methods most commonly used for the preparation of nucleoside-5’-di- or -tri-phosphates consists of treatment of the 5’monophosphate with carbonyldi-imidazole to form the nucleoside-5’-phosphorimidazolidate, which is subsequently treated with orthophosphate or pyrophos56

57 58 59

6o

63

P. E. Brodelius, R. A. Lannom, and N. 0. Kaplan, Arch. Biochem. Bioplzys., 1978,188,228. C. M. Clarke and J. R. Knowles, Biochem. J., 1977, 167, 405, 419. G. W. K. Kuntz, S. Eber, W. Kessler, H. Krietsch, and W. K. 6. Krietsch, European J . Biochem., 1978, 85, 493. W. Weber and H. Hilz, Eiiropean J. Biochem., 1978, 83, 215. E. Rieke, J. Hoppe, and K. G. Wagner, European J. Biochem., 1978, 83, 419. P. D. Wagner, F.E.B.S. Letters, 1977, 81, 81. G. R. Jacobson and J. P. Rosenbusch, F.E.B.S. Letters, 1977, 79, 8.

7

180

Organophosphorus Chernistr-y

phate to obtain the required product. It has now been shown that treatment of ribonucleoside-5’-phosphateswith excess carbonyldi-imidazole results in formation of the 2’,3’-cyclic carbonate of the nucleoside 5’-phosphorimidazolidate (46) in fair and, after phosphorylation, the 2’,3’-cyclic carbonate of the required nucleotide is formed. The cyclic carbonates are easily destroyed by hydrolysis at PI-110.5,however. Their formation may be avoided by the ‘reversed’ procedure, namely activating ortho- or pyro-phosphate with carbonyldiimidazole, destroying excess reagent with methanol, and using the nucleoside monophosphate as the attacking nucleophile. P,P6-Di(adenosine-5’)pentaphosphate may be prepared by treating ATP with diphenyl phosphorochloridate, to activate the y-phosphate group, and subsequently with ADP.64The pentaphosphate is an inhibitor of adenylate kinase, and the 31Pn.m.r. spectrum shows that it is bound asymmetrically to the enzyme.65 Treatment of the methylenediphosphonate analogues of ATP [(47) and (48)] with molten DCC in pyridine results in the formation of (49) and (50)respectively.6 6 Both were characterized on the basis of their 31P1i.m.r. spectra. Compound (49) is symmetrical; (50) could be isolated, and exists as stereoisomers which were formed in unequal quantity. Both (49) and (50) were readily hydrolysed to regenerate (47) and (48), demonstrating that in (50) only the Pa-O-P, bond is hydrolysed. Treatment of (chloromethy1)phosphonicacid with alkali and arsenious oxide yields (arsonomethy1)phosphonic acid (51). If this is treated with excess 2’,3’00-isopropylideneadenosine and DCC and then deprotected, the arsenical

l0-

HO

Hb

0

K

O \

o\p/o-p\

Ad0-5’-0/

(47) X = CH,, Y = 0 (48) X = 0,Y = CH,

0

(46)

/*” X

\ Y-P / / .No HO

(49) X = CH,, Y = 0 (50) X = 0 , Y = CH, 133

e4 65 68

OH

0

0

HO

HO

I/ I1 R’0 -AS-C H, -P -0 Rz I

(51) R1 = R2 = €I (52) R’ = H, R2 = Ado-5’ (53) R‘ = Rz = Ado-5’ (54) R‘ = Ado-5’, R2 = H

M. Maeda, A. D. Patel, and A. Hampton, Nucleic Acids Res., 1977, 4, 2843. J. Kohrle, K. S. Boos, and E. Schlimme, Annalen, 1977, 1160. B. D. N. Rao and M. Cohn, Proc. Nat. Acad. Sci. U.S.A., 1977,74, 5355. T. Glonek, R. A. Kleps, J. R. van Wazer, and T. C. Myers, Bioinorg. Chem., 1976, 6,295.

181


analogue (52) of ADP is obtained in modest yield.67Presumably esterificationcan occur at either end of (51), and (53) and (54) are also formed, but, since arsenate esters are hydrolysed spontaneously in aqueous medium, (53) will form (52) and (54) give rise to (51). Some evidence for this supposition was adduced. Species (52) was a poor substrate for 3-phosphoglycerate kinase. Treatment of ATP with 1-aminonaphthalene-5-sulphonateand a water-soluble carbodi-imide affords a new fluorescent ATP analogue, adenosine-5'-triphosphoro-y-l-(5-sulphonicacid)napthylamidate ( 5 9 , which is a substrate for RNA polymerase and valyl-tRNA synthetase from E. coli, snake venom phosphodiesterase, and other enzymes.ss Cleavage of the Pa--O-P~ bond results in a bathochromic shift of 15 nm in the fluorescenceemission spectrum, which may render (55) valuable for kinetic studies involving this cleavage. 0

I1

0

0

II -!-0 I HO

-P-

II I

HO

v

0

Ade

HO OH

(55)

~-~~P-Labelled ribonucleoside diphosphates are not generally commercially available. However, [E-~~PJADP may be obtained readily in high yield by using [LX-~~PIATP as a substrate for yeast hexokinase and glucose at 25 "C, and, with more enzyme and at a higher temperature, [LX-~~PIGDP, [E-~~PIUDP, and [aT]CDP can be obtained similarly from the labelled tripho~phates.~~ [E-~~P]dATP of high activity may be prepared by treating the nucleoside with labelled orthophosphate and trichloroacetonitrile in DMSO (to form the monophosphate) evaporation of all volatile materials, and addition to the residue of a mixture of pyruvate kinase and myokinase with phospho-en01 pyruvate and a trace of dATP.70Myokinase catalyses the reaction: dAMP

+ dATP F==+ 2dADP

and the [ E - ~ ~ P I ~ Athus D P formed is phosphorylated to the triphosphate by pyruvate kinase and PEP, and is thus available to re-enter the myokinase reaction. The procedure may also be applied to preparing [E~~PIATP (using a trace of ATP instead) and also [cc-32P]GTPand [CX-~~PI~GTP, with appropriate modification. P-32P-Labelledpurine nucleoside triphosphates may be prepared by juggling the same enzymes. [Y-~~P]ATP and AMP are incubated with myokinase to afford [/3-32P]ADP;the myokinase is then inactivated by extraction with phenol, and pyruvate kinase and PEP are added to afford [/3-32P]ATP.71 dAMP may also be used as a substrate for myokinase, or GMP, dGMP, and dIMP for guanylate kinase, which effects the comparable reaction in guanosine nucleotides. 67 6g 69

70

71

D. Webster, M. J. Sparkes, and 13. B. F. Dixon, Biochem. J., 1978, 169, 239. L. R. Yarbrough, Biochem. Biophys. Res. Comm., 1978, 81, 35. I. L. Cartwright and D. W. Hutchinson, NucIeic Acids Res., 1977, 4, 2507. R. H. Symons, Niicleic Acids Res., 1977, 4, 4347. Y. Furuichi and A. J. Shatkin, Nitcleic Acids Res., 1977, 4, 3341.

182


ATP may be enzymically prepared from adenosine on a large scale, using a three-enzyme reactor in which the enzymes are immobilized on cross-linked polyacrylamide gel particles. Adenosine is phosphorylated to AMP by adenosine kinase and a trace of ATP; Myokinase converts the AMP with more ATP into ADP; and ADP is constantly phosphorylated to ATP by acetyl phosphate and acetate k i n a ~ e Starting .~~ with 40 gram of adenosine, a 36% yield of ATP could be isolated after 10 days, and recovery of the enzymes was high. The acetyl phosphate-acetate kinase regenerative system for ATP has also been used to drive the formation of creatine phosphate from creatine and ATP by creatine kinase on a preparative scale.73 It has been reported that purified Fl ATPase from yeast mitochondria catalyses the phosphorylation of ADP by oleyl phosphate to give ATP and oleic In the presence of th2 oxidative phosphorylation uncoupler 2,4-dinitrophenol, the hydrolysis of oleyl phosphate occurs without formation of ATP. This and other evidence has prompted the proposal that this ATP synthesis corresponds to the terminal chemical step in oxidative phosphorylation. Clearly, P X is not yet dead ! A critical overview of theories concerning formation of ATP by energized protons has been given.'6 Much of the experimental work in this field and others concerned with the ATPase mechanism has involved measurements of isotopic exchange between ATP, orthophosphate, and water, and a useful review has been published.7s As an example, the oxygen atoms of the y-phosphoryl group of Mg-ATP are able to exchange with those of water during a reversible step in the hydrolysis of ATP by myosin:

-

M*-ATP

+M**-ADP-Pi kcs

k-3

The time available for this exchange may be varied by altering the concentration of actin in the medium, and the rate constants for exchange of the oxygen atoms of enzyme-bound phosphate may thus be determined.77Only three of the four oxygen atoms are exchangeable. However, if myosin is cleaved at the 'hinge' region, the non-exchanging oxygen also becomes exchangeable, suggesting that it was originally bound to the enzyme at the hinge, and also suggesting how ATP cleavage may be coupled to hinge movement in muscle contraction. Exchange of oxygen between solvent water and the lsO-labelled terminal phosphate group of ATP in chloroplast lamellae has been examined.78 In the absence of net ATP synthesis, almost full equilibration occurs (lSO washout), but when net synthesis occurs only about one molecule of solvent water enters. The difference is kinetic: ATP dissociates from its binding site faster when net photophosphorylation is occurring. Comparison of the washout rate with the rate of p-bridge to p-non72

73 74

75 76

77 7*

R. L. Baughn, 0.Adalsteinsson, and G. M. Whitesides, J . Amer. Chem. SOC.,1978, 100, 304. Y.-S.Shih and G . M. Whitesides, J. Org. Cheni., 1977, 42, 4165. R. Johnston and R. S . Criddle, Proc. Nat. Acad. Sci. U.S.A., 1977, 74, 4919. R. J. P. Williams, F.E.B.S. Letters, 1978, 85, 9. P. D. Boyer, Accounts Clzem. Res., 1978, 11, 218. K. K. Shukla and H. M. Levy, Biochemistry, 1977, 16, 5199. M. J. Wimmer and I. A. Rose, J. Biol. Chem., 1977, 252, 6769.


183

bridge l 8 0 scrambling (for a description of this technique, see last year’s Report79) indicates that washout is faster than scrambling, but both reactions occur in almost the same fraction of molecules in the same incubation. The washout reaction is probably due to multiple cycles of reversible hydrolysis of ATP on the chloroplast coupling factor. The stereochemistry of inter-nucleotidic bond formation by tRNA nucleotidyltransferase from bakers’ yeast has been investigated, using the stereoisomers of adenosine 5‘-(cc-thio)triphosphate (56).80 One isomer (‘A’) was a substrate, the other (‘B’) a competitive inhibitor. The tRNA molecule prepared using isomer A thus has a terminal phosphorothioate link in the -CpCpA end. Limited hydrolysis with RNase A followed by deamination with bisulphite affords solely the endo-isomer of uridine-2’,3’-OO-phosphorothioate, and the terminal phosphorothioate link in the tRNA molecule possessed the R configuration. This is essentially the same result as that detailed previously79for RNA polymerase. Adenosine5’-O-phosphorothioate is a substrate for adenylate kinase from rabbit muscle, affording (57). The sample of (57) is a substrate for pyruvate kinase and PEP, affording isomer A of (56), but not for arginine pliosphokinase and phosphoarginine, a system that is selective for isomer B of (57).81 Thus the adenylatekinase-catalysed phosphorylation of adenosine-5’-O-phosphorothioateis stereospecific, involving binding and rotational immobilization of the thiophosphate group, and affording only isomer A of (57) as the product. Y 0 HO--P-O-~-O-P-O~

I1 i HO

II I

HO

X

0

I1 I

0

QB

HO

II HOI

S

I1

HO-P-O-P-OvAde

HOI

HG OH ( 5 6 ) B = Ade, ( 5 8 ) B = Ade, ( 5 9 ) B = Gua,

X = S, Y = 0 X = 0, Y = S X = 0,Y = S

HO OH (5 7)

If DNA templates are transcribed by E. coli RNA poIymerase, using a nucleoside 5’-(y-thio)triphosphate [(58) or (59)] as one of the nucleotide substrates, the rate of synthesis is unaffected, but the 5’-terminal purine nucleoside (if the appropriate one was selected) bears a 5’-(y-thio)triphosphate chain and binds with high efficiency to mercuriated agarose.8 2 If the thiotriphosphate substrate is used only for elongation, but not initiation, the transcript is not bound. This affords a very sensitive assay for RNA synthesis in uitro which has been applied to bacteriophage ADNA transcription, and the isolated transcripts have been examined to show that accuracy of initiation and fidelity of transcription are maintained despite using the triphosphate analogues.83 79 80

81 82

83

J. B. Hobbs in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1978, Vol. 9, p. 151. F. Eckstein, H. Sternbach, and F. von der Haar, Biochemistry, 1977, 16, 3429. K.-F. R. Sheu and P. A. Frey, J . Biol. Chem., 1977, 252, 4445. A. E. Reeve, M. M. Smith, V. Pigiet, and R. C. C. Huang, Biochemistry, 1977, 16, 4464. M. M. Smith, A. E. Reeve, and R. C. C. Huang, Biochemistry, 1978, 17,493.

184


Analogues of ATP and GTP continue to find much application for the study of adenylate cyclase from various sources. In particular, (60) stimulates adenylate cyclase activity on binding to a regulatory site for guanine n u ~ l e o t i d e s , ~as~ - ~ ~ also do (59) 87 and (61).88GTP also stimulates this activity, but the stimulation is less, and relatively short-lived. There is a GTPase activity associated with the regulatory which, according to one model, is only potent in the fully activated enzyme,9oand which is inhibited by cholera toxin. Hydrolysis of the guanine nucleotide results in loss of adenylate cyclase stimulation. While (61) is not hydrolysed, GTP and (60) are substrates for the GTPase activity,88and partially purified rat liver membranes also contain pyrophosphorohydrolaseactivities capable of hydrolysingATP, (62),9l and (47)g2which may or may not be associated with the enzyme, but which may complicate the interpretation of other stimulatory effects. Curiously, (58) has been reported to stimulate adenylate cyclase, the effect being additive to that induced by (60).93It is possible that a small quantity of (59) contaminated the sample of (58), giving the anomalous result. Adenylate cyclase will accept (58) as a s ~ b s t r a t e ?but ~ is strongly inhibited by the noncyclizable (63),g4 which becomes tightly bound to the active (but not the regulatory) site. But, caveat lector: the results summarized here were obtained for adenylate cyclase from a number of different sources, and any generalizations made may be quite unfounded. In another guanine-nucleotide-associatedreaction, (61) has been found to be a far more effective promoter of tubulin polymerization than C J T P . ~ ~ A stringent factor associated with a particulate fraction from stringent strains of E. coli transfers pyrophosphate from ATP to the 3’-hydroxy-groups of GDP or GTP in a single step to afford (64) and (65), respectively, as shown by experiments employing ATP that is labelled at the ci-, p-, and y-phosphate groups as 0 0 0 HO-P-X-P-Y-P-OwB

It

I

HO

I1

I

HO

0 0 HO-/{O-()-O~~Ade

I/

I

HO

HO

HO OM (60) B = Gua, X = NH, Y = 0 (61) B = Gila, X = 0,Y = CII, (62) B = Ade, X = NW, Y = 0 84

85 86

87

88 89 90

91

92 93 94 95

HO

2

0 0 H

XOEt

J. L. Young and D. A. Stansfield, Biochem. J., 1978, 169, 133. M. Svoboda, P. Robberecht, J. Camus, M. Deschodt-Lanckman, and J. Christophe, European J. Biochem., 1978, 83, 287. F. F. Snyder and G . I. Drummond, Arch. Biochem. Biophys., 1978, 185, 116. D. Cassel and Z. Selinger, Biochem. Biophys. Res. Comm., 1977, 77, 868. C. Londos, M. C . Lin, A. F. Welton, P. M. Lad, and M. Rodbell, J. Biol. Chem., 1977,252, 5180. D. Cassel and 2. Selinger, Proc. Nat. Acad. Sci. U.S.A., 1977, 74, 3307. M. S. Rendell, I’d. Rodbell, and M. Berman, J. Biol. Chem., 1977, 252, 7909. R. A. Johnson and J. Welden, Arch. Biochem. Biophys., 1977, 183, 216. H. Flodgaard and C. Torp-Pedersen, Biochem. J., 1978, 171, 817. A. Monneron and J. d‘Alayer, F.E.B.S. Letters, 1978, 90, 157. S. Hynie and J. Smrt, F.E.B.S. Letters, 1977, 81, 331. I. V. Sandoval, E. McDmald, J. L. Jameson, and P. Cuatrecasas, Proc. Nut. Acnd. Sci. U.S.A., 1977, 74, 4881.

185

0 OH

A

O=P--OH

I

(64) n = in = 2 (65) n = 3, rn = 2

s ~ b s t r a t e s .Compound ~~ (64) is degraded to GDP by a separate riboson-nalfraction-associated enzyme activity, pyropl-nosphatebeing apparently cleaved off in a single step.g7>gs No ppGp of the corresponding 2’-phosphate or 2’,3’-cyclic phosphate could be detected as an intermediate in the hydrolysis. The activity of ADP-glucose synthetase, the rate-limiting enzyme of bacterial glycogen synthesis, is regulated by (64) and (65) at physiological coiicentrati~ns.~~ When mouse L-cells are treated with interferon or double-stranded DNA, an inhibitor of ribosomal protein synthesis is formed, having a low molecular weight and being effective at subnanomolar concentrations. The enzyme responsible for its formation may be isolated by binding to poly(1). poly(C)-agarose, and extensive chemical and enzymic degradative studies of the inhibitor itself lead to the conclusion that its structure is pppA2’p5’A2’p5’A, containing the ‘unnatural’ 2’,5’-phosphodiestcr link.loOThe corresponding dimer (inactive) and the tetrainer and higher oligomers (active) are also formed by the enzyme. Final corroboration of the structure will need to await its total synthesis. It is noteworthy that the same material seems to be fornied in interferon-treated chick embryo cells,1o1and in rabbit reticulocyte lysates treated with double-stranded DNA.lo2pppA2’pS’A2’p5’A is thought to exert its influence by activating an endonuclease which degrades rnRNA.lo3 It has been conjectured lo4that the molecule may be a ‘pleiotypic effector’. Studies on DNA-polymerizing activities from normal and leukaemic human cell lines suggest that ara-ATP and ara-CTP are competitive inhibitors of dATP and dCTP, respectively, as substrates for DNA polymerases cc and p, and of deoxyribonuclcoside triphosphates generally as substrates for terminal deoxyiiucleotidyl transferase.lo5Similar conclusions were reached using ara-CTP as an H. Schmale, M. Farnung, S. Fehr, and D. Richter, Z . physiol. Chem., 1977, 358, 1613. J. Sy, Proc. Nat. Acnd. Sci. U.S.A., 1977, 74, 5529. 9 8 E. A. Heinemeyer and D. Richter, F.E.B.S. Letters, 1977, 84, 357. 99 D. N. Dietzler and M. P. Leckie, Biochem. Biophys. Res. Comm., 1977, 77, 1459. looI. M. Kerr and R. E. Brown, Proc. Nut. Acad. Sci. U.S.A., 1978, 75, 256. lol L. A. Ball and C . N. White, Proc. Nat. Acad. Sci. U.S.A., 1978, 75, 1167. lo2A. G. Hovanessian and 1. M. Kerr, European J . Biochcm., 1978, 84, 149. 103 C . Baglioni, M. A. Minks, and P. A. Maroney, Nature, 1978, 273,684. lo4T. Hunt, Nature, 1978, 273, 97. lo5R. A. Dicioccio and B. I. Srivastava, European J . Biochem., 1977, 79, 41 1. 9(i

g7

186


inhibitor of the DNA polymerases CL and from calf thymus.1o6The 2’,3’dideoxythymidine analogue (66) is a powerful inhibitor of DNA polymerases ,B and y from HeLa cells, but barely inhibits DNA polymerase a, and is ineffective for all aspects of DNA synthesis when dTTP is present, suggesting that DNA polymerase CL is the enzyme of primary importance for cellular synthesis of DNA.lo7ara-ATP has been found to inhibit the polyadenylation of RNA that is catalysed by chromatin-associated poly(A) polymerase, and hence it has been suggested that the primary target of the anti-tumour drug ara-adenosine is the post-transcriptional addition of the poly(A) tail that is normally associated with rnRNA.Ios 0

0

0

H H (66) B (67) B (68) B (69) B

Thy = Ade = Gua =

= Cyt

Mercuriated pyrimidine nucleotides ostensibly offer a valuable method for studying RNA synthesis de novo in isolated nuclei. The mercuriated pyrimidine deoxyribo- and ribo-nucleoside-5’-triphosphatesare substrates for DNA and RNA polymerases respectively, although some reduction in the rate of synthesis of polynucleotide occurs.1ogThus, if care is taken to remove endogenous globin mRNA,II0de novu production of globin mRNA may be quantitated by isolation of the mercuriated RNA on thiol-bearing columns, and the fidelity of synthesis may be examined.lll However, it appears that a number of snags are associated with the use of these analogues. Mercuriated RNA transcripts are shorter than the corresponding non-mercuriated transcripts, suggesting premature chain termination.logMethylation of RNA in vitro by S-adenosylmethionine is severely reduced, as also is polyadenylation of the transcript terminus. And, most seriously, the demercuriation of the mercuriated nucleotides and nucleic acids by thiols will lead to under-estimates of mRNA synthesis. The mercuriated nucleotides are substrates for the polymerizing enzymes as their thiomercuri-derivatives, but a careful study 112has shown that these are unstable, the rate of decomposition depending on the nature of the thiol present. Scheme 3 summarizes the reactions deduced from treatment of 5-mercuriuridylic acid with thiols. From this Scheme it is evident that any product of synthesis in vitro can only be partially mercuriated in any one pyrimidine residue; that the products of demercuriation are also lo6 107 108 109 110 111 112

S. Yoshida, M. Yamada, and S. Masaki, Biochim. Biophys. Acta, 1977, 477, 144. M. A. Waqar, M. J. Evans, and J. A. Huberrnan, Nucleic Acids Res., 1978, 5 , 1933. K. M. Rose and S. T. Jacob, Biochem. Biophys. Res. Comm.,1978,81, 1418. IS. P. Schafer, Nucleic Acids Res., 1977, 4, 4465. M. Zasloff and G. Felsenfeld, Biochemistry, 1977, 16, 5135. S. H. Orkin, Biochemistry, 1978, 17, 487. C. Van Broeckhoven and R. De Wachter, Nucleic Acids Res., 1978, 5, 2133.

187


pU-5HgSR

PU-5Hgf

Scheme 3

substrates for the polymerizing enzymes; and that cross-links between polynucleotides may be formed. Several analogues of ribonucleoside triphosphate bases have been studied, to determine their effect on the termination of transcription in vitro by RNA polymerase from E. culi,l13 and considerable numbers of ATP analogues have been used to study the substrate specificity of the same enzyme in initiation and elongation steps, 114the substrate specificity of aminoacyl-tRNA synthetases,l15 and that of mitochondria1 adenine nucleotide translocase.ll6 Certain ATP and CTP analogues are substrates for tRNA nucleotidyl transferase, becoming incorporated into the CpCpA Lastly, various GTP analogues, including mRNA ‘cap’-type structures, have been investigated for their ability to interact with Elongation Factor 1 (EF 1) in the synthesis of wheat protein.l18 Affinity Labelling.-Upon irradiation, at 254 nm, of ATP-aminoacyl-tRNA synthetase complexes, the nucleotide is cross-linked directly to the enzyme.l19By using ATP that is labelled in different regions of the molecule, the whole nucleotide molecule has been shown to be incorporated. While irradiation of the enzyme alone leads to dose-dependent loss of activity, the inactivated enzyme cannot cross-link to ATP, suggesting that the process requires active enzyme and takes place at the ATP receptor site. On proteoIytic digestion of the cross-linked enzyme, a labelled hexapeptide has been isolated. In the absence of ribosomes, irradiation of Elongation Factor G (EF-G) in the presence of GTP or GDP results in attachment of the nucleotide to the protein, apparently via a sulphur atom, with concomitant inactivation of the EF-G function. The kinetics of inactivation are the same in the absence of nucleotide, but, if EF-G is treated with N-ethylmaleimide to block the nucleotide-binding site, no nucleotide becomes attached on subsequent irradiation, suggesting that the guanine nucleotide does cross-link to the nucleotide-binding site.120 113 114 115

N. F. Neff and M. J. Chamberlin, J. Biol. Chem., 1978, 253,2455. S. A. Kumar, J. S. Krakow, and D. C. Ward, Biochim. Biophys. Acta, 1977, 477, 112. W.Freist, H. Sternbach, F. von der Haar, and F. Cramer, European J. Biochem., 1978,84, 499.

116

E. Schlimme, K.S. BOOS,D. Bojanovski, and J. Lustorff, Angew. Chem. Internat. Edn.,

117

M.Sprinzl, H.Sternbach, F. von der Haar, and F. Cramer, European J. Biochem., 1977,

118 11Q

J. E.Allende, A. Tarrago, and A. J. Shatkin, Arch. Biochem. Biophys., 1978, 187,335.

1977, 16,695. 81, 579.

120

V. T. Yue and P. R. Schimmel, Biochemistry, 1977, 16,4678. M.S. Rohrbach and J. W. Bodley, Arch. Biochem. Biophys., 1977, 183,340.

188


Many of the affinity-labelling studies reported recently have involved azidonucleotides in which the azido-group is attached to the heterocyclic base. For instance, CAMPis brominated and treated successively with chloroacetaldehyde and triethylammonium azide to afford S-azido-l,Ns-ethenoadenosine-3’,5’phosphate (70), which is a fluorescent photoaffinity label for CAMP-receptor sites121 The corresponding 5’-triphosphate has also been prepared and used for photoaffinity labelling of F1 ATPase from Micrococcus Zilteus.1228-Azidoadenosine-5’-diphosphatehas been used to photolabel the atractylate-sensitive adenine nucleotide carrier of mitochondria1 membranes,123and the analogous triphosphate binds to the mitochondria of brown adipose tissue, and on irradiation it labels both the adenine nucleotide translocator and another protein, thought to be the regulatory site of an ion-unipolt which dissipates the trans-membrane electrochemical gradient, without ATP synthesis, when cell metabolism does not require it .lZ4S-Azidoguanosine-5’-triphosphatehas been prepared by bromination of GMP, displacement of bromine using triethylammonium azide, and phosphorylation to the triphosphate, and has been used to photolabel the ,8monomer of t ~ b u 1 i n . l6-Azidopurine ~~ ribonucleoside-5’-triphosphate(73) has been prepared by phosphorylating 6-methylthiopurine riboside (71) to the 5’triphosphate (72) and then treating this with N-chlorosuccinimide and sodium azide.12‘-?The ribonucleoside moiety of (73) has also been incorporated as the 3’-terminus of an analogue of CpA, and, on forming the 2’(3’)-phenylalanyl ester, the analogue supports partial reactions of protein synthesis. Photolabelling studies are planned. Following the revelation that azidopurine nucleotides are very readily reduced to the corresponding aminopurine nucleotides by dithiols comes a report that aryl azides are also readily reduced by the same agents,lZ7the haIf-life being of the order of 10 minutes in a five-fold excess of dithiothreitol at pH 8. An arylazido analogue of ADP, (74), has been used to photolabel mitochondrial F1 ATPaselZ8and photophosphorylation Coupling Factor 1 (CF-1).lZ Compound (79, prepared by condensation of GTP with 4-azidoaniline, using a watersoluble carbodi-imide, has been used for the photolabelling of GTP-binding proteins in pigeon erythrocyte A very similar analogue (76) has been used to localize the GTP-binding site on ribosome-bound EF-G.131 G.Dreyfuss, K.Schwartz, E. R. Blout, J. R. Barrio, F.-T. Liu, and N. J. Leonard, Proc. Nat. Acnd. Sci. U.S.A., 1978, 75, 1199. 122 H.-J. Schafer, P. Scheurich, G. Rathgeber, and K. Dose, Nucleic AcidsRes., 1978, 5 , 1345. l23 G.Schafer and S. Penades, Biochem. Biophys. Res. Comm., 1977, 78, 81 1 . 124 G . M. Heaton, R. J. Wagenvoosd, A. Kemp, jun., and D . G . Nicholls, Europenn J. Biochern., 1978, 82, 515. 125 R. L. Geahlen and 5. E. Haley, Proc, Nat. Acad. Sci. U.S.A., 1977, 74, 4375. 126 K. Quiggle, M. L. Wejrowski, and S. Chladek, Biochemistry, 1978, 17, 94. 127 J. V. Staros, H. Bayley, D. N. Standring, and J. R. Knowles, Biochem. Biophys. Res. Comm., 1978, 80, 568. 128 J. Ianardi, G. J. M. Lanquin, and P. V. Vignais, F.E.B.S. Letters, 1977, 80, 317. 129 G. Schiifer, G. Onur, K. Edelmann, S. Bickel-Sandkotter, and H. Strotman, F.E.B.S. Letters, 1978, 87, 318. 130 T. Pfeuffer, J . Biol. Chem., 1977, 252, 7224. 131 A. S. Girshovich, T. V. Kurtskhalia, V. A. Pozdnyakov, and Yu. A. Ovchinnikov, F.E.B.S. Letters, 1977,80, 161 ; A. S. Girshovich, E. S. Bochkareva, V. A. Pozdnyakov andYu. A. Ovchinnikov, ibid., 1978, 85, 283. 121

189

Ncrcleotides and Nucleic Acids

(71) R1 = H, Rz = MeS (72) K’ = P,O&, FP = MeS ( 7 3 ) R’ = P,O,I&, R’ = N,

COO OH

0

0

0

HO

HO

HO

I

(CHZ), N3

NO2

(74)

HO OH

(75) R = 4azidophenyl (76) R = 4azidobenzyl

Despite the preponderance of photoaffinity-labelling reagents, some studies have involved alkylating nucleotide derivatives. 5’-O-(N-bromoacetyl-4-aminophenylphosphoryl)-3’-N-~-phenylalanyl puromycin aminonucleoside (77) forms a covalent bond to 23s RNA in the active centre of peptidyltransferase of E. coli ribosomes, and the sequence of the pentanucleotide to which it becomes attached has been determined.132Mitochondria1 F, ATPase has been alkylated by the nitrogen-mustard ATP analogue (78), the /3-subunit of the enzyme becoming labelled.133The same subunit of Fl ATPase from a strain of Micrococcus is also labelled by the 6-(3-carboxy-4-nitrophenyl)thiopurineanalogue (79).134 The products of treatment of GMP and ADP with periodate, i.e. (80) and (81), have been used as affinity reagents for hypoxanthine phosphorib~syltransferase~~~ and phenol sulph~transferase,~~~ respectively, While this Reporter does not abstract conference reports, the Report of the Spring Meeting of the Gesellschaft fur Biologische Chemie contains several interesting accounts of the use of affinitylabelling reagents. D . J. Eckermann and R. H. Symons, European J. Biochem., 1978, 82, 225. V. G. Budker, I. A. Kozlov, V. A. Kurbatov, and Y. M. Milgrom, F.E.B.S. Letters, 1977, 83, 11. 134 F. W. Hulla, M. Hockel, M. Rack, S. Risi, and K. Dose, Biochemistry, 1978, 17, 823. 135 W. Gutensohn and H. Jahn, 2.physiol. Chem., 1977, 358, 939. 136 R. T. Borchardt, S. E. W u , and C. S. Shasteen, Biochem. Biophys. Res. Comm., 1978, 81, 841. 137 2. physiol. Chem., 1978, 359, 251, et seq. 132 133

190


HN OH

I

co H,N-CH

I

I

CH,Ph (7 7)

Cl

HO OH (79)

(80) B = Gua, n = 1 (81) B = Ade, n = 2

4 Oligo- and Poly-nucleotides Chemical Synthesis.-A new review on the synthesis of oligoribonucleotides via phosphotriester intermediates has appeared.13* Cyclic enediol pyrophosphates such as di(1,2-dimethylethenylene) pyrophosphate (82) have been employed in the synthesis of oligodeoxyribonucleo188

J. H. van Boom, Heterocycles, 1977, 7, 1197.

191

Nucleotides and Nucleic Acids 0

Ph0 -PM e p p

I

C1

T T M e

0-P-0-P-0

tI

0

It

NO*

0 (82)

OH

II

MMTrO

(85)

0-P-0

0 (83)

MMTr = monomethoxytrityl

0

I

CHMeCOMe (84)

Reagents: i, (82); ii, Et3N in CHzClz; iii, thymidine; iv, Et3N in DMF

Scheme 4

tide^.^^^^^^^ An example of their use is shown in Scheme 4. 5’-O-Monomethoxytritylthymidine reacts with (82) to form enediol phosphotriester (83) in high yield, which on treatment with unprotected thymidine affords (84). Esterification takes place almost exclusively at the 5’-hydroxy-group of thymidine, but about 2% of the 3’-phosphotriester is produced. Phosphotriester (84) may be used as starting material for further chain elongation, or deprotected with trifluoroacetic acid (to remove the trityl group) and triethylamine in aqueous acetonitrile (to remove the 1-methylacetonyl group). It is claimed that less than 2 % of cleavage of inter-nucleotide bonds occurs, and no isomerization. 4-Nitrophenyl phenyl phosphorochloridate (85), prepared by treating phenyl phosphorodichloridate with 4-nitrophenol, in the presence of 5-chloro-1-ethyl-2methylimidazole has been described as a new phosphorylating agent for oligonucleotide synthesis.l 41 2’,5’-Pro tected ribonucleosides are phosphorylated by (85) at the 3’-position, affording the corresponding phosphotriesters in high yield. The 4-nitrophenyl group is removed quantitatively by treatment with 4-thiocresol and triethylamine in acetonitrile. Much attention has been focussed on the ease of introduction and removal of protecting groups for the inter-nucleotide linkage in the triester synthesis. In a rather limited study of the comparative merits of the 2-cyanoethyl, 2,2,2-trichloro139 140

141

F. Ramirez, E. Evangelidou-Tsolis, A. Jankowski, and J. F. Marecek, J . Org. Chem., 1977, 42, 3144. F. Ramirez and J. F. Marecek, Accounts Chem. Res., 1978, 11, 239. C. B. Reese and Y . T. Y. Kui, J. C. S. Chem. Comm., 1977, 802.

192


ethyl, 2-nitrobenzyl, and anilido-groups in protecting the phosphate group of 2’-O-benzoyluridine-3’-phosphate, protection as the trichloroethyl phosphoranilidate was judged to offer advantages in stability and selective The trichloroethyl group may be rapidly and specifically removed, using zinc and acetylacetone in ~ y r i d i n e ,the l ~ ~acetylacetone solubilizing the zinc salts that are formed in the deprotection reaction as chelates. Phosphorus-31 n.m.r. spectroscopy has been used to follow the course of deprotection. The 2-cyanoethyl group is frequently used as a protecting group for the phosphate moiety in the triester synthesis, as demonstrated in the synthesis of an anticodon loop oligoribonucleotide containing N6-(N-threonylcarbony1)adenosine from subunits of type (86).144 The 2-cyanoethyl group is readily removed, using triethylamine in p ~ r i d i n e . l145 ~ ~Oligomers * of thymidylic acid up to d(Tp),,T have been synthesized, using the phosphotriester method, in a study in which each coupling step to form the inter-nucleotide phosphotriester was followed by treatment with bis(triazolyl)-4-chlorophenylphosphate, to phosphorylate any unreacted 5’-hydroxyl component and facilitate subsequent chromatographic Novel methods of protection of sugar hydroxy-groups have been employed in oligoribonucleotide syntheses. The 5’-hydroxy-group has been protected as the laevulinate ester by esterification using DCC in a synthesis of (UpAp),UpA that is based on building blocks of type (87).146The laevulinate group is removed MeCO(CH,),CO,

MMTrO

-YYB

-k0J

\H/

OMe

0 OAc

I

Cl,CCH,O-P=O

I

OCH,CH,CN

rapidly and quantitatively using hydrazine. Following the assembly of the oligomer, the 2-chlorophenyl groups are removed, using fluoride ion in aqueous medium. This is important : otherwise phosphofluoridate intermediates react with unprotected 5’-hydroxy-groups to form 5’-5’ phosphodiesters. The 2-nitrobenzyl group has been employed as protection for the 2’-hydroxy-group in phosphodiester It is introduced by treatment of the relevant and phosphotriester nucleoside with 2-nitrobenzyl bromide and sodium hydride, and removed follow142 149 144

145

146 147

E. Ohtsuka, H. Tsuji, T. Miyake, and M. Ikehara, Chein. and Pharm. Bull. (Japan), 1977, 25,2844. R. W. Adamiak, E. Biala, K. Grzeskowiak, R. Kierzek, A. Kraszewski, W. T. Markiewiez, J. Stawinski, and M. Wiewiorowski, Nucleic Acids Res., 1977, 4, 2321. R. W. Adamiak, E. Biala, K. Grzeskowiak, R. Kierzek, A. Kraszewski, W. T. Markiewicz, J. Okupniak, J. Stawinski, and M. Wiewiorowski, Nucleic Acids Res., 1978, 5 , 1889. A. K. Sood and S. A. Narang, Nucleic Acids Res., 1977, 4, 2757. J. H. van Boom and P. M. J. Burgers, Rec. Trav. chin?., 1978, 97, 73. E. Ohtsuka, S. Tanaka, and M. Ikehara, Chem. and Pharm. Bull. (Japan), 1977,25, 949.


193

ing oligonucleotide synthesis by irradiation with U.V. light of wavelength > 280 nrn. No photohydration or dimerization of cytidine nucleotides was observed. In another study, 2’,5’-disilylated nucleosides have been used as building blocks for oligoribonucleotides, the silylating agent of choice being t-butyldimethylsilyl chloride (TBDMS).148Treatment of an unprotected nucleoside with TBDMS affords the 2’,5’-disilylated derivative (from which the 5’-O-silyl group may be selectively removed with 80 % acetic acid). The disilyl derivative is treated with 2,2,2-trichloroethylphosphodichloriditeat low temperature, and subsequently with 2’,3’-00-isopropylideneuridine,to form a phosphite triester, which is oxidized with aqueous iodine, afiording (88). The specificity of the phosphorylating agent for providing the 3’,5’-linked material (as opposed to 3’,3’- or 5’,5’-phosphodiesters) is claimed to be good. Both the silyl and trichloroethyl groups are removed simultaneously with fluoride ion in THF. This appears a risky procedure, with the attendant likelihood of producing free 2’- and 5’hydroxy-groups adjacent to a phosphorofluoridatelink, and hence the formation of a triester, with isomerization or cleavage of the inter-nucleotidic link.

““VB 0 OR

I

0

II

Cl,CCN,O -?=0 I

O

w

r

0 0

X

Me

a

?I

Bu‘SiPh,

Me

(88) R = Me,CSiMe,

(89)

The synthesis by the phosphotriester method of several oligonucleotides designed as versatile adaptors for molecular cloning has been described.149The popularity of arylsulphonyltetrazoles as condensing reagents to form the internucleotidic link is increasing,144, 149 although tri-isopropylsulphonyl chloride (TPS) still finds wide usage.150 The 8-quinolyl group has been introduced as a protecting group at the 5’phosphate terminus during ‘phosphodiester’ synthesis of an oligodeoxynucleotide bearing a 5’-phosphate.151 The group is introduced as described previously, and removed using cupric chloride in aqueous DMSO. If a deoxyribonucleoside-5’-phosphate is treated with t-butyldiphenylsilyl chloride in pyridine in the presence of imidazole,both the 3’-hydroxy-groupand the phosphate 1459

150

K. K. Ogilvie, N. Theriault, and K. L. Sadana, J. Amer. Chem. SOC., 1977, 99, 7741. C . P. Bahl, R. Wu, R. Brousseau, A. K. Sood, H. M. Hsuing, and S. A. Narang, Biochem. Biophys. Res. Comrn., 1978, 81,695. P. Cashion, N. Notman, G . Sathe, T. Cadger, K. Porter, and E. Jay, Nucleic Acids Res.,

151

H. Takaku, R. Yamaguchi, and T. Hata, J.C.S. Perkin 1, 1978, 519.

148 149

1977, 4, 2593.

194


group are silylated.ls2The silyl phosphate is unstable in aqueous pyridine, however, and good yields of the 3’-O-silylated nucleotides (89) are obtained. These are admirable starting materials for ‘phosphodiester’ synthesis. After each coupling stage, the bulky lipophilic silyl group allows facile solvent extraction of intermediates and strong, selective retention on reverse-phaseh . p . l . ~ . for l ~ ~separation of the products. It is claimed that the time required for oligonucleotide synthesis may be cut by half by using this technique. The silyl group is finally removed using fluoride ion. Despite the popularity of the ‘phosphotriester’ method, the ‘phosphcrdiester’ synthesis of oligodeoxyribonucleotides continues to find wide 555

Attractive improvements in solid-phase oligonucleotide synthesis have been described. In one, thymidine is bound to a support via an alkali-labile linkage to the 5’-hydroxy-group, and the chain is extended by successive condensation and deblocking of 3’-O-monomethoxytrityl thyrnidine-5’-phosphate.ls6After each addition, acetylation is performed to block free 3’-hydroxy-groups (‘failure sequences’) prior to removal of the trityl group. At the completion of synthesis the product is cleaved from the column and the ‘success’ sequence, bearing a terminal monomethoxytrityl group, is selectively retained on a column of tritylcellulose. Elution and deblocking affords the required product. Automated oligonucleotide synthesis has now been realized,15’ using a procedure which employs phenyl isocyanate to block failure sequences and, simultaneously, to act as a water scavenger. On treatment of pdT-Ac, pdTpdT-Ac, Tr-dTpdT-Ac, and Tr-dTpdTpdT-Ac with TPS in pyridine, investigation using pulsed 31P n.m.r. shows that several different classes of reactive phosphorylating intermediates are formed. In one class, phosphornonoesters are converted into phosphorylpyridiniurn residues, in the second, phosphornonoesters and phosphodiesters condense to form trisubstituted pyrophosphates, and in the third, phosphodiesters condense to afford tetrasubstituted pyrophosphates. In particular, cyclic pyrophosphates are formed. The reactivity of these intermediates with alcohols has been examined, and rate constants have been In a similar study, the interaction of mesitoyl chloride with PA, Tr-dTpdT, and pdTpdT-Ac has been examined.159The reagent forms mixed anhydrides with terminal and inter-nucleotidic phosphate groups rapidly and quantitatively at 0 “C,the latter being particularly reactive. If poly(U) is treated with mesitoyl chloride159 or other condensing agents,lG0cyclization and phosphotriester formation occur. Subsequent hydrolysis gives partial cleavage 152 153

154 155

156 157 158

159

160

R. A. Jones, H.-J. Fritz, and H. G. Khorana, Biochemistry, 1978, 17, 1268. H.-J. Fritz, R. Belagaje, E. L. Brown, R. H . Fritz, R. A. Jones, R. G. Lees, and H. G. Khorana, Biochemistry, 1978, 17, 1257. E. Kawashima, T. Gadek, and M. H. Caruthers, Biochemistry, 1977, 16, 4209. M. S. Poonian, W. W. McComas, and A. L. Nussbaum, Gene, 1977, 1, 357. H. Seliger, M. Holupirek, and H.-H. Gortz, Tetrahedron Letters, 1978, 21 15. M. J. Gait and R. C. Sheppard, Nucleic Acids Res., 1977, 4, 4391. D. G. Knorre, V. F. Zarytova, A. V. Lebedev, L. M. Khalimskaya, and E. A. Sheshegova, Nucleic Acids Res., 1978, 5 , 1253. V. L. Drutsa, V. F. Zarytova, D. G. Knorre, A. V. Lebedev, N. I. Sokolova, and Z. A. Shabarova, Nucleic Acids Res., 1978, 5, 185. V. F. Zarytova, V. K. Rait, and T. S. Chernikova, Bio-org.Khim., 1977, 3, 1626 (Chem. Abs., 1978, 88, 170 424).


195

and isomerization of the internucleotide bonds. If the reaction sequence is applied to UpC, some 20 % of bond cleavage is obtained, and equal amounts of U3’p5’C and U2’p5’C are recovered. The triphenylphosphine-2,2’-dipyridyl disulphide reagent has been used to prepare nucleoside-5’-phosphorodianilidates from nucleoside-5’-phosphoromonoanilidates.161The use of phosphoryl tri-imidazolideto block inter-nucleotide phosphodiester groups in oligodeoxyribonucleotides has been described.ls2 Reaction initially converts the inter-nucleotide link into the corresponding phosphorimidazolidate diester, which may be treated with 2-cyanoethanol to give the protected phosphotriester. Oligonucleotidesbearing triphosphate groups at the 5’-terminus have been prepared from the corresponding oligonucleotides bearing a 5’-terminal monophosphate by direct phosphorylation with DCC and pyrophosphate.le3Protection of the 2’-hydroxy-group is necessary if oligoribonucleotides are used. The syntheses of oligonucleotides containing unusual nucleoside residues such as 1-(2’-deoxy-j3-~-ribofuranosyl)-2( 1H)-pyridonels4 and 3’-amino-3’-deoxyadenosineles have been described. As an alternative to organic synthesis, attempts have been made to obtain pyrimidine oligonucleotides direct from natural sources. Herring sperm DNA has been depurinated and ion-exchange chromatography of the products allows reliable size fractionation up to tetrapyrimidine nucleotides, and, thus far, limited separation of sequences.lG6 If a mixture of thymidylic acid, cyanamide, and 4-amino-5-imidazolecarboxamide at pH 7 is evaporated and heated to 60 “C for an extended period, P1,Padideoxythymidine-5’-pyrophosphateis formed in good yield. If dTTP is added to the original mixture and the process repeated, high yields of oligomers are obtained, which contain linear polynucleotides up to the octamer level.lS7Such reactions may have been important in prebiotic oligonucleotide formation. However, non-enzymatic formation of inter-nucleotidic links usually leads to a preponderance of the 2’,5’-isomer. Condensation of the methyl esters of AMP, CMP, GMP, and UMP with uridine-5’-phosphorimidazolidatein the presence of MgCl, and 1-methylimidazoleat neutral pH leads to formation of the corresponding dinucleotides in modest yield, in which the proportion of the 3’,5’linked isomer was not higher than 15 %.16*Repetition in the presence of poly(U) resulted in faster reaction, but an even lower proportion of the 3’,5’-linked isomer. It is not clear why the 2’-hydroxy-group should be more reactive than that at the 3’-position, but the inductive effect of the heterocyclic ring at C-l’, and steric effects resulting from the ribose conformation, probably play a part. 161

D. G . Knorre, G . F. Mishenina, V. V. Samukov, and T. N. Shubina, Doklady Akad. Nauk

S.S.S.R.,1977, 236, 613 (Chem. Abs., 1977, 87, 201 995). 162 163 164

165 166

167

168

N. F. Sergeeva, Z . A. Shabarova, and M. A. Prokofiev, Doklady Akad. Nauk S.S.S.R., 1977, 234, 607 (Chem. Abs., 1977,87, 201 968). V. G . Budker, V. F. Zarytova, D. G . Knorre, N. D. Kobets, and 0. I. Ryazankina, Bioorg. Khim., 1977, 3, 618 (Chem. Abs., 1977, 87, 136260). N. Cerletti and C. Tamm, Helv. Chim. Acta, 1977, 60, 1182. A. V. Azhayev, A. A. Krayevsky, and J. Smrt, Coll. Czech. Chem. Comm., 1978,43, 1647. H. Schott and M. Schwarz, Z . physiol. Chem., 1977, 358, 949; ibid., 1978, 359, 617. E. Sherwood and J. Oro, J. Mol. Evol., 1977, 10, 183; A. Joshi and J. Oro, ibid., p. 193. R. Lohrmann and L. E. Orgel, Tetrahedron, 1978, 34, 853.

196


N.m.r. studies of 2’,5’-linked and 3’,5’-linked dinucleoside monophosphates have led to the suggestion that nucleic acids contain 3’,5’-phosphodiester bonds because only this arrangement allows the formation of a helical array that is stabilized by base-stacking.16sThe geometry of the 2’,5’-link is such that, if the bases are stacked, no helix can be formed, and if the structure is constrained to form a helix, the bases cannot stack, Enzymatic Synthesis.-Novel homopolynucleotides reported during the past year have included poly(2’-fluoro-2’-deoxyadenylic acid),170 poly(2’-chloro-2’-deoxyadenylic acid),171 poly(2’-bromo-2’-deoxyadenylic acid),171 poly(2’-azido-2’All were deoxyinosinic and poly(1-methyl-6-thioguanylic synthesized by polymerization of the corresponding nucleoside-5’-diphosphates, using polynucleotide phosphorylase, and investigated for their ability to form stable complexes by themselves in salt or acid solution, or complexes with complementary homopolynucleotides. have been tested for their A series of 5-alkyl-2’-deoxyuridine-5’-triphosphates ability to act as substrates with dATP in poly[d(A-T)]-primed polymerization by DNA polymerase I.174While the 5-isopropyl, -t-butyl, and -n-hexyl analogueswere not incorporated, the deoxyuridine analogues bearing a straight-chain alkyl group up to n-pentyl were incorporated, and analysis indicated a ratio of 1 :1 with adenosine residues in the copolymers formed. If conditions are chosen carefully, polynucleotide phosphorylase will accept a 2’-deoxynucleoside-5’-diphosphateas a substrate and transfer a single residue to the 3’-end of an oligodeoxynucleotide primer. A systematic study of the transfer of dADP, dCDP, dGDP, and dTDP to d(pT-T-A-G) (a ‘good’ primer) and d(pT)G(a ‘poor’ primer) has been made.175Generally, a primer with purine residues at the 3’-terminus is a better acceptor than one with pyrimidine residues at the 3’-terminus. Nucleotide analogues such as 5-methyl-2’-deoxycytidine-5’-diphosphate, N4-hydroxy-2‘-deoxycytidine-5’-diphosphate,and 2’-deoxyuridine-5’diphosphate were also single-addition substrates for the enzyme. 5-Mercuri-2’deoxyuridine-5’-diphosphateafforded no mercury-containing oligonucleotides, but gave the same pattern of products as that resulting from dUDP addition, thus reinforcing the reporfsll on thiol-mediated demercuriation of these species. RNA polymerase from E, coZi will also perform single-step addition reactions. In the presence of poly[d(A-T)] template and ATP, ApU is extended to ApUpA, and UpApU to U ~ A P U ~Similarly, A . ~ ~ using ~ UTP, UpA is extended to UpApU. Analogous results were obtained with GpC and GTP, and with CpG and CTP, using poly[d(I-C)] primer. Using ApA as primer and CDP as substrate, under controlled conditions, polynucleotide phosphorylase from Thermus thermophilus will transfer cytidylic acid residues to the end of the primer to afford ApApCpC. If this product is M. M. Dhingra and R. H. Sarma, Nature, 1978, 272, 798. M. Ikehara, T. Fukui, and N. Kakiuchi, Nucleic Acids Res., 1978, 5 , 1877. 171 M. Ikehara, T. Fukui, and N. Kakiuchi, Nucleic Acids Res., 1977, 4, 4249. 172 T. Fukui, N. Kakiuchi, and M. Ikehara, Nucleic Acids Res., 1977, 4, 2629. 173 V. Amarnath and A. D. Broom, Biochim. Biophys. Acta, 1977, 479, 16. 174 J. T. Sagi, A. Szabolcs, A. Szemzo, and L. Otvos, Nucleic Acids Res., 1977, 4, 2767. 175 E. M. Trip and M. Smith, Nucleic Acids Res., 1978, 5 , 1529, 1539. 176 H. Oen and C.-W. Wu, Proc. Nat. Acad. Sci, U.S.A., 1978, 75, 1778. lBQ 170


197

incubated with the same enzyme in the presence of GDP and RNase T,, the product is ApApCpCpGp, in a yield of 5% based on the original primer.177 Orthophosphate must be removed during the second reaction to suppress phosphorolysis of the starting material. RNA ligase from bacteriophage T,-infected E. coli utilizes ATP and a nucleoside or oligonucleotide bearing a 5’-phosphate group as substrates. Initially, a 5’-5’-pyrophosphate of general structure A5’pp5’N is formed, and then pN is transferred to the 3’-hydroxy-group of an oligoribonucleotide containing three or more nucleoside residues in an ATP-independent reaction. A fair degree of variation in the nature of N is permissible; for instance, NADf is a substrate.17* This useful enzyme may thus be employed for joining synthetic oligoribonucleoIt is advisable to phosphorylate any 3’-hydroxy-group on N, the group to be transferred, since otherwise multiple additions may occur,178although they are not always 0 b s e r ~ e d . The l ~ ~ enzyme also presents a promising method for stepwise elongation in the synthesis of defined-sequence oligonucleotides, elongating primers such as ApApA with pNp (N is a ribonucleoside) to afford ApApApNp.lso As an example of the enzyme’s applicability, ApApA and pCp are joined by T4RNAligase and ATP to form ApApApCp, which is treated with alkaline phosphatase to afford ApApApC. Also, pUpUpU, on treatment with polynucleotide phosphorylase, GDP, and RNase T1, affords pUpUpUpGp. The ligase is then used, with ATP, to join the two tetranucleotides to form ApApApCpUpUpUpGp, a segment of bacteriophage QB coat protein gene.lsl Such syntheses can be performed on the milligram scale. T 4 Polynucleotide ligase has been used for the oligomerization of a self-complementary octadeoxyribonucleotide, affording products up to 120 nucleotides in length.lS2While it shows strong specificity for ATP as substrate, it is also able to utilize (62) for the joining reaction.ls3 Trinucleoside diphosphates containing guanosine or inosine as the S’-terminal nucleoside have been prepared by incubation of inosine- or guanosine-2’,3’-cyclic phosphates and diribonucleoside monophosphates in the presence of a guanylspecific ribonuclease from Penicillium chrysogenum or Aspergillus c l a v a t ~ s . ~ s ~ If DNA from bacteriophages 4X 174 or fd is used as template for E. coli DNA polymerase I, and three deoxyribonucleoside-5’-triphosphatesand one deoxyribonucleoside-5’-(oc-thio)triphosphateare used as substrates, a DNA copy is obtained in which every inter-nucleotide link on the 5’-side of one of the four bases present is a phosphorothioate diester.ls5 If 35S-labelledmaterial is used, the amount of label incorporated suggests complete substitution, and nucleotide composition Y . Kikuchi, K. Someno, and K. Sakaguchi, Agric. and Biol. Chem. (Japan), 1977,41, 1531. T. E. England, R. I. Gumport, and 0. C. Uhlenbeck, Proc. Nat. Acad. Sci. U.S.A., 1977, 74, 4839. 179 E. Ohtsuka, S. Nishikawa, R. Fukumoto, S. Tanaka, A. F. Markham, M. Ikehara, and M.Sugiura, European J. Biochem., 1977, 81, 285. 1x0 Y . Kikuchi, F. Hishinuma, and K. Sakaguchi, Proc. Nat. Acad. Sci. U.S.A., 1978,75, 1270. 1 8 1 Y . Kikuchi and K. Sakaguchi, Nucleic Acids Res., 1978 5, 591. 182 K. V. Deugau and J. H. van de Sande, Biochemistry, 1978,17,723. lS3 A. J. Raae and K. Kleppe, Biochem. Biophys. Res. Comm., 1978, 81, 24. 1 8 4 S. M. Zhenodarova, V. I. Gulyaeva, and S. I. Bezborodova, Bio-org. Khim., 1977, 3, 1475 (Chem. A h . , 1978, 88,47 187). lX5 H.-P. Vosberg and F. Eckstein, Biochemistry, 1977, 16, 3633. 177

178

I98


and restriction-enzyme data indicate that the fidelity of transcription is very high. By altering the nucleoside thiotriphosphate supplied, each base position may be labelled in turn. Certain platinum complexes bind very tightly to thiophosphate groups, and it is hoped that this will provide a method for the sequencing of nucleic acids by electron rnicroscopy.lS6 Sequencing.-An improved form of the ‘plus’ technique of DNA sequencing has been described.187A restriction endonuclease fragment of DNA is end-labelled and partially digested with snake venom phosphodiesterase, generating a random array of all chain lengths. An aliquot of the digest is then incubated with a template strand that is complementary to that being sequenced, DNA polymerase I, dATP, dCTP, dGTP, and (66). Copy synthesis takes place in all primer strands, up to the point at which thymidine would normally be inserted, but 2’,3’dideoxythymidine is now inserted in its place, as a chain terminator. Hence a complete array of lengths ending at the positions normally occupied by thymidine is generated. Successive replacements of dATP, dCTP, and dGTP by (67), (68), and (69) [for structures of these, see p. 2861 in other incubations generate different arrays for the different chain-terminators. Polyacrylamide gel electrophoresis of all four incubation products followed by autoradiography generates a ‘ladder’ from which the sequence may be read by inspection. The use of thin gels (0.4mm) improves resolution.ls8The use of chain terminators removes ambiguities associated with cumulative runs of a single base, which were a difficulty in the original technique.lS7 Working at higher voltages maintains the gels at higher temperatures, and suppresses any tendency to form loops, which could give anomalous results.l88 In one experiment, a 465-nucleotide sequence could be determined. Small wonder that there is an explosion in papers on nucleic acid sequencing! The only technique of comparable power is the Maxam-Gilbert technique for DNA sequencing reported last year.79This has been used to determine the sequence of 5224 base pairs of SV 40 DNA,189and the 1859-residuesequence of chicken ovalbumin mRNA, the latter via synthesis and cloning of a complementary DNA duplex copy.19o The Maxam-Gilbert method relies on basespecific modification leading to chain cleavage, and two further reactions, namely photo-oxidation of guanine using methylene blue and oxidation of thymine using osmium tetroxide, have been tested for this purpose and shown to be effective.lglSubsequent treatment with piperidine causes chain cleavage at the modified residue, in each case. Inevitably, ladder-sequencing methods for RNA have been devi~ed.l9~-l~s Limited digestion of end-labelled RNA with RNase T, generates an array of lE6S .

J. Lippard, Accounts Chem. Res., 1978, 11, 211. F. Sanger, S. Nicklen, and A. R. Coulson, Proc. Nat. Acad. Sci. U.S.A., 1977, 74, 5463. F. Sanger and A. R. Coulson, F.E.B.S. Letters, 1978, 87, 107 W. Fiers, R. Contreras, G. Haegeman, R. Rogiers, A. Van de Voorde, H. Van Heuverswyn, J. Van Heereweghe, G. Volckaert, and M. Ysebaer, Nature, 1978, 273, 113. lg0L. McReynolds, B. W. O’Malley, A. D. Nisbet, J. E. Fothergill, D. Givol, S. Fields, M. Robertson, and G. G. Brownlee, Nature, 1978, 273, 723. lgl T. Friedmann and D. M. Brown, Nucleic Acids Res., 1978, 5, 615. lg2 H. Donis-Keller, A. M. Maxam, and W. Gilbert, Nucleic Acids Res., 1977, 4, 2527. lg3 A. Ross and R. Brimacombe, Nucleic Acids Res., 1978, 5 , 241. lg4 A. Simoncsits, G. G. Brownlee, R. S. Brown, J. R. Rubin, and H. Guilley, Nature, 1977, 269, 833. lg6 R. C. Gupta and K. Randerath, Nucleic Acids Res., 1977, 4, 3441. lS7 ISE lSg


199

lengths ending with guanosine-3’-phosphate, and RNase U, cleaves after adenosine residues. These digests, together with another digest formed by limited alkaline hydrolysislg2(random cleavage after all residues) or pancreatic RNase hydrolysis (cleavage after uridine and cytidine)lg3can be separated on polyacrylamide gels to allow mapping in terms of adenine, guanine, and pyrimidine residues. Two methods are available for assignment of the pyrimidine residues. A ribonuclease isolated from Physarurn polycephalum will cleave the RNA chain under controlled conditions after all residues except cytidine, and running a gellg4or PEI-cellulose platelg5of this digest beside one resulting from hydrolysis with pancreatic RNase allows assignment of the sequence. Alternatively, twodimensional polyacrylamide gel electrophoresis of the products of limited alkaline hydrolysis and mobility-shift analysis, combined with the known results on purine residue positions, allow identification of the full sequence.lg6Oligoribonucleotides up to 25 residues in length may be sequenced by 5’-end-labelling, partial endonucleolytic digestion with nuclease PI (Penicillium citrinum) or snake venom phosphodiesterase (which break the chain at random), and separation of the products by two-dimensional homochromatography, autoradiography, and mobility-shift ana1~sis.l~’ Alternatively, unlabelled products of digestion with snake venom phosphodiesterase may be treated with alkaline phosphatase, oxidized with periodate, and the terminal dialdehyde residues reduced with sodium b0r0triti-ide.l~~ Separation of the labelled products by two-dimensional t.1.c. on PEI-cellulose plates allows sequence determination by mobility-shift analysis. Two micro-methods for base analysis of oligoribonucleotideshave been described. One requires a 32P-labelledsample, which is degraded to 3’-mOnOnucleotides with a mixture of RNases T1 and Tz, and the products are separated by two-dimensional chromatography on PEI-cellulose plates.lg9 The other utilizes unlabelled material, which is hydrolysed and dephosphorylated to give ribonucleosides. These are treated with periodate and 4-hydra~inobenzene[~~S]sulphonic acid, and the products are separated by t.l.c., localized by autoradiography, and determined by scintillation counting.200The latter method has also been used to measure sequential nucleotide release by snake venom phosphodiesterase from oligoribonucleotides, thus affording a sequencing procedure.,01 When guanine residues in DNA or RNA are modified with glyoxal or kethoxal, the phosphodiester links adjacent to the modified residues on the 3’-side become resistant to snake venom phosphodiesterase and ribonuclease TI,respectively. This affords a method for determining the positions of deoxyguanosine residues and in oligodeoxyribonucleotidesZo2and also allows the topography of 16SZo3 235 RNAZo4in ribosomal subunits to be investigated. E. Lockard, B. Alzner-Deweerd, J. E. Heckman, J. MacGee, M. W. Tabor, and U. L. RajBhandary, Nitcleic Acids Res., 1978, 5, 37. Ig7 M. Silberklang, A. M. Gillum, and U. L. RajBhandary, Nucleic Acids Res., 1977, 4, 4091. lg8E. Y. Chen and B. A. Roe, Nucleic Acids Res., 1977, 4, 3563. 1g9 G. Volckaert and W. Fiers, Analyf. Biochem., 1977, 83, 222. M. W. Johnson and G. 0. Osuji, F.E.B.S. Letters, 1977, 83, 81. 201 G. 0. Osuji and M. W. Johnson, F.E.B.S. Letters, 1977, 83, 85. Zo2 V. G. Metelev, V. D. Smirnov, Z . A. Shabarova, and E. D. Sverdlov, F.E.B.S. Letters, 1978, 90, 112. 203 J. J. Hogan and H. F. Noller, Biochemistry, 1978, 17, 587. 204 W. Herr and H. F. Noller, Biochemistry, 1978, 17, 307.

1913 R.

200


Other Studies.-An extensive study of the reactivity of the phosphodiester link in DNA and dTpdT towards dimethyl sulphate, ethyl methanesulphonate, N-ethylN-nitrosourea, and N-methyl-N-nitrosourea has been Alkylated DNA was degraded enzymically and the digests were analysed, using h.p.l.c., to measure the quantity of alkylated dTpdT formed and to determine the reactivity of each alkylating agent towards dTpdT as model compound and towards DNA overall. Reactivity was lowest towards dimethyl sulphate and highest towards N-ethyl-N-nitrosourea. More ethylation of DNA inter-nucleotide links was observed than predicted by the Swain-Scott value of 1 for the nucleophilicity of the phosphodiester group. However, the nucleic acid bases are the primary sites of attack by alkylating agents,206-208 and more attention has been focussed on the ability of alkylated bases to mispair, giving rise to point mutations in DNA replication or transcription. 208 This mispairing property of alkylated bases has been used ingeniously to introduce new restriction-endonuclease cleavage sites into DNA.2o9 On treatment with syrz- or anti-benzo[a]pyrenediol epoxides, both superhelical DNA and MS 2 RNA exhibit concentration-dependent strand nicking.42The event is rare, being less than 1 % of the DNA modification observed to result from treatment with these agents, but poses an interesting mechanistic problem. Base alkylation might result in depurinated sites in DNA, but RNA would not be degraded in this manner. Kinetic evidence suggests that unstable phosphotriesters may be formed, and a speculative mechanism to account for strand cleavage has been proposed (Scheme 5). In RNA, the 2’-hydroxy-group could also take part in strand scission as indicated. The antibiotics bleomycin and neocarzinostatin both induce strand cleavage in DNA. Bleomycin appears to remove certain bases from DNA, leaving sites which, like those in depurinated DNA, are readily hydrolysed at alkaline pH.210 Cleavage by neocarzinostatin seems to be an oxidative process 211 involving base release, opening of the sugar ring, and destruction of one or more nucleosides to leave a gap that is bounded by 3’- and 5’-phosphoryl termini.212 2079

5 Analytical Techniques and Physical Methods Phosphorus-31 n.m.r. has been used to differentiate the sites that bind nucleotides and those that bind metal-nucleotide complexes in adenylate kinase 213 and to study the structures of metal-nucleotide complexes bound to pyruvate k i n a ~ e . ~ ~ ~ The spectra of adenosine-5’-phosphorothioate, (57), adenosine-S’-(P-thio)diphosphate, (56), (58), and adenosine-Y-(B-thio)triphosphate,and the sensitivity 205 206

207 SO*

SO9

210 211

213 21s 214

D. H. Swenson and P. D. Lawley, Biochem. J., 1978, 171, 575. J. D. Engel and P. H. von Hippel, J. Biol. Chem., 1978, 253, 927, 935. R. Saffhill and P. J. Abbott, Nucleic Acids Res., 1978, 5, 1971. B. Singer, H. Fraenkel-Conrat, and J. T. Kusmierek, Proc. Nat. Acad. Sci. U.S.A., 1978, 75, 1722. B. Gronenborn and J. Messing, Nutwe, 1978, 272, 375. S. L. Ross and R. E. Moses, Biochemistry, 1978, 17, 581. S.-K. Kim and J. W. Lown, Biochem. Biophys. Res. Comm., 1978,81, 99. L. S, Kappen and I. H. Goldberg, Biochemistry, 1978, 17,729. B. D. N. Rao, M. Cohn, and L. Noda, J. Biol. Chem., 1978,253,1149. R. K. Gupta and A. S. Miidvan, J. Biol. Chem., 1977, 252, 5967.

201


i

0

d (pN),-O-P-O-N-

(PN),

1

I

OH

HO

1

0

d (pN),-0-P-0-

0

/I

II

I

Ho'-al 0

HO"

HO

Scheme 5

of these compounds to protonation and magnesium binding have been studied.21s It was found possible to distinguish the diastereoisomers of (57) and adenosine5'-(@-thio)triphosphateby their 31P n.m.r. parameters, thus offering increased scope for determining the stereospecificityof enzymatic reactions involving these analogues. The isotope oxygen-18, bonded to phosphorus, causes a shift in the 31 P resonance, and indeed there is a difference of 12 Hz between the 31Presonances in H3Pla0 and H3P180 216 This affords a new double-labelling technique: the exchange between H3Pls04and the B-phosphate of ADP that is catalysed by polynucleotide phosphorylase can be shown to involve cleavage of the bond between the a-phosphorus and the a-@ bridge oxygen, by observing the shifts of the phosphorus resonances. This technique ogers considerable potential, including that of observing washout of oxygen isotope and scrambling reactions of bridge oxygen7sdirectly. Other 31Pn.m.r. studies of note have concerned the binding of 2'-AMT to dihydrofolate reductase217and of adenine nucleotides to catecholamine,21smetal complexes of CAMP, ADP, and ATP,219t220 and the 215 217 218

219 220

E. K. Jaffe and M. Cohn, Biochemistry, 1978, 17, 652. M. Cohn and A. Hu, Proc. Nat. Acad. Sci. U.S.A., 1978, 75, 200. B. Bridsall, G. C. I(.Roberts, J. Feeney, and A. S. V. Burgen, F.E.B.S. Letters, 1977, 80, 313. J. Granot, F.E.B.S. Letters, 1978, 88, 283. S. Fan, A. C. Storer, and G. G. Hammes, J. Amer. Chem. Soc., 1977, 99, 8293. R. D. Cornelius, P. A. Hart, and W. W. Cleland, Inorg. Chem., 1977, 16, 2799.

202


structures of polynucleotides in aqueous solution 221-223 and in the solid Some 31Pn.m.r. kinetic measurements have been made on the reaction described earlier which is catalysed by adenylate k i n a ~ e It. ~is~possible ~ to invert the spin population of a phosphorus nucleus in one chemical environment selectively and to observe the inversion transfer to another environment. The chemical transfer time between free AMP in solution and free ADP in solution is found to depend on the enzyme:substrate ratio, in this case. Proton n.m.r.226and 13C r ~ . m . r measurements .~~~ on poly(ADP-ribose) and monomers derived by cleavage of the pyrophosphate links indicate the presence of an unusual a(l"-2')-ribofuranosyl ribofuranoside moiety. The structure is thought to be (90).

Infrared studies on CMP and 2'-CMP bound to RNase A at different pH values have been performed to determine the ionization state of the phosphate group at the pH that gives maximum binding, and thus the likely nature of hydrogen-bonding to phosphate in the complex.228A method for computing nearest-neighbour frequencies in double-stranded DNA from c.d. spectroscopic measurements has been described.229It relies on the assumption that only firstneighbour interactions contribute to the formation of the total c.d. signal. Electric field pulses have been used to dissociate oligonucleotide-oligopeptide complexes in a thermodynamic and kinetic study of oligonucleotide-oligopeptide interactions. 230 The chief contribution to complex formation comes from electrostatic interaction between negative charges on the oligonucleotide and positive charges on the oligopeptide. A. Yamada, K. Akasaka, and H. Hatano, Biopolymers, 1978, 17, 749. G. J. Garssen, C. W. Hilbers, J. G. G. Schoenmakers, and J. H. van Boom, European J . Biochem., 1977, 81, 453. 2Z3 K. Akasaka, A. Yamada, and H. Hatano, Bull. Chem. SOC.Japan, 1977, 50, 2858. Z z 4 T. Terao, S. Matsui, and K. Akasaka, J. Amer. Chem. SOC.,1977, 99, 6136. 225 T. R. Brown and S. Ogawa, Proc. Nat. Acad. Sci. U.S.A., 1977, 74, 3627. 2 2 6 A. M. Ferro and N. J. Oppenheimer, Proc. Nat. Acad. Sci. U.S.A., 1978, 79,809. 227 M. Miwa, H. Saito, H. Sakura, N. Saikawa, F. Watanabe, T. Matsushima, and T. Sugimura, Nucleic Acids Res., 1977, 4, 3997. 228 M. Matthies, F.E.B.S. Letters, 1977, 81, 183. 229 C. Marck and W. Guschlbauer, Nucleic Acids Res., 1978, 5 , 2013. z3* D. Porschke, European J. Biochem., 1978, 86,291. 221 222


203

Picomolar quantities of UTP may be estimated by treatment with [14C]glucose1 -phosphate and UDP-Glc pyrophosphorylase to form UDP-D-glucose, which is selectively adsorbed on to charcoal and estimated by scintillation co~nting.~3l Picomolar UMP and UDP may be estimated similarly, following enzymic conversion into UTP. Similarly small quantities of CTP may be estimated by treatment with labelled phosphorylethanolamine in the presence of CTP: phosphorylethanolamine cytidyltransferase.23 The CDP-ethanolamine formed is isolated on an ion-exchangecolumn, using borate complexing, and then counted. Labelled deoxyribonucleoside triphosphates in cell extracts may conveniently be estimated by treating the extract with periodate and then performing twodimensional chromatography on P E I - ~ e l l u l o s eRibonucleoside .~~~ triphosphates which would otherwise interfere are eliminated as the dialdehyde derivatives, which do not migrate. The separated deoxyribonucleotides are estimated by scintillation counting.

231 z32 233

C. P. Cheung and R. J. Suhadolnik, Analyt. Biochem., 1977, 83, 52. D. E. Leelavathi and R. W. Guynn, Analyt. Biochem., 1977, 83, 258. E. C. Reynolds and L. R. Finch, Analyt. Biochem., 1977, 82, 591.

9 Ylides and Related Compounds BY D. J. H. SMITH

1 NPethylenephGsphsraies Preparation and Structure.-The development of synthetic methods, reactions, and structure of phosphacurnulene and phospha-allene ylides, e.g. (l), have been substantially reviewed.l Ph,P=C=CR, (1)

Heating together triphenylphosphitie and (chloromethy1)trimethylsilane produces methylenetriphenylphosphorane, which is trapped by ketones in situ (Scheme 1). If the ketones used have an a-hydrogen, silyl enol ethers are produced together with the terminal alkene.2

Me,S;KH,CI + Ph,P

Me,SiCH,hh,

__+I

---I-

Me,SiCl

+ Ph,P===CH,

c1-

W'RC =cPI, Scheme 1

Dichloromethylenetriphenylphosphoranecan be prepared by dechlorination of the phosphonium salt (2) with E-IMPT.3 (Me,N),P

+

+

Ph,PCCI, -+

Ph,P=CC1,

C1'

(2)

The addition of carbon tetrahalides to phosphines which contain acidic a-hydrogens results in formation of the ylides (3).4 The halogen on phosphorus can be replaced by alcohols, amines, and thiols. The preparation of an ylide (4), stabilized by the trifluoromethylsulphonyl group, by the reaction of (chlorornethy1)trifluoromethylsulphone with triphenylphosphine in the presence of triethylarnine, has been r e p ~ r t e d . ~

*

H. J. Bestmann, Angew. Chem. Internat. Edn., 1977, 16, 349. A. Sekiguchi and W. Ando, Chem. Letters, 1977, 1293. R. Appel and H. Veltmann, Tetrahedron Letters, 1977, 399. 0. I. Kolodyazhnyi, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1971. 0 . 1 . Kolodyazhnyi, L. I. Shevchuk, and U. P. Kukhar, J. Gen. Chem. (U.S.S.R.), 1977,47, 658.

204

Ylides and Related Compounds Rl2PCHR',

+

CX,

205 HA

-+ RI2P=CR',

+ R12P-=CR',

I X

I

A

(3)

R' = Et, OEt, or Ph R2 = CO,Et, SO,Ph, or SQ2CF3 A = OR,SR, or NHR ClCH,SO,CF,

+

a Ph,P=CHSQ,CF,

Ph,P

(4)

Under certain conditions, tetramethylphosphonium chloride reacts with sodamide in THF to yield the conjugated bis-ylide (5),6 which is subject to rapid proton scrambling in solution. Compound ( 5 ) is converted into the bromide salt (6) with hydrogen bromide.

I

(6)

CH3

Br-

(5

The elimination of hydrogen fluoride from (7) by heat or the addition of base produces hexamethylcarbodiphosphorane, spectroscopic data of which indicate high carbanionic character for the central carbon atom.

4 or BuLi

Me,P-CH=PMe,

I

Me,P=C=pMe,

Imidoylphosphoranes (8) can be prepared by treatment of imidoyl chlorides with two equivalents of methylenetriphenylphosphorane. The N-tosyl-substituted ylides have no reactivity towards aldehydes, but the N-aryl compounds are converted into +'-unsaturated ketimines which are not easily accessible by other condensations.8 ? 9 2Ph,P=-CH,

+

---+

9'

ArN===C

e'l

6

7 8

9

Ph,P=CH

+

-C

p

r

(8)'R'

P h , k H , C1R' = Ph, OMe, or SMe R2 = Ar or Me

H. Schmidbaur and H. J. Fuller, Chem. Ber., 1977, 110, 3528. H. Schmidbaur, 0. Gasser, and M. S . Hussain, Chem. Ber., 1977, 110, 3501. H. Yoshida, T. Ogata, and S. Inokawa, Synthesis, 1977, 626. H. Yoshida, T. Ogata, and S . Inokawa, Bull. Chem. SOC.Japan, 1977, 50, 3315.

206


The addition of halogen to the ylide (9) gives phosphonium salts which can be easily dehydrohalogenated. O A synthesis, suitable for large-scale work, of the ylide (10) has been described.ll H,NCONHCOCH=PPh,

(91

+

xz

-+

H,NCONHCOCHX;Ph,

+H,NCONHCOCX=PPli,

X‘ BuCOCH-PPh, (10)

Methylenetri-t-butylphosphoranehas been prepared. l 2 It is thermally unstable, eliminating isobutene at room temperature. The authors have proposed a mechanism for this unusual behaviour based upon the extreme steric crowding in the molecule. Restricted C-P bond rotation was detected by lH and 13Cn.m.r. spectroscopy. It has been reported13 that the ylide (11) is thermolabile and slowly, reversibly, dimerizes.

The structures of a number of phosphoranes have been determined in the gas phase by electron diffraction. Such measurements show that the P-C-P unit of hexamethylcarbodiphosphoraneis linear,14 and that the P-C ylide bond of methylenetrimethylphosphorane is extremely short, with a bond order of 2.0.l5 The bond distances found from the crystal structure of (phenyliminoviny1idene)triphenylphosphorane are in agreement with theoretical values,l6 Reactions.-A2dehyde.s. It has been suggested that reactions of ylides (12) with aromatic aldehydes proceed via a one-step formation of an oxaphosphetan at the rate-determining step. Kinetic measurements indicate that the individual bonds, P-0 and P-C, must be formed to different extents.17 Evidence has been presented which indicates that the reaction of ,8-oxidoylides with an aliphatic or aromatic aldehyde affords stereoselectively a racemic dioxidophosphonium adduct (13). It was also shown that it is the preference of this intermediate to form an (E)-alkene which determines that it is the oxygen of the second aldehyde, except formaldehyde, which is lost. l8 V. N. Kushnir, M. I. Shevchuk, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.), 1978, 47, 1570. l1 D. Pirillo and G. Rescia, Farmnco, Ed. Sci., 1977, 32, 311 (Chem Abs., 1977, 87, 135 596). l 2 H. Schmidbaur, G. Rlaschke, and F. H. Koehler, 2. Nnturfbrsch., 1977, 32b, 757. 13 H. Schmidbaur, H. P. Scherm, and U. Schubert, Chem. Ber., 1978, 111, 764. l4 E. A. V. Ebsworth, T. E. Fraser, and D . W. H. Rankin, Chem. Ber., 1977,110, 3508. 15 E. A. V. Ebsworth, T. E. Fraser, and JD. W. H. Rankin, Chem. Ber., 1977, 110, 3494. 1 6 H. Burzlaff, E. Wilhelm, and H. J. Restmann, Chem. Ber., 1977, 110, 3168. 17 B. Giese, J. Schoch, and G . Ruchardt, Chem. Ber., 1978, 111, 1395. l8 E. J. Corey, P. Ulrich, and A. Venkateswarlu, Tetrahedron Letters, 1978, 3231.

207

Ylides and Related Compounds

OH

I

0-

1

H

RI~H

R'dHC=PPh,

I

t RTIIO

' C = >

4

Me

Me

'R'

(1 3)

The synthesis of cis-divinylcyclopropane (14) has been achieved by the condensation of 2-vinylcyclopropanecarboxaldehyde with methylenetriphenylphosphorane. This preparation emphasizes how rapid Wittig reactions can be, since the reagents were mixed in DMSO at 5 "C for 30 s, and the product was isolated at - 80 "C.l9 t Ph,P=CH,

--+

(i) LDA, THF, -78 "C (ii) RCHO

iPh,

Unsaturated cyclic phosphonium salts, e.g. (1 5), prepared by Diels-Alder cycloadditions with vinyltriphenylphosphonium bromide, react quite well in Wittig condensations with aldehydes. No reactions occur with ketones.20 l9 2o

J. M. Brown, B. T. Golding, and J. J. Stofko, J.C.S. Perkin II, 1978, 436. R. Bonjouklian and R . A. Ruden, J . Org. Chem., 1977, 42, 4095.

208


Polarographic data suggest that the reaction of the phosphonium salt (16) with benzaldehyde in the presence of lithium methoxide occurs in stages, as shown.21The phosphonium salt (17) undergoes a trans-ylidation reaction with benzylidenetriphenylphosphorane, but, when it is treated with more stable ylides, Wittig products are produced.22

($

$

CH,$Ph,

CH-CHPh

+ FhCHO

CH,$Ph,

CH=CHPh

_.)

C H P Ph,

CH=CHPh

(16 ) +

Ph,PCH,C,H,CIIO

-t

Ph,P=CHPh

--+

+

-+ Ph,PCH,Ph

Ph,P=CHC,H,CHO

(17)

+

(1 7) + Ph,P--CIICO2Et

Fh,PCH,C,H,CH=CHCO,Et

The alkene (18), required in the total synthesis of kadsurin, was formed by a Wittig condensation as an E:Z mixture.23

2-Ethoxyallylidenetriphenylphosphoranecan be obtained by treatment of the corresponding triflate salt with DBU. Condensation with benzaldehyde leads to the expected product as a mixture of isomers24(Scheme 2). €l,C=CCII,~Ph,

I OEt

-%

-O,SCF,

IJ,C=CCH=PPh,

I OE t

-%

H,C====-CCH===CIIj?i

I

OEt

Reagents: i, DBU; ii, PhCHO

Scheme 2

Treatment of substituted o-hydroxy-benzaldehydes or acetophenones with ethoxycarbonylmethylenetriphenylphosphoraneleads to coumarins (19). In some cases the uncyclized ester can be isolated, but it is readily cyclized to (19) on heating. 2 5 L. Y. Malkes, T. P. Boronenko, and V. N. Dmitrieva, Zhrrr. obshchei Khim., 1977,47, 1468 (Chem. Abs., 1977,87, 134 148). z 2 R. I. Yurchenko and 0. M. Voitsekhovskaya, J . Gen. Chem. (U.S.S.R.),1977, 47, 60. 23 M. Mervic and E. Ghera, J. Amer. Chem. Soc., 1977, 99, 7673. 24 E. Vedejs, D . A. Engler, and M. J. Mullens, J. Org. Chern., 1977, 42, 3109. 25 R. S. Mali and V. J. Yadav, Synthesis, 1977, 464. 21


+ Ph,P==CHCO,Et

209

-+

0 R’ = H or M e R2,R3,R-‘ = H, Me, GMe

R2

R‘

(19)

The thermolysis of azines (20), which are readily synthesized from the appropriate phosphorane and aldehydes, has been found to be an efficient and general route to the pyrazoyl esters (21). 2 G The addition of aldehydes, such as azulene-lcarboxaldehyde, to the ylide (22) yields unsymmetrical p-divinylbenzenes as mixtures of isomers, easily separated by fractional crystallization. Ph,P -

H

-2=

N-N=CWCO,E

t

Me

-I-

_j

ArCHO

It has been reported that stabilized ylides react with arsabenzaldehyde (23) at the carbonyl group.28 p-(Dipheny1phosphino)benzaldehyde (24) undergoes normal Wittig reactions. 2 9 26

27 28 29

T.A. Albright, S. Evans, C. S. Kim, C. S. Labaw, A. B. Russiello, and E. E. Schweizer, J . Org. Chem., 1977, 42, 3691. R. I. Yurchenko, 0. M. Voitsekhavskaya, and A. A. Rykov, J. Gen. Chem. (U.S.S.R.), 1976,46, 2049. G. Markl, J. B. Rampal, and V. Schoberl, Tetrahedron Letters, 1977, 2701. I. N. Zhmurova, V. G . Yurchenko, R. I. Yurchenko and T. V. Savenko, J . Gen. Chem. (U.S.S.R.), 1977, 47, 2015.

210


6

+ Ph,P=CHCOR

._)

(2 3). CHO t Ph,P=CHR

--+

Ph2P

(24)

The direct cyclization of (25) to (26) on acid hydrolysis is used in the synthesis

of analogues of /3-lactam antibi~tics.~ O Condensation of aldehydes with ylides derived from (27) gives trans-alkenes which can be converted into n o r - s t e r ~ i d s . ~ ~ PhOCH2CON$

c"

O

NYpph3 CO,CH,Ph

r-l

(25)

n

A series of vinylphosphonium salts has been prepared by interception of the betaine intermediates (28) with hydrogen bromide followed by dehydration.32 Ph,P=CH 4-

R2CH0

OH

0-

R'

I

__f

Ph3kH-CHR2

I R'

I

_t

Ph,kHCHR2 --+

I R'

Br-

Ph3kR1=CHR2 Br-

(28) 80

31 82

J. Finkelstein, K. G. Holden, and C. D. Perchonock, Tetrahedron Letters ,1978, 1629. M. B. Groen and F. J. Zeelen, J. Org. Chem., 1978, 43, 1961. J. M. Mclntosh and R. S. Steevenz, Canad. J. Chem., 1977, 55, 2442.


211

A variety of aldehydes and ketones may be converted into ag-unsaturated aldehydes by a 3-carbon homologation, as shown in Scheme 3.33The corresponding reaction with ap-unsaturated ketones proceeds in normal fashion to give 1-methoxy-l,3,5-hexatrienes,e.g. (29).

'OMe Reagent: i, HsO+

Scheme 3

2(E),4(Z)-Unsaturated esters can be prepared from reactions of the aldehyde (30) with alkylidenetriphenylph~sphoranes.~~ The ylide (3 l), which is easily prepared from maleic anhydride and triphenylphosphine, reacts with aldehydes to produce compounds (32), which are useful precursors for butenolides and furans.35 RHC=PPh,

f

(30)

Ph3PPPh3

or

H C0,R'

__f

+

Ph,P

R3

N-Phenyliminoketenylidenetriphenylphosphorane reacts with carbon dioxide to give the cyclic product (52; X,Y=O) by rearrangement of an initial cycloaddition product (53). With carbon disulphide and carbon oxysulphide the reaction stops at (53). Compound (52) reacts normally with aldehydes and ketones.63

X,Y=OorS

Cycloheptatrienylphosphonium salts (54) can be prepared by alkylation of stabilized ylides with tropylium

ox..-.

+

Ph,P=CHCOR

I

--+ TJH -(COR 'PPh3 X-

(5 4)

It has been shown that the ylide generated from (55) has a rather complex reaction with aldehydes.65On the other hand, (56) can be isolated, and reacts normally with p-nitrobenzaldehyde.The addition of 1-azido-4-nitrobenzeneleads to a triazole which on hydrolysis yields the corresponding amino-derivative. Methylenetrialkylphosphoranes react with chloromethylsilane at silicon, followed by a 1,2 hydride shift- that displaces chloride.5s Bis(sily1)methylenephosphoranes (57) are isolated from the subsequent transylidation reaction. 52

53 54

55 56

M. J. Devos, J. N. Denis, and A. Krief, Tetrahedron Letters, 1978, 1847. H . J. Bestmann and G. Schmid, Tetrahedron Letters, 1977, 3037. G . Gavicchio, M. D'Antonio, G. Gaudiano, V. Marchetti, and P. P. Ponti, Tetrahedron Letters, 1977, 3493. R. I. Yurchenko and 0. M. Voitsekhovskaya, J. Gen. Chem. (W.S.S.R.), 1977,47, 57. H. Schmidbaur and B. Zimmer-Gasser, Angew. Chem. Internat. Edn., 1977, 16, 639.

YIides and Related Compounds

217

Ph3kH,C,H,$OCH,hh,

2Br-

(55)

Ph,P=NC,H4COCH=PPh3

+ 20,NC,H,CHO

-+ O,NC,H,CH=NC,H,

COCH= C,H,NO,

(5 6)

(56) t 0,NC,H4N, --+ O,NC,H,N

3R3P=CH, + 2H3SiCH,C1 --+

2[R,PCH,]' C1'

R = Me or Et

+ R,P=C (57)

/ IHJC H3 \,

SlH,CH,

Pyridine N-oxides and phenylethynyltriphenylphosphonium bromide react in the presence of base to produce the ylides (58), which, when sublimed at 200 "C, yield phenylethynylpyridines. PhCGCiPh, Br'

+

Is0thiocyanates react with fluorenylidenetripheny lphosphorane cleanly at either sulphur or nitrogen, depending upon the nature of the groups attached (Scheme 5).58

+ Ph,P=O

Ph,P=NR

Scheme 5 57

68

N. Morita and S. I. Miller, J. Org. Chem., 1977, 42, 4245. T. Saito and S. Motoki, J. Org. Chem., 1977,42, 3922.

21s


Substituted cyclopentadienyltriphenylphosphoranes (59) have been obtained directly from cyclopentadienyltriphenylphosphorane and isocyanates.6 9 Pyrimidotriazines are formed by treatment of the nitrosouracil (60) with ylides.60

2 Reactions of Phosphonate Anions One of the most significant advances during the year has been the preparation and use of the phosphonate equivalents of vinylphosphonium salts. Heathcockel has prepared ethyl 2-diethylphosphonoacrylate (61) as shown in Scheme 6.

CO,E t Reagents: i, NaH; ii, PhSeBr; iii,

H202;

ivy&0+;v, R1R2C=0

Scheme 6

When (61) is added to a solution of a carbanion such as the lithium enolate of pinacolone, a phosphonate (62) is formed. If, after warming to room temperature, the anion is allowed to react with an aldehyde or ketone, unsaturated esters are formed. In a similar way, Japanese workerss2have prepared ethyl l-(diethylphosphono)acrylate as shown in Scheme 7. These authors noted that the 59 60

61 62

Z. Yoshida, S. Yoneda, H. Kajita, and Y . Kumada, Japan. Kokai 76 47 705 (Chem. Abs., 1977, 87, 117 958). K. Senga, M. Ichiba, Y. Kanomori, and S. Nishigashi, Heterocycles, 1978, 9, 29 (Chem. Abs., 1978, 88, 89 631). W, A. Kleschick and C. H. Heathcock, J. Org. Chem., 1978,43, 1256. T. Minami, H. Suganuma, and T. Agawa, Chem. Letrers, 1978, 285.


219 0 iv __f

‘0

X = C0,Et or CN

Reagents: i, NaH; ii, PhSCl; iii, NaI04; ivy A

Scheme 7

phosphonate, generated by the addition of nucleophiles, reacts with intra- or inter-molecular carbonyl functions, as shown by the preparation of (63)6291 3 ~ and (64)62 respectively.

H,C 4P(OEt)i $.

Y‘

a YCH,C=CHR I

COzEt

CO,E t

Y = EtO,CCH, or MeCOCH,

(64)

Deprotonation of the en01 phosphate (65) gives an ally1 anion which can be alkylated at C-3 by trimethylsilyl chloride or at C-1 by methyl iodide. Deprotonation of the latter product followed by the addition of carbonyl compounds leads to dienes (Scheme 8).64 Diene phosphonates (66) and (67) have been prepared from the appropriate dipho~phonates.~~ 0

II

(R.LO)J’CH,CP(OR’),

I1 II 0 CH,

NaH

(R’O),P-CCH=CRW

I1 CH, I1

0

(66)

(R’O),PCH,CH=C HP(OR’),

II 0

63 64

65

I! 0

NaH R7RT =o

*

(R’O),PCH=CHC

II 0

H= CR2R3

(67)

3. Ide, R. Endo, and S. Muramatsu, Chem. Letters, 1978, 401. H. Ahlbrecht, B. Konig, and H. Simon, Tetrahedron Letters, 1978, 1191. G. Sturtz, B. Damin, and J.-C. Clement, J. Chem Res. (S), 1978, 89,


220 0

'OP(OEt),

II.

0

1 0

0

Reagents: i, ButLi; ii, MeaSiCl; iii, MeI; iv, RlCOR2

Scheme 8

Phosphonates may be prepared by treatment of active methylene compounds with base and diethyl phosphorochloridate.Two equivalents of base are necessary since the product is more acidic than the starting material; i.e. phosphonate anions are generated directly, and can be used in situ in alkene-forming reactions, as shown in Scheme 9.6s

'CH, 0 Reagents: i, PreNLi; ii, (Et0)2PCl; iii,

"

om2 ' CHo

Scheme 9

The optically active sulphoxide (68) reacts with a variety of carbonyl compounds to afford optically active @-unsaturated sulphoxides. ' The addition of the lithium anion of diethyl l-chloroethanephosphonateto carbonyl compounds, e.g. benzaldehyde, followed by acid hydrolysis, gives the phosphonates (69). The lithium alkoxides of (69) are quite stable and do not undergo elimination to give chloro-alkenes. However, if one equivalent of (MeO),PCH,S G

II II

0

0

C

H

3

+ R'R'C=O

R I R C = C H S a C H , II 0

(643) 66

67

D. L. Comins, A. F. Jacobine, J. L. Marshall, and M. M. Turnbull, Synrhesis, 1978, 309. M. Mikolajczyk, W. Midura, S. Grzejszczak, A. Zatorski, and A. Chefczynska, J. Org. Chem., 1978,43,473.

Ylides and Related Compounds 221 HMFT is added, 1,2-epoxyalkenephosphonatesare formed.s8 A similar one-step synthesis of diethyl 1,Zepoxyphosphonates (70) has been d e ~ c r i b e d . ~ ~ Li

CH3

1 (EtO),P-CCH, ll I

+ PhCHO

\

O

I +

i II I I 0 C1 OH

(EtO),P-C-CH,Ph

(69)

CH3

I

H

(Et O),P-C-C( '0'

II

Ph

0

V

R'

+ L

/ R2

o

a-Chloro-erg-unsaturated ketones70 and esters71 can be obtained from the lithium anion of diethyl dichloromethanephosphonate by acylation and condensation with aldehydes (Scheme 10). c1

X = COR' or C0,Et Reagents: i, 2 BuLi; ii, CIX; iii, R2CH0

Scheme 10

It has been shown that displacement of chlorine atoms in 1,l-dichloroalkanephosphonates is catalysed by copper(1) salts. 72 The synthesis of alk-2-enoic acids has been improved as shown in Scheme 11. The (@-isomers are obtained from aldehydes whereas ketones form mixtures. 73 (E t0)J'CHS

II

0

i , i i c_

(EtO),PCH,CO,H

' 9

'5 :

RIR~=cHCO,H

.0I1

Reagents: i, BuLi; ii, COz; iii, R1R2C=0

Scheme 11 P. Perriot, J. Villieras, and J. F. Normant, Synthesis, 1978, 33. P. Coutrot and P. Savignac, Synthesis, 1978, 34. J. Villieras, P. Perriot, and J. F. Normant, Synthesis, 1978, 27. 7 1 J. Villieras, P. Perriot, and J. F. Normant, Synthesis, 1978, 31. 73 J. Villieras, A. Reliquet, and J. F. Normant, Synthesis, 1978, 27. 7 3 P. Coutrot, M. Snoussi, and P. Savignac, Synthesis, 1978, 133.

08

69

70

222


The reaction of the phosphonate (71) with 2-butanone, using thallium ethoxide as base, gave (72) as a mixture of isomers in a 1:1 ratio. If other bases are used, the (E)-isomer is the major product.74 The use of five-membered cyclic phosphonates, e.g. (73), in alkene synthesis leads to a slight preferential formation of cis-alkenes.75 (MeO),PCH,CO,Me + MeCEt

II 0

I1 0

--+

EtC=CHCO,Me

i

Me

(72)

(71)

+ RCHO

RCH-CHX

--F

(73) X = C0,Et or CN

cu

The enamine (74) can be formed using the anion of diethyl N-(pyrro1idino)methyl phosphonate.76

+

c

0

II

N-CHP(OEt),

u

0

2-Azadienes are prepared in very high yields by the condensation of (75) with aldehydes or ketones. Acid hydrolysis produces the appropriate aldehyde or ketone.

R'

I (EtO),PCHN=CHR'

II

R'

+ R3R4C=0

1 + R3R4C=C-N=CHR2

0

I/

RJR4GHCR1

Phosphonato-enaminescan be prepared by lithiation of the phosphonate (76) followed by treatment with dimethyl disulphide and elimination of methanethiol (Scheme 12).78 74

F. Camps, J. Coll, A. Guerrero, and M. Riba, Anales de Quim., 1977,73, 1057 (Chem. A h . ,

75

E. Breuer and D. M. Bannet, Tetrahedron, 1978, 34, 997. S. F. Martin and T. Chou, J. Org. Chem., 1978,43, 1027. A. Dehnel, J. P. Finet, and G. Lavielle, Synthesis, 1977, 474. H. Ahlbrecht and W. Farnung, Synfhesis, 1977, 336.

1978, 88, 104 630). 76 77

78


223 NRZ,

N Rz2

I R’CI-I,-CH I

i, ii

--+

I !

,NR22

RICH,-C-SMe

RCH=C

\

//P(OEt)Z

0

0

(76) Reagents: i, BuLi; ii, MeSSMe; iii, A

Scheme 12

Phase-transfer-catalysed asymmetric C-C bond formation has been achieved in a sequence of reactions using a Wittig-Horner reaction. Treatment of (77) with dimethyl phosphonates and base under phase-transfer conditions leads to (78) with approximately 50 % diastereomeric excess. 79980

0

II

+ (MeO),PCH,X

-

X = CN or C0,Me 0

Yh

0 (78)

I

(77) R = C--ti

1

Me Compound (79), an integral part of the synthesis of an antitumour macrocycle, was prepared using di-isopropyl ethylphosphonate (Scheme 13).81

Anions of a-trimethylsilyloxyphosphonates can be alkyiated (Scheme 14). Mild treatment with hydroxide ion converts the products directly into ketones.8* T. Wakabayashi and K. Watanabe, TetrahedronLetters, 1978, 361. T. Wakabayashi, K. Watanabe, Y. Kato, and M. Saito, Chem. Letters, 1977, 223. 81 A. I. Meyers, K. Tomioka, D. M. Roland, and D. Comins, Tetrahedron Letters, 1978, 1375. 82 T. Hata, A. Hashimme, M. Nakajima, and M. Sekine, Tetrahedron Letters, 1978, 363. 79

80

224

Organophosphorus Chemistry OSiMe,

I PhCH-P(OEt),

II 0

*

OSiMe,

I I II R O

PhC-P(OEt),

% PhCR

i1

0

Reagents: i, LDA; ii, RX;iii, NaOH, H20

Scheme 14

The ring size of cyclic phosphonates affects their reactions with the nitrone (80). Thus (81) gives an aziridine whereas thereaction using (82) leads to a p y r r ~ l i d i n e . ~ ~

A general synthesis of benzo-l,4dithiafulvenes based on the condensation of 1,3-benzodithiolephosphonate(83) with ketones has been described. 8 4 Reactions of phosphonate anions with steroidal 17-ketonesa6and with the piperidinone (84)86 have been studied. Amongst those phosphonates used in alkenation reactions are (85) and (86).87

m;""' - fJJ-(12 0

II

+0 4 ;

(8 3)

6

CH2Ph

(MeO),PCHPh,

II

0 (85)

83 84 86

88

87

S. Zbiada and E. Breuer, J.C.S. Chem. Comm., 1978, 6 . K. Akiba, K. Ishikawa, and N. Inamoto, Synthesis, 1977, 861. J. Wicha, K. Bal, and S. Piekut, Synth. Comm., 1977, 7 , 215. J. M. Bastian, U.S.P. 4 034 095 (Chem. A h . , 1977, 87, 135 097). R. S. Tewari,N. Kumari, and P. S. Kendurkar, J. Indian Chem. Soc., 1977,54,443 (Chem. Abs., 1978,88, 89 424).


225

Reactions of the anions of phosphine oxide (87) with bicyclic ketones, e.g. (88), have been described.88These reactions proceed stereospecifically, retaining the (2)geometry of the precursor and having an (E) geometry in the newly formed bond,88in this case to give vitamin D Bafter removal of the protecting group.

R’

R’

H (87)

R’ = PhCO (88)

R’ -

3 Selected Applications in Synthesis Pheromones.-The synthesis of achiral components of insect pheromones from carbonyl compounds using Wittig and Ielated reactions has been reviewed.8g A key step in the synthesis of an optically active precursor of the sex pheromone of pine sawflies involves the use of the ylide (89).90 THPO

I

Me

Me

I

MeCH-CHCHO

I

+ Me(CH,),CHCH$H=PPh,

\4

(89)

THp(iYe

Me

I

MtCH-CCCH=CHCH,CH(CH,),Me

Diethyl trimethylsilyloxycarbonylmethanephosphonate (W),prepared as shown, is useful for making ag-unsaturated acids from carbonyl compounds, since the silyl ester is hydrolysed on aqueous work-up. Queen substance (91) can be prepared directly in this way.B1 0 ‘BrCH,CO,SiMa, + (EtO),P

0

II

(90) + MeC(CH,),CHO

ll

-+ (EtO),PCH,CO,SiMe,

-

(90) 0

II

MeC(CH,),

H /c==c\co,H (91) 88

89 90 91

B. Lythgoe, M. E. N. Nambudiry, and J. Tideswell, Tetrahedron Letters, 1977, 3685. R. Rossi, Synthesis, 1977, 817. A. Tai, M. lmaida, T. Oda, and H. Watanabe, Chem. Letters, 1978, 61. L.Lombard0 and R. J. K. Taylor, Synthesis, 1978, 131.

226


cis-Jasmone has been obtained by treatment of the aldehyde (92) with propylidenetriphenylphosphorane.g2

+ EtCH=PP$

--+

(9 2)

Prostaglandins.-Use of the #l-oxido-ylide (93) in a prostaglandin synthesis gave a secondary allylic alcohol, and not the desired tertiary .O

4-

+ Ph,P-

I

00 3)

OH

A number of l4C-label1ed Fz,analogues have been prepared with the labelled salt (94) and the labelled phosphonate (95).94

Phi(CH,),'4C0,H Br'

(MeO),PCH, 14CCH,0Ar

(94)

(95)

Many akialogues of prostaglandins continue to be synthesized by standard techniques, Amongst those described this year are those incorporating a thiophen nucleus, prepared using (96),g6those using the aldehydes (97) and (98)96 and the usual phosphonates, and syntheses incorporating the pyrroline (99), leading to azapro~taglandins.~ Carbohydrates.-The ylide generated from the 8-D-ribophosphonium salt (100) with butyl-lithium at -50°C gave good yields of alkenes having the cc-L-Zyxo configuration. These presumably result from epimerization of the ylide prior to reaction (Scheme 15).9s However, stereochemistry can be retained in similar 92

93 94 95

96 97

9s

M. Iwamoto, S. Ryo, K. Kogami, and K. Hayashi, Japan. Kokai 77 51 341 (Chem. Abs., 1977, 87, 134 040). H. Niwa and M. Kurono, Chem. Letters, 1977, 1211. D. F. White, J. Labelled Compounds, Radiopharm., 1977, 13, 23 (Chem. Abs., 1977, 87, 38 949). T. K. Schaaf and J. S. Bindra, Ger. Offen. 2 640 692 (Chem. Abs., 1977, 87, 53 065). T. A. Eggetie, H. de Koning, and H. 0. Kuisman, Chem. Letters, 1977, 433. D. B. Reuschling, K. Kuehlein, and A. Linies, Ger. Offen. 2 557 748 (Chem. Abs., 1977,87, 117 630). J. A. Sccrist and S.-R. Wu, J. Org. Chem., 1977, 42, 4085.


227 OTHP

L

Ph,PCH,

OMe

PI-

Me O X "Me

Ph,P=CH

OMe

*"'

Ph3kH

Me O X Me 0

Me

Me

Scheme 15

condensations if the aldehyde component is incorporated into the carbohydrate, as shown by the preparation of (lOl)gg and (1O2).lo0 The readily accessible dialdehyde (103), isolated as the dihydroxydioxepan, reacts with carboethoxymethylenetriphenylphosphoraneto give a D-eythrUhexanoate.lo1A key step in the synthesis of a fructose 1-phosphonicacid derivative involves the condensation of the aldehyde (104) with the ylide (105).loa Carotenoids.-The importance of the Wittig reaction and its variants in the industrial synthesis of fine chemicals, particularly carotenoids, has been reviewed.lo3 R. C. Anderson and B. Fraser-Reid, Tetrahedron Letters, 1977, 2865. H. Ohrui and S. Emoto, Tetrahedron Letters, 1978, 2095. 101 C. L. Bhardwaj, J. C. Ireson, J. B. Lee, and M. J. Tyler, Tetrahedron, 1977, 33, 3279. 102 J.-C. Tang, B. E. Tropp, and R. Engel, TetrahedronLetters, 1978, 723. 103 H. Pommer, Angew. Chem. Internat. Edn., 1977, 16, 423. 99

100


228

O H C O Y

+ Ph,P=CHC,H,,

o?OHC

OH

OH

CH

II

CH

II

CHC0,Et CHC0,Et

V

Resonance-stabilized alkylidenetriphenylphosphoranesare oxidized to symmetrical alkenes and triphenylphosphine oxide using hydrogen peroxide. O 4 A preferred procedure consists of mixing aqueous solutions of the phosphonium salt and hydrogen peroxide in the presence of weak bases. /?-Carotene(106) and other symmetrical carotenoids can be obtained in good yields. The polyenes (107)105and (1O8)lo6 have been prepared by condensations using ylides and phosphonate anions respectively. The reaction of the oxido-ylide generated from optically active (109) and the cis,cis-aldehyde (110) gave an intermediate, with the new double bond trans, used in the total synthesis of HETE, a human metabolite of arachidonic acid.lo7 lo4A. Nurrenbach, J. Paust, H. Pommer, J. Schneider, and B. Schulz, Annalen, 1977, 1146. lo5 M. L. Klaus and B. A. Pawson, Ger. Offen. 2 651 968 (Chern. A h . , 1977, 87, 102 151). lo6 K. K. Chan and B. A. Pawson, Ger. Offen. 2 651 979 (Chem. Abs., 1977, 87, 102 063). lo7 E. J. Corey, H. Niwa, and J. Knolle, J. Amer, Chern. Soc., 1978, 100, 1942.

Ylides and Related Cornpourids

229

(106)

Wittig reactions with the dialdehyde (111) have been used to produce enolic 0-ketone carotenoids.108 The isolation of new derivatives of fossil carotenoids such as (112) and (113) and their syntheses from dialdehydes and two moles of a phosphorane followed by catalytic hydrogenation have been described.lo9 Ylides prepared from a3-, 8' 2-, and pionylidene-ethyltriphenylphosphonium bromides react with the polymer-bound aldehyde (114) to yield polymer-bound apocarotenoids. Cleavage under acidic conditions leads to carotenoids in good yield.l1°

A. K. Chopra, G. P. Moss, and B. C. L. Weedon, J.C.S. Chem. Comm., 1977, 467. Schaefle, B. Ludwig, P. Albrecht, and G. Ourisson, Tetrahedron Letters, 1977, 3673. 110 C. C.Leznoff and W. Sywanyk, J. Org. Chem., 1977,42, 3203.

10*

logJ.

230


R = Ar,

Non-benzenoid Aromatic Compounds.-An excellent general discussion of the use of bis-ylides and dialdehydes to prepare cyclophanes has been published.lll A number of new ortho-, meta-, and para-[2,]cycIophanes, e.g. (115), have been prepared using Wittig reactions at low temperature.

Ph3kH,

u

CH26Ph,

3.

(115a) LiOEt, EtOH DMF

3.

OHC

(115b)

111

B. Thulin, 0. Wennerstrom. and I. Somfai, Acta Chern. Scand. (B). 1978,32, 109.


23 1

Improved syntheses of benzannelated annulenes incorporating many Wittig reactions, particularly the use of (1 16) with o-phthalaldehyde, have been reported.l12Reaction with one equivalent of the salt leads to (117), whereas that with two equivalents gives (1 18). Both are useful for subsequent condensation stages.

R+ OHC

112

CHO

N. Darby, T. M.Cresp, and F. Sondheimer, J . Org. Chern., 1977,42, 1960

10 Phosphazenes BY R. KEAT

1 Introduction The output of publications dealing with the phosphazenes has now remained roughly the same over a three-year period. However, the proportion of these publications dealing with potential applications continues to increase, with work mainly originating in the U.S.A. and Japan. Crystal structure determination is also a growth area. Reviews related to this topic include those on phosphorus nitrides,l compounds of two-co-ordinate phosphorus, aspects of cyclophosphazene chemi~try,~,and cyclophosphazene clathrates.6Phosphazene chemistry has also been given wide coverage in two recent books6S7 on phosphorus chemistry.

2 Synthesis of Acyclic Bhosphazenes From Amines and Phosphorus(v) Halides.-Reactions in this category are very diverse in nature and include only two examples of the conventional Kirsanov reaction, by which (l)*and (2)9 have been prepared. The reaction with urea is much more complex than previously realized, and (1) may also be obtained * by reactions of the urea derivatives H,NC(O)NHP(O)Cl, or of (Me3SiNH),C0 with phosphorus pentachloride. The melamine derivatives (2) have been ammonol y ~ e dand , ~ find applications as flame retardants for cotton. Fluorophosphazenes (NH,),CO + PCl,

._*_

(CI,P==N),CO + POCl,

+ HCl + CI,P(O)NCO

+

(11

Cl,P=N-CN C,N,(NH,), + PCI,

__f

C,N,(NH,),-.(n=PCl,),

+ other by-products

+ HCl

(2) n = 1 - 3 1 2

3 4 5 6

7 6 9

E. V. Borisov and E. E. Nifant’ev, Russ. Chem. Reu., 1977, 46, 842. N. I. Shvetsov-Shilovskii, R. G. Bobkova, N. P. Ignatova, and N. N. Mel’nikov, Russ. Chem. Rev., 1977,46, 514. R. A. Shaw, Phosphorus and Sulfur, 1978,4, 101. R. A. Shaw and M. Woods, 1st. Internat. Congress on Phosphorus Compounds, Rabat, 1977, Abstracts, p. 249. H. R. Allcock, Accounts Chem. Res., 1 9 7 8 , l l . 81. J. W. Emsley and D. Hall, ‘The Chemistry of Phosphorus’, Harper and Row, London, 1976. D. E. C. Corbridge, ‘Phosphorus - An Outline of its Chemistry, Biochemistry, and Technology’, Elsevier, Amsterdam, 1978. L. Riesel and M. Henkel, 2. anorg. Chem., 1977, 435, 268. A. Y. Garner, U.S.P. 4 020 224 (Chem. Abs., 1977, 87, 7446).

232

Phosphazenes

233

+

PF, + LiN(SiMe,), -+ (Me,Si),NF,P=NSiMe,

LiF

+

Me,SiF

(3) RPF t I.iN(Sihte,),

RF,P=NSiMe,

__f

+

LiF

+

Me,SiF

(4) R = Ph, NMe,, or Me

(3) and (4), rather than phosphoranes, are producedlO by the reaction of phosphorus pentafluoride or its derivatives with LiN(SiMe,),. The diphenyl derivative Ph,FP=NSiMe, was similarly obtained from Ph2PF3,but (Me,N),PF, was unreactive towards LiN(SiMe,),. Thermal decomposition of (3) and (4) provides10 a new route to cyclic phosphazenes (see Section 4). The formation of phosphazenes, e.g. (5) and (6), from phosphorus(v) chlorides and bis(phosphiny1)[(RO),P(O)I,NY + ClP(0) (OR), Y = Na or SiMe, [(R,N),P(O)I,NY + ClP(0) (OEt), Y = Na or SiMe,

-

-

YCI

+ (RO),P(O)N=P(OR),[OP(O)(OR),] (5) R = Et

YCI + (R,N),P(O)N=P(NR,),[OP(O)(OEt),] (6) R = MeorEt

amides [X,P(O)],NY (X = OR or NR,; Y = H, Na, SiMe,, or MgBr) has also been realized,ll albeit as a result of a tautomerization step. The well-known condensation of amines with phosphines that is induced by CCll and Et3N has also been used to effect the formation of (6; R=Et), as shown in reaction (1). (Et,N),P(O) -N=P(NEt,

[(Et,N),P(O)I,NH + HUO) (OEt),

+ CCI,

+

-

NEt,

[OP(0) (OEt),l

(6) R = Et

+ CHCI,

+

Et,NHCl

(1)

Reactions with other phosphorus(v) chlorides also included PCI and P(O)CI,, the former being believedll (largely on the basis of 31P n.m.r. data) to give zwitterionic species such as (7) with [(R,N),P(O)],NH (R= Me or Et). Sodamidel*

(7)

as well as alkyl- (or aryl-)amines13has also been used to synthesizephosphazenes, e.g. (8) and (9), from phosphoranes, the main objective in the latter case13being the synthesis of thioureas (lo), as shown in Scheme 1. 10 11

P. Wisian-Neilson, R. H. Neilson, and A. H. Cowley, Itzorg. Chem., 1977, 16, 1640. L. Riesel, A. Claussnitzer, C. Ruby, and P. Kindscherowsky, 2.anorg. Chem., 1977, 437, 275.

18 13

H. Schmidbaur and H. J. Fueller, Ger. Offen. 2 557 611 (Chem. Abs., 1977, 87, 184 674). Y. Tamura, M. Adachi, T. Kawasaki, and Y. Kita, Tetrahedron Letters, 1978, 1755.


234

+ NaNH,

Me,PBr

H

R'R'NH

+

Me,P=N-P(=CH,)Me,

__t

NaBr

S

I II + Ph3P(SCN), --+ Ph3$--N-CNR'R2 R'R2NH

II

S P$PO + H,NCNR'R2

HO _I

R', R2 = alkyl or Ph

1 1

Ph,P=NCNR'R2

(9) Scheme 1

(10)

From h i d e s and Phosphorus(m) Compounds.-This route remains one of the most versatile for organo-substituted phosphazenes. When the phosphorus(1n) compound contains a P-H bond, tautomerization of the phosphazene can occur, as demonstrated1* by the isolation of (11) and its further reaction with azide to give (12). (Et,N),PH

+ PhN,

- N,

(Et,N),P-

NHPh

+ PhN,

(Et,N),f;NHPh It N-N=NPh (12)

The phosphazene (14) was synthesizedls to identify the azide (13), the latter being generated by azide-ion-induced cleavage of a P-N bond in a phosphorylgyrazole. Me0

1

'P-N3

Ph'

0

+

PPh, --+

Me*,ll

P-NEPPh,

+ N,

Ph' (13)

(14)

Unexpectedly, the silyl azide Me,SiN, reacts l6 with the phosphine Me,SiPMe, to give an amino-phosphine (15) by cleavage of a Si-P bond, but this then undergoes a normal azide reaction, leaving (16). The affinity of silyl groups for oxygen is demonstrated by the oxidation of (16) by molecular oxygen to give (17), as shown in Scheme 2. Trimethylsilyl azide is also effective in the oxidation of silyl phosphites17 and cyclodiphosph(nI)azanes,l* to give (17) (by a different route) and (18) respectively. Compound (18) was further identified by the sulphuration and quaternization (by methyl iodide) of the tervalent phosphorus atom. Trimethylgermyl azide and triphenylgermyl azide are equally effective in l4 l5 l6

l7 l8

V. S. Sergeev and Yu. G. Gololobov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 868. U. FeIcht and M. Regitz, Annalen., 1977, 1309. J. C. Wilburn and R. H. Neilson, Inorg. Chem., 1977, 16, 2519. M. Volkolz, 0. Stelzer, and R. Schmutzler, Chem. Ber., 1978,111, 890. W. Zeiss, Ch. Feldt, J. Weis, and G. Dunkel, Chem. Ber., 1978, 111, 1180.

Phosphazenes Me; SiPMe,

+

- N* --+

(Me, Si),NPMe,

235

Me,SiN,

- N,

Me

I

(Me,Si),NP=NSiMe, I

Me

I I Me

Me,SiN=POSiMe,

(17)

Scheme 2 Me Me,POSiMe,.

+

I I Me

Me,SiN, --+ Me,SiN=POSiMe,

- N,

(17)

SiMe,

R1,P + R2,GeN,

- N*

R1,P=N--GeR2, (19) R', R2 = alkyl or Ph

givingl9good yields of N-germylphosphazenes (19), which can also be obtained by other routes (see below). The selection2o of suitable phosphines (20) as substrates for the azide reaction can lead to phosphazenes (21) which are the precursors of polymers with carbon backbones, these polymers having good heat resistance. Ph,PR + (PhO),P(O)N,

(20)

(PhO),P(O)N=PPh, R (21) R = styryl

A less conventional example of the oxidation of phosphines by azides is provided by the observationz1that phosphine ligands can be converted into phosphazene ligands in complexes of cobalt(n), e.g. forming (22), at ambient temperatures. It is not clear whether oxidation occurs at the free phosphine, but in one case an intermediate complex, Co-{furN,P(C,H,l),) Et,O - Br,, was 19 2o

21

W. Wolfsberger, 2. Naturforsch., 1977, 32b, 152. K. Paciorek, U.S. Pat. Appl. 706 424 (Chem. Abs., 1977, 87, 40 200). W. Beck, W. Rieber, and H. Kirmaier, 2.Naturforsch., 1977, 32b, 528.

236

Organophosphorus Chemistry Et,O

+ N,

[Co(PR,),X,l + furN, --+ [Co(furN=PR,),X,] (22) fur = furoyl R = alkylor Ph X = C1 or Br

isolated at sub-ambient temperatures. Reactions with ortho-phenolic azides are far from straightforward 2 2 and can result in the formation of phosphoranes (23), but, when the phenolic group is modified, two courses are followed, depending on the type of phosphorus(rz1) compound, as shown in Scheme 3.

y-7 HN-P’

,Ph

I

’Ph OMe

(23)

aN3 -

-

OEt

OCOPll

px,

\

- PhCONMe,

X = NMe,

Scheme 3

Reactions of diazoalkanes with phosphorus(m) compounds also provide a route to phosphazenes, and a further example has been demonstratedz3by the synthesis of (24).

,co,et

(RO),P

+

(MeO), P( O)C(OH)MeC(N, )@O,E t

I___*_

(RO)3P=N-N===C

‘C(OH)MeP(O)

( OMe),

(24)

Other Methods.-The reactions of nitriles with phosphorus pentachloride continue to be exploited for the synthesis of N-chloroalkyl-phosphazenes,e.g. (25) 24 and (26).z 5 The phosphorus(v) chloride [C13P=NPC13]+C1- undergoes 2 6 related reactions to give phosphazenes (27) and (28). With suitable nitriles, these reactions may be adapted to give cyclic phosphazenes (see Section 4). 22

23 24 25

z6

J. I. G. Cadogan, N. J. Stewart, and N. J. Tweddle, J.C.S. Chem. Comm., 1978, 182. R. D. Gareev and A. N. Pudovik, J. G m . Chem. (U.S.S.R.), 1976,46,2381. P. P. Kornuta, A. I. Kalenskaya, and V. I. Shevchenko, J. Gen. Chem. (U.S.S.R.), 1977, 49, 314. A. I. Kalenskaya and V. I. Shevchenko, J. Gen. Chem. (U.S.S.R.), 1977,47,43. E. Fluck, E. Schmid, and W. Haubold, 2.anorg. Chem., 1977,433,229.

Phosphazenes

237 R'R'CCICN + PC1,

R' R2CClCC1,N=PC1,

__f

(25) R' = Me Rz = C1, CH,Cl, or Me

AlkC(CN),

+ PCl,

-

AlkC(CN),CCl,N=PC1, (26)

-

R',PCl + R2,PNXNa

R',P--PPR2,

R',PNX(PR2,)

-+

II

(29) X = aryl

NX

An interesting relationship between diphosphinoamines and P-P-bonded phosphazenes is shown by the synthesis2' of (29); unfortunately, few details of the R groups were given. When R1=Pri and R2=OEt, the =NX group in (29) can be thermally induced to transfer to the -PPri2 group. Finally, amino-sugars have been converted 2 8 into their triphenylphosphazenyl derivatives by their reaction with a mixture of Ph,P and CCI,, as shown in reaction (2). RNH, + Ph3P + CCl,

- CHCl, .___f

RNH$Ph, C1-

+ Et,N - HCl

RN=PPh,

(R = various deoxyglucopyranose groups)

3 Properties of Acyclic Phosphazenes Halogeno-derivatives.-The initial product of methanolysis of C12P(0)N=PCI, is a phosphazene (30), but, at ambient temperatures, rearrangement to a diphosphinylamine occurs.29 Cl,P(O)N=PCl,

+ nIeoH

- HCI

C1, P(O)N=PCI,OMe (30)

-

CI,P(O)N(Me)P(O)CI,

+

The acyclic phosphazene Cl3P=NCI2P=NPCI3 PC1,-, when mixed with polydimethylsiloxane,improves the resistance of phenols to oxidation,30and the N-acyl compounds R1C(0)N=P(NHR2),CI (R1= chloroalkyl, R2= aryl), presumably obtained from R1C(0)N=PC13, are active f~ngicides.,~ 27 28

29

30 31

V. L. FOSS,Yu. A. Veits, T. E. Tret'yakova, and I. F. Lutsenko, J . Gen. Chem. (U.S.S.R.), 1977, 47, 870. I. Pint&, J. KovBks, and A. Messmer, Carbohydrate Res., 1977, 53, 117. L. Riesel, M. Willfahrt, W. Grosse, P. Kindscherowsky, A. A. Chodak, V. A. Gilyarov, and M. I. Kabachnik, 2. anorg. Cliem., 1977, 435,61. J. Burkhardt, Ger. Offen. 2 538 818 (Chem. Abs., 1977, 87, 6641). E. A. Shomova, Zh. S. Kuprina, A. I. Smolina, V. I. Kondratenko, and V. P. Rudavskii, Fiziol. Akt. Veshchesrva, 1976, 8, 30 (Cfiem.Abs., 1977, 87, 1121).

238


Some 36Cln.q.r. data, including the results of TI measurements, have been reported for a further series of P-chlorophosphazenes RN=PCI, (R =chloroand alkyl3,1 3 3 or Ph32),XN=PCI(CCl,), (X=POCl,, SOCl, S02CI, or RN=PCCI2CCl3(R =But or C6H4CI-p).33 Amino-, Alkoxy-, Alkyl-, and Aryl-derivatives.-In an impressive piece of work,34 the relationship between phosph(II1)azene.s (3 1) and cyclodiphosph(n1)azanes(32) has been explored. The synthetic route employed is shown in Scheme 4. The

[R' R2N'PNR31,

R'

R2

(32) Me

&

R' RzNP=NR3

7

R3

R2

R'

R3

Me

But

SiMe,

Pri

But

Pri

SiMe,

SiMe,

Me

But

SiMe,

Pri

Pri

Pri

Pri

But

Pri

Pr'

SiMe,

SiMe,

(31)

Reagents : i, R1R2NLi; ii, LiN(SiMe3)Ra

Scheme 4

dimerization of (3 1;R1= Ra= Pri, R3= But) occurs over a period of months, and, more interesting, the equilibrium between (33) and (34) depends on the physical state. R,NN(Me)P=NR (33)R = SiMe,

PCI,

+

MeRNNRLi --+

R = SiMe,

solid gas, solution,

[R,NN(Me)PNR],

heating

R,NN(Me)P==N-NRMe (35)

(34)

+

RMeNN(R)P=N-NRMe

(36)

The synthesis of the P-hydrazinophosph(1u)azenes (35) and (36), and their reactions, have also been Interesting new di-ylidic species (37) have been obtained36by the addition of diazoethanes to a phosph(1rI)azene. The compounds (37) do not dimerize, as in the case of the di-ylide (Me3Si),NP(=NSiMe3),, but they do add to diazoethanes 82

33

34 35

E. A. Romanenko and M. I. Povolotskii, Teor. i eksp. Khim., 1977, 13, 70 (Chem. Abs., 1977, 87,4884). E. S . KOZIOV, S. N. Gaidamaka, I. A. Kyuntsel', V. A. Mokeeva, and G. B. Soifer, J. Gem Chem. (U.S.S.R.), 1977, 47, 930. 0. J. Scherer and W. Glassel, Chem. Ber., 1977, 110, 3874. E. Niecke and D. A. Wildbredt, Angew. Chem. Znternat. Edn., 1978, 17, 199.

Phosphazenes

239 R',N

R',NP=NR'

MeR'CN,

- N,

'P=CR%

R'N @

RZ ,C=CH,

R',N,

MeR'CN, + II'

'H

D

R' = Me or But

R'N @'

(37) R' = SiMe, RZ = Me, Et, P r y o r But

N-N==CR'Me

to give (38). Proton addition38 to the same phosph(1u)azene under selected conditions gives a hitherto unknown class of amino-phosphane (39). The oxidation of phosph(1n)azenes with t-butyl azide gives 37 the phospholine ring system (40),as indicated by an X-ray study of (40; R = SiMe,). Spectroscopic data on (40;R = Pri) were, however, consistent with the presence of phosphorus(v), but this assignment3 8 has now been revised.37 R,N-P-NR

+ Me,NH*BH,

R,NP=NSiMe,

+

-

H,B-NMe,

Me,SiN,

+

R,N-PH(NHR)

(39) R = SiMe,

-

SiMe, NAN, 11 PNR,

N.+

SiMe, (40)

Further addition reactions of the diphosphazenyl compounds (41) have been and the structures of the zwitterionic compounds (42) were indicated by an X-ray study of (42; E=Ti, n = 3). This confirmed the presence of a roughly trigonal-bipyramidal distribution of bonds about the T i I V atom, as indicated by the n.m.r. inequivalence of the R groups attached to the ring.

(42) R = SiMe,; X = C1 E = Sn, AI, FeIII, TiIv, or Nbv

The addition of (41) to phosph(1n)azenes results in the formation of cyclodiphosphazanes (42a),40the structures of which were established by n.m.r. data [including the lSN labelling41 of (42a; R1=Me, Ra=R3=NM%)] and by the results of thermolysis reactions. A variation on the same theme was also provided by the synthesis of the cyclodiphosphazanes (43) and (44). E. Niecke and G . Ringel, Angew. Chem. Internat. Edn., 1977, 16, 486. S. Pohl, E. Niecke, and H.-G. Schafer, Angew. Chem. Internat. Edn., 1978, 17, 136. E. Niecke and H.-G. Schafer, Angew. Chem. Internat. Edn., 1977, 16, 783. 39 E. Niecke, R. Kroher, and S. Pohl, Angew. Chem. Internat. Edn., 1977, 16, 864. 4O M. Halstenburg and R. Appel, Chem. Ber., 1978, 111, 1815. 41 R. Appel, M. Halstenburg, and F. Knoll, 2.Naturforsch., 1977, 32b, 1030. 3t3 37


240

(41)

+

(42a) R' = alkyl or SiMe, RZ = Ph, Me, or NMe, R3 = Ph, Me, or NMe,

-

RN=PR~,(CH,),RZ,P=NR

R N

RN

R2N

V'\ N / 'PR1,

(cH, 1, R2, P-NR

R = R = R1 = R2 =

(43) n

1,2,or4 SiMe, PhorMe Ph

= 2 or 4 R' = M e o r Ph R2 = Ph

(44) n

A vast range of N-silyl-phosphazenes (45)42 and (46)43 have been prepared recently, largely using exchange reactions of the type shown. In two cases, the chlorosilyl derivatives (45) were found to dimerize to give ionic species, e.g. (47). Methoxy- [R3P=NSiMe,-,(OMe)n] 4 4 and fluoro-derivatives [R,P=NSiMe,-,Fn]46of (45) were obtained by reactions with sodium methoxide and sodium R,P=NSiMe,

-

+ Me,-,SiCl,

R,P=NSiMe,SiMe,N=PR,

+

R,P=

NSiMe,-,Cl,

+

Me,SiCl

(45) R = Alkyl

C1Me2SiSiMe2C1 -+

R,P=N(SiMe,),CI

(46) R = Alicyl Me2 N=PMe, Si Me2

42

43

44 45

W. W. W. W.

12+

2C1-

(47) Wolfsberger, 2. Naturforsch., 1977, 32b, 961. Wolfsberger, Chem.-Ztg., 1977, 101, 360 (Chem. Abs., 1977, 87, 152 319). Wolfsbergec, Chem.-Ztg., 1977, 101, 359 (Chem. Abs., 1977, 87, 152 318). Wolfsberger, J. Fluorine Chem., 1978, 11, 159.

241

Phosphazenes

fluoride respectively. The fluorides, which could also be obtained by exchange reactions with silicon fluorides MenSiF4-, (n= 2 or 3), are monomeric in solution at ambient temperatures and above, but n.m.r. spectroscopy showed that, at low temperatures, the dimeric species analogous to (47)are formed. The 13C,31P, and 29Sin.m.r. spectra of a series of N-silyl-phosphazenes of the types shown above have been with particular emphasis on 29Sishifts, which appear to be interpretable in terms of hyperconjugative rather than (p-d)n-bonding interactions. The versatility of these exchange reactions is demonstrated by the synthesis4 7 of N-germyl-phosphazenes (48). Other N-germyl-phosphazenes, e.g. (49) and (50), have been obtained by the azide route (see Section 2) and by the reactions shown.lg R',P=NMMe,

+ Me,MX

+ RZ4-,GeXn -+- R1,P=NGeR2,-,,X, (48) R1 = R2 = Me

R',P=NLi

f

ClCeR2,

__f

+

R',P=NGeR2,

Licl

(49) R' = Ph, R2 = Me R' = Bun, R2 = Me

+ MeLi -+ R,P=NGeMe, R,P=NGeCl, (R includes alkyl and Ph) (50)

+

LiCl

The reactions of N-silyl- and N-germyl-phosphazenes with other acid species have been explored by several workers. Thus hydrogen halides initially protonate the nitrogen atom and cleave the M-N, rather than the P-N, bond to give (51).48 Boron halides give49a new group of N-boryl-phosphazenes (52), which are monomeric in the gas phase (mass spectra), but dimeric, with structure (53), R,P=NMMe,

+ HX

-+

[R,;NHMMe,]X-

3

R = MeorEt M = Si,Ge,or Sn X = C1, Br, or 1 Ph,P=NSiMe,

+ R,BX

__f

R,P=NBR, R (52)F

[R,{NH,]X(5 1)

+ Me,SiX

X F

c1 c1

X" Bd Ph3P=N / 'N=PPh, 'BY

Br Br Bun C1 Ph C1

XZ (5 3)

46

W. Buchner and W. Wolfsberger, 2. Naturforsch., 1977, 32b, 967.

47

W.Wolfsberger and H. H. Pickel, J. Organometallic Chem., 1978, 145, 29.

48

W. Wolfsberger, Z . anorg. Chem., 1978, 438,206.

49

W. Maringgele, A. Meller, H. Noth, and R. Schroen, 2. Naturforsch., 1978, 33b, 673.


242

+ ClCN

R'R2,P=NSiMe,

+ Me,SiCl

R'R2,P=NCN

_ +

(54) R', R2 = Me and/or Ph

PbP(=NSiMe,)

+ ClCN

(CH,),PPh,(=NSiMe,)

\

(n = 2-4)

PhP(=NCN)

+ Me,SiCl

(CH,),P(=NCN)Ph, (55)

+ C,F,

R,P=NSiMe,

+ Me,SiF

R,P=NC,F,

_j.

( 5 6 ) R = Me, Ph, or NMe,

in solution when R=hal. Cyanides (54) and (55) have been obtained60 in an analogous manner, and even the C-F bond in C6F6can be cleaved to give (56).61 However, when the acidic species is CO, or CS,, it is the phosphazene linkage that is cleaved,6aand other rearrangements also occur with P-P-bonded compounds, as shown in Scheme 5. Me,P--PMe,+

II II Me,SiN S,

-

CO,

+ Me,PSiMe,

I1

S

0

Me, P -0-P( co2

Me,P-PMe,

__f

II II Me,SiN NSiMe,

S)Me,

Me,P(O)OSiMe,

+ Me,SiNCO

\cs2

\ Me,P(S)P(S)Me, + Me,P(S)SiMe, Scheme 5

The phosphonium salts (57) and (58) have been prepared63by Si-N cleavage. R*,M=NP(R2,)=NSiMe,

+ Me,MX,

__f

R1,P=N6(R2,)N=

bond

MMe, X- + hte,SiX

(57) R' = alkyl; R2 = Ph or But M = P or As; X = C l o r Br [Me, SiN=PPh+NSiMe,]-

+ Me, AsCl,

63

+

Me,As=NPPh,N=AsMe,

C1- + Me,SiCI

(58)

Ruppert and R. Appel, Cliem. Ber., 1978, 111, 751. D. Dahmann and H. Rose, Chem. Ztg., 1977, 101, 401 (Chern. Abs., 1978, 88,22 257). R. Appel and R. Milker, Chern. Ber., 1977, 110, 3201. W. Wolfsberger and W.Hager, 2.anorg. Chem., 1977,433, 247.

so I. 51

Na'

243

Pliosphazenes

In nitrogen and carbon di-ylidic species it is the latter (methylenephosphorane) grouping that undergoes preferential reaction with epoxides to give (59).54 The phosphazenyl group occupies an axial position in the trigonal-bipyramidal distribution of bonds about phosphorus in (59). N-PMe, A 0\

Me,P===NP(Me,)=CH,

f

H2C-

CH,

__f

Me-Pl’

I

.Me

‘3

0

The isomerization of phosphinothioyl-phosphazenes,e.g. (60) 5 5 and (61),56 has been studied in detail. The compound (61) follows second-order kinetics, and researchers favour the intervention of the ion-pair intermediate (62) as being the mechanism as the result of investigations into the effects of temperature and the dielectric constant of the solvent on the reaction. (EtO),P=NP(S)(OEt)Me

--+

(EtO), P(O)N=P(OEt)

(SEt)Me

(60) (MeO),P== NP(S) (OPh),

---+ (MeO),P(O)N=

(MeO),P=NP(S)(OPh),

I

T

P(SMe) (OPh),

+ (MeO),P =NP(OPh),

I

0-

SMe

(62)

Other equilibria involving the affinity of a trimethyIsily1group for nitrogen or oxygen are dependent 5 7 on the nature of the substituents in (63) and (64). The IH, 31P,and 29Sin.m.r. shifts for these compounds have also been reported. X,P-N-P(O)X,

I1 I 0 SiMe,

(63) X = OEt or NMe,

==F

X,P=N-PX,

I

OSiMe, ‘64) X = OMe, NEt,, or NPr“

Intramolecular addition 5 8 of a phenolic hydroxy-group across a phosphazene linkage in (65) leads to the phosphorane (66). The equilibria between these compounds, followed by 31Pn.m.r. spectroscopy at different temperatures and in different solvents, were dependent on the substituents R1-R3. 54 55 56 57

H. Schmidbaur and P. Holl, 2. Naturforsch., 1978, 33b, 572. A. A. Khodak, V. A. Gilparov, T. M. Shcherbina, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1976, 46, 2376. A. A. Khodak, V. A. Gilyarov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1977,47, 251. L. Riesel, A. Claussnitzer and C . Ruby, 2. anorg. Chem., 1977, 433, 200. H. B. Stegmann, R. Haller, and K. Scheffler, Chem. Ber., 1977, 110, 3817.

9


244

R’ (65) Ri = CPh, or But RZ = P h o r E t R3 = Ph or alkyl

(66)

Experimental and theoretical interest in the protonation of phosphazenes has been expressed. Thus the structure of the quaternary salt (67) was deduced 59 from i.r. data; further protonation occurs at a dimethylamino-group in this salt. (Me,N),P=NMe

+ HCI + SbCl,

-

[(Me,N),PNHMe]+[SbC1,1(67)

The determination6o of the enthalpies of mixing of propanol with Ph3P=NH and with Ph,C=NH, from i.r. spectra, shows that the former is more exothermic. Analogous conclusions*f have been reached from M.O. studies on imines and phosphazenes, for the degree of base ‘hardness’ increases in the order HN=NH < HN=CH, < NH=PH, with respect to the reference acid BeF,. The versatility of the [Ph3P=NPPh3]+cation has been demonstrated by the preparation of salts of the type n[Ph3P=NPPh3]+ Xn- (X= hal, SO4, NO3, NO2, CrO,, CN, OCN, SCN, etc.). The lSF n.m.r. shifts have been for the (n = 1 or 3 ; X= Me, OMe, hal, CN, phosphazenes (FC6H4)nPh3_nP=NC6HsX NOz, etc.) and (XC6H4)3P=NC6&F, and for their salts with methyl iodide. These indicate considerable electron delocalization from the nitrogen atoms to the attached aryl ring in the phosphazene, but not in the salts. Photolysis of phosphazenes, e.g. (68) and (69), can result 6 4 in the formation of triphenylphosphine, or simply result in rearrangements of alkyl groups, whereas stabilized phosphazenes, e.g. Ph3P=NX (X = SO,Ph, COPh, C02Me, or Ph,P=NAr

Ph,P

+

ArN=NAr

(68) Ar = aryl

Ph,P=NR

Ph,P=NR’

(rearranged)

(69) R = alkyl K.-D. Press1 and A. Schmidt, 2.anorg. Chem., 1977, 435, 69. E. V. Ryl’tsev, A. K. Shurubura, I. F. Tsymbal, N. N. Kalibabchuk, and Yu. P. Egorov, Muter. Vses. Soueshch. Fiz. Zhidk., 1974, 233 (Chem. A h . , 1978, 88, 37 078). 61 N. N. Kharabaev, V. A. Kogan, and 0. A. Osipov, Zhur.jiz. Khim., 1977,51,1775 (Chem. Abs., 1977, 87, 157 423). * a A. Martinsen and J. Sonstad, Acta Chem. Scand. ( A ) , 1977, 31, 645. 83 I. Schuster, Tetrahedron, 1977, 33, 1075. 64 A. S. Yim, M. H. Akhtar, A. M. Unrau, and A. C. Oehlschlager, Canad. J. Chem., 1978, 56, 289. 59 60

245

Phosphazenes

CPh=CHPh), are unaffected under these conditions. The dissociation of (68) is believed to proceed via excited structures such as Ph,P-fiAr, rather than by nitrene formation. Molecular orbital calculations, within the CNDO/2 framework, have been performed on Me,P=NH, (F3PNMe),,65and R1,P=NR2 (R1=H, Me, or F; R 2= H, Me, CCl,, Ph, or CH=CH2) 6 6 in order to assess the tendency for the dimerization process phosphazene -+ cyclodiphosphazane to occur.

4 Synthesis of Cyclic Phosphazenes There are few new cyclic phosph(rn)azenes,the first examples of which were based on structures (70) and (71).67A new synthetic route 6 * to this class of compounds involves reductive elimination of cyclic disulphides, leading to (72); (71 ; R1= R 2= Me) was obtained in an analogous manner.

N-PCI2 \ p h d ,NMe N

- 2HCl

Further methods of optimizing yields of cyclic phosphazenes from the reaction of NH4Cl with PC16 have been describedYs9~ 70 with relatively large-scale production in view. New pyrolytic methods for the synthesis of cyclic phosphazenes (73) have been developed,1° in which the presence of cyclic homologues (n=3-6) was indicated from mass spectroscopic data. heat

R1R2FP=NSiMe,

1

(RiR2P=N),,

R’ (73)

65

68 67 68 69

70

F F F Ph Me

+

Me,SiF

R2 Ph NMe, Me Ph Me

A. S. Tarasevich and Yu. P. Egorov, Teor. i eksp. Khim., 1977, 13, 809 (Chem. Abs., 1978, 88, 73 941). A. S. Tarasevich, V. V. Pen’kovskii, and Yu. P. Egorov, Teor. i eksp. Khim., 1977,13, 589 (Chem. A h . , 1978, 88, 50 086). Y. Charbonnel and J. Barrans, Tetrahedron, 1976, 32, 2039. A. Schmidpeter, J. Liiber, and H. Tautz, Angew. Chem. Internat. Edn., 1977, 16, 546. J. T. F. Kao, U S . P. 4 065 546 (Chem. Abs., 1978, 88, 76 053). T. M. Fekete and J. F. Start, U.S. P. 4 046 857 (Chem. Abs., 1977, 87, 154 246).

246


The hexaphenyl-derivative N,P,Ph, has again been separated 71 from the products of pyrolysis of Ph,P(S)NHCH,Ph, as shown in reaction (3). By contrast, the N-methyl analogue gave an acyclic phosphazene (74), which was separated by t.1.c.

heat

Ph,P(S)NHCH,Ph

Ph,P(S)NHMe

heat

300-310 "C

310 "C

N,P,Ph,

+

Ph,P(S)NH,

(3)

Ph,P(S)NMe,

+

Ph,P(S)N=P(Ph,)N=PPh,NHMe

(74)

3-

Ph, P(S)SMe

The reactions of nitriles with phosphorus(v) chlorides form the subject of several papers. Thus cyano-benzamidines(75) react 7 2 with phosphorus pentachloride to give the cyclophosphazenes (76). When (76) is treated with glacial acetic acid, or n-butyl alcohol, (77) is obtained.

Whereas highly chlorinated nitriles H,CC13-nCN (n = 0 or 1) give acyclic phosphazenes with [CI,P=NPCI,]+ C1- (see Section 2), CHQCN reacts 2 6 with the same substrate to give the cyclodiphosphazene (78 ; R = C1). Analogous reactions 73 with acetonitrile gave (78; R = C1) and (78; R = H) (1 :4 ratio), PhCH,CN gave (78; R = Ph), and NC(CH,),CN gave (78 ; R = CN) mixed with Cl3P=NCI2P=NCCl=CHCN. With acrylonitrile and related compounds RICH=CHCN (R1= H, C1, CN, CH2CI,or Ph), addition of chlorine occurred 7 4 at the olefinic linkage, leaving (78; R = CHRlCl). The lH, 13C,and 31Pn.m.r. data for compounds (78) are discussed at length in the latter paper.

RCH,CN + [Cl,P=-NPCl,]'Cl-

I ClC\

71 '2

73

11

C

,Pa,

N. S . Sridhara, Z . Nuturforsch., 1978, 33b, 212. P. P. Kornuta, N. V. Kolotilo, and L. N. Markovskii, J. Cen. Chem. (U.S.S.R.), 1977, 47, 317. E. FIuck and E. Schmid, Phosphorus and SulJitr, 1977, 3, 209. E. Fluck, E. Schmid, and W. Haubold, 2.anorg. Chem., 1977, 434, 95.

247

Phosphazenes

A modification of the Kirsanov reaction has been employed 78 to obtain the cyclophosphazenes(79), which are potential anti-corrosion additives. Sulphur(vI) and titanium(iI1) have also been incorporated into phosphazene ring systems to give (80) (as well as S-fluoro- and C-chloro-analogues)7 7 and (81) 78 respectively. The presence of a TiIII atom (dl) was established by examination of its e.s.r. spectra. The novel zwitterionic species (82) was obtained by the reactions shown, and its constitution was established by 31P n.m.r. spectroscopy, and by the synthesis of the 16N-labelledcompound (bridge N-atom only). 759

(79) R1 = pertluoroalkyl or fluoro-ether

Rz = Ph or C,F,

+ SO,(NH,),

CF3CC1,N=-PCl,

- HCl

CF3

0

CF3 ,N=C \ +Pa, * OzS, N // - HCI, N-P -POCI, H C1,

V=G N-P

c1

C12

Me, Cp,TiCl

+

Me,P=NP(=CH,)Me

+ LiBu"

- Bu"H

HyC-5 Cp,Ti :N &-P'

Me2

(81)

+ [(Et,N),P(O)],NY

Y = H,Na, or SiMe,

+ PCl, (or POCl,, or ClP(O)(OEt),)

_.)

(Et,N),P#NkP(NEt2),

' A

o\-,P

'\ 0

(82) (other canonical forms possible)

5 Properties of Cyclic Phosphazenes Halogeno-derivatives.-The chlorocyclophosphazenes (NPClz)3or 75

76 77 78 79

have been

R. H. Kratzer, K. J. L. Paciorek, J. Kaufman, and T. I. Ito, J. Fluorine Chem., 1977, 10, 231. K. L. Paciorek, D. W. Karle, and R. H. Kratzer, NASA Contract Report, 1976, NASACR-135090; Sci. Tech. Aerosp. Rep., 1977, 15, N77 (Chem. Abs., 1977, 86, 190 791). W, Heider and 0. Glemser, Chem. Ber., 1978, 111, 731. H. Schmidbaur, W. Scharf, and H.-J. Fuller, 2. Naturforsch., 1977, 32b, 858. L. Riesel, A. Claussnitzer, and B. Thomas, 2. anorg. Chem., 1977, 437, 269.

248


converted into the hitherto unknown cyanophosphazenes "p(CN),], or by their reaction with potassium or sodium cyanides, although no experimental details are available. The electrical conductivities of the cyclic compounds (NPX,), (X=CIs1 or SCNS2)and polymers (NPX,)n (X=CIsl or SCNs2)have been studied. Of the chlorides, the conduction in the cyclic compound is governed by ions, and in the polymer by n-electrons. A patent application83 describes how chloro- and bromo-cyclophosphazenesmay be used in tungsten-halogen lamps. N3P3C16is finding applications in organic syntheses. It has been used to obtain the heterocycles (83; R = alkyl or Ph) from ~-(methylthio)anilides,~~ in the formation of penicillins (carboxy-group a c t i v a t i ~ n )and , ~ ~ in condensation reactions leading to the peptide tuftsin.86The homologues (NPCI,), or have been employed 8 7 to vulcanize a hydroxy-terminated butadiene rubber in the presence of 1,4-diazabicyclo-octaneas the acceptor of HCI.

(8 3)

The six-membered ring compounds N3P3Cla, (NPCI,),(NSOCI), (NPC1,)(NSOCI),, (NSOCl), and NPCI,(NSOF), form the subject 8 8 of a series of M.O. calculations at the CNDO/2 level which indicate the importance of the Dewar ('island') model of n-bonding, and that transannular bonding interactions decrease in the order P.- * P >P - * * S> S - * S . Crystal-structure information on the same compounds was also compared with 35Cln.q.r., 31Pn.m.r., and i.r. data, and basicity measurements on phenyl- and piperidino-derivatives of the above halogeno-compounds have been reported.s8By contrast, CNDO calculationssgon (NPX2)3(X=F or CI) and (NPF,), favour a bonding model in which the nelectrons are delocalized. ESCA determinationg0of the P(2p), C1(2p), F(ls), and N(ls) core-electron binding energies of (NPX,), ( X = F or C1) and (NPX,), (X=F, CI, or Me) show that there is very little difference in analogous six- and eight-membered rings; it was concluded that the extent of n-bonding should therefore be similar in the different sized rings. 14Nn.m.r. data have been obtained 91 for (NPX,), (X = F, C1, Br, NCS, OMe, or NMe,) and (NPX,), (X = F, C1, or OMe).

-

so M. Stodola and J. Terc, Czech. P. 168 164 (Chem. Abs., 1977, 87, 152 284).

M. Kajiwara and H. Saito, Polymer, 1977, 18, 351. M. Kajiwara and H. Saito, Macromol. Sci., Chem., 1977, A l l , 1081. J. R. Coaton, U.S.P. 4 027 189 (Chem. A h . , 1977, 87, 47 222). s4 G. Rosini and A. Medici, Synthesis, 1977, 892. 85 Ferrer Internat. S.A., Spanish P. 440 479 (Chern. Abs., 1977, 87, 135 316). 8 6 J. Martinez and F. Winternitz, Pept. Proc. Eur. Pept. Symp., 14th., 1976, 551 (Chem. Abs., 1978, 88, 7348). 87 S. Yamahita, K. Nose, and N. Kawabata, Nippon Gomu Kyokaishi, 1977, 90, 204 (Chem. Abs., 1977, 86, 191 071). 8 8 J.-P. Faucher, J. C. Van de Grampel, J. F. Labarre, S. N. Nabi, B. de Ruiter, and R. A. Shaw, J. Chem. Res. ( S ) , 1977, 112; ( M ) , 1977, 1257. 89 G . Hojer, M. Costas, and F. Martin Polo, Rev. Latinoamer. Quim., 1977, 8 , 110 (Clzem. Abs., 1977, 87, 206 918). S. C. Avanzino, W. L. Jolly, T. F. Schaaf, and H. R. Allcock, Inorg. Chem., 1977,16,2046. 91 J. Mason. W. Van Bronswijk, and J. G . Vintner, J.C.S. Dalton, 1977, 2337. 81

83 83

249

Phosphazenes

Amino-derivatives.-Addition 92 of the phosph(iI1)azene (84) to a series of ketimines leads to a series of phosphoranes, e.g. (85), in which the tertiary nitrogen atom occupies an axial position in the trigonal bipyramid.

(85)

An improved methodg3 for the synthesis of cis-bis(amino)-derivatives N3P3C14(NR1R2)2 (R1, R 2 = H , Me; Me, Me; Et, Et; C5H,o; C,H, or C4HBO) has been described. In essence, the use of acetonitrile as a solvent for the reaction increases the proportion of cis- relative to the trans-isomers, although further refluxing was necessary to obtain an appreciable yield of the cis-bis-diethylaminoderivative (R1= R2= Et). A re-investigationg4of the reaction of N3P3CI6with ethylenediamine and with ethanolamine shows that spirocyclic compounds (86; X = N H or 0),rather than ‘ansa’ compounds (in which the substituent spans two phosphorus atoms), are formed. The structures of compounds (86) and their dimethylamino-derivatives were established from lH and 31P n.m.r. data. The same n.m.r. methods were usedg5to establish the structures of the previously reported ammonolysis products N3P3C13R(NH2), and N3P3C12R2(NH2)2 (geminal NH, groups) and of N3P3R2(NH2)4 and N3P3R3(NH2)3 (non-geminal R groups), where R is -NMeP(O)(OEt),. Amino- and mixed amino-derivatives of N3P3CI, containing NH,, NHMe, and NMe, groups have been subjected to pyrolysis reactions 9 G (see Section 6). Silicon-nitrogen compounds have not been widely employed for the aminolysis of N3P3CI,because of the sluggish nature of the reaction. However, the formation of diethylamino-derivatives (see Scheme 6 ) is catalysedg7by a mixture of poly-

CI,P

NN/

PCI,

(86) (87) A. Schmidpeter, M. Junius, J. H. Weinmaier, J. Barrans, and Y. Charbonne1,Z. Nutiirforsch., 1977,32b, 841. 9 3 Z. Biran and J. M. Goldschmidt, Synth. React. Inorg. Metal-Org. Chem., 1978, 8, 185. 94 S. S. Krishnamurthy, K. Ramachandran, A. R. Vasudeva Murthy, R. A. Shaw, and M. Woods, Inorg. Nuclear Chem. Letters, 1977, 13, 407. 95 B. Thomas, P. Gehlert, H. Schadow, and H. Scheler, Z . anorg. Chem., 1978, 438, 249. 96 H. R. Allcock, C. H. Kolich, and W. C. Kossa, Inorg. Chem., 1977,16, 3362. 97 G. S. Gol’din, S. G. Federov, L. S. Baturina, and A. N. Novikova, J. Gen. Chem. (U.S.S.R.), 1977, 47, 751. 92

250 N3P3C16

i

-Me,SiCr

N3P3CI5NEt2

ii

Organophosphorus Chemistry N,P3CI,(NEt2), + N3P3C13(NEt2)3

Reagents: i, MeaSiNEtz ; ii, MesSiNEtz, polyphosphoric acid, pyridine Scheme 6

phosphoric acid and pyridine. 1.r. evidence indicates that compound (87) is obtained from non-geminal N3P3C14(0R)2[where R = CH,(CF,),H] and Me,SiNEt,. A silicon-nitrogen spirocyclic compound (88) is formed by the reaction Attempts to repeat this reaction with Ph2SiC1, and with BhSiC1, led to incompletely characterized linear compounds. The selective cleavage of tin-nitrogen bonds in N3P3F5N(SiMe3)2 has been usedg9to effect the synthesis of unusual heterocycles (89), where the cyclophosphazenyl group, (N,P,F,), acts as a stabilizing substituent.

Cyclophosphazenes in which carbon forms one or more of the ring atoms, such as (90), undergoloopreferential aminolysis at carbon to give (91). Exhaustive aminolysis of (90) gives compounds (92; R = Me or CH,). Preferential aminolysis at carbon also occur^^*^ with (93), leading to (94)-(97), but the exocyclic -N=PCI, group in (98) is more reactive than the endocyclic =CCI group, aminolysis giving (99) and (100). N3P3F, N(SnMe,), f

+ CH,(SO,NSnMe,N,P,F,),

+ xc1,

-Me,SnCl

CH, (SO,Cl),

O*S-SO, I N3P,F,"X/",P3F5

(89) X = S

98

99

100 101

/

\

or MeP

M. Kajiwara, M. Makihara, and H. Saito, Polymer, 1977, 18, 1045. H. W. Roesky and M. Banek, Synth. React. Inorg. Metal-Org. Chem., 1978,8, 111. E. Ruck and E. Schmid, Z. Naturforsch., 1977, 32b, 254. W. Pinkert. G. Schoning, and 0. Glemser, 2.anorg. Chem., 1977, 436, 136.

I

\

Phsphazenes

251

(95) R' = R2 = MeorEt

I

Me, SiNR'R2

R'R' N NR'R2 P'' N@ \N CNR'R'

N ''

_3

t

,N=PCl,

C1,

NH~\N

NHR,

II clc+N,ccl I

__t

Cl,

N/'\N ClC\

/I

N ,CCl

ll

86 )

,N=PC12NR2

1

NR'R'

R'R2NC+ ,CNR'R2 N

(97) R' = R2 = MeorEt

Cl,

/

N//'\N

Me SWR'R'

Ii

I

R'R'NC,

cf\

-

NHR,

I

,N=PCl,NR,

N/~\N

It

CIC\*CNR,

Several spirocyclic compounds have been synthesizedlo2 from the cyclophosphazene (101) by a combination of aminolysis and Kirsanov reactions. A rearrangement of fluorine from sulphur to phosphorus occurs1o3during the methylaminolysis (or ethylaminolysis) of (102) to give (103). Aminolysis of (102) occurs preferentially at the phosphorus atom, and the product (104) was fluorinated to give (105).

\\P/N=pc13

'

\N=PCl,

I

(Me,Si),NMe

Me

pc1

\\ /N=p, P

/ \N=p

Me

lo2 103

G. Schoning and 0. Glemser, Chem. Ber., 1977, 110, 3231. W. Heider, B. Hoge, and 0. Glemser, Chem. Ber., 1978,111, 737.

c12

,NMe

c12


252

MeNII,

+

Me,N

\

R~N~I

(-105) R = Me

Pyridine forms adductslo4with the heterocycles (106) which, on the basis of 13C and 31P n.m.r. data, can be formulated [(NP(py)CI}(NSOX),]+ OH- or [{NP(O)CI}(NSOX),]- pyH+, although the latter seems less likely.

(106) X = C1 or I:

Further details of the complexes formed between platinum halides and aminocyclophosphazenes, which have anti-cancer activity, have appeared.lo6 Both [NP(NHMe),], and [NP(NHMe),ln react with K,PtCI, in the presence of 18-crown-6 ether (in chloroform solution) to give [PtCl,{NP(NHMe),),] and [(PtC1,),{NP(NHMe)2]n] ( x :n N 1 :17) respectively. The N+Pt co-ordination in the former has been demonstrated by a crystal structure determination (see Section 8). In aqueous hydrochloric acid (no crown ether), a complex formulated as [H2N4P4(NHMe)8]2+ [PtC1,I2- is obtained. Similar complexes were obtained with N4P4Me8,using the crown ether solution, and using acid solution. In a detailed investigationlOe into the reactions of N4P4C18with t-butylamine, a series of derivatives N4P,C18-n(NHBut)n[n= 1, 2 (two isomers), 3, and 81, and N,P,(NHBU~)~ .HCl were isolated. By contrast with the reactions with N3P3CI6, the products of partial replacement of chlorine atoms ( n = 2 or 3) had nongeminal structures, which were established by lH and 31P n.m.r. spectroscopy as well as by the preparation of mixed amino-derivativesN,P,(NMe,),(NHBut), (X) (X = nothing or HCl) (two isomers) and N,P,CI,(NHEt)(NHBut) (two isomers).

-

104 105

108

A. Iedema and J. C. Van de Grampel, 2. Naturforsch., 1977, 32b, 873. H. R. Allcock, R. W. Allen, and J. P. O'Brien, J. Amer. Chem. Suc., 1977, 99, 3984. S. S. Krishnamurthy, A. C. Sau, A. R. Vasudeva Murthy, R. Keat, R. A. Shaw, and M. Woods, J.C.S. Dalton, 1977, 1980.

253

Phosphazenes

Alkoxy- and Aryloxy-derivatives.-Reactions107 of N3P3Cl, with fluoro-alkoxides MOCH,RF (M=Li or Na) gave a mixture of products N3P3Cl,-n(OCH,R~)n (n= 1-6), of which the fully substituted derivatives N3P3(0CH2CF3),, N3P3(OCH2C2F4H),, and N3P3(OCH,C,F,), were separated by g.1.c. A new synthetic roufel0* to alkoxy-derivatives (107) is provided by the opening of epoxide rings by N3P3C16,although experimental details are limited. N,P,CI,

f

0 a R 1

5 C2H2CI.l

N,P,(OCH,CHClR),

(107) R = H, Me,CH,Cl, or Ph

Selected physical (u.v., 31P n.m.r., dielectric constants) properties of the alkoxyphosphazenes N3P3(OR),(R= Me, Et, Prn, or Bun) have been rneasured,lOg as well as their tendency to polymerize on heating. The thermal behaviour of N,P,(OMe),, and of the analogous polymer [NP(OMe),ln, has also been examined.llo Proton and 13Cn.m.r. spectroscopy was used to follow the known rearrangement in these derivatives, shown in reaction (4).

The methoxy(hydroxy)phosphazenes N3P3(OMe),0H and N4P,(OMe),0H have been subjected to a detailed i.r, study,lll in which it was shown that hydrogen-bonded dimers, linked as shown in (108), are present in solvents of low polarity, and that dissociation of the dimers occurs in chloroform solution. A series of bromoaryloxycyclophosphazenes N3P3C13(OC6H,-nBrn)3 (n= 1, 3, or 5 ) has been obtained112by the reaction of N3P,C16 with the corresponding sodium bromoaryloxides.

(108)

Alkyl and Aryl Derivatives-When the phosphazene linkage forms part of a fivemembered ring, e.g. (109) and (lll), it is activated in addition reactions113with V. N. Prons, M. P. Grinblat, V. N. Sharov, and A. L. Klebanskii, J. Gen. Chem. (U.S.S.R.), 1977,47, 1149. B. Laszkiewicz and H. Struszczyk, Polish P. 87 269 (Chern. Abs., 1977, 87, 168 196). M. Kajiwara, Y. Mori, and H. Saito, Polymer, 1976, 17, 898. 110 V. D. Mochel and T. C. Cheng, Macromolecules, 1978, 11, 176. 111 R. Vilceanu and P. Schulz, Z. anorg. Chem., 1977, 436, 283. 1 1 2 B. Laszkiewicz and J. Dutkiewicz, Polish P. 86 996 (Chem. Abs., 1977, 87, 135 941). 113 A. Schmidpeter and T. Von Criegern, J.C.S. Chem. Comm., 1978, 470. 107

108 109


254

methyl isocyanate. The adducts (110) and (112) are generally stable with respect both to redissociation and to Wittig-type decomposition, except in the case of (110; X = NMe,), which loses methyl isocyanate on standing.

CO, Me

(109)

C0,Me

(110) X = Me, Ph, or NMe,

Y (112) X = Me or Ph Y = C0,MeorCN

Reactions of fluoro-cyclophosphazenes with organometallic reagents are generally cleaner than with chloro-cyclophosphazenes,and advantage of this has been taken in the synthesis of a cyclohexyl derivative (113)114and enolates, e.g. (11 4 ) P The carbonyl stretching frequency in (114) is somewhat lower than expected, and an interaction such as that shown in (114a) has been postulated to account for this. Further detai1s1ls of the deprotonation and rearrangement of quaternary salts derived from cyclophosphazeneshave appeared. Typical of these results is the formation of (115), and analogous results were obtained for

114 115 116

N, P, F, C,HI,

N, P, F, CH,COPh

(1 13)

(114)

I

(114a)

J. Blumentritt and T. Moeller, Inorg. Nuclear Chem. Letters, 1978, 14, 263. J. G. DuPont and C. W. Allen, Inorg. Chem., 1977, 16, 2964. R. T. Oakley and N. L. Paddock, Cunud. J. Chem., 1977,55, 3651.

255

Phosphazenes

N3P3Ph4M~ - Me1 and for N4P4Me,* MeI. Proton n.m.r. spectroscopy indicates that there is rapid proton exchange on the n.m.r. time-scale between the endocyclic carbon and the exocyclic nitrogen; this can be slowed by the addition of pyridine. The nature of the nucleophile effecting deprotonation is important, for KOBut gives linear oxides (MeNH)(Me,PN).P(O)Me, (n= 2-4) in addition to products such as (115). Compound (115) and related derivatives can be converted into cyclic oxides (116) in aqueous ethanol, and reactions with methyl iodide and with benzoyl chloride have been explored. H

H,

Mass spectroscopic results for the compounds (117), where R1 is CF,(CF,), or groups derived from fluorinated ethers and R2 is Ph,l17and for the phenylated cyclophosphazenes N,P3PhnCl,-n (n= 2-4, or 6) and N4P,C14Ph4118have been reported. In the latter study it was found that loss of chlorine and hydrogen atoms from SPPhC1 and -PPh2 groups respectively enables positional isomers to be distinguished. Thus the product of the reaction of N4P,CI, and PhMgBr, known to be N4P4CI,Ph2,was shown to have a geminal structure. The temperature dependence of the four signals observed in the 35Cln.q.r. spectrum of geminal N,P,CI,Ph, has been studied.llg

6 Polymeric Phosphazenes This topic forms the subject of two reviews,120g121 and a third122is concerned with fluorinated phosphazene polymers. as a Lewis acid The alkylaluminium chloride Et3Al,C13 has been catalyst for the generation of (NPC12)nfrom N3P3C16.Other synthetic routes to oligomeric chlorophosphazenes (NPCI,). and their conversion into cross-linked 117 118

119 120

121 122 123

K. J. L. Paciorek, J. H. Nakahara, and R. H. Kratzer, J. Fluorine Chem., 1978, 11, 536. C. W. Allen, R. L. Dieck, P. Brown, T. Moeller, C . D. Schmulbach, and A. G . Cook, J.C.S. Dalton, 1978, 173. K. R. Sridharan, V. S. S. Sastry, J. Ramakrishna, and S. S. Krishnamurthy, Proc. Nucl. Phys. Solid State Phys. Symp., 1975, 18C, 345 (Chem. Abs., 1977, 87, 109 009). C . Gheorghiu and M. Chirea, Rev. Chim. (Roumania), 1977,28, 835 (Chem. Abs., 1978,88, 23 915). H. Inoue, Kagaku To Kogyo, 1977,51, 128 (Chem. Abs., 1977,87, 160 908). J. A. Beckman, Hule Mex. Plast., 1977, 32, 16 (Chem. Abs., 1977, 87 40 519). Firestone Tire and Rubber Co., Neth. Appl. 76 09 253 (Chem. Abs., 1977, 87, 152 733).

256


polymers have also been described.la4Further examples of the use of force-field calculations for the conformational analysis of polymeric phosphazenes have been r e p ~ r t e dl.Z~6~ ~ ~ The pyrolysis of a series of aminophosphazenes, i.e. [NP(NHMe)&, N,P,(NH,),, N3P3(NHMe),, gemha1 N3P3(NH2)2(NMe2)a, and non-geminal N3P3(NH2)3(NMe2)3, has been explored,06phospham-type products being formed. Thermal stability conferred by amino-groups decreases in the order NMe, > NHMe > NH,. Substitution of the chlorine atoms in the linear polymer (NPCI,), by amino-acid alkyl ester groups gives novel series of degradable polymers with potential biomedical applications.127Complete replacement of chlorine was only achieved with glycine ethyl ester, but replacement of the unreacted chlorine by methylamino-groups was readily achieved, as shown in Scheme 7.

R', R2 = alkyl, corresponding to glycino ethyl, leucino methyl, alanino methyl, and phenylalanino methyl esters Reagents: i, H3kRlC02R2 C1-, Et3N; ii, MeNHs

Scheme 7

The electrical conductivities of the aminophosphazene polymers [NP(NHR)Jn (R= C6H13,CH2CH=CH,, or CH,Ph) have been measured,lZ8and the polymer [NP(NHMe)& forms lo6a complex with platinum(@ dichloride, of stoicheiometry (PtC12)JNP(NHMe),ln(x: n N" 1:17). The thermal polymerization of the trifluoroethoxy-derivatives N,P,CI,_,(OCH,CF& [n- 1, 2 (trans, non-geminal), 3 (trans, non-geminal), 4 (cis, nongeminal), or 51 has been 130 but linear-type polymers are only formed when n is 1,2, or 3. A related series of elastomers were obtained by copolymerization of N3P3C16and N3P3(0CH,CFs),; this also resulted in ring-expansion reactions, as demonstrated by n.m.r. spectroscopy. An interesting new route lS1to trifluoroethoxyphosphazenepolymers [NP(OCH,CF,>,], of relatively low molecular weight is provided by the thermolysis of the monophosphazene (CF,CH,O),P=NSiMe,, at 200 "C.A polymer of the same stoicheiometry, i.e. [NP(OCHsCF3)Jn,was studied by X-ray diffraction and by broad-line n.m.r. spectroscopy to obtain information on its mesomorphic transition. In another Ethyl Corporation, Fr. Demande 2 310 378 (Chem. Abs., 1977, 87, 24 749). R. H. Boyd and L. Kesner, J. Amer. Chem. SOC.,1977,99,4248. R. H. Boyd, U.S. NTIS A D Report, 1977, AD-A037092; Gov. Rep. Announce Index (U.S.), 1977, 77, 119 (Chern. Abs., 1977, 87, 53 728). 127 H. R. Allcock, T. J. Fuller, D. P. Mack, K. Matsumura, and K. A. Smeltz, Macromolecules, 1977, 10, 824. l 2 8 T.Hayashi and H. Saito, Bull. Chem. SOC.Japan, 1977, 50, 1023. 12Q H. R. Allcock, J. L. Schmutz, and K. M. Kosydar, Macromolecules, 1978, 11, 179. lSoJ. L. Schmutz and H. R. Allcock, Ger. Offen. 2 721 826 (Chem. Abs., 1978, 88, 51 368). 131 E. P. Flindt and H. Rose, Z . anorg. Chem., 1977, 428, 204. 133 M. N. Alexander, C. R. Desper, P. L. Sagalyn, and N. S. Schneider, Macromolecules, 1977, 10, 721. l-24 l25 126

257

Phosphazenes

the mesomorphic changes in the polymers [NP(OR)Jn (R = CH,CF,, C,H&k, or C6H4Ph) were also investigated. Other routes to alkoxy-substituted phosphazene polymers are limited to the reaction of (NPC12)nwith epoxides in the presence of aluminium trichloride,134 but numerous examples of aryloxy-substituted derivatives have been r e p ~ r t e d , l ~ these ~ - l ~ generally ~ being obtained from (NPCl& and the corresponding sodium aryloxide. Fluorophosphazene polymers hold considerable potential for the synthesis of alkyl- or aryl-substituted polymers because the fluorophosphazene chain is not readily cleaved by organometallic reagents.141 However, attempts to effect complete replacement of fluorine atoms resulted in shortening of the polymer chain, so that the route shown in Scheme 8 was employed to remove potentially reactive fluorine atoms. -(NPF2)n--

i _t

-(NPFRln--

-%

-[NP(OCH,CF,)R

1,-

R = Et, Bun, or Ph Reagents: i, RLi or RzMg; ii, NaOCHzCF3

Scheme 8

Alkynyl-phosphazenes, e.g. [NP(CCPh)&, are reported142to be formed from (NPCl& and the alkali-metal acetylide; as expected, these polymers readily add bromine across the acetylenic bond. N3P3(OCSF5)6does not polymerize on heating.142Polyphosphazene rubbers have been vulcanized,143using both cyclic and linear organosilicon hydrides, and the addition144of polyols to the geminal compounds N3P3CI4(XR),(X=O, S, or NH; R=alkyl, aryl etc.), results in the formation of biodegradable polymers. 7 Phosphazenes as Fire Retardants This topic has been covered in a series145of short review articles. Anilino133

C. R. Desper, N. S. Schneider, and E. Higginbotham, J. Polymer Sci., Polymer Letters Edn.,

134 135 136 137

B. Laszkiewicz and H. Struszczyk, J. Macromol. Sci., 1977, A l l , 2143. R. L. Dieck and E. J. Quinn, Gerl Offen. 2 708 319 (Chem. Abs., 1977, 87, 169 034). R. L. Dieck and E. J. Quinn, U.S. P. 4 055 520 (Chem. Abs., 1978, 88, 7903). R. L. Dieck, A. B. Magnusson, and E. J. Quinn, U.S. P. 4 055 523 (Chem. A h . , 1978,88,

138 139 140

T. C. Cheng, Ger. Offen. 2 706 771 (Chem. Abs., 1977, 87, 153 198). J. E. Thompson and K. A. Reynard, J. AppI. Polymer Sci., 1977, 21,2575. V. V. Korshak, S. V. Vinogradova, M. A. Andreeva, and E. G. Lagutkina, U.S.S.R. P. 472 560 (Chem. Abs., 1977, 87, 169 037). H. R. Allcock, D. B. Patterson, and T. L. Evans, J. Amer. Chem. SOC.,1977, 99, 6095. A. H. Gerber, U.S. NTIS Report, 1977, AD-A042912; Coo. Rep. Announce Zndex(U.S.), 1977,77, 103 (Chem. Abs., 1978,88, 51 200). V. V. Korshak, K. A. Andrianov, S. V. Vinogradova, M. A. Andreeva, E. G. Lagutkina, A. A. Zhdanov, E. F. Rodionova, and N. G. Vasilenko, U.S.S.R. P. 566 853 (Chem. A h . ,

1977, 15, 457.

8245).

141 142 143

1977, 87, 137 107). 144

I. Tabuse, S. Arita, and K. Kamamura, Japan. Kokai 76 134 800 (Chem. Abs., 1978, 88, 7676).

145

146

M. Kajiwara, Sen'i Kako, 1977,29, 9, 131,201,319,495, 543, 596,650 (Chem. Abs., 1977, 87, 23 989, 152 756, 137 113, 168 643; 1978, 88, 51 821, 106035, 75 211, and 122 254 respectively). A. H. De Edwardo, F. Zitomer, R. W. Stackman, and (Chem. Abs., 1977, 87, 118 861).

C. E, Ktamer, U.S. P. 4 042 561

258


derivatives of the polymer (NPCI,), confer 146 flame resistance on poly(ethy1ene terephthalate), and other amino-derivatives of N,P&& or N4P4C18improve the fire resistance of butadiene rubbers 14' and fabrics containing viscose 149 The products of the reaction of N3P3C16with mixtures of epichlorhydrin and ammonia are also useful additives to rayon.150-162Propoxy-derivatives of cyclic and linear phosphazenes have so far found the widest range of applications in this area, and new patent applications apply to cellulose-based f i b r e ~ , l ~ ~ - - l ~ ~ 15' and ~ 0 0 1 Aryloxy-substituted . ~ ~ ~ phosphazenes impart flame polyesters,156~ resistance to closed-cell foam^,^^^-^^^ polyester^,^^^^ l B 4and unspecified mat e r i a l ~The . ~ ~smoke ~ evolution of aryloxy-phosphazenesis suppressed by trimesic acid,lss and the toxicity of their products of thermal decomposition is less than that of those from PTFE or PVC.lS7 8 Molecular Structures of Phosphazenes that have been determined by X-Ray Diffraction Methods Compound

Comments

(Me,Si),NP=NSiMe,

Determined at - 130 "C. P-N 1.545(2) A P-N 1.674(1) A

168

(Me, Si),NP(=NSiMe,),

Determined at + 18 and - 130 "C. Planar distribution of bonds about P, with P--N 1.515(3) A , P-N 1.638(4) A.

169

Re5.

K. Nose, Japan. Kokai 77 101 293 (Chem. Abs., 1978, 88, 38 810). K. Mimura, Y.Isome, and T. Norimatsu, Japan. Kokai 77 139 156 (Chem. Abs., 1978,88, 122 607). 149 K. Mitsumura, T.Nakahama, and A. Kawai, Japan. Kokai 77 85 153 (Chem. Abs., 1978, 88, 50 454). 150 K. Mimura, Y.Kametani, and T. Nakahama, Japan. Kokai 77 42 913 (Chem. Abs., 1977, 87, 24 705). 151 M. Kametani, T.Nakahama, and K. Mimura, Japan. Kokai 77 46 028 (Chem. Abs., 1977, 87, 54 497). lS2 K. Mitsumura, H.Yamamori, and T.Nakahama, Japan. Kokai 77 88 616 (Chem. Abs., 1977,87,202 991). 153 R. S . Mohomed and B. C. Gardner, B. P. 1 464 545 (Chem. Abs., 1978,88, 122 635). 154 B. R. Franko-Filipasic and J. F. Start, U.S. P. 4 040 843 (Chem. Abs., 1977, 87, 137 275). 155 Ecil Corporation, Japan. Kokai 76 139 197 (Chem. Abs., 1977, 86, 191 298). 156 C. H. Kolich, H. G. Braxton, and U. A. Lehikoinen, U.S. P. 4 026 964 (Chem. Abs., 1977, 77, 40 234). 15' S. Hirakawa and T. Inoue, Japan. Kokai 77 96 676 (Chem. Abs., 1978,88, 8450). 15* G. S. Gol'din, S. G. Federov, S. F. Zapuskalova, V. V. Rozhkova, L. M. Sukhova, and R. G. Fomma, U.S.S.R. P. 558 080 (Chem. Abs., 1977, 87,40 702). 159 J. E. Thompson and K. A. Reynard, J. AppE. Polymer Sci., 1977, 21, 2575. 160 R. L. Dieck and E. J. Quinn, U.S. P. 4 053 456 (Chem. Abs., 1977, 87, 202 571). 1 6 1 R. L. Dieck and E. J. Quinn, U.S. P. 4 026 839 (Chem. Abs., 1977, 87, 24 536). 162 R. L. Dieck and E. J. Quinn, Ger. Offen. 2 712 542 (Chem. Abs., 1978, 88, 7890). 163 P. L. Meredith, U.S. P. 4 029 634 (Chem. Abs., 1977, 87, 54 138). 164 R. J. Guschl, Ger. Offen. 2 726 786 (Chem. Abs., 1978,88, 106 724). l65 K. Saito and S. Suganuma, Japan. Kokai, 77 31 030 (Chem. Abs., 1977, 87, 85 134). 166 R. L. Dieck and E. J. Quinn, U.S. P. 4 026 838 (Chem. Abs., 1977, 87, 24 275). 167 K. Sebata, J. H. Magill, and Y. Alarie, U.S. NTlS AD Report, 1977, AD-A046778; Gou. Rep. Announce Index (US.),1978,78, 137 (Chem. Abs., 1978, 88, 165 033). 168 S. Pohl, Z.Nuturforsch., 1977, 32b, 1344. lB9 S. Pohl and B. Krebs, Chem. Ber., 1977, 110,3183. 147 148

259

Ref.

c1

Unit cell contains two monomers and one dimer. P-N (monomer) 1.572(8) A P-N (dimer) 1.638(8) A

170

(Me3 Si)2N,

Planar co-ordination about P. P-N 1.519(4) A.

171

BU'NH

Planar c o a d i n a t i o n about P. P=N 1.505(4) A (very short) connected with large angle a t imine N (159.4').

172

N +Cd co-0r d ina t ion ;extensive NH-a.1 interactions. P-N not given.

173

Deep blue compound, which does not have zwitterionic acyclic structure. P-N 1.605(6) A.

174

2.;

Me,P=N,

)

,N=PMe,

Ge

\

Me, SiN [CdI, (NH=PPh3),],*2CHCl,

(Me,SiNH),P /N=s\N

\ N-S /

P=N

1.521(3) A.

175

P-N

1.590(10) A

176

F2p\N/pFz Me

/\

F2

OCFe -Fe-P=NMe

Me 170 171 172 173

13

W. S. Sheldrick, D. Schomburg, and W. Wolfsburger, Z . Naturforsch., 1978, 33b, 493. S. Pohl, J. Organometallic Chem., 1977, 142, 185. S. Pohl, J. Organometallic Chem., 1977, 142, 195. E. W. Abel, S. A. Mucklejohn, T. S. Cameron, and R. E. Cordes, 2.Nuturforsch., 1978, 33b, 339.

174 175

J. Weiss, Actu Cryst., 1977, B33, 2272. M. G. Newton, R. B. King, M. Chang, and J. Gimeno, J. Amer. Chem. SOC.,1978, 100,

176

M. G. Newton, R. B. King, M. Chang, and J. Gimeno, J. Amer. Chem. SOC.,1978,100,

1632. 326.


260 Comments P=N

Ref.

1.573(57) A

177

L PNP 136.6(37)

'P=N

1.554(18) A

L PNP 144.5(10)

pllcoMeN\P/Me

N //

\c/

NH N'

I AS

Mean endo P-N 1.59(1) A. N-H* *N interactions.

179

Distorted chair conformation.

180

P-N

1.599(2)-1.612(2) A.

P-N

(endo) 1.579-1.614(2) A. ( ~ x o )1.742(3) A.

C(0)Ph P-N

I1

I Me, P

178 O

II PPh,

181

Disordered structure; corrected P=N 1.635, 1.557 A.

182

'Saddle' shaped P=N ring, the P-N bonds flanking Pt-N being 1.611.54(2) A and other P-N bonds 1.57-1.6,1(2) A.

183

Phosphazene ring has 'boat' conformation, with P=N 1 S44-1.593(9) A.

184

"/ (MeNH),P'

/ N\\

(MeNM)2.P,

/N

' P (N HM el, \\ PtC1,+N /

,N

P(NHMe), /

N,P,Cl,(NMePh), (2 -tram -4) 177 178 179 180

181 182 183 184

J. J. Guy and G. M. Sheldrick, Acta Cryst., 1978, B34, 1718. J. J. Guy and G. M. Sheldrick, Actu Cryst., 1978, B34, 1722. Y. Sudhakara Babu, H. Manohar, K. Ramachandran, and S. S. Krishnamurthy, Z. Naturforsch., 1978, 33b, 588. R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Cunad. J. Chem., 1977,55,4206. R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Cunad. J. Chem., 1977,55,2534. M. J. Begley, D. B. Sowerby, and R. J. Tillott, Actu Cryst., 1977, B33, 2703. R. W. Allen, J. P. O'Brien, and H. R. Allcock, J. Amer. Chem. SOC.,1977, 99, 3987. Y.S. Babu and H. Manohar, Cryst. Struct. Comm., 1977, 6 , 803.

Phosphazenes

261

Compound

Comments

Ref.

N,P,CI,(NMePh), (2-trans-6)

Ring has centrosymmetric ‘chair’ conformation, with P-N 1.54-1.61(2) A .

185

N4P, CI, N =PPh,

exo P=N,

186

N,PGMe,,

‘Double tub’ conformation. Mean P-N 1.593(6) A .

187

N, P8Melri

C, Symmetry.

188

1.587(9) A , is longer than exo P--N, 1.566(9) A.

Mean P-N

1.590(13) A.

185

K. Krishna Bhandary, H. Manohar, and Y. Sudhakara Babu, Acta Cryst., 1977, B33,

186

Y.Sudhakara Babu, H. Manohar, T. S. Cameron, and R. A. Shaw, 2. Nuturforsch., 1978,

187

33b, 682. R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Canad. J . Chem., 1977,55, 3118. R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Canad.J. Chem., 1977,55,2530.

3548.

I1 Physical Methods BY

J. C. TEBBY

The abbreviations PIII, PIv, and Pv refer to the co-ordination number of phosphorus, and the compounds in each subsection are usually dealt with in this order. A number of relevant theoretical and inorganic studies are included in this chapter. In the formulae the letter R represents hydrogen, alkyl, or aryl, X represents electronegative substituents, Ch represents chalcogenides (usually oxygen and sulphur), and Y and Z are used to indicate groups of a more varied nature.

1 Nuclear Magnetic Resonance Spectroscopy Biological Applications.-The application of 31P n.m.r. spectroscopy, often in combination with lH and 13Cn.m.r., to biological chemistry has increased considerably. Some applications have been given in Chapter 7, and this method has also been used to follow the levels of various phosphorus-containingcompounds in cells1 and living tissue,2to follow pH changesY3 to distinguish malignant from non-malignant tissuey4and to study binding mechanisms.'j Biolayer structure,g transport numberY7 conformation,8and quaternary structureg have been studied,

1 2

3

6

* 7

T.R. Brown, K. Ugurbil, and R. G. Shulnian, Proc. Nat. Acad. Sci. U.S.A., 1977,74,5551; G . Navon, R. Navon, R. G. Shulman, and T. Yamane, ibid., 1978,75, 891. J. Dawson, D. G. Gadian, and D. R. Wilkie, in N.M.R. Biol., (Proc. Br. Biophys. SOC. Spring Meet.), ed. R. A. Dwek, Academic Press, London 1977, p. 289; S. J. W. Busby, D. G. Gadian, G. K. Radda, R. E. Richards, and P. J. Seeley, Biochenz. J., 1978,170,103; P. J. Seeley, P. A. Sehr, D. G. Gadian, P. B. Garlick, and G. K. Radda, N.M.R. Biol., (Proc. Br. Biophys. SOC. Spring Meet.), 1977, 247; J. Dawson, D. G. Gadian, and D. R. Wilkie, J. Physiol (London) 1977, 267, 703; D. G. Gadian, Contemp. Phys., 1977,18, 351 ;W. E. Jacobus and G. J. Taylor, Nature, 1977,265,756; D. P. Hollis, R. L. Nunnally, W. E. Jacobus, and G. J. Taylor, Biochem. Biophys. Res. Comm., 1977,75, 1086. K. Yoshizaki, H. Nishikawa, S. Yamada, and H. Watari, Chem. Abs., 1977, 87, 148 200. J. A. Koutcher and R. Damadian, Physiol. Chem. Phys., 1977, 9, 181. E. K. Jaffe and M. Cohn, Biochemistry, 1978, 17, 652; P. Gettins, M. Potter, S. Rudikoff, and R. A. Dwek, F.E.B.S. Letters, 1977, 84, 87; A. J. R. Costello, W. E. Marshall, A. Omachi, and T. 0.Henderson, Biochim. Biophys. Acta, 1977, 491, 469; H. Grasdalen, L. E. Eriksson, J. Westman, and A. Ehrenberg, ibid., 1977, 469, 151; D. S. Tran and M. ROUX, European J. Biochem., 1977,76,245; D. S . Tran and J. M. Neumann, Nucleic Acid Res., 1977, 4, 397; M. Gabriel, D. Larcher, J. C. Boubel, A. A. Peguy, and J. Torreilles, Inorg. Chim. Acta, 1978, 26, 77. D. A. Wilkinson, H. J. Morowitz, and J. H. Prestegard, Biophys. J., 1977, 20, 169; C. F. Schmidt, Y. Barenholz, C. Huang, and T. E. Thompson, Biochemistry, 1977, 16, 3948; P. R. Cullis and B. De Kruijff, Biochim. Biophys. Acta, 1978,507, 207. R. De Kruijff and K. W. A. Wirtz, Biochim. Biophys. Acta, 1977, 468, 318; B. J. Forrest and R. J. Cushley, Atherosclerosis, 1977, 28, 309.

262

Physical Methods

263

sometimes with the assistance of shift reagentslo and relaxation phenomena.ll There has been some further work on cell membranes labelled with phosphonium phosphatidy1choline,l2and the shielding tensors of serine and cytidine phosp h a t e ~have ~ ~ been determined. Phosphorus-31 anisotropy studies of solid nucleic acids show that the chemical-shift tensors are independent of the base, ribose species, or whether the polynucleotides are single- or double-stranded.l* Phorphorus-31 n.m.r. spectroscopy has also been used for structural l6 and mechanistic studies,le and to estimate polyphosphates in frozen chickens.17 Chemical Shifts and Shielding Effects.-Phosphoru~-3I. Positive shifts are downfield from 8 5 % phosphoric acid and are given without the appellation p.p.m. D,PO, (isotopic shift +0.29) has been used as an internal reference.18 Spinning samples at an axis inclined with respect to Ho has been used to narrow dipolar broadened lines in pulsed n.m.r. spectra.lg 8p of PI1 Compounds. The phosphorus nuclei of phosphaferrocene compounds (1) have been found to be strongly shielded.20 dp of PIII Compounds. The n.m.r. spectra of some fluorocarbon PII1compounds

(2) have been determined.21In cyclic compounds such as the phospholens (3) R. G. Griffin, L. Powers, J. Herzfeld, R. Haberkorn, and P. S. Pershan, Magn. Reson. Relat. Phenom., Proc. Congr. AmpPre 19tJ1, 1976, 257; D. Marsh and A. Watts, F.E.B.S. Letters, 1978, 85, 124; D. M. Cheng and R. H. Sarma, J. Amer. Chem. Soc., 1977, 99, 7333 ; C. H. Lee and I. Tinoco, jun., Biochemistry, 1977,16,5403;J. L. Alderfer and P. 0. P. Ts'o, ibid., p. 2410; P. L. Yeagle, R. G. Langdon, and R. B. Martin, ibid., p. 3487; P. R. Cullis and C. Grathwohl, Biochim. Biophys. Acta, 1977, 471, 213; P. R. Cullis and A. C. McLauchlin, Trends Biochem. Sci., 1977, 2 , 196; Y. F. Lam, and G. Kotowycz, Canad. J. Chem., 1977, 55, 3620; K. J. Longmuir, and R. A. Capaldi, Biochemistry, 1977, 16, 5746. 9 G. J. Garssen, C. W. Hilbers, J. G. G. Shoenmakers, and J. H. Van Boom, European J. Biochem., 1977, 81, 453; N. H. Kolodny, A. C. Neville, and D. L. Coleman, Biopolymers, 1977, 16, 259. lo G. W. Feigenson, P. R. Meers, and P. B. Kingsley, Biochim. Biophys. Acta, 1977, 471, 487; G. V. Fazakerley and M. A. Wolfe, European J. Biochem., 1977,74,337; R. J. Cushley, and B. J. Forrest, Canad. J. Chem., 1977, 55, 220; B. De Kruijff, Biochim. Biophys. Acta, 1977,506, 173. 11 T. Imoto, S. Shibata, K. Akasaka, and H. Hatano, Biopolyrners, 1977,16, 2705; D. S. Tran and C. Chachaty, Biochim. Biophys. Acta, 1977,500,405; W. Gruender, R. Goeldner, and H. Schneider, 2. phys. Chem. (Leipzig), 1977, 258, 280; T. Glonek, Biochem. Med., 1978, 19, 246; K. Arnold, K. Gawrisch, A. Hofmann, M. Hoehne, H. P. Keitscher, P. Nuhn, H. J. Rueger, and R. Scholl, Studia Biophys., 1977, 64, 173. 12 E. Sim and P. R. Cullis, F.E.B.S. Letters, 1977, 79, 340. 13 S. J. Kohler and M. P. Klein, J. Amer. Chem. Soc., 1977, 99, 8290. 1 4 T. Terao, S. Matsui, and K. Akasaka, J. Amer. Chem. SOC.,1977, 99, 6136. 1 5 I. M. Armitage, D. L. Shapiro, H. Furthmayr, and V. T. Marchesi, Biochemistry, 1977, 16, 1317. 1 6 V. F. Zarytova and A. V. Lebedev, Bioorg. Kfzim., 1977,3, 1211; A. Marker, L. G. Paleg, and T. M. Spotswood, Plant Growth Regul., Proc. 1976 Internat. Conf. Plant Growth Subst., 9th, publ. 1977, p. 44; R. Katz, H. J. C. Yeh, and D. F. Johnson, Mol. Pharmacol, 1977, 13, 615; R. W. Adamiak, E. Biala, K. Grzeskowiak, R. Kierzek, A. Kraszewski, W. T. Markiewicz, J. Stawinski, and M. Wiewiorowski, Nucleic Acids Res., 1977,4,2321. 1 7 I. K. O'Neill and C. P. Richards, Chem. and Ind., 1978,65. 18 C . Glidewell, J. Organometallic Chem., 1977, 142, 171. 19 R. A. Haberkorn, J. Herzfeld, and R. G. Griffin, J. Amer. Chem. Soc., 1978, 100, 1296. 2 0 F. Mathey, J. Organometallic Chem., 1977, 139, 77. 21 A. B. Burg, Inorg. Nuclear Chem. Letters, 1977, 13, 199. 8

264


steric crowding appears to enhance the P-effect used in empirical calculations of 8 ~The. shielding ~ ~ effects of silicon, germanium, and tin atoms bound to PII1 atoms have been investigated.23 The chemical shifts of para-substituted triarylphosphines (4)correlate with Hammett 0 constants; the large upfield shifts caused

(2)

(1)

(3)

(4)

by ortho-orientated substituents have been attributed to conformational effects.24 The diphosphacyclopropane ( 5 ) gives a signal at high field (8p - 122) 2 5 and in a similar region to those of the cyclotriphosphines.26The factors determining the chemical shifts of the tetraphosphacyclopentanescan be separated into substituent and configurational effects. 2 7 The cis-trans geometries of the cyclic phosphite derivatives of thymidine nucleosides can be assigned from their 8p values.28The stereochemistry of the cyclic phosphites (6) 29 and diazaphosphorinans (7) 30 has been investigated by n.m.r. spectroscopy. The upfield shift for the trans-isomers of dioxaphosphorinans also applies to the diaza-analogues (7). The mixed methoxy(dialky1amino)phosphine (8; X = OMe; Y =NR,) has dp 121.9,31which

(5)

(6)

(7)

(8)

is, as expected, closer to that of the dialkoxy-phosphine(dp 171) 32 than that of the bis-dialkylamino-phosphine(8 ; X =Y =NR2), for which 8p is 34. The chemical shift of the cyclic amino-phosphine (9) is further upfield than expected;33however, studies of the four-membered cyclic compounds (10) showed that 8p is very sensitive to stereochemical changes.34A new di-ylide (1 1) has been described which has a co-ordination number of 3. The chemical-shift range is downfield, at dp 75-87.36 22 L. D. Quin and R. C. Stocks, Phosphorus and Sulfur, 1977,3, 151. 23 24

25

H. Schumann and H. J. Kroth, Z . Naturforsch., 1977, 32b, 513. S . 0. Grim and A. W. Yankowsky, Phosphorus and Sulfur, 1977, 3, 191. M. Baudler and B. Carlsohn, Z. Nuturforsch. 1977, 32b, 1490.

M. Baudler, C. Pinner, C. Gruner, J. Hellman, M. Schwamborn, and B. Kloth, 2.Naturforsch., 1977,32b, 1244; M. Baudler, B. Carlsohn, B. Kloth, and D. Koch, 2. anorg. Chem., 1977, 432, 67. 27 M. Baudler, E. Tolls, E. Cleff, B. Kloth, and D. Koch, 2. anorg. Chem., 1977,435, 21. 28 G. S. Bajwa and W. G . Bentrude, Tetrahedron Letters, 1978,421. tD G . Pouchoulin, J. R. Llinas, G . Buono, and E. J. Vincent, Org. Magn. Resonance, 1976,8, 518. 3 0 J. A. Mosbo, Tetrahedron Letters, 1976, 4789. 31 E. Niecke and G. Ringel, Angew. Chem. Internat. Edn., 1977, 16, 486. 5 2 M. J. Gallagher and H. Honegger, Tetrahedron Letters, 1977, 2987. 33 S. Pohl, E. Niecke, and H. G. Shafer, Arzgew. Chem. Internat. Edn., 1978, 17, 136. s4 R. Keat and D. G. Thompson, Angew. Chem. Internat. Edn., 1977, 16, 797; W. F. Zeiss, C. Feldt, J. Weis, and G. Dunkel, Chem. Ber., 1978,111, 1180. 35 E. Niecke and D. A. Wildbredt, Angew. Chem. Internat. Edn., 1978, 17, 199. 26

Physical Methods

265

Y BdN,/"="\ ,NBut P

NR*

R,NP\/N\ ,PNR, N Y

RP,

R,

//P=C

RN

M 'e

6~ of PIv Compounds. The 31Pand I9F chemical shifts of some phosphonyl

halides (12) vary with the number of hydrogen or fluorine atoms bound to the a-carbon; this has been attributed to hyperc~njugation.~~ The very large y-effect which influences BP of protonated ortho-substituted phosphines (13) is not observed in the corresponding methylphosphonium salts.,' The shielding effect of axial and equatorial C-10 substitution in the oxides (14)3shas been discussed, as have the electronic and anisotropic effects in the heteroarylphosphinates (1 5).30

A delocalized anion, as in (16), is believed to produce a downfield shift relative to a more localized anionic The chemical shifts of a number of N-silyland N-germyl-iminophosphoranes(17; Z = SiMe, or GeMe,) have been recorded.41 Quasi-phosphonium salt intermediates have been identified by 31P n.m.r. spectros~opy;~~ the salt (1 S) remains ionic (although strongly associated) in non-polar solvents. B p of Pv Compounds. A large number of new phosplzoranes have been reported during the year, and the fact that their 31Pchemical shifts are usually to high field of phosphoric acid is important evidence for their having five-co-ordinate 36

37 38

39 40

41 42

43

A. V. Fokin and M. A. Landau, Bull. Acad. Sci., U.S.S.R., 1976, 2271. S. 0. Grim and A. W. Yankowsky, J. Org. Chem., 1977,42, 1236. Y . Segall, R. Alkabets, and I. Granoth, J. Chern. Res. ( S ) , 1977, 310. D. W. Allen, B. G . Hutley, and M. T. J. Mellor, J.C.S. Perkin 11, 1977, 789. T. Bottin-Strzalko, J. Seyden-Penne, and M. P. Simonnin, J.C.S. Chem. Comm., 1976,905. W. Wolfsberger, 2. Nczturforsch., 1977, 32b, 152; W. Buchner and W. Wolfsberger, ibid., p. 967; E. P. Flindt, H. Rose, and H. C. Marsmann, Z . anorg. Chem., 1977, 430, 155. K. S. Colle and E. S. Lewis, J. Org. Chem., 1978,43,571; C. Symmes and L. D. Quin, ibid., p. 1250. L. V. Nesterov, N. A. Aleksandrova, I. D. Temyachev, A. A. Musina, and R. G . Gainullina, J. Gen. Chem., (U.S.S.R.), 1977, 47, 1161.


266

structures. Thus the latest claim for the detection of the elusive hydroxyphosphoranes is made more acceptable in the case of the intermediate (19) by its chemical shift of - 27.44

OH

(19)

Carbon-13. The 6~ values of the methylphosphorinans (20) and their chalcogenides have been especially helpful in qualitative conformational analysis, The signals of the axially orientated P-methyl groups are in all cases upfield of those of the equatorial groups.46 There have been several reports in which aryl 13C chemical shifts have been correlated with substituent constants. The importance of the correct assignment of 6~ for thepara-carbon atom has been emphasized. Using the dual-substituent parameter approach, the phenyl-phosphines (21) and 1 9 . 7 9 ~and ~ their chalcogenides gave the relationships AdcQara)= 3 . 9 8 ~ 1 + A comparison of phenyl-phosphorus, -arsenic, A&(meta) = 1.5401- 1.61 -antimony, and -bismuth derivatives gave the relationship &(para) - Gc(meta)= - 2 2 . 0 6 0 ~The ~ , ~chemical ~ shift of the ylidic carbon of the ylides (22) correlates linearly with dual-substituentparameters; the resonance term predominates, and it has been suggested that n-polarization may be responsible for transfer of electron density into the P-phenyl rings.48 A study of some dialkyl cyclohexylphosphonates (23) indicates that, in addition to the expected y-shielding effects, the phosphorus group also induces an upfield shift by 1 p.p.m. at carbon atoms to which the group bears an anti-periplanar relation.49 High-resolution 13C n.m.r. spectroscopy (68 MHz) has been shown to be a good method for studying the kinetics and mechanism of hydrolyses of cyclophosphamide and related phosphoramic compounds.50 N

44 45 46

47 48 49 50

F. Ramirez, M. Nowakowski, and J. F. Marecek, J. Amer. Chem. Sac., 1977,99,4515. L. D. Quin and S. 0. Lee, J. Org. Chem., 1978, 43, 1424. T.A. Modro, Canad. J. Chem., 1977, 55, 3681. L. F. Wuyts, D. F. Van de Vondel, and G. P. Van der Kelen, J. Organometallic Chem., 1977,129, 163. P. Froeyen and D. G. Morris, Acta Chem. Scand. (B), 1977, 31, 256. G. W. Buchanan and J. H. Bowen, Canad. J. Chem., 1977,55, 604. G. Zon, S. M. Ludeman, and W. Egan, J. Amer. Chem. Sac., 1977,99, 5785.

Physical Methods

267

Fluorine-19. Further work has been reported on electronic effects in iminophosphoranes (24); trends in ~b have been interpreted in terms of a polar P-N bond with considerable delocalization from nitrogen into the attached aryl ring and a modest degree of P-aryl c o n j ~ g a t i o n .Fluorine-19 ~~ n.m.r. has been used to determine the heats and entropies of association of sodium perfluorohexylpho~phinate.~~ Oxygen-I7 and Nitrogen-I5 and -I4. Oxygen-17 and nitrogen-15 spectra of some simple phosphorus compounds have been recorded.53The 14Nchemical shifts of cyclophosphazenes resemble those of the acyclic compounds, and are 27-1 15 p.p.m. downfield of those of aqueous ammonium ions.54 Hydrogen-I. The NMe, proton chemical shifts of the phosphaimidazolidines (25) correlate with the Hammett u substituent constants of Y; the possibility of through-space transmission of electronic effects has been

Equilibria and Shift Reagents.-N.m.r. spectroscopy is a particularly suitable method for the study of tautomeric equilibria. In addition to prototropic equilibria in keto-enol 5 6 or trans-ylidation5 7 systems, fluoride exchange in the carbodiphosphorane precursor (26),5 8 exchange of TMS in the imido-compounds (27 ; Y = TMS),59 tellurium exchange in the diazaphosphetidine (28),60 and intermolecular exchange of selenium between diphenyl(a1kyl)phosphines and their selenides have been studied. The equilibrium constant and thermodynamic parameters for the valence tautomers (29) and (30) have been determined by n.m.r.s2 The existence of large upfield shifts of CSP upon the addition of triethylamine to the equilibrium mixture of (31) and (32) has been presented as evidence for a shift in the equilibrium towards the Pv species.63N.m.r. spectroscopy has also provided information on the interactions of phosphonyl groups with NH groupss4 51 52

54

55 56

57

68 59

60

61 62

63 64

I. Schuster, Tetrahedron, 1977, 33, 1075. N. N. Kalibabchuk, V. Ya. Semenii, V. S. Kuts, L. K. Dyachek, and V. N. Zavatskii, Teor. i eksp. Khim, 1977, 13,174. G. A. Gray and T. A. Albright, J. Amer. Chem. SOC.,1977,99, 3243. J. Mason, W. Van Bronswijk, and J. G . Vinter, J.C.S. Dalton, 1977, 2337. M. K. Das and J. J. Zuckerman, J. Amer. Chern. Soc., 1977, 99, 1354. B. A. Arbuzov, 0. A. Erastov, S . N. Ignat’eva, E. I. Gol’dfarb, and T. A. Zyablikova, Doklady Akad. Nauk S.S.S.R., 1977, 233, 858; N. A. Nesmeyanov, S. T. Berman, P. V. Petrovskii, A. I. Lutsenko, and 0. A. Reutov, J. Organometallic Chem., 1977, 129, 41. H. Schmidbaur and H. J. Fuller, Chem. Ber., 1977, 110, 3528. H. Schmidbaur, 0. Gasser, and M. S. Hussain, Chem. Ber., 1977, 110, 3501. L. Riesel, A. Claussnitzer, and C. Ruby, 2.anorg. Chem., 1977, 433, 200. 0. J. Scherer and G. Schnabl, Angew. Chem. Internat. Edn., 1977, 16, 486; R. Keat and D. G. Thompson, J. Organometallic Chem., 1977, 141, C13. D. H. Brown, R. J. Cross, and R. Keat, J.C.S. Chem. Comm., 1977, 708. H. B. Stegmann, R. Haller, and K. Schefller, Chem., Ber., 1977, 110, 3817. C. Bui Cong, A. Munoz, M. Sanchez, and A. Klaebe, Tetrahedron Letters, 1977, 1587. G. B. Sergeev, V. A. Polyakov, and L. A. Tyurina, Zhur. fiz. Khim., 1978,52,290.

268


Me,P(

CH >PMe, F

and with chlor~silanes,~~ and on the conformation, configuration, and lability of PH in the phosphorane (33).66 The ratio of contact and pseudo-contact contributionsto the lanthanide-induced shifts of phosphonates 6 7 and other phosphoryl compounds 68 has been estimated from the ratio of Pr and Eu shifts for different nuclei along the skeleton of each molecule. The contact term was more important for 31P nuclei than for The effects of lanthanide on the H1 and H2 chemical shifts of the phosphorinan (34) have been used to establish its configurati~n.~~ Shift reagents have been used in the conformational analysis of several biologically important phosphates,70 and of alkenylpho~phonates.~~ The optical purities of the sulphoxide (35) 72 and cyclophosphamide73 have been established, using chiral shift reagents, and a report has appeared on effects of europium on the chiral compounds (36).74The 65

66 67

6s 69

70

71 72 73 74

P. Mahta and M. Zeldin, Inorg. Chim. Acta, 1977, 22, 233. J. Devillers, D. Houalla, T. Moucheich, and R. Wolf, Org. Magn. Resonnnce, 1976,8, 558. G. A. Berkova, V. I. Zakharov, S. A. Smirnov, N. V. Morkovin, and B. I. Ionin, Zhur. obshchei. Khim., 1977, 47, 1431. G. A. Berkova, V. I. Zakharov, S. A. Smirnov, N. V. Morkovin, and B. I. Ionin, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1315. J. A. Mosbo and J. G. Verkade, J. Org. Chem., 1977,42, 1549. J. Mossoyan and D. Benlian, Rev. Chim. mine'rale, 1976, 13, 595; F. Inagaki, M. Tasumi, and T. Miyazawa, Biopolymers, 1978, 17, 267; F. Hayashi, K. Akasaka, and H. Hatano, J. Magn. Resonance, 1977, 27,419; M. J. Robins, M. Maccoss, and J. S. Wilson, J. Amer. Chem. Soc., 1977,99,4660. G. A. Berkova, A. M. Shekhade, V. I. Zakharov, B. I. Ionin, and A. A. Petrov. J. Gen. Chem. (U.S.S.R.), 1977, 47, 873. M. Mikolajczyk, W. Midura, S. Grzejszczak, A. Zatorski, and A. Chefczynska, J. Org. Chem., 1978, 43,473. G. Zon, J. A. Brandt, and W. Egan, J. Nat. Cancer Inst., 1977, 58, 1117. E. V. Konovalov, T. Ya. Lavrenyuk, Yu. P. Egorov, S. N. Gaidamaka, and A. M. Aleksandrov, Tear. i eksp. Khim., 1977, 13,407.

Physical Methods

269

dissociation constants of (ethylenediaminetetramethy1)phosphonic acid-lanthanide complexes have been estimated.75 Pseudorotation.-A relatively simple method has been proposed for the qualitative analysis of first-order variable-temperature 31Pn.m.r. spectra of fluorophosphoranes in order to examine the character of the pseudorotation processes without the use of complex computer calculations. Examples have been given for the phosphoranes (37) and (38).76 Plots of t.b.p. angles el, and Og4 [see (39)]

against the dihedral angle 24, or comparisons of dihedral angles with idealized t.b.p. and rectangular pyramidal (r.p.) angles, indicate that there is little difference in the energies of t.b.p. and r.p. structures, and that the Berry mechanism is the correct mode of pseudor~tation.~~ Good agreement has also been reported between the computer-simulated geometries and X-ray diffraction data of a series of pho~phoranes.~~ The lH and 13C resonances of the simplest penta-alkylphosphorane (40) so far prepared show no splitting upon cooling the sample to - 105 0C.78Several n.m.r. studies have been reported which concern the steric influences on pseudorotation and apicophilicities, in particular steric comp r e s ~ i o n the , ~ ~influence of six-membered rings,*O and the inclusion of the Pv atom in more than one ring.81Double decoupling of the 31Pand 19Fnuclei in the IH n.m.r. spectrum of the tetracyclic phosphorane (41) reduced it to an AABB’ pattern which broadened at -47 “C but retained its symmetry, in accordance with the presence of rapid pseudorotation.82 A number of phosphoranes (42) 75

1. N. Marov, L. V. Ruzaikina, V. A. Korovaikov, and N. M. Dyatlova, Koord. Khim.,

1977, 3, 1333. J. Brocas, J. Buschen, A. M. Decoster, D. Fastenakel, and R. Willem, Bull. SOC.chim. belges, 1977, 86, 139; R. R. Holmes and J. A. Deiters, J. Amer. Chem. SOC.,1977, 99, 3318; J. Chem. Res. ( S ) . 1977, 92. 77 J. A. Deiters, J. C. Gallucci, T. E. Clark, and R. R. Holmes, J. Amer. Chem. Soc., 1977,99, 5461. 7 8 H. Schmidbaur, P. Holl, and F. H. Koehler, Angew. Chem. Ivtcrnat. Edn., 1977, 16, 722. 7 9 S. A. Bone, S. Trippett, and P. J. Whittle, J.C.S. Perkin I, 1977, 437. 8 0 N. J. De’Ath and D . B. Denney, Phosphorus and Sulfur, 1977,3,51; S. A. Bone, S . Trippett. and P. J. Whittle, J.C.S. Perkin I, 1977, 80; B. A. Arbuzov, Yu. Yu. Samitov, Yu. M. Mareev, and V. S. Vinogradova, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1852. s1 J. Devillers, D. Houalla, J. Roussel, and R. Wolf, Org. Magn. Resonance, 1976, 8, 500; N. A. Razumova, Yu. Yu. Samitov, V. V. Vasil’ev, A. Kh. Voznesenskaya, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 289. 8 2 J. E. Richman, Tetrahedron Letters, 1977,559.

76

270


containing P--CF, groups have been studied and give n.m.r. spectra suitable for studying pseudorotation and determining relative apicophilicities. The throughspace F-F coupling shown in the spectra of the phosphoranes (43 ; X = CF,) has been used diagnostically to assess ground-state s t r u c t ~ r e sThe . ~ ~ presence of PN groups often complicates the interpretation of the variable-temperature spectra, and the dynamic processes observed in the spectra of (44; X = CFS)86and (45)86 could not be assigned confidently. Some structures of phosphoranes have been proposed for synthesis which may give interesting variable-temperature n.m.r.

Restricted Rotation.-Non-equivalence of n.m.r. signals of amino-phosphines frequently originates from restricted rotation about the P-N bond,ss although in some cases, e.g. the N-silyl-phosphines (46), pyramidal inversion at nitrogen is included, giving a hybrid process.89These processes have been studied using CND0/2 calcuIation~.~~ Restricted rotation has also been invoked to explain the non-equivalenceof the N-methylene I3Cresonances (CTis 97"when Y = CH,CH,) in the spectra of the sulphides (47), even though a double bond separates the phosphorus and nitrogen The spectra of the amidines (48) show similar phen~mena.~ Low-temperature non-equivalence of the methyl groups of t-butyl groups bound to nitrogen in (49)93and bound to phosphorus in (50)!j4has also been reported. In some phosphoranes, non-equivalence due to restricted rotation K. 1. The and R. G. Cavell, Inorg. Chem., 1977, 16, 2887, 1463. J. A. Gibson, G. V. Roschenthaler, and V. Wray, J.C.S. Dalton, 1977, 1492. J. A. Gibson, G. V. Roschenthaler, R. Schmutzler, and R. Starke,J.C.S. Dalton, 1977,450. 86 A. H. Cowley and R. C. Lee, J.C.S. Chem. Comm.,1977, 111. 87 J. I. Musher, Phosphorus and Sulfur, 1977, 3, 247. 88 J. H. Hargis, S. D. Worley, W. B. Jennings, and M. S . Tolley, J. Amer. Chem. Soc., 1977, 99, 8090; G. Bulloch, R. Keat, and D. G. Thompson, J.C.S. Dalton, 1977, 1044. a9 T. H. Neilson, R. C. Lee, and C. H. Cowley, Inorg. Chem., 1977, 16, 1455. 90 E. V. Borisov, Zhur. fiz. Khim., 1977, 51, 1322. 91 R. S. Jain, H. F. Lawson, and L. D. Quin, J. Org. Chem., 1978,43, 108. Q2 A. D. Sinitsa and V. I. Kal'chenko, Dopovidi Akad. Nauk Ukrain R.S.R., Ser. By 1977, 1007. 93 R. Keat, K. W. Muir, and D. G. Thompson, Tetrahedron Letters, 1977, 3087. 94 H. Schmidbaur, G. Blaschke, and F. H. Kohler, Z. Narurforsch., 1977, 32b, 757. 83 84

Physical Methods

271 /-Y

(46)

(47)

about a P-N bondg5and about a P-S bondgs can be distinguished from pseudorotation. Inversion, Configuration, and Medium Effects.-Silicon or germanium atoms attached to the phosphorus atom increase the rate of inversion for phosphines, so that the energy barriers can be studied by variable-temperaturen.m.r., e.g. for the cyclic compounds (51)97 and (52)98 and the chiral phosphine (53)."O

The different diastereoisomers of the di- and tri-phosphines (54) and (55) can be readily identified from their 31Pn.m.r. spectra.loOThe doubling due to Statistically Controlled Associate Diastereoisomerism,lol which occurs in the n.m.r. spectra of certain optically 'impure' enantiomers, has been reviewed.lo2 The absolute configuration at phosphorus and the diastereomeric purity of the menthy1 ester (56) have also been deduced by n.m.r.lo2 The degree of diastereomeric

95 96 97

98 g9 100 101

102

S. C. Peake, M. J. C. Hewson, 0. Schlak, R. Schmutzler, R. K. Harris, and M. 1. M. Wazeer, Phosphorus and Sulfur, 1978,4, 67. R. G. Cave11 and K. I. The, Znorg. Chem., 1978, 17, 355. C. Couret, J. Satgk, J. Escudik, and J. D. Andriamizaka, J. Organometallic Chem., 1977, 132, C5. A. Zschunke and I. Nehls, 2. Chem., 1977, 17, 335. H. Schumann and R. Fischer, J. Chem. Res. (S), 1977, 272. M. Baudler, D. Koch, and B. Carlsohn, Chem. Ber., 1978, 111, 1217; M. Baudler, B. Carlsohn, D. Koch, and P. K. Medda, ibid., p. 1210. M. J. P. Harger, J.C.S. Perkin 11, 1977, 1882; M. I. Kabachnik, Phosphorus and Surfur, 1977, 3, 239. R. Luckenbach and H. H. Bechtolsheimer, Z . Naturfursch., 1977, 32b, 589.

272


anisochromism has been found to vary for the pyranose and furanose derivatives of dioxapho~phorinans.1~~ The non-equivalence of the phosphorus atoms in the spectra of the diacid (57) has been attributed to its inner salt Nonequivalence, which probably originates from a chiral centre, has been reported for the esters (58)lo6and the fluoridates (59).loBUnusual shielding effects in the phospholen oxide (60) cause apparent loss of non-equivalence, and a simple methylene doublet (JPCH11 Hz) is observed; further splitting can be detected only in the 270 MHz

U

(60)

(61)

N.m.r. studies of the 13C-and fSN-labelleddiphosphine (61) in a nematic liquid crystal gave a PNP angle of 117" and P-N bond length of 166.4 pm.lo8Similar studies of 13C-labelledtrimethylphosphine and its chalcogenides have also been completed.109 Spin-Spin Coupling.--Jpp. The generally larger values of ~ J Pfor P PIIIPrv compounds (124-323 Hz)l10 fall dramatically to 27 Hz for the PIVPIV compound (62).ll1 The differences are much less for JPCP,many of which fall in the range 50-90 Hz.l12 On the other hand, JPNP varies widely (0-70 Hz),l13 and for the PIIINPIII compounds it may vary in sign.l14 Whilst the PIII-O-PIII coupling E. E. Nifant'ev, D. A. Predvoditelev, M. K. Grachev, and V. A. Shin, Doklady Akad. Nauk S.S.S.R., 1977, 235, 595. l o 4 M. Fukuda, Y.Okamoto, and H. Sakurai, Chem. Letters., 1977, 529. l o 5 C. D. Hall, R. Ardrey, R. Dyer, and P. G. Le Gras, J.C.S. Perkin ZI, 1977, 1232. 1 0 6 Y.Margalit, G. Amitai, and Y . Ashani, Phosphorus and Sulfur, 1977, 3, 315. 107 K. Moedritzer and P. A. Berger, J. Org. Chem., 1977, 42, 2023. 108 I. J. Colquhoun and W. McFarlane, J.C.S. Faraday ZZ, 1977, 73, 722. l o 9 J. P. Albrand, A. Coyne, and J. B. Robert, Chem. Phys. Letters, 1977, 48, 524. l10 M. Baudler, J. Vesper, B. Kloth, and D. Koch, Z. anorg. Chem., 1977,431,39; V. L. FOSS, Yu. A. Veits, T. E. Tret'yakova, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1977, 47, 870; V. L. Foss, Yu. A. Veits, N. V. Lukashev, Yu. E. Tsvetkov, and I. F. Lutsenko, ibid., p. 439; V. L. FOSS,Yu. A. Veits, P. L. Kukhmisterov, and I. F. Lutsenko, ibid., p. 438; V. L. Foss, Yu. A. Veits, P. L. Kukhmisterov, V. A. Solodenko, and I. F. Lutsenko, ibid., p. 437; V. L. Foss, Yu. A. Veits, P. L. Kukhmisterov, and I. F. Lutsenko, ibid., p. 656. 111 R. Appel and R. Milker, Chem. Ber., 1977, 110, 3201. 112 A. Wohlleben and H. Schmidbaur, Angew. Chem. Znternat. Edn., 1977, 16, 417; Z. S. Novikova, A. A. Prishchenko, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1977,47,707. 113 A. A. Khodak, V. A. Gilyarov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1977, 47, 251; R. Appel and M. Halstenberg, Angew. Chem. Znternat. Edn., 1977, 16, 263; W. Wolfsberger and W. Hager, 2. anorg. Chem., 1977, 433, 247. 114 R. Keat and D. G. Thompson, J.C.S. Dalton, 1978, 634.

103

273

Physical Methods

constants of the anhydrides (63) are strikingly high (100 Hz),l15 the PIv-O-P1v and PIV-S-PIv couplings are quite low, and fairly constant, at 30-34 and 1416 Hz respectively.l16The vicinal P-P coupling constant (24.2 Hz) of the diphosphine (64) was obtained from proton-decoupled 31P( l3C ) satellite spectra.l17 The PIV-C-C-PIV couplings can be quite high [50 Hz for the diphosphorane (65)],118 and a study of a series of benzene- and naphthalene-diphosphonates [66; E = PO(OEt),] showed couplings across five to nine bonds;llg thus there may be a considerable n-electron contribution to the coupling mechanism.

“.R

P

ECH~+-JJ-CB,E

NTMS NCN (65)

Y (66)

(67)

and J P ~ ~The N . Fermi-contact mechanism is believed to dominate ~ J P O (90-205 H z ) . ~ The ~ coupling ~ J Pfor N cyclic guanidines (67) and parent amine varied in the range 11-50 Hz120 but can extend up to 90 Hz for PIIr comp o u n d ~lo* .~~~ JPC.The direct PC coupling constant of a series of cyclic PI11 esters (68) varies smoothly (44-27 Hz) according to the ring size, except when an additional transannular oxygen atom is present; e.g., ~ J PisC12.5 Hz for (69).121The large values of lJpc (89-92 Hz) for the salts (70) have been attributed to conjugation.122 This coupling is similar for the arylphosphine oxide (71)123 but may be considerably larger for other a-keto-compounds, e.g. 108-118 Hz for the compounds (72);124it is in the range 50-79Hz for a series of phosphine ~u1phides.l~~

&I70

115 116 117 118

119 120

121 122

123 124

125

V. L. FOSS, Yu. A. Veits, and I. F. Lutsenko, Phosphorus and Suvur, 1977, 3, 299. R. K. Harris, E. M. McVicker, and G. Haegele, J.C.S. Dalton, 1978, 9. S. Srarensen and H. J. Jakobsen, Org. Magn. Resonance, 1977, 9 , 101. I. Ruppert and R. Appel, Chem. Ber., 1978, 111, 751. L. Ernst, J.C.S. Chem. Comm., 1977, 375; Org. Magn. Resonance, 1977, 9, 35. G. E. Struve, C. Gazzola, and G. L. Kenyon, J. Org. Chem., 1977,42,4035. J. P. Dutasta and J. B. Robert, J. Amer. Chem. SOC.,1978, 100, 1925. E. E. Schweizer and M. A. Calcagno, J. Org. Chem., 1977, 42, 2641. J. A, Miller and D. Stewart, J.C.S. Perkin I, 1977, 1898. R. Appel and M. Montenarh, Chem. Ber., 1977, 110,2368. R. S. Postle, Phosphorus and Sulfur, 1977, 3, 269.


274

0 PkPCOMe

I1

s

R&OY

s

Me,ll II,Me Ph/p-Kph

CF3

I

F,C-P’* Y ’I

-we

CF3

(71) (7 2) (7 3) (74) Selective pulsed excitation has been used to suppress the resonance due to a per-12C-isotopomer of the disulphide (73) to overcome dynamic range problems when observing 13C satellite lines in the 31P n.m.r. spectra.lZsSteric and conjugation effects in phosphonatesll9,12’ have been investigated using P-C coupling constants, and in one report the trends were interpreted in terms of p-o conjugation of lone pairs of oxygen with the P-C bonds.12*The lower ~ J P values C (less than 90 Hz) for apical trifluoromethyl groups in phosphoranes such as (74), as compared to the radial groups, have been used to determine ground-state structure^.^ ee Geminal P-C couplings constants of 3-phospholens(75) are strongly dependent upon the configuration at phosphorus; it is OHz for the structure shown but 28-31 Hz for its isomer with a pseudo-axial PR group.13oThe geminal couplings for the phosphonate (76) showed a less dramatic but still strong dependence on stereochemi~fry.~~~ The vicinal couplings for the phosphorinanium salts (77) have been related to dihedral angles,132 and the PII1-X-C-C couplings for the phosphorinans (78) have been used to estimate steric preferences.133However, the PI1I--PIv--OC couplings for the phosphorins (79) do not appear to follow the normal Karplus-type re1ation~hip.l~~

(77) 127 126

1aQ 190 181

Is* 188

194

(78)

(79)

R. K. Harris, R. H. Newman, and A. Okruszek, Org. Magn. Resonance, 1977, 9, 5 8 . G. W. Buchanan and F. G. Morin, Canad. J. Chem., 1977, 55, 2885; J. Thiem and B. Meyer, Tetrahedron Letters, 1977, 3573. M. V. Sigalov, V. A. Pestunovich, V. M. Nikitin, A. S. Atavin, and M. Ya. Khil’ko, Bull. Acad. Sci. U.S.S.R.,1977, 26, 1086. R. G. Cavell, J. A. Gibson, and K. I. The, J. Amer. Chem. Soc., 1977, 99, 7841. P. J. Hammond and C. D. Hall, Phosphorus and Sulfur, 1977,3, 351. M. Moreau, H. Cohen, and C. Benezra, Tetrahedron Letters, 1977, 3091. S. Samaan, Chem. Ber., 1978, 111, 579. E. E. Nifant’ev, A. I. Zavalishina, S. F. Sorokina, A. A. Borisenko, E. I. Smirnova, and I. V. Gustova, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1793; E. E. Nifant’ev and A. A. Borisenko, ibid., p. 443. A. Okruszek, W. J. Stec, and R. K. Harris, Org. Magn. Resonance, 1977, 9, 497.

laa

Physical Methods

275

Protonated phosphites show a steady increase in ~ J P(826-928 H Hz) upon increasing constraint of the alkoxy-groups ; CND0/2 calculations indicate that there is a concomitant rise in the positive charge on phosphorus but no related trend with 1iybridi~ation.l~~ Finite-perturbation INDO calculations of JPHin phosphine have been

JPIL

JPC,H. The geminal P-C-H coupling constant has been used for the conformational analysis of phosphonyl compounds because its magnitude is dependent on dihedral a ~ i g 1 e .This l ~ ~ parameter has also been used to estimate the O=P-C--H the stereochemistry of /3-disubstituted olefinic However, for vinyl compounds possessing a @-hydrogen atom, the vicinal coupling constant is usually a more reliable steric For the saturated coupling pathway as in (80), the influences of electronic factors have also been taken into account.140The larger P-C-C-H coupling constant (12.7 Hz) for the cyclopropylphosphonates (8 1) has been assigned to the cisoid pathway.141 A fivebond coupling (1.6 Hz) has been observed for the methyl group of dibenzophosphorin (82) which is not observed in the spectra of its

JPXCEI. The P-S-C-H coupling constants of the thioesters (83) are solventdependent,143 a phenomenon which is probably related to the presence of a polar group. A revised relationship between JPOCH and dihedral angle in sevenmembered cyclic phosphates has been pr0p0sed.l~~ L. J. Van de Griend, 3 . G. Verkade, 5. F. M. Pennings, and H. M. Buck, J. Amer. Chem. Soc., 1977, 99, 2459. 1 3 6 M. D. Beer and R. Grinter, J. Magn. Resonance, 1977, 36, 421. 137 0. A. Raevskii. A. N. Vereshchagin, N. G. Mumzhieva, T. A. Zyablikova, N. A. Alexandrova, and A. E. Arbuzov, J. Mol. Structure, 1977, 36, 299; A. N. Pudovik, 1. V. Konovalova, M. G. Zimin, T. A. Dvoinishnikova, L. 1. Vinogradov, and Yu. Yu. Samitov, J. Gen. Clwm. (U.S.S.R.), 1977, 47, 1555; Yu. Yu. Samitov, E. A. Suvalova, I. E. Boldeskul, Zh. M. Ivanova, and Yu. G. Gololobov, ibid., p. 937. 13* H. Yoshida, T. Ogata, and S . Inokawa, Bull. Chenz. SOC.Japan, 1977, 50, 3315; M. S . Chattha, Clwm. and I d . , 1976, 1031. 130 J. D. L'vova, Yu. P. Kozlov, and V. I. Gunar, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1153; V. G. Salishchev, M. L. Petrov, and A. A. Petrov, ibid., p. 690; G. Haegele and H. Dolhaine, Phosphorus and Suljlur, 1977, 3 , 47; E. A. Berdnikov, F. K. Mukhitova, and F. R. Tantasheva, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1096; D. Gloyna, K. G. Berndt, H. Koeppel, and H. G. Menning, J. prukt. Cliem., 1977, 319,451. l 4 0 R. D. Gareev, Yu. Yu. Samitov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1977, 47, 256. 141 H. Dolhaine and G. Haegele, Phosphorus and Su&r, 1978,4, 123. 142 K. C. Chen, S . E. Ealick, D. Van Der Helm, J. Barycki, and K. D. Berlin, J. Org. Chem., 1977, 42, 1170. 143 J. Paasivirta, J. Simanainen, R. Vesterinen, and L. Virkki, Org. Magn. Resonance, 1977, 9, 708. 144 W. J. Kung, R. E. Marsh, and M. Kainosho, J. Amer. Chem. Soc., 1977, 99, 5471.

135

10

276

Organophosphorus Chemistry OPPh,

I1 (MeO),PSCH,CONHR

Ch

II

Ch

NI-IMesityl

R2P\

Ch

II

,PR, Ch

Double-resonance, Relaxation, C.I.D.N.P., and N.Q.R. Studies.-The presence of an N H group in the phosphinate (84)was established by Fourier difference spectroscopy between the lH n.m.r. spectra with and without 15Nde~oup1ing.l~~ The prediction of relaxation behaviour is quite complex for phosphorus nuclei. The relaxation times can vary by a factor of 10, and the efficiency of the 31P pulse may be improved in some cases by cooling, e.g. tetraethylphosphonium In a study of a related iodide, and in others by heating, e.g. triethy1pho~phine.l~~ series of anhydrides (85), the relaxation times followed no consistent trend.l16 C.I.D.N.P. effects have been observed for the reactions of HMPT with amide oximes 14' and of ethoxide ion with a (phenyldiazo)ph~sphonate,~~~ showing the intermediacy of radical pairs. N.q.r. studies have been reported on the mobility of trichlorophosphazogroups.149Other studies of chloro-phosphoranes,150and of other have related the absorption frequencies to the ionic character of the P-CI bonds. For several phosphorochloridates the n.q.r. frequencies correlated linearly with the P-CI bond length.152

2 Electron Spin Resonance Spectroscopy A study of phenylphosphonium radicals (86), produced by y-irradiation of phenylphosphines or their chalcogenides, has shown a steady decrease in a(P) upon the introduction of aryl groups, in accordance with some n-delocalization into the aryl rings.153The spectrum of the triphenylphosphine radical anion has also been r e ~ 0 r d e d . A l ~review ~ of phosphoranyl radicals includes a discussion of the spectral evidence related to their configurations and stereochemistry.166The temperature-dependent spectra of the phosphoranyl radicals (87) and (88) 145

146 147

148 149

l50

151

A. S. F. Boyd, J. 1. G. Cadogan, D. S . B. Grace, and N. S . Tweddle, J, Chern. Res. ( S ) , 1977, 240. N. J. Koole, A. J. De Koning, and M. J. A. De Bie, J. Magn. Resonance, 1977, 25, 375. L. Lopez and J. Barrans, J.C.S. Perkin I , 1977, 1806. Yu. A. Levin, I. P. Gozman, and E. I. Gol'dfarb, B i d . Acad. Sci. U.S.S.R., 1976, 2606. E. A. Romanenko and M. I. Povolotskii, Teor. i eksp. Khim., 1977, 13, 70. E. S. Kozlov, S. N. Gaidamaka, I. A. Kyuntsel, V. A. Mokeeva, and G. B. Soifer, J. Gen. Chem. (U.S.S.R.),1977, 47, 930; B. V. Timokhin, V. P. Feshin, V. I. Dmitriev, V. I. Glukhikh, G. V. Dolguishin, and M. G. Voronkov, Doklady Akad. Nauk S.S.S.R.,1977, 236, 4. J. P. Faucher, J. C . Van de Grampel, J. F. Labarre, S. N. Nabi, B. D. Ruiter, and R. A. Shaw, J. Chem. Res. ( S ) , 1977, 112; V. P. Feshin, M. G. Voronkov, B. V. Timokhin, A. V. Kalabina, V. I. Dmitriev, and P. A. Nikitin, J. Gen. Chern. (U.S.S.R.), 1977, 47, 1354.

152

153 154

155

W. H. Dalgleish, R. Keat, A. L. Porte, and R. A. Shaw, J.C.S. Dalton, 1977, 1505. G. W. Eastland and M. C . R. Symons, J.C.S. Perkin IZ, 1977, 833. R. Nasirov, S . P. Solodovnikov, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1976, 2230. W. G . Bentrude, Phosphorus and Sulfur, 1977, 3, 109.

Physical Methods

277

indicate that the apicophilicities of substituents attached to phosphorus closely parallel their group electronegativitie~,~~~ and that an apical trifluoromethyl group lowers a(P) l 5 (cf. ~ J PofCtrifluoromethylphosphoranes).12gWhereas the splittings in the spectra of the cyclic radical cation (89) show that the electron density is mainly on the ring the radical cation (90) gives spectra with splitting by the peripheral methylene groups.159The e.s.r. spectrum of [rnethylene13C]triphenylphosphoniumion (91), trapped in a crystal matrix, showed coupling corresponding to an electron localized on the methylene carbon atom; after comparison of the spectra at 300 and 70 K it has been suggested that there is a small rotational barrier with a two-fold component.160Conformational studies of phosphoniomethylphenoxy radicals indicate that there is hindered rotation of the phenoxy-group.161 Spin densities for azophosphonate radicals have been estimated,162and the spectrum of photolysed ylide (92) is in accordance with the formation of the radical (93).163The phosphinimino radical (94) has been found to be very ~ t a b 1 e . A l ~ number ~ of studies of phosphorus compounds possessing n i t r o ~ y l , liminoxyl,le6 ~~ and nitro radicals16’have been reported. A wide variety of phosphorus splittings were observed for the radicals produced upon the y-irradiation of trialkyl phosphates.lGs E.s.r. studies of naturally occurring Ph3k---bHz (91)

Ph, P=CHCO, (9 2)

Et

Ph, k = C H C O , Et (9 3)

Ph,P=NC

,C14d(C, C15)2 (94)

J. W. Cooper, M. J. Parrott, and B. P. Roberts, J.C.S. Perkin IZ, 1977, 730. W. Dennis, I. E. Elson, and B. P. Roberts, J.C.S. Perkin ZZ, 1977, 889. 158 R. D. Rieke, R. A. Copenhafer, C . K. White, A. Aguira, J. C . Williams, and M. S. Chattha, J. Amer. Chem. Soc., 1977, 99, 6656. 1 5 9 R. D. Rieke and C. K. White, J. Org. Chem., 1977, 42, 3759. 160 M. Geoffroy, L. Ginet, and E. A. C. Lucken, Mol. Phys., 1977,34, 1175. 1131 K. H. Schemer, K. Hieke, P. Schuler, and H. B. Stegmann, Z , Naturforsch., 1976, 31a, 1620. 162 A. V. Il’yasov, Ya. A. Levin, A. Sh. Mukhtarov, A. A. Vafina, I. P. Gozman, and T. G. Valeeva, Bull. Acad. Sci., U.S.S.R., 1976, 2453. l 6 S M. Zanger and R. Poupko, Spectroscopy Letters, 1977, 10, 737. 164 M. Ballester, J. Riera, and C . Rovira, Anales de Quim., 1976, 72, 489. 165 P. Tordo, M. Boyer, V. Cerri, and F. Vila, Phosphorus and Sulfur, 1977, 3, 373; P. Tordo, M. Boyer, F. Vila, and L. Pujol, ibid,, p. 43; K. Torssell, Tetrahedron, 1977, 33, 2287; A. Sh. Mukhtarov, A. V. Il’yasov, and Ya. A. Levin, Bull. Acad. Sci. U.S.S.R., 1976, 25, 2625. A. V. Il’yasov, B. 6 . Liorber, A. A. Barlev, A. Sh. Malchtarov, M. P. Sokolov, V. A. Pavlov, and A. T. Razumov, Teor. i eksp. Khim., 1977, 13, 693. 167 A. V. Il’yasov, Ya. A. Levin, A. Sh. Mukhtarov, M. S. Skorobogatova, and A. A. Barlev, Zhur. strukt. Khim., 1978, 19, 69. 16* D. Nelson and M. C. R. Symons, J.C.S. Perkin II, 1977, 286. 156

157 R.

278


phosphates have been carried out either by irradiation 169 or ~pin-labellingl~~ techniques.

3 Vibrational and Rotational Spectroscopy Band Assignments.-Several studies of phosphine have been published,171 and the i.r. spectra of ethylphosphonic acid,17 of some aryl(azoary1)phosphonic and of several amino-phosphonic acids of the type (95)174have been analysed. The multiplicity of the v(P0) band for diethyl ethylphosphonates (96) is caused mainly by Fermi resonance of the PEt and PO ~ i b r a t i 0 n s . Assignl~~ ments of bands in the i.r. and Raman spectra of some phosphoramidates (97) have also been made.176

Stereochemistry.-Torsional and structural data for dimethylphosphine (98) and its deuteriated analogues have been determined.177 The conformational analysis of diphosphine 178 and dimethyldiphosphine 179 by i.r. and Raman spectroscopy indicates that there are certain preferences for gauche conformers. The spectra of t-butylphosphine indicate that the barrier to internal rotation of the PH2 group is nearly 1 kcalmol-l, and higher than for methylphosphine.180 The preferred conformations of trimethyl phosphite,lgl the cyclic phosphite (99; Y =OAr),ls2 a range of trialkylphosphine oxides (100; R = C1-C10),183 and D. M. Close, G. W. Fouse, and W. A. Bernhard, J. Chem. Phys., 1977, 06, 4689; S . Gregoli, M. Olast, and A. Bertinchamps, Radiation Res., 1977, 72, 201 ; S. Kominami, S. Rokushika, and H. Hatano, ibid., p. 89. 1 7 0 A. 1. Petrov and B. I. Sukhorukov, Biofizika, 1977,22,924; L. R. Brown and K. Wuethrich, Biochim. Biophys. Acta, 1977,468, 389; A. H. Koyama, T. Maeda, S . Toyama, S. Ohnishi, and H. Uetake, ibid., 1978, 508, 130. 1 7 1 A. J. Van Straten and W. M. A. Smit, J . Mul. Spectroscopy, 1977, 65, 202; D. A. Helms and W. Gordy, ibid,, 1977, 66, 206; T. FI. Huang, J. C . Decius, and J. W. Nibler, J. Phys. and Chem. Solids, 1977, 38, 897. 1 7 2 M. P, Noskova, 0. I. Kondratev, and D. I. Mostafin, Zhur. priklad. Spektroskopii, 1977, 26, 941. 173 G. Zuchi and G. Morait, Rev. Chim. (Roumania), 1977, 28, 774. 174 V. Jagodic, Croat. Chem. Acta, 1977, 49, 127; P. M. Drozdzewski, K. Nakamoto, and B. B. Kedzia, Bull. Acad. polon. Sci., Ser. Sci. Chim., 1977, 25, 209; G. Zuchi, Rev. Chim. (Roumania), 1977, 28, 290. 175 D. F. Fazliev, R. R. Shagidullin, and L. Kh. Ashrafullina, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1841. 1 7 6 C. D. Press1 and A. Schmidt, Z . anorg. Chem., 1977, 434, 171; V. E. Bel'skii, R. R. Shagidullin, and L. Kh. Ashrafullina, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1097. 1 7 7 J. R. Durig, M. G. Griffin, and W. J. Natter, J. Phys. Chem., 1977, 81, 1588; J. R. Durig, P. Groner, and Y . S . Li, J. Chem. Phys., 1977, 67, 2216. 178 M. Baudler, M. Vogel-Raudschus, and J. Dobbers, 2. aiiorg. Chem., 1977, 437, 78. 1 7 9 J. R. Bard, A. A. Sandoval, C. J. Wurrey, and J. R. Durig, Znorg. Chem., 1978, 17, 286. 180 J. R. Durig and A. W. Cox, J. Mol. Structure, 1977, 38, 77. 1 8 1 A. B. Remizov, S . A. Katsyuba, 0. B. Sobanova, I. S . Pominov, and B. P. Khalep, J. Gen. Chem. (U.S.S.R.), 1977, 47, 209. 1 8 2 B. A. Arbuzov, R. P. Arshinova, T. D. Sorokina, A. B. Remizov, and G. E. Koroleva, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1856. 183 V. G. Koval, Zhur. priklad. Spektroskopii, 1977, 26, 766. 169

Physical Methods

279

the diphosphine disulphide (101)184have also been studied. The conformational energies of the dioxaphosphorinans (99; Y = alkyl) and their sulphides have been ~alculated.~ Bonding.-The N-H stretching frequency in the spectra of amino-phosphines (102) correlates with the P-N bond order.ls6 A theoretical study has been performed on H2PNH2.lS7 The bonding relationships upon the diprotonation of the phosphinimine (103) have been studied by i.r. spectroscopy.1ssVariation of v(P0) for the chloromethyl-phosphonicacids (104) has been interpreted in terms of changes in d,-p, bonding.lsg Calculations of vibrational frequencies and structural studies of protonated trimethylphosphine oxide (105; R = H) and its

methylated derivative (105; R = Me) have been reported.lgOStudies of hydrogenbonding are numerous. The relative basicities of 4-cyclohexylphosphorins and a series of 4-substituted triarylphosphines have been determined from their ability to form hydrogen bonds with 4-trifl~oromethylphenol.~~~ Aliphatic alcohols were used in related studies of tertiary phosphineslg2and phosphine chalcogenide~.~~~ Diphosphoryl compounds combined with nitric acid to give a crystalline 1:2 complex, which has been studied by i.r. The association of some dihydroxy-diphosphonyl compounds (106) has also received attention.lg5 The interaction of a series of methylphosphonates with phenol was followed by monitoring the values of v(OH), which was found to be linearly related to inductive cc constants.1gsThe variation of v(0H) for phenol and various phosG. P. McQuillan and I. A. Oxton, Spectrochim. Acto, 1977, 33a, 233. R. P. Arshinova, Doklady Akud. Nauk S.S.S.R.,1978, 238, 858. 186 R. Mathis, F. Mathis, and N. Ayed, J.C.S. Chem. Comm., 1977, 614; N. Ayed, A. El Borgi, B. G. Baccar, F. Mathis, and R. Mathis, Compt. rend., 1977, 285, C, 221. M. Barthelat, R. Mathis, and F. Mathis, J.C.S. Chem. Comm., 1977, 615. 188 K. D. Press1 and A. Schmidt, Z . anorg. Chem., 1977, 435, 69. ls9 B. J. Van der Veken and M. A. Herman, J. Mol. Structure, 1976, 34, 229. 190 E. 1. Matrosov, M. P. Komarova, and M. 1. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1211. lgl H. P. Hopkins, 13. S. Rhee, C. T. Sears, K. C. Nainan, and W. H. Thompson, Inorg. Chem., 1977, 16, 2884. 192 J. Mendel and A. Kolbe, Phosphorus and Suljkr, 1977, 3, 21. l g 3 V. G. Koval, Zhur. priklud. Spektroskopii, 1977, 26, 722. 194 N. P. Nesterova, A. I. Zarubin, E. 1. Matrosov, T. Ya. Medved', and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R.,1977, 26, 1637. Ig5 A. N. Pudovik, M. G . Zimin, and A. A. Sobanov, J. Gen. Chem. U.S.S.R., 1977, 47,918. lg8 R. R. Shagidullin, I. P. Lipatova, L. V. Nesterov, S. A. Samartseva, L. I. Vachugova, and A. Ya. Kessel, Zhur. priklad. Spektroskopii, 1977, 27, 284. Is4

195

280


phorinans (107) correlates with the half-bandwidth of v(PO).lg7The association of the amides (1Q8)198and of the a-amino-phosphine oxides (1O9)lg9has also been sudied.

0

II (B uO), PNI-IBu

Ch

II

KPCHPhNHPh

Microwave Spectra.-The microwave spectrum of FC=P has been recorded and the CP bond length estimated to be 153.6 pm.200The microwave spectra of isopropylphosphine 202 and t-butylphosphine 202 have been analysed and structural data calculated. 4 Electronic Spectroscopy Absorption.-The U.V. spectra of triphenylphosphine and trimesitylphosphine have been compared with those of the arsenic, antimony, and bismuth analogues; trimesitylphosphine, at 77 K, gave a sharp band similar to that of mesitylene, and it was attributed to one ring that is orientated out ofp, conjugation with the phosphorus atom.203 Calculated n localization energies of para-substituted arylphosphines have been found to correlate with pKa values but not with ionization potentials. 204 U.V. spectroscopy has been used as supporting evidence for the aromaticity of 1,l-dihalogeno-phosphorins (1 lo), 2 0 5 and to assist in the assignment of the geometries of the oxides (111).206

lg7 l9*

l99

aoo 201 202

203 204

205 206

T. Gramstad and K. Tjessem, Acta Chem. Scand. ( B ) , 1977, 31, 345. B. N. Laskorin, V. V. Yakshin, and B. N. Sharapov. J. Gen. Chem. (U.S.S.R.), 1977,47, 2164. R. G. Islamov, M. G. Zimin, T. A. Dvoinishnikova, I. S. Pominov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1335. H. W. Kroto, J. F. Nixon, N. P. C . Simmons, and N. P. C . Westwood, J. Amer. Chem. SOC.,1978, 100, 446. J . R. Durig and Y . S. Li, J. Mol. Spectroscopy, 1978, 70, 27. Y.S . Li, A. W. Cox, and J. R . Durig, J. Mol. Spectroscopy, 1978, 70, 34. K. L. Rogozlin, A. N. Rodionov, S. G. Smirnov, D. N. Shigorin, E. M. Panov, and K. A. Kochesdov, Bull. Acad. Sci. U.S.S.R., 1977, 26, 949. H. Goetz, H. Hartan, H. Juds, F. Marschner, and H. Pohle, Annalen, 1977, 556. H. Kanter, W. Mach, and K. Dimroth, Chem. Ber., 1977, 110, 395. A. Hauser, H. Koeppel, T. Forner, K. D. Schleinitz, and 13. G. Henning, J. prakt. Chem., 1977.319.263.

28 1

Physical Methods

Photoelectron.-The photoelectron spectra of some phosphites have been The spectra of the triaminophosphines (1 12) indicate that the molecules have C3 symmetry, with two lone pairs of nitrogen interacting in a 0 manner and a third lone pair in a n The multi-peak nature of the spectrum of the phosphinimine (1 13) was explained as a shake-up phenomenon involving intramolecular transfer of charge. 209 The structures of triplienyl phosphate and of methylphosphonic acid have been investigated, in the solid and liquid states. 210 5 Diffraction

X-Ray Diffraction.-The crystal structure of the diacylphosphine (114) has a symmetrical hydrogen bridge with a very short 0 -- - - 0 distance (240 pm).211 Trithienylphosphine (115) has two rings which have sulphur atoms on the On the other hand, the methyl opposite side to the lone pair of derivative (116) has all the rings twisted, so that all the methyl groups are on the

same side as the phosphorus lone pair.213 The 3-phosphindole (117) has the phosphorus atom 10 pm from the phosphole plane. 214 The dibenzophosphorin (118) has a boat-shaped heterocyclic ring and a planar arrangement about the nitrogen atom.215A crystallographic study showed that the diphosphine (119) has a cis conformation about the central C-C bond, but it revealed no unusual features which could explain its photochromic properties. 210 The tetracyclohexyldiphosphine (120; R = C6Hll) possesses a semi-eclipsed conformation with

(117) 207

(118)

(119)

A. H. Cowley, M. Lattman, R. A. Montag, and J. G. Verkade, Znorg. Chim.Acta, 1977, 25, 151.

209

210

211 212

213 214

215

216

J. H. Hargis and S . D. Worley, Znorg. Chem., 1977, 16, 1686. S. Tsuchiya and M. Seno, Chem. Phys. Letters, 1978, 54, 132. V. I. Povstugar, V. I. Kodolov, V. A. Zhilyaev, and V. A. Trapeznikov, Zhur. strukt. Khim., 1977, 18, 701. G. Becker and H. P. Beck, Z. anorg. Chem., 1977, 430, 77. A. C. Hazell, R. G. Hazell, and G. S. Pawley, Acta Cryst., 1977, B33, 1105. A. C. Hazell and K. G. Hazell, Acta Cryst., 1977, B33, 1102. W. Winter, Chem. Ber., 1977, 110, 2168. S. N. Gurkova, A. I. Gusev, V. A. Sharapov, L. A. Yagodina, A. I. Bokanov, and B. I. Stepanov, Zhur. strukt. Khim., 1977, 18, 62. S. J. Rettig and J. Trotter, Canad. J. Chem., 1977, 55, 3065.

282


equatorial P-C The tetraphosphine (121) has an envelope conformation with phenyl groups on alternate sides. The corresponding disulphide has its heterocyclic ring in a twist conformation.21sThe silylated phosphinimine (122) has a P-N bond length of 154.5 pm, indicating a sp,-2p interaction.21s

RP ’P -

‘ *.

R

P?-pjPh

& *

k

phpvpph (TMS,N) PNTMS

(120) (121) (122) The X-ray crystallographic data on the anisyl salt (123) confirm theP+. * - 0 M e interaction indicated by the n.m.r. data.220The structures of the methiodide of the phosphine (117),221the salt (124),222the ylide (125),223and the diselenide (126) 2 2 3 have also been determined. The molecular structure of the phosphacumulene (127) has been determined 2 2 4 and compared with those of phospha-allene y l i d e ~It. ~has ~ ~been shown that protonated triphenylphosphine oxide (128) has a short linear hydrogen bond. 2 2 6 The crystal structure of tris(cyclohexy1)phosphine sulphide (129) exhibits one of the longest P-S bonds (196.6 pm) yet almost as long as the P-Se bond (212 pm) for the selenide (130).228

-

Me

\

Ph-PSe

Ph,P&c\c

,ph N N -. (1 27)

Ph,G-OH

C1‘

(C,H,, ),PS

/

Pr

(128) (129) (130) R. Richter, J. Kaiser, H. Hartung, and C. Peter, Acta Cryst., 1977, B33, 1887. 218 J. Lex and M. Baudler, 2. anorg. Chcm., 1977, 431, 49. 219 S. Pohl, 2. Naturforsch., 1977, 32b, 1344. 220 J. S. Wood, R. J. Wikholm, and W. E. McEwan, Phosphorus and Sulfur, 1977, 3, 163. 221W. Winter and J. Straehle, Chem. Bcr., 1977, 110, 1477. 222 M. Foulon, F. Baert, J. P. Henichart, and R. Houssin, Cryst. Struct. Comm. 1977,6, 587. 223 P. J. Carroll and D. D. Titus, J.C.S. Dalton, 1977, 824. 224 H. Burzlaff, E. Wilhelm, and H.J. Restmann, Chem. Ber., 1977, 110, 3168. 225 H. J. Bestmann, Angew. Chem. Znternat. Edn., 1977, 89, 349. 226 H. J. Haupt, C. Krueger, H. Prent, and D. Thicrbach, Z . anorg. Chem., 1977, 436, 229. 227 K. A. Kerr, P. M. Boorman, B. S. Misener, and J. G. H. van Roode, Canad. J. Chem., 1977, 55, 3081. 2 2 8 2.Galdecki, M. L. Glowka, J. Michalski, A. Okruszek, and W. J. Stec, Acta Cryst., 1977, B33,2322. 217

Physical Methods

283

%Ray diffraction studies of the bisphosphonyl compound (131),229a trisp h o s p h ~ r i n ,and ~ ~ ~the phosphinic esters (132) 231 and (133)232have been published. Twist-chair and chair conformers with an equatorial phosphonate group occur in the crystals of the ester (134).233Two conformers are also present in the unit cell of the furanose (135), one form adopting a nearly ideal boat c ~ n f o r m a t i o n .X-Ray ~ ~ ~ diffraction studies of the amino-phosphonic acid (136),235FONOFOS (137),236and the arsonomethylphosphonate (138) 2 3 7 have appeared. The structures of poly- (and some P4-)p h o ~ p h a z a n e s , several ~ ~ ~ phosp h a ~ e n e sand , ~ ~a~diazaphosphorin (139) 240 have been described. The conforma-

0

II

5(oMe)z (1 34)

H

229

230 231 232 233

234 235 236

237 238

239 240

S. Hoehne, H. Lesiecki, H. D. Ebert, E. Lindner, and J. Straehle, 2. Naturforsch,, 1977, 32b, 707. T. Debaerdemaeker, H. H. Pohl, and K. Dimroth, Chem. Ber., 1977, 110, 1497. Z. Galdecki and M. L. Glowka, Roczniki Chem., 1976,50, 1639. Z. Galdecki and M. L. Glowka, Acta Cryst., 1977, B33, 2650. G. I. Birnbaum, G. W. Buchanan, and F. G. Morin, J. Amer. Chem. SOC.,1977,99,6652. J. Thiem, M. Guenther, H. Paulsen, and J. Kopf, Chem. Ber., 1977, 110, 3190. T. Glowiak and W. Sawka-Dobrowolska, Tetrahedron Letters, 1977, 3965. R. Allahyari, P. W. Lee, G. H. Y.Lin, R. M. Wing, and T. R. Fukuto, J. Agric. Food Chem., 1977,25,471. L. Falvello, P. G. Jones, 0. Kennard, and G. M. Sheldrick, Acta Cryst., 1977, B33, 3207. G. J. Bullen, N. L. Paddock, and D. J. Parmore, Acta Cryst., 1977, B33, 1367; W. Zeiss, W. Schwarz, and H. Hess, Angew. Chem. Internat. Edn., 1977,16,407; M. N. Alexander, Macromolecules, 1977, 10, 721. R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Canad. J. Chem., 3577, 55, 2530; R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, ibid.,p. 3118. R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Canad. J. Chem., 1977.552534,

284


and there is a tional energies of some polyphosphazenes have been review which includes a discussion of bond lengths, angles, and conformations of phosphazanes and phosphazenes.242 Crystallographic studies of the half-chair sulphide (140),243the dioxaphosphoran (141),244 the benzodioxaphosphoran (142),245and (+)-cycl~phosphamide~~~ have been completed. A review of glycol cyclic phosphates includes a comparison of molecular The strucand of a phostures of two uridine phosphates,248of a furanose phatidylethan~larnine,~~~ and a related theoretical study of P-0 bond rotation in phosphoric acid and its anions,251have been published. Me

NHCHO

1

OPh i

The crystal structures of five-co-ordinate phosphoranes have been used to estimate the most favourable pseudorotation processes. Their structures vary from an almost ideal t.b.p., e.g. (143),252via a structure that is 31 % distorted towards a rectangular pyramid, as in (144),253to a structure close to a square pyramid, e.g. (145).264On the other hand, the distortion of (146) from a t.b.p.

Po I ,Ph

0-P

0 Me

241 242

243 244 245 246

247 248

249 250 251

252 253 254

R. H. Boyd, Chem. Abs., 1977, 87, 53 728. R. A. Shaw, Phosphorus and Sulfur, 1978, 4, 101. T. Prange, C. Pascard, J. Devillers, and J. Navech, Bull. SOC.chim. France, 1977, 185. T. S. Cameron and J. KaroIak-Wojciechowska, Acta Cryst., 1977, B33, 2342. Z. Galdecki and M. L. Glowka, Roczniki Chem., 1977, 51, 1041. I. L. Karle, J. M. Karle, W. Egan, G. Zon, and J. A. Brandt, J. Amer. Chem. Soc., 1977, 99, 4803; D. A. Adamiak, W. Saenger, R. Kinas, and W. J. Stec, Z . Naturforsch., 1977, 32c, 672. F. Ramirez and I. Ugi, Phosphorus and Sulfur, 1976, 1, 231. W. Depmeier, J. Engels, and K. H. Klaska, Acta Cryst., 1977, B33, 2436; J. Engels and J. Hoftiezer, Chem. Ber., 1977, 110, 2019. F. Ramirez, J. S. Ricci, 0. P. Madan, J. F. Marecek, and H. Tsuboi, J. Amer. Chem. SOC., 1977,99, 5135. M. Elker, P. Hitchcock, R. Mason, and G. G. Shipley, Proc. Roy. SOC.1977, A354 157. D. M. Hayes, P. A. Kollman, and S . Rothenberg, J. Amer. Chem. SOC.,1977, 99, 2150. M. Willson, F. Mathis, R. Rugada, R. Engalbert, J. J. Bonnet, and J. Galy, Acta Cryst., 1978, B34, 629, 637. J. S. Szobota and R . R. Holmes, Inorg. Chem., 1977, 16, 2299. J. R. Devillers and R. R. Holmes, J. Amer. Chem. SOC.,1977, 99, 3332.

Physical Methods

285

structure has been rationalized as being in a turnstile direction.255The unusual bisphosphoranes (147a) and (147b; X = CF,) also have distorted t.b.p. structures and a planar 2 5 7 The boat conformation adopted by the bicyclic phosphorane (148; X = CF,) allows the lone pair of electrons on nitrogen to lie in the radial

x (147a)

(148)

Electron Diffraction.-A combination of spectroscopic data for trimethyl phosphine and other Group V analogues has been used to calculate vibrational force fields, amplitudes, and zero-point structures.259 The structure of acetyldimethylphosphine (149) has been discussed further with regard to its flattened configuration at phosphorus 2Go and CND0/2 calculations of conformational energies; 261 a preference for one conformation was not established. The chlorophosphines (150) and (151) have been found to prefer gauche conformations. Difluorophenylphosphine (152) has also been studied. 2 6 3 The methylenephosphorane (153) has been found to have a very short P=C bond (164 pm) which corresponds to a bond order of 2.264The electron-diffraction data for the carbodiphosphorane (154) correspond to a PCP bond angle of 147.6'; evidence has been presented to support the proposal that a shrinkage effect caused by a vibration of large amplitude makes the PCP bonds appear bent by 32", whilst the

0

(149)

EtPCI,

EGPCl

PhPF,

(150)

(151)

(152)

P. Narayanan, H. M. Berman, F. Ramirez, J. F. Marecek, Y . F. Chaw, and V. A. V. Prasad, J. Amer. Chem. Soc., 1977, 99, 3336. 256 V. G. Andrianov, A. E. Kalinin, and Yu. T. Struchkov, Zhur. strukt. Khim., 1977,18, 310 257 J. A. Gibson, G. V. Roschenthaler, and D. Schomburg, Chem. Ber., 1977, 110, 1887. 258 J. H. Barlow, S. A. Bone, D. R. Russell, S. Trippett, and P. J. Whittle, J.C.S. Chem. Comm., 1976,24, 1031. 259 B. Beagley and A. R. Medwid, J. Mol. Structure, 1977, 38, 229. 260 L. S. Khaikin, L. G. Andrutskaya, and L. V. Vilkov, Chem. Abs., 1977, 87, 184603; L. S. Khaikin, L. G. Andrutskaya, 0. E. Grikina, L. V. Vilkov, Yu. I El'natanov, and R. G. Kostyanovzkii, J. Mol. Structure, 1977, 37, 237. 2*1 0. E. Grikina, N. F. Stepanov, L. S. Khaikin, E. A. Bovina, and L. V. Vilkov, J. Mol. Structure, 1977, 37, 2 5 1 . 262 V. A. Naumova, L. L. Tuzova, and N. M. Zaripov, Zhur. strukt. Khim., 1977, 18, 67. 2G3 A. W. Burt, D. W. H. Rankin, and 0. Stelzer, J.C.S. Dalton, 1977, 1752. 2G4 E. A. V. Ebsworth, T. E. Fraser, and D. W. H. Rankin, Chem. Ber., 1977, 110, 3494.

255

286


average structure is linear. It has also been concluded that there is free rotation about the P=C The molecular structure of trimethylphosphine selenide (155) is similar to that of the corresponding sulphide.266The structure of the amino-fluoro-phosphorane (156) has been determined by electron diffraction; CND0/2 calculations indicate that the amino-groups are planar and perpendicular to the radial plane.2e7 F

H-P; Me, P-CH,

(153)

Me,P=C=PMe, (154)

Me,PSe

(155)

I I

NI1, I‘

NH2

F

(156)

6 Dipole Moments, Conductance, and Polarography The dipole moments of isopropylphosphine and t-butylphosphine have been calculated from their microwave parameters. 201s 2o Several reports have appeared concerning triarylphosphines and their chalcogenides, and the discrepancy of the dipole moments reported for trimesitylphosphine has been discussed with reference to data on a wide range of triarylphosphines,268including tridurylphosphine. A consistent set of data has been prepared which allows the calculation of bond moments and configurations of substituted tertiary phenyl-phosphines, -arsines, -stibines, and -bismuthines.269 Suitable group moments ,u(PhP) have been proposed for trihalogenoarylphosphines and their chalcogenides.270 The calculation of P-C bond moments of the phenyl ethyl tertiary phosphines (157) 271 and an M.O. study of fluoro-phosphines272 have also been presented. Dipole moments, combined with Kerr constants, have been used in the conformational analysis of dimethyl- and di-t-butyl-arylphosphines. 273 Dipole moments of para-substituted triaryl phosphites (158) and the corresponding thiophosphates are linearly related to the substituent constants.274 The conformational analyses of the PIIr isocyanates (159), of the corresponding chalcog e n i d e ~ and ,~~~ of the phosphorus heterocycles (160) 276 and (161) 277 have 265 266 267 268

269

270 271 272 273

274 275 276 277

E. A. V. Ebsworth, T. E. Fraser, D. W. H. Rankin, 0. Gasser, and H. Schmidbaur, Chem. Ber., 1977, 110, 3508. E. J. Jacob and S. Samdal, J. Amer. Chem. SOC.,1977, 99, 5656. D. E. J. Arnold, D. W. H. Rankin, and G. Robinet, J.C.S. Dalton, 1977, 585. I. P. Romm and E. N. Gur’yanova, J. Gen. Chem. (U.S.S.R.), 1977,47,705; I. P. Romm, E. N. Guryanova, N. A. Rozanelskaya, and K. A. Kocheshkov, TetrahedronLetters, 1977, 33. E. G. Claeys, G. P. Van der Kelen, and R. F. De Ketelaere, J. Mol. Structure, 1977, 40, 89. E. G. Claeys and G. P. Van der Kelen, J. Mol. Structure, 1977, 40, 97. A. S. Gel’fond, F. Yu. Akhmadullina, and B. D. Chernokal’ski, J. Gen. Chem. (U.S.S.R.), 1977,47,2030. A. Schmildekamp, S. Shaarup, P. Pulay, and J. E. Boggs, J. Chem. Phys., 1977, 66, 5769. 0. A. Raevskii, A. N. Vereshchagin, Yu. A. Donskaya, J. G. Malakhova, Yu. 1. Sukhorukov, E. G. Tsvetkov, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R.,1976,2092. H. Waeschke and R. Mitzner, Z. Chem., 1977, 17, 228. Yu. Ya. Borovikov, Yu. P. Egorov, A. A. Kisilenko, and V. A. Shokol, J. Gen. Chem. U.S.S.R., 1977, 47, 304. R. P. Arshinova and R. N. Gubaidullin, Bull. Acad. Sci. U.S.S.R.,1977, 26, 986. R. P. Arshinova, R. Kraemer, and J. Navech, Phosphorus and Suuur, 1977, 3, 281.

Physical Methods

287

Y

utilized dipole moments. The contribution of the diethoxyphosphoryl groups to the moment of the diphosphonate (162) has been calculated 278 and the trends in the polarity of the P-N bond have been investigated.279 The dipole moments of complexes of phosphine oxide with hydroxyl compounds corresponded to a coordination angle of 109k 6°.280

Me

Et (161)

(160)

(162)

Conductance has been used to study the association of a variety of phosphoryl compounds with lithium and potassium cations 281 and to determine the structure of halogen adducts of phosphines such as (163).282 Polarographic studies of phosphonium salts such as (164) 2 8 3 and of phosphonates (165) 2 8 4 show the reversible formation of radical anions. The half-wave potentials of the amide salts (166) were linearly related to Taft (r*

(ClCH,CH, IzNP

\

(16 6 ) 278 279

280 281

282 283

284 285

NHNH,*HCl

0 (167)

L. Maijs and 0. Lukevics, Latv. P.S.R. Zinat. Akad. Vestis., Kim. Ser., 1977, 367. E. A. Ishmaeva, M. A. Pudovik, and I. Ya. Kuramshin, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1977, 178. E. I. Matrosov, G. M. Petov, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1405. N. G. Osipenko, E. S. Petrov, Yu. I. Ranneva, E. N. Tsvetkov, and A. I. Shatenshtein, J . Gen. Chem. (U.S.S.R.), 1977, 47, 1984. J. B. Lambert and H.-N. Sun, J. Org. Chem., 1977, 42, 1315. E. A. Berdnikov, F. R. Tantasheva, V. I. Morozov, A. V. Il’yasov, and A. A. Vafina, Bull. Acad. Sci. U.S.S.R., 1977, 26, 731. G . N. Nikolaev, M. K. Saikina, and V. G . Stavinchuk, J. Gen. Chem. (U.S.S.R.)1977, 47, 1173. V. M. Ovrutskii, L. D. Protsenko, L. G. Sachenko, and N. D. Denisov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1588.

288


The polarographic behaviour of AMP, 286 pyridoxal 5’-pho~phate,~*~ and PHOSMET (167) 288 and the dielectric relaxation of phosphine sulphidesp89 have also been investigated.

7 Mass Spectrometry The mass spectra of the pliospholes (168) showed intracyclic P-C bond cleavage and loss of CO as facile processes; this contrasts with pyrrole and thiophen compounds, and indicates that 2pn-3pn delocalization is considerably less in the phospholes.290 The fragmentation patterns of isomers are usually very similar; however, the a- and P-ribopyranoside phosphates gave distinguishable spectra.291 Phosphites have been used in the development of field ionization mass spectros c o ~ y The . ~ ~mass ~ spectra of oxazaphosphorus heterocycles (169) and (170)

were characterized by loss of alkoxy-groups and ring cleavage.293 Electron bombardment of a range of oxides (171) gave ions at m/e 21 5,216, and 229 which appear to arise by a- and @-cleavageof the alkyl chain; the chemical ionization spectra contained abundant M + 1 ions.294The major fragmentation pathways of a number of thioates (172) have been determined, and show that aryl migration from oxygen or phosphorus to sulphur is facile.296Fluorine migration from

286 287

288 289

290

291 292

293 294

295

K. Wienhold and H. Sohr, Analyt. Chim. Acta, 1977, 89, 297. J. Llor and M. Cortijo, J.C.S. Perkin ZZ, 1977, 1715. J. Davidek, M. Nemethova, and J. Seifert, Z . analyt. Chem., 1977, 287, 286. Yu. Ya. Borovikov, S. I. Vdovenko, V. Ya. Semenii, and V. I. Katolichenko, Teor. i eksp. Khim., 1977, 13, 229. F. Mathey, Tetrahedron, 1976, 32,2395. A. C. Bellaart, H. M. Buck, P. A. Leclercq, and L. J. M. Van de Ven, Rec. Trau. chim., 1977, 96, 293. V. B. Labintsev, Yu. K. Gusev, N. N. Grishin, V. N. Chistokletov, and A. A. Petrov, Zhur. org. Khim., 1977, 13, 1141 ;V. B. Labintsev, N. N . Grishin, and A. A. Petrov, Zhur. analit. Khim., 1977, 34, 842. R. 2.Musin, Yu. Ya. Efremov, and M. A. Pudovik, Kliitn. geterotsikl. Soedinenii, 1977, 749. S. D . Goff, B. L. Jelus, and E. E. Schweizer, Org. Mass Spectrometry, 1977, 12, 33. W. Steurbaut, N. De Kimpe, L. Schreyen, and W. Dejonckheere, Bull. Soc. chim. belges, 1977, 86, 65; T. R. B. Jones, J. M. Miller, and M. Fild, Org. Mass Spectrometry, 1977, 12. 317.

Physical Methods

289

carbon to phosphorus has also been detected in the mass spectra of pentafluorophenyl Studies of the thiophosphoryl chlorides (173) 296 and (174) 2 9 7 and some urethane derivatives (175) 298 are reported. Mass spectrometry provides a method of determining the sequence of di- and tripeptides containing aminomethylphosphonyl residues.299 The mass spectra of some very stable polycyclic dioxyphosphoranes such as (176) have been analy~ed.~OO

s’ Reports have appeared on the use of g.c.-mass spectrometry for the estimation of pesticides,301aspartic acid derivatives,302silylated phosphatidyl~holines,~~~ and cycloph~sphamide.~~~ The determination of cyclophosphamide and its metabolites using electron-impact and field-desorption methods was improved by the use of benzylthiol derivatives.305 8 pKa and Thermochemical Studies ortho-Effects on the pKa values of trimesityl- and triduryl-phosphines have been investigated.306The basicity of the silyl-phosphine oxide (177) was an order less than expected, and cannot be used as an initial Five-membered cyclic phosphites (178) are stronger proton donors than the six-membered

n

o\p/* (TMSCH,),P=O

H’

\Ch

n

o,p/o H/

\ell

M. S. Bhatia and Pawanjit, Org. Mass Spectrometry, 1977, 12, 1. M. S. Bhatia and Pawanjit, Indian J. Chem., 1977, 15B, 1151. 298 Yu. A. Strepikheev, V. A. Kolesova, N. A. Guttman, and V. A. Valovoi, Chem. Abs., 1977, 86, 170 208. 299 K. Yamauchi, Y . Mitsuda, and M. Kinoshita, Org. Mass Spectrometry, 1977, 12, 119. 300 D. Hellwinkel and W. Krapp, Chem. Ber., 1978, 111, 13. 301 H. J. Stan, Lebeiismittelclwm. Gerichtl. Chem., 1977, 31, 113; Z. Lebensm.-Untersuch, 1977, 164, 153; Chromatographia, 1977, 10, 233. 302 A. R. Braufman, K. H. Valia, and R. J. Bruni, J. Chromatog., 1978, 151, 71. 303 T. Curstedt, Biochim. Biophys. Acta, 1977, 489, 79. 304 I. Jardine, C . Fenselau, M. Appler, M. N. Kan, R. B. Brandrett, and M. Colvin, Cancer Res., 1978, 38, 408. 305 M. Przybylski, H. Ringsdorf, U. Lenssen, G. Peter, G. Voelcker, T. Wagner, and H. J. Hohorst, Biomed. Mass Spectrometry, 1977, 4, 209. 306 A. I. Bokanov, P. Yu. Ivanov, N. A. Rozanel’skaya, and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1977, 47, 702. 307 N. K. Skvortsov, B. I. Ionin, and V. 0. Reikhsfel’d, J. Gen. Chem. (U.S.S.R.), 1977, 47, 655. 296 297


290

compounds (179).308The pKa values of the amides (180),309 (hydroxyethy1)diphosphonic acid,310and the diphosphonic acid (1 81)y1 have been studied. The acidities of the PH groups in five-co-ordinate phosphoranes (1 82) have been determined and found to be considerably greater for the tetraoxyphosphorane (182; Y=O) (pKa 5.89) than for the diamino-analogue (182; Y=NH) (pKa 11.96).312

EtF, LOEt

‘NHSO, ~r

Thermochemicalstudies are reported on the basicities of phosphoryl extractants towards nitric on the solvating power of phosphoryl compounds towards lithium and potassium t-butoxide~,~l* and upon the heats of formation of stannane-phosphoryl complexes.316 The application of differential thermal analysis to organophosphorus chemistry has been reviewed.31s 9 Chromatography G.1.c.-The molecular association constants for the phospholen oxides (1 83) 317 and tributyl phosphate 31* with alcohols and chloroforms have been determined by g.1.c. The g.1.c. analysis of fluoroalkoxycyclophosphazenes319 and a wide 308 809

310 311 512

313

V. V. Ovchinnikov, V. 1. Galkin, R. A. Cherkasov, and A. N. Pudovik, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1869. L. Almasi, R. Popescu, and R. Grecu, Tetrahedron, 1977, 33, 1327. A. J. Collins and P. G. Perkins, J. Appl. Chem. Biotechnol., 1977, 27, 651. Yu. M.Polikarpov, G. V. Bodrin, E. I. Babkina, T. Ya. Medved, and M. I. Kabachnik Bull. Acad. Sci. U.S.S.R., 1977, 26, 1094.

V. V. Ovchinnikov, M. A. Pudovik, V. I. Galkin, R. A. Cherkasov, and A. N. Pudovik, Bull. Acad. Sci. U.S.S.R.,1977, 26, 393. A. I. Zarubin, A. M. Rozen, and A. V. Volnukhina, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1819.

314

315

N. G. Osipenko, E. S. Petrov, Yu. I. Ranneva, E. N. Tsvetkov, and A. I. Shatenshtein, J. Gen. Chem. (U.S.S.R.), 1977, 47, 1789. L. V. Kucheruk, I. P. Gol’dshtein, Yu. I. Ranneva, N. G. Osipenko, E. S. Petrov, E. N. Gur’yanova, A. I. Shatenshtein, and K. A. Kocheshkov, Bull. Acad. Sci. U.S.S.R., 1977, 26, 1319.

316

G. V. Romanov, A. N. Pudovik, R. Ya. Nazmutdinov, V. M. Pozidaev, and I. A. Akhmadeev, in 1st Proc. Eur. Symp. Therm. Anal., ed. D. Dallimore, Heyden, London,

317

F. K. Nasyrova, R. S. Giniyatullin, an3 M. S. Vigderganz, Usp. Gazov. Khromatogr.,

318 319

F. K. Nasyrova and M. S. Vigderganz, Usp. Gazov. Khromatogr., 1975, 4, 157. V. N. Prom, M. P. Grinblat, V. N. Sharov, and A. L. Klebanskii, J. Gen. Chem. (U.S.S.R.),

1976, p. 221. 1975, 4, 147. 1977,47, 1149.

Physical Methods

291

range of pesticides 320 has been reported. Phosphorus-oxygen bond cleavage during derivatization of condensed polyphosphates and related nucleotides precluded silylation as a useful approach for their g.1.c. analysis.321Dimethylthiophosphinyl esters of steroids gave good c h r o m a t o g r a m ~as , ~ did ~ ~ the acetyl derivatives of phospholipid^.^^^ Several new detectors have been described, such as an ionization detector which is switchable between C , N, and P,324a dual P and S flame detector,325and an inexpensive helium flow T.1.c.-The separation of a range of thiophosphonyl compounds (184; Y = R, Ar, R2N, or RO),327of the partial esters of phosphoric and of phosphatidic acid 329 has been described.

Paper Chromatography.-A sensitive method for the detection of polyphosphates involves staining with toluidine blue and uranyl acetate in acetic Column Chromatography.-The comparative analysis of peaks by using a computer has been described.331Alkyl methylphosphonateg-nitrophenyl esters may be separated according to molecular weight on a Sephadex and phosphates may be separated on a molybdate-treated column333or on an ionexchange

K. Fukuhara, M. Takeda, and M. Uchiyama, Eisei Shikenjo Hokoku, 1976, 94, 14; K. Fukuhara, M. Takeda, and M. Uchiyama, ibid., p. 18; Y . Yamato, M. Suzuki, and T. Watanabe, Shokuhin Eiseigaku .%iSShi,1977, 18, 273; R. J. Bussey, M. A. Christenson, and M, S . O'Connor, J. Agric. Food Chem., 1977,25,993; W. Strubert and J. M. Schwarz, Git Fachz. Lab., 1977, 21, 670, 672; L. M. Varca, E. D. Magollona, and J. A. Pasco, Philipp. Entomol., 1975, 3, 5 5 ; S. 2. Masud, Agric. Pak., 1975,26, 543; J. Hild and H. P. Thier, 2. Lebensm.-Untersuch., 1978, 166, 9 ; J. Hild and H. P. Thier, Deut. Lebensm.Rundschau, 1977, 73, 330; J. Hurter, M. Manser, and B. Zimmerli, J. Agric. Food Chem., 1978, 26, 472. 321 W. 13. Griest and T. W. Martin, J. Chromatog., 1978, 148, 405. 323 K. Jacob and W. Vogt, J. Chromatog., 1978, 150, 339. 323 E, M. Sterns and VJ. T. Morton, Microchem. J., 1977, 22, 283. 3 2 4 B. Kolb, M. Auer, and P. Pospisil, J. Chromatog. 1977, 134, 65. 325 P. L. Patterson, R. L. Howe, and A. Abu-Shumays, Analyt. Chem., 1978, 50, 339. 326 C. Feldman and D. A. Batistoni, Analyt. Chem., 1977, 49, 2215. 327 V. Trdlicka and J. Mostecky, J . Chromatog., 1977, 130, 437; Sb. Vys. Sk. Chem.-Technol. Praze, Technol. Paliv, 1977, D36, 127. 328 I. M. Makarenko and T. F. Aksenova, Chem. Abs., 1978, 88, 89 258. 329 E. B. Rodriguez de Turco and N. G. Bazan, J. Clzromatog., 1977, 137, 194. 330 E. Hatieganu and D. G. Constantinescu, J. Chromatog., 1978, 151, 428. 331 J. F. Bernstein, L. S. Chan, S. P. Azen, E. C . Layne, and P. J. Geiger, Analyt. Biochem., 1978, 85, 492. 332 A. Osa, H. Arukaevu, and A. Aaviksaar, J. Clzromatog., 1977, 135, 196. 333 S. T. Ohnishi, Analyt. Biochem., 1978, 86, 201. 334 K, C. Blanshard, I. Das, and A. J. Thomas, Analyt. Biochem., 1977, 83, 1 . 320

Author Index Aaviksaar, A., 291 Abalonin, B. E., 71, 84 Abbas, K. A., 149 Abbott, P. J., 200 Abbott, S. J., 124, 169 Abel, E. W., 259 Abeles, R. H., 155 Abul'khanov, A. G., 96 Abu-Shumays, A., 291 Acharekar, A. R., 78 Achiwa, K., 8 Achmatowicz, O., jun., 15 Adachi, M., 14, 71, 233 Adair, W. L., 159 Adalsteinsson 0 182 Adamiak, D. k , ' i 5 0 , 284 Adamiak, R. W., 192, 263 Adolin, G., 31 Agafonov, M. N., 18 Agawa, T., 2 18 Aguiar, A., 25, 277 Ahlbrecht, H., 103, 134,219, 222 Ahmed, J., 19 Ajisaka, K., 152 Akasaka, K., 202,263, 268 Akhmadeev, I. A., 290 Akhmadullina, F. Yu., 286 Akhmedov, Sh. T., 143 Akhrem, A. A., 172 Akhtar, M. H., 244 Akiba, K., 98, 224 Akintoniwa, D. A. A., 122 Aklyan, Zh. A., 24 Aksenova, T. F., 291 Alarie, Y., 258 Albrand, J. P., 92, 272 Albrecht P 229 Albright 'T.*'A 209, 267 Alderfer' J. L "263 Aleksanhrov, M., 268 Aleksandrova, N. A., 27,265 Alexander, D. C 34 Alexander, M. N:, 256,283 Alexandrova N. A 275 Alkabets R ' 9 89'265 Allahyari, R' f49 '283 Allcock, H. R., 23i, 248,249, 252,256,257, 260 Allen. C. W.. 254.255 Allen; D. W.; 23,'29, 30, 83, 149, 265 Allen, J. G., 160 Allen. R. W.. 252. 260 Allende, J. E:, 187 Alley, W. D., 114 Allfrey, V. G., 166 Almasi, L., 290 Alparova, M. V., 147 Alzner-Deweerd, B., 199 Al'zoba, T. G., 63 Amarnath, V., 196 Amitai, G., 136 272,

A.

Anderegg, G., 93 Anderson, A. J., 168 Anderson, R. C., 227 Ando, W., 99, 204 Andreae, S., 102 Andreeva, M. A., 257 Andriamizaka, J. D., 271 Andrianov, K. A., 257 Andrianov, V. G., 34, 150, 285 Andrutskaya, L. G., 285 Ang, H. G., 16 Angenault, J., 94 Anoshina, N. P., 50, 61, 147 Antonio, M. D., 216 Antonov, I. V., 173 Appel, R., 12, 13, 38, 68, 69, 71, 81, 204, 239, 242, 272, 273 Applier, M., 289 Arbuzov, A. E., 275 Arbuzov, B. A., 11, 18, 47, 100, 267, 269, 278 Archibald, A. R., 167, 168 Ardrey, R., 272 Arita, S., 257 Arnold, D. E. J., 53, 286 Arnold, D. P., 105 Arnold, K., 151, 263 Armitage, I. M., 151, 263 Armitani, H., 121 Arshinova, R. P., 150, 278, 279,286 Arthurs, M., 5 Artyukhin, P. I., 93 Arukaevu, H., 291 Ashani, Y., 136, 272 Ashe, A. J., Tert., 30 Ashrafullina, L. Kh 278 Asubiojo, 0. I., 134" Atavin, A. S., 150, 274 Atherton, F. R., 160 Auer, M., 291 Autzen, H., 63 Avanzino, S. C., 248 Ayed, N., 279 Azen, S. P., 291 Azhayev, A. V., 171, 195 Babaeva, T. A,, 143 Babidge, P. J., 215 Babkina, E. I., 290 Baboulene, M., 128 Babu, Y. S . , 260 Baccar, B. G., 279 Baccolini, G., 100, 149 Bachman, G. L., 9 Baddiley, J., 167 Baer, E., 160 Baert F., 282 Baglioni, C., 185 Bahl, C. P., 193 Baler, H., 7

292

Bajwa, G. S., 113, 176, 264 Bal, K., 224 Ball. L. A.. 185 Ballester, M.,17, 277 Balszuweit, A., 5 Banek, M., 250 Bangerter, B. W., 3 Bannet, D. M., 146,222 Baran, J. S., 135 Baranov, A. P., 93 Baranov, G. M., 149 Bhrhny, M., 152 Barchietto, G., 214 Bard, J. R., 278 Barenholz, Y., 262 Bariou, B., 11 Barlev, A. A., 277 Barlow, J. H., 285 Barrans, J., 19, 34, 45, 106, 110,111,120,245,249,276 Barrio, J. R., 188 Barsanti, S., 1 Barta, M. A., 40 Barthelat, M., 279 Bartholin, M., 4 Bartholomew, J. C., 177 Bartlett, P. A., 137 Bartlett, P. D., 41 Baryeki, J., 275 Bass, A. I., 178 Bastian, J. M., 224 Bastian, V., 14, 36, 67 Batistoni, D. A., 291 Battioni, J-P., 59, 80 Baturina, L. S., 249 Batyeva, E. S., 11, 102 Baudler, M., 5, 10, 16, 264, 271, 272, 278, 282 Bauer, G., 36, 68, 97 Bauer, S., 173 Baughn, R. L., 182 Baumann, M., 211 Bayley, H., 188 Bazan, N. G., 291 Beagley, B., 285 Beatty, R. P., 3 Bechtolsheimer. H. H.. 271 Beck, H. P., 65; 281 Beck, M. T., 93 Beck, W., 8, 235 Becker. G.. 65. 281 I

Bel'skii,'V. E.,'136, 149, 278 Benezra, C., 274 Benkovic, S. J., 156, 163 Benlian, D., 268

Author Index Bentrude, W. G., 113, 114, 176, 264, 276 Berariu, V., 152 Berdnikov, E. A., 25,85, 147, 275.287 Berger, P. A., 92, 272 Berkova, G. A., 268 Berlin, K. D., 21, 75, 80, 275 Berman, H. M., 34,285 Berman. M.. 184 Berman; S. T., 267 Berndt, K. G., 275 Bernhard, W. A., 278 Bernstein, J. F., 291 Berry, F. J., 14 Bertelo, C. A., 3 Bertinchamps, A., 278 Besolova, E, A., 57 Bestmann, H. J., 39, 204, 206,214,216,282 Bezborodova, S. I., 197 Bhardwaj, C. L., 227 Bhatia, M. S., 289 Biala, E., 192, 263 Bickelhaupt, F., 31, 213 Bickel-Sandkotter, S., 188 Bidan, G., 10 Billington, D. C., 14 Bindra, J. S., 226 Biran, Z., 249 Birnbaum, G. I., 283 Blanshard, K. C., 291 Blaschke, G., 206, 270 Blout, E. R., 188 Blumentritt, J., 254 Bobkova, R . G., 28, 109, 110, 232 Bochkareva, E. S., 188 Bockerman, G. N., 53 Bodley, J. W., 187 Bodrin, G. V., 290 Bohringer, H., 121 Bogel’fer, L. Ya., 28, 110 Boggs, J. E., 286 Boigegrain, R., 13 Boigegrain, R. A., 26 Boisdon, M. T., 34, 111 Bojanovski, D., 162, 187 Bokanov, A. I., 1, 78, 281, 289 Boldeskul, I. E., 93, 150, 275 Bol’shakova, A. S., 93 Boltz, S. C., 163 Bone, S. A., 269, 285 Bonjouklian, R., 207 Bonnet, J. J., 284 Boorman, P. M., 91, 282 Boos, K. S., 162, 180, 187 Borchardt. R . T.. 189 Bore, P. J:, 152 Borisenko, A. A., 113, 157, 173. 274 Borisov, E. V., 232,270 Borisova, E. A., 96 Boronenko, T. P., 208 Borovikov, Yu. Ya., 286,288 Boshart. G., 142 Bosnich; B.; 3 Bottin-Strzalko, T., 265 Boubel, J. C., 262 Bovina, E. A., 285 Bowen, J. H., 266 Bowman, D. A., 36 Boyd, A. S. F., 276 Boyd, R. H., 256,284

293 Boyer, M., 277 Boyer, P. D., 182 Bragg, P. D., 162 Braitsch, D. M., 63 Brand, M. D., 162 Brandrett, R. B., 289 Brandt, J. A., 150, 268, 284 Brandt, W., 6 Braufman, A. R., 289 Brauman, J. I., 134 Braxton, H. G., 258 Breathnach, R., 162 Bredikhina, Z. A., 85, 147 Brems, D. N., 166 Breque, A., 29 Breuer, E., 86, 146, 222, 224 Bridsall, B., 201 Bright, H. J., 178 Brimacombe. R.. 198 Brinkman, U. A:, 93 Brocas, J., 269 Brodelius, P. E., 179 Broom. A. D.. 196 Brousseau, R.;193 Broverman, S., 145 Brown, C., 116 Brown, D. H., 16, 83, 267 Brown, D. M., 198 Brown, E. L., 194 Brown, J. M., 207 Brown, L. D., 19 Brown, L. R., 278 Brown, P., 255 Brown, R. E., 185 Brown, R . K.. 34 Brown; R. S.,-198 Brown, T. R., 151, 202, 262 Brownlee. G. G.. 198 Bruni, R.’J., 289’ Brunner, H., 9, 119 Buchanan, G. W., 266, 274, 283 Buchner, W., 241, 265 Buck, H. M., 42, 135, 275, 288 Budker, V. G., 189, 195 Bugge, B., 159 Bui Cong, C 50,267 Buina, N. A:,’ 119, 149 Bullen, G.-J., 283 Bulloch, G., 270 Bunnett, J. F., 97 Bunton, C. A., 136 Bunus, F. T., 93 Buono, G., 264 Burg, A. B., 263 Burgen, A. S. V., 201 Burger, K., 47 Burgers, P. M. J., 192 Burkhardt, J., 237 Burt, A. W., 285 Burt, C. T., 152 Burton, D. J., 95 Burzlaff, H., 206, 282 Busby, S. J. W., 262 Buschen, J., 269 Bussey, R. J., 291 Butler, L. G., 163 Butorina, L. S., 133 Butters, T., 131 Bychkov, N. N., 78 Byers, L. D., 163 Bystrek, R., 11 Cable, M. B., 159

Cabral, J. De O., 8 Cabral, M. F., 8 Cadger, T., 193 Cadogan, J. I. G., 30, 45,47, 87, 96, 104, 236, 276 Calcagno, M. A., 273 Calvin, M., 177 Cameron, T. S., 259,261,284 Camps, F., 222 Camus, J., 184 Cantarelli, G., 174 Capaldi, R. A,, 263 Capka, M., 4 Carey, J. G., 98 Carissimi, M., 174 Carlsen, D., 140 Carlsohn, B., 5, 10, 264, 271 Carrico, R. J., 154 Carrie, R., 212 Carroll, P. J., 282 Cartwright, I. L., 181 Carty, A. J., 6 Caruthers, M. H., 194 Carver, M. A., 161 Case, J. R., 98 Cashion, P., 193 Casper, J. M., 92 Cassel, D., 184 Castelijns, M. M. C. F., 42 Castillo, C. L., 151 Castro, B., 13, 25, 26 Cavell, R. G., 36, 50, 67, 69, 270, 271, 274 Cavicchio, G., 20 Cerletti N 195 Cerny, M.,*’4 Cerri, V., 277 Chachaty, C., 263 Chaiken, I. M., 178 Chalovich, J. M., 152 Chamberlin, M. J., 187 Chambers, J., 135 Chan, K. K., 228 Chan, L. S., 291 Chan, S., 16 Chan, W. H., 140 Chan, Y., 34 Chander, K., 93 Chang, M., 259 Chang, T. M. S., 152 ChaDleo, C. B., 61 Chapleur, Y., 13 Charbonnel, Y., 45,110,245, 249 Charrier, C., 9, 91 Chatterjee, N. K., 178 Chattha, M. S., 20, 25, 275, 277 Chauzov, V. A., 9, 91 Chaw, Y. F., 285 Chefczynska, A., 220, 268 Chen, E. Y., 199 Chen, K. C., 275 Cheng, D. M., 263 Cheng, T. C., 253, 257 Chentsova, N. M., 141 Cherepinskii-Malov, V. D., 150 Cherkasov, R. A., 138,290 Chernikova, T. S., 194 Chernokal’skii, B. D., 84, 286 Cheung, C. P., 203 Cheung, N. H., 144 Chinali, G., 171

Author Index

294 Chirea, M., 255 Chistokletov, V. N., 30, 288 Chladek. S.. 171. 188 Chlebowski; J. F., 151 Chock, P. B., 151 Chodak, A. A., 237 Chodkiewicz, W., 2, 52, 59, 80. Chojnacki, T., 159 Chojnowski, J., 122 Chopra, A. K., 229 Chou, P. Y., 166 Chou, T., 222 Chrktien, F., 26 Christeller, J. T., 163 Christenson, M. A., 291 Christophe, J., 184 Chuang, D.-M., 153 Chung, D. W., 153 Claeys, E. G., 286 Clark, D. A., 20 Clark, P. W., 4 Clark, T. E., 34, 269 Clarke, C. M., 179 Claussnitzer.~, A.. 233., 243. 247, 267 Cleff, E., 5,264 Cleland, W. W., 154, 20 Clement, J.-C., 219 Clive, D. L. J., 139 Close, D. M., 278 Closson, W. D., 135 G a t e s , H., 116 Coaton, J. R., 248 Cogne, A., 92 Cohen, H., 274 Cohen, S. M., 151, 152 Cohn, M., 151,180,200,201, 262 Coleman, D. L., 263 Coleman, J. E., 151 Coley, J., 167 Coll, J., 222 Colle, K. S., 21, 95, 265 Collier, R. J., 153 Collins, A. J., 290 Colquhoun, I. J., 272 Colvin. M.. 289 Comfurius,-P., 160 Comins, D., 223 Comins, D. L., 220 Commercon, M. B., 135 Conan, J., 4 Conley, R. R., 166 Constantinescu, D. G., 291 Contreras. R., 198 Cook, A. b.,255 Cook, R. D., 149 Cooper, D. B., 121 CooDer. J. W.. 277 Cooper; M. K:, 7 Copenhafer, R. A., 25, 277 Corbridge, D. E. C., 232 Cordes. R. E.. 259 Corey, ‘E. J., 206, 228 Cornelius, R. D., 201 Cortijo, M., 288 Costas, M., 248 Costello, A. J. R., 262 Costisella, B., 20 Cotta. F.. 121 Coulson,A. R., 198 Couret, C., 19, 65, 271 Coutrot, P., 140, 145, 146, 22 1

Couturier, J. C., 94 Covenya, V. A., 63 Cowley, A. H., 63, 73, 233, 270, 281 Cox, A. W., 278,280 Coyne, A., 272 Cradock, S., 53 Cragg, G. M. L., 34, 57, 113 Craig, D. J., 13 Cramer, F., 187 Crean, E. V., 159 Cresp, T. M., 230 Crews, P., 55 Criddle, R. S., 161, 182 Cristol, S. J., 13, 71 Cromie, E. R., 53 Cross, R. J., 16, 83, 267 Croteau. R.. 167 Cuatrecasas; P., 184 Cullen, W. R., 2, 9, 117 Cullis, P. R., 151, 262, 263 Curstedt. T.. 289 Cushley,‘R. J., 263 Cypryk, M., 122

~~

Dagleish, J., 13 Dagnac, P., 92 Dahl, O., 11 Dahmann, D., 242 Dakternieks. D., 67 D’Alayer, J.; 184 Dalgleish, W. H., 276 Dalla Croce, P., 20 Damadian. R.. 262 Damin, B.; 219 D’Antonio, M., 20 Danyluk, S. S., 176 Darby, N., 230 Das, I., 291 Das, M. K., 267 Dashevskii, V. G., 93 Davidek, J., 288 Davidowitz, B., 34, 57, 113 Davjdson, A. H., 88 Davidson, R. S., 78 Davis, R. E., 5 Dawson, J., 262 Dean, P. D. G., 178 De’ath, N. J., 49, 269 Debaerdemaeker, T., 283 De Bie, M. J. A., 276 De Boer, W. R., 168 Decius, J. C., 278 Decoster, A. M., 269 De Edwardo, A. H., 257 De Filippi, L. J., 168 Dehnel, A., 222 Dehnicke, K., 118 Deiters, J. A., 34, 269 Dejonckheere, W., 288 De-Jong, G. J., 93 De Ketelaere, R. F., 286 De Kimpe, N., 288 De Koning, A. J., 276 De Koning, H., 226 De Kruijfl‘, B., 262, 263 Deldonno, T. A., 7 Demay, C., 36, 69 Denis, J. N., 216 Denisov, N. D., 287 Denney, D. B., 36, 42, 49 68,269 Denney, D. Z., 11, 36,42,68 Dennis, R. W., 277 Depmeier, W., 177, 284

De Ruiter, B., 248 Deschodt-Lanckman, M., 184 Descotes, G., 3 Desper, C. R., 256, 257 Deugau, K. V., 197 Devillers, J., 150, 268, 269, 284 Devillers, J. R., 34, 284 Devos, M. J., 216 De Wachter, R., 186 De Wolf, W. H., 213 Dhingra, M. M., 196 Diaz, S., 136 Dicioccio, R. A., 185 Dickerman, H. W., 178 Dieck, R. L., 255, 257, 258 Dietzler, D. N., 185 Dills, W. L., jun., 171 Dimand, R. J., 53 DiMiele, G., 42, 68 Djmroth, K., 280, 283 Dixon, H. B. F., 181 Dmitriev, V. I., 74, 276 Dmitrieva, N. V., 57 Dmitrieva. V. N.. 208 Doak, G. 0.) 47,*69 Dobbers, J., 278 Dolguishin, G. V., 276 Dolhaine, H., 149, 275 Dombrovskii, A. V., 21,206, 1 1 1

LlL

Domin, G., 13 Domocos, V. C., 93 Donis-Keller, H., 198 Donovan, S. F., 211 Donskaya, Yu. A., 286 Doppelberger, J., 9, 119 Dormoy, J.-R., 25 Dose, K., 188, 189 Dotsev, G. V., 63 Dousse, G., 43, 59 Downes, J. M., 7 Dozsa, L., 93 Drach, B. S., 130 Drake, G. L., jun., 23, 27 Dreiding, A. S., 61 Drenth, W., 3 Drew, M. G. B., 8 Dreyfuss, G., 188 Drocourt, J. D., 166 Drozdzewski, P. M., 278 Drummond, G. I., 184 Drutsa, V. L., 194 Dubois, J.-E., 140 Dubois, R. J., 21 Dudkin, S. M., 173 Dudman, N. P., 163 Dumitrescu, P., 93 DuMont, W.-W., 65 Dunkel. G.. 108. 234.264 Dupont, G., 254 ’ Du-Preez, J. G., 94 Durie, J. R., 278, 280 Dutasta. J. P.. 115. 150. 273 ’ ‘ Dutka, F., 135 Dutkiewicz, J., 253 Dvoinishnikova, T. A., 100, 120, 131, 275, 280 Dwek, R. A., 262 Dyachek, L. K., 267 D’vakov. V. M.. 10 Dfatlova, N. M:, 269 Dyer, R., 272 Dyllick-Brenzinger, R., 61

295

Author Index Dymova, S. F., 21, 28, 110, 112 Dzidovskaya, L. M., 123 Ealick, S. E., 21, 80, 275 Eargle, D. H., 92, 93 Earnshaw, C., 88 Eastland, G. W.. 92. 276 Ebenito, ‘F. F., 100 ’ Eber, S., 179 Ebert, H.-D., 91 283 Ebsworth, E. A.’V., 53, 206, 285.286 Eckeimann, D. J., 189 Eckstein, F., 183, 197 Edelmann, K., 188 Edlund, B., 166 Efraty, A., 11 Efremov. Yu. Ya.. 288 Egan, W;, 142, 150,266, 268, 284 Eger, R., 154 Eggetie, T. A., 226 Egorov, Yu. P., 244, 245, 268,286 Eguchi, S., 213 Ehrenberg, A,, 262 El Borgi, A., 279 El-Deek. M.. 75 El-Kateb. A.‘ A.. 98 Elker, M:, 284 . El’natanov, Yu. I., 285 Elson, I. H., 277 Emel’yanova, 0. N., 112 Emoto, S., 227 Empsall, H. D., 2, 8 Emsley, J. W., 232 Endo, R., 219 Engalbert, R., 284 Engel J. D., 200 Engel: R., 156, 173, 227 Engelhardt, G., 50 Engels, J., 177, 284 England, T. E., 197 Engler, D. A., 208 Engler, E. M., 106 Engstrom, E. L., 166 Epstein, A. J., 106 Erastov. 0. A.. 267 Eriksson, L. E:, 262 Ermolin, S. V., 171 Emst, L., 273 Escudie, J., 271 Eskola, S., 213 Eto, M., 121 Eto, T., 137 Evangelidou-Tsolis, E., 191 Evans, D. A., 41, 77, 99 Evans, F. E., 151 Evans, M. J., 186 Evans, S., 209 Evans, T. L.,257 Evin, G., 25 Ezra, F. S., 176 Falvello, L., 283 Fan, S., 201 Farnung, K., 185 Farnung W., 222 Fasman,’G. D., 166 Fastenakel, D., 269 Faucher, J.-P., 248, 276 Fazakerley, G. V., 34, 113, 263 Fazliev, D. F., 278

Federov, S. G., 249, 258 Fedin, E. I., 1 Fedorov, A. A., 1 Fedorova, G. IS.,149 Fedorova, L. F., 141 Feeney, J., 201 Fehr, S., 185 Feigenson, G. W., 263 Fekete, T. M., 245 Felcht, U., 234 Feldman, C., 291 Feldt, Ch., 108, 234, 264 Felsenfeld, G., 186 Fenselau, C., 126, 289 Ferro, A. M., 202 Feshchenko, N. G., 53 Feshin, V. P., 276 Fick. H. G.. 8 Fields, S., 198 Fiers, W., 198 199 Fild, M., 2 2i8 Finch, L. R., 203 Findlay, J. B., 34, 136 Finet, J. P., 222 Finkelstein, J., 210 Fiorini, M., 9 Fischer, G. W., 134, 148 Fischer, R., 10, 271 Fisher, A. P., 106 Fisher, C., 3 Fisher, R., 65 Flindt, E. P., 256, 265 Flodgaard, H., 184 Florentiev, V. L., 171, 172 Fluck, E., 21, 47, 61, 236, 246,250 Flynn, R. M., 95 Fokin, A. V., 265 Fomma, R. G., 258 Fookes, C. J. R., 112 Forner. T.. 280 Forrest, B.’J., 263 Fortuniak, W., 122 FOSS, V. L., 63, 80, 237, 272, 273 Fothergill, J. E., 198 Foulon, M., 282 Fouse, G. W., 278 Fraenkel-Conrat, H., 200 Frank. A. W.. 23. 27 Frank; J., 135 ‘ Franke, G. Th., 213 Franko-Filipasic, B. R., 258 Fraser, T.. E., 206, 285, 286 Fraser-Reid, B., 227 Freist, W., 187 Freitag, H., 162 Frenkel. M. M.. 147 Frenzeli J., 151 . Frey, P. A., 183 Fridland, S. V., 57 Friedmann, 0. M., 126 Friedmann, T., 198 Friedrich, P., 27, 110 Friedrich, W., 49 Fritz, G., 6 Fritz, H.-J., 194 Fritz, R. H., 194 Froeyen, P., 266 Fruchey, 0. S., 13, 71 Fryzuk, M. D., 3 Fuchita, T., 61 Fuchs, P. L., 20 Fueller, H. J., 205, 233, 247, 267

Fujii, K., 166 Fujino, S., 32 Fujita, T., 166 Fukuda, M., 272 Fukuhara, K., 291 Fukui, K., 8, 16 Fukui, T., 154, 196 Fukumoto, R., 197 Fukuto, T. R., 149, 283 Fuller, C. W., 178 Fuller, T. J., 256 Furin, G. G., 97 Furuichi, Y., 181 Furthmayr, H., 263 Gabriel, M., 262 Gadek, T., 194 Gadian, D. G., 262 Gadzhiev, G. G., 143 Gaidamaka, S. N., 238, 268, 276 Gainullina, R. G., 27, 265 Gait, M. J., 194 Gajda T., 121 GaldeLki. Z., 91. 150, 282, 283, 284 . Galkm, V. T., 290 Gallagher, M. J., 111, 112, 118.264 Cali&. J. C., 34. 269 Galy, J:, 284. Gamper, H. B., 177 Gancarz, R., 100, 131 Ganina, 0. N., 136 Gardner, B. C., 258 Gardner, J. H., 163 Gareev, R. D., 47, 96, 147, 236. 275 Garliik, P. B., 262 Garner, A. Y..232 Garriques, B.,-33, 41 Garrison, P. J., 21 1 Garssen, G. J., 202, 263 Gasser, O., 205, 267, 286 Gatehouse, J. A., 162 Gatilov, Yu. F., 71, 84 Gaudiano, G., 20, 216 Gavicchio, G., 216 Gawrisch, K., 263 Gazizov, M. B., 61 Gazizov, T. Kh., 59, 61, 98 Gazzola, C., 127, 273 Geahlen. R. L.. 188 Gefter, E. L., 136 Gehlert, P., 249 Geiger, P. J., 291 Gel’fond. A. S.. 286 Gellatly,’B. J., 94 Genies, M., 10 Genkina, G. K., 31, 140 Gentili. P.. 174 Geoffroy, M., 277 Gerber, A. H., 257 Germa, H., 120 Gettins. P.. 262 Gheorghiu; C., 255 Ghera, E., 208 Gibson, D. R., 162 Gibson. J. A.. 36. 37, 57, 67, 270, 274,285 ’ Gibson, M. L., 94 Gibson, Q. H., 168 Giese, B., 206 Gilbert, W., 198 Giles, R. G. F., 57 ~

296 Gillum, A. M., 199 Gilyarov, V. A., 38,237,243, 272 Gcmeno, J., 259 Ginet, L., 277 Giniyatullin, R. S., 290 Giniyatullina, M. A,, 119, 149 Giongo, M., 9 Girshovich, A. S., 188 Gival, D., 198 Glassel, W., 238 Glaser, E., 43, 97 Glemser, O., 247, 250, 251 Glidewell, C., 63, 80, 116, 263 Gloede, J., 50, 86 Glonek, T., 152, 180,263 Glowiak, T., 102, 283 Glowka, M. L., 91, 150,282, 283, 284 Gloyna, D., 275 Glukhikh, V. I., 73, 74, 128, 143.276 G$nn,P., 151 Goel, R. G., 19 Goeldner, R.,263 Goetz, H., 280 Gortz, H.-H., 194 Goff. S. D.. 288 Gogte, V. N.,78 Goldberg, I. H., 200 Goldfarb, E. I., 267,276 Gol'dm. G. S.. 249.258 Golding, B. T', 14,'207 Goldschmidt, J. M., 249 Gol'dshfein, I. P., 290 Goldwhite. H.. 16 Gololobov, Yu. G., 57, 150, 234,275 Gombler, W., 63 Gorbatenko, Zh. K., 53 Gordy, W., 278 Gorecka. A.. 121 Gorenstein, D. G., 34, 136 Gorokhovskaya, I. V., 138 Gosczvnska. Z.. 138 Gottich, B. P., '171 Gozman, I. P., 276, 277 Grace, D. S. B., 45, 276 Grachev. M. K.. 272 Gracy, R. W., 162, 165 Gramstad, T., 280 Grandjean, J., 115 Grange, D. K., 159 Granot, J., 201 Granoth, I., 9, 17, 89, 265 Grasdalen, H., 262 Grathwohl, C., 263 Graves, D. J., 163 Graves, G. E., 11 Gray, G. A., 267 Grayson, J. I., 87, 88 Grecu, R., 290 Greengard, P., 165 Gregoli, S., 278 Griend, L. V., 50 Griest, W. H., 291 Griffin, M. G., 278 Griffin, R. G., 151,263 Griffiths, D. E., 161, 162 Grikina, 0. E., 285 Grim, S. O., 8, 264, 265 Grinblat, M. P., 253, 290 Grinter, R., 275

Author Index Grishin, N. N., 288 Groen, M. B., 210 Gronenborn, B., 200 Groner, P., 278 Gross, B., 13, 26 Gross, H., 20, 50, 86 Grosse, W., 237 Gruender, W., 263 Gruk, M. P., 41 Gruner, C., 5 , 264 Grunwald, J., 152 Grutzner, J. B., 151 Grynkiewicz, G., 15 Grzejszczak, S., 220, 268 Grzeskowiak, K., 192, 263 Gubaidullin, R. N., 286 Giinther, M., 98, 129, 158, 283 Guerrero, A., 222 Guillerm, D., 2, 52 Guilley, H., 198 Gulyaev, N. N., 173 Gulyaeva, V. I., 197 Gumport, R. I., 197 Gumz, J. P. 117 Gunar, V. I., 275 Gunduz, N., 14 Gupta, B. G. B., 14, 73 Gupta, C. K., 214 Gupta, C. M., 159 Gupta, K. C., 214 Gupta, R. C., 198 Gupta, R. K., 151, 200 Gurevich, A. Z.. 173 Gurevich; P. A.; 59, 78, 88 Gurkova, S. N., 281 Gur'yanova, E. N., 286,290 Guschl. R. J.. 258 Guschlbauer; W., 202 Gusev, A. I., 281 Gusev, Yu. K., 288 Gustova, I. V., 274 Gutekunst, G., 65 Gutensohn, W., 189 Guthrie, J. P., 36, 136 Guttman, N. A., 289 Guy, J. J., 260 Guynn, R. W., 203 Guyot, A., 4 Gyul'akhmedov, L. M., 143

H aake, P., 136 H aberkorn, R. A., 151, 263 H agele, G., 36, 68, 97, 149, 198,273,275 ager, D. C., 82 ager, W., 242,272 ahn, J., 5 aines. R. J.. 34. 57. 113 aley, 'B. E.,'188 all, C. D., 18, 272, 274 all, C. R., 83, 121, 124, 142 H all. D.. 232 H all; D.'O., 162 H all, M. J., 160 H aller, R., 45, 243, 267 H alpern, J., 16 H alstenberg, M., 38,239,272 H amana, H., 32 H ammerschmidt, F., 24 H ammes, G. 0.. 201 H ammond, P. J:, 18, 274 H ampton, A., 180 H ansch, C., 172 H anzawa, Y.,32

Harger, D. C., 5 Harger, M. J. P., 149, 271 Hargis, J. H., 270, 281 Harris, G. S.,71, 84 Harris, R. K., 36, 69, 150, 271,273,274 Harrison, J. M., 121 Hart, P. A., 201 Hartan, H., 280 Hartman, F. C., 162, 163 Hartung, H., 282 Hashizume, A., 99, 223 Hassal, C. H., 160 Haszeldine, R. N., 6, 18 Hata, T., 99, 102, 103, 128, 173, 174, 193, 223 Hatano, H., 202, 263, 268, 278

Hitieganu, E., 291 Haubold, W., 236, 246 Haupt, H. J., 93, 282 Hauser. A.. 280 Havens, J. L 40 Hayaishi, 0.1'166 Hayashi, F., 268 Hayashi, M., 135 Hayashi, T., 256 Hayes, D. M., 284 Hazell, A. C., 281 Hazell, R. G., 281 Heathcock, C. H., 129, 218 Heaton, G. M., 188 Heckman, J. E., 199 Hehemann, D., 8, 57, 84 Heider, W., 247, 251 Heinemeyer, E. A., 185 Heinze, J., 2 Hellmann, J., 5 , 264 Hellwinkel, D., 40, 82, 289 Helms,. D. A., 278 Hemming, F. W., 159 Henderson. T. 0.. 262 Henichart,'J. P., 282 Henjes, H., 11 Henkel, M., 73, 232 Henning, H. G., 275, 280 Henriksen, L., 11 Herman, M. A., 279 Herr. W.. 199 Herscovics, A., 159 Herzfeld, J., 151, 263 Hess, H., 63, 108, 283 Hewson, M. J. C., 36, 69, 27 1 Heydt, H., 86 Heys, P. N., 2 Hickey, M. E., 166 Hieke, K., 277 Hietkamp, S., 19 Higa, M. T., 144 Higginbotham, E., 257 Hilbers, C. W., 202, 263 Hlld, J., 291 Hilstrom, W. W., 100 Hilz. H.. 179 Hirakawa, S., 258 Hirano Y 22 Hishin&;' F 197 Hitchcock,'P.,''284 Hobbs, J. B., 183 Hocker, J., 97 Hodgson, P. K. G., 45 Hockel. M.. 189 Hoehne, M:, 263 Hoehne, S., 91, 283

Author Index H[olderich, W., 6, 18 H[offmann, R., 34 Hjoffmann, W., 21 1 H.ofmann, A., 263 Hroftiezer, J., 284 H‘ogan, J. J., 199 H‘ogarth, D., 29 H’oge, B., 251 H‘ohorst, H. J., 289 H:ojer, G., 248 H‘olah, D. G.. 28, 29 H olden, K. G., 210 H 011, P., 39, 40, 243, 269 H ollis, D. P., 262 H olmes, R. R., 34, 36, 269, 284 H olmes, S. W., 160 H olmes, T. J., 106 H olupirek, M., 194 H olweger, W., 131 H onegger, H., 111, 112, 118, 264 H opkins, H. P., 31, 279 H oppe, J., 175, 179 H orio, T., 166 H orner, L., 9, 24 H oualla, D., 43, 268, 269 H oussin, R., 282 H ovanessian, A. G., 185 H owe, R. L., 291 H owell, J. M., 34 H oz, s., 97 H suing, H. M., 193 H u, A., 151, 201 H uang, C., 262 H uang, G.-F., 172 H uang, R. C. C., 183 H uang, T. H., 278 H uber, F., 93 H uber, J. W., tert., 102, 132, H uberman, J. A., 186 H udson, C. W., 5 H udson, R. F., 116 H uebner. M.. 16 Hughes, A. N., 28,29 Hui, B. C., 29 Hulla, F. W., 189 Hullar, T. L., 95, 144 Hunt. T.. 185 Hunt; W:, 164 Hupe, D. J., 164 Hurst, K. M., 41, 77, 99 Hurter, J., 291 Hussain, M. S 205 267 Hutchinson, D: W.,’181 Hutley, B. G., 23, 83, 149, 265 Huttner, G., 27,110 Hyams, R. L., 161, 162 Hyde, E. M., 2, 8 Hynie, S., 177, 184 Ibers, J. A., 19 Ichiba, M., 218 Ide, J., 219 Iedema, A.. 252 Ignat’ev, V: M., 130, 143 Ignat’eva, S. N., 267 Ignatova, N. P., 28,109, 110, 232 Ihara, Y., 136 Iio, M., 121 Ikehara, M., 172, 192, 196, 197 Ikeno, M., 99

297 Illger. W.. 86. 131 Il’yasov, A. V., 25, 277, 287 Imai, H., 3 Imaida, M., 225 Immirzi. A.. 19 Imoto, T., 263 Inaba, M., 106, 116 Inagaki, F., 268 Inamoto, N., 98, 224 Inch, T. D., 121, 124, 142 Indzhikyan, M. G., 23, 24, 27 Tndzhikyan, M. H., 21 Inokawa, S., 76, 205, 275 Inoue, H., 255 Inoue. T., 258 Ionin,’B. I., 78, 93, 130, 143, 268,289 Ionov, L. B., 84 Iordanov. N.. 93 Ireson, J.>C.,‘227 Iriskina, L. B., 63 Isaev, V. L., 141 Ishikawa, K., 98, 224 Ishmaeva, E. A., 138, 287 Islamov, R. G., 280 Ismagilova, N. M., 59, 78 Ismailov, V. M., 143 Isome, Y., 258 Issleib, K., 5,7, 17,28 Ito, T. I., 247 Ivanov, B. A., 149 Ivanov, P. Yu., 1, 289 Ivanov, V. F., 1 Ivanova, N. P., 30 Ivanova, Zh. M., 150, 275 Iwahori, S., 93 Iwamoto, M., 226 Iwata, T., 125, 126 Izawa, Y., 22 Izmailova, Z. M., 71, 84 Jacob, E. J., 92, 286 Jacob, K., 291 Jacob, S. T., 186 Jacobine, A. F., 220 Jacobson, G. R., 179 Jacobus, J., 159 Jacobus, W. E., 262 Jaffe, E. K., 201 262 Jagdale, M. H., i 3 6 Jagodic, V., 278 Jahn, H., 189 Jain, R. S., 270 Jakobsen, H. J., 273 Jameson, J. L., 184 Janczura, E., 159 Jankowski, A., 191 Janta, R., 112 Jardine, I., 289 Jarvis, B. B., 14 Jasperse, J. L., 22 Jastorff, B., 170 Jay, E., 193 Jeanloz, R. W.. 159 Jeck, R:, 152 . Jefford, C. W., 214 Jelus. B. L.. 288 Jennhgs, Mi. B., 270 Jentzsch, R., 134 Jernstedt, K. K., 137 John, A. M., 5 Johncock, P., 14 Johnson, A. W., 105 Johnson, D. F., 263

Johnson, D. K., 6 Johnson, E. M., 166 Johnson, M.W., 199 Johnson, N. A., 114 Johnson, R. A., 184 Johnson, R. D., 154 Johnson, W. L., 13, 71 Johnsson, S., 93 Johnston, R., 161, 182 Jolly, W. L., 248 Jones, P. G., 283 Jones, R. A., 194 Jones, S. R., 124, 169 Jones, T. R. B., 288 Joniaux, D., 54, 76 Jore, D., 2, 52 Joshi, A.. 195 Joussen, R., 5, 84 Juds, H., 280 Junius, M., 45, 110, 249 Juodka, J., 177 Kabachnik M.1 19 31 38, 93, 133, i40,2?7, i43,!271 272 276,279,286 287,296 Kadeibach. B.. 1 6 i Kainosho, M.,’152, 177, 275 Kaiser, J., 282 Kajita, H., 218 Kajiwara, M., 248, 250, 253, 257 Kakeya, 8, 73, 84 Kakiuchi, N., 196 Kalabina, A. V., 276 Kal’chenko, V. I., 270 Kalenskaya, A. I., 236 Kalibabchuk, N. N., 93,244, 267 Kalinichenko, E. N., 172 Kalinin, A. E., 34, 285 Kalyanova, R. M., 31, 140 Kamamura, K., 257 Kametani, M., 258 Kametani, T., 100 Kametani, Y., 258 Kan, M. N., 289 Kanaoka, Y.,174 Kandel, J., 153 Kaneko, M., 172 Kanomori. Y., 218 Kanter, HI, 280 Kao, J. T. F., 245 Kaplan, N. O., 151, 179 Kapoor, P. N., 4 Kappen, L. S., 200 Karelov. A. A.. 98 Karle, D. W., 247 Karle, I. L., 150, 284 Karle, J. M., 150, 284 Karolak-Woiciechowska., J.., 284 Karp, F., 167 Karpeisky, M. Ya., 173 Karsch. H. H.. 5 Kartasheva, N: A., 93 Kasheva, T. N., 47, 69 Kashina, N. V., 138 Kashman, Y., 54, 76 Kaskin, B. A., 21 Kato, M., 173, 175 Kato, Y., 223 Katolichenko. V. I.. 288 Katsyuba, S. A., 278 Katz R., 263 Kauffmann, T., 5 , 84

Author Index

298 Kaufman, J., 247 Kawabata, N., 248 Kawai, A., 258 Kawasaki, T., 14, 71, 233 Kawase,T., 100, 106,116 Kawashima, E., 194 Kawashima, T., 125 Kayashi, K., 226 Kazakova. N. D.. 47.63 Kazankova, M. A., 57 Keat, R. 16, 83, 107, 108, 252, 264, 267, 270, 272, 276 Kedzia, B. B., 278 Kees, F., 31 . Keith, A. N., 108 Keitsher, H. P., 263 Keldsen. G. L.. 11 Kellner,’K., 9 ‘ Kemp, A., jun., 188 Kendurkar, P. S., 214, 224 Kennard, O., 283 Kenyon, G. L., 92, 93, 127, 273 Kerfanto, M., 11 Kerr, A. K. A., 159 Kerr, I. M., 185 Kerr, K. A., 9 1, 282 Kesner, L., 256 Kessel, A. Ya., 279 Kessler, W., 179 Khachatryan, R. A., 23, 24 Khaikin, L. S., 285 Khalep, B. P., 278 Khalimskaya, L. M., 194 Khammatova, 2. K., 147 Kharabaev, N. N., 244 Kharlamov, V. A., 59,61,98 Khaskin, B. A., 21, 133, 139 Khil’ko, M. Ya., 150, 274 Khodak, A. A., 243, 272 Khomutov, R. M., 171 Khorana, H. G., 159, 194 Khropov, Y. V., 173 Khusainova, N. G., 85, 147 K!bardin, A. M., 98 Kiel, W. A,, 139 Kielbasinski, P., 138 Kierzek, R., 192, 263 Kikuchi, Y., 197 Killedar, A. V., 136 Kim, C. S., 209 Kim, S.-K., 200 Kimura. M.. 172 Kimura; Y.,’16,105 Kinas, R., 150,284 Kjndscherowsky, P., 233,237 King, H. L., Jun., 166 King. K. G.. 136 King; R. B.,’259 Kingsley, P. B., 263 Kinoshita, M., 135,289 Kinovan. F. S.. 24 Kirmaier, H., 235 Kirpichnikov, M. P., 171 Kirsanov, A. V., 53 Kisilenko, A. A., 286 Kita, J., 8, 16 Kita, Y., 14, 71, 233 Klaebe, A., 267 Klaui, W., 118 Klaska, K. H., 177, 284 Klaus, M. J., 228 Klebach, T. C., 31 Klebanskii, A. L., 253, 290

Kleemola, D., 28 Klein, M. P., 263 Kleppe, K., 197 Kleps, R. A., 180 Kleschick, W. A,, 129, 218 Klimov, Yu. A., 73, 143 Klingebiel, U., 107 Kloth, B., 5 , 10, 16,264,272 Kluger, R., 163 Knoll, F., 12, 38, 239 Knolle, J., 228 Knorre, D. G., 194, 195 Knowles. F. C.. 168 Knowles; J. R., 124,162, 165, 169, 179, 188 Knowles, W. S., 9 Knunyants, I. L., 141 Kobayashi, S., 105 Kobayashi, Y., 32, 121, 149 Kobets, N. D., 195 Koch, C. W., 92 Koch, D., 5 , 10, 16, 264, 271. 272 Kocheshkov. K. A,. 280. 286,290 Kochetkov, N. K., 113, 157, 171 Kodolov, V. I., 281 39. 206,269. Koehler, F. H.,~, . 270 Komives, T., 135 Konig, B., 103, 134, 219 Kohrle. J.. 180 Koenig, M.,33, 50 Koeppel, H., 275,280 Koerner, T. W., jun., 156 Kogami, K., 226 Kogan, V. A., 244 Kohler, S. J., 263 Kohut, J., tert., 171 Koizumi, T., 121, 137, 149 Kok, R. A., 125 Kolb. B., 291 Kolbe, A,, 279 Kolbe, H., 162 Kolbina, V. E., 73, 143 Kolesova. V. A.. 289 Kolich, C. H., 249, 258 Kollman, P. A., 284 Kolodii, Ya. I., 123 Kolodny, N. H., 263 Kolodyazhnyi, 0. I., 13, 88, 204 Kolotilo, N. V., 246 Kolubushkina, L. I., 172 Komarova, M. P., 279 Kominami, S., 278 Kondratenko, V. I., 237 Kondratev, Yu. A., 112 Kondratov, 0. I., 278 Konieczny, M., 123, 141 Konishi, T., 174 Konovalov, A. I., 85, 147 Konovalov, E. V., 268 Konovalova, I. V., 100, 120, 131, 147, 148, 275 Konstantinova. M.. 93 Koole, N. J., 276 ‘ Kopf, J., 98, 129, 158, 283 Kormachev. V. V.. 136 Kornuta, P.’ P., 236, 246 Koroleva, G. E., 278 Koroteev, M. P., 113, 157 Korovaikov, V. A., 269 Korovyakov, A. P., 84 ~~

~

Korshak, V. V., 257 Koskinen, A. L., 213 Kossa, W. C., 249 Kost, A. A., 171 Kostyanovzkii, R. G., 285 Kosydar, K. M., 256 Kotowycz, G., 263 Kotynski, A., 160 Kouba, J. K., 3 Koutcher, J. A., 262 Kovaks, J., 13 237 Koval, V. G., 278, 279 Kovalenko, V. I., 59 Kovalev, V. A., 130 Kovaleva, T. V., 53 Kowalik, J., 102 Koyama, A. H., 278 Kozlov, E. S., 10, 82, 238, 276 Kozlov, I. A., 189 Kozlov, Yu. P., 275 Kraemer, R., 120, 286 Krakow, J. S., 187 Kramer, C. E., 257 Krapp, W., 40, 82, 289 Kraszewski, A,, 192, 263 Kratzer, R. H., 247, 255 Kravtsov, D. N., 1 Krayevsky, A. A., 171, 195 Krebs, B., 258 Krech, F., 5 Kreuger, C., 93 Krief, A., 216 Krietsch, H., 179 Krietsch, W. K. G., 179 Krishna Bhandary, K., 261 Krishnamurthv, S. S., 249.

Krueger, C., 282 Kriiger, W., 2 Kryukov, L. N., 141 Kryukova, L. Yu., 141 Kucheruk, L. V., 290 Kudryavtseva, L. A., 149 Kudyakov, N. M., 10 Kudzin. Z. H.. 132 Kuehlein, K., 226 Kui, Y.T. Y., 191 Kuisman, H. O., 226 Kukhanova, M. K., 171 98,. Kukhar, V. P.,. 47, 69, . 204 Kukhmisterov, P. L., 63, 80, 272 Kukhtin, V. A., 133, 136 Kulys, J., 177 Kumada, Y.,218 Kumadaki, I., 32 Kumar. S. A., 187 Kumari, N., 224 Kung, W., 177 Kung, W. J., 275 Kuntz. G. W. K., 179 Kunz,’H., 25 . Kuprina, Zh. S., 237 Kuramashin, I. Ya., 287 Kurbatov, V. A., 189 Kurono, M., 226 Kurshova, N. A., 40 Kurtskhalia, T. V., 188

~

299

Author Index Kushnir, V. N., 21, 133, 206, 212 Kusmierek, J. T., 200 Kuts, V. S., 267 Kutyrev, G. A., 138 Kuzina, N. G., 78 Kvasyuk, E. I., 172 Kwart, H., 136 Kyba, E. P., 5 , 34 Kyuntsel, I. A., 238, 276 Labanov, 0. P., 130 Labarre, J. F., 248, 276 Labaw, C. S., 209 Labintsev. V. B.. 288 Lad, P. Mi.. 184‘ Lafaille, L.; 19, 34 Lafont, D., 3 Lagutkina, E. G., 257 La John. L.. 154 Lam, Y.’F.,’263 Lambert, J. B., 287 Lambert, R. W., 160 Landau, M. A., 265 Landis, M. E., 41 Landt, M., 163 Langdon, R. G., 263 Langford, D. D., 135 Lannom, R. A., 179 Lanquin, G. J. M., 188 Laos, I., 135 Lapidot, Y., 172, 173 Lapp, E., 5 Larcher, D., 262 Lardy H. A., 154 LarioGova, L. A., 73, 128 Laskorin, B. N., 280 Laszkiewicz, B., 253, 257 Laszlo, P., 115 Latimer, L. H., 212 Lattman, M., 281 Laurence, C., 146 Lavayssiere, H., 43, 59 Lavielle, G., 222 Lavrenyuk, T. Ya., 268 Lawesson, S. O., 139, 140 Lawley, P. D., 200 Lawson, H. F., 270 Layne, E. C., 291 Lazzaroni, R., 1 Leader, H., 17, 89 Lebedev, A. V., 194,263 Lebedev, E. P., 10 Leckie, M. P., 185 Leclercq, P. A., 288 Lednor, P. W., 8 Lee. C. H.. 263 Lee; J. B.,’227 Lee, J. D., 82 Lee, P. W., 149, 283 Lee. R. C.. 63, 270 Lee; S. 0.; 1, 92, 266 Lee, S. P., 140 Leelavathi, D. E., 203 Lees, R.-G., 194 Le Gras, P. G., 272 Lehikoinen, U. A., 258 Lehle, L., 159 Lehmann, V.. 151 Lehninger, A: L., 162 Leimontaite, R., 177 Leissring, E., 6 Leneker, K. L., 63 Lenssen, U., 289 Leonard, N. J., 188

Leont’eva, T. N., 138 Leplawy, M., 121 Leseicki, H., 91 Lesiak, K., 122 Lesiecki, H., 283 Levin, R. H., 134 Levin, Ya. A., 277 Levin, Yu. A., 276 Levy, H. M., 182 Lewis, E. S., 21, 25, 95, 96, 265 Lex, J., 282 Leznoff, C. C., 229 Li, Y. S., 278,280 Liebl, R., 7 Lien. W. S.. 16 Light. R. W.. 109 LiK, C.-c., 21 Lin, G. H. Y., 149,283 Lin, M. C., 184 Lindner. E.. 91. 117. 283 Linies, A., 226 ‘ Linke, K. H., 6 Liorancaite, L., 177 Liorber, B. G., 146, 147, 277 Lipatova, I. P., 279 Lippard, S. J., 198 Ljttlefield, L. B., 47, 69 Litvinenko, L. M., 141 Liu, F.-T., 188 Liu, H. J., 140 Liu, M. Y., 173 Llinas, J. R., 264 Llor, J., 288 Lockard, R. E., 199 Loginova, G. M., 47, 96 Lohrmann, R., 171, 195 Loibner, H., 15 Loktionova, R. A., 57 Lombardo, L., 225 Londos, C., 184 Longmuir, K. J., 263 Lopez, L.,.106, 120, 276 Lopusinski, A., 134 Lorenz. K.. 1, 78 Lown, 3. W.,’200 Luber, J., 27, 37, 69, 110,245 Lucken, E. A. C., 277 Luckenbach. R., 1, 78,271 Luczak, J., 80 . . Ludeman, S. M., 142,266 Ludger, E., 169 Ludwig, B., 229 Lustorff, J., 162, 187 Lukashev, N. V., 80, 272 Lukevics, O., 287 Lukszo. J.. 102 Lulukyan,’R. K., 21 Lunardi, J., 188 Lutsenko, T. F., 52, 57, 63, 80. 95. 237. 267. 272. 273 Luxon, B. A.‘, 34,-136 L‘vova, J. D., 275 Lythgoe, B., 225 Lyubman, Ts. A., 47 ’

Maas, G., 86, 131 McClure, W. R., 154 McComas, W. W., 194 McConnell, M. L., 53 MacCoss, M., 176, 268 McDonald, E., 184 Macdonell, G. D., 21,75, 80 McEwan, W. E., 282 McFarlane, W., 272

MacGee, J., 199 Mach, W., 280 McIntosh, J. M., 20, 210 Mack, D. P., 256 Mack, I. M., 71, 84 McKechnie, J. S., 71, 84 McKenna, C. E., 144 McKenna, M. C., 144 McLauchlin, A. C., 263 McMurry, J. E., 211 Macomber, R. S., 59, 144, 145 McPhaul, M. J., 5 Macphee, A., 108 Macphee, J. A., 140 McQuillan, G. P., 92, 279 McReynolds, L., 198 McVicker, E. M., 273 Madan, 0. P., 157, 284 Maeda, H., 178 Maeda, M., 180 Maeda, T., 278 Magallona, E. D., 291 Magid, R. M., 13, 71 Magill, J. H., 258 Magnusson, A. B., 257 Mahendron, M., 105 Mahta, P., 268 Maijs, L., 287 Majoral, J. P., 120 Makarenko, I. M., 291 Makhtarov. A. Sh., 277 Makihara, M., 250 Makino, I., 125, 126 Malakhova, J. G., 286 Malavaud, C., 34, 111 Mali, R. S., 208 Malinauskas, A., 177 Malisch, W., 112 Malkes, L. Y., 208 Mal’kevich, N. Yu., 9, 91 Malovik, V. V., 93 Malpass, D. B., 8 Manchanda, V. K., 93 Mankowski, T., 159 Manohar, H., 260, 261 Manser, M., 291 Maracek, J. F., 157 Marcati, F., 9 Marchesi, V. T., 263 Marchetti, V., 20, 216 Marck, C., 202 Marconi, W., 9 Marecek, J. F., 33, 34, 123, 135, 141, 191, 266, 284, 285 Mareev, Yu. M., 47, 100, 269 Mareva, S., 93 Margalit, Y., 136, 272 Marien. B. A., 14 Maringgele, W., 241 Marker, A., 263 Markham, A. F., 197 Markiewiez, W. T., 192, 263 Markl, G.,.7, 31, 209 Markovskii, L. N., 10,82 97, 246 Markowska, A., 138 Marmer, R. S., 129 Maroney, P. A., 185 Marov, I. N., 269 Marschner, F., 280 Marsh, D., 263 Marsh, R. E., 177, 275 9

Author Index

300 Marshall, J. L., 220 Marshall, W. E., 262 Marsi, K. L., 22 Marsmann. H. C.. 265 Martell, A; E., 154 Martin, R. B., 263 Martin, S. F., 21 I , 222 Martin, T. W., 291 Martinez. J.. 248 Martin Polo, F., 248 Martinsen, A., 244 Marton, A. F., 135 Marx, A., 5 Masaki, M., 8, 16, 73, 84 Masaki, S., 186 Mashlyakovskii, L. N., 78 Mason, J., 248, 267 Mason, R., 284 Massy-Westropp, R. A., 215 Mastalerz, P., 102, 132 Mastryukova, T. A., 31, 133, 140,149 Masud, S. Z., 291 Masuda, T., 3 Mathey, F., 9, 28,29, 84,91, 145,263,288 Mathis, F., 19, 34, 111, 279, 284. Mathis, R., 279 Matrosov, E. I., 147, 279, 287 Matschiner, H., 121 Matsui, S.. 202 263 Matsumoto J ’16 125,126 Matsumoto’ Matsumura’ K’ 256 Matsushimi T.: 202 Matthews W. A., 135 Matthies, M.,202 Maxam, A. M., 198 Medda, P. K., 5,271 Medici, A., 248 Medved’, T. Ya 93 279,290 Medvedeva, M.”D.,’ 141 Medwid, A. R., 285 Meehan, G. V., 13 Meers, P. R., 263 Meijer, J., 3 Meiners, J. H., 2 Meister, A., 156 Meller, A., 107, 241 Mellor, M. T. J., 83, 149, 265 Mel’nichuk, E. A., 53 Mel’nik, S. Ya., 173 Mel’nik, Ya, I., 123 Mel’nikov, N. N., 21, 28, 109,110,133,139, 232 Menchen, S. M., 139 Mendel, J., 279 Mengel, R., 175 Mentzer, E., 2 Meredith, P. L., 258 Merrifield, R. B., 166 Merten, R., 97 Mervjc, M., 208 Messing, J., 200 Messmer, A., 13, 237 Meszaros, Z., 135 Metelev, V. G., 199 Meyer, B., 274 Mever. H.. 28 Meyer; H.‘J., 140 Meyers, A. I., 223 Mhala, M. M., 136 Michaels, G., 166

s”

Michalska, M., 138, 157 Michalski, J., 42, 91, 122, 133,134,138,157,282 Middlebrooks, M., 102, 132 Middlemas, E. C., 75 Midura, W., 220, 268 Miftakhove, A. K., 93 Mikes, F., 142 Mikhailopulo, 1. A., 172 Mikolajczak, J., 42, 80, 122, 138,220,268 Milbrath, D. S., 93, 115 Mildvan, A. S., 151, 200 Milgrom, Y. M., 189 Milker, R., 69, 81, 242, 272 Miller, J. A., 78, 89, 99, 102, 273 Miller, J. M., 288 Miller, R. E., 56,76 Miller, S. I., 26,217 Millington, D., 83 Milner, Y., 166 Mimura, K., 258 Minami, S., 16 Minami, T., 218 Minks, M. A., 185 Minoura, Y., 63 Mironova, Z. N., 93 Misener, B. S., 91, 282 Mishenina, G. F., 195 Mitchell, J. D., 8 Mitsuda, Y., 289 Mitsumura, K., 258 Mitzner, R., 286 Miwa, M., 202 Miyake, T., 192 Miyamoto, T., 16, 139 Miyatake, K., 174 Miyazawa, T., 268 Mizuno, Y., 137 Mochel, V. D., 253 Modro, T. A., 266 M:m!ritzer, K., 56, 76, 92, L / L

M oeller, T., 254, 255

M ohomed, R. S., 258 M okeeva, V. A., 238, 276 M olodtsov, S. S., 84 M omii, R., 34, 136 M onneron, A., 184 M ontag, R. A., 281 M ontemayor, R. G., 19 M ontenarh, M., 273 M orait, G., 278 M orbach. W.. 12 Moreau, ‘M., 274 Mori, H., 99 Mori, Y., 253 Morin, F. G., 274, 283 Morita, N., 26, 217 Morita, T., 144 Morkovin, N. V., 268 Morowitz. H. J.. 262 M orozov,-V. I., ’25, 287 M orr, M., 169, 175 Morris, D. G., 266 M orton, W. T., 291 M osbo, J. A., 264, 268 Moses, R. E., 200 Mosher, H. S., 3 Moskalevskaya, L. S., 149 M oskovitz, B. R., 166 Moskva, V. V., 143 M oss, G. P., 229 M ossoyan, J., 268

M ostafin, D. I., 278 M ostecky, J., 291 M otoki, S., 217 M oucheich, T., 268 M ucklejohn, S. A., 259 M uhlradt, P. F., 151 M uetterties, E. L., 34 M uir, K. W., 108, 270 M ukai, H., 93 M ukhitova, F. K., 275 M ukhtarov, A. Sh., 277 M‘ullens, M. J., 208 M uller, G., 28 M‘umzhieva, N. G., 275 M unakata, K., 59 M unoz, A., 33, 41, 50, 267 M rurai, R., 93 M lurakami, M., 114 M [uramatsu, M., 152 M [uramatsu, S., 219 A., 19 . MUSCO, Musher, J. I., 74, 270 Musierowicz. S.. 89 Musin, R. Z.‘, 288 Musina, A. A., 27, 141, 265 Muslimov, S . A., 59, 78, 88 Myers, T. C., 180 Myles, A., 126 Naaktgeboren, A. J., 3 Nabi, S. N., 248, 276 Nainan, K. C., 31, 279 Nair, G. M., 93 Najdzionek, J., 63 Nakahama, T., 258 Nakahara, J. H., 255 Nakajima, M., 99, 223 Nakamoto, K., 278 Nakamura, A., 19 Nakamura, H., 174 Nakano, K., 154 Nakata, F., 213 Nakatsukasa, Y., 76 Nakazawa, H., 152 Nabudiry, M. E. N., 225 Narang, S. A., 192, 193 Narang, S. C., 14, 73 Narayanan, P., 34, 285 Nasirov, R., 19, 276 Nassimbeni, L. R., 34, 113 Nasyrova, F. K., 290 Natter, W. J., 278 Naumova, V. A., 65,285 Navech, J., 120,150,284,286 Navon. G.. 151.262 Navon; R.;262‘ Nazmutdinov, R. Ya., 147, 290 Neff, N. H., 153,187 Negita, H., 65 Negrebetskii, V. V., 28, 110, 112 Nehls, I., 271 Neidlein, R., 49 Neilson, R. H., 10, 63, 233, 234.270 Neimysheva, A. A., 63 Nelson, D., 277 Nelson, S. M., 5, 8 Nemethova, M., 288 Nesmeyanov, N. A., 267 Nesterov, L. V., 27, 265,279 Nesterova, N. P., 279 Neumann, J. M., 262 Neville, A. C., 263

Author Index

301

Newkome, G. R., 5,82 Newman, R. H., 274 Newton, M. G., 259 Nibler, J. W., 278 Nicholls, D. G., 188 Nicklen, S., 198 Niecke, E., 109, 238, 239, 264 Nielsen, K. E., 140 Nifant’ev, E. E., 147, 232, 272.274 Nifanpev. E. Ye.. 113. 157 Niitsu, M’., 93 Nikitin, P. A., 276 Nikitin, V. M., 150, 274 Nikitina. V. 1.. 138 Nikolaev, G. N., 287 Nikolotova, Z. I., 93 Nisbet, A. D., 198 Njsbet, L, J., 160 Nishigashi, S., 218 Nishikawa, H., 262 Nishikawa, S., 197 Nishikida, K., 114 Niwa, H., 226, 228 Nixon, J. F., 9, 280 No. B. I., 61 Noda, L.; 200 Noth, H., 241 Noller, H. F., 199 Nolte. R. J. M.. 3 Norimatsu, T., 258 Normant, J. F., 135,146,221 North, R. A., 47, 96 Nose, K., 248, 258 Noskova, M. P., 278 Notman, N., 193 Notter, R. H., 160 Novikova, A. N., 249 Novikova, L. S., 149 Novikova, Z. S., 52, 95, 272 Nowak, T., 151 Nowakowski, M., 33, 135, 266 Nowell, I. W., 30 Nowicki. T., 138 Nuhn, P., 151,263 Nunnally, R. L., 262 Nuretdinov, I. A., 119, 149 Nurrenbach, A., 228 Nurtdinov, S. Kh., 59, 78 Nussbaum, A. L., 194 Nuzzo, R. G., 8 Nyu, K., 100 I

,

Oades, A. C., 30 Oae, S., 83 Oakley, R. T., 254, 260, 261, 283 O’Brien, J. P., 252,260 O’Connor, M. S., 291 Oda, T., 225 Oehlschlager, A. C., 244 Oehme, H., 6,28 Oen, H., 196 Ofengand, J., 171 Ofitserov, E. N., 11, 102 Ogata, T., 76,205,275 Ogawa, S., 151,202 Ogilvie, K. K.. 193 Ogini, W. o., 19 Ohmura, H., 121 Ohnishi, S., 278 Ohnishi. S. T.. 291 Ohrui, H., 227

Ohtsuka, E., 192,197 Oka, J., 166 Okada, H., 152 Okamoto. Y.. 144. 148.272 Okazaki, H., ‘123, 141 ‘ Okimoto, K., 102 Okruszek, A., 17, 91, 150, 274,282 Okuda, T., 65 Okupniak, J., 192 Olah, G. A., 8, 14, 57, 73, 84 Olast, M., 278 Oleksyszyn, J., 102, 132, 160 Omachi, A., 262 O’Malley, B. W., 198 O’Mallev. M. A.. 160 O’Neil1,-I. K.. 263 Onoue,~Y.,175 Onur, G., 188 Oppenheimer, N. J., 202 Oram, R. K., 57 Orrzel. L. E.. 195 OrEin, S. H:, 186 Orlich, I., 138, 157 Oro, J., 195 Osa, A., 291 Osipenko, N. G., 80,287,290 Osipov, 0. A., 244 Osipova, M. P., 133 Osman, F. H., 43 Ostanina L. P., 61 Osuji, G.’O., 199 Oth, J. F. M., 61 Otsuka, S., 19 Ottlinger, R., 47 Otvos, L., 196 Ouali, M. S.,212 Ourisson, G., 229 Ovakimyan, M. Zh., 21, 23, 27 Ovchinnikov, V. V., 290 Ovchinnikov, Y. A., 188 Ovrutskii, V. M., 287 Oxton, I. A,, 92, 279 Paasivirta, J., 275 Paciorek, K., 235 Paciorek, K. J. L., 247, 255 Paddock, 254, 260, 261, 283 Paine, R. T., 109 Pakulski. M.. 42 Palamarczyk; G., 159 Paleg, L. G., 263 Panov. E. M.. 280 Parishchenko, A. A.. 52 Park, C., 136Parmore, D. J., 283 Parrett. F. W.. 52 Parrish; R. F.,’ 163 Parrott, M. J., 277 Parry, R. W., 53 Partis, M. D., 161, 162 Pascard, C., 150, 284 Pascard-Billy, C., 54, 76 Pasco, J. A., 291 Pashinkin. A. P.. 59. 61 Patel, A. D., 180 ‘ Patel, V. V., 106 Patlina, S. I., 147 Patterson, D. B.. 257 Patterson; P. L.,-291 Paulsen, H., 98, 129, 158,283 Paust. J.. 228 Pavlov, V. A., 146, 277 Pawanjit, 289

Pawley, G. S., 281 Pawson, B. A., 228 Pawson, D., 8 Peake, S. C., 36, 69, 271 Pedersen, B. S., 139 Pedersen, E. B., 140 Peguy, A. A., 262 Penades, S., 188 Pen’kovskii, V. V., 245 Pennings, J. F. M., 275 Perchard, C., 94 Perchonock, C. D., 210 Peregudov, A. S., 1 Perekalin, V. V., 149 Perkins, P. G., 290 Perlmutter, H. D., 211 Perregaard, J., 139, 140 Perriott, P., 146, 221 Pershan, P. S., 263 Pestunovich, V. A,, 150, 274 Peter, C., 282, 289 Peterson, G. L., 168 Petov, G. M., 287 Petriehazy, I., 107 Petrina, N. B., 21 Petrov A. A 30 40 41, 50, 130,’268, 569, ’27

Organophosphorus Chemistry

Organophosphorus Chemistry

Organophosphorus Chemistry