Chemistry of Carbon Compounds: 2nd Supplement to 2r.e v.3B, C, D

Second Supplements to the 2nd Edition of RODD' S CHEMISTRY OF CARBON COMPOUNDS Second Supplements to the 2nd Edition...

Author: Malcolm Sainsbury

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Second Supplements to the 2nd Edition of

RODD' S CHEMISTRY OF CARBON COMPOUNDS


RODD'S CHEMISTRY OF CARBON COMPOUNDS VOLUME I

ALIPHATIC COMPOUNDS ,k

VOLUME II

ALICYCLIC COMPOUNDS ~r

VOLUME III

AROMATIC COMPOUNDS ,k

VOLUME IV

HETEROCYCLIC COMPOUNDS

VOLUME V

MISCELLANEOUS GENERAL INDEX ,k


RODD'S CHEMISTRY OF CARBON COMPOUNDS A modern comprehensive treatise Edited by M A L C O L M SAINSBURY

School of Chemistry, The University of Bath, Claverton Down, Bath BA2 7AY, England Second Supplement to VOLUME III AROMATIC C O M P O U N D S Part B: Benzoquinones and Related Compounds: Derivatives of Mononuclear Benzenoid Hydrocarbons with Nuclear Substituents Attached through an Element other than the Non-metals in Groups VI and VII of the Period Table Part C: Nuclear-substituted Benzenoid Hydrocarbons with more than one Nitrogen Atom in a Substituent Group Part D: Monobenzenoid and Phenolic Aralkyl Compounds, their Derivatives and Oxidation Products" Depsides, Tannins, Lignans, Lignin and Humic Acid (Partial" Chapter 12 in this volume)

1995 ELSEVIER Amsterdam - Lausanne - New York- Oxford-Shannon-Tokyo

ELSEVIER SCIENCE B.V. Sara Burgerhartstraat 25 EO. Box 211, 1000 AE Amsterdam, The Netherlands

ISBN: 0-444-82242-9

9 1995 ELSEVIER SCIENCE B.V. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the publisher, Elsevier Science B.V., Copyright & Permissions Department, P.O. Box 521, 1000 AM Amsterdam, The Netherlands. Special regulations for readers in the U.S.A. - This publication has been registered with the Copyright Clearance Center Inc. (CCC), 222 Rosewood Drive Danvers, MA 01923. Information can be obtained from the CCC about conditions under which photocopies of parts of this publication may be made in the U.S.A. All other copyright questions, including photocopying outside of the U.S.A., should be referred to the copyright owner, Elsevier Science B.V., unless otherwise specified. No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. This book is printed on acid-free paper. Printed in The Netherlands.

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vi

Contributors to this Volume J. MALCOLM BRUCE Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, U.K. S.M. FORTT School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K. STEPHEN T. MULLINS Department of Chemistry, Brunel University, Uxbridge, Middlesex UB8 3PH, U.K. A.J. PEARSON Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7078, U.S.A. MALCOLM SAINSBURY School of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, U.K. P.D. WOODGATE Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7078, U.S.A.

vii

Preface to Volume III B/C/D (partial) This volume spans several very important areas of aromatic chemistry. It includes chapters devoted to benzoquinone, nitro compounds, metallo derivatives and aromatic hydrocarbons with substituents which contain more than one nitrogen atom, e.g., azobenzenes, azides, etc. The first chapter is written by Dr. Malcolm Bruce. It is fitting that I should recognise Dr. Bruce's special contribution to Rodd, since it was he who wrote on this subject in the 2nd edition in 1974 and again in the 1st Supplement. Dr. Bruce's enthusiasm and lifelong interest in this subject is still very evident, and this can easily be judged by the style with which he has surveyed progress in benzoquinone chemistry in the last decade. The application of organometallic chemistry to synthesis has been spectacular, and two chapters in this volume emphasise this development. With so much information, the task of condensing the most significant new knowledge into a readable and informative account is a daunting one. Yet the authors, Dr. Mullins and Professors Pearson and Woodgate, have managed this with skill and flair. Dr. Simon Fortt has written on the chemistry of the nitroarenes. This is a subject steeped in history, but it is still very much alive and relevant today as is highlighted in Dr. Fortt's contribution. I would like to thank all the authors for making my job as editor an easy and intellectually rewarding one. Malcolm Sainsbury

Bath March 1995


ix

Contents Volume III B/C/D (partial)

A r o m a t i c Compounds: Benzoquinones a n d related compounds: Derivatives of mononuclear benzenoid hydrocarbons with n u c l e a r s u b s t i t u e n t s a t t a c h e d t h r o u g h an e l e m e n t othe r t h a n the n o n - m e t a l s in Groups VI and VII of the Periodic Table N u c l e a r - s u b s t i t u t e d benzenoid h y d r o c a r b o n s with more t h a n one nitrogen a t o m in a s u b s t i t u e n t group Monobenzenoid a n d phenolic a r a l k y l compounds, their derivatives a n d oxidation products: Depsides, tannins, lignans, lignin a n d h u m i c acid List of contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . List of common abbreviations a n d symbols used . . . . . . . . . . . . . . . . . . . . . . . .

vi vii xiii

Chapter 8. Benzoquinones and Related Compounds by J. M A L C O L M BRUCE 1. I n t r o d u c t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. O ve r vie w of quinone reactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) Electron t r a n s f e r . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) Addition of nucleophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) Cycloaddition reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) S u b s t i t u t i o n reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (e) P h o t o c h e m i s t r y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (f) Complexes a n d molecular assemblies . . . . . . . . . . . . . . . . . . . . . . . . . . (g) Ring f r a g m e n t a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. S y n t h e s i s of benzoquinones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) F r o m phenols and h y d r o q u i n o n e s and their ethers . . . . . . . . . . . . . . . . (b) F r o m cyclobutene-1, 2-diones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. B e nz oquinone m e t h i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) Overview of quinone m e t h i d e reactivity . . . . . . . . . . . . . . . . . . . . . . . . . (b) 1,2-Benzoquinone m e t h i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) 1, 4-Benzoquinone m e t h i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Thiobenzoquinones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. B e n z oquinone imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) 1, 2-Benzoquinone imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) 1, 4-Benzoquinone imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. H o m o b e n z o q u i n o n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Benzoquinols (hydroxycyclohexadienones) . . . . . . . . . . . . . . . . . . . . . . . . . . (a) 1, 4-Benzoquinols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) 1, 2-Benzoquinols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) 1, 4-Benzoquinol imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 2 3 3 7 14 20 21 25 27 29 29 31 35 35 36 42 45 46 46 47 48 49 50 52 53

X

Chapter 9. Derivatives of Benzenoid Hydrocarbons with Substituents containing a single Nitrogen Atom by S.M. F O R T T 1. N i t r o d e r i v a t i v e s of benzene, its homologues a n d o t h e r s u b s t i t u t e d b e n z e n e s (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) O x i d a t i o n of a r o m a t i c a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. N i t r o s o d e r i v a t i v e s of benzene a n d its homologues . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. N - A r y l h y d r o x y l a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. N - A r y l n i t r o n e s a n d N - a r y l n i t r o x i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. A r o m a t i c a m i n e s derived from b e n z e n e and its homologues n u c l e a r p r i m a r y monoamines ................................................ (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. B e n z e n e d i a m i n e s a n d b e n z e n e t r i a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. N - S u b s t i t u t e d a r y l a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. N - A r y l a m i d e s (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. N - A r y l i s o c y a n a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. N - A r y l u r e a s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. N - A r y l c a r b a m a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12. N - A r y l c a r b o d i i m i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13. N - A r y l i s o c y a n i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14. N - A r y l i s o t h i o c y a n a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15. N - A r y l a m i d e s of sulfur acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16. N - A r y l a m i d e s of p h o s p h o r u s acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

55 55 59 60 64 64 65 66 66 67 69 70 70 74 76 76 77 78 78 83 84 84 85 87 87 87 89 89 89 89 89 90 91 91 91 92 92

Chapter 10. Aromatic Compounds of the Non-Transition Metals by S T E P H E N T. M U L L I N S 1. I n t r o d u c t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. G r o u p 1 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 L i t h i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

95 95 95

xi 2.2 S o d i u m , p o t a s s i u m , r u b i d i u m , c a e s i u m . . . . . . . . . . . . . . . . . . . . . . . . . 3. G r o u p 2 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 B e r y l l i u m , m a g n e s i u m , calcium, s t r o n t i u m , b a r i u m . . . . . . . . . . . . . . . 3.2 Zinc, c a d m i u m a n d m e r c u r y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. G r o u p 3 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 B o r o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 A l u m i n i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. G r o u p 4 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Silicon a n d g e r m a n i u m . . . . . ................................ 5.2 T i n a n d lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. G r o u p 5 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. G r o u p 6 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

109 112 112 117 123 123 126 128 128 139 145 149

Chapter 11. Aromatic Compounds of the Transition Elements by A.J. P E A R S O N A N D P.D. W O O D G A T E 1. I n t r o d u c t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. M a n g a n e s e , t e c h n e t i u m a n d r h e n i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 ~6 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 7/2 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 ~1 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Iron, r u t h e n i u m a n d o s m i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 ~6 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 ~2 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. C h r o m i u m , m o l y b d e n u m a n d t u n g s t e n . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 (~-Arene)Cr(CO)3 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n s ............................................. (b) S t r u c t u r e of (rl~-arene) complexes: influence of the Cr(CO)3 group . . . . . (c) R e a c t i o n s of (~6-arene)Cr(CO)~ complexes . . . . . . . . . . . . . . . . . . . . . . . 4.2 Nucleophilic A d d i t i o n to t h e ~ - a r e n e ring . . . . . . . . . . . . . . . . . . . . . . (i) A d d i t i o n d i s p l a c e m e n t ; SNAr, 1 9 4 - (ii) Nucleophile a d d i t i o n - o x i d a t i o n , 1 9 7 - (iii) N u c l e o p h i l e a d d i t i o n - e l e c t r o p h i l e addition, 2 0 0 4.3 (~6-Arene)M(CO)3 complexes (M = Mo, W) . . . . . . . . . . . . . . . . . . . . . . . 5. O t h e r m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

151 152 152 162 163 165 165 183 185 186 186 192 193 194

211 212

Chapter 12. Nuclear Substituted Benzenoid Hydrocarbons with more than one Nitrogen Atom in the Substituent by M A L C O L M S A I N S B U R Y 1. A r y l n i t r o s a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 (i) S y n t h e s i s , 215 - (ii) Reactions, 216 2. A r y l d i a z e n e c a r b o n i t r i l e s (arylazo c y a n i d e s ) . . . . . . . . . . . . . . . . . . . . . . . . 216 3. A r y l a z o s u l p h i d e s a n d oxidised d e r i v a t i v e s . . . . . . . . . . . . . . . . . . . . . . . . . 216 (i) S y n t h e s i s , 2 1 6 - (ii) Reactions, 2 1 7 4. 2 - A l k y l - l - a r y l d i a z e n e s ( a r y l a z o a l k a n e s ) , 2 - a l k e n y l - l - a r y l d i a z e n e s (arylazoalkenes) and related compounds ................................. 219 (i) S y n t h e s i s , 219 - (ii) Reactions, 220 5. A r y l d i a z e n e oxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223

xii 6. A z o a r e n e s (1, 2 - d i a r y l d i a z e n e s ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 (i) S y n t h e s i s , 2 2 4 - (ii) Reactions, 2 2 9 7. A z o x y a r e n e s (1, 2 - d i a r y l d i a z e n e N-oxides) . . . . . . . . . . . . . . . . . . . . . . . . . . 232 (i) S y n t h e s i s , 2 3 2 - (ii) Reactions, 2 3 4 8. A r e n e d i a z o n i u m salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 (i) S y n t h e s i s , 2 3 6 - (ii) Reactions, 2 3 8 9. A r y l h y d r a z i n e s a n d a r y l h y d r a z o n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256 (i) S y n t h e s i s ( a r y l h y d r a z i n e s ) , 256 - (ii) Reactions ( a r y l h y d r a z i n e s ) , 257 - (iii) P h y s i c a l p r o p e r t i e s ( a r y l h y d r a z o n e s ) , 260 - (iv) S y n t h e s i s ( a r y l h y d r a z o n e s ) , 261 - (v) C h e m i c a l reactions ( a r y l h y d r a z o n e s ) , 262 10. N - A r y l h y d r a z o n o y l h a l i d e s a n d a r y l n i t r i l i m i n e s (arylnitrile imides) . . . . . . 301 (i) S y n t h e s i s ( h y d r a z o n o y l halides), 3 0 1 - (ii) Reactions, 3 0 2 11. S u b s t i t u t e d a r y l h y d r a z i n e s a n d 1 , 2 - d i a r y l h y d r a z i n e s ( h y d r a z o b e n z e n e s ) . . 311 (i) S y n t h e s i s , 3 1 1 - (ii) Reactions, 3 1 3 12. F o r m a z a n s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 (i) S y n t h e s i s , 3 1 4 - (ii) Reactions a n d physical properties, 3 1 9 13. A r y l a z i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 (i) Reactions, 320 - (ii) U s e s in heterocyclic s y n t h e s e s , 322 14. A r y l t r i a z e n e s (diazoamino c o m p o u n d s ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 (i) Biological i m p o r t a n c e , 327 - (ii) Synthesis, 328 - (iii) Reactions, 333 15. H e x a z e n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 Guide to t h e i n d e x . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Index .........................................................

339 341

xiii

List of Common Abbreviations and Symbols Used

A /~ Ac a as, a s y m r n ,

at. B Bu b.p. c, C CD conc. D D D d dec., decomp deriv, E E l , E2 E lcB ESR Et e f.p. G GLC g H h Hz I IR J J K k kcal M Me rn m.p. Ms

acid ,~,lgstr6m units acetyl axial asymmetrical atmosphere base butyl boiling point concentration circular dichroism concentrated Debye unit, 1 x 10-is e.s.u. dissociation energy dextro-rotatory; dextro configuration density with decomposition derivative energy; extinction; electromeric effect uni- and bi-molecular elimination mechanisms unimolecular elimination in conjugate base electron spin resonance ethyl nuclear charge; equatorial freezing point free energy gas liquid chromatography spectroscopic splitting factor, 2.0023 applied magnetic field; heat content Planck's constant hertz spin quantum number; intensity; inductive effect infrared coupling constant in NMR spectra Joule dissociation constant Boltzmann constant; velocity constant kilocalories molecular weight; molar; mesomeric effect methyl mass; mole; molecule; m e t a melting point mesyl (methanesulphonyl)

xiv

N NMR NOE n

molecular rotation Avogadro number; normal nuclear magnetic resonance Nuclear Overhauser Effect normal; refractive index; principal quantum number

0

ortho-

ORD P Pr Ph P PMR R S

optical rotatory dispersion polarisation; probability; orbital state propyl phenyl para-; orbital proton magnetic resonance clockwise configuration counterclockwise configuration; entropy; net spin of incompleted electronic shells; orbital state uni- and bi-molecular nucleophilic substitution mechanism internal nucleophilic substitution mechanism symmetrical; orbital secondary solution symmetrical absolute temperature p-toluenesulphonyl triphenylmethyl time temperature (in degrees centrigrade) tertiary ultraviolet optical rotation (in water unless otherwise stated) specific optical rotation dielectric constant; extinction coefficient dipole moment; magnetic moment Bohr magneton microgram micrometer wavelength frequency; wave number magnetic; diamagnetic and paramagnetic susceptibilities dextrorotatory laevorotatory negative charge positive charge

S~I, Ss2 SNi S sec

soln. symm. T Tosyl Trityl t temp. tert UV O~

s

# PB #g #m A /J X, Xd, X~

(+) (-) +

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.III B, C,D(Partial), edited by M. Sainsbury 9 1995 Elsevier Science B.V. All rights reserved.

Chapter 8 BENZOQUINONES AND RELATED COMPOUNDS J. MALCOLM BRUCE 1.

Introduction

Chapter 8 of Volume III, Part B, of the First Supplement to the Second Edition of "Rodd's Chemistry of Carbon Compounds" covered the literature on benzoquinones and related compounds from early 1973 to mid-1979. The present Chapter contains, mainly, information published from then until mid-1994. Overall, this period has been one of consolidation, with earlier methods of synthesis being complemented by new ones, and modes of reaction being extended successfully to new systems, often of greater complexity than those used previously, thus further establishing the selectivity of oxidation of phenols, hydroquinones, and catechols, and the ability of the 1,2- and 1,4-benzoquinonoid moieties to behave as one-electron acceptors and as electrophiles, and, in cyclo-addition reactions, as both dienophiles and, for the 1,2-series, as heterodienes. Notable advances include a general method of synthesis of variously substituted quinones via thermal ring expansion of alkenyl- and alkynyl-cyclobutenolones (the former affording hydroquinones, which can be oxidised to benzoquinones, the latter benzoquinones directly), and a definitive study of the regiochemistry of nucleophilic substitution in 2-chloro-l,4-naphthoquinone, the results of which appear to be applicable to halogeno-1,4benzoquinones. New examples of the photochemistry of benzoquinones have continued to appear.

Benzoquinone methides and dimethides have attracted growing attention, particularly with respect to their applications in synthesis, especially in intramolecular Diels-Alder reactions, and to their roles in biological systems. 7,7,8,8-Tetracyano-1,4benzoquinone dimethide (TCNQ) and its congeners continue to be of interest for the preparation of electrically-conducting polymers, and the results have triggered interest in heterocyclic analogues (hetero-TCNQs) in which an endocyclic double bond of the sixmembered ring of the classical quinone methide system has been replaced by a hetero-atom, often sulfur. Improved procedures for the synthesis of benzoquinols (hydroxycyclohexadienones) have been developed, enabling the r01e of these compounds in synthetic methodology to be extended. 2.

Bibliography

Several major publications have appeared during the period under review, and together provide extensive coverage of a large part of it. "The Chemistry of the Quinonoid Compounds", Volume 2 (eds. S. Patai and Z. Rappoport, Wiley-lnterscience, Chichester, 1988) is in two parts, and totals 1711 pages. Part 1 deals with synthesis, analysis, spectroscopic properties, ground and excited state reactions, and electrochemistry. Part 2 covers radiation chemistry, quinhydrones and semiquinones, solid-state photochemistry, quinones as oxidants, quinone ketals and imines, and the biochemistry of quinones. "Naturally Occurring Quinones III, Recent Advances" (R.H. Thomson, Chapman and Hall, London, 1987) runs to 732 pages, of which the first 134 relate to benzoquinones. The same author devotes 12 pages to their synthesis in his Chapter "The Total Synthesis of Naturally Occurring Quinones" (in "The Total Synthesis of Natural Products", ed. J. ApSimon, Wiley, Chichester, 1992, Vol. 8, pp. 312 -531). Dopaquinone (a 1,2-benzoquinone) is an intermediate in the biosynthesis of melanins from tyrosine; research in this area has been reviewed in "Melanins and Melanogenesis" (G. Prota, Academic Press, San Diego, 1992). K.T. Finley's "Quinones: The Present State of Addition and Substitution Chemistry", originally scheduled to appear in the quinones "Update" volume of S. Patai's "The Chemistry of Functional Groups", has been published in "Supplement E: The

Chemistry of Hydroxyl, Ether and Peroxide Groups" (ed. S. Patai, Wiley, Chichester, 1993, Volume 2, Chapter 19, pp. 1027-1134). It covers addition and substitution by halogens and by nitrogen, oxygen, and sulfur nucleophiles, reactions at the carbonyl group(s), alkylation and acylation, cyclo-additions, including Diels-Alder and 1,3-dipolar cyclo-additions, and tandem reactions. Its inappropriate location notwithstanding, it provides an extensive review of the literature from 1983 to 1990. These publications, together with those cited in the present Series in Chapter 8 of Volume III, Part B, in the Second Edition, and in its First Supplement, highlight the development over the last 30 years of an extensive collection of reviews on quinone chemistry. The present Chapter supplements them in a selective, rather than an exhaustive, manner. 1

(a)

Overview of Quinone Reactivity

Electron Transfer

A characteristic of the quinonoid system is its ability to accept an electron, resulting in reduction to the corresponding semiquinone, an aromatic anion radical, viz (2) from 1,4benzoquinone (1), and (4) from 1,2-benzoquinone (3). Under comparable conditions, 1,2-benzoquinone is more readily reduced than 1,4-benzoquinone, a contributory factor being the

O

O~

o

oG

(1)

(2)

(3)

(4)

relief of dipolar and lone pair repulsions which are peculiar to the vicinal dione moiety in which rotation about the carbon-oxygen bond

is precluded (cf. A.R. Katritzky, et a/., J. Chem. Soc., Chem. Commun., 1990, 715). Electron-accepting substituents favour the reduction by stabilising the semiquinone. Donor substituents exert the opposite effect. This holds true in both solution and the gas phase, although in the gaseous state (P. Kebarle et al., J. Phys. Chem., 1986, 90, 2747; J. Am. Chem. Soc., 1988, 110, 400) the inductive effect of the oxygen atom of the methoxy group is markedly more important in stabilising the semiquinone than is the lone pair in conjugatively destabilising it. The reduction potentials of a variety of 2,5diaziridino-3,6-disubstituted-1,4-benzoquinones have been calculated to +50 mV using the COSMO continuum solvation model (H.S. Rzepa and G.A. SuSer, J. Chem. Soc., Chem. Commun., 1993, 1743); aziridino-1,4-benzoquinones are reductive bioalkylating agents, and show promise in cancer chemotherapy (Z.-D. Huang et a/., J. Med. Chem., 1993, 36, 1797). Addition of a further electron to the semiquinone to give the dianion (of the hydroquinone or catechol) is a higher energy process. Both one- and overall two-electron steps, denoted by E 11/2 and E21/2 respectively, can be quantified by cyclic voltammetry, conveniently using a glassy carbon electrode in an aprotic solvent, e.g. anhydrous dimethylformamide containing a supporting electrolyte such as tetrabutylammonium tetrafluoroborate. This technique provides corresponding data for the reverse (oxidation) process in which electrons are removed stepwise, one from the dianion to yield the semiquinone, the second from the semiquinone to regenerate the quinone (R.C. Prince et al., Methods Enzymol., 1986, 125, 109). The greater the electron affinity of the quinone, the more easily it effects oxidation/dehydrogenation of appropriate substrates. The high potential quinones 2,3-dichloro-5,6-dicyano1,4-benzoquinone (DDQ) (5) and tetrachloro-1,2-benzoquinone (6) (respectively E 11/2 +597 mV and +197 mV in dimethylformamide versus saturated calomel reference; cf. 1,4-benzoquinone, -401 mV) are frequently employed for this purpose. The distinction between electron and hydride transfer from substrate to oxidant is difficult to establish, and the precise mechanism may be governed by the medium in which the process occurs (cf. C Reichardt, "Solvents and Solvent Effects in Organic Chemistry", Second Edn, VCH, Weinheim, 1988; C.I.F. Watt, Adv. Phys. Org. Chem., 1988,

24, 57; J.W. Bunting, Bio-org. Chem., 1991, 19, 456; C.A. Coleman, J.G. Rose and C.J. Murray, J. Am. Chem. Soc., 1992, 114, 9755; J.-P. Cheng et al., J. Org. Chem., 1993, 58 5050). CI

O CI

~N

CI

N

CI

O

O

CI

(5)

(6)

Free energy hydride affinities (-AGH) in dimethyl sulfoxide for simple 1,2- and 1,4-benzoquinones range from 58 kcal mol-1 for tetramethyl-l,4-benzoquinone (duroquinone) to 101 kcal mol-1 for 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ); for chlorosubstituents, the effect of electronegativity dominates over that of lone pair polarisation (J.-P. Cheng et al., J. Org. Chem., 1993, 58

5050). Electron transfer to DDQ is likely to be the first step in each of the following cases where it is used for the cleavage of silyl ethers (K. Tanemura, T. Suzuki and T. Horaguchi, J. Chem. Soc., Perkin Trans. 1, 1992, 2997), acetals (K. Tanemura, T. Suzuki and T. Horaguchi, J. Chem. Soc., Chem. Commun., 1992, 979; A. Oku, M. Kinugasa and T. Kamada, Chem. Lett., 1993, 165), and dithioacetals (L. Mathew and S. Sankararaman, J. Org. Chem., 1993, 58, 7576). It is also likely to be involved in the oxidative polymerisation by DDQ of diphenyldisulfide to poly(p_-phenylene sulfide), (-C6H4S-)n (E. Tsuchida et al., Macromolecules, 1992, 25 2698); lower-potential benzoquinones also effect this polymerisation, but only in the presence of trifluoroacetic acid; electron transfer is then probably to the protonated quinone, which is a more effective acceptor (E. Tsuchida and K. Yamamoto, in J. Reedijk, ed., "Bioinorganic Catalysis", Marcel Dekker, New York, 1993, Chap. 4). Similarly, the arylation of 1,4-benzoquinones by aromatic hydrocarbons (the Pummerer reaction) requires the presence of a

Lewis acid, aluminium(lll) chloride, to complex with the quinone; arylation by phenols probably involves the aluminium phenolate also (G. Sartori et al., J. Chem. Soc., Perkin Trans. 1, 1993, 39; cf. H.-J. Kn61ker and N. O'Sullivan, Tetrahedron, 1994, 50 10893). Low potential quinones, such as 2,6-di-t-butyl-1,4benzoquinone, act as electron relays in the ruthenium(ll)-catalysed oxidation of secondary alcohols to ketones by cobalt complexes (G.-Z. Wang, U. Andreasson and J.-E. B&ckvall, J. Chem. Soc., Chem. Commun., 1994, 1037) and by manganese dioxide (U. Karlsson, G.-Z. Wang and J.-E. B&ckvall, J. Org. Chem., 1994, 59, 1196). At the other extreme of the redox potential scale are the benzoquinones which mediate electron transfer cascades in key bioprocesses such as photosynthesis, e.g. the ubiquinones (7) and the plastoquinones (8) [E 11/2 (n = 10) -602 mY, and (n = 9) -619 mV respectively], in these systems, changes in the number of

MeO

H n

MeO"-~r~-Me O (7)

Me

H

n Me" O (8)

isoprene units in the side-chain have relatively little effect on the reduction potential (R.C. Prince, P.L. Dutton and J.M. Bruce, FEBS Lett., 1983, 160, 273), although the side-chains play vital rSles in anchoring the quinones within photosynthetic reaction centres; the first three isoprene units are especially important (K. Warncke et al., Biochemistry, 1994, 33, 7830). Addition of an electron to a ubiquinone or to a plastoquinone produces the semiquinone, which can transfer a single electron to a neighbouring quinone, thus regenerating the initial quinone and enabling the stepwise transport of electrons to continue (G. Lenaz, ed., "Biochemistry, Bioenergetics, and Chemical Application of Ubiquinone", Wiley, Chichester, 1985; M. Iwaki and S. Itoh, in J.R.

Bolton, N. Mataga and G. McLendon, eds, "Electron Transfer in Inorganic, Organic, and Biological Systems", American Chemical Society, Washington, D.C., 1991, Chap. 10; B.L. Trumpower, "Function of Quinones in Energy Conserving Systems", Academic Press, New York, 1992; A. Labahn et al., J. Phys. Chem., 1994, 98, 3417). It is less likely that under biological conditions a second electron will be transferred to the semiquinone to afford the hydroquinone dianion in isolation. However, such a transfer becomes feasible within the hydrated protein network of the reaction centre, where electron transfer to the semiquinone may occur following, or concomitantly with, proton-abstraction involving, e.g. water, a feature which both results in proton transfer and highlights the r61e of the medium in controlling overall reactivity (J.M. Keske, J.M. Bruce and P.L. Dutton, Z. Naturforsch, 1990, 45c, 430; cf. T.H. Fife, Acc. Chem. Res., 1993, 26, 325). Examples of this aspect of the reactivity of quinones in vitro are cited elsewhere in this Chapter.

(b)

Addition of Nucleophiles

Nucleophilic addition is more complex than electron addition, and can lead to several types of product, the nature of which is dependent on the nucleophile, the counterion, and the medium. In general, soft nucleophiles give products of attack at alkenic carbon; hard nucleophiles afford products arising from addition to carbonyl carbon (M. Solomon et al., J. Am. Chem. Soc., 1988, 110, 3702). The latter process may be reversible unless the incipient oxyanion, or hydroxy group, is subsequently trapped, as in the formation of trimethylsilyl ethers (9) by reaction with trimethylsilyl cyanide in the presence of zinc(ll) iodide; treatment with fluoride ion regenerates the carbonyl group (D.A. Evans and R.Y. Wong, J. Org. Chem., 1977, 42,350). However, complexing of the quinone with the Lewis acid probably precedes or accompanies addition of the cyano moiety. Complexation of this type is also involved in other reactions which lead to attack at the ethenic double bond, e.g. allylation effected with allyltrimethylstannanes in the presence of boron(Ill) fluoride etherate, which affords the hydroquinone counterparts of the ubiquinones (7) (Y. Naruta and K. Maruyama, Org. Synth., 1993, 71,125).

NC

SiMe 3

OH

O SO3H

OH SO3H

SO2Ph

O

OH

OQ

OH

(9)

(10)

(11)

(12)

Hydrogen sulfite (HSO3-) adds reversibly to carbonyl carbon in 1,4-benzoquinone, but irreversibly to alkenic carbon to afford, ultimately, the sulfonic acid (10) (M.P. Youngblood, J. Org. Chem., 1986, 51, 1981). The irreversibility is a consequence of enolisation of the initial adduct (11) to give the (aromatic) hydroquinone. Overall, the quinonoid moiety is reduced following, in principle, a Michael addition (P. Perlmutter, "Conjugate Addition Reactions in Organic Synthesis", Pergamon, Oxford, 1992). If the ultimate objective is to obtain the quinone, e.g. a ubiquinone (7) resulting from prenylation, then the corresponding intermediate hydroquinone must be oxidised in a subsequent step. Since the hydroquinonesulfonic acids are troublesome to isolate, this type of nucleophilic addition is more conveniently studied using benzenesulfinic acid as the nucleophile, particularly under overall acidic conditions, affording the corresponding sulfone (12). These reactions are particularly clean because the initial quinone is incapable of oxidising the hydroquinone (12), and complicating redox equilibria are therefore avoided (e.g. Ell/2, vide supra, 1.4-benzoquinone,-401 mV; phenylsulfonyl-l,4benzoquinone, -40 mV). The effects of substituents carried by the quinone on the orientation of nucleophilic addition, which is essentiallygoverned by the criteria for Michael addition, can therefore be evaluated conveniently (J.M. Bruce and P. LloydWilliams, J. Chem. Soc., Perkin Trans. 1, 1992, 2877). Interestingly, consideration of electronic effects usually enables the position of nucleophilic attack to be predicted reliably; the predictions of molecular orbital calculations are generally in agreement (M.D. Rozeboom, I.-M. Tegmo-Larsson and K.N. Houk, J. Org. Chem. 1981, 46, 2338). Thus for monosubstituted 1,4-

benzoquinones (13), when R is an electron donor, the order of reactivity towards addition of the nucleophile is position 5 > 6 > 3, and when R is an acceptor, the order is 3 > 6 > 5 unless the system is otherwise perturbed by effects of the medium in which the reaction is performed. O

OH

R

O

SO2Ph

O

OH

(13)

(14)

O

i ~

O

~]} O (15)

Reactions with sulfinic acids are frequently effected in aqueous media, with the fairly readily oxidised sulfinic acid being generated in situ from its sodium salt. The medium is therefore acidic. According to prediction, acetyl-l,4-benzoquinone (13; R = COMe) affords the hydroquinone (14)in high yield (J.M. Bruce and P. Lloyd-Williams, J. Chem. Soc., Perkin Trans. 1, 1992, 2877). The xanthone-1,4-quinone (15) can be regarded as a vicdisubstituted-1,4-benzoquinone in which the lone pair from the oxygen atom in the ring is delocalised on to the peri carbonyl groups, thus devolving control of the position of nucleophilic addition to the 4-carbonyl moiety. Michael addition at the 2-position would therefore be expected. Under the usual experimental conditions (the quinone in dichloromethane shaken with aqueous sodium benzenesulfinate acidified with trifluoroacetic acid) the hydroquinone (16) is formed almost exclusively, indicating that the quinone is protonated between the carbonyl groups (as 17) prior to reaction with the sulfinic acid; the protonated 1-carbonyl group thus controls the regiochemistry of the Michael addition (J.M. Bruce and I.M. Farhat, unpublished work). In this example, protonation under mild conditions is particularly favourable because it removes lone pair-lone pair repulsion between the peri carbonyl groups (cf. A.R. Katritzky et al., J. Chem. Soc., Chem. Commun., 1990, 715). Nonetheless, it serves to illustrate the dramatic effect which the medium can exert

]0 on the outcome of the reaction. Thus protonation, and, equivalently, Lewis-acid complexation, can play a dominant r61e in controlling the reactivity of even simple quinones towards nucleophiles. The phenomenon is in no way unexpected: it is a particular example of the chemistry of the carbonyi group. Further examples, including nucleophiles other than those which are sulfurbased, are given in the sequel.

O

OH

O

~,,,~ L . SO2Ph OH

O

O

(16)

(17)

Due to their relative instability, simple 1,2-benzoquinones have been less extensively studied, although, overall, vinylogous Michael [1,6-] addition is preferred, perhaps reflecting the extent of stabilisation in the formal intermediate: addition of the nucleophile (Nu-) at a position adjacent to a carbonyl group leads to the maximally (cross) conjugated enolate (18), in contrast to the enolate (19) which would be the result of formal 1,4-addition. Protonation and enolisation of (18) then leads to the 3-substituted catechol (cf. D.J. Liberato et al., J. Med. Chem., 1981, 24, 28).

Nu_CX oOo Nu H (18)

H (19)

]! The highly reactive dopaquinone is a key intermediate in melanogenesis, and undergoes both intermolecular addition of, particularly, thiols, and intramolecular addition (i.e. cyclisation) to yield, subsequently, 5,6-dihydroxyindole and related species (G. Prota, "Melanins and Melanogenesis", Academic Press, San Diego, 1992; R.V. Bensasson, E.J. Land and T.G. Truscott, "Excited States and Free Radicals in Biology and Medicine", Oxford Science Publications, Oxford, 1993, Chap. 8). Of the more stable 1,2-benzoquinones, the reactions of 3-tbutyl- (20) and, particularly, 3,5-di-t-butyl-l,2-benzoquinone (21) have been studied to a greater extent. Whilst the 3-t-butyl compound allows for addition to occur at positions 5- and/or 6-, all nuclear positions other than the 1-carbonyl carbon in the di-tbutylquinone are extensively shielded by the bulk of the t-butyl groups, with the result that reactions at oxygen (e.g. heterodiene addition: see below) have been highlighted. 4,5-Dialkoxy-l,2-benzoquinones, e.g. (22), are comparatively stable, but behave atypically from the parent: the two adjacent vinylogous ester moieties are responsible, and may direct addition reactions to the carbonyl groups (e.g. organolithium reagents: K.F. West and H.W. Moore, J. Org. Chem., 1982, 47, 3591), although vinylogous amides, e.g. (23), result from reaction with amines (Z.-D. Huang et al., J. Med. Chem., 1993, 36, 1797).

{ ~ O O

M e O ~ O MeO" ~

(20)

(21)

MeO~O CICH2CH2NH"

~ (23)

"O

"O

(22)

]2 Formation of a semiquinone from a quinone involves single electron transfer. However, although nucleophilic addition has been shown in the foregoing examples as a two-electron (polar) process, bond formation and breaking may occur via successive singleelectron transfer steps (S.S. Shaik, Progr. Phys. Org. Chem., 1985, 1.5, 197; A. Pross, J. Am. Chem. Soc., 1986, 10.8.,3537; E.C. Ashby, Acc. Chem. Res., 1988, 24, 414; J.-M. Sav~ant, Acc. Chem. Res., 1993, 2__66,455) in which the semiquinone would be implicated as a transient intermediate, with the nucleophile becoming, again transiently, a 'free' radical. However, intervention of the semiquinone per s_eeseems unlikely, since the radical-radical combination which would ensue in order to form the nucleophilecarbon bond in the initial adduct, e.g. (18), would have to be sufficiently energetic to overcome the aromaticity of the semiquinone. Transfer of the two electrons is thus likely to be virtually simultaneous, and the process becomes formally analogous to a classical Michael addition (S. Hoz, Acc. Chem. Res., 1993, 26, 69; P. Perlmutter, "Conjugate Addition Reactions in Organic Synthesis", Pergamon, Oxford, 1992; A. Pross, in J.M. Harris and S.P. McManus, eds, "Nucleophilicity", American Chemical Society, Washington, D.C., 1987, Chap. 23). Readily polarised nucleophiles such as enamines (e.g. CH2=CH.NR2) add readily to quinones, usually via a deeplycoloured ~-complex. The arguments of the previous paragraph concerning mechanism then apply" semiquinone and cation radical (as 24) versus zwitterion (25) formed directly, this then collapsing by proton-loss, as shown, to afford the dihydrobenzofuran (26).

OQ

O (~

IL

OH

+.

Oo (24)

NR2

~(~ O (25)

(~NR2

NR2 (26)

]3 The corresponding vinyl ethers (CH2=CH.OR) and ketene acetals [CH2=C(OR)2] are usually insufficiently reactive for the corresponding addition to occur 'spontaneously'; prior protonation, or Lewis-acid complexation, at quinonoid oxygen is a prerequisite [protonated quinones are potent oxidents, i.e. electron-acceptors (O. Hammerich and V.D. Parker, Acta Chem. Scand., B, 1982, 36, 63)]. Similarly, phenols add to the 3-position of 2-acyl-l,4benzoquinones in the presence of trifluoroacetic acid, protonation at the oxygens of both the acyl group and the 1-carbonyl group of the quinone providing the driving force (P. Kuser et al., Helv. Chim. Acta, 1971,54, 980). Overall, a complement of electrophilicity (the quinone) and nucleophilicity (the substrate) is required, and can be achieved via either of the components. Control by the former is well-illustrated by the regiospecific addition to the 3- position of acetyl-1,4benzoquinones of silyl vinyl ethers (M.A. Brimble, M.T. Brimble and J.J. Gibson, J. Chem. Soc., Perkin Trans. 1, 1989, 179; G.A. Kraus et al., J. Org. Chem., 1990, 55, 1105; 1990, 55, 4922). The r61e of single electron transfer, developed for other systems (cf. A. Pross, Acc. Chem. Res., 1985, 18, 212; E.C. Ashby, Acc. Chem. Res., 1988, 21,414) remains to be established. The diversity of quinonoid systems available for study may in due course lead to a fuller understanding of the factors which control these reactions, ranging from the extremes of single electron transfer and electron pair transfer to a continuum of reactivity governed by the redox chemistry of the reactants and the nature of the environment in which the reaction occurs. Formal addition to the quinonoid nucleus, and its consequences, is well exemplified by the reaction of 1,4benzoquinone with chlorine in diethyl ether: the 2,3-dichloro-adduct (27) is formed in high yield. Enolisation with hydrogen chloride in dry diethyl ether affords the corresponding hydroquinone (28) (J.Y. Savoie and P. Brassard, Can. J. Chem., 1966, 44, 2867). However, when the enolisation is effected with concentrated hydrochloric acid in acetone, the isomeric 2,5-dichlorohydroquinone (29) is formed in high yield, possibly via elimination of hydrogen chloride to afford chloro-1,4-benzoquinone and subsequent readdition-enolisation (J.M. Bruce and P. Marshall, unpublished work).

]4 O

(c)

OH

OH

c,

CI

CI

CI

CI CI

O

OH

OH

(27)

(28)

(29)

Cycloaddition Reactions

Diels-Alder additions to 1,4-benzoquinones have been studied extensively. 1,3-Butadiene and its simple congeners afford 1:1 adducts (30) and, under more forcing conditions, especially in media of low polarity, bis-adducts (31). In more polar media, or at high temperature, the initial adduct may enolise to afford the corresponding hydroquinone (32). Complications then ensue because this hydroquinone carries two electron-donating alkyl substituents, and is oxidised to the corresponding quinone (33) by unreacted 1,4-benzoquinone, which is reduced to the hydroquinone concomitantly. This process is redox driven, e.g. Ell/2: 1,4benzoquinone,-401 mV; 2,3-dimethyl-l,4-benzoquinone,-543 mY. O

O

OH R

O

O (30)

(31)

OH (32)

Further dehydrogenation of (33) to the 1,4-naphthoquinone (34) may ensue [cf. R.T. Brown eta/., J. Chem. Res. (S), 1994, 220], with the formation of more hydroquinone. This forms the

].5 deeply coloured quinhydrone (the 1:1 1,4-benzoquinone hydroquinone complex) and mixed quinhydrones with the newly formed quinones (33) and (34). Complex mixtures thus result. Appropriate attention to experimental conditions, particularly the choice of solvent, can minimise or eliminate these side-reactions. Bis-adducts (31) are usually unaffected. O

O R

O

R O

(33)

(34)

Under kinetic control, the addition is endo, readily established for the addition of cyclopentadiene which, with 1,4benzoquinone, affords (35); the bis-adduct is endo-anti-endo (36) (R. Brown et al., J. Chem. Soc., Perkin Trans. 2, 1974, 132). Although the mono-adduct (35) can be enolised, more forcing conditions are required than those needed for enolisation of the non-bridged analogues (30): a norbornadiene is formed from (35). In consequence, additions involving cyclopentadiene usually occur cleanly. O

O

O

O (35)

(36)

]6 Addition of cyclopentadiene to methyl-1,4-benzoquinone (toluquinone) in ether affords the endo mono-adduct at the unsubstituted enone moiety, in high yield. The presence of lithium perchlorate leads to the formation of the corresponding endo-antiendo adduct, but, unusually, accompanied by about 15% of the endo-anti-exo isomer (P.A. Grieco et al., J. Am. Chem. Soc., 1990, 112, 4595). Complications due to enolisation of the initial 1:1 adduct are precluded by a substituent at the ring junction. These adducts are formed from, e.g., 2,5- and 2,6-disubstituted 1,4-benzoquinones. Those carrying a methoxy group provide clear exemplification of the r61e of complexation with Lewis acids. Thus 2-methoxy-5-methyl1,4-benzoquinone and 1,3-pentadiene afford a 1:1 mixture of the adducts (37) and (38) in the absence of Lewis acid, whereas (37) predominates in the presence of tin(IV) chloride, and (38)is the major product when boron(Ill) fluoride is used. The former may complex with the oxygens of the 1-carbonyl and the methoxy groups, whilst the latter may bind selectively t5 the 4-carbonyl group (J.S. Tau and W. Reusch, J. Org. Chem., 1980, 45, 5012). O

MeO

O

. H. ~ O (37)

MeO

H O (38)

2,3-Dichloro-5,6-dicyano-l,4-benzoquinone (DDQ, 5) reacts with cyclopentadiene in cold benzene to afford the expected endoadduct (39), the electron-accepting cyano groups controlling the regiochemistry of the addition. At reflux, the adduct (39) undergoes dissociation-recombination to give the thermodynamically-favoured isomeric exo-adduct (40). Both reactions are quantitative (J.M. Bruce and H. Finch, unpublished work). Clean endo-exo transformations of this type are, inevitably, rare in the Diels-Alder chemistry of benzoquinones.

]7 O CI

CN

CI

CI

O C N

CI

CN

O

O (39)

(40)

Strongly electron-accepting substituents dominate in controlling the regiochemistry of Diels-Alder additions. Thus acyl- and aroyl-, cyano, arylsulfonyl- and nitro-l,4-benzo-quinones (41; X as specified) afford the corresponding 1,3-pentadiene adducts (42) in high yield. Treatment of the acyl and aroyl compounds (42; X = COAIk, COAr) with organic bases such as pyridine result in enolisation, to (43), and subsequent [1,5] migration of X to yield the corresponding acyl- and aroyl-hydroquinones (44; R = AIk, Ar) (J.M. Bruce et al., J. Chem. Soc., Chem. Commun., 1981, 166, 169, 171; 1982, 686; S.C. Cooper and P.G. Sammes, J. Chem. Soc., Perkin Trans. 1, 1984, 2407 ).

,(

o x

O

o

O

(41)

OH (42)

O

OH

OH (44)

=

(43) O

-

O (45)

]8 When the substituent, X, is a good leaving group (CN, SO2Ar, NO2), similar treatment leads to elimination, probably via the enol (43), and formation of the corresponding 5,8-dihydro-1,4naphthoquinone (45) (cf. J.M. Bruce and P. Lloyd-Williams, J. Chem. Soc., Perkin Trans. 1, 1992, 2877). Recently, there has been a renewal of interest in the DielsAlder reaction of 1,4-benzoquinones (46) with substituted styrenes (47), which, although it requires forcing conditions, provides a useful synthesis of 1,4-phenanthraquinones (48). An excess of the benzoquinone is employed in order to oxidise the initial adduct, via its bis-enol (the corresponding hydroquinone), to the phenanthraquinone (N.D. Willmore, L. Liu and T.J. Katz, Angew. Chem., Internat. Ed. Engl., 1992, 31, 1093; A.B. Padias, T.-P. Tien and H.K. Hall, J. Org. Chem., 1991,56, 5540; L. Liu and T.J. Katz, Tetrahedron Lett., 1990, 31, 3983). O ii/JJ~~]

O a2

R2 R 1--;-~,

R1--~[,[

R3 R3

0 (46)

(47)

(48)

Interestingly, [2 + 2] additions, previously in the province of excited state (photo) chemistry, can be effected in the presence of titanium(IV). Thus methoxy-l,4-benzoquinone and (E)propenylbenzene in the presence of a mixture of titanium(IV) chloride and titanium(IV) isopropoxide yield, inter alia, the adduct (49) (T.A. Engler, K.D. Kombrink and J.E. Ray, J. Am. Chem. Soc., 1988, 110, 7931). Under similar conditions, benzyloxy-1,4benzoquinone and 7-methoxy-2H-chromene probably afford the corresponding [2 + 2] adduct (50), transiently: it isomerises to the pterocarpan system (51), providing a novel entry to this series of compounds (T.A. Engler, K.D. Combrink and J.P. Reddy, J. Chem. Soc., Chem. Commun., 1989, 454).

]9 O

O MeO

~~,~OMe

BnO.v~

h

O

H

0

(49)

(5o) OH BnO

o-7( `

(51)

o

OMe

Studies of the Diels-Alder chemistry of 1,2-benzoquinones have been much less extensive, to some extent as a consequence of the lower stability of the 1,2-quinones. However, even those carrying electron-accepting groups afford the expected Diels-Alder adducts when the quinones are generated in situ by oxidation of the corresponding catechols (R. AI-Hamdani and B. Ali, J. Chem. Soc., Chem. Commun., 1978, 397; D. Pitea et al., J. Org. Chem., 1985, 50, 1853; J. Lee, H.S. Mei and J.K. Snyder, J. Org. Chem., 1990, 55, 5013). Addition of the diene to monoalkyl-l,2-benzoquinones occurs at the least-substituted enone moiety (S. Knapp and S. Sharma, J. Org. Chem., 1985, 50, 4996). 1,2-Benzoquinones can also behave as heterodienes (D.L. Boger and S.M. Weinreb, "Hetero-Diels-Alder Methodology in Organic Synthesis", Academic Press, San Diego, 1987, pp. 167213; T.-L. Ho, "Polarity Control for Synthesis", Wiley, New York, 1991, pp 224-231), especially via inverse electron-demand. Thus, 4-t-butyl-1,2-benzoquinone reacts readily with the enamine (52) to afford the dihydrodioxin (53) (Y. Omote, A. Tomotake and C.

20 Kashima, J. Chem. Soc., Perkin Trans. 1, 1988, 151), whilst 3,5-dit-butyl-1,2-benzoquinone reacts, under more forcing conditions, with a variety of acyclic 1,3-dienes to produce adducts analogous to (54) (V. Nair and S. Kumar, J. Chem. Soc., Chem. Commun., 1994, 1341).

Cj (52)

(53)

H

1

R2

(54) (d)

Substitution Reactions

Studies of the nucleophilic displacement of chlorine from 2[13C].2_chloro_ 1,4-naphthoquinone highlight two addition-elimination mechanisms which have important regiochemical consequences for parallel substitutions in 1,4-benzoquinones (55) where X is the leaving group. Ipso attack, as (56), leads to substitution at the centre carrying the leaving group, whereas vicinal attack, as (57), followed by isomerisation to (58), results in attachment of the nucleophile (Nu-) at the adjacent alkenyl carbon. Attack by hard nucleophiles is predominantly ipso, and that by soft nucleophiles is exclusively vicinal; amines are borderline in reactivity, but ipso attack is favoured in polar media, whereas vicinal attack predominates in solvents of low polarity (D.W. Cameron, P.J. Chalmers and G.I. Feutrill, Tetrahedron Lett., 1984, 25, 6031).

2] These observations must be taken into account in rationalising the substitution chemistry of 1,4-benzoquinones, especially that described in the older literature.

o

,1~].[I ~ X

('c3

o

R--

o--

X~-Nu

R

o

~~r,.x

R-~~

R

xJ~H

Nu o

(55)

Nu

o

(56)

(57)

(58)

Displacement of leaving groups, particularly methoxy, from the 4- position of 1,2-benzoquinones appears to occur via ipsosubstitution, although yields are not high (Z.-D. Huang et al., J. Med. Chem., 1993, 36, 1797).

(e)

Photochemistry

Since quinones are coloured, much of their photochemistry, including that involved in photosynthesis, can be explored using visible light. Hydrogen-abstraction from the formyl group of aldehydes by excited 1,4-benzoquinones is particularly clean, the resulting acyl or aroyl radicals being scavenged by ground-state quinone either at the alkene moiety to yield, ultimately, the corresponding acyl- or aroyl-hydroquinone, or at oxygen to afford the mono-ester. The latter predominates with high-potential quinones, and has been explained in terms of initial electron transfer from the radical to the quinone in its ground state. Cyclodimerisation of 1,4-benzoquinones to afford cyclobutanes is common, whilst [2 + 2] cyclo-addition of alkenes can occur at both the ethene moiety, affording cyclobutanes, and the carbonyl group, affording spiro-oxetanes. Cyclo-addition of alkenes to photoexcited 1,2-benzoquinones occurs in the [4 + 2] mode, giving dihydrodioxins. Hydrogen-abstraction from, and fragmentation and

22 cyclisation involving, side-chains of 1,4-benzoquinones can occur. These aspects have been reviewed (J.M. Bruce, in S. Patai, ed., "The Chemistry of the Quinonoid Compounds", Wiley, l-ondon, 1974, Chap. 9; K. Maruyama and A. Osuka, in S. Patai and Z. Rappoport, eds., "The Chemistry of the Quinonoid Compounds", Vol. 2, Wiley, London, 1988, Chap. 13). Electron transfer from metalloporphyrins to triplet 1,4benzoquinone (S. Yamauchi et al., J. Photochem. Photobiol. A: Chem., 1992, 65, 177; M.N. Paddon-Row, Acc. Chem. Res., 1994, 27, 18) and from thianthrene to the triplets of 2,5-dichloro- and tetrachloro-l,4-benzoquinone (G. Jones, B. Huang and S.F. Griffin, J. Org. Chem., 1993, 58, 2035; see also G. Jones and B. Huang, Tetrahedron Lett., 1993, 34, 269; M.M. Ayad, Spectrochim. Acta, A, 1994, 50, 671) affords the corresponding substrate cation radicals and semiquinones. Similar electron transfer occurs from N,Ndimethylaniline and from triphenylamine to excited 1,4benzoquinone and duroquinone (tetramethyl-1,4-benzoquinone), and has been studied by CIDNP (N.E. Polyakov and T.V. Leshina, J. Photochem. Photobioi. A: Chem., 1990, 55, 43), and from tbutyldimethylamine to 2,5-dichloro-1,4-benzoquinone in sunlight (Zhong-Li Liu et al., J. Chem. Soc., Chem. Commun., 1991, 1054), which results in the formation of aryloxy-1,4-benzoquinones. CIDNP has also been used to establish that photo-excited 1,4-benzoquinone can function as a mediator of electron transfer from 1,4-dimethoxynaphthalenes as donors to 1', l'-dicyanomethylenecyclohexane as the ultimate acceptor (Y.-C. Liu et al., J. Photochem. Photobiol. A: Chem., 1992, 67 279). The quantum yield for formation of triplet 1,4-benzoquinone is high in solvents of low polarity, but decreases progressively as the polarity of the medium is increased; intermolecular electron transfer eventually predominates (R. Marquardt, S. Grandjean and R. Bonneau, Photochem. Photobiol. A: Chem., 1992, 69, 143). Analogous, intramolecular, processes occur in systems containing 1,4-benzoquinones linked to porphyrin moieties (Z.-M. Liu, W.-Z. Feng and H.-K. Leung, J. Chem. Soc., Chem. Commun., 1991,209; J.R. Bolton et ai., in J.R. Bolton, N. Mataga and G. McLendon, eds, "Electron Transfer in Inorganic, Organic, and Biological Systems", American Chemical Society, Washington, D.C., 1991, Chap. 7; M.R. Wasielewski, Chem. Rev., 1992, 92, 435; D. Gust, T.A. Moore and A.L. Moore, Acc. Chem. Res., 1993,

23 26, 198; H. Grennberg, S. Faizon and J.-E. B&ckvall, Angew. Chem. Int. Ed. Engl., 1993, 32 263; H.A. Staab et al., Chem. Ber., 1994, 127, 231; Angew. Chem. Int. Ed. Engl., 1994, 33, 1463; L. Sun et al., Angew. Chem. Int. Ed. Engl., 1994, 33, 2318). Irradiation of the 1,4-benzoquinone-di-aquabridged [Mn(N,N'3,5-dichlorosalicylidene-1,2-diaminoethane)(H20)2]2 complex with visible light results in photolysis of water, with evolution of oxygen (N. Aurangzeb et al., J. Chem. Soc., Chem. Commun., 1994, 1153). Photoreduction of 1,4-benzoquinone by electron transfer from porphyrin - ~-cyclodextrin systems has been studied (Y. Kuroda et al., J. Am. Chem. Soc., 1993, 115, 7003), and the synthetical usefulness of the formation of acylhydroquinones from photo-excited 1,4-benzoquinones and aldehydes (vide supra) has been re-examined, in particular as an alternative to the classical FriedeI-Crafts acylation of aromatic compounds (G.A. Kraus and M. Kirihara, J. Org. Chem., 1992, 57, 3256). Triplet tetramethyl- and tetrachloro-1,4-benzoquinone cause cleavage of O-O, C-C, and o~-C-H bonds in hydroperoxides such as PhCHMe.OOH, whereas triplet 2,3-dichloro-5,6-dicyano-l,4benzoquinone (DDQ) abstracts o~-C-H exclusively (G. M6ger and M. Gy6r, J. Photochem. Photobiol. A: Chem., 1991,59, 37). In some respects analogously, irradiation of a benzene solution of 1,4benzoquinone containing benzyl phenyl ether leads to the acetal (59), together with phenol and benzaldehyde (J.H. Penn et al., J. Org. Chem., 1994, 59, 3037). Similarly, irradiation of tetrachloro1,4-benzoquinone (chloranil) in the presence of the aziridine (60) and water in dichloromethane results in the formation of benzaldehyde and the Schiff's base PhCH=N.CH2Ph, in high yield (E. Hasegawa et al., J. Org. Chem., 1992, 57, 6342); the fragmentation may be initiated by single-electron transfer from aziridine nitrogen to the excited quinone. Proof of the anti head-to-tail structure (61) of the solid state [2 + 2] photodimer of 2-isopropyl-5-methyl-1,4-benzoquinone (thymoquinone) has been presented (R.J. Robbins and D.E. Falvey, Tetrahedron Lett., 1993, 34, 3509), and rates and stereochemistry of [2 + 2] spiro-oxetane formation from excited 1,4-benzoquinone and alkenes has been studied (D. Bryce-Smith et al., J. Chem. Soc., Perkin Trans., 2, 1991, 1587; cf. K. Maruyama and H. Imahori, J. Chem. Soc., Perkin Trans. 2, 1990, 257).

24 OPh

O

r

Ph

CH2Ph _

O

H O

N

Ph"" / \ "~Ph

I

I

OH

O

(59)

(60)

(61)

Phenylcyciopropane is a good electron-donor, and quenches triplet chloranil: in methanol, the product (62) of ionic cleavage is formed in high yield; irt dichloromethane, [2 + 3] cycloaddition occurs to afford the spiro-tetrahydrofuran (63) (Y. Takahashi et al., J. Chem. Soc., Chem. Commun., 1994, 1127). Ph O.,'L,,v-'~OMe o

CI

CI

ph

CI

CI

OH

0

(62)

(63)

A photo-[2 + 3] cycloaddition of potential generality is the formation of 2,3-dihydrobenzofurans (as 64) when mixtures of hydroxy-1,4-benzoquinones and alkenes are irradiated in acetone; the hydroquinones (64) are readily oxidised, in air, to the corresponding quinones (K. Kobayashi, Y. Kanno and H. Suginome, J. Chem. Soc., Perkin Trans. 1, 1993, 1449). Dihydroisosilabenzofurans, e.g. (65), are formed quantitatively when the corresponding disilanylquinone (66) is irradiated with visible light in hexane containing acetone, benzophenone or fluorenone

25 (H. Sakurai, J. Abe and K. Sakamoto, J. Photochem. Photobiol. A: Chem., 1992, 65, 111).

OH

O"SiMe3 ,,~

O

S[Me2

,7

R

OH

SiMe 3 I SiMe 2

O

(64)

(65)

(66)

Remarkably, the stereochemistry of the classical endo [4 + 2] Diels-Alder addition of cyclopentadiene to 1,4-benzoquinone and to toluquinone, giving the respective mono-adducts (67; R = H, Me), is inverted, giving the corresponding adducts (68; R = H, Me) with greater than 98% exo selectivity when the reaction is effected by irradiation at 300 nm in dry ethanol containing triethylamine; the mechanism has not been established (B. Pandey and P.V. Dalvi, Angew. Chem., Int. Ed. Engl., 1993, 32_ 1612). O

H

0

H

0

(67) (f)

O

(68)

Complexes and Molecular Assemblies

In the crystal, methoxy-1,4-benzoquinone is networked into a planar hexagonal array by intermolecular dipole-dipole and

26 extensive CH.-.O hydrogen bond interactions; one hydrogen of the methyl group, the three alkene hydrogens, and the three oxygen atoms are involved in hydrogen bonding (E.M.D. Keegstra et a/., J. Chem. Soc., Chem. Commun., 1994, 1633). Steady-state and transient absorption spectra of solid quinhydrones (1 "1 complexes between 1,4-benzoquinones and hydroquinones) have been shown to be dependent on the method of preparation of the crystals (K.K. Kalninsh et al., J. Photochem. Photobiol. A: Chem., 1994, 77. 9). The 'quinhydrone' between 1,4benzoquinone and 4,4'-dihydroxydiphenyldisulfide forms black crystals containing parallel chains of alternating quinone-phenol moieties linked by carbonyl-hydroxy hydrogen bonds (K. Sugiura et a/., Angew. Chem. Int. Ed. Engl., 1992, 3.j.1,852). The properties of covalently bound cage structures involving quinones and hydroquinones have been summarised as part of a wider review of "super" phanes (R. Gleiter and D. Kratz, Acc. Chem. Res., 1993, 2_.66,311). Macrocyclic bolaphiles containing two 1,4-benzoquinone units linked at their 2- and 5- positions have been employed to incorporate the quinonoid moieties into membrane systems, thus generating redox-active regions within the membranes (J.-H. Fuhrhop and M. Krull, in H.-J. Schneider and H. DQrr, eds, "Frontiers in Supramolecular Organic Chemistry and Photochemistry", VCH, Weinheim, 1991, pp. 223-249; G.H. Escamilla and G.R. Newcombe, Angew. Chem. Int. Ed. Engl., 1994, 3_33,1937). These systems are related to naturally occurring ones in which electron-storage and electron-transfer occur, such as enzymes and photosynthetic reaction centres where substituted 1,4-benzoquinone moieties play a key r61e (M. Iwaki and S. Itoh, in J.R. Bolton, N. Mataga and G. McLendon, eds, "Electron Transfer in Inorganic, Organic, and Biological Systems", American Chemical Society, Washington, D.C., 1991, Chap. 10; J.A. Duine and J.A. Jongejan, in J. Reedijk, ed., "Bioinorganic Catalysis", Marcel Dekker, New York, 1993; M. Baumgarten, W. Huber and K. MQllen, Adv. Phys. Org. Chem., 1993, 2_88,1; A. Labahn et al., J. Phys. Chem., 1994, 9__68,3417; K. Warnke et al., Biochemistry, 1994, 3,3, 7830). A range of macrocycles has been synthesised which contain cavities into which 1,4-benzoquinones can be incorporated, and

2"7 held in place by hydrogen bonding to each of the carbonyl oxygen atoms (C.A. Hunter et al., J. Am. Chem. Soc., 1992, 114, 5303; J. Chem. Soc., Chem. Commun., 1994, 1277; Chem. Soc. Rev., 1994, 2,3, 101). 1,4-Benzoquinones carrying polyether bridges linking the 2,6- positions have been described (M. Delgado et al., J. Am. Chem. Soc., 1992, 114, 8983). Monolayers prepared by reaction of gold surfaces with 11mercaptoundecanoic acid incorporate 2,2",4,4"-tetramethyl-4,4"diphenoquinone, which under electrochemical conditions can be redox cycled in situ with its hydroquinone, 2,2",4,4"-tetramethyl-4,4"dihydroxybiphenyl (M. Kunitake eta/., J. Chem. Soc., Chem. Commun., 1994, 563; see also C. Duschl, M. Liley and H. Vogel, Angew. Chem. Int. Ed. Eng., 1994, 3,3, 1274; A. Badia, R. Back and R.B. Lennox, Angew. Chem. Int. Ed. Engl., 1994, 3,3, 2332). Monolayers of substituted 1,4-benzoquinones result when a side-chain terminates in a thiol group through which binding to a gold surface can occur (J.J. Hickman et al., Science, 1991,2..52, 688).

(g)

Ring Fragmentation

Contraction of the 1,4-benzoquinone ring occurs when the quinone is treated with 4-nitrophenylazide" the enamine (69) is formed (I.T. Barnish and M.S. Gibson, J. Chem. Res. (S), 1992, 208; (M), 1740-1757). Extensive reorganisation takes place when the 3-azido-1,2-benzoquinone (70) is themolysed in boiling benzene, affording, possibly via a benzyne intermediate, the solvent-adduct (71) (K. Chow, N.V. Nguyen and H.W. Moore, J. Org. Chem., 1990, 5.5, 370). Analogous thermolysis of azidoquinones, as (72), results in symmetrical fragmentation to afford 2 mol of the corresponding cyanoketene (73) (H.W. Moore et a/., J. Org. Chem., 1990, 5.5, 3876). Electro-oxidative desorption of 2,2'-bisdehydrohydroquinone adsorbed at a benzenoid moiety on a platinum surface probably results in initial formation of the bis-quinone followed by oxidative cleavage of the adsorbed ring to afford the dicarboxylic acid (74); a more detailed understanding of electrochemical processes of this type may lead to the development of new synthetic methodology (A.T. Hubbard, Heterogeneous Chemistry Rev., 1994, 1, 3, and references therein).

28 CI

O

Me3S,~" ""3

O (69)

(70)

O

OH

,oC'X

R

R~~- x~ -N3

O II R~~CN

CN (71)

(72)

(73)

The oxidative cleavage of catechols to the corresponding (Z, Z)-muconic acids has long been considered to occur via the 1,2benzoquinones, and evidence of their transient involvement has been obtained from studies of the auto-oxidation of compounds such as 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylalanine (DOPA)in the presence of ~cyclodextrins in alkaline media (A.V. Eiiseev and A.K. Yatsimirskii,

CO2H

c~ "~,

__. OH

O O (74)

O2H CO2H . ~

(75)

"CHO (76)

29 J. Org. Chem., 1994, 5_99,264). However, cleavage of the 3,5-di-tbutylcatechol ring, to afford breakdown products such as (75) and (76), by oxygen in the presence of catalytic iron(ll) and water occurs via catechol-iron complexes; 3,5-di-t-butyl-l,4-benzoquinone is also formed, and survives (T. Funabiki et a/., J. Chem. Soc., Chem. Commun., 1994, 1453, 1951). Similar chemistry may be involved in the degradation of lignins (K. Valli et al., Appl. Environ. Microbiol., 1992, 5_88,221), and in the iron(Ill) catalysed oxidative degradation of 4-substituted-l,2-dimethoxybenzenes (veratroles): electronaccepting substituents such as formyl and acetyl induce the formation of muconic acids, whereas donor substituents such as tbutyl and hydroxymethyl lead to the formation of 5-substituted-2methoxy-l,4-benzoquinones (1. Artaud, K. Ben-Aziza and D. Mansuy, J. Org. Chem., 1993, 5._88,3373). Although 1,2- and 1,4-benzoquinones can be destroyed by oxidation, a route favoured in Nature involves reduction to the corresponding hydroquinones followed by oxygenation prior to ringcleavage (cf. D.L. IIIman, C&EN, 1993, 7.j.1,July 12, p.26).

1

(a)

Synthesis of Benzoquinones From Phenols and Hydroquinones and their Ethers

Treatment of 2,3,5-trisubstituted (variously H, Me, OMe) anisoles with dimethyl dioxirane affords the corresponding 1,4benzoquinones, sometimes quantitatively (W. Adam and M. Shimizu, Synthesis, 1994, 560). Oxidation of 2,5-dimethylphenol with hydrogen peroxide catalysed by a cerium(IV)-calix[8]arene gives a moderate yield of 2,5-dimethyl-1,4-benzoquinone, but similar treatment of phenol and 2,6-dimethylphenol results in hydroxylation only, the products being hydroquinone and its 2,6-dimethyl homologue respectively (H.M. Chawla, U. Hooda and V. Singh, J. Chem. Soc., Chem. Commun., 1994, 617). Calix[1-6]-para-quinones can be obtained by oxidative de-tbutylation of the corresponding 4-t-butylcalixarenes using thallium(Ill) trifluoroacetate (J.-D. van Loon et al., J. Org. Chem., 1990, 55, 5639; C.D. Gutsche et al., Isr. J. Chem., 1992, 32, 89; J.

30 Org. Chem., 1993, 5__88,3245; see also M. Tashiro et al., J. Org. Chem., 1990, 5,5, 2404). The calix[4]quinone is formed in good yield by oxidation of the corresponding hydroquinone with iron(Ill) chloride (Y. Morita et a/., J. Org. Chem., 1992, 5"7, 3658). Substituted 4-hydroxy-N,N-dimethylbenzylamines afford the corresponding 1,4-benzoquinones, including prenyl-1,4benzoquinones, when oxidised with Fremy's salt in a two-phase aqueous buffer - dichloromethane system (J.M.Sa& et a/., J. Org. Chem. 1992, 5.!, 589; 1993, 5_88,328). Hydroquinone monomethyl ether yields 1,4-benzoquinone when treated with aqueous nitric acid (B.D. Beake, J. Constantine and R.B. Moodie, J. Chem. Soc., Perkin Trans. 2, 1994, 335). Ammonium cerium(VI) nitrate continues to find use for the conversion of substituted hydroquinone monomethyl ethers into the corresponding 1,4-benzoquinones (T. Yoon, S.J. Danishefsky and S. de Gala, Angew. Chem. int. Ed. Engl., 1994, 3__33,853); the use of this reagent as a one-electron oxidant has been reviewed (G.A. Molander, Chem. Rev., 1992, 9._22,29). Treatment of hydroquinone with periodate-doped silica gel in dichloromethane affords 1,4-benzoquinone essentially quantitatively (M. Daumas et al., Synthesis, 1989, 64); ammonium cerium(VI) nitrate can also be used for the heterogeneous oxidation of hydroquinones to the corresponding benzoquinones (J. Morey and J.M. Sa&, Tetrahedron, 1993, 4_.99,105), as can silver(I) carbonate in benzene (J.S. Yadav, V. Upender and A.V. Rama Rao, J. Org. Chem., 1992, 5._7.7,3242). Gaseous nitrogen oxides (NOx) catalyse the auto-oxidation of hydroquinones suspended in dichloromethane to give 1,4-benzoquinones, in very high yield (E. Bosch, R. Rathore and J.K. Kochi, J. Org. Chem., 1994, 59, 2529; R. Rathore, E. Bosch and J.K. Kochi, J. Chem. Soc., Perkin Trans. 2, 1994, 1157). The traditional industrial route to hydroquinone from benzene, via mononitration, reduction to aniline, manganese(IV) oxidation to 1,4-benzoquinone and then reduction with iron(ll), generates environmentally unfriendly by-products, and alternative routes are being sought. One involves the bacterial conversion of D-glucose into quinic acid, from which hydroquinone, and 1,4benzoquinone, can be obtained by treatment with aqueous manganese(IV) oxide ( K.M. Draths, T.L. Ward and J.W. Frost,, J. Am. Chem. Soc., 1992, 114, 9725). Another is based on the wellestablished synthesis of phenol and acetone from cumene hydroperoxide. Thus alkylation of benzene with propene is allowed

3] to proceed to 1,4-bisisopropylbenzene, catalytic oxidation with oxygen then affords the o~,o~'-bishydroperoxide, and rearrangement cleavage of this under acidic conditions yields hydroquinone and 2 mol of acetone (J. Haggi n, C&EN, 1994, 7_22,April 18, p.22). One-electron oxidation, via pulse radiolysis, of hydroquinones and catechols in aqueous solution produces the semiquinones which disproportionate to form the corresponding quinones, thus enabling these quinones, particularly very unstable ortho-quinones, to be studied in aqueous media under conditions which may resemble those encountered in vivo (C.J. Cooksey eta/., Melanoma Res., 1992, 2,283; E.J. Land, J. Chem. Soc., Faraday Trans., 1993, 8_99,803). Representative of these transient compounds are 3,4-mandeloquinone (77) (M. Bouheroum, J.M. Bruce and E.J. Land, Biochim. Biophys. Acta, 1989, 998, 57) and Nacetyldehydrodopaquinone (78) (M. Sugumaran et a/., J. Biol. Chem., 1992, 267, 10355). -

O~o O

CO2H

H

(77)

O~,",,~ NHAc O (78)

Further evidence for the stabilisation of ortho-benzosemiquinones by complexation with zinc(ll) in aqueous solution has been provided by electron spin resonance spectroscopy (R.P. Ferrari et a/., Spectrochim. Acta, A, 1993, 4_.99,1261 ).

(b)

From Cyclobutene- 1,2-diones

Insertion of cobalt into 2,3-dimethylcyclobutenedione gives maleoylcobalt complexes such as (79) which on photolysis afford a transient diketene which can be effectively trapped with alkynes, R'C=-C.R2 to yield, following removal of the cobalt, the corresponding 1,4-benzoquinones (80) (L.S. Liebeskind et al., Organometallics, 1986, 5, 1086; J. Am. Chem. Soc., 1987, 109,

32 2759). In a further development, involving different ligands and Lewis acid (rather than photochemical) activation, the benzoquinone (81) has been prepared from 3-isopropyl-4methoxycyclobutene-l,2-dione (L.S. Liebeskind et al., Tetrahedron Lett., 1990, 31,3723). O

O

O

Cp /

-~ O (79)

CO

R2 O (80)

i

O (81)

The route developed by H.W. Moore and his collaborators is of particular importance because of its versatility, which enables it to be used for the regiospecific synthesis of not only a wide variety of substituted 1,4-benzoquinones per se, but also '1,4-benzoquinones' carrying fused heterocyclic systems (see, e.g., S.T. Perri, P. Rice and H.W. Moore, Org. Synth., 1990, 69,220). It is based on the addition of alkenyl- and alkynyl-lithiums to mono- and di-substituted cyclobutene-1,2-diones to yield the corresponding e~-ketols (82) and (83) in which R ] - R4 may be variously alkyl, aryl, heteroaryl, alkoxy, and trialkylsilyl. Thermolysis, under comparatively mild conditions, affords, respectively, transient ketenes (84) and (85) which cyclise to yield, probably, diradicals, such as (86) from the alkene (84), and (87) from the alkyne (85); hydrogen transfer, which may be intermolecular, then affords the hydroquinone (88), which can be oxidised conventionally to the corresponding quinone, and, in the case of (87), the quinone (89; R4 = H) directly (H.W. Moore, et al., J. Am. Chem. Soc., 1990, 112, 1897, 5372; J. Org. Chem., 1991, 56, 4048; 1992, 57, 3765, 6896; 1994, 59, 2276). Methyl ethers (82; OMe instead of OH) can also be used (L.S. Liebeskind, K.L. Granberg and J. Zhang, J. Org. Chem., 1992, 57, 4345).

33

R~..

R2

R3

II

R 1"

O

R3

I \ OH R4

R

(82)

(83)

R 2,,,,,,,,~e~'% R 3

R3

RI~R 4 OH

OH

(84)

(85)

O

O

@

R3

Rlf-~

o

OH

OH

(86)

(87)

, R3

O

OH

RI.."~

R4

R2

R3

R1

R4

OH

O

(88)

(89)

A recent variation, which extends the alkyne route to the direct synthesis of tetrasubstituted 1.4-benzoquinones. involves

34 thermolysis of the o~-ketol (83) in the presence of tributyltin(IV) methoxide, which affords the stannylquinones (89; R4 = SnBu3); palladium-induced coupling with aryl iodides, including substituted phenyl (methoxy, nitro and amino groups are tolerated) and various heterocyclic iodides, then yields the corresponding 1,4benzoquinones (89; R4 = aryl, heteroaryl) (L.S. Liebeskind and B.S. Foster, J. Am. Chem. Soc., 1990, ! 12, 8612; L.S. Liebeskind and S.W. Riesinger, J. Org. Chem., 1993, 58,408; see also J.P. Edwards, D.J. Krysan and L.S. Liebeskind, J. Org. Chem., 1993, 58, 3942). Moore's group has recently introduced the vinylcyclobutenone (90) as a new synthon for precursors of his thermolysis route to 1,4-benzoquinones; alternative substitution patterns can be generated via conjugate [1,6] Michael addition of nucleophiles to the dienone system (H. Liu et al., J. Org. Chem., 1994, 59, 3284).

\

OMe

I [i [ OMe (90)

Thermolysis of (83; R 1 = OMe, R2 =, e.g., CH2CH2S-9anthracenyl, R3 = CH2Ph), in which R 2 is a potential intercalator, in the presence of supercoiled DNA results in strand-cleavage, possibly via the diradical intermediate, as (87) (H.W. Moore et al., J. Org. Chem., 1994, 59, 2276). The use of substituted 2-alkoxy-4-vinyl-2-cyclobutenones allows catechols, which can be oxidised subsequently to yield the corresponding ortho-benzoquinones, to be prepared by an analogous sequence of reactions (A. Gurski and L.S. Liebeskind, J. Am. Chem. Soc., 1993, 115, 6101 ). Overall, the development of these versatile and synthetically useful methods represents a new era in the synthesis of quinones.

3.5 11

(a)

Benzoquinone Methides Overview of Quinone Methide Reactivity

The benzoquinone monomethides, of which the ortho (91) and para (92) isomers are the parents, occupy a unique position in that conjugate Michael addition of nucleophiles to the methylene groups of either, and cyclo-addition to the exocyclic enone system of the ortho-isomer, lead immediately to a benzenoid product, and are therefore thermodynamically favoured processes. In each case, Michael addition of the nucleophile affords a phenolate directly (two steps, addition and enolisation, are required to reach this level with a benzoquinone); the corresponding addition to a benzoquinone dimethide is less favourable since the immediate product is a benzylic carbanion. The properties of 1,2- and 1,4-benzoquinone dimethides have been reviewed (J.L. Charlton and M.M. Alauddin, Tetrahedron, 1987, 43, 2873). As with 1,2-benzoquinones, [4 + 2] cycloaddition to both 1,2benzoquinone mono- and di-methides occurs readily, in the dimethides with inverse electron demand (D.L. Boger and S.M. Weinreb, "Hetero Diels-Alder Methodology in Organic Synthesis", Academic Press, San Diego, 1987), because benzenoid systems [dihydrobenzopyrans and benzopyrans from the monomethides with alkenes and alkynes respectively (G.C. Paul and J.J. Gajewski, J. Org. Chem., 1993, 58, 5060), and the corresponding tetra- and dihydronaphthalenes from the dimethides (H. Fujihara, M. Yabe and N. Furukawa, J. Org. Chem., 1993, 58, 5291)] are formed directly.

CCo

~

H2

,(,) 0

(91)

(92)

36 This special reactivity towards nucleophiles is an important contributor to the mechanism of cancer chemotherapy via bioreductive alkylation with quinones (H.W. Moore and R. Czerniak, Med. Res. Rev., 1981, !, 249) exemplified particularly by the mitomycins (based on indole-4,7-quinones) and the anthracyclines (in which a 9,10-anthraquinone is central) where reduction to the semiquinone, or to the hydroquinone dianion or its equivalent, results in expulsion of a strategically placed leaving group with concomitant generation of a quinone methide; alkylation of DNA bases can ensue (see, e.g., M.G. Peter, Angew. Chem. Int. Ed. Engl., 1989, 28,555; G.E. Adams et al., eds, "Selective Activation of Drugs by Redox Processes", Plenum, New York, 1990; see also D.C. Thompson et al., Chem.-Biol. Interactions, 1992, 86, 129). Further, 1,4-benzoquinone monomethides are involved in the sclerotisation (tanning) of insect cuticle (M. Sugumaran et al., Arch. Insect Biochem. Physiol., 1990, 14, 93, 237; 1991, 16, 31; FEBS Lett., 1991,279, 145; J. Biol. Chem., 1992, 267, 10355), and in the biosynthesis of melanins (M. Sugumaran, H. Dali and V. Semensi, Bioorg. Chem., 1990, 18, 144) and eumelanins (M. Sugumaran and V. Semensi, J. Biol. Chem., 1991, 266, 6073). They also contribute to the formation of neolignans (S.R. Angle and K.D. Turnbull, J. Org. Chem., 1993, 58, 5360) and lignins (S.M. Shevchenko and A.G. Apushkinskii, Russ. Chem. Rev., 1992, 61,105; E. Tsuchida and K. Yamamoto, in J. Reedijk, ed., "Bioinorganic Catalysis", Dekker, New York, 1993, Chap. 4; H. Set&l& et al., J. Chem. Soc., Perkin Trans. 1, 1994, 1163).

(b)

1,2-Benzoquinone Methides

In solution, the epoxides (93) are in equilibrium with the corresponding dark red monomethides (94), which predominate when R = OMe rather than H; they are trapped by methanol to yield the phenols (95), and by ethyl vinyl ether to give the chromans (96) (W. Adam et al., Angew. Chem. Int. Ed. Engl., 1993, 32, 735; Synthesis, 1994, 111). Substituted 1,2-benzoquinone monomethides are also formed, conveniently, by thermolysis of benzoxaborins (97), and can be trapped in the presence of Lewis acid activators by a variety of nucleophiles including alcohols, enols (at carbon), amines, and thiols (C.K. Lau, et al., Can. J. Chem., 1989, 67, 1384; 1992, 70, 1717; see also S.H. Woo, Tetrahedron Lett., 1993, 34, 7587).

3"7 Thermolysis of 4H-1,2-benzoxazines has also been employed (M. Yato, T. Ohwada and K. Shudo, J. Am. Chem. Soc., 1990, 112, 5341); the parent compound is formed by gas-phase pyrolysis of chroman, and can be trapped stereospecifically by both (E)- and (Z)-2-butene (G.C. Paul and J.J. Gajewski, J. Org. Chem., 1993, 58,

506o). Ph

Ph

N

(94) O

(95) R2

R1 R

O B

Et (96)

OMe

R

R

(93)

Ph.

"Ph

(97)

Conjugate elimination of the elements of water from substituted saligenins (2-hydroxybenzyl alcohols) has often been used as a route to the corresponding 1,2-benzoquinone monomethides, and is involved in the formation of phenolformaldehyde resins, and, relatedly, of calixarenes (C.D. Gutsche, in J.L. Atwood, J.E.D. Davies and D.D. MacNicol, eds, "Inclusion Compounds", Oxford University Press, Oxford, 1991, Vol. 4, Chap. 2; I. Alam, S.K. Sharma and C.D. Gutsche, J. Org. Chem., 1994, 59, 3716), but the generality of the method has recently been enhanced by the use of better leaving groups at the benzylic position, e.g. as (98) in which X is thiolyl (T. Inoue, S. Inoue and S. Kato, Chem. Lett., 1990, 55; Bull. Chem. Soc. Japan, 1990, 63, 1647) or benzotriazolyl (A.R. Katritzky et al., J. Org. Chem., 1994,

38 5_99,1900); synthetically useful trapping at the methylene group, in situ, then ensues. a2

R1 ,

SiMe3 X

HO'~'~

O.~~

R2~~

R2

(98)

cH2 "O

R1

R1

(99)

(100)

Elimination can also be effected from 1,4-benzoquinones, as (99); the resulting methides (100) can be trapped with alcohols, carboxylic acids and enol ethers, the latter affording 2alkoxychromans (K. Karabelas and H.W. Moore, J. Am. Chem. Soc., 1990, 11.2, 5372). 1,2-Benzoquinone monomethides may be intermediates in the photoregeneration of alcohols which have been protected as I](o-hydroxystyryl) dimethylsilyi ethers (M.C. Pirring and Y.R. Lee, J. Org. Chem., 1993, 58, 6961), and in the formation of coumarins by gas-phase pyrolysis of o-hydroxycinnamates (M. Black et al., J. Chem. Soc., Chem. Commun., 1993, 959). 1,2-Benzoquinone dimethides have been extensively studied, particularly as transient reactants in syntheses, notably those based on [4 + 2] cycloadditions. The parent compound is conveniently prepared by thermolysis (at 80 oC) of 1,4-dihydro-2,3benzoxathiin 3-oxide, with extrusion of sulfur dioxide (M.D. Hoey and D.C. Dittmer, J. Org. Chem., 1991,56, 1947; see also G. Kanai, N. Miyaura and A. Suzuki, Chem. Lett., 1993, 845). It has also been obtained by an improved (potassium iodide - [18]crown-6) Finkelstein elimination from (~,o~'-dibromo-o-xylene, and trapped with buckminsterfullerene (C6o) (P. Belik et al., Angew. Chem. Int. Ed. Engl., 1993, 32, 78); various substituted 1,2-benzoquinone dimethides, prepared by the thermolysis of benzocyclobutenes, also form adducts with C60 (A. Gegel et al., Angew. Chem. Int. Ed.

39 Engl., 1994, 3,3,559; M. lyoda et al., J. Chem. Soc., Chem. Commun., 1994, 1929). (z-Substituted 1,2-benzoquinone dimethides can be generated by thermal extrusion of sulfur dioxide from cyclic sulfones (S.P. Maddaford and J.L. Charlton, J. Org. Chem., 1993, 5_88,4132), and by treatment of the corresponding 13-substituted o(tributylstannylmethyl)styrenes with arylsulfenyl chlorides (H. Sano, K. Kawata and M. Kosugi, SYNLETT, 1993, 831). Fluoride-induced elimination from benzylsilanes (101) may produce the ketenes (102) which can be scavenged with aldehydes to yield 3,4-dihydroisocoumarins, with fumarates to afford o~tetralones, and with 3,4-dihydroisoquinolinium salts to give 8oxoberbines; some of the products may arise directly from the benzylic carbanion without loss of X; the balance is controlled by the leaving-group power of X and the nucleophilicity of the medium (S.V. Kessar, eta/., J. Org. Chem., 1992, 57, 6716; cf. H. Fujchara, M. Yabe and N. Furukawa, J. Org. Chem., 1993, 5_.68,5291). Interestingly, the parent ketene (102; R = H) is formed By Xradiolysis of benzocyclobutenone in an argon matrix (T. Bally and J. Michalak, J. Photochem. Photobiol. A: Chem., 1992, 6_.99,185). Generation of an imino analogue of (102) has been described (A.R. Deshmukh et al., Synthesis, 1992, 1083). Treatment of the chromium carbonyl compound (103) with butyllithium at low temperature generates the alcoholate which fragments to the corresponding dimethide, which can be trapped by methyl acrylate; photochemical removal of chromium then affords cis-2-methoxycarbonyl-l-tetralol (E.P. KQndig, G. Bernardinelli and J. Leresche, J. Chem. Soc., Chem. Commun., 1991, 1713). R

O

~SiMe3

R

[~.~,OcH2

~~OAc Cr(CO)3

(101)

(102)

(103)

40 The most important route to 1,2-benzoquinone dimethides involves the thermolysis of benzocyclobutenes (vide supra, and, e.g., K. Kobayashi et al., J. Chem. Soc., Perkin Trans. 1, 1992, 3111; J.J. Fitzgerald, N.E. Drysdale and R.A. Olofson, Synth. Commun., 1992, 22, 1807; A.R. Deshmuhk et a/., J. Org. Chem., 1992, 5_!, 2485). It has been employed successfully in the construction of a wide range of fused-ring systems via intramolecular [4 + 2] cycloaddition, e.g. the formation of (104) from (105) in boiling o-dichlorobenzene, where R contains a chiral auxiliary which allows (104) to be taken on to complete the first enantioselective total synthesis of (+)-cortisone (K. Fukumoto et al., J. Org. Chem., 1990, 5.5, 5625); an extensive review of these and related reactions is available (T.-L. Ho, "Tandem Organic Reactions", Wiley-lnterscience, New York, 1992). The outcome of some of these cyclisations may be influenced by the presence or absence of oxygen (K. Kobayashi et al., J. Chem. Soc., Chem. Commun., 1992, 780).

R ..

~

H

H

H MeO

MeO (104)

(105)

An example of cyclisation on to a phenyl group is provided by the methylenecyclobutenol (106), which thermolyses in 50% yield to the 9,10-anthraquinone methide (107); a dehydrogenation, possibly effected by an intermediate or a by-product, is required in order to complete the process (J.-C. Bradley, T. Durst, and A.J. Williams, J. Org. Chem., 1992, 57, 6575); an example of rearomatisation of a dimethide by a [1,5] hydrogen shift has been described (G. Dyker, Angew., Chem. Int. Ed. Engl., 1994, 33, 103).

4]

OH

O ph

I Ph (106)

~ Ph (107)

Intramolecular abstraction of benzylic hydrogen by a photoexcited ortho carbonyl group has also provided a useful entry to 1,2benzoquinone dimethides, which have been trapped by alkenes to afford 1-hydroxytetralins (J.L. Charlton and M.M. Alauddin, J. Org. Chem., 1986, 51,3490; J.L. Charlton and K. Koh, J. Org. Chem., 1992, 57, 1514; R.M. Wilson and K.A. Schnapp, Chem. Rev., 1993, 93, 223) and, from (108), allowed to collapse to the benzocyclobutenol (109) as a single diastereoisomer (P.J. Wagner, D. Subrahmanyam and B.-S. Park, J. Am. Chem. Soc., 1991, 113 709).

O

(108)

OH

(109)

The quinone dimethide resulting from photo-induced extrusion of carbon monoxide from 1,1,3,3-tetramethylindanone has been used for the detection of nitric oxide, with which it gives a nitroxide having a characteristic electron spin resonance spectrum; it could be useful for the detection of nitric oxide in biological systems (H.-G. Korth et al., Angew. Chem. Int. Ed. Engl., 1992, 31,

42 891; see also I.M. Gabr, U.S. Rai and M.C.R. Symons, J. Chem. Soc., Chem. Commun., 1993, 1099). An unusual, quantitative, preparation of 1,2-benzoquinone dimethide is by photolysis, in a variety of solvents, of the bisselenoether (110): in situ scavenging with electron-poor alkenes and alkynes affords the corresponding [4 + 2] adducts in 84 - 97% yield (H. Fujihara, M. Yabe and N. Furukawa, J. Org. Chem., 1993, 58, 5291).

~

Se Se (110)

(111)

(112)

Benzo[b]thiete (111) represents a source of 1,2-benzothioquinone monomethide (K. Saul et al., Chem. Ber., 1993, 126, 775; Liebigs Ann. Chem., 1993, 313). The bisthiete (112) behaves analogously, stepwise, on photolysis or thermolysis; interestingly, scavenging with either maleate or fumarate results in trans addition (H. Meier and A. Mayer, Angew. Chem. Int. Ed. Engl., 1994, 33, 465).

(c)

1,4-Benzoquinone Methides

Monomethides can be obtained under mild conditions via oxidation of appropriately substituted catechols to the corresponding 1,2-benzoquinones: both (77), by decarboxylation (M. Bouheroum, J.M. Bruce and E.J. Land, Biochim. Biophys. Acta, 1989, 998, 57), and (78), by tautomerisation (M. Sugumaran et al., J. Biol. Chem., 1992, 267, 10355), afford the corresponding 1,4benzoquinone methides, that from the decarboxylation of (77) tautomerising to 3,4-dihydroxybenzaldehyde. Direct oxidation of 4-alkylphenols can also be used. Thus treatment of the phenol (113) with a large excess of silver(I) oxide in dichloromethane yields the comparatively stable methide (114),

43 which on treatment with zinc(ll) chloride cyclises to the methylenecyclopentane (115) in high yield (S.R. Angle and K.D. Turnbull, J. Am. Chem. Soc., 1989, 111, 1136): samarium(ll) iodide is also effective for this type of cyclisation (S.R. Angle and J.D. Rainier, J. Org. Chem., 1992, 57, 6883), although cyclisation on to methoxy-activated phenyl residues can occur 'spontaneously' in aqueous acetonitrile at pH 6.8 (U.T. Bhalerao, C.M. Krishna and G. Pandey, J. Chem. Soc., Chem. Commun., 1992, 1176; see also H. Set&l& et al., J. Chem. Soc., Perkin Trans. 1, 1994, 1163). Intermolecular [3 + 2] cycloaddition of styrenes has also been observed (S.R. Angle and D.O. Arnaiz, J. Org. Chem., 1992, 57, 5937). OH

.SiMe3 (113)

O

OH

--(, SiMe 3 (114)

CH2 (115)

Treatment of a mixture of 2,6-di-t-butyl-4-methylphenol and acetylacetone with manganese(Ill) acetate in acetic acid affords, in low yield via a radical-driven 13-elimination of the 4-methyl group, the methide (116) (H. Nishino et al., J. Org. Chem., 1992, 57, 3551); the parent monomethide is formed when 4-bromomethyl-2,6-di-tbutylphenol is treated with triethylamine (K. Omura, J. Org. Chem., 1992, 57, 306). o~,o~-Bistrifluoromethyl-l,4-benzoquinone monomethide has also been prepared (J.P. Richard et al., J. Am. Chem. Soc., 1990, 112, 9507, 9513).

44 O

O

O

Ph~

Ph

O

(116)

(117)

(118)

Cyclic voltammetry has been used to study the redox chemistry of the monomethides (117; R = Me, But ) and the dimethide (118) (M.F. Nielsen et al., J. Chem. Soc., Chem. Commun., 1994, 1395), and of bis-ketene systems (J.H.P. Utley, Y. Gao and R. Lines, J. Chem. Soc., Chem. Commun., 1993, 1540). The parent 1,4-benzoquinone dimethide has been prepared by pyrolysis of the corresponding para cyclophane" it forms oligomers with C60 in toluene at -78~ C (D.A. Loy and R.A. Assink, J. Am. Chem. Soc., 1992, 114, 3977). The structure of a highly strained multiply substituted bis-cyclobutene-fused benzoquinone dimethide has been established by X-ray crystallography (J.-D. van Loon, P. Seiler and F. Diederich, Angew. Chem. Int. Ed. Engl., 1993, 32, 1706). The chemistry of 7,7,8,8-tetracyano-1,4-benzoquinone dimethide (TCNQ) continues to attract attention. It forms cyclophanes by addition to spiro-cyclopropanes (T. Tsuji, T. Ishihara and S. Nishida, J. Org. Chem., 1993, 58, 1601), and suffers displacement of a cyano group and concomitant reductive aromatisation to a merocyanine-type zwitterion under prolonged treatment with triethylamine (M. Szablewski, J. Org. Chem., 1994, 59, 954). However, the major effort has been directed towards the synthesis of lipophilic derivatives and analogues [J. Miura eta/., J. Org. Chem., 1988, 5,3, 439; H.E. Katz and M.L. Schilling, J. Org. Chem., 1991,56, 5318; C.A. Panetta et al., SYNLETT, 1991, 301; S.L. Vorob'eva and N.N. Korotkova, J. Chem. Res. (S), 1993, 34; H. Isotalo et al., J. Chem. Soc., Chem. Commun., 1994, 573] for the

45 development of novel redox systems (K. Takahashi, Pure Appl. Chem., 1993, 6.5, 127; K. Takahashi and S. Tarutani, J. Chem. Soc., Chem. Commun., 1994, 519; S. Yoshida et al., J. Org. Chem., 1994, 5_99,3077), synthetic metals (T. Nakamura et a/., Synth. Met., 1993, 5__7,3853), and organic and organometallic molecular magnetic materials (J.S. Miller and A.J. Epstein, Angew. Chem. Int. Ed. Engl., 1994, 33, 385). Thiobenzoquinones

,

Few data are available for these often very reactive compounds. The sulfones (119; R = H) (S. Thea et al., J. Org. Chem., 1985, 50, 2158), and (119; R = CI) and (120) (L. Field and C. Lee, J. Org. Chem., 1990, 55, 2558), and the thianthrene systems (121) and (122) (S.-R. Shin and H.J. Shine, J. Org. Chem., 1992, 57, 2706) have been described. CI R

O

R

O~ CI

SO 2

SO

(120) (121) NH ~S

,~~~S

O_ Ph

| (122)

(123)

SO 2

(124)

46 Treatment of 4-methyl-2-(phenylthio)phenol sulfoxide with thionyl chloride affords the cation (123) which can be trapped by conjugate addition (arrow) of phenols to yield biaryls (M.E. Jung, C. Kim and L. von dem Bussche, J. Org. Chem., 1994, 59, 3248). The formation of 1,2-benzoquinone monomethides from benzo[b]thiete (111) and the bisthiete (112) has been noted in Section 5(b). The imine (124) has also been prepared (L. Field and C. Lee, J. Org. Chem., 1990, 55, 2558). ,

(a)

Benzoquinone Imines

1,2-Benzoquinone Imines

N-Aroylimines such as (125) are N-arylated on treatment with 2,6-disubstituted phenols in methanol (H.W. Heine et al., J. Org. Chem., 1990, 5.5, 4039); they behave as heterodienes in DielsAlder reactions with alkenes (G. Desimoni, G. Faita and P.P. Righetti, Tetrahedron, 1991,47, 5857), and irt additions to anthracenes (at the 9,10- positions) (H.W. Heine eta/., J. Org. Chem., 1989, 5_44,5926). In these instances the quinonoid moiety becomes benzenoid, providing the driving force (cf___,1,2. benzoquinone monomethides). O

OH

CI N.Ar

Ar

CI (125)

Ar H

(126)

(127)

Treatment of o-aminopheny113-styryl ketones (126) with trifluoroacetic acid gives 2-aryl-2,3-dihydro-4-quinolones in high yield, possibly via iminomethides (127) (C.M. Brennan et al., Can. J. Chem., 1990, 68, 1780; C.D. Johnson, Acc. Ch. Res., 1993, 26, 476).

4"7

(b)

1,4-Benzoquinone Imines

Condensation of hydroxy-1,4-benzoquinones with phenylhydrazines and primary amines occurs at the carbonyl group adjacent to the hydroxy function, and probably yields the corresponding quinone imines which in the former case tautomerise to the azobenzenes (F. Wang et a/., J. Org. Chem., 1994, 5_fi, 2409); a corresponding, but equilibrium, tautomerisation has been observed for 4-hydroxyazobenzenes in which the hydroxy group is encircled by a macrocycle attached at the two positions ortho to it (E. Chapoteau et al., J. Org. Chem., 1991,5_.66,2575). Selective electro-oxidation of N,N'-bis-4-methoxyphenyl-2,2,2trifluoroethanimidamide and related compounds in aqueous acetonitrile produces the corresponding quinone monoimines (K. Uneyama and M. Kobayashi, J. Org. Chem., 1994, 5_.99,3003). N-Chloro-1,4-benzoquinone monoimines undergo Nhydroxyarylation in the presence of phenolates, providing intermediates for the synthesis of substituted acridines (P.F. Corey, et al., Angew. Chem. Int. Ed. Engl., 1991,30, 1646). The mechanism of acidic hydrolysis of N-acetyi-1,4-benzoquinone monoimines has been studied (M. Novak and K.A. Martin, J. Org. Chem., 1991,5_66, 1585). Selective mono-oxidation of calix[6]arene with alkaline ferricyanide in the presence of 4-diethylamino-2-methylaniline produces a quinone imine which acts as a selective sensor for the uranyl ion (UO22+) (Y. Kubo et al., J. Chem. Soc., Chem. Commun., 1994, 1725). The spiro-dienone (128) opens to the quinone imine (129)in light, and can be regenerated thermally, suggesting that the system may be useful in molecular switching (J. Salbeck et al., Angew. Chem. Int. Ed. Engl., 1992, 3.~.1,1498). Acetaminophen (paracetamol; 4-acetamidophenol)is bioactivated by oxidation to N-acetyl-1,4-benzoquinone imine, which scavenges nucleophiles via Michael addition (R.B. Silverman, "Organic Chemistry of Drug Design and Drug Action", Academic Press, 1992, Chap. 7). Photolysis of the diazo-compounds (130; R = H, Me) affords the carbenes, which react with oxygen to give the corresponding 1,4-benzoquinone-O-oxides, which have lifetimes in excess of 20

48 ILLS(B.R. Arnold et al., J. Org. Chem., 1992, 5.!, 6469; see also G. Bucher and W. Sander, J. Org. Chem., 1992, 5"7, 1346).

NHMe

0

a N

O [1

-(,)i

R

N2 (128)

(129)

(130)

1,4-Benzoquinone N-benzoyl N-phenylsulfonyldi-imines react with enamines to afford 2,3-dihydro-5-phenylsulfonamido-indoles (D.L. Boger and H. Zarrinmayeh, J. Org. Chem., 1990, 5.5, 1379). N,N-Dicyano-1,4-benzoquinone di-imines have received attention as electron acceptors in organic and organometallic complexes which conduct electricity (A. Aum(~ller and S. H(~nig, Angew. Chem. Int. Ed. Engl., 1984, 2,3, 447; Liebigs Ann. Chem., 1986, 142; S. Henig, Pure Appl. Chem., 1990, 62,395; S.H(~nig et a/., Adv. Mater., 1991, 3, 225, 311; M.R. Bryce, Chem. Soc. Rev., 1991,20, 355; M.R. Bryce et al., J. Org. Chem., 1991,5_!7, 1690; S. HOnig et a/., Angew. Chem. Int. Ed. Engl., 1992, 3_!, 859). Poly(aniline) containing a 1"1 ratio of secondary amino and 1,4-benzoquinone di-imino residues becomes electrically conducting when the di-imino moiety is monoprotonated (R. Baum, C&EN, 1993, April 19, p. 36; see also J.C. Michaelson and A.J. McEvoy, J. Chem. Soc., Chem. Commun., 1994,79). ,

Homobenzoquinones

Homo-1,4-benzoquinones (131) are conveniently obtained by treatment of the 1,4-benzoquinone with a diaryldiazomethane (T. Oshima et al., Bull. Chem. Soc. Japan, 1988, 61,2507; 1989, 62, 2580; Tetrahedron Lett., 1993, 649; Chem. Lett., 1993, 1977). Some of these undergo thermal rearrangement, e.g., at 100 oC in

49 benzene, (131, R1 = R3 = Br; R2 = H; Ar = Ph) gives the xanthylium salt (132) (T: Oshima, K. Tamada and T. Nagai, J. Chem. Soc., Perkin Trans. 1, 1994, 3325). O RI,~,~Ar R2~ " ~ ~ 3

Ph He Ar

Br

(~

O (131)

O <J~~ ,~ gr ~

(132)

O (133)

The parent 'homo-1,4-benzynoquinone' (133) has a transient existence, but has been trapped with anthracene (T. Watabe, K. Oda and M. Oda, J. Org. Chem., 1988, 53, 216). Substituted 3,4-homo-1,2-benzoquinones isomerise to tropones when treated with boron(Ill) fluoride etherate (M.G. Banwell and M.P. Collis, J. Chem. Soc., Chem. Commun., 1991, 1343). ~

Benzoquinols (Hyd roxycyclohexadienones)

The most widely used methods of preparation involve the oxidation of ortho or para substituted phenols, particularly alkylphenols, but also 4-arylphenols, with phenyliodine bisacetate or trifluoroacetate (A. Varvoglis, "The Organic Chemistry of Polycoordinated Iodine", VCH, Weinheim, 1992; A. Pelter eta/., J. Chem. Soc., Perkin Trans. 1, 1992, 2246; 1993, 1891; P. Wipf eta/., J. Org. Chem., 1993, 5_68,1649, 7195; M. Kacun, D. Koyuncu and A. McKillop, J. Chem. Soc., Perkin Trans. 1, 1993, 1771; A. McKillop, L. McLaren and R.J.K. Taylor, J. Chem. Soc., Perkin Trans. 1, 1994, 2047), or by anodic oxidation (J.S. Swenton et al., J. Org. Chem., 1991,5_.66, 6156; 1992, 5_Z7,5568; 1993, 5__68,3308). The original Wessely oxidation [lead(IV) acetate in acetic acid] continues to be used (N.K. Bhamare, eta/., J. Chem. Soc., Chem. Commun., 1990, 739). Other oxidants include thallium(Ill) nitrate (T. Horie et al., J. Org. Chem., 1992, 57, 1038) and

50 chromium(VI) compounds [J. Muzart, J. Chem. Res.(S), 1990, 96]. Both sodium periodate (V. Singh and B. Thomas, J. Chem. Soc., Chem. Commun., 1992, 1211), and singlet oxygen, generated using Rose Bengal and visible light, have also proved effective (E. Navarro et al., Fitoterapia, 1992, 63, 251). Addition of alkyl- and aryl-lithiums to 1,4-benzoquinone affords the corresponding 1,4-benzoquinols (M. Solomon et al., J. Am. Chem. Soc., 1988, 110, 3702); perfluoroalkyl-lithium compounds behave similarly (H. Uno and H. Suzukib, SYNLETT, 1993, 91). Trifluoromethyltrimethylsilane, in the presence of potassium fluoride, behaves analogously, yielding the trimethylsilyl ether of the trifluoromethylbenzoquinol (G.P. Stahly and D.R. Bell, J. Org. Chem., 1989, 54, 2873).

(a)

1,4-Benzoquinols

Anodic oxidation of the hydroquinone diether (134) in the presence of methanol affords the bisketal (135) which can be hydrolysed selectively to the mono-protected 1,4-benzoquinone (136) (T.N. Biggs and J.S. Swenton, J. Org. Chem., 1992, 57, 5568). The corresponding dimethyl ketal reacts with Grignard reagents at the carbonyl group; cleavage of the resulting ketal with oxalic acid on silica gel affords the 1,4-benzoquinol (A. McKillop et a/., J. Chem. Soc., Chem. Commun., 1992, 1589). Aryl-lithiums behave analogously (J.S. Swenton et al., J. Org. Chem., 1993, 58, 3308). O~ O H

OMe

(134)

MeO

OMe

(135)

0

(136)

MeO

0

(137)

5] The resulting benzoquinols can be reductively aromatised to the corresponding 4-substituted phenols by treatment with sodium dithionite (K.A. Parker et al., J. Org. Chem., 1992, 51,5547) or zinccopper couple (J.S. Swenton et al., J. Org. Chem., 1993, 58, 3308). The corresponding ethers, such as 4-benzyl-4-methoxy-2,6dimethylcyclohexadienone, undergo quantitative dienone-phenol migration of the benzyl group when treated with aqueous acid, a rearrangement which is catalysed by certain antibodies (Y. Chen, J.-L. Reymond and R.A. Lerner, Angew. Chem. Int. Ed. Engl., 1994, 33, 1607). Treatment of 1,4-benzoquinone bisdimethylketal with titanium(IV) phenolates affords aryloxyhydroquinone dimethyl ethers in high yield (G. Sartori et al., J. Chem. Soc., Perkin Trans. 1, 1991, 3059). Oxidation of 4-methoxyphenol in the presence of sorbyl alcohol gives the transient benzoquinol ether (137), which undergoes spontaneous intramolecular Diels-Alder addition (A.E. Fleck, J.Ao Hobart and G.W. Morrow, Synth. Commun., 1992, 22, 179).

O

O

O

CO2Et

O

EtO2C (138)

CO2Et (139)

(140)

Several spiro-analogues and their ethylene ketals have been described (V.H. Pavlidis, H. Medcalf and I.G.C. Coutts, Synth. Commun., 1989, 19, 1247; J.S. Swenton, A. Callinan and S.J. Wang, J. Org. Chem., 1992, 57,78). Thermolysis of the spirocompound (138) at 145 oC results in cleavage of the cyclopropane

.52 ring to yield the enol ether (139); sensitised photolysis of (138) in the presence of penta-l,3-diene gives the o~-tetralone (140) (T.N. Biggs and J.S. Swenton, J. Org. Chem., 1992, 5__7_7,5568). Thermolysis of the cyclobutenones (141; R 1 = Bu or MeO; R2 = H or Me respectively) affords the corresponding spiro-oxiranes (142) (R.W. Sullivan et a/., J. Org. Chem., 1994, 5_99,2276). O RI~ Bn MeO

O.CH2R2

O Bn

MeO O

(141)

R2

(142)

O-O (143)

Peroxides, including the highly reactive spiro-dioxirane (143) (W.W. Sander, J. Org. Chem., 1988, 53, 2091), and the t-butyl peroxides (144, R 1 = H, OMe; R2 = AIk, Ar) [J. Muzart, J. Chem. Res.(S), 1990, 96] have also been described. O

OMe R1

~

I

Bu t~O (144)

(b)

O~CO2Et OAc (145)

(146)

1,2-Benzoquinols

The acetate (145), prepared by the lead(IV) acetate method, has been used as an intermediate in the synthesis of isotwistanes

53 (N.K. Bhamare et al., J. Chem. Soc., Chem. Commun., 1990, 739), and the transient spiro-oxirane (146), obtained by periodate oxidation of o-vanillyl alcohol, behaves as a diene towards [4 + 2] cycloaddition of spirocyclopentadienes (V. Singh and B. Thomas, J. Chem. Soc., Chem. Commun., 1992, 1211). Intramolecular mono- and bis-spirocyclisation of p_-tertbutylcalix[4]arene has been observed, the bis material being a mixture of three stereoisomers (A.M. Litwak et al., J. Org. Chem., 1993, 5_88,393).

(c)

1,4-Benzoquinol Imines

Electrolysis of 4'-alkyl- and 4'-aryl-acetanilides in methanolic lithium perchlorate - sodium hydrogen carbonate yields the imines (147) which can be hydrolysed to the corresponding ketones (J.S. Swenton et al., J. Org. Chem., 1993, 58, 867, 5607). Diazotisation of the aminoterephthalate (148) with nitrous acid followed by treatment with nickei(li) cyanide yields the protected, 'stable' (m.p. 152-153 oC), quinone diazide (149), the structure of which has been confirmed by X-ray crystallography (C.A. Panetta, Z. Fang and N.E. Heimer, J. Org. Chem., 1993, 58, 6146). O N.~R ~

O~ O H

O.

CO2Me

MeO

R2

(147)

MeO2C

O

MeO2C NH2 (148)

N(~

NQ

(149)

CO2Me


Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.III B, C,D(Partial), edited by M. Sainsbury 9 1995 Elsevier Science B.V. All rights reserved.

55

Chapter 9

DERIVATIVES OF BENZENOID HYDROCARBONS SUBST1TUENTS CONTAINING A SINGLE NITROGEN ATOM

WITH

S. M. Fortt

This chapter deals with material in much the same order as the 2nd edition, 1st supplement. The literature is covered from 1980 to 1993 inclusive. Other, more general reviews which contain much relevant information are: "Aromatics and Arenes" in "Methoden der Organischen Chemic" Eds. E. Mtiller and O. Bayer, Georg Thieme Verlag, Stuttgart, 1981, Vol 5/2b, "Comprehensive Organic Chemistry" Eds. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, Vol 4, p.423 and 'Whe Chemistry of the Functional Group: Supplement F, The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives" Eds. S. Patai and Z. Rappoport, W'dey Interscience, Chichester, 1982. 1. Nitro Derivatives of Bcrlzene. it~ Homologues and other Substituted Benzenes (a) Prevaration Nitration General and Mechanistic Aspects A comprehensive treatise on the mechanism and kinetics of nitration has been published (K. Schofield, Aromatic Nitration, Cambridge University Press, Cambridge, 1980). Aspects of industrial nitration have also been discussed (K.L. Dunlap in Kirk-Othmer Encyclopaedia of Chemical Technology. Eds. M. Grayson, D. Eckroth, Wiley Interscience, Chichester, 3rd Edition, Vol. 15, p.916 and G. Booth in Ullman's Encyclopaedia of Industrial Chemistry, Eds. B. Elvers, S. Hawkins and G. Schulz, VCH, Weinheim, 5th Edition, 1991, Vol. A17, p a l l ) . The possible formation of radical cations as intemaexfiates in aromatic nitration is of current interest (J. H. Ridd and J. P. B. Sandall, J. Chem. Soc., Perkin Trans., 2, 1986, 327; R. B. Moodie et al., ibid., 1985, 467; 1986, 1097). The relevance of electron donor-acceptor (EDA) complexes is highlighted in a detailed study of electrophilic aromatic substitution (J. K. Kochi, Pure Appl. Chem., 1991, 63, 255). Interestingly, the nitration of arenes by oxidation of

56

their charge-transfer complexes with nitrosonium salts has been demonstrated. Products and isomer ratios are similar to those arising from ordinary clcctrophilicnitration(E. K. Kim and J. K. Kochi, J. Org. Chem., 1989, 54, 1692). The directing effect of the trifluoromethyl group in nitration has been studied under a variety of conditions (G. A. Olah et al., J. Am. Chem. Soc., 1987, 3708). Ipso-nitration continues to attract attention. Nitration of anilines with p-alkyl substituents occurs by ipso-attack followed by 1,3 rearrangement of the nitro group (J. H. Ridd et al., J. Chem. Sot., Perkin Trans. 2, 1981, 518). The mechanism, rate-profiles and isotope effects of this reaction have been thoroughly studied (J. H. Ridd et al., ibid., 1983, 331, 1185, 1191). 2Alkylphenols are similarly nitrated at low temperature in acetic anhydride to give initially cyclohexa-2,4-dienones that rearrange to o-nitrophenols (A. Fischer and G. N. Henderson, Tetrahedron Lea., 1980, 21,4661).

~

OH

HNO3Ac20 -4(PC

OH NO2

R

R

R

Nitration of 2,4,6-trimcthylphenolleads to a mixture of 4-nitzocyclohcxa-2,5dienone and 4-nitrocyclohexa-2,4-dienone, the latter rearranging to the former. This can be isolated, but is slowly converted into 2,6Mimcthyl-4nitrophenol (G. G. Cross et al.,Can. J. Chem., 1984, 62, 2803). 0

OH OH 0

NO2 NO 2

57 The direct observation (1H,13C N ~ ) of a monocyclic dienone, formed by addition of nitronium ion to an unsubstituted position of 2,6-di-t-butylphenol, has be~n reported. The relative stability of the dienone is attributed to steric effects. Thus nitration of 2,6-di-t-butylphenol leads to 2,6Mi-t-butyl-4nitrophenol and 2-t-butyl-4,6-dinitrophenol via intermexfiates 2,6Mi-t-butyl-4nitrocyclohexa-2,5-dienone and 2,6-di-t-butyl-4,6-dinitrocyclohexa-2,4dienone respectively (G.G. Cross, A. Fischer and G.N. Henderson, ibid., 1984, 62, 1446).

H

-2~

.

NO2

NO2

~ ~) ~-,2 NO2

NO2 NO2

Preparative Aspects Much recent work is characteriseA by the need for the regioselective mononitration of reactive arenes. Nitrobenzene is best prepared with a deficit of nitric acid-sulfuric acid (K. Gramatikov et al., Bioteknol. Khim., 1989, 1, 23). Toluene, when nitrated with nitric acid in the presence of m o n ~ o n i t e clay, shows little msubstitution and a 2:1 preference for the formation of the p-isomer over the oisomer (H. Suzuki, H. Koide and T. Ogawa, Bull. Chem. Soc. Jpn., 1988, 61, 501). Nitronium tetrafluoroborate complexed with crown ethers mononitrates benzene and toluene (B. Masci, J. Chem. Sot., Chem. Commun., 1982, 1262). The mononitration of phenols can be achieved by metal nitrates absorbeM onto silica gel (R. Tapia, G. Torres and J. A. Valderrana, Synth. Commun., 1986, 16, 681), or various clay supports (A. Cornelius and P. l.aszlo, Synthesis 1985, 909). Sodium nitrate-lanthanium (III) nitrate in a 2phase system is also effective for mononiwation of phenols (M. Ouertani, P. Gerard and H. B. Kagan, Tetrahedron Lett., 1982, 4315). Anilines are pnitrated by urea nitrate in sulfuric acid. Interestingly, if the p-position is

58 blocked m-substitution occurs selectively (T. P. Sura, M. M. V. Ramana and N. A. Kudav, Synth. Commun., 1988, 18, 2161). The transfer-nitration of arenes with N-nim>-pyridinium and N-nitro-quinolinium salts is reported (G. A. Olah et al., J. Am. Chem. Sot., 1980, 102, 3507). N-Nitropyrazole in the presence of Lewis acids provides a useful reagent for the mononitration of arenes (G. A. Olah, S. C. Narang and A. P. Fung, J. Org. Chem., 1981, 46, 3533). The use of silver nitrate in acetonitrile with boron trifluofide as catalyst allows the selective mononitration of a variety of polymethylbenzenes in good yield, although treatment of hexamethylbenzene with an excess of nitronium tetrafluoroborate provides a very clean dinitration leading to dinitroprehnitene (G. A. Olah et al., ibid., 1981, 46, 3533; Helv. Chem. Acta, 1990, 73, 1167). 4-Methyl-4-nitro-2,3,5,6-tetrabromocyclohexa-2,5-dienone mononitrates activated arenes (A.M. Kashmttri and A.M. Munawar, J. Mat. Sci. Math,, 1988, 28, 289) via a radical mechanism (J.H. Ridd, S. Trevellick and J.P.B. Sandall, J. Chem. Sot., Perkin Trans. 2, 1992, 1535). The preparation of polynitrobenzenes and polynitrotoluenes is of continuing interest. Three isomeric aminotetranitrotoluenes are prepared by mixed acid nitration of appropriate aminodinitrotoluenes and subsequent aromatic nitramine rearrangement. (R.L. Atldns, R.A. Hollins and W.S. Wilson, J. Org. Chem., 1986, 51,3261). Me

Me I-I2SO4

NI--I2

-,~ -NO2 NHNO2

Me H2SO4

O2N

NO2

NH2

The apparent ipso nitration of 4-amino-2,6-dinitrotolucnr to pentanitroanilinr under these conditions is described and oxidation, or ammonolysis, allows the synthesis of hexanitrobenzene and 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), respectively. Oxidation of these polynitroanilines is best achieved using ozone in oleum or hydrogen peroxide in oleum (R.L. Atldns et al., ibid., 1980, 45, 2341; 1984, 49, 503). The thermal rearrangement of the intermediate niwamine to diazo-phenols is also studied (R.L. Atkins and W.S. Wilson, ibid., 1986, 51, 2572). More recent work is described in which 2,3,4,5-tetranitrotoluene is prepared via deamination of the corresponding

59 tetranitrotoluidine by treatment with nitrosylsulfuric acid and hypophosphorus acid (A.T. Nielson et al., ibid., 1994, 59, 1714).

Me O2N~~]~ NO20NOSO3 H

Me O2N~'~ NO2

o2N

o2N-'T++ -No2

NH2

NO2

H2SO+

then

Me H3PO2 -O2N_O2N~L~ NO2.~ 'NO2

N2

A similar strategy has been used for the preparation of other polynitroarenes such as decanitrobiphenyl (A.T. Nielson et al., ibid., 1983, 48, 1056). The nitration of m-dinitrobenzene to 1,3,5-trinitrobenzene by metal nitrate salt in superacid solution is suggested to involve a protonitronium cation as the nitrating species (G.A. Olah et al., J. Am. Chem. Sot., 1992, 114, 5608). The side chain nitration of a variety of acylpentanitrobenzenes is shown to be o-selective and can be of some synthetic utility (T.Keumi et al., J. Org. Chem., 1989, 54, 4034; 1986, 51, 3439). The reaction mcxtes involved in side chain nitration are discussed (H. Suzuki et al., Chem. Lea., 1987, 891).

o

Me

HNO3 .

Me

Me

Ac20

~'Y

Me

NO2 Me

R = pentyl

(b) Oxidation of Aromatic Amines Aromatic amines arc oxidiscd to the corresponding nitro compounds by dimethyldioxirane under phase-transfer conditions in excellent yield (D.L. Zabrowski, A.E. Moormann and K.R. Beck, Jr, Tetrahedron Lett., 1988, 29, 4501; R.W. Murray, S.N. Rajadhyaksha and L. Mohan, J. Org. Chem., 1989, 54, 5783). Sodium perborate in acetic acid is an effective reagent for the oxidation of electron-deficient anilines (A. McKillop and J.A. Tarbin, Tetrahedron Lett., 1983, 24, 1505). Fluorine reacts with wet acetonitrile to produce an oxidising agent for the oxidation of aromatic amines to nitroarenes. The procedure has been applied to the preparation of an 180 containing nitro derivative (M. Kal and S. Rozen, J. Chem. Soc., Chem. Commun., 1991, 567).

60 (c) Properties and Reactions The syntheses, structures and properties of the g-complexes, Meisenheimer complexes and anion radicals formed by aromatic nitro compounds have been reviewed (A. Goraczko and K. Kozlowski, Pr. Wydz. Nauk. Tech., Bydgoskie Tow. Nauk., Ser. A, 1985, 15, 73). The formation of MeisenheingT complexes has been specifically and comprehensively reviewed (F. Terrier, Chem. Rev., 1982, 82, 77; E. Buncel in The Chemistry of the Functional Group, Supplement F, The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives. Eds. S. Patai and Z. Rappoport, Wiley Interscience, Chichester, 1982, Chap.27, p.1225). A review on the history, structure and mechanism of formation of coloured Janovsky complexes is also available (J. Prousek, Chem. Listy, 1986, 80, 714). The aromatisation of anionic Janovsky a-complexes by Noxopiperidinium perchlorate allows the substitution of nitroarenes by acetone (A.K. Sheinkman, T.S. Chmilenko and G.G. Vdvokina, Zh. Org. Khim:, 1983, 19, 2218). The electron donor-accepter (EDA) complexes formed by tri- and dinitrobenzenes with hydroxyaromatic Schiff bases and N-substituted anilines have been studied (M. Gaber, G.B. Mohamed and M. Abd-el-Ghafa, J. Chem. Soc. Pak., 1987, 9, 423; N. Radha, D. Begum and J.S. Mary, Ind. J. Chem., See. A, 1987, 26A, 1006). The relative acidities of 4-nitro, 2,4-dinitro and 2,4,6-trinitrotoluene are considered ( J. Lelievre, P.G. Farrell and F. Terrier, J. Chem. Sot., Perkin Trans. 2, 1986, 333). The X-ray structure of cis-2-nitrostilbene shows that the molecule is in fact not planar and that there is no hydrogen bond between the nitro group and hydrogen atom on the central double bond (Z.V. Todres et al., Zh. Org. KhirrL, 1987, 23, 1805). The photochemical reduction of nitroarenes has been studied by timeresolved ESR spectroscopy in order to elucidate the initial processes involved (K. Akiyama et al., Bull. Chem. Soc. Jpn., 1986, 59, 3269). The first observation of chemically-induced dynamic electron-spin polarisation (CIDEP), due to nitrobenzene anion radicals in the presence of an electron donor, proves that radical generation takes place through a triplet mechanism. Photoreduction of nitroarenes with 10-methyl-9,10-dihydroacridine ( a NADH analogue) in the presence of perchloric acid leads to anilines (S. Fukuzumi and Y. Tokuda, Bull. Chem. Soc. Jpn. 1992, 65, 831), as does photo-reduction in the presence of semi-conductor particles (F. Mahdavi,

61 T.C. Bruton and Y. Li, J. Org. Chem., 1993, 58, 744). The use of nitroarenes containing groups such as 2-nitrobenzyl and 3-nitrophenyloxycarbonyl for the preparation of so-called "caged" compounds relies on their photolability. The subject has been reviewed (V.N.R. PiUai, Synthesis, 1980, 1). Nitroarenes can be used as radiosensitisers to hypoxic tumour cells and the effect of sterically demanding o-substituents on reduction potentials has been examined (M. Boyd et al., J. Chem. Sot., Perkin Trans. 2, 1994, 29). Nitroarenes (and nitrosoarenes) are commonly used as dyestuffs (R. Raue and J.F. Corbett in Ullman's Encyclopaedia of Industrial Chemistry, Eds. B. Elvers, S. Hawkins and G. Schulz, VCH, Weinheim, 5th F~tion, 1991, Vol. A17, p.383). The first Friedel-Crafts reaction of nitrobenzene has been reported (Y. Shen, H. Liu and Y. Chen, J. Org. Chem., 1990, 55, 3961): nitrobenzene is ethylated by ethanol-sulfuric acid. Nitroarenes can be ftmctionalise~ by the addition of Grignard reagents, followed by oxidation of the resultant aryl nitronate adducts back to nitroarenes (G. Bartoli, Ace. Chem. Res., 1984, 17, 109). - O.~rOMgX ~2

RMgBr ~

~R

KMnO,

~R

Hydrolysis of the intemm~tr nitronatr allows the preparation of nitroso compounds. Alternatively, reduction with LAH, or sodium borohydridr in the presence of Pd/C, leads to a l k y ~ e s (G. Bartoli et al., Tetrahextmn, 1987, 43, 4221). A variety of nitroarenes undergo nucleophific substitution. The subject is reviewed (C. Paradisi, Comprehensive Organic Chemistry, Eds. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, Vol 4, p.423). Halogenonitroarenes are most commonly employed. Sulfodechlorination of 2,4-dinitrochlorobenzene with potassium dithionite under phase-transfer conditions leads to a high yield of the corresponding benzenesulfonic acid (M. Gisler and H. Zollinger, Angew. Chem., 1981, 93, 184). Similarly, nucleophilic substitution of halogenonitroarenes by ammonia and simple amines is commonly reported to proceed under moderate pressure (T. lbata, Y. lsogami and J. Toyoda, Chem. Lett., 1987, 6, 1187; H. Kotsuki et al., Synthesis., 1990, 1147; T. Watanabe et al., ibid., 1980, 39; N.S. Nudelman, S.E. Socolovsky, Tetrahedron. Lett., 1980, 21, 3331; J.J. Kulagowski and

62 C.W. Rees, Synthesis, 1980, 215), although nitroaryl triflates are substituted in acetonitrile under reflux at ordinary pressures (H. Kotsuld et al., ibid., 1990, 1145). The difference in behavior of 1~ amines and 2 ~ amines of similar basicity when the substrate contains an o-nitro group has been further discussed (R.E. Akpojivi, T.A. Emokpae and J. Hirst, J. Chem. Soc., Perkin Trans. 2, 1994, 443). However, treatment of o-bromo or o-iodonitrobenzenes with stable enolate anions and cuprous iodide in hot DMF leads to symmetrical 2,2'-dinitrobiaryls and not the expected substitution products (S.V. Thiruvikraman and H. Suzuki, Bull. Chem. Soc. Jpn., 1985, 58, 1597). Nitro groups themselves are substituted if suitably activated by other substiments (J.H. Gorvin, J. Chem, Res. S ynop., 1992, 7, 226). Aromatic fluoro compounds can be prepared by nucleophilic exchange of nitro group by fluoride anion (F. Effenberger and W. S treicher, Chem. Ber., 1991, 124, 157) - yields are dramatically improved if the leaving nitrite ion is immediately trapped (M. Maggini et al., J. Org. Chem., 1991, 56, 6406). Alkoxides react with m-dinitrobenzene under basic, platinum catalyse~ conditions to give aryl ethers (M.D. Conner and M.E. Ford, Chem. Ind., 1992, 47, 359). The uncatalysed displacement of aromatic nitro group by phenoxides is considered to involve a radical mechanism (P.G. Sammes and D. Thefford, J. Chem. Soc., Chem. Commun., 1987, 1373). The so-called vicarious nucleophilic substitution (VNS) of hydrogen in nitroarenes by certain carbanions has been reviewed (M. Makosza and J. W'miarski, Acc. Chem. Res, 1987, 20, 282). The carbanion must generally contain a good leaving group and a carbanion stabilising group. Good pselectivity (relative to the nitro group) is often obtained (M. Makosza et al., J. Org. Chem., 1984, 49, 5273, 4562, 1494; Chem. Lett. 1984, 1623, 1619). Y ~.. H,-~.CRY

proton

+ X NO 2 N+

-o" "o-

R=H,SPh,Ph

_ , .+_

X = S P h , C I , S R ~'

o NO

No2

Y = S P h , SOzPh, S R ~

The mechanism of such substitutions is thought to involve an intermediate Meisenheimer complex, but other details are by no means clear. The subject

63 has been discussed (G.P. Stably, B.C. Statdy and J.R. Maloney, J. Org. Chem., 1988, 53, 690). One notable example is provided by the VNS of hydrogen, not halogen, in 2,4-dinitrofluorobenzcne (M. Makosza and J. Stalewski, Liebigs Ann. Chem., 1991, 6, 605). The method is of synthetic utility for the preparation of (chloromethyl)nitroarenes (M. Makosza and M. Bialecki, Synth. Lett., 1991, 3, 181). Direct hydroxylation of nitroarenes occurs by VNS of hydrogen using t-butylhydroperoxide anion (T. Brose et al., J. Prakt. Chem. / Chem. Zeitung, 1992, 334, 497). The VNS method is also used for the direct amination of nitroarenes (see later). The rearrangement of o-nitrobenzylidene malonate derivatives - prepared via a modified Knoevenagel reaction - in the presence of 2 ~ amine leads to 2amino-4-nitrobcnzoic acids (S. Kinastowski, S. W n u k and E. Kaczmarek, Synthesis, 1988, I 11). The rcductive carbonylation of nitroarcnes continues to attract intense interest.The individualreaction steps that arc believed to occur during metal camlyse~ carbonylation of nitroaromatics to isocyanatcs, carbamatcs, amines and ureas arc reviewed (S.H. Han, G.L. Gcoffroy, Polyhedron, 1988, 7, 2331). Ph_NH 2

CO -CO 2

Ph-N

I N

/\

M---M

Ph-N-M

Ph

Ph M

M _-

I

M

*

/ \N

CO

Ph-N=C=O

M--M

\I

M

Halides dramatic~y promote the formation and earbonylation of imido ligands at the metal centre. The proposed reaction steps for the ruthenium dodecaearbonyl catalyse~ water gas reduction of nitrobcnzenr to aniline have been individually observed (S. Bahaduri et al., J. Chem. Soe., Dalton Trans., 1984, 1765). An IR study has also been reported (J.D. Gargulak, W.L. Gladfeltcr and R.D. Hoffman, J. Mol. Catal., 1991, 68, L89; J. Am. Chem. Soc., 1991, 113, 1054). The use of palladium and ruthenium complexes as catalysts has been reviewed (T. Ikariya, Shokukai, 1989, 31, 271) as have those of rhodium (K. Nomura, M. Ishino and M. Hazana, Bull. Chem. Soc. Jpn, 1991, 64, 2624; J. Mol. Catal., 1991, 66, L1, L11, L19; 1992, 73, L1).

64 The area has been comprehensively discusse~ in a recent review (S. Cenini, M. Pizzotti and C. Crotti, Aspects Homog. Catal., 1988, 6, 97). Methods for reducing nitroarenes to the corresponding nitroso, hydroxylamino or amino compounds are discussed under those specific headings. 2. Nitroso Derivatives of Benzene and its Homoloeues

(a) Preparation

Nitrosation Aspects of aromatic nitrosation are discussed in more general reviews (Nitrosation, D.L.H. Williams, Cambridge University Press, Cambridge, 1987 and 1988; R.B. Moody, Org. React. Mech., 1986, 263; 1985, 265; 1984, 269). The kinetics and mechanism of nitrosation using HNO 2 in H2SO4 / CF3CO2H-H20 have been thoroughly examined (V.L. Lobachev, E.S. Rudakov and O.B. Savsunenko, Kinet. Katal., 1990, 31,795, 789). The gasphase nitrosation of benzene has also been studied using ab initio M.O. calculations (K. Raghavachari, W.D. Reents Jr. and R.C. Haddon, J. Comput. Chem., 1986, 265).

Preparative Aspects An electrosynthetic method for the preparation of nitrosobenzenes is reported (C. Lamoureux and C. Moiret, Bull. Soc. C']aim. Fr., 1988, 59). The method is based upon the reduction of nitroarene at a first porous electrode, followed by oxidation of the phenylhydroxylamine at a ~ n d . Pure, unpromoted trimanganese tetraoxide is reported to be a suitable catalyst for the selective reduction of nitrobenzene to nitrosobenzene (T.L.F. Fauvre, P.J. Seijsener and P.J. Kooyman, Catal. Lea., 1988, 1,457) Pyridinium chlorochromate oxidation of arylhydroxylamines leads to nitrosoarenes (W.W. Wood and J.A. Wilkin, Synth. Commun., 1992, 22, 1683). A new general method for the conversion of aromatic amines to the corresponding nitroso compounds has been described (E.C. Taylor et al., J. Org. Chem., 1982, 47, 552; 1984, 49, 2500) DMS, NCS

,~

9 NaOH

,nC

^

+

A

-N-SM OH

,

A

-N-O

65 (b) Prot)erties and Reactions The mutagenicity of certain p-substituted nitrosobenzenes has been related to their electron releasing ability (R.I. Gupta, M. Singh and T.R. Juneja, Ind. J. Exp. Biol., 1987, 25, 445). The substituent and solvent effects in the UV absorption spectra of nitrosoarenes have been detailed (G. Wan and M. Giurginca, Rev. Roum. Ofim., 1986, 31, 857). The EDA complexes of nitrosodimethyl~iline have been studied (J. Moskal, A. Moskal and P. Milart, Pol. Acad. Sci. Chem., 1984, 32, 317). The formation of mixed dimers in systems containing aliphatic and aromatic nitroso compounds have also been studied (V.A. Batyuk et al., Vesta. Mosk. Univ. Ser 2 Khim:, 1988, 29, 270). The use of nitroso compounds for the spin-trapping of inorganic radicals has been recently reviewed (D. Rehorek et al., Chem. Soc. Rev., 1991, 20, 341; Free Radical Res. Commun. 1990, 10, 75). The chemistry of aromatic nitroso compounds has been recently describext (Y.E. Belyaev, Khimiya, Leningradskoe Otcl, Leningrad, 1989). The reaction of nitrosoarenes with glyoxylic acid provides a new path for the preparation of N-arylhydroxamic acids (M.D. Corbett and B.R. Corbett, J. Org. Chem., 1980, 45, 2834; Experentia 1982, 38,1310). NO

0

No2

CHO

'

HO'N"CHO

0 ~

The Diels-Alder reactions of nitrosoarencs (and the similar, more commonly used nitrosocarbonylarcncs) are reviewed (S.M. Wcinreb and D.L. Bogcr, Hetcro-Dicls-Aldcr Methodology in Organic synthesis, Academic Press, N.Y. 1987, p71 ; S.M. Weinreb and P.R. Staib, Tetrahedron, 1982, 38, 3087). The reaction of nitrosoarencs with oxygenated dicnes is particularly efficient and can have some synthetic utility (E.C. Taylor, K. McDaniel and J.S. Skotnicki, J. Org. Chem.,1984, 49, 250(>, K.F. McClure and S.J. Danishefsky ibid., 1991, 56, 850). The cycloaddition of nitrosoarenes to benzothiete leads to two new heterocyclic ring systems (K. Saul et al., Chem. Ber., 1993, 126, 775). So called 'cascade reactions' involve addition of nitrosoarenes to dicnes followed by a series of rapid reactions and rearrangements of the unstable Diels-Alder adducts (A. Dcfoin et al., Helv. Chitin Acta, 1989, 72, 1199).

66 The product of the reaction of nitrosobenzene with pyran-2-thione arises from no less than six consecutive steps (A. Defoin et al., Helv. Cbirn~ Acta, 1985, 68, 1998). Nitrosoarenes with stericaHy demanding substituents are often used as radical traps leading to nitroxide radicals that do not react further. However nitrosobenzene itself traps the 2-diphenylmethylene-l,3-cyclopentadienyl diradical to give an unusually fused isoxazoline (W. Adam, S.E. Bottle and K. Peters, Tetrahedron Lett., 1991, 32, 4283). The reaction of nitrosoarenes with anilines in the presence of hypervalent iodine provides a useful method for the preparation of unsymmetrical azoxyarenes (R.M. Moriarty et al., Synth. Commun., 1990, 20, 2353). Treatment of nitrosoarenes with arylaminodimagnesium reagents also allows preparation of unsymn~tical azoarenes (M. Okubo, T. Takahashi and K. Koga, Bull. Chem. Soc. Jpn., 1983, 56, 302). Nitrosoarenes are reductively carbonylated (H. Alper and G. Vasapollo, Tetrahedron Lett., 1987, 28, 6411). 3. N-Arylhydroxylamin~s (a) Preparation Traditionally N-arylhydroxylamines are prepared by the electrolytic reduction of the corresponding nitroarenes. However, other methods for accomplishing this transformation, without concomitant formation of products of overreduction are available. Tin (II) complexes, prepared by treatment of tin (II) chloride with appropriate amounts of thiol and triethylamine, reduce aromatic nitro compounds to the corresponding hydroxylamines (M. Bartra et al., Tetrahedron, 1990, 46, 587). Sodium borohydride in ethanol catalysed by tellurium rapidly reduces p-substituted nitrobenzenes to the corresponding arylhydroxylamines (S. Uchida et al., Chem. Lett., 1986, 1069). Transferhydrogenation of a variety of substituted nitroarenes by hydrazine hydrate in ethanol-dichloromethane and Raney-nickel leads tO arylhydroxyamines, isolated as their benzohydroxamic acids (N.R. Ayyangar et al., Synthesis, 1984, 938). N-Arylhydroxylamines are also available from nitroarenes using o-xylene-cz,~-dithiol-iron complexes (K. Yanada, T. Nagano and M. Hirobe, Tetrahedron Lea., 1986, 27, 5113). The oxidation of secondary anilines by mCPBA in acetone affords o~, Ndiphenylnitrones which are reduced to the corresponding N-benzyl-Nphenylhydroxylamines by LAH in ether (J.W. Gorrod and N.J. Gooderhan, Arch. Pharm., 1986, 319, 261).

67 _ O.~w,,.ph HO.NAp FIN/ x Ph ~ mCPBA ~ IAH. ~ R

R

h

R

R=H,CI,Me Interestingly, N-allyl-N-arylhydroxylamines are available via the unusual 1,2addition of allyl Grignard reagents to nitroarenes, followed by LAH reduction in the presence of palladium on carbon (G. Bartoli et al., Tewahedron Lett., 1988, 29, 2251).

Ar --NO2

.

THF, -70aC

At'-

! ' OMga

OH

Co) Properties and Reactions Recent studies indicate that phenylhydroxylamine is intimately involved in aniline induced haemolytic anaemia (D.J. JoUow, S.J. Grossman and J.H. Harrison, Adv. Exp. Med. Biol., 1986, 197 (Biol. React. Intermed.3), 573). ESR studies show that the oxidation of phenylhydroxylamine by oxyHb to the phenylhydronitroxide radicalin turn leads to the thiyl radicals that arc causal in hacmolytic anaemia (K.R. Maples, P. Eycr and R.P. Mason, Mol. Pharmacol., 1990, 37, 311; T.P. Bradshaw et al., Adv. Exp. Med. Biol., 1991, 2831 (Biol.React. Intcrmcd. 4), 253). The 'selfoxidation reduction'of N-arylhydroxylamincs has received attention (C.H. Yang and Y.C. Lin, J. Chinese Chem. Soc., 1987, 34, 19). The prc-cquilibrium between phcnylhydroxylamincs and nitrosoarcnes has been further studied. It is shown that more electron-attractingp-substituents are obtained on the phcnylhydroxylaminc and more electron-releasing psubstitucnts are obtained on the nitrosobcnzcnc in accord with expcctcd maximisation of resonance stabilisation.(M.G. Hzzolatti and R.A. Yunes, Quire. Nova 1988, 11, 303). The subsequent condensation between these compounds in aqueous solution has been shown to be under general acid and base catalysis (A.R. Bccker and L.A. Stcmson, J. Org. Chem., 1980, 45, 1708).

68

NO

+

NHOH R2

RI

,

IdO_~H RI

o

1 R2

Rl and R2 interchange

RI

R2

mixture

The mechanism and kinetics of the Bambergcr-rcarrangemcnt have been studied in detail (T. Sone et al., J. Chem. Soc., Pcrkin Trans. 2, 1981, 29, 298; 1443). It is concluded that the reaction mechanism follows SN1 kinetics with the elimination of water from protonated phcnylhydroxylamine as the rate determining step. An intermediate nitrenium ion is then attacked intermolecularly by water. Treatment of N-arylhydroxylamines with acids in benzene leads to nitrenium ions that substitute the arcne. Thus in the presence of trifluoroacetic acid diphcnylamincs arc obtained and in the presence of the stronger acid, tfifluoromcthanesulfonic acid aminobiphcnyls are obtained (K. Shudo, T. Ohta and T. Okamato, J. Am. Chem. Soc., 198 l, 103, 645). Nitrenium ions are also generated by photolysis of aryl azides in benzene leading to diarylamincs (H. Takcuchi, K. Takano and K. Koyama, J. Chem. Soc., Chem. Commun., 1982, 1254). More recently the photolysis of some 1arylamino/alkylamino-2-mcthyl-4,Gdiphcnylpyridinium salts has been described, allowing the direct amination of benzene via nitrenium ions (H.Takcuchi et al., ibid., 1987, 961). The chemistry of arylnitrcncs has been specifically reviewed (E.F.V. Scrivcn et al., Angcw. Chem., 1979, 9 l, 965). Treatment of N-phcnylhydroxamic acids with vinyl acetate in the presence of Li2PdC14 affords 2,3-unsubstimted N-acylindolcs via a hetcro-Cope rearrangement of the N-phcnyl-O-vinylhydroxylaminc derivatives (P. Martin, Hclv. Chim. Acta, 1984, 67, 1647).

••'•S

OH ~"'OA'c ,cocH3

N-O , COCH3

",~ -NHCOCI_I3

, COCH3

The mechanism of nitrone formation by phenylhydroxylamine and furftwals under acid catalysis has bccn comprehensively studied (R. Fett, E.L. Simionatto and R.A. Yunes, J. Phys. Org. Chem., 1990, 3, 620).

69 Phenylhydroxylamine is employed in a variety of cycloaddition reactions which nomaally involve intermediate nitrones. For example, reaction with unsaturated aldehydes leads to isoxazolidinols and dioxazolidines (K.N. Zelenin et al., Khirrt Geterotsiki Soedin., 1987, 127ff, T. Sugimoto, M. Nojima and S. Kusakayashi, J. Org. Chem., 1990, 55, 4221). Reaction with allenic nitriles leads to quinolines (S.R. Landor et al., J. Chem. Sot., Perkin Trans 1, 1989, 251) 4. N-Arvlnitrones and N-Arvlnitroxides The preparation, properties and chemistry of N-arylnitrones and Narylnitroxides is discussed in more general reviews (H.G. Aurich in The Chemistry of the Functional Group Supplement F, The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives. Ed S. Patai, Wiley Interscience, 1989, Chichester;, The Chemistry of Nitrones, Nitronates and Nitroxides, p.313-399 and Nitrones, Nitronates and Nitroxides, E. Breuer, H.G. Aurich and A. Nielson, Wiley lnterscience, 1989, Chichester). Reaction of pcntyl nitrite with an excess of aryl Grignard reagent leads to N,N-diarylhydroxylamines which are oxidised to diarylnitroxides (C. Bertie, Synthesis, 1983, 793). Similarly, N-nitrosodiphenylamine reacts with aryl Grignard reagents forming symmetrical diarylhydroxylamines which are oxidised by lead dioxide to diarylnitroxides (L. Cardellini, L. Greci and G. Tosi, Synth. Commun., 1992, 22, 201). A tetramethylene-bridged thiazolium salt catalyses the reaction of nitrobenzene with benzaldehyde and lriethylamine to give a, Ndiphenylnitrone (H. Inoue and S. Tamura, J. Chem. Sot., Chem. Commun., 1985, 279). A variety of r N-arylnitrones are prepared by the reactions of nitrosoarenes with the hydrolysis products of pyridinium salts formed by reaction of primary amines with 2-(ethoxycarbonyl)-4,6-diphenylpyrliums (A.R. Katritzky et al., Reel. J R. Neth. Chem. Sot., 1983, 102, 51). Ph

t. Hyd.

~/~co2m

9

2. ArNO

t. R

Ar = ~ N M e

2

70 cz-Aroyl-N-phenylnitrones are prepared by the silver oxide oxidation of the adducts of silyl enol ethers and nitrosobenzene (T. Sasuki, K. Mori and M. Ohno, Synthesis, 1985, 279). An interesting example of an acyl nitrone is provided by N-acetyl-l,4benzoquinonimine N-oxide. The nitrone undergoes rapid N-O rearrangement and is a strong acetylating agent (P.F. Alewood and I.C. Calder, Tetrahedron Lea., 1985, 26, 2467). A~-N-O

q5 0

N-OAt

q5 0

5. Aromatic Amines derived from Benzene arid its Homolo~es. Nuclear Primary Mono~mines (a) Prepara~ion Reduction of the Nitro Group Most papers published in this area describe protocols for the mild and selective reduction of nitro group in the presence of other reducible groups. Rapid reduction of nitroarenes is achieved with AI-NiCI2-THF (P. Sarmah and N.C. Barua, Tetrahedron Lett., 1990, 31, 4065) and Zn-NiCI2-MeOH (A. Nose and T. Kudo, Chem. Pharm. Bull., 1990, 38, 2097) - the latter system allowing reduction of nitro groups in the presence of car~nyl and carboxyl groups. Ni-A1 alloy, employed under basic conditions, is a useful reagent for the reduction of nitro, as well as nitroso, azoxy, azo and hydrazo compounds to aromatic amines (W. Oppolzer and P. Dudfield, Tetrahedron Lett., 1985, 26, 5037). A1 amalgam is also used (A.P. Krapcho and T.A. Collins, Synth. Commun., 1982, 12, 293) as are various metals in liquid ammonia (L. Maat, J.A. Peters and M.A. Prazeres, Reel. Tray. m . Pays-Bas, 1985, 104, 205). The use of iron powder in cone. hydrochloric acid continues (D.H. Klaubert et al., J. Med. Chem., 1981, 24, 742) and even A1 scrap has been used under these conditions (M.S. Khan et al., J. Chem. Soc. Pak., 1988, 10, 393; J. Mat. Sci. Math., 1990, 30, 63). The sensitivity of the Zinin reduction to the steric environment of the nitro group is further reported (T.E. Nickson, J. Org. Chem., 1986, 51, 3963). Sodium sulfide in aqueous 1,4-dioxan (Y. Lin and S.A. Lang, Jr., J. Heterocycl. Chem., 1980, 17, 1273) and under phase-transfer catalysis by _

71 tetrabutylammonium bromide (V.F. Shner et al., Zh. Org. Khim. SSSR, 1989, 25, 879) allows sele~ive reduction of nitro groups to amines. SnCI2 (F.D. Bellamy and K. Ou, Tetrahedron Lett., 1984, 25, 839), HgCl 2, MgC12, T~CI4 (J. George and S. Chandrasekaran, Synth. Commun., 1983, 13, 495) and SmI2 (Y. Zhang and R. Lin, ibid., 1987, 17, 329) all reduce nitroarenes to amines under mild conditions. Electrocatalytic reductions of nitroarenes using Devarda-copper electrodes in basic media are reportedly milder and more selective than those with conventional electrodes (G. Belot, S. Desjardins and J. Lessard, Tetrahe~on Lett., 1984, 25, 5347). Aromatic nitro groups are selectively reduced by thiols in the presence of iron or iron complexes (S. Murata, M. Miura and M. Nomura, Chem. Lett., 1988, 361; M. Kijima et al., J. Org. Chem., 1984, 49, 1434). Lithium cobalt (I) phthalocyanine is also used for the selective reduction of nitroarenes (H. Eckert, Angew. Chem. Int. Ed. Eng., 1981, 20, 208). Borane in THF is used for the reduction of nitro groups to amines (R.S. Varma and G.W. Kabalka, Synth. Commun., 1985, 15, 843), as has lithium aluminium hydride (A. Handan and J.W.F. Wasley ibid., 1985, 15, 71) and sodium borohydride (F. Rolla, J. Org. Chem., 1982, 47, 4327). A wide range of transition metal chlorides have been used in conjunction with sodium borohydride: TiCI4 (S. Kano et al., Synthesis, 1980, 695), SnCl2 (T. Satoh et al., Chem. Pharm. Bull., 1981, 29, 1443) FeCI2 (A. Ono, H. Sasaki and F. Yaginuma, Chem. Ind., 1983, 480), NiCI2 (J.O. Osby and B. Ganem, Tetrahedron Lett., 1985, 26, 6413; see also A. Nose and T. Kudo, Chem. Pharm. Bull., 1986, 34, 3905), CuCI (A. Ono, M. Hiroi and K. Shinazaki, Chem. Ind., 1984, 75). Sodium telluride (H. Suzuki, H. Manaki and M. Inouye, Chem. Lett., 1985, 1671) and benzenetellurol (N. Ohira et al., ibid., 1984, 853) are also efficient reagents for reduction of nitroaromatics to amines. Heterogeneous metal-catalysed hydrogenation of nitroarenes (see for example M.A. Avery, M.S. Verlander and M. Goodman, J. Org. Chem., 1980, 45, 2750) appears less widely used than the homogeneous metal-catalyse~ equivalent. The nature of the platinum catalyst and solvent effects in the hydrogenation of some chloronitrobenzenes have been discussed (J. Strutz and E. Hopf, Chem.-Ing.-Tech., 1988, 60, 297). A wide range of transition metal complexes have been used based principally on rutheniurn (F. Wada, M. Shimuta and T. Matsuda, Bull. Chem. Soc. Jpn., 1989, 62, 2709; Y. Watanabe et al., ibid., 1984, 57, 2440) palladium (P.K.

72 Santra and C.R. Saha, Chem. Ind., 1984, 713; S. Bhaltacharya and P. Khandual, Chem. Ind., 1982, 600) and platinum (Y. Watanabe et al., Tetrahedron Lett., 1983, 24, 4121) for the homogeneous metal catalyse~ reduction of a variety of nitroarenes. The use of such catalysts, immobilised on solid supports can lead to unusual selectivities (K. Mukkanti, S.Y.V. Rao and B.M. Choudray, ibid., 1989, 30, 251). Catalytic transfer-hydrogenation has been further studied. The transfer of hydrogen using triethylammonium formate or eyclohexene with Pd/C catalyst, (M.O. Terpko and R.F. Heck, J. Org. Chem., 1980, 45, 4926, 4992; S. Ram and R.E. Ehrenkaufer, Tetrahedron Lett., 1984, 25, 3415; R.A. Ranpulla and R.K. Russell, Synth. Commun., 1986, 16, 1229), hydrazine and Raney-nickel, (F. Yuste, M. Saldafia and F. Walls, Tetrahedron Lett., 1982, 23, 147; N.R. Ayyanger et al., Bull. Chem. Soc. Jpn., 1983, 56, 3159) and secondary alcohols and rhodium catalysts (K.F. Lion and C.H. Ching, J. Org. Chem., 1982, 47, 3018) allows selective reduction of nitroarenes to aromatic amines. Primary arylamines are also prepared by hydrogenolysis of aryl azides by catalytic transfer-hydrogenation using ammonium formate and Pd/C catalyst (T. Garteser, C. Selve and J.J. Delpeuch, Tetrahedron Lett, 1983, 24, 1609), or by (Ph3P)2CuBH4 reduction (S.J. Clarke, G.W.J. Fleet and E.M. Irving, J. Chem. Res. (S), 1981, 17). Sodium borohydride supported on ion-exchange resin has also been used (G.W. Kabalka, P.P. Wadganonkar and N. Chatla, Synth. Commun., 1990, 20, 293). Nuclear Amination

Aqueous NH 3 in formamide is reported to give high yields of anilines from activated halogenoarenes (H.J. Niclas et al., Z. Chem., 1985, 25, 137). The ammonolysis of simple aryl halides is reportedly improved using quaternary ammonium salts as phase-transfer catalysts (G. Barak and Y. Sasson, J. Chem. Sot., Chem. Commun., 1987, 1267). Phenols are converted to ~ilines by heating NH 3 and NH4C1 in a bomb at 180~ (A.M. Becker, R.W. Richards and R.F.C. Brown, Tetrahedron, 1983, 39, 4189). Electrophilic amination of aryUithiums and aryl Grignards is popular. A number of organic azides function as NH2+ synthons by metal hydride reduction of the lithiotriazene, or triazene, adducts formed. These include tosyl azide (J.N. Reed and V. Snieckus, Tetrahedron Lett., 1983, 24, 3795; N.S. Narasinhan and R. Ammanmanchi, ibid., 1983, 24, 4733), phenylthiornethylazide (B.M. Trost and W.H. Pearson, ibid., 1983, 24, 269), vinyl azides (E.W. Colvin, G.W. Kirby and A.C. Wilson, ibid., 1982, 3835)

73 and diphenylphosphorazidate (S. Mori, T. Aoyana and T. Shiori, Chem. Pharm. Bull., 1986, 34, 1524). O O

"

Ar-MgBr

N3--P(OPh)2 ,,- A r - N = N - N- - P (IIO P h ) 2

LAH

._ Ar_NH 2 .

Tetraphenylcyclopentadienone oxime-O-tosylate (R.A. Hagopian et al., J. Am. Chem. Sot., 1984, 106, 5753) and acetone oxirne-O-mesitylate (E. Erdik and M. Ay, Synth. React. Inorg. Metal-Org. Chem., 1989, 19, 663) also serve as NH2+ synthons by reactionwith aryl Grignards and reduction of the imines formed. O-(Diphenylphosphinyl)hydroxylamine also directly aminates aryl Grignard reagents (M. Bernheim and W. Schrott, Tetrahedron Lea., 1982, 5399). Anilines can also be prepared by the direct amination of arenes using trimethylsilyl azide (G.A. Olah and T.D. Ernst, J. Org. Chem., 1989, 54, 1203), or hydrazoic acid in the presence of both CF3SO3H and CF3CO2H (T. Takeuchi, T. Adachi and H. Nishiguchi, J. Chem. Sot., Chem. Commun., 1991, 1524). Vicarious nucleophilic substitution of nitroarenes leading to anilines has been described using 4-amino-1,2,4-triazole (A.R. Katritzky and K.S. Laevenzo, J. Org. Chem., 1986, 51, 5039) and sulfenamides (M. Makosza and M. Bealecki, ibid., 1992, 57, 4784) in the presence of strong bases. N-N

-

Nil ,IR

H2N-N ~ ~

B

NH 2

N

NI-~Cl

tBuOK, DMSO

_O.N-O -

NO2

_O,N,O_

Miscellaneous

Primary arylamines are prepared by the direct Ixrane-dimethylsulfide reduction of arylamides (H.C. Brown, S. Narasinhan and Y.M. Choi, Synthesis, 1981, 996, 605, 441). Reaction of aroyl chlorides with hydroxylamine-O-sulfonic acid in toluene at reflux leads to 1~ arylamines in a reaction similar to the Neber rearrangement (R.G. Wallace, J.M. Barker and M.L. Wood, ibid., 1990, 1143).

74

O

O

Ar.~Cl NH2OSO3H Ar.,JI,.N.O..sOzOH acidcaL

Ar-N=C=O

~

Ar--NI~

H

Treatment of 1~ N-arylamides with iodobcnzcne and formic acid in aq. acetonitrile also leads to 1~ arylamines as their formate salts (A.S. Radhakrishna et al., ibid., 1983, 538). Other well-known re.arrangements involving formation of isocyanates arc discussed later. Anilines can be prepared by Semmlcr-Wolff aromatisation of cyclohexenone oximes (Y. Tamura et al., ibid., 1980, 483, 887). The mechanism of this transformation has be~n studied (M.M. Yousif, S. Sacki and M. Hamana, J. Hetcrocycl. Chem., 1980, 17, 1029). The synthesis of 2-aminobcnzophenones has been reviewed (D.A. Walsh, Synthesis, 1980, 677). (b) Prooerties and Reactions 13C NMR data on m/p-substituted anilines is described in tcnns of substiment effects.(M. Budescnsky et al., Collect. Czech. Chem. Commun., 1991, 56, 368) and is also reported for aromatic amine-boranr adducts (M.A. Paz-Sandoval, Spe~trocim. Acta, Part A, 1987, 43A, 1331). The properties, manufacture and reactions of aniline (Y.T. Nikolacv and A.M. Yakukson, Khimiya, Moscow, 1984; S.A. Kudchadker, American Petroleum Institute Publication 718, Washington 1982) and o-anisidine (M.N. Morathe, Chem. Eng. World, 1987, 22, 36) have been reviewed. Anilines may be protected as their stabasr adducts by cyclocondcnsation with Me,2SiCICH2CH2SiMc2CI in the presence of tdcthylaminr (T. Hocgberg, Acta Phamm. Suec., 1986, 23, 414). Deprotr is achieved under mildly acidic conditions. Oxidation The oxidative dimerisation of aniline to ~nzidinr has been the subject of a molecular nmchanics study (D. I.ananbr et al., J. Chem. Soc., Perkin Trans. 2, 1991, 1437). The chemistry of the bcnzoquinonr in~e.s continues to attract attention. The kinetics and mechanism of the oxidative coupling reactions involving N,Nbis(2-hydroxyethyl)-p-phenylenextiaminr is describe~ (D.J. Palling, K.C. Brown and J.F Corbctt, J. Chem. Soc., Perkin Trans. 1, 1986, 65; 1981, 886). Benzoquinonr imines, not bcnzoquinonr N-chloramines, are the

75 reacting species involved in the Gibbs phenol assay (I. Pallagi and P. Dvortsak, J. Chem. Sot., Perkin Trans. 2, 1986, 105). The oxidation of arylamines to the corresponding nitroarenes has been previously mentioned (vide supra). Interestingly, a reexamination of samples of mauveine made by Perkin has shown that the literature structure is incorrect (O. Meth-Cohn and M. Smith, J. Chem. Sot., Perkin Trans. 1, 1994, 5). The Boyland-Sims (persulfate) oxidation of anilines gives not only o-sulfates, but also, contrary to previous work, substantial amounts of p-sulfates. The intermediates of the reaction are the arylhydroxylamine-O-sulfonates (E.J. Behrman, J. Org. Chem., 1992, 57, 2266; J. Chem. Sot., Perkin Trans. 1, 1992, 305). Halogenation Although electrophilic halogenation of anilines is well known, reliable and mild methods for selective monohalogenation are scarce. Regioselective monobromination of anilines has been reported using Nbromosuccinimide in DMF (F. Xu and Q. Wang, Huaxue Shiji 1986, 8, 374), bromine a b s o ~ onto zeolite (M. Onaka and Y. lzumi, Chem. Lett., 1984, 2007) and tetrabutylammonium tribromide (J. Berthelot et al., Synth. Commun., 1986, 16, 1641; Can. J. Chem., 1989, 67, 2061). A simple highly selective monobromination of anilines is afforded by treatment of the derived arylaminosilanes with N-bromosuccinimide in CO 4 and subsequent desilylation (W. Ando and H. Tsunaki, Synthesis, 1982, 263).

6 Br

Br

Treatment of anilines with 5,5-dibromo-2,2-dimethyl-l,3-dioxane-4,6-dione in DCM leads to p-bromoanilines in high yields (X. Huang and G. Wu, Huaxue Shiji, 1991, 13, 1). Deamination via Dediazotisation Dediazonisation by Sn/HCI in PEG-DCM gives good yields of arenes free from chlorinated products (N. Suzuki et al., Chem. Ind., 1985, 698). The synthetic applications of arenediazonium compounds are reviewed (Y. Hashida and S. Sekiguchi, Yuki Gosei Kogaku Kyokaishi, 1982, 40, 752) and their radical reactions discussed (C. Galli, Chem. Rev., 1988, 88, 765).

76 Fluorodiazotisation is perhaps the most common means of introducing fluorine into aromatic rings. The subject is reviewed (N. Yoneda and T. Fukuhara, Yuki Gosei Kagaku Kyokaishi, 1989, 47, 619). Nitrosonium tetrafluoroborate is a good reagent for accomplishing this transformation directly (D. Milner, Synth. Commun., 1992, 22, 73). Decomposition of the triazene formed by trapping diazonium ions with pyrrolidine in the presence of potassium iodide in CF3CO2H leads to aryliodides (N.I. Foster et al., Synthesis, 1980, 572). 3-Aryl-l-tetrazol-5-yltfiazenes have been used as a bench stable source of diazonium ion. The dediazoniation process is induced by acetic acid and does not involve free radicals (R.N. Buffer, P.D. O'Shea and D.P. Shelly, J. Chem. Sot., Perkin Trans. 1, 1987, 1039). Aromatic amines containing nitro substituents are deaminated by t-butyl nitrite in chloroform. Use of deuteriochloroform allows the preparation of deuterionitrobenzenes (K. Kikukawa and T. Koyama, Kinki Daigaku Kyushi Kogakubu Kenkyu Hokoku, Rigogaku-hen, 1989, 18, 1). Aryliminodimagnesiums The aryliminodimagnesiums derived from primary arylamine and ethyl magnesium bromide are especially useful for the preparation of antis by reaction with diaryl ketones (M. Okubu, S. Hayashi and M. Matsunaga, Bull. Chem. Soc. Jpn, 1981, 54, 2337) and for the preparation of unsymn~trical azo and azoxyarenes by reaction with nitroso and nitroarenes respectively (M. Okubu, K. Matsuo and A. Yamauchi, ibid., 1989, 62, 915; M. Okubu and IC Koga, ibid., 1983, 56, 203). The mechanistic aspects of these transformations are under study (M. Okubu et al., ibid., 1989, 62, 1621; 1991, 64, 196). N-Alkylation The N-alkylation of 1o arylamines is discussed more comprehensively below. 1o Arylamines add to terminal acetylenes in the presence of HgC12 as catalyst to give imines ( 2 ~ arylamines give enamines, J. Barluenga, F. Aznar and R. Liz, J. Chem. Sot., Perkin Trans., 1, 1980, 2732) and react regiospecifically with allylic alcohols in monoallylations catalysed by mercury (II) tetrafiouroborate (J. Barluenga, J. Perezprieto and G. Ascensio, Tetrahedron, 1990, 46, 2453). 6. Benzenediamines and Benzr (a) PreparatiQrl Phenyleneamines are most commonly prepared via the reduction of the corresponding nitroanilines (see, for example, E.A. Karakhanov et al., Neftekhimiya 1991, 31, 312; K. Nomura, M. Ishino and M. Hazama, Bull.

77 Chem. Soc. Jpn., 1991, 64, 2624; T.A. Parchevskaya, L.V. Bogutskaya and M.V. Belousov, Ukr. Khim. Zh., 1990, 56, 1268). o-Phenylenediamine is manufactured in a two step procedure involving nitration of aniline in acetic anhydride with 65% HNO 3 followed by reduction of the o-nitroanilide so obtained (CA, 1991, 115, P231846). o/p-Phenyleneamines are also manufactured from the corresponding dihalogenobenzenes by ammonolysis at elevated temperature, pressure in the presence of zinc or copper bromides and hydrocarbons (eg. n-nonane). Methods for the preparation of pphenylenediamine have been reviewed (M. Ignatowicz, Przem. Chem., 1984, 63, 520). o-Phenylenediamines are available via the rearrangement of aryl ketones in polyphosphoric acid (T. Benincori et al., J. Chem. Sot., Perkin Trans. 1, 1988, 10, 2721). Ph2CffiN-NHPh

acid cat -Ph2CO

~

NH2

Nil2

Catalytic reduction of phloroglucinol trioxime by Raney-nickel provides a convenient preparation of 1,3,5-triaminobenzene (I. Arai, Y. Sei and I. Murmatsu, J. Org. Chem., 1981, 46, 4597). NOH

.NH2 Ra-Ni, BuOAc

HON

NOH

H2N

NII2

(b) Propertie~ and Reactions N :5 Chemical shifts of 1,2-diaminobenzenes are reported (M. Sibi, Mag. Reson. Chem., 1991, 29, 400) and their energetics considered (D.A. Dixon A.C.S. SyrrL Ser. 1989, 404, 147). The charge-transfer spectra of the EDA complex of m-phenylenediamines with tetracyanoethylene have been compiled (B. Uno et al., Spectrochim. Acta, Part A, 1987, 43A, 995). Phenyleneamines find use in the preparation of synthetic fibres and dyes, as cross-linking agents as inhibitors in radical polymerisation and as antioxidants. Like some other aromatic amines they are mutagenic. Phenylenediamines are important for the preparation of drugs and pesticides (CA, 1989, 111, P57253z) and are monomers for the preparation of polyamides. The thermodynamics of polymerisation of phenylenediamines

78 with iso or terepthalic acids have been studied (N.V. Koryakin and I.B. Rabinovich, Vysokomol. Soextin. Ser. A, 1987, 29, 675). o/m-Phenylenediamines undergo a wide variety of cyclocondensations and are useful for the preparation of heterocycles, o-Phenylenediamine reacts with aminoacids to give benzimidazole derivatives with anti-bacterial activity (T.M. Aminabhavi et al., Inorg. C'him. Acta, 1986, 125, 125; O. Cherkaoui E.M.Essassi and R. Zniker, Bull. Soc. m . Fr. 1991, 225). Reaction with bis(dithiocarbamates) leads to bisCt~nzimidazoles) (J. Gavin et al., J. Heterocycl. Chem., 1990, 27, 221). o-Phenylenediamine is used to derivatise malto-oligosaccharides to quinoxalines in a HPLC method for the measurement of the degree of polymefisation (M. Takagi, Y. Daido, N. Morita, Anal. Sci., 1986, 2, 281) and commonly acts as a bidentate ligand in transition metal complexes ( see, for example, A. Prasad, L. Mishra and V.C. Agarwala, J. Chem. Sect.A: Inorg. Bio-inorg. Phy. The,or. Anal. Chem., 1991, 30A(2), 162). 7. N-Substitutexi Arvlamines (a) Preparatign

N-Alkylation A review of the methods for the mono and dialkylationof amines has been punished (H. Wurziger, Kontaktr 1987, 3, 8). Methods for the monoalkylation, of a~ilines most commonly involve the formation of intermediate arylimines (Schiff bases) or equivalents and subsequent convertion to alkylarylamine.Treatment with formaldehyde in the presence of sodium borohydridr (A.G. Giumanini et al.,Synthesis, 1980, 743; A.R. Katdtzky and A. Akutagawa, Org. Prep. Procedure Int., 1989, 21,340; S. Bhattacharyya, A. Chaterj~ and S.K. Duttachowdhury, J. Chem. Soc., Perkin Trans. I, 1994, I), or with ketones and diboranr in T H F (H.R. Morales and P-J Martin, Synth. Commun., 1984, 14, 1213) allows, monomethylation, or monoalkylation, of I~ arylamines l'r Monomethylation of anilines can also be achieved by treatment of N(alkoxymethyl)-N-arylamines, with sodium borohydddr in ethanol at reflux (J. Barluenga, A.M. Bayon and G. Ascensio, J. Chem. Soc., Chem. Commtm., 1984, 1334; L.E. Overman and R.M. Burk, Tetrahexiron Left. 1984, 25, 1635). Alternativelytreatment with mcthyllithium at -60~ leads to monomeric methyleneaxylamines which react on w a m ~ g with alkyllithiums to afford an overallmonoalkylation of I~ aromatic amines (J.Barluenga et al., J. Chem. Soc., Chem. Commun. 1983, I I09).

79

NHMo HN~OR

NaBH4 N=CH2 9 /

6

R

MeLi

~ R ~i~,,, HNAR

Thus N-(methoxymethyl)-N-phenylamine is used as a synthetic equivalent to N-methylenephenylamine (J. Barluenga et al., J. Chem. Sot., Perkin Trans. 1, 1988, 1631). lsolable monomeric N-methylenearylamines generally rely on steric hindrance by substituents at the o-position to prevent oligomerisation (F.P. Cortolano et al., Tetrahedron Lett., 1988, 29, 5875; A.G. Giumanini, G. Verardo and M. Poiana, J. Prakt. Chem., 1988, 330, 161). Similarly, N-(benzotriazolylmethyl)arylamines function as Schiff base equivalents and treatment with Grignard reagents leads to substitution of the benzotriazolyl moiety and the overall N-monoalkylation of 1~ arylamines (A.R. Katritzky, S. Rachwal and B. Rachwal, J. Chem. Sot., Perkin Trans., 1, 1987, 805). The method has been extended to the preparation of unsymmetrical N,N-dialkyanilines (A.R. Katritzky S. Rachwal and J. Wu, Can. J. Chem., 1990, 68, 456).

1. RIMgBr 2. R2MgBr

/"'R2 R~''NAr

Various N,N-diarylbenzylamines can be synthesised by reactions of N(arylmethylene)arenamines with (arylmethoxy)arenes in DMF in the presence of a strong base as a catalyst, which is obtained by reacting sodium metal with this solvent (M. Paventi and A.S. Hay, J. Org. Chem., 1991, 56, 5875). PhN= /

Ph

Na DMF '

ph~O v Ph

.

Ph Ph- N"

{" Ph

80 2 ~ and 3 ~ Arylamines are also available by treatment of thioamides with triethyloxonium tetrafluoroborate, followed by reductions with uxtium borohydride (S. Raucher and P. Klein, Tetrahedron Lett., 1980, 21, 4061). Similarly, 3 ~ amides are reduced to the corresponding amines by reduction of thioimidates with sodium cyanoborohydride (R.J. Sundberg, C. P. Walters and J.D. Bloom, J. Org. Chem., 1981, 46, 3730). Diborane reduction of amides in the presence of boron trifluoride also leads to 2 ~ and 3 ~ arylamines (H.C. Brown, S. N a r a s ~ and Y.M. Choi, Synthesis, 1981, 996, 605,

441). The formylation of anilines with acetic formic anhydride, followed by boranedimethylsulfide reduction, affords monomethylated anilines (S. Krishnamurphy, Tetrahedron Lett., 1982, 23, 3315).

CHO /~

AcOCHO

BH3SMe2

_20~C

Tt~

Trimethyl orthoformate in the presence of tosic acid monoalkylates 2 ~ arylamines (R.A. Swaringen, J.F. Eaddy and T.R. Henderson, J. Org. Chem., 1980, 45, 3986) and anilines are menoalkylate~ by alcohols in the presence of zeolites (M. Onaka et al., J. Chem. Soc., Chem. Commun., 1985, 1202 ; Chem. Lett., 1982, 11, 1783). Formamidines, based on N-methylaniline, can be deprotonated at the exposition and the resulting carbanions alkylate~ to give homologous amines (A.I. Meyers and S. Hellring, Tetrahedron Lett., 1981, 22, 5119).

~N.Me t.. N

t

1.BuLi 2.E 3.hyd.

ON~E H

Similarly, dimethylsulfoxide methylates anions derived from N-fonnylate~ ~ilir~es under phase-umlsfer conditions leading to monomethylated anilines, after aqueous work-up (V.K. Sharma, Ind. J. Chem. Se~t.B., 1983, 22B, 1153).

81 Unsymmetrical diarylamines have been prepared using methodology based on 1-aryl-2-ethoxycarbonyl-4,Gdiphenylpyridinium salts (A.R. Katritzky and A.J. Cozens, J. Chem. Sot., Perkin Trans. 1, 1983, 2611). Ph

Ph

NaH Ar migration Ar

At"

NHAr I

Ph hydrolysis "

HN/Arl ~Ar

Ar- N',Ar I

Arene Substitution Unsymmetrical diarylamines are synthesise~ by the coupling of arenes with nitrenium ions derived from aryl azides in the presence of triflic acid (H. Takeuchi and K. Takano, J. Chem. Sot., Chem. Commun., 1983, 447). Exchange reactions for the preparation of 2 ~ and 3 ~ anilines have been previously discussed. Palladium catalysed reaction of aryl bromides with N,Ndiethylamino(tributyl)tin leads to the corresponding diethylanilines (M. Kosugi, M. Kameyama and T. Migita, Chem. Lea., 1983, 927).

N-Dealkylation N,N-Dialkylanilines can be N-dealkylated selectively by photo-induced single electron-transfer in methanol (G. Pandey, K.S. Rani and U.T. Bhalerao, Tetrahedron Lea., 1990, 31, 1199).

Ring Synthesis The Diels-Alder reaction of vinylketenimines with acetylene esters leads to anthranilate esters (E. Differding and O. Vandevelde, ibid., 1987, 28, 397).

R TIPS

N~

NH2

TIPS

2Me

+ R~ ~

CO2Me

R

R

82 A one-step synthesis of 2,6-disubstimted 3~ anilines from aliphatic compounds is reported (P. Camps, C. Jaime and J. Molas, ibid., 1981, 22, 2487). The cycloaromatisation reactions of various enamines leads to 3~ arylamines (T.H. Chan and GJ. Kang, ibid., 1983, 24, 3051).

TMSCO2Me

~

Me~ ,

Me

Me" " ~ "OH

Miscellaneous

Alkyldiphenylsulfonium percklorates (B. Badet, M. Julia and M. RamirezMunoz, Synthesis, 1980, 926) and alkylsulfates also alkylate arylamines (I. Pop et al., Rev. Roum. Chim., 1988, 33, 283). N-Phenylation of anilines using triphenylbismuth acetate, or phenyllead triacetate in the presence of copper catalyst is reported (D.H.R. Barton et al., Tetrahedron Lett., 1987, 28, 3111 ; 1986, 27, 3615). 2-Oxazolidinones behave as aziridine equivalents for the aminoethylation of 1~ arylamines (G.S. Poindexter and D.A. Owens, J. Org. Chem., 1992, 57, 6257). N-Ethynylarylamines are available by flash pyrolysis of isoxazolones at 650~ (I-I. W. Winter and C. Wentrup, Angew. Chem., 1980, 92, 743), M e ~

N.O,,,~0

NHPh

FVP

HNPh =

tautomerises

~

HNPh~ m m

Reductive alkylation of nitro groups by methanol in the presence of ruthenium-phosphine catalysts gives N,N-dimethylanilines in high yields (K.T. Huh et al., Chem. Lett., 1988, 449). Treatment of nitroarenes with ethyl cyanoacetate and potassium hydroxide followed by hydrolysis leads to the corresponding amino derivatives in which an o-substituent is incorporated (Y. Tomioka, K. Ohkubu and M. Yamazaki, Chem. Pharm. Bull. 1985, 33, 1360).

83 (b) Properties and Reactions Oxidation

3 ~ Aromatic amines (when p substituted) form stable radical cations on oneelectron oxidation. The rate constants for the deprotonation of pAn2NCH3AsF6 (An = anisyl) by quinuclidine have been describe~ in a detailed kinetic study (J.P. Dinnocenzo and T.E. Banach, J. Am. Chem. Soc., 1989, 111, 8646; see also S.F. Nelson and J.T.lppoliti, ibid., 1986, 108, 4879). Nuclear Functionalisation

Methods for the regioselective nuclear alkylation, or alkenylation, of arylamines are reviewed (W.F. Burgoyne, Chemtech, 1989, 19, 690). In general acid catalysed alkene-alkylation of arylamines leads to good yields of o-alkylated compounds and allows the introduction of branched alkyl groups into this position (W.F. Burgoyne and D.D. Dixon, Appl. Cat., 1990, 63, 17). N-Alkylarylamines undergo exclusive o-acylation by alkyl nitriles in the presence of boron trichloride to give 2-acyl-N-alkylarylamines (K. Sasakura, Y. Terui and T. Sugasawa, Chem. Pharm. Bull., 1985, 33, 1836). N-(t-BDMS)-N-methylarylamine, when activated as its rl6-chromium tricarbonyl complex is substituted almost exclusively at the m-position by treatment with base and electrophile. This is attributed to the bulkiness of the silyl group. (M. Fukui, T. Ikeda and J. Oishi, ibid., 1983, 31,466). Me" N.TBDMS

/~e, N Me 1. BuLi, 2. PhCHO tL

Cr(CO)3

2.deproteet

Ph

OH A synthetic equivalent to o-lithio-N-methylaniline is described (H. Tanaka et al., Tetrahedron Lett., 1988, 29, 3811).

Me'N'OPr

Me'N'OPr

NHMc -Ni

84 The amino-Claisen reanmlgement has been further studied, but appears to give quite complex mixtures of products (I.B. Abdrakhmanov et al., Zh. Org. Khim., 1984, 20, 620; 1982, 18, 1466). The Fischer-Hepp rearrangement of some N-nitrosodiphenylamines has also been surveyed (S.P. Tetoria, A.K. Arinich and M.V. Gorelik, ibid., 1986, 22, 1562). The Meisenheimer reanangement of a series of N-(2- or 4-nitrophenyl) tertiary amine oxides has been the subject of a NMR and a kinetic study (AH. Kuthier et al., Org. Mag. Res. 1982, 18, 104; J. Org. Chem., 1981, 46, 3634). The mechanism is best descdbe~ as an intramolecular cyclic process and not as a homolytic dissociation-recombination sequence. 8. N-Arvlamides (a) Preparation The Beckmann rearrangement of oximes to anilides (often exploited for the preparation of anilines) has been reported to be promoted by aluminium iodide (D. Konwar, R.C. Boruah and J.S. Sandhu, Tetrahedron Lett., 1990, 31, 1063), or acidic clay (H.M. Meshrau, Synth. Commun., 1990, 3253). Ketoxime trirnethylsilyl ethers rearrange under the influence of antimony (V) salts (T. Mukuiyama and T. Harada, Chem. Lett., 1991, 9, 1653). Omius rearrangement of aroylazides under phase-transfer conditions leads to anilides (J.R. Pfister and W.E. Wymann, Synthesis, 1983, 38). Anilides can also be obtained via the diazotisation-rearrangement of tosylhydrazones of o/m-substituted benzophenones and a-substituted acetophenones (V. Joshi and R.K. Sharma, J. Ind. Chem. Sot., 1988, 65,

564). Formanilide is prepared via the formylation of aniline by pentafluorophenyl formate (L. Kisfaludy and L. Otvos Jr.,Synthesis, 1987, 5 I0), enol formates in the presence of ruthenium (H) (M. Neveux, C. Bruneau and P.H. Dixreuf, J. Chem. Soc., Perkin Trans. I, 1991, I197), and by N-formylformamide (prepared by ozonolysis of oxazole) (C. Kashima et al.,Tetrahedron Lett., 1989, 30, 156 I). Formanilide can also be prepared by reaction of aryl azides with the enolate of acetaldehyde (often formed by cycloreversion of T H F by BuLi) via the intermediate hydrotriazoles (L. Di Nunno and A. Scilimata Tetrahedron, 1986, 42, 3913) and by the sequential reductive N-formylation of nitroarenes in the presence of ruthenium (E.M. Nahmed and G. Jenner, Tetrahedron Lett., 1991, 32, 4917).

85

N3

6

OHC

+ H2C~L-S BuLl

THF

[~

~-c.o

proton

C~

~-~176

(b) Properties and Reactions The F ~ rotomerism of the amidc bond in formanflidc has been studied by dielectric polarisation showing considerable amounts of the Z isomer (K. Pralat and J. Jadzyn, Fiz. Dielektr. Radiospcktrosk., 1986, 13, 89). Fatty-acid anilides are suspected of causing toxic oil syndrome (A. Martinez Conde Ibanez, An. Quim. Ser.C, 1987, 83, 107; B. Kaphalia and G.A.S. Ansari, J. Anal. Toxicol. 1991, 15, 90). Diaminobenzan~des are useful for the preparation of certain polyng~ (polyamidines, CA, 1989, 110, P115509e). The telomerisation of anilides with butadiene in the presence of palladium catalyst is described (R.M. Safuanova, R.N. Fakhretdinov and U.M. Dzhemilev, Izv. Akad. Nauk. SSR. Ser. Khim. 1988, 821). The ruthenium catalyse~ N-alkylation of anilides with alcohols is also reported (Y. Watanabe, T. Ohm and Y. Tsuji, Bull. Chem. Soc. Jpn., 1983, 56, 2647). The photo-bromination of anilides by hexabromobenzene has been the subject of a mechanistic and kinetic study (M.M. Aly, I.M.A. Awad and A.M. Fahmy, Bull. Pol. Accad. Sci. Chem. 1987, 35, 77; Rev. Roum. Chim. 1983, 33, 167). Cyclocondensation of formanilides with benzofuroxane leads to unusual 2aryl-2H-benzotriazole-l-oxides (H.J. Niclas and B. G6hrmann, Synth. Commun., 1989, 19, 2141). N-Acylureas are prepared by the reaction of formanilides with phenylisocyanate (H.G. Schweim, Arch. Phann., 1987, 320, 430). N-Chloroanilides oxidise 1~ arylamines to the corresponding trans-azo compounds. A mechanism for this process has been proposed (A. Kumar and G. Bhattacharjee, J. Ind. Chem. Soc., 1991, 68, 523).

86

Nuclear functionalisation Acetaminophen (paracetamol) is manufactured from acetanilide by genetically engineered microbial synthesis (CA, 1987, 107, P5737h). The directed o-metalation reactions of N-arylamides have been recently reviewed (V. Snieckus, Chem. Rev., 1990, 90, 879; V. Snieckus and P. Beak, Acc. Chem. Res., 1982,15,3069. N-(t-Butyloxycarbonyl)aniline via the corresponding dilithio species gives a wide range of o-substituted anilines ( J.M. Muchowski and M.C. Venuti, J. Org. Chem.,1980, 45 4798; W. Fuhrer and H.Z. Gschwind, ibid., 1979, 44, 1133; S. Marburg and R.L. Tolman, J. Heterocycl. Chem., 1980, 17, 1333). H

tBu

uN'~oOtBu 2BuLi ~ N y O H EO

'Bu

{~~N.. ]{.-O hyd.

~ E NH2

The mechanism of the acid-catalyse~ Orton rearrangement in aprotic solvents has been studied for some N-bromo-4-chloroacetanilides. (P.D. Golding et al., Can. J. Chem., 1981, 59, 839). The mechanism is determined to be intramolecular, involving protonation of the substrate, followed by heterolytic fission of the N-Hal bond and intramolecular rearrangement of the resulting ion-pair to a g-complex. The Fries rearrangement of benzanilide in the presence of ZrOC12 (also TiC14, ThC14) gives good yields of p-aminobenzophenone (S. Ravi et al., Ind. J. Chem., Sect B, 1991, 30B, 443). The photo-Fries rearrangement in the presence of cyclodex~ leads to high o-selectivity (M.S. Syamala, N.B. Rao and V. Ramamurthy, Tetrahexiron, 1988, 44, 7234; M. Nassetta, R.H. De Rossi and J.J. Cosa, Can. J. Chem., 1988, 66, 2794). The translocation of the radical derived from o-iodoanilides by 1,5 H-atom transfer so as to give a radical adjacent to the anilide carbonyl is describe~ (D.P. ~ , A.C. Abraham and H. Liu, J. Org. Chem., 1991, 56, 4335).

87 9. N-Arvlisocvanates (a) Preparation Thermolysis of disilylated hydroxamic acids (prepared by reaction of hydroxamic acids with hexamethyldisilazide) gives isocyanates (J. Rigaudy and E. Lytwyn, Tetrahedron Lea., 1980, 21, 3367). TMSO. Ph~ = = N - O T M S

thermolysis -9

Ph- N=C=O

Arylisocyanates are synthcsised by the trifluomacetalisation of N,Ndiarylureas and subsequent thcrmolysis ( M.V. Vork and L.I. Samarai Ukr. Khim. Zh., 1990, 56, 1313), or by reaction of aryl carlxxiiimidcs with carboxylic acids (D.B. Guldcncr and D.J. Sikhema, Chem. Ind., 1980, 15, 628). Transition metal carbonylation of phcnylazidcs leads to phcnylisocyanatcs (G. La Monica and S. Cenini, J. Organomct. Chem., 1981, 216, C35) as does the reaction of carbon dioxide with aryliminophosphorancs (P. Molinai, M. Alajarin and M. Arques, Synthesis, 1982, 596). Adducts of nitrosocarbonylarenes and dimethoxyanthracene are decompose~ at 80~ in the presence of triphenylphosphine to give arylisocyanates in high yield. (J.E.T. Corrie, G.W. Kirby and R.P. Sharma, J. Chem. Sot., Perkin Trans. 1, 1982, 1371). (b) Prooerties and ReaCtions Quantum mechanical calculations on the conformation of phenylisocyanate suggest C-5 symmetry (M. Rernko et al., Z. Phys. Chem. 1987, 268, 874). A reinvestigation of the dipole moments of a series of p-substituted phenylisocyanates suggests a value of 7.93 x 10 -30 (ha-: as the dipole moment of the isocyanate group. (I. Daniel, F.Barnibol and P. Kristian, Collect. Czech. Commun., 1989, 54, 1441). A MINDO study is also reported (idem, Chem. Pap. 1989, 43, 609). Associative interactions of phenylisocyanate with nitrobenzene in hexadecane have been studied (M.G. Ivanov et al., Zh. Obshch. Khim., 1990, 60, 1209) and the O :7 (natural abundance) NMR spectra of a variety of substituted phenylisocyanates is reported (D.W. Boykin, Spectrosc. Lea., 1987, 20, 415). The mechanism and kinetics of cyclotrimerisation of arylisocyanates in the presence of base catalysts containing 4 ~ ammonium groups has been studied. (Y.M. Tsarfin, V.V. Zharkov and A.K. Zhitinkina, KineL Katal., 1988, 29, 1238; A.V. Selivanov et al., ibid., 1988, 29, 586; K. Matsunaga and Y. Yameshita, Toyo Daigaku Kogakuku Kenkyu Hokoku, 1985, 21, 57).

88

A new reaction of arylisocyanates with nitrite anion is described (N.P. Botting and B.C. Challis, J. Chem. Soc., Chem. Commun., 1989, 1585). 1,3Diaryltriazcnesare obtained via an intcnne~ate aryldiazotatcion. Ar-I~--C=O f O-NO

O Ar_ N_JNO O=N'J

Ar-..-N=N-O

O Ar-N=C=O

At- -N~~N,O

Ar- N=N=N-Ar

H+

Ar--~-N=N-Ar

The reaction of phcnylisocyanate with n-butanol in the presence of 3 ~ amines has been studied kinetically as a model process for polyurethane formation (R. Bacaloglu et al., J. Prakt. Chem. 1988, 330, 530). The rate determining step is the nucleophilic attack of the 3~ amine on the association of isocyanate with the alcohol forming a very reactive uronium salt. In the presence of tin compounds, rather than amines the rate determining step is the transfer from tin to isocyanate of alkoxide (idem, ibid., 541). Phenylisocyanate undergoes a wide variety of cycloaddition and cyclocondensation reactions and is useful for the synthesis of various heterocycles. Reaction with 1,1-dimethyloxirane gives a dioxolan-2-imine which rearranges to an oxazolidin-2-one (A.Baba and K. Seki, J. Heterocycl. Chem., 1990, 27, 1925). Enamines give azetidenones (C. Nisole et al., J. Chem. Res. Synop. 1991, 204). Reaction with vinylcycloproanes under palladium (0) catalysis leads to pyrrolidinones (K. Yamamoto, T. Ishida and J. Tsuji, Chem. Lett., 1987, 1157) and cycloaddition to iminophosphoranes leads to carbodiimides (H. Seifert, R. Noack and K. Schweflick, Z. Chem., 1990, 30, 368; P. Molina, M. Alajarin and A. Vidal, Tetrahedron, 1990, 46, 1063; P. Molina, E. After and A. Lorenzo, ibid., 1991, 47, 6737). Cyclocondensation of phenylisocyanate with ketene S,N-acetals leads to pyrimicliones (M. Gelbun and D. Martin, J. Prakt. Chem., 1987, 753, 329). 2Isocyanotobenzoyl chloride is a useful reagent for the elaboration of heterocycles (B.P. Acharya and R.Y. Rao, J. Sci. Ind. Res. 1988, 47, 152). The laser induced fluorescence UV specman of phenylisocyanate is due to the phenyl nitrene radical (G. Hancock and K.G. McKendrick, J. Chem. Soc., Faraday Trans 2, 1987, 83, 2011) although the signal long attributed to triplet phenylnitrene has unambiguously been shown to be due to the

89 cyanocyclopentadienyl radical (by rearrangement of "hot" phenylnitrene radical and a second photolysis, D.W. Oallin et al., J. Phys. Chem., 1990, 94, 8890; T. Ishida et al., Chem. Phys. Lea., 1990, 425, 170; 1988, 249, 150). 10. N-Arvlureas (a) Preparation N,N'-Diarylureas are available via the reductive carbonylation of aromatic nitro-compounds (A. Bassoli, B. Rindone and S. Cecini, J. Mol. Catal., 1991, 66, 163; 1990, 60, 155). A non-phosgene route for the synthesis of symmetrical NN,N~'diethyldiphenyl urea involves the condensation of aniline with urea and subsequent phase-transfer alkylation of N,N'-diphenylurea with diethyl sulfate (N.R. Ayyangar et al., Chem. Ind., 1988, 599). (b) Properties and Reactions The computational analysis of the crystal structure of N,N'-diphenylurea in relation to hydrogen-bonding is reported (J.S. Murray et al., Mol. Eng., 1991, 1, 75). The transamination of symmetrical diarylureas with diisobutylamine is descdbe~ (A.L. Chemiskyam, W.D. Gulyaev and V.T. Leonara, Zh. Org. Khim., 1988, 24, 2047) and the nitrosation of some N-phenylureas has been the subject of a kinetic and mechanistic study (A. Castro et al., J. Chem. Sot., Perkin Trans 2, 1988, 2021; 1987, 1759; 1986, 1725). It is suggested that the N-nitroso compound is formed via an initial O-nitrosation step, followed by rate-controlling loss of proton and that two parallel reaction paths operate, one being the reversible formation of the N-nitroso compound the other being irreversible formation of benzenediazonium ion, the only product from this reaction. N,N'-Diphenylurea undergoes a variety of cyclocondensation reactions. Reaction with benzoin leads to imidazolinones (M.H. Chawla and M. Pathak, Tetrahextron, 1990, 46, 1331). Photo-oxygenation of these intermediates in the presence of methylene blue leads to diacylureas. Similarly reaction with hydroxybutanones in the presence of CsF leads to oxazolidones (S. Sebti and A. Foucaud, J. Chem. Res. Synop., 1987, 72). 11. N-Arvlcarbamates (a) Preoaration N-Arylcarbamates are normally available via the reductive carbonylation of nitroarenes in the presence of alcohols (CA, 1990, 113, P152057p; 1989,

90 111, P239; 1987, 106, P32090c) but may also be manufactured via the alcoholysis of N,N-diphenylurea (CA, 1987, 107, P96448d, P96446b). N-Alkylation of N-arylcarbamates under phase-transfer conditions has been described (Kh. M. Shakhidoystov, D.N. Rakhimov and N.P. AbduUaev, Dokl. Akad. Nauk. UzSSR, 1988, 33). N-Alkylation of ethyl phenylcarbamate by 1,4--dichlorobut-2-ene is the first step in a stereospecific synthesis of Naryloxazolidinones, e.g., Toloxatane, which are analogue inhibitors of monoamine deoxygenase (J.P.Genet et al., Tewahedron Lea., 1990, 31, 515). (b) Properties and Reactions The structure-activity relationship of 69 substituted methyl, N-phenyl carbamates as fungicides has been considered (J. Takahashi et al., Pestle. Biochem. Physiol., 1988, 30, 262). The condensation of alkyl N-phenyl carbamates with methylenating agents such as formaldehyde has been much studied, since thermal decomposition of the resulting oligo/polymeric methylene bridged phenyl carbamates leads to isocyanates, useful for the preparation of polyurethane elastomers (CA, 1991, 115, P279615r, P71159n; 1990, 112, P180045f, P36704c; 1989, 109,

P191051u) The kinetics of reactions of urethanes with isocyanates, leading to aUophanates, have been analysed (L.V. Rakhlevskii, L.A. Bakalo and V.M. Fedorchenko, Kinet. Kaml., 1988, 29, 1062). The mechanism of thermal degradation of diphenyl alkyl allophanates has been studied providing a model for the cross-link sitesin polyurethane networks under thermal decomposition (M. Furukawa, N. Yoshitake and T.Yokoyama, Polyax Degrad. Stab., 1990, 29, 341). Reaction of methyl N-arylcarbamates with phosphorus pentachloride, or phosphorus oxychloride, at 140~ leads to N-arylisocyanates (D.N. Rakhimov, N.P. AbduUaev and K.M. Shakhidoyatov, Zh. Org. Khim., 1989, 25, 885). The sodium reduction and photoreduction of some arylcarbamates in the presence of HMPT has been considered.and the various competing reactions for both reaction conditions have been identified (A. Denbele, H. Deshayes and J.P. Pete, Bull. Soc. Chirn. Ft., 1988, 671). The interaction of alkyl phenylcarbamates with eerie ammonium nitrate provides an initiator for the free-radical polymerisation of acrolein (Z. Zhang et al., Gaofenzi Xuebao, 1990, 233). Nuclear benzoylation of methyl N-phenylcarbamate using (trichloromethyl)benzene in the presence of aluminium trichloride proceeds in

91 very high yield and has synthetic utility for the preparation of diaminobenzophenones, including the antithelmintic mebendazole (N.R. Ayyangar et al., Synthesis, 1991, 322 ; Org. Prep. Proced. Int., 1991, 33, 6271). Alkyl N-alkylarylcarbamates have herbicidal and fungicidal activity (K.F. Barnes, I.R. Browning and N.G. Clark, Pest.Sci., 1988, 23, 83). 12. ~-Arylcarbodiimides Symmetrical d i a r y l c ~ d e s are prepared from iminophosphoranes and carbon disulfide (N. De Kimpe et al., Org,. Prep. Proced. Int., 1982, 14, 213; Synthesis, 1982, 596). Treatment of thioureas with dipyridyltl~'onyl carbonate in the presence of DMAP also affords unsynmaetrical carbodiimides (S. Kim and K.Y. Yi, Tetrahedron Lea., 1985, 26, 1661). 13. Fl-Arylisocyanides Isocyanides can be prepared by the electrochemical reduction of caflxmimidoyl dichlorides ( A. Guirado et al., ibid., 1992, 33, 4779). PhN=CCh

e

,

phN=_.C

A general method for the preparation of o-diisocyanoarenes depends upon the dehydration of the corresponding formamides with trichloromethyl chloroformate (Y. Ito et al., Synthesis, 1988, 714). 14. lq-Arylisothiocyanates N-Arylisothiocyanates can be prepared by the base catalyse~ decomposition of methyl N-aryldithiocarbamates (C.S. PaL I.K. Youn and Y.S. Lee, ibid., 1982, 969). Treatment of N-aryldithiocarbamic acid tdethylammonium salts with triphenylphosphine and triethylamine in CO 4 also leads to Narylisothiocyanatcs ( I. Furukawa, N. Akr and S. Hashimoto, Chem. Express. 1988, 3, 215). Metathesis of aryl isothiocyanates has been used in a novel synthesis of st~cally hindered arylisothiocyanatcs ( N.S. Habib and A. Ricker, Synthesis, 1984, 825).

92 15. N-Arvlamides of Sulfur Acids The chemistry of the N-arylamidcs of sulfuracids is dcscribe~ in more general reviews contained in the three volumes of "The Chemistry of the Functional Group: The Chemistry of Sulfonic Acids, Esters and their Derivatives"; and "The Chemistry of Sulfenic Acids, Esters and their Derivatives"; as well as "The Chemistry of SulfinicAcids, Esters and theirDerivatives" (Eds. S. Patai and Z. Rappoport, Wiley Intcrscience,Chichestcr, N.Y. 1990, 1991).

Sulfamic acids The first isolation and characterisation of free phenylamidosulfuric acid, an intermediate postulated in the sulfonation of arylamines, is describe~. The phenyhmidosulfin'ic acid is prepared by adding concentrated. HC1 to a cold aqueous solution of the corresponding ammonium salts. They are zwitterionic, non-hygroscopic, crystalline solids that are stable at room temperature (F. Kanetani, Chem. Lett., 1980, 965).

Sulfenamides N-(4-Nitrophenylthio)-2,4,6-tri-t-butylphenylaminyl radical is prepared by oxidation of the corresponding sulfenamide with PbO2/K2CO 3 in benzene under nitrogen (Y. Miura et al., J. Chem. Soc., Chem. Commun., 1980, 37). The chemistry of sulfenamides is specifically reviewed (L. Cmine and M. Raban, Chem. Rev. 1989, 89, 689; I.V. Koral, Usp. Khim., 1990, 59, 681).

N-Thiosulfinylanilines The reaction of 2,4-di-t-butyl-6-methyl-N-thiosulfmylaniline with various electrophiles such as mCPBA and bromine has been investigated.(Y. Inagaki, R. Okazaki and N.Inamoto, Bull. Chem. Soc. Jpn., 1979, 52, 3615).

Sulfur Diimides The synthesis of diphenylsulfur diimide from N-sulfinyl~iline using a nickel (0) catalyst has been describeA (D. Walther, E. Dinjus and H. Wolf, Z. Chem., 1979, 19, 381). 16. N-Arvlamidcs of Phosohorus A~ids The chemistry of N-arylamides of phosphorus acids is described in more general reviews contained in the series Royal Society of Chemistry, Specialist Periodical Reports: Organophosphorus Chemistry, Volumes 13-24.

Phosphazenes The increasing importance of these intermediates is highlighted by the emergence of a fullchapter in the above publication.Readily availablevia the Staundingcr reaction, N-arylphoshazcncs are pcrphaps most commonly used in aza-Wittig reactions leading to hetcrocycles.

93 The NMR (31p, 15N, 13C) and cyclic voltammetry of substituted Narylphosphazenes have been studied with respect to substiment effects and their correlation with molecular orbital calculations. (M. Pomeranz et al., J. Org. Chem., 1986, 51, 1223). A compound containing the first stable P-N triple bond is reported (E. Niecke, M. Nieger and F. Reichert, Angew. Chem. Int. Ed. Eng., 1988, 7, 1715).


Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.lll B, C,D(Partial), edited by M. Sainsbury

95

9 1995 Elsevier Science B.V. All rights reserved.

Chapter 10

AROMATIC COMPOUNDS OF THE NON-TRANSITION METALS

Stephen T. Mullins

1.

Introduction

Main group organometallic chemistry has continued to expand during the past decade and progress is mirrored by the publication of several reviews, as detailed annually in Organometallic Chemistry and Royal Society of Chemistry Annual Reports A. New text books include 'Organometallic Chemistry', A.W. Parkins and R.C. Poller, Macmillan Publishers Ltd, Hong Kong, 1986 and 'Chemistry of the Metal-Carbon Bond', vol 4, ed. F.R. Hartley, John Wiley & Sons, 1987, which focus primarily upon the use oforganometallics in synthesis and 'Principles of Organometallic Chemistry', Second Edition, P. Powell, Chapman and Hall, New York, 1988, which considers in detail the structure of organometallics as well as their use in synthesis and general chemistry.

2.

Group 1 Metals

2.1

Lithium

The preparation and use of aryl organolithium derivatives in synthetic

96 chemistry is now standard practice. Reviews have been published covering nitrogen and oxygen assisted lithiation (G.W. Klumpp, Recl. Trav. chim. PaysBas, 1986, 105, 1). The classical halogen-lithium exchange method for the preparation of aryllithium reagents (H. Cfilmanand A.L. Jacoby, J. org. Chem., 1938, 3, 108) has been applied to the preparation of aromatic organolitium reagents bearing electrophilic groups (W.E. Parham and C.K. Bradsher, Ace. chem. Res., 1982, 15, 300). Benzene is dilithiated efficiently using a combination of n-butyllithium and hydrocarbon soluble potassium tert-alkorddes (L. Lochmann, M. Fossatelli, and L. Brandsm, Recl. Trav. chim. Pays-Bas, 1990, 1.09, 529) for example MeaCEtOK, Et2CMeOK or Et3COK. A solution of n-butyl lithium in hexane is added to benzene, followed by a heptane solution of the potassium tertalkoxide in the temperature range -10 to -40~ This results in the formation of a mixture of mono- and dimetallated benzenes which can be quenched by adding dimethyl sulphide. Results for a variety of conditions are shown in table 1. Benzene dianion (1) (scheme 1) is also obtained by the reduction of hexakis(trimethylsilyl)benzene (2) using excess lithium metal in tetrahydrofuran (H. Sakurai et al., J. Amer. chem. Soc., 1991, ! 13, 1464).

_ SiMe3 Me3Si~

SiMe 3

SflVIe3

MeaSiF ~-~~ S i M e 3 SiMea

Li THF

(2)

Me3S~~

S~'Ie3

Me3Si-- ~-~~ S i M e 3 SiMe3 (i)

Schen~1

2+

[L~r~)]2

97 ,,

.

.

.

Bases

.

,

.

.

,

Equiv. of the Base

,,

Reaction time (h) at 20~

Yield PhSMe

Yield C6H4(SMe)2 t

BuLi and KOCMe2Et

2and2

1.5

45

47

BuLi and

2and2

3

45

49

BuLi and KOCMe2Et

8and8

2

17

81

BuLi and KOCMe2Et

2and6

1.5

50

35

BuLi and KOCEtzMe

2 and 2

2

33

48

BuLi and KOCEt2Me

4 and 4

2

32

57

BuLi and KOCEt3

2 and 2

2

25

46

BuLi and KOCEta

2and2

2.5

20

55

BuLi and

2 and 2

2.5

46

30

K0CM,Et

i

KOCMe, BuLi and

,

3 and3

34

,

,

,

27

KOCM, Table 1 Formation of mono- and dimetallated benzene from mixtures of potassium tert-alkoxides, n-butyllithium and benzene

98 The dianion (1) when generated at room temperature in oxygen free THF imparts a dark red colouration to the solution and is isolated as red crystals from hexane. As would be expected the dianion is very susceptible to oxygen and water and readily reverts to the silyl derivative (2) in contact with air. Reaction of (1) with water results in the formation of 1,2,3,4,5,6hexakis(trimethylsilyl)cyclohexa- 1,4-diene (3) (scheme 2). H

S~Nle3

Me3Si

SiMe 3

I-I20 (1) Me3Si"

/~

Me3Si

"SflVIe3 H

(3) Scheme 2 The most interesting feature of the structure of (1), as determined by X-ray crystallography, is that the Li ions are situated on the same side of the benzene ring, and despite electrostatic repulsions, are only 2.722 A apart. This structure is different from those previously reported for polynuclear aromatic dianions where the cations are above and below the plane of the aromatic ring, for example in the lithiation complexes of naphthalene, anthracene and fluorene (J.J. Brooks, W. Rhine, and G.D. Stucky, J. Amer. chem. Soc., 1975, 94, 7339, and 7346, and W.E. Rhine, J. Davis, and G.D. Stucky, J. Amer. chem. Soc., 1975, 97, 2079).

99 A structural determination of the 10~x electron dianion dilithium pentalenide (4) shows the two lithium cations to be on opposite sides of the aromatic dianion (P. von Ragu~ Schleyer et al., Chem. Comm., 1985, 1263). This agrees with MNDO calculations which also favour this opposite arrangement of metal ions. The two lithium ions are 115 and the five possible arrangements are shown in figure 1. Structure (4) is 5 kcal mol1 more stable than its nearest rival and at least 20 kcal mol q more stable than the others.

Li

Li A HtO = 9.4 kcal mol- 1 (4) Li

Li

Li A HtO =30.7 kcal mol- 1

AHtO = 14.4 kcal mol- 1 ,,,,L.i

.,,"Li

A Hto = 43.5 kcal mol- 1

A HtO = 39.5 kcal mol- 1 Figure 1

100 Aryllithium and aryl-metal-lithium clusters of the general formula AraM2Li2 (M = Cu, Ag, Au) have been prepared and their structures assigned by X-ray crystallography (G.van Koten and J.G. Noltes, J. Amer. chem. Soc., 1979, 101, 8593). These clusters have polynuclear structures with a metal core to which each of the aryl groups is bound by a three-centre two electron bond to two metal atoms. For example the structure of (2-Me3NCH2C6Ha)aM2Li2 is shown in figure 2.

Li

Me2

Me~

Figure 2 If the complexes of the type Ar4M4 and Ar4U2Li2 contain unsymmetrical aromatic groups, then they can exist as four unique stereoisomers which can be detected by proton n.m.r, spectroscopy. When the C(1) carbon of an asymmetrically substituted aromatic ring bridges two dissimilar metals then it becomes a centre ofchirality. Two such situations can occur; a) when the two metals bridged are not the same i.e. Cu and Li, or b) when the metal atoms are the same but differ in their coordination geometry. Again these isomers can be distinguished by proton n.m.r.

101 Other cluster organometallics of lithium which comain multicemre bonds have been reported such as intramolecularly chelated di and tetranuclear aryllithium compounds for example Li4[C6H4(2-CH2NMe2)]4 (G. van Koten, J. Amer. chem. Soc., 1982, 104, 5490). The structure of this compound, as determined by X-ray crystallography, contains four-cemre-two-electron=bonded C(aryl) atoms and hepta coordinate lithium atoms as shown in figure 3.

Li -~"

"-" '%~t, .

Mo,i Figure 3

This cluster was prepared by slow crystallisation from an ether-hexane solution containing an exact equimolar mixture of n-butyllithium and N,Ndimethylbenzylamine (scheme 3). CH2NMe2

CH2NMe 2

Et2o 4

+

Li

4 BuLi -BuH Scheme 3

-4

102 Other mixed metal organometallics containing lithium have been prepared, for example phenyl and p-tolyl-iron-lithium trans dihydrides (A.E. Silov et al., J. organomet. Chem., 1992, 428, 107). The action of excess phenyllithium on iron(II) chloride gives a zero valent iron complex [FePh4]Li4.4Et20 (A.E. Shilov et al., 1983, 244, 265) which reacts with nitrogen to produce a new iron-lithium complex containing dinitrogen coordinated to iron. A similar dihydrogen complex is formed when [ F e m r 4 ] L i 4 . 4 E t 2 0 , where Ar is phenyl, mor p-tolyl, interacts with hydrogen. Binuclear complexes are formed by interaction of the trans dihydride complexes with solvents such as diethyl ether and THF. Scheme 4 shows how the mixed metal complexes are formed. -30oc 7 PhLi + FeC13

[Li4FeIIph6] + 3 LiCI + 0.5 Ph 2

Et20 20oc

[Fe0ph4]Li4 . 4 Et20

+ ek2

Scheme 4

Both the Feu and Fe~complexes react readily with hydrogen to give dihydrides as well defined dark crystals. Infra red spectroscopy and X-ray crystallography reveal that the Fe n complex dihydrides show a central oetahedral unit Ar4FeH2with the hydrogens trans at the Fe atom. Fe-H bond lengths are typical of iron hydrides, and the i.r. stretching frequency for the Fell bond is about 1200 em"~. Although the preparation of the m-tolyl complex is successful, the o-tolyl and mesityl complexes can not be prepared, presumably due to sterir hindrance of the ortho-methyl groups.

103 Reactions of these iron complexes with hydrogen are carried out at room temperature. Reaction of the p-tolyl complex is complete within 3 hours whereas the m-tolyl complex takes 24 hours. This difference in reactivity is explained by steric hindrance to cis-trans isomerisation in the dihydride complex. It is evident that the cis-dihydride must form first, followed by isomerisation to the more stable trans isomer. This isomerisation requires the bending of the Fe-Ar bond, which is hindered by adjacent methyl groups. Mixed metal organometallics containing lithium and tin have been proposed as intermediates in lithium-tin exchange reactions used for the preparation of organolithium derivatives when more robust methods are not mild nor selective enough (H.J. Reich and N. Phillips, Pure and Applied Chem., 1987, 59, 1021 and J. Amer. chem. Sot., 1986, 108, 2102). Functionalised organolithium derivatives bearing electrophilic groups are regularly synthesised by this exchange method. The proposed intermediate is a pentavalent tin "ate" complex (5) based on kinetic studies and spectroscopic, mainly n.m.r., characterisation of lithium pentaarylstannate complexes.

Li+

R' .I..R R-~-~ R

R

(5) 1-Methyl-2-(methylthio)benzene (6) when treated with two equivalents of nbutyllithium in the presence of N,N,N',N'-tetramethyl-l,2-ethanediamine (TMEDA) gives the dilithio compound (7) (S. Cabiddu, C. Floris, and S. Melis, J. organomet. Chem., 1989, 366, 1).

104

M0 (e

c,~...sH2cLiH2Li

2 n-BuLi

SMe

(6)

(7)

When the methyl group in (6) is meta or para to the methylthio group the second lithiation does not occur at the benzylic position but ortho to the methylttfio group. The benzylic metallation of (6) can be explained in terms of methyl thio group metallation, aided by the unoccupied d orbitals on sulphur, followed by metallation of the benzylic position. The latter is mediated by interaction of the negative sulphur atom with a second molecule of butyllithium (8).

CH2 ' s~Li"'Bu I

CH2Li (8) Scheme 5 details the products from quenching the dilithium derivative (7) with eleetrophiles. Attempts to form a dicarboxylic acid by reaction

105 Et

~SE,

T /i

~

CH2CH2CH=CH2

"

'SCH2CH2CH=CH2

2 MeI

2 CH2=CHCH2Br

2 Me3SiCI (7)

sc,~/

PhCOCl

I CO ~SS

~S

(9) OLi (7)

2 CO2 +

0o)]

~

O

(11)

OLi H+

(9) Scheme 5

106 with carbon dioxide result in very low yields of the acid together with the sulphur heterocycle (9) which is formed in about 50% yield. Formation of (9) can be explained by addition of one molecule of CO2 to give intermediate (10) or (11), followed by intramolecular addition of the second lithiated site to the carbonyl function of the monoacid. This reaction is unusual in that it occurs when there is an excess of CO2. Normally this type of cyclisation only takes place when there is a deficiency of CO2. The dilithiated derivative (7) resists attempts to introduce regioselectively two different functional groups. For example, treating (7) with one equivalent of methyl iodide followed by an excess of methanol results in the formation of an equimolar mixture of (12) and (13).

Et

~ S M e (12)

,Me

~~I~SEt (13)

Reactions of the lithio derivative (7) with gem-dihalides provide useful routes to benzo-eondensed six membered heteroeylees, containing sulphur and one other heteroatom (scheme 6).

107 Me ;LMe ~ kS~ C l 2 p h

Me

2SIC12 [~s~Si~,,M~h

s~t~

/ph

Scheme6 Reaction of 1-bromo-2-[(trimethylstannyl)methyl]benzene(14) with n-butyl and tert-butyUitl,fium leads to 1-bromo-2-(lithiomethyl)benzene(15) and 1lithio-2-[(trimethylstannyl)methyl]benzene(16) respectively (H.J.R. de Boer, O.S.Akkermen, and F. Bickelhaupt, Organomet., 1990, 9, 2898). nButyllithiumeffects a lithium-tin exchange whereas tert-butyllitMum reacts by the more conventional lithium-halogen exchange process. The dilithiated derivative ~,2-dilithiotoluene (17) has also been prepared by reaction of (16) with tert-butyllittfium.

108 This remarkable selectivity is explained by making the following assumptions: i) lithium-tin exchange is faster than lithium-halogen exchange under identical conditions, ii) lithium-tin exchange is more sensitive to steric hindrance than lithium-halogen exchange, iii) exchange of both tin and halogen is retarded by the presence of electron donating substituents. Scheme 7 shows how these assumptions are applied to the selectivity of reactions of n- and tertbutyllithium with (14).

m

~

SnMeanB ~70~ ~ S n M e 3 ,r

j

tBuLi -70~ ow ls - ~

SnM3e

fast L 1

(14)

(16)

tBuLi I very .70Oc ', sbw

lBuLi I fist 25~ _

~

SnMe3tBu L~ ~ L i

(15)

SnMe3tBuL~ (18)

~~Li (17)

Scheme7

Li

109 n-Butyllithium is sterically undemanding and reacts by lithium-tin exchange (bearing in mind assumption i). Further reaction with n-butyllithium to give the dilithiated derivative (16) is strongly retarded by the presence of the benzylic carbanion, tert-Butyllitl,fium is much more sterically demanding than its n-butyl counterpart and so it reacts via lithium-halogen exchange to give (16) (N.B. assumption ii). Only when the temperature of the reaction is increased to 25~ does the lithium-tin exchange reaction take place to give the much more sterically congested stannate complex (18). This loses trimethyltert-butylstannane to give (17). 2.2

Sodium, Potassium, Rubidium, C~esium

Much less has been reported during the past decade regarding the heavier Group 1 metals. The reaction of organolithiums with heavier alkali metal alkoxides generates an aryl compound of the heavier alkali metal and lithium alkoxide (L. Lochman, J. Pospisil, and D. Lim, Tetrahedron Letters, 1966, 257 and L. Lochman and D. Lim, Organomet. Chem., 1971, 28, 153). When toluene is introduced as a third component to this reaction benzylpotassium is formed in good yield. Likewise when benzene is added phenylpotassium is produced (scheme 8) (L. Lochman, Coll. Czech. chem. Comm., 1987, 52, 2710).

+ RLi +

. M~

+ RH + OK

M~

OLi

K Scheme 8 Arylsodium derivatives can be prepared by a similar reaction of sodium alkoxides with aromatics and alkylithium derivatives. This reaction forms the

110 basis of a method for the facile coupling of non-activated aromatics (L. Lochman and J. Trekoval, Coll. Czech. chem. Comm., 1986, 51, 1439). When aryl bromides or iodides are added to the reaction mixture containing sodium or potassium alkoxide and butyllithium, the major organic reaction products are those due to coupling (scheme 9).

E. f ~ . Me + KBr + Me:

_.•.

Me

+ BuLi + OK

Me?

Br

OLi

Bu

Scheme 9 The reaction of potassium hydride with PfiMe2SiOH, followed by crystallisation of the product from benzene results in [(C6H6)KOSiMe2Ph]4. This complex has been characterised by elemental analysis, proton n.m.r., 29Si n.m.r, and its structure elucidated by X-ray crystallography (K.G. Caulton et al., Polyhedron, 1991, 2371). The complex is interesting due to the rl 6 bonding of the benzene to potassium. The benzene ring binds to potassium via its n-system as there are no better donors available in the complex. Here such bonding can occur without the back bonding found in transition metal arene complexes. The complex K2[la-N(SiMe3)2]22toluene also exhibits rl6-arene binding to potassium, and solutions of alkali metal compounds with low coordination numbers, in benzene are also likely to exhibit this type of arene/potassium binding. This shows that a hard Lewis acid such as K + has an affinity even for as soft a donor as the n-arene system. Arylsodium and potassium derivatives can be solubilized in benzene by the addition of magnesium 2-ethoxyethoxide (C.G. Screttas and M. MichaScrettas, Organometallics, 1984, 3, 904). One reason for the limited synthetic use of arylsodium and potassium derivatives is their intractability, they are

111 insoluble in solvems in which they might survive long enough to be useful. Organosodium and potassium derivatives do have certain advantages over the more ot~en used organolithium derivatives in that they are more reactive and so they do not require a Lewis base catalyst in order to effect more difficult metallations (C.G. Screttas and J.F. Eastham, J. Amer. chem. Soc., 1965, 87, 3276). The orientation of metallation is metal dependant (M. Schlosser and P. Schneider, Helv. 1980, 63, 2404) thus having a selection of Group 1 metal aryl derivatives, which are hydrocarbon soluble, would be a useful tool for any synthetic chemist. Scheme 10 shows the reaction of arylalkalimetal reagents with magnesium alkoxides. The resulting complex is quite stable in benzene for long periods of time at 13-22~ but at higher temperatures crystalline precipitates form.

nArM + mMg(OR)2

~

(ArM)n[Mg(OR)2]m

Scheme 10

The solutions exhibit normal organometallic reactivity towards carbon dioxide and benzophenone, and phenylsodium and potassium complexes effect metallation in the same way as organometallic reagents. For example they metallate toluene and dibenzofuran readily and react with thioanisole to metallate the methyl group. Arylc~esium derivatives are extremely reactive and of little synthetic use. Aryl complexes of c~esium of the type Cs[AI(CH3)212]:C6H4(CH3)2 have been prepared and their crystal structures reveal that the c~esium ion is sandwiched between two p-xylene molecules with an average Cs-C bond distance of 3.83A. The c~esium ion also has four iodine atoms within bonding distance, 3.925~, (Figure 4) (RD Rogers and J.L. Atwood, J. Cryst. tool. Structure, 1979, 9, 45).

112

o

~

o o = carbon

0

0

6b

db

O0

= iodine

O0

b ~

o

Caesium environment in C s[Al(CH3)212] P-C6H4(CH3)2 Figure 4 Potassium analogues of these complexes show a much stronger bonding interaction as revealed by rather shorter metal-carbon bond distances. The average K-C distance is in these complexes is 3.36A (J.L. Atwood, K.D. Crissinger, and R.D. Rogers, 1978, 155, 1). The reaction of benzene with CSC24results m an intercalation compound in which each c~esium is surrounded by two benzene tings, tilted at 36 ~ to the c axis (P. Touzain and A. Hamwi, Materials Science and Engineering, 1991, a l 0 , 275).

3.

Group 2 Metals

3.1

Beryllium, Magnesium, Calcium, Strontium, Barium

The chemistry of Grignard reagents is well established as is that of the corresponding beryllium analogues. Many reviews and papers have been published on these compounds and their chemistry. The preparation of highly functionalised aryl organometallics is of great

113 interest due to their versatility as reagents in the preparation of a wide range of highly functionalised organic molecules (see for example, S. Achyutha-Rao and P. Knochel, J. Amer. chem. Soc., 1991, 113, 5735 and H. Tsujiyama et al., Tetrahedron Letters, 1990, 31,4481). The preparation of these highly functionalised organometallics, which contain eleetrophilic groups, is not, however, straightforward as direct metal insertion is often difficult and can lead to mixtures of products. It has been reported that functionalised aryUithiums can be used to prepare organometallic derivatives of magnesium, zinc and copper. Functionalised aryl halides (19) can be converted in organolithium derivatives (20) by slow addition of butyllithium to the arylhalide at -100~ (scheme 11). Addition ofMgBr2, ZnI2, or CuCN:2LiCI to the organolithium at -100~ results in a transmetallation and furnishes more stable highly functionalised organometaUics (C.E. Tucker, T.N. Majid, and P. Knochel, J. Amer. chem. Soc., 1992, 114, 3983).

Y

y

Y

BuLl (1.5 eq) ,

X

~

~'~

- 100 oc 3 nimaes IHF

(19)

Li

ZnI2 or MgBr2 or CuCNLi or C uCNZnX

(20)

Y = CO2R, CN, CI, N 3, NO2 X=IorBr M = Z.n.I,MgBr, CuCN Scherr~ 11

M

114 Various eylopentadienyl magnesium complexes have been prepared by the reaction of dibutylmagnesium with eyelopentadienes (M.F. Lappert et al., J. organomet. Chem., 1985, 293,271). Such magnesium complexes are useful as mild ligand transfer reagents as is illustrated by the synthesis of Zr(CsH3Xz)C13, where X is H or SiMe3. An unusual reaction of aryl Grignards is that with (NPCI/)3 (21) which gives arylcyclotriphosphazines (22) and bis(arylcyclotriphosphazines) (23) (scheme 12) (H.R. Allcock, J.L. Desoreie, and P.J. Harris, J. Amer. chem. Soc., 1983, 105,2814).

CL\ / CI N~PxN CI~P~N/P~CI c/

Cl

(21)

PhMgBr

Ph_\ / CI N~PxN CI----~,,~N/P~Ph Ph

CI

(22)

Ph_-'___~P~N Cl p h ~ ~ ' N ~' " P h C1 (23)

Scheme 12 The mechanism of this reaction has been studied it seems that (22) and (23) are not related and form independently. In the case of (23), coupling of a monomeric cyclophosphine is implicated (scheme 13). Oxidation and reduction potentials of reactants have been correlated with product distribution in the reaction of various organomagnesium reagents with aromatic earbonyl and nitro compounds (M.Okubo, T. Tsutsumi, and K. Matsuo, Bull. chem. Soc. Jpn., 1987, 60, 2085).

115 CI\ /C1

CI\ /R

N~P~N

N~PxN

Cl--~. N/P----CI CI CI (21)

C1 (22)

t

-RCI

CI\ N/I~NIMgX l)

CI

l

R

R\ ,

N/I~N.~-MgX

~VlgX

II

r

I

CI

CI

Cl (22)

CI\ /CI CI\ /CI N~pxN N/P~N I

II

II

I

CI---'~',~N/P~ ~-N ~'P~- C I C1 RR C1 (23)

Scl'~'n~13

116 The electron-donating ability (EDA) of a series of Grignard reagents and the electron-accepting ability (EAA) of various arylnitro and carbonyl compounds have been detem~ed by cyclic voltametry. The relative efficiency of electron transfer in individual reactions is dependent on the combination of EDA and EAA values, a correlation can then be made between the distribution of normal and abnormal (free radical) products and AE, the difference between EDA and EAA. It is found that in reactions where AE is small, typically less than 2.2, high yields of products due to free radicals reaction are obtained; vigorous electron transfer occurs in these reactions. For cases where the AE value is 2.2 -2.8, good yields of normal products, in most cases above 65%, are obtained as the electron transfer process is subdued. Arylcalcium derivatives are far less well understood than their beryllium and magnesium counterparts principally due to their reactivity and difficulty of synthesis. Metal vapour reactions of calcium with aromatic compounds to give arylcalcium derivatives has been studied (K. Mochida et al., Organometallics, 1987, 6, 2293). Calcium is generated by vaporisation from a tungsten filament at 20 mg minq while an excess of the aromatic compound is co-condensed on the walls of a quartz reaction vessel. Arylcalciums are obtained as black solids in which the calcium atom is inserted into the C-H bond. They are very reactive and combine with electrophiles with ultimate displacement of calcium ion (scheme 14).

Ca(g)+ ~

(g) 77K

(24) Schen~14

ii)1-/20

S~/Ie3

117 3.2

Zinc, Cadmium and Mercury

Benzyllithium and magnesium compounds are otten difficult to prepare by conventional methods and decompose to give cross-coupled products even at low temperatures. Benzylic derivatives of zinc, however, can be prepared in high yield with little evidence of cross-coupling (S.C. Berk, P. Knochel, and M.C.P. Yeh, J. org. Chem., 1988, 53, 5791 and T.N. Majid and P. Knochel, Tetrahedron Letters, 1990, 31, 4413). The reactivity of the organozinc derivatives (25) towards electrophiles is much increased by transmetallation to the copper containing organometallics (26) (scheme 15).

R

Br

~ X

R

ZaBr

Zn, TI-IF 0oc, 2-3h

R

.Cu(CN)ZnBr

CuCN.2IziC1~ X (25)

R

E

E X (26)

X

X = COR, OAc, CN. CI, I E = aldehydes,acidchlorides,enones,allylicbromides R= CH3, H

Scheme 15 This methodology has been developed for the preparation of polyfunctional organometallics bearing sulphur (P. Knochel et al., Tetrahedron, 1992, 48, 2025).

118 Regioselective addition of copper-zinc arylorganometallics to 3-substituted pyridinium salts results in the formation of predominantly 4-arylpyridines, especially if the substituent is electron donating (M-J. Shia0 et al., J. chem. Res (S), 1992, 247). Pyridinium salts with electron withdrawing groups at the 3-position tend to give mixtures of both 2- and 4-arylated compounds. The ratio of 4 : 2 substitution is between 2.5 : 1 and 4 : 1. Analysis of the lowlying vacant orbitals on the pyridinium ring predicts that sott nucleophiles should preferentially substitute at the 4-position. Since mixed copper-zinc aryl organometallics generally act as soft nucleophiles the prediction is fulfilled in practice. Electroreduction of aryl chlorides or bromides in a cell fitted with a sacrificial zinc anode, in the presence of nickel-2,2'-bipyridine complex results in the formation of the corresponding zinc organometallic in good yield (S. Sibille, V. Ratovelomanana, and J. Perichon, Chem. Comm., 1992, 283). Perfluoroaryl cadmium reagents (27) have been prepared, under mild conditions, by the direct reaction of bromofluoroaromatics with powdered cadmium (P.L. Heinze and D.J. Burton, J. fluorine Chem., 1985, 29, 359). Both the mono and bis(aryl) cadmiums are formed in the ratio 85 : 15.

C6H5Br + Cd X = Br, C6F 5

DMF, RT ~

[C6F5CdX] (27)

Regiospecifie monoacetoxymercuration of a series of aryl substituted thiazolines results in derivatives which have increased fungicidal activity (J. Mohanty and G.N. Mahapatra, Indian J. Chem., 1982, 52).

119 Mercury acetate has been used to effect cyclisations of ortho substituted arylacetylenes (28) to afford a variety of chloromercuryheterocycles (29) (scheme 16) (R.C. Larock and L.W. Harrison, J. Amer. chem. Sot., 1984, 106, 4218). The cyclisations are carried out at either 0 or 25~ in acetic acid, in the presence of sodium chloride.

X-oC_) ( y/C ~'CR

NaCI

(28)

Y

HgCI

(29)

X = O, S, CO 2 Y=-,CO Scheme 16 Mercury trichloroacetate can also be used to effect aryl mercuration (M. Niemyjska et al., Bull. Poilish Acad. Sci. Chem., 1990, 38, 1). Mercury trichloroacetate, prepared in situ from mercury(H) oxide and trichloroacetic acid, reacts with benzene in the presence of sodium chloride to afford phenylmercury chloride, rather than phenylmercury trichloroactate. Metal exchange reactions provide a general route to organomeeurials. Silatranes (30) react with mercury(H) chloride to yield arylmercury chlorides (J.D. Nies, J.M. Bellama, and N. Ben-Zvi, J. organomet. Chem., 1985, 296, 315).

120 ArSi(OCH2CH3)3N + HgCI2

-

=

ArrtgCl + XSi(OCH2CH3)3 N

(30)

Mercury(II) chloride also reacts with ortho-manganated arylketones (31) to afford arylmercury chlorides (J.M. Cooney et aL, J. organomet. Chem., 1987, 336, 293). Yields ofmercurated products are generally good, about 65%, and the transmetallation is specific to the position ortho to the acyl group.

HgCI

P'2

R2

(31) R1 = CH3, Ph R2 = H, OCH3

A similar transmetallation reaction occurs between the gold trichloride complex (32) and the mercury complex (33) (scheme 17). A further transmetallation of the resulting complex (34) occurs when it is treated with the bisarylmercury (35) in the presence of tetramethyl ammonium chloride (J. Vincetnte et al., J. chem. Soc. Dalton, 1990, 10, 3083).

121

AuCl3(tht) + Hg(C6H4N=NPh)2 CI/ (32)

Ncl

(34)

(33)

I HgR

--Ph R = p-NO2C6H4, or C6F5

/

R

tht = tetrahydrothiophene

Ncl

(35) Scheme 17

Arylmercuric halides react with with [Et3NH][(I,t-CO)(B-RS)Fe2(CO)6] to give bridged acyl complexes of the type (la-R'C=O)(la-RS)Fe2(CO)6 (D. Seyforth et al., Organometallics, 1991, 10, 3363). N.m.r. has been used to determine the structure of coordinatively unsaturated aryliridium(III) complexes which comain iridium-mercury bonds. In particular, mercury coupling in the 3,p n.m.r, spectrum of (36) confirms the presence of Ir-Hg bonding, J(3~p-~99Hg)= 204.5 Hz. (W.R. Roper and G.C. Saunders, J. organomet. Chem., 1991,409, C 19). Complexes of this type are prepared by the reaction of arylmercurials with IrHCI2(PPh3)3 (Scheme 18).

122 IrHCI2(PPh3)3 + Hg(o-tolyl)2 I Ben~ne, rettux, 1.5h, 20%

Ph3P. I ,,,5~'~

C1---Ir~'

(36) Reduced

--

Pressur~o,

1 atm

12 78% or N~C150%

PhaP CI,,.... .] ....... /

Ph3P

....

~.

INHgx PhaP ~X

/

X - I or C1 IrCI(CO)(PPh3)2 + Hg(tolyl)2 S c h e m e 18

123 Sustituent effects on ~99Hgchemical shit,s in bisarylmercurials has been studied (Y-J. Wu et al., Chem. Res. in Chinese Universities, 1992, 8, 81). In general electron donating substituents in the aromatic tings of bisarylmercurials cause a downfield shit~ of the ~gHg chemical shift. This occurs because there is an increase in the electron density in the 6pz orbital of mercury by p-n conjugation, which results in paramagnetic shielding.

4

Group 3 Metals

4.1

Boron

The degree of involvement of the available 2p~-orbital on the sp 2 hybridised boron in triarylborirenes has been investigated (J.J. Eisch et al., J. Amer. chem. Soc., 1990, 112, 1847). These boron containing analogues of cyclopropene are readily prepared by the photolysis of diaryl(arylethynyl)boranes (scheme 19). Mes\

hv B----C~C----Mes

Mes'/

~ donor solvent

MeS~C__C/Mes \ / B[ Mes

Scheme 19 Triarylborirenes are surprisingly stable despite their considerable ring strain. Stabilisation is afforded by extensive delocalization of the two n-electrons of the ring among the boron and carbon p-orbitals, and the ring can be said to have H0ckel aromaticity analogous to that of the triphenylcyclopropenium cation. The alternative valence bond description involves the canonical forms shown (scheme 20) with considerable electron density residing on boron.

124

Xc=c \/

ArXc_cr \\/

~

~

B

B-

\11 _B

Ar

Ar

Ar

I

I

I

Scheme 20 The aromatic nature of various three membered rings containing boron has been studied using ab mJtio molecular orbital methods (P.H.M. Budzelaar and P.vonR. Schlyer, J. Amer. chem. Soc., 1989, !08, 3967). The studies reveal that the 2r~-species (37) and its amino derivatives are planar and aromatic with a resonance stabilisation energy of 55 kcal mol~. Derivatives of the diazaboridine ring system (38) are antiaromatic 4r~ systems. However, amino substituents on the boron relieve this destabilising effect by electron donation.

H

I N

/\ H/B~B~H

(37)

H

I

/N\ H/N--B~H

(38)

The unsaturated B3P3ring system is also aromatic as indicated by the shortness (1.84 A) of the B-P bonds (P.P. Power, Pure and Appl. Chem., 1991, 63, 859 and H.V.R. Dias and P.P. Power, J. Amer. chem. Soe., 1989, 111, 144).

125 Pentaaryl boroles can be prepared by two routes, (i) the interaction of an (E,E)-( 1,2,3,4-tetraaryl- 1,3-butadien- 1,4-ylidene)dilithium with an aryl(dihalo)borane and (ii) the exchange reaction between a 1,1-dialkyl2,3,4,5-tetraarylstannole and an arylboron dichloride (scheme 21) (J.J. Eisch, J.E. Galle, and S. Kozima, J. Amer. chem. Sot., 1986, 108, 379). R

RC~-CR

R

'

Method (ii) Me2SnCI2 J R

Me

R

"Me

~ R

R

{

Method (i) RBC12 R

R.R

R

R

Scheme 21 Pentaaryl boroles are strong Lewis acids, they complex with amines, ethers and nitriles and are very prone to oxidation, solvolytic cleavage, and DielsAlder reactions. This high reactivity and their unusual proton n.m.r, and electronic spectra can be explained by considering them as Huckel antiaromatic systems, the destabilization arising from the interaction of the 4r~electron four carbon fragment and the 2p~ orbitals on the boron.

126

4.2

Aluminium

Aluminium is known to interact with benzene (R. Srinnivas, D. SOlze, and H. Schwartz, J. Amer. chem. Soc., 1990, 112, 8334) affording complexes which are easily studied by e.s.r spectroscopy. Theoretical methods have now been applied to these complexes in order to establish their structure (M.L.McKnee, J. phys. Chem., 1991, 9_5, 7247). Figure 5 shows the three possible modes of interaction of aluminium with a benzene ring, i.e. 1,2- 1,3- and 1,4-addition. Calculations indicate that the most stable interaction is 1,4-addition, associated with a calculated binding energy of 7.4 kcal molq. This is in agreement with experimental observations.

A1

AI

A1

z ~ l H

H

1.350

Hd "

'N~H

,.....,H

H, ..... /~.453x..... ,H

H

1.4sl

.-,o,7 ,ii7 H

H

H

Bond lengths are given in Angs~oms Figure 5

Further calculations on the complex formed between alumim'um and benzene suggest there is little evidence for a stable AI ~-complex. The fine structure of the e.s.r, spectrum of the Al-benzene complex can be explained by the low distortion energy of the benzene boat structure which is enforced by bonding to the metal (S.J. Silva and J.D. Head, J. Amer. chem. Soc., 1992, 114, 6479). Theoretical studies have been undertaken on benzene complexes of univalent gallium salts (G.A. Bowmaker and H. Schmidbaur, Organometallics, 1990, 9,

127 1813). The model structures used in this study are shown in figure 6.

~+

Ki +

i I I !

I I ! I

l

,

"Ca*

a* ! !

i

J

' !

HgI2 >> Hgls. Measurement of activation parameters, which are low, suggests that an initial ~-complex is formed between PhSnE h and the mercury salt. This is supported by the high values for activation parameters obtained for the reaction of EtaSn with mercury halides; here the formation of ~x-complexes is not possible.

140 Reaction of YC6H4SnEt3 with mercury salts in THF is also second order (M.R. Sedaghat-Herati and T. Sharifi, J. organomet. Chem., 1989, 363, 39). The rate determining step involves reaction of the n complex formed between the reactants; the rate is not sensitive to substituents in the aromatic ring. The solid state structures of organotin halides of the type R3SnX and R2SnX 2 (R = aryl, X = CI, Br) have been elucidated by solid state 1195n n.m.r. (R.K. Harris et al., Organometallics, 1988, 7, 388). Comparison of solid state and solution state ll9Sn n.m.r, reveals that no gross changes in co-ordination of the metal occur between solution and solid state structures. Aryltributylstannanes bearing electron withdrawing groups have been prepared by palladium catalysed reaction ofhexabutylditin with aryl iodides (M. Kosugi, T. Ohya, and T. Migita, Bull. chem. Soc. Jpn, 1983, 56, 3855).

Pd(PPh3)4 Bu3SnSnBu3

+

ArI

~

ArSnBu3

+

Bu3SnX

This route to arylstannanes provides an alternative to the reaction of an arylorganometallic with an organotin halide, a method which is unsuccessful when the aromatic ring bears a reactive substituent (e.g. NOz, -COR, CN). Cross coupling of aryl triflates with stannylcuprates is also catalysed by tetrakis(triphenylphosphine)palladium to give arylstannanes (W.D. Wulff et al., Tetrahedron Letters, 1988, 29, 4795)

141 OSO2CF3

SnBu3 Pd(Ph3P)4

+ 03u3Sn)2Ct~NLi

H

'~CF3CO2 H

Neighbouring tertiary amine groups bonded to arylstannanes increase the rate by which these catalyse the palladium mediated arylation of furoyl chloride (scheme 31) (J. Brown et al., Chem. Comm., 1992, 1440).

Sn reagent Ph O

Ph3P\ /El ph Pq

Feb3 O Scheme 31

O

142 Furoyl chloride does not react appreciably with Ph3SnMe at 40~ but if compound (52) is used as the tin substrate the reaction shown in scheme 31 goes to completion in 30h at 20~ Thus, the amino substituent is involved in the key transmetallation step.

(52) Rate constants for the abstraction of bromine atoms by tributyltin radicals from a series of aryl bromides (D.P. Curran et al., J. org. Chem., 1991, 56, 7162) show that electronegative substituents on the arorhatic ring increase the rate of bromine abstraction. These measurements can be used in planning synthetic procedures where more than one radical precursor is present. Reaction of tetraarylstannanes or triphenyltin halides with diborane results in the transfer of one or more aryl groups from tin to boron. These arylboron intermediates yield phenols upon oxidation and boronic and borinic acids when hydrolysed (F.G. Thorpe et al., J. organomet. Chem., 1994, 62__~,7). The transfer of aryl groups is a stepwise process. Scheme 32 shows the possible sequence of reactions for tetraaryl stannanes.

Ar4Sn

+

BH 3

~

Ar3SnH

+

BH 3

,~

Ar2BH

+

Ar2SnH2

Ar4Sn

+

ArBH2

~- Ar2BH

+

Ar3SnH

Scheme 32

ArBH2

+

Ar3SnH

143 The presence of A r B H 2 is suggested by the formation ofboronic acids upon hydrolysis and the formation of borinic acids suggests Ar2BH is formed. The sequence of reaction for triaryltin halides is shown in scheme 33.

Ar3Sn

+

BH3

~

Ar3SnH

+

XBH2

Ar3Sn H

+

BH3

~

Ar2SnH2

+

ArBH2

Ar3SnH

+

XBH2

.~

Ar2SnH2

+

ArBHX

Scheme 33 The nature of X determines the reaction pathway, but the formation ArBH2 explains why monoarylboron species are observed aider hydrolysis in the presence of excess diborane. When stoichiometric quantities of diborane are used XBH2 becomes the dominant species formed. Structure (53) is believed to be the important reaction intermediate in the aryl transfer process.

Ar3S

1-13

(53)

144 Selective mono-fluorination of aromatic substrates can be achieved by ipsosubstitution oftrialkytin groups. The fluorination proceeds v i a an electrophilic substitution pathway and can be effected by elemental fluorine, caesium fluoroxysulphate (M.R. Bryce, R.D. Chambers, S.T. Mullins and A. Parkin, Bull. Soc. chim. France, 1986, 1624), or by trifluoromethyl hypofluorite (M.R. Bryce, R.D.Chambers, S.T. Mullins, and A. Parkin, J. fluorine. Chem., 1984, 26, 533). This methodology has been developed in order to selectively fluorinate imidazole derivatives

/~N~M Me3Sn~

e

F2/N2~

~ Me

/~N~M

e

F~}~ Me

Arylboronic acids undergo rapid boron-lead exchange with lead tetraacetate in the presence of catalytic quantities of mercury(II) acetate (J. Morgan and J.T. Pinhey, J. chem. Soc., Perkin I, 1990, 715). Hg(OAc)2 PhB(OH)2 + Pb(OAc)4

PhPb(OAc)3

This reaction has been developed as a convenient method for 'in situ' preparation of useful electrophilic C-arylating agents for ketones.

145 O ArB(OH)2 O2Et

i) Pb(OAc)4, Hg(OAc)2, CHC13 ii) 2- Ett~xycarbonylcyclopentanone

A series of tetraaryllead compounds have been studied by electron impact and fast atom bombardment mass spectrometry (M. Gielen, H.O. Van der Kooi, and J. Wolters, Main Group Metal Chemistry, 1987, 1_.0, 1).

6.

Group 5 metals

A series of arsenic compounds of general structure (54) have been prepared by the condensation of benzaldehydes, pyruvie acid, and p-arsanilir acid. Investigation of their antimicrobial activity shows them to be very effective against Staphyllococcus aureus, but not particulary potent against Escherichia coli (D.J. Bhatt, G.C. Kamdar, and A.R. Parikh, J. Inst. Chem., 1984, 56, 233).

~

C.O2H

H

o-- I OH

R (54)

146 The reaction of benzene with arsenic pentafluoride results in diphenylfluoroarsonium hexafluoroarsenate which reacts with CsF to give PhEAsF3 and C s A s F 6. 19F n.m.r, studies reveal that Ph2AsF3 is trigonal bipyramidal with the phenyl groups in equatorial positions (F.L. Tanzella and N. Bartlett, Anorg. Chem. org. Chem., 1981, 36B, 1461). Arsabenzene (55) is aromatic; it undergoes electrophilic substitution at the 2and 4-positions. For example, Friedel-Crafis acetylation results in a mixture of 2- and 4-acetylated products, nitration also gives a mixture of 2- and 4substituted products (A.J. Asche III. et al., J. org. Chem., 1981, 46, 881).

COMe +

~.COMe

+ CH3COC

(55)

Treating SbC13with naphthalene, anthracene or phenanthacene results in the formation of adducts of the general formula SbCI3.Ar (where Ar is the aromatic substrate). Further treatment of the adducts with cyclopentadienyl, or indenylsodium (RNa), then results in RESbCI3.Ar (R.C. Sharma and M.K Rastogi, Curr. Sci., 1983, 5_22,862). The non-benzenoid aromatic, lithium 2,5-dimethylstibacyclopentadienide (56) has been prepared as shown in scheme 34. This compound reacts with metals to give analogues (for example 57 and 58), of more familiar cyclopentadienyl complexes.

147 c~ R2Snn2

R

CCH3

R

I PhSbCl Li

I Li

I Ph

(56)

.,~CO) 5

FeCl2~

.CH3

i ~ Sb [ cH~

Mn(CO)3

b H3c

(57)

Fe

H3c

(58)

Scheme34

148 Cyclopentadienyl complexes containing bismuth have also been prepared (scheme 35) (A.J. Asche HI and J.W. Kampf, J. Amer. chem. Soc., 1992, !14, 372). Again, analogous compounds to ferrocene can be prepared using this new heterocycle in combination with Fe(II) salts.

Me3Si

\

SiMe 3

Me

/

i

i \ I

"

i)

i--Ph

SiMe 3

~--

~Li

"

Me" SiMe3

\

Me" SIMe3

\ SiMe 3

i) = BuLi ii) = PhBiI2 Scheme 35

Sterically crowded arylbismuth complexes are prepared by the reaction of BiC13 with 2,4,6-tris(trifluoromethyl)phenyllithium in ethereal solution. The products (1L,)2BiC1and (Rr)3Bi are monomeric in solution and in the solid state and whereas (Rr)2BiC1is relatively stable (Rf)3Bi is not, even in solution under an inert atmosphere (K.H. Whitmire et al., J. organomet. Chem., 1991,402,

55). The aryl groups in pentavalent bismuth organometallic complexes may migrate from bismuth to carbon. The rates of migration vary according to the substituents on the aryl ring, but the mechanism involved appears to be one of reductive elimination, without the generation of discrete ions or radicals (D.H.R. Barton, N.Y. Bhatnagar, J.-P. Finet, and W.B. Motherwell, Tetrahedron, 1986, 42, 3111).

149 7

Group 6 Metals

The organic chemistry of selenium and tellurium has been reviewed in two volumes of'The Chemistry of Functional Groups' (The Chemistry of Organic Selenium and Tellurium Compounds Vols 1 and 2, Ed, S. Patai, John Wiley, 1987, Chichester). A more recent text dealing with the organic chemistry of tellurium was published in 1994 (N. Petragnani, Tellurium in Organic Synthesis, Academic Press, 1994, London). Aromatic tellurides and ditellurides are receiving increasing attention as starting materials for the preparation of organic conductors and imaging systems, they are also useful as synthetic reagents. An efficient synthesis involves reaction of sodium telluride, from metallic tellurium and sodium hydride, with nonactivated aryl iodides (H. Suzuki and T. Nakamura, Synthesis, 1992, 549). Aryltellurides are also readily prepared by the action of tellurium tetrachloride with trivalent organometallic compounds of boron and aluminium. Aryl groups are transferred from the group 13 metal to tellurium (D.P. Rainville and R.A. Zingaro, J. organomet. Chem., 1980, 190, 277). Treatment of the teUuronium salt (59) with an organolithium, followed by addition of an aldehyde results in the formation of secondary alcohols (L.-L. Shi, Z.-L. Zhou, and Y.-Z. Huang, J. chem. Sot., Perkin I, 1990, 2847). The reaction (scheme 36) involves alkylation of (59) to give an unstable tetraorganotellurium, which undergoes nucleophilic addition to the aldehyde to produce the secondary alcohol (60).

150 OH R'Li

RCHO

!

RCHPh + (telluroniumhydroxide)

Ph2(Me)Te+BP1M-

H2o (59)

(60)

R= Ph, p-CIC6H4, p-BrC6H4, p-FC6H4, p-MeC6H4, p-MeOC6H4, 2-naphthyl, 2-pyridyl R' =

Me, Bu, Bu t, Ph Scheme 36

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.Ill B, C,D(Partial), edited by M. Sainsbury

151


Chapter 11 AROMATIC COMPOUNDS OF THE TRANSITION ELEMENTS A. J. PEARSON and P. D. WOODGATE 1. Introduction The preparation, structural characterization and properties of aromatictransition metal organometallics was treated in detail by M. A. Bennett in Volume IIIB, Chapter 11 of this Series, and the literature to around 1974 was covered therein. Much of the research on this area of chemistry during the last two decades has been directed towards applications in organic synthesis, and in materials chemistry, so these two themes will be focused upon in the present chapter. Advances in our understanding of the chemistry of organometallic complexes often occur alongside efforts to apply them in synthesis, which justifies this focus at the present time. Those readers who wish to acquire information on structure, spectroscopic properties, etc., are referred to Bennett's earlier review, as well as the references cited in the present chapter. The main advances that have taken place over the last ten years have been in the chemistry of arene-metal n:-complexes of the chromium, iron and manganese groups. Accordingly, the discussion will focus heavily on these metals. Also, while there have been many noteworthy advances in the use of the Heck reaction, involving the catalytic generation of aryl-palladium ~-complexes, these are considered to be outside the scope of this chapter and are not discussed (for reviews, see: A. D. Ryabov, Synthesis, 1985, 233-252; R. F. Heck, "Palladium Reagents in Organic Synthesis", Academic Press, New York, I985). A transition metal that is rt-complexed to an aromatic ring can mediate a wide variety of transformations, which are summarized diagrammatically in Figure 1. Not all metals allow the exploitation of all of these reactivity phenomena. For example, while the [Mn(CO)3] + group is the most activating with regard to nucleophile attack on an attached arene ligand, it does not effectively promote many of the other reactivity patterns shown in Figure 1, owing in part to its sensitivity toward reagents and reaction

152 conditions that are employed for such processes. The Cr(CO)3 group, on the other hand, being the least activating, shows the full range of chemistry shown in Figure 1. The activating power toward nucleophile additions has been reported to follow the order: Cr(CO)3 < Mo(CO)3 -~94% e.e., the pro-S pendant ester being cleaved preferentially (B. Noezieux et al., Tetrahedron: Asymm., 1992, 3, 375). The rl6-Cr(CO)3 complexes of some o-substituted (Me3Si, Me, OMe) benzyl alcohols are resolved kinetically by lipase-catalyzed asymmetric transesterification with isopropenyl acetate. The S alcohol reacted enantioselectively (K. Nakamura et al., Tetrahedron Lett., 1990, 31, 3603).

190 Direct asymmetric introduction of the Cr(CO)3 moiety onto a 1,2disubstituted arene ring has been achieved (A. Alexakis et al., J. Am. Chem. Soc., 1992, 114, 8288), the aminal derived from (R,R)-l,2-bis(Nmethylamino)cyclohexane being very efficient in directing highly stereoselective transfer of Cr(CO)3 from the rl6-naphthalene complex at room temperature. Inversion of planar chirality was effected by submitting the resulting kinetically formed 2S 1"16 complex to the Mahaffy-Pauson solvent mixture at 140 ~ giving the 2R diastereomer. MeN~4e

(TI6_CloHs)Cr(CO)3 R

MeN_

NMe

Bu20-THF 140 ~

r.t. THF 4 days R = Me, 80%

enantiopure

2R 95%

(95) 01"(00)3 R = Me, 94% d.e.

R = Me, OMe

20 h

CHO

CHO

H3O§

Advantage has been taken of the enhanced susceptibility of an (1"16haloarene)Cr(CO)3 complex to undergo SNAr reactions to provide a catalytic asymmetric synthesis of an optically active molecule. Thus, treatment of (vl6-1,2-dichlorobenzene)Cr(CO)3 (a m e s o complex) with either a vinylmetal or a vinylborane reagent in the presence of an optically active ~:-allylpalladium catalyst [L* = BINAP or (S,R)-RPFA] resulted in a monocoupled product [CH2=CHZnCI, 44%; ratio of mono:di improved from 2:1 to 19:1 using CH2=C(Me)B(OH)2] with moderate enantioselectivity (CH2=CHZnCI, 42% e.e.) (M. Uemura, H. Nishimura, and T. Hayashi, Tetrahedron Lett., 1993, 34, 107). That is, one of the enantiotopic C-CI bonds reacts selectively with a non-racemic Pd(0) species to form a PdCarene bond, leading to the optically-enriched vinylated arene complex.

(OC)3Cr

!

CH2=CH.M

I

PdCI(=-allyl) 2 L* (0C)3Cs

(96)

The increased ability of (~6-arene)Cr(CO)3 complexes to undergo arene deprotonation (see later) has also been utilized. Thus, the asymmetric directed o r t h o metalation of a tartrate-derived aryl aldehyde Cr(CO)3 complex gives, after quenching with an electrophile, (q6-o-disubstituted arene) complexes with a high degree of diastereoselectivity (Y. Kondo, K. R. Green, and J. Ho, J. Org. Chem., 1993, 58, 6182).

191

MeO ~ . . Y O

Me

MeO ~ y O

Me

MeO ~ . Y O

Me

1) BuU (2.4 eq.),-30 ~ 2) e.g. M%SiCI

(OC)3Cr

(97)

I[r162-~,s

+

(OC)3Cr#

(OC~ 93:7 (86%d.e.)

The observed diastereoselectivity, which is thermodynamic in origin, reflects preferential removal of the pro-R ortho arene proton. The C2 symmetric chiral auxiliary can be hydrolyzed to afford a benzaldehyde complex without loss of optical activity. MeO~ / ~ ' O M e 0

0 '

C6H6'65%60% H2S04'~

CHO ~Me

(98)

Me

(oc)3cr~ (OCgCr4

(-) 93%e.e.

9 2 * d.e.

A similar approach has been used by the Aub6-Heppert group (J. Aub6 et al., J. Org. Chem., 1992, 57, 3563) on some chiral acetals derived from reaction of acetophenone with e!ther (S,S)-2,3-bis(methoxymethYnl 6) butanediol or enantiopure N,N,N ,N -tetramethyltartramide, followed by - i coordination using Cr(CO)6. The stereoselectivity, which increased with the Lewis basicity of the distal substituent on the dioxolane ring, again corresponds to preferential abstraction of the pro-R arene proton. XH2C4k .,,C1-12X Me3Si~

XH2C~,/~.CH2X

o

,o

1)tBuLi,-78~i=,. ~ M oe

2) Me3SiCI Cr(CO) 3

-~ (OC)3Cr

,,o

XH2C~)~.~,,CH2X o

,o

, ~ M e

i 89iMe3 (OC)3Cr

(99)

X = OMe, 82%" 78:22 (89% d.e.) X = NMe2, 62%" 94:6 (97% d.e.)

Very recently (B. A. Prise et al., J. Or g. Chem., 1994, 59, 1961) the enantioselective syntheses of some (rlt'-arene)Cr(CO)3complexes via deprotonation mediated by a non-racemic lithium amide base were reported. Hence enantiomerically enriched (rl6-arene)Cr(CO)3 complexes are now available directly via asymmetric deprotonation-electrophile quenching.

192

h•

X

1) P

" N " ~ Ph

Li

2) Me3SiCI

(oc)3cr~

X ..,~ ,,SiM~ O~

(100)

*'~

( )3Cr X = OMe, 83%, 84% e.e X = 2-(1,3-dioxolanyl), 36%, 84% e.e X = CONiPr2, 87%, 48% e.e X = CI, 27%, 51% e.e X = F, 57%, 16" e.e

(b) Structure of (Tl6-Arene) Complexes; Influence of the Cr(CO)3 Group From the highly diastereoselective or enantioselective reactions discussed above, it is obvious that there must be a high degree of specific orientation available to the transition states leading to the stereochemically-enriched substituted complexes. It has long been established that the Cr(CO)3 moiety can assume a preferred conformation in a substituted arene complex (e.g. syn-eclipsed for an electron-donating group, anti- eclipsed for an electronwithdrawing group; or staggered). Recently, X-ray analysis of a variety of complexes has established that the nature of the substituent can influence not only the preferred tripod orientation, but also that the geometry of the arene ring can alter slightly. For example, ~-donor substituents and their ipso-carbon are bent away from the Cr(CO)3 group, whereas r~-acceptor substituents and their ipso-carbon are bent slightly towards the Cr(CO)3 group in the solid state (A. D. Hunter et al., Organometallics, 1992, 11, 1550, and 2251). -

r.

.cr

.dr -

OC"" | ~CO

OC"" J ~CO

OC

~Q----~ i

OC ,,,,,.~r~co oc

Acceplor

OC

,-acceptance

~-~/~cceplor ~.

s S

o c " " *_.dr96.5

SAMP S

(OC)3Cr R

SAMP

93% e.e.). Similarly, sequential transformations of bis(alkoxides) derived from (T16-1,2dioxobe.,,zocyclobutane)Cr(CO)3 have enabled a double anionic oxy-Cope rearrangement to be carried out under mild conditions, affording a cyclopenta[a]indanone and two benzocyclooctadienones (M. Brands et al., J. Chem. Soc., Chem. Commun., 1994, 999; Eq. 141). O O Me ~ i 1' 6 CH2=O(Me)II ~ ~e - 7 8 2) H" , (141) (OC)3Cr 0)30 . Me (OC)3Cr 0 Me 48% 16% The acrylates of non-racemic (q6-1,2-disubstituted arene)Cr(CO)3 complexes with an amine and an hydroxyl group in the two benzylic positions serve as ~:-face selective auxiliaries in Lewis acid catalyzed DielsAlder cycloadditions (M. Uemura, Y. Hayashi, and Y. Hayashi, Tetrahedron: Asymm., 1993, 4, 2291; Eq. 142).

Me

I(.."T "mMe ~ O C O C H (OC)3Cr" - z. | s R

= C H 2

O Lewis ~ acid -78 ~ to rt

F COXc+ endo adducts

L/Xc= 0 ~ 0 . ~1 COXc (OC)3

4 /J (142)

(+ exo)

High endo selectivities (R = Ph, 80:20; R = 1-naphthyl or 2,4,6-C6H3Me3, > 99:1) were obtained, the diastereoselectivity in the endo adducts being

209 dependent largely on the nature of the substituent R at the carbinol stereocenter (R = aryl > alkyl) and on the Lewis acid. The conformational rigidity (essential for good stereocontrol) of an acrylate such as that where R 2,4,6-C6H3Me3 is determined by the strong electron-withdrawing ability of the Cr(CO)3 group. Chelation by the Lewis acid across NMe2 and the acrylate carbonyl imposes an s-transoid conformation on the enoate moiety. Consequently, the alkene undergoes C-C bond formations across the less shielded si face, leading to an R endo adduct. =

0.1 SnCI4,PhCH3 e

98%

(OC)3Cr I~le H i/i

~r(CO)3

Lewis acid-catalyzed hetero-Diels-Alder reactions have been investigated using (imino rlO-arene)Cr(CO)3 complexes with a non-activated alkene tethered to the 2-azadiene system (S. Laschat, R. Noe, and M. Riedel, Organometallics, 1993, 12, 3738). The tethered dienophile can attack only the face of the azadiene exo to that occupied by Cr(CO)3. Diastereoselective intramolecular cycloaddition resulted, the trans selectivity being controlled mainly by the coordinated metal, and to a minor extent by the catalyst, solvent, and substituents (Eq. 143). The cycloaddition of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide to enantiopure Cr(CO)3-complexed styrenes proceeds with complete regioselectivity and with high stereoselectivity, affording a new route to optically active 3,5-disubstituted 4,5-dihydro-4-isoxazolines (C. Baldoli et al., Tetrahedron Lett., 1993, 34, 2529; Eq. 144). The preferred formation of the (1R, 5S) Cr(CO)3 complex requires that the nitrile oxide attacks the double bond from the face opposite that occupied by the rl6-Cr(CO)3, and that the reactive rotamer of the dipolarophile has a t r a n s o i d disposition (to minimize steric interactions). Ar Ms~R~.N

Me 70-2)~- -

(OC)3Cr/

(OC)3Cr/

~ 0

Ar M U N +

(144)

(OC)3Cr/ 98:2; 98% e.e.

Reactions at Side-chain Carbons: Remote Stereocontrol

The stereocontrol evident at the side-chain olefin in the previous example is also exemplified in many cases of diastereoselection during addition of a nucleophile to the carbonyl group of complexed benzaldehydes or acetophenones (some of which have been referred to earlier in this review). Addition of a ketone enolate to a chiral (benzaldehyde)Cr(CO)3 complex

210 occurs with complete stereocontrol (J. Brocard, L. Pelinski, and L. Maciejewski, Tetrahedron, 1990, 46, 6995), as does an ester enolate if the ortho substituent is an OMe group. Cr(CO) 3

7

cr,co,

_ z o (_ c.oc. co o so OMe

(145)

R1 R1 - H, Me, OMe

R1

Stereocontrol by a Cr(CO)3 moiety can also be manifested at sites more remote from the complexed ring. For example, some highly diastereoselective 1,2-additions of nucleophiles to an arylamine-derived imine carbon have been reported (P. B loehm et al., J. Organomet. Chem.,

1991,407, C 19). H

Nu

"~

(146)

Ph

-"-

--" Ph Cr(CO~ Nu = NaBD4, 50%; 93% d.e. Nu = MeLi, 42%; 85% d.e.

Cr(CO)3

Good diastereoselection results from reaction of the boron enolate derived from a chiral non-racemic (acetophenone)Cr(CO)3 complex with an aldehyde (M. Uemura et al., J. Org. Chem., 1992, 57, 5590; Eq. 147). Elimination of water from the aldol product affords an E enone complex; double stereoselection during conjugate addition with an optically active organocopper reagent can occur with high diastereoselectivity, again reflecting remote stereocontrol by the (rl6-arene)Cr(CO)3 unit (M. Uemura, et al., Organometallics, 1992, 11, 3705; Eq 148). Moreover, RCu.BF3 reagents gave mainly one diastereomer, while R2LiCu reagents gave mainly the epimer. O ..~oMM

O e 1) Bu2BOTI,IPr2NEI e 2") EtCHO

(OC)3Cr"

OH

s ~

El +

(OC)3Cr"

0

Me

0

(147)

8O%, 9:1

Me

Me

Me F 3 B . C u ~ O B u t

~s-OMo

R,S,R

Me

2) Ac20

8s%

'q

Me

Me

'"

(148)

3) Me~=

Cr(CO)3

Cr(CO)3

Or(CO)3

>98.5% d.e. O R

~

Me Me

LiCu@OBJ)2 86%

Cr(CO)3

O ~ ~.~s "OPri Cr(CO)3

Me Me OBut 95.5%d.e.

(149)

211 This control can be extended to 1,3,5-diastereoselection in the side-chain by conversion of the aryl ketone into a benzylic methyl substituent using the sequence shown. Rationalization of the stereochemical results for the conjugate additions is based on X-ray and NMR data, which indicate a preferred conformation for both the OMe and the enone group (anti disposed and s-cisoid), and on facially selective delivery of the alkyl group to the carbonyl and exo to Cr(CO)3. For R2CuLi, si face delivery occurs; for RCu.BF3 coordination of the aryl ketone with the Lewis acid could result in an s-transoid and anti-disposed conformer, to which re face delivery occurs. Further demonstrations that an ~6-Cr(CO)3 moiety can have both rateenhancing and steric effects at a site remote from the periphery of the complexed ring are provided by the highly diastereoselective conjugate addition of the carbanion from nitromethane to a 2-arylidene-l-tetralone complex (S. Ganesh, Tetrahedron Lett., 1991, 32, 1084), and by the exclusive endo attack during cyclopropanation of the same substrate (S. Ganesh et al., J. Chem. Soc., Chem. Commun., 1993, 224). O~ ~r(CO)3

+ Me2S=OI_ ~ Ar Bu,N.Br.,HO. 800/*

0

0 H KF, 18_crown_6 ~L .,,,~ /c H2N02 Ar CH3NO2 I1~.-"'~""T "~'~ ~ ~ A' (150) Cr(CO)3 (OC)3Cr 80-90%d.e.

The latter unprecedented example of endo selective nucleophilic addition is due presumably to initial attack of the ylide being rapid (exo) but reversible, and ring closure of the endo adduct being very fast in order to relieve unfavorable steric interactions. The non-complexed tetralone was unreactive under the conditions used. Applications in Catalysis Finally, mention must be made of the applications of (rl6-arene)Cr(CO)3 complexes as catalysts in hydrogenation and isomerization reactions (for a review of this area see M. Sodeoka and M. Shibasaki, Synthesis, 1993, 643). 4.3 (u6-Arene)M(CO)3 Complexes (M = Mo, W) In contrast to the well-developed and increasingly sophisticated use of (q6_ arene)Cr(CO)3 complexes in the synthesis of polyfunctional organic molecules, the analogous complexes of Mo and W have not been exploited. Although many (q6-arene)M(CO)3 complexes of molybdenum and tungsten have been prepared, in the main they incorporate a simple alkylarene. The broad structural and spectroscopic features, and dynamic behavior, which are characteristics of the Cr complexes, are also found in the Mo and W congeners. That is, a tripodal disposition of the carbonyl ligands around the metal is ubiquitous. However, in contrast to (q6-toluene)Cr(CO)3, (TI6-

212 toluene)Mo(CO)3 shows (X-ray) a preferred staggered orientation (D. Braga and F. Greponi, J. Chem. Soc., Dalton Trans., 1990, 3143). In general, (rl6-arene)tricarbonyl complexes of Cr are both thermally and oxidatively less stable than their Mo and W analogs. The chemistry of the Mo and W complexes is dominated by substitution at the metal (and displacement of the arene) by c~-donor ligands. Such reactions, which produce LnM(CO)3, become increasingly exothermic from Cr to Mo to W, in accord with the expected increase in bond strength going from from first to second to third row metals (S. L. Mukherjee et al., Inorg. Chem., 1992, 31, 4885). Consequently, it is not surprising that nucleophilic addition of a carbanion to the coordinated arene, followed by oxidative aromatization, has not been demonstrated for Mo and W. There is a single report of a de protonation - methylation sequence (Nail, DMF; presumably assisted bxy q~ followed by Mel treatment) at a benzylic site in T1UM(CO)3 complexes (M - Cr, Mo, W) derived from 2,4,6-trinitrotoluene (J. U. Ahmed et al., J. Bangladesh Acad. Sci., 1992, 16, 193; Chem. Abstr., 1993, 119, 8972d). Largely, however, (q6-arene)M(CO)3 (M = Mo, W) complexes have been used as catalysts for oligomerization or polymerization of alkenes (J. Astrar, Macromolecules, 1992, 25, 5150; J. S. Hamilton, J. J. Rooney, and D. G. Snowden, Makromol. Chem., 1993, 194, 2907) or alkynes (K. Tamura, M. Toshio, and T. Higashimura, Polym. Bull. (Berlin), 1993, 30, 537). 5. Other Metals

Arene-CoCp* dications have been subjected to electrochemical and EPR studies, and INDO calculations have been performed. During cyclic voltammetry, two reversible one-electron reductions were observed, and their separation is constant for a series of substituted arene complexes. Methyl substitution causes a shift of the reduction potential to more negative values, and MO calculations indicate that this is related to bonding of the ligand (U. Koelle, et al., J. Am. Chem. Soc., 1984, 106, 4152). Cyclic voltammetry studies on [(q6-hexamethylbenzene)RhCp*] 2+ show two oneelectron reductions: dication ~ monocation ~ neutral; NMR experiments suggest that the Rh(I) complex is q4 bound, thereby maintaining a 18 electron count. The corresponding iridium(III) complex undergoes a chemically reversible two-electron reduction to the Ir(I) species. The process appears to consist of two sequential one-electron reductions, but these are very close in potential (W. J. Bowyer and W. E. Geiger, J. Am. Chem. Soc., 1985, 107, 5657). The electrochemical behavior of these complexes has prompted an investigation of dimetallic cyclophane complexes. Both monoand dicobalt complexes can be prepared in good yield (Eq. 151), and have been studied using cyclic voltammetry. Electrochemistry is complicated by solvolysis, but the Cp* complexes are better behaved than the Cp ones. The

213 Co(III) complexes show two reversible reductions in their cyclic voltammograms, while the Co(II) complexes show very complex CV data, and are also paramagnetic (and not amenable to NMR study). (K.-D. Plitzko and V. Boekelheide, Organometallics, 1988, 7, 1573.) 2§

[benzeneCoCP2+][BF4"]2~(~CoCp -~___ 2(BF4")

~

Excess / [Cp'CoCI~,/ TIPF6

F

/

§

C.oCp"

CoCp*

C.oCP*2(BF 4. orPFe. ) NOPF6

,+ 2(PF6 ) CoCp" (70%)

(50%

(65%)

Arene-MCp* complexes (M = Ru, Rh, or Ir) react with hydride nucleophiles, allowing a sequence of reactions that ultimately results in the formation of cyclohexenes (S. L. Grundy and P. M. Maitlis, J. Organomet. Chem. 1984 , 272, 265; S. L. Grundy and P. M. Maitlis, J. Chem. Soc., Chem. Commun., 1982, 379). Benzene-CoCp 2+ also reacts with nucleophiles to give cyclohexadiene complexes, but the range of nucleophiles that can be used, coupled with the instability of the diene complexes, detracts from the synthetic utility of this system (Y-H Lai, W. Tam, and K. P. C. Vollhardt, J. Organomet. Chem., 1981, 216, 97). An rl2-pyridine-tantalum complex has been obtained from the reaction of pyridine with Ta(OSiBut3)3 at low temperature. Similar reaction with benzene affords a ditantalum complex in which the metals are in an unusual 1,2:4,5 anti arrangement (X-ray), contrasting with the rhenium complex shown earlier in Eq. 26. It is not possible to rule out an rl3-allyl structure for both metals because the remaining Ta-C lengths are within bonding distance (2.7]k vs 2.1-2.3A for other Ta-C distances; D. R. Neithamer et al., J. Am. Chem. Soc., 1988, 110, 4421; Eq. 153). Ta(OSiBut3)3 + pyridine

-78 "C -65%

(152) Ta(OSiBut3) 3 T.a(OSiBut3)3

Ta(OSiBut3)3 + benzene

-- ~ 0 ) ~.. - - , , j

I Ta(OSiBut3)3

(153)

214

Rh(H) (PMea) C p" hexane. 60 ~ +

- - Rh(PMe3) C p " "

(154)

Rh(H)(PMe3) C p "

0

-~

--

'-

"-

1155)

It has been postulated that the formation of 1"12 arene complexes provides a low energy path for arene C-H oxidative addition reactions; prior complexation could be followed by an intramolecular insertion process (G. W. Parshall, "Homogeneous Catalysis", John Wiley & Sons, New York, 1980, p. 123; J. Chatt and J. M. Davidson, J. Chem. Soc., 1965, 843). Investigations by Jones and co-workers have provided support for this proposal. Reaction of C5Me5Rh(PMe3)(C7D13)D with p-di-t-butylbenzene a t - 2 0 ~ results in the formation of rl2-(But2C6H4)Rh(CsMes)(PMe3), characterized by NMR spectroscopy (W. D. Jones and F. J. Feher, J. Am. Chem. Soc., 1984, 106, 1650) It was also shown that a o-bound phenylrhodium complex reacts witl~ phenanthrene at 60 ~ to give an 1"12 phenanthrene complex, characterized crystallographically (Eq. 154), and that the same reaction with naphthalene affords an equilibrium mixture of 1"11 and 1"12 complexes (W. D. Jones and L. Dong, J. Am. Chem. Soc., 1989, 111, 8722; Eq. 155). The latter equilibrium is very sensitive to the electronic character of the naphthalene; with.2-methoxynaphthalene only the 3,4-rl complex is observed. Further demonstration of the rll-naphthyl/rl 2naphthalene equilibrium was demonstrated by NMR methods, using magnetization transfer between 31p nuclei, and it was shown conclusively that the 1] 2 complex is an intermediate during C-H activation. (S. T. Belt et al., J. Chem. Soc., Chem. Commun., 1991,266).

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.lll B, C,D(Partial), edited by M. Sainsbury

215


Chapter 12 NUCLEAR SUBSTITUTED BENZENOID HYDROCARBONS WITH MORE THAN ONE NITROGEN ATOM IN THE SUBSTITUENT MALCOLM SAINSBURY Introduction

Nomenclature and organisation In the chemical literature a variety of systems are used to describe the types of compounds included in this chapter. Here the system employed generally follows Chemical Abstracts since this is the primary source from which the data for the review was collected and such terms as arenediazonium, rather than aryldiazonium, are retained. Some sub-divisions of the subject matter have been made in order to provide a more readable account. Thus 1-alkyl-2-aryldiazenes are considered separately from 1,2-diaryldiazenes (azoarenes) and an attempt has been made to split the syntheses of closely related compounds such as arylhydrazines and arylhydrazones. However, to segregate the reactions of these compounds this is not a simple matter and there is much overlap. As a result all relevant sections should be consulted to provide a true reflection of progress in the area.

1. Aryinitrosamines (i) Synthesis

N-Nitroso-N,N-diphenylamine is synthesised from N-chloroformyl-N,N-diphenylamine by heating it with sodium nitrite in acetonitrile. This appears to be a general method applicable to the preparation of the N-nitroso derivatives of other secondary amines from the corresponding chloroformyl compounds (M.Nakajima and J.P.Anselme, Tetrahedron Letters, 1979, 3831). The N-nitrosation of 3,3-dialkyl-l-arylureas (ArNHCONR2) can be

216 accomplished by reacting them with sodium nitrite in formic acid at 0 ~ The products [ArN(NO)CONR z] decompose when heated to 33 ~ in argon, affording a mixture of arylisocyanates, N-nitrosodialkylamines, arylureas, and aryltriazenes (M.Tanno, S.Sueyoshi and S.Kamiya, Chem. Pharm. Bull., 1990, 38, 2644). N-Aryl-N-nitrosoacetamides [ArN(NO)Ac] are formed from the parent N-arylacetamides through reactions with dinitrogen trioxide. These products can be used to arylate alkenes in the presence of palladium bis(dibenzylideneacetone). Cycloheptene, for example, reacts with N-nitroso-N-phenylacetamide to give 3-phenylcycloheptene, but 1-octene is attacked randomly to afford a mixture of four isomeric phenyloctenes. Styrene yields a mixture of stilbene and 1,1-diphenylethene (K.Kikukawa et al., J. Org. Chem., 1985, 50, 299) (for other arylation methods and examples see sections 3, 4, 8 and 9 below). (ii) Reactions When aryl-N-nitrosoamines are heated in a mixture of hydrochloric acid and acetic acid they undergo the Fischer-Hepp rearrangement to give 4-nitrosoarylamines (S.P.Titova, A.K.Arinich and M.V.Goreelik, Zh. Org. Khim., 1986, 22, 1562).

2. Aryldiazene carbonitriles (arylazo cyanides) Aryl 1,4-bis(diazo carbonitriles) (2) form charge-transfer complexes with tetrathiofulvalenes. The former are synthesised in situ from 1,4-aminoarenes by diazotisation in the presence of sodium cyanide [S.Hiinig and T.Metzeuthin, Ger. Often., D.E. 401727 (1991); C.A., 1992, 116, 105876g]. Alternatively, 1,4-bis(N-nitrosoacetylamino)arenes (1) may be treated with trimethylsilyl cyanide (idem, Angew. Internat. Ed. Engl., 1991, 30, 563).

3. Arylazo suiphides and oxidised derivatives (i) Synthesis Arylazo sulphides (ArN=NSR), in which the SR unit is an acetylcysteine residue, are available from arenediazonium chlorides and N-acetylcysteine. The reagents are reacted together in an aqueous medium maintained at pH

217 N=NCN

N(NO)Ac

R

R

Me3SiCN iw--

N(NO)Ac

N=NCN

(1) 7-7.4 (V.I.Nifontov et al., Khim.- Farm., 1990, 24, 63).

(2)

(ii) Reactions Silver ions promote the decomposition of arylazo sulphides (4-RC6H4N=NSPh; R = Ac, Bn, or MeO) in pyridine/hydrogen fluoride to give arylfluorides (4-RC6HnF) (S.A.Haroutounian et al., J. Org. Chem., 1991, 56, 4993). The potassium salt of pentanedione reacts with (E)- or (Z)-arylazo sulphides to yield 3-arylpentanediones in modest yields (C.Dell'Erba et al., Tetrahedron, 1991, 47, 333). Similarly arylazo tbutyl sulphides (1) can be used to C-arylate other potassium enolates in dimethylsulphoxide solution. The mechanisms of the reactions are designated as SRNt dark types (idem, ibid., 1992, 48, 325; 1993, 48, 235).

Ar -- N - N - SC(Me)3 + (1)

,•R O

"K

.tBuSK

-N 2

Ar

R

O

Phenols react in much the same way and, for example, (2-cyanoaryl)azo tbutyl sulphides (2) combine with a range of phenols to afford 2-cyano-2'-hydroxybiphenyls (3) (G.Petrillo et al., Tetrahedron, 1991, 47, 9297). However, when the aryl group of the arylazo sulphide has an o-methyl substituent (see 4) indazoles (5) are produced. In this case 2-(methylidene)hydrazonocyclohexadienes may be reaction intermediates (for related work see C.Dell'Erba et al., Tetrahedron, 1994, 50, 3529).

218

X ~ [ ~

y

N=NsC(Me)3+

X

Y

DMSO. hv

CN

CN Z

(2)

(i) tBuOK

(ii) H +

(3)

X = H. Me. or MeO; Y = H. or Me; Z = H. Me. MeO. Br. NO2,CF3

N

m

N

II

R

N.SC(Me)3 (4)

R

R

H (5)

Arylazoxy aryl sulphones [ArN(O)=NSO2Ar'] plus carbon monoxide and a palladium catalyst, tetrakis(triphenylphosphine)palladium, yield benzoic acids and minor amounts of biaryls and diaryl ketones. If alcohols are added esters form, and with amines amides are produced. It seems that both aryl groups of the sulphones can be transferred and the reactions involve catalytic cycles in which diarylpalladium(II) species may participate (N.Kamigata et al., Sulphur Letters, 1990, 11, 177; J. Chem. Soc., Perkin 1, 1990, 549). In an extension of this work it has been shown that the same reagent combination serves to arylate tx,~-unsaturated esters and nitriles. Thus ethyl cinnamate is obtained from a reaction between ethyl acrylate and phenylazoxy phenyl sulphone (N.Kamigata, M.Satoh and T.Fukushima, Bull. Chem. Soc., Japan, 1990, 63, 2118). In yet another example, Kamigata et al. (Chem. Letters, 1987, 347) have demonstrated that aryl arylazo sulphones (ArN=NSO2Ar') can be used to arylate styrenes in the presence of tetrakis(triphenylphosphine) in benzene solution at 80 ~ Unfortunately these last reactions are unselective and a complex mixture of stilbenes and arylstyrenes is formed, together with aryl 2-(arylazo)-2-(phenyl)ethyl sulphones [PhCH(N=NAr)CH2SO2Ar' ]. In a similar procedure aryl arylazo sulphones can be reacted with norbom-

219 ene to afford norbomane-fused 2,3-dihydrobenzothiophene 1,1,-dioxides (N.Kamigata et al., Phospor. Sulphur Silicon., 1992, 69, 129).

Ph

"N~

N

+

~

Pd(PPh3)4,_

C oS.o

"~

"S02Ph

4. 2-Alkyl-l-aryldiazenes (arylazoalkanes), (arylazoalkenes) and related compounds

2-alkenyl- 1-aryldiazenes

(i) Synthesis 2-Alkyl-l-phenyldiazenes (PhN=NR, R = alkyl) are synthesised through the reactions of alkylamines (RNH2) with nitrosobenzene. Other products include azoxybenzene and a trace of aniline. Previously reactions of this type were considered unlikely. (Y.M.Wu, L.Y.Ho and C.H.Cheng, J. Org. Chem., 1985, 50, 392). Aryldiazenes are also formed by reacting acetanilides with nitrobenzenes in xylene with powdered sodium hydroxide, potassium carbonate and a phase transfer catalyst at 130 ~ Nitrosobenzenes, rather than nitrobenzenes, are assumed to be the reactive species leading to 1-acyl-l-arylhydrazine 2-oxides as intermediates (N.R.Ayyanger, S.N.Naik and K.V.Srinivasan, Tetrahedron Letters, 1989, 30, 7253). 0

O" ~Me

Ar -" N "

H

/~Me

B ~ -BH+

N \

O~ /

Ar "

N - N .. R Ar

N -N /

OP

~1~ Ar

MeCO2"-

RNO

t

220 Alkyl radicals couple with arenediazonium salts in the presence of metal ions (Ti3§ or Fe 2+) to give 2-alkyl-l-aryldiazenes. The reactions may proceed as follows, but appear to be highly sensitive to polar effects (A.Gitterio and F.Minisci, J. Org. Chem., 1982, 47, 1759; 1992, 57, 3929): ArN2 + + Ti(IIl) --* Ar" + N 2 + Ti(IV) At" + RI --> Arl + R" R ~+ N-N+Ar ~ R_N=N+*_Ar R-N=N+'-Ar + Ti(III) --~ R-N=N-Ar + Ti(IV) (R = primary, secondary, or tertiary alkyl, alkenyl, benzyl etc., Ar = 4-C1C6H4).

Phenylhydrazones of alkanals (PhNHN=CHCHR2) are converted into 2-alkenyl-l-phenyldiazenes (PhN=NCH=CR2) either by reaction with iodine and pyridine, followed by elimination of pyridinium iodide, or from (Na-tosyl)phenylhydrazones [PhN(tosyl)N=CHCHR 2] by treatment with potassium tbutoxide and elimination of toluenesulphinic acid. Both routes give configurationally mixed products, although the E,E-isomers are thermodynamically most stable (J.G.Schantl and T.Hebeisen, Tetrahedron, 1990, 46, 395). Acetone 4-chlorophenylhydrazone (4-C1-C6H4NHN=CMe2) reacts with bromine/acetamide to give 2-(2-bromoprop-2-yl)-l-(4-chlorophenyl)diazene [4-C1-C6H4N=NC(Br)Me2], which is unstable, and 2,2-bis[1-(4-chlorophenyl)azo]propane [(4-C1-C6H4N=N)2CMe2]. The fin'st product reacts with a wide range of nucleophiles which displace the bromine atom as bromide ion giving the corresponding derivatives [4-C1-C6H4N=NC(R)Me2; R - CN, 2-phthalimido, 4-morpholino, AcO, EtO, HS etc.] (J.G.Schantl and H.Gstach, Monatsh. Chem., 1985, 116, 1329). Catechol (1,2-hydroxybenzene) reacts with benzene diazonium chloride to give a mixture of 4- and 5-(phenylazo)-2,4-cyclohexadien-l-ones, the latter predominating (A.A.Matnishyan and A.M.Arzumanyan, Arm. Khim. Zhur., 1991, 44, 469; CA., 1992, 117, 191403a). (ii) Reactions Alcohols (ROH) undergo 1,4-additions to the diazadiene system of 1-phenyl-2-(1,2-diphenylethenyl)diazene in the presence of copper(H) and iron(II) cations. The products, phenylhydrazones of ct-alkoxybenzyl phenyl ketones, are normally formed in 90-95% yield (O.Attanasi, P.Battistoni and G.Fava, J. Org. Chem., 1981, 46, 447).

221

Ph '~1

Ph

ROH

H Ph

Cu2+/Fe2+

~N=-~k Ph

1H-4,5-Dihydro-l,3,4-benzotriazepines are formed when 1-aryl-2-iminodiazenes are heated. Probably the reactions proceed through initial isomerisation of the starting materials to give ortho-quinonoid tautomers, followed by intramolecular nucleophilic attack which regenerates the aromaticity of the benzenoid ring in the products (R.Fusca, A.Marchesini and F.Sannicolb, J. Het. Chem., 1986, 23, 1795). R1 A

N--~NAr

R~ ~1 R

"H

R

1

/N N~H R Ar

y

R~'e,-~ " ~

N,,Ar

R

Essentially the same type of process is implicated in the cyclisation of 1-(2-methylphenyl)diazenes (1; R= CONH 2, CO2Et, or COPh) to the corresponding indazoles in the presence of DBCO (idem, ibid., 1987, 24, 773).

--R ~

N ~ / \H

--R

(1) 1-Arylazo-2,2-dichloroethenes react with amines by addition/elimination

222 to afford the corresponding 1-arylazo-2,2-bis(diamino)ethenes. When the starting compounds are treated with benzene-1,2-dithiol benzo-1,3-dithioles (2) are produced (T.L.Gilchrist, J.A.Stevens and B.Parton, J. Chem. Soc., Perkin Trans.1, 1985, 1737). CI

H

R2NH

CI

N=NAr

R2'"~_~' ~" u' /

SH

R2N

\

N=NAr

s

H

S

N=NAr

(2) Treatment of 6-amino-5-(1-aryldiazen-2-yl)-l,3-dimethyluracils with ethyl propiolate gives Michael type adducts (3), which on treatment with a mixture of hydrochloric and acetic acids undergo acid catalysed rearrangements and cyclisations to form 8-(N-arylaminomethyl)theophyllines (4) (F.Yoneda and R.Koga, J. Het. Chem., 1982, 19, 813). 0

0

J.L O

N~ I

I

Me

(,3)

H

ii

H

CO2Et

_

I~ CH2NHAr

O

N I

Me

(4)

Other similar cyclisations are noted in reactions between 5-phenylazo-6-arylidene)hydrazino-l,3-dimethyluracils (5) and dimethylformamide dimethylacetal which afford pyrimido-l,2,4-triazines (6)

223 (S.Nishigaki et al., J. Het. Chem., 1982, 19, 769).

Me.Ij.EL . O

O

Me

I

Me

N

~

R

oL .o'

N"

I

,, L

I

H

Me

(6)

(5)

5. Aryldiazene oxides Synthesis

1-Aryl-2-bromodiazene 1-oxides [ArN(O)=NBr] are prepared by reacting nitrosobromides with nitrogen tribromide, generated in situ from ammonia and N-bromosuccinimide (A.M.Churakov et al., Ivz. Akad. Nauk. SSSR., Ser. Khim., 1990, 953). They react with terminal alkenes (CH2=CHR) to form 1-aryl-2-bromoethyldiazene 1-oxides [e.g. ArN(O)=NCH2CH(Br)R] (A.M.Churakov et al., Mendeleev. Commun., 1991, 141). 1,2,3,4-Tetrazine-l,3-oxides (2) are formed when 1-(2-aminophenyl)-2-tbutyldiazene 1-oxides (1) are treated with nitrosofluoroborate in acetonitrile, and the products are oxidised by exposure to 3-chloroperbenzoic acid (A.M.Churakov et al., lvz. Akad. Nauk. SSSR., Ser. Khim., 1990, 718; for similar reactions see A.M.Churakov, S.L.Ioffe, and V.A.Tarakovskii, Mendeleev. Commun., 1991, 101).

OI

[~

N+"N- C(Me)3 NH2 (i)

0I

~N+" N I+ ~ [ ~ J ~ N~.N-o -

(2)

224 6. Azoarenes (1,2-diaryldiazenes) (i) Synthesis Azoarenes are frequently synthesised by coupling reactions between electron-rich arenes and arenediazonium salts (also see section 8). In addition, the trialkylstannyl unit is an excellent leaving group and this can be exploited in formation of azoarenes. Thus various trialkylstannylarenes (R3SnC6H4R'; R = Me, or Bu) when treated with nitrobenzenediazonium tetrafluoroborates [2,4-X(NO2)C6H3N2BF4] !n acetoniwile solution at 20 ~ afford the corresponding azobenzenes [R C6H4N=NC6H3(NO2)X-4,2 ). Yields can exceed 80% (W.P.Neumann and C.Wicenec, Chem. Ber., 1991, 124, 2297). The oxidative coupling of aryliminodimagnesium bromides to afford symmetrical azobenzenes is promoted by the addition of copper(II) chloride, whereas condensations with nitrobenzenes to produce azoxybenzenes are improved if nickel(II), or cadmium(H) chlorides are added to the reaction mixtures (M.Okubo and H.Shiku, Bull. Chem. Soc., Japan, 1991, 64, 196; for related work see M.Okubo et al., ibid., 1983, 56, 199). Symmetrical azoarenes are also obtained by the cathodic reduction of aromatic nitro compounds in an undivided cell. The reductions are best carded out in alkaline methanol at constant current. In this way 2,2'-dimethylazobenzene can be prepared from 2-methylnitrobenzene in 95% yield (H.Tanaka, Y.Murami, and S.Torii, Chem. Express, 1989, 4, 531). Arylamines are oxidised by chromyl chloride (C.rO2C12) in carbon tetrachloride, or in chloroform, solution to yield Etard adducts. The products upon hydrolysis give azobenzenes, plus 1,4-benzoquinones, for example, 4-chloroaniline affords 4,4'-dichloroazobenzene, the iminobenzoquinone (7) and the imines (8) and (9) (C.Naillaiah and J.A.Strickson, Tetrahedron, 1986, 42, 4083). Bipyridylsilver permanganate is an effective oxidant for the conversion of 3-nitroaniline into 3,3'-dinitroazobenzene (H.Firouzabadi, B.Vessal and M.Naderi, Tetrahedron Letters, 1982, 23, 1847). Alternatively, potassium permanganate in benzene-water containg the phase-transfer agent tetrabutylammonium bromide is recommended (M.Heyayatullah and A.Roger, Bull. Soc. Chim., Belg., 1993, 102, 59).

225

O

"CL CI

O

CI 84 (8)

(7) CIl.~

N/ H

(9) Arenediazonium chlorides (ArN2C1) couple with 1,3-diaminobenzene at the ortho positions to afford tris(arylazo)diamines (10), whereas with diethylphenylamine para-coupling occurs to give azobenzenes (11) (Z.V.Stepanova, P.I.Grebneva and G.G.Skvortsova, Zh. Org. Khim., 1982,

18, 1711). The oxidation of anilines, using either superoxide ion in the presence of 18-crown-6 ether in dry benzene, or molecular oxygen in the presence of hydroxide ion, gives a mixture of the corresponding nitrosobenzene, nitrobenzene, and azobenzene in a constant molar ratio of (19:19:13). Aniline and hydrazobenzene both afford azobenzene in almost quantitative yield under these conditions: a result which suggests that hydrazobenzene, formed by the coupling of aniline, may be the precursor of azobenzene (E.B.-Hergovich, G.Speier and E.Winkelmann, Tetrahedron Letters, 1979, 3541). The major products from the irradiation of aniline in dichloromethane, chloroform, or carbon tetrachloride, with ultraviolet light are" azobenzene, hydrazobenzene, phenylisocyanide, 2- and 4-(phenylamino)anilines, N-(methylidene)aniline (PhN=CH2) and di(N-phenylamino)methylimine [(PhNH)2C=NH] (W.Bosyczyk and T.Latowski, Z. Naturforsch. B, Chem. Sci., 1989, 44, 1585; 1589).

226

ArN=N

NH2

NH2

ArN2CI \

N=NAr ArN=N

NH2

NH2

(~o)

~ ~ INEt2

i NEt2

ArN2CI v

ArN=N

(11) (Ar = 4-CH2=CHOC6H4)

N-[(Diphenylphosphinyl)oxy]arylamines [ArNHOP(O)Ph2] combine with N-methylaniline to give hydrazo compounds [ArNHN(Me)Ph], however, in the preence of a secondary aliphatic amine, such as dipropylamine, symmetrical azoaryls (ArN=NAr) are formed (G.Boche, C.Meier and W.Kleemiss, Tetrahedron Letters, 1988, 29, 1777). In related work hydroxamic acid derivatives (4-RC6H4N(OAc)OSOEMe) combine with butylamine to give azepines (12) as well as azoarenes (13) (F.Bosold, G.Boche and W.Kleemiss, ibid., p.1781). It is argued that the initial step in these last reactions is the formation of a singlet nitrene. The nitrene may then either undergo inter-systems crossing to afford a triplet which then gives the azoarene, or combine directly with butylamine to yield the azepine.

, ~ N

NHBu

(13)

(12) (R = NO2, COMe, CO2Me,CN)

227 The dianion of 1,4-dinitrocyclooctatetrene reacts with arenediazonium tetrafluoroborates to displace one of the nitro groups and to form 1-arylazo-4-nitrooctatetraenes (Z.V.Todres and G.Ts.Ovsepyan, Ivz. Akad. Nauk. SSSR., Ser. Khim., 1985, 2830).

O2N~

NO2

ArN2BF4.._._ THF/-10 to-50~

O2N " ~

N=NAr

In reactions with the dianion of 1,2-dinitrobenzene similar results are observed and 1-aryl-2-(2-nitrophenyl)diazenes are produced (Z.V.Todres, G.Ts.Ovsepyan and E.A.Ionina, Tetrahedron, 1988, 44, 5199). Perchloroazobenzene and 2,2',3,3',5,5",6,6'-octachloroazobenzene (16) have been synthesised from 1,4-diamino-2,3,5,6-tetrachlorobenzene. The common precursor is the 1,4-iminoquinone salt (14), formed from the diamine by treatment with chlorine and iodine in carbon tetrachloride. When this salt is treated with methanol 4,4-diamino-2,2',3,3',5,5',6,6'-octachloroazobenzene (15) is produced, this compound can be deaminated to give the octachloro derivative (17) by diazotisation and treatment with methanol, or be subjected to a Sandmeyer chlorodeamination reaction to afford the perchloro derivative (16) (M.Ballesteros et al., Tetrahedron Letters, 1980, 21, 4119). Solid benzenediazonium sulphate suspended in hexane reacts with sodium diethyl malonate to give the phenylhydrazone (18) of diethyl 2-formylmalonate, and the diazenes (19), (20), and (21) (M.U.Ahmad et al., J. Bangladesh Chem. Soc., 1990, 2, 33). CI

CI

H2N

Cl NH2

CI

CI

~

CI

HN

NH2 CI

CI (14)

CI21-

228 CI

CI

N I~"

MeOH H2N CI

NH2

CI

(15)

C'

CI

C'

_ ~

C'

N 4'

c~

C'__

Cl CI

CI

Cl

Cl

CI

CI

N 4'

CI

CI

CI

CI

(16)

(17)

[2.2] (4,4')Azobenzenophane 4,4'-dinitrobibenzyl. The two deformed from planarity both (N.Tamooki et al., Tetrahedron,

is formed by the reduction of azobenzene units of this compound are in the crystalline state and in solution 1990, 46, 5931).

NO2 I

LAH

N--N

=

N--N

NO2

CI

229 R i

H I

N_N

(CO2Et) 2

(18)

(19)

R

N" PhN=N

PhN=N

N -R (21)

(20) R = Biphenyl

(ii) Reactions (a) Reduction \ cyclisation Azoarenes are reduced to hydrazobenzenes, in good yield by reacting them with tributyltin hydride in boiling benzene. However, if the azobenzene is substituted in the ortho-position then cyclisation to a heterocycle may occur as a competitive process. For example, 1-(2-acylphenyl)-2-aryldiazenes (1) form indazoles (2), and 2,2'-dicyanoazobenzene (3) affords l l-aminoisoquinolino[4,3-b]indazole (4). These reactions do not normally require the presence of an initiator, but the addition of AIBN is necessary to effect the cyclisation of 2'-iodo-2-[Na-(4-methylphenylazo)]biphenyl (5) to N-(4-methylphenylamino)carbazole (6). This product is accompanied by 2'-iodo-2-[Np-(4-methylphenyl)hydrazino]biphenyl (7) (A.Albertini et al., J.

230

Org. Chem., 1992, 57, 607). R

[~

Bu4Sn

COR

N - Ar

v

N=NAr

(1)

(2)

NH 2 N.... CN

N- N

Bu4Sn

CN

(4)

(3)

Bu4Sn/AIBN I

Ar = 4-CH3C6H4

(6)

(5)

C

NHAr

NHNHAr

(7) (1,2,3-Benzotriazol-2-yl)phenols can be formed through the cyclisation of 2-[(2-nitrophenyl)azo]phenols with thiourea-S,S-dioxide (S.Tanimoto and T.Kamano, Synthesis, 1986, 647).

231

R HO

R

NH2CS(O)2NH2

II

N

N'

R [ ~ NO2

R

2-Arylcinnolines are available by the cyclodehydration of 2-(arylazo)phenylacetic acids by the action of oxalyl chloride (M.G.Hutchings and D.D.Devonald, Tetrahedron Letters, 1989, 30, 3715).

"•••

CO2H CIOCCOCIR , ~ ~ ~ ~ N'Ar

NO N" "Ar

(b) Reactions with carbenes Azoarenes react with carbenes to form 2-arylindazoles, but it is uncertain whether these reactions proceed through ylide intermediates, or by concerted cycloadditions (K.Krageloh, G.H.Anderson and P.J.Stang, J. Amer. Chem. Soc., 1984, 106, 6015). R

.~N

II

In view of this it is

:CXY

.~

N

R

surprising that azobenzene reacts with

232 dichlorocarbene, generated from chloroform by treatment with potassium hydroxide under phase-transfer conditions, to give N-phenyltetrachloroaziridine (8) plus smaller amounts of 2-chloro-l-phenylbenzimidazole (9) and 1-phenylbenzimidazol-2(3H)-one (10) (T.Fujiu, K.Izumi and S.Sekiguchi, Bull. Chem. Soc., Japan, 1985, 58, 1055). Ph i

Ph

o o, CI

Ph i

o,

CI (8)

(9)

(10)

H

(c) Isomerisation The thermal equilibrium of cis and trans-azobenzenes in solution normally favours the trans forms. Access to the cis isomers can be effected by photoexcitation, but in the dark such isomers undergo thermal relaxation back to the trans forms. However, for certain azobenzenes beating a 4-(N,N-dimethylamino) substituent the relaxation process is strongly inhibited by the presence of hydroxide anion (A.Sanchez and R.H.Rossi, J. Org. Chem., 1993, 54, 2094).

7. Azoxyarenes (1,2-diaryldiazene N-oxides) (i) Synthesis Nitrobenzenes can be reduced by sodium hydride and cadmium(II) chloride to afford azoxyarenes, whereas if the reductant is zinc(H) chloride the products are azoarenes (G.Feghouli et al., J. Chem. Soc., Perkin Trans.1, 1989, 2069). An alternative method is to use sodium borohydride in alkaline ethanol containing a catalytic amount of diphenyl ditelluride. In this case the active reductant is sodium benzenetellurolate and azoxyarenes are formed selectively in good to high yields (K.Ohe et al., J. Chem. Soc., Chem. Commun., 1988, 591). Electrochemical reduction of nitroarenes in acetonitrile at a mercury pool cathode can also be used to prepare azoxyarenes. Here the reactions are promoted if carbon dioxide is present and a proton source is unnecessary (T.Ohba et al., J. Chem. Soc., Chem. Commun., 1994, 263). Arylamines can be oxidised to azoxyarenes by a variety of oxidants,

233 however, most methods are not catalytic. An exception employs dilute aqueous hydrogen peroxide in boiling acetone over a TS-1 zeolite (H.R.Sonawane et al., J. Chem. Soc., Chem. Commun., 1994, 1215). Oxidation of 2,6-dimethylaniline with hydrogen peroxide/sodium tungstate gives 2,2',6,6'-tetramethylazobenzene dioxide (1). Reduction of this product with hexachlorodisilane in chloroform gives 2,2',6,6'-tetramethylazobenzene (2) (J.C.Stowell and C.M.Lau, J. Org. Chem., 1986, 51, 1614).

+OI1+

Si2CI 6

lb...

/

0-" N ~ ~ }

CHCI3

(1)

(2)

Certain 4,4'-dialkylazoxybenzenes, such as (3), show liquid crystalline properties. Compound (3) is synthesised from 4-pentylaniline as shown in scheme 1 [J.P., 60 32 757 (1985); C.A., 1985, 103, 71042w]"

CH3(CH2)4~

4-NH2C6H4Pr

EtMgBr

NH2

CH3(CH2)4

CH3(CH2)4

/

N(MgBr)2

O-

N+

v

Pr

02

(3) Scheme 1

The thermolysis of zwitterionic 2-nitro-N-(pyrid-l-yl)anilines (4) gives 1,2-bis[(Z)-(2-nitrophenyl)-O,N,N-azoxy]benzenes (5), not tris(N-2-nitrophenyl)triaziridines as previously thought (H.Hilpert, L.Hoesch and

234 A.S.Dreiding, Helv. Chim. Acta, 1981, 64, 2095). ~

O2N~

R

\ +

A O2N

i,~'~ N,,-N

(R = H,Me,Cl)

(4)

O2N ~_~.~jN.R (5)

(ii) Reactions (a) Reduction Azobenzene and azoxybenzene can be reduced by dihydrolipoamide in the presence of Fe 2§ to give hydrazobenzene, without the co-production of aniline (M.Kijima et al., J. Org. Chem., 1983, 48, 2407). Anilines are formed from azoxybenzenes if the reductants are sodium alkylthiolates (M.T.Dario et al., Tetrahedron Letters, 1994, 35, 301). This is unusual, since the reaction conditions (heating in propanol) are non-acidic, suggesting that the initial step is the formation of nitrosoarenes and sulphenamides. The former are recycled, but the latter are reduced to anilines"

RSNa Ar .N;N(O)Ar T

RS-

Ar.NO + Ar.NHSR PrOH

~ [H]

Ar.NH2

A

2,2'-Dimethylazoxybenzene undergoes nitration to afford 2,2'-dimethyl-4'-nitroazoxybenzene, which can be reduced with stannous chloride to give 2-methylaniline and 2-methyl-l,4-diaminobenzene (6). In addition, the unexpected product 4,4'-diamino-3,3'-dimethylbiphenyl (7) is obtained

235 (J.Urbanski and I.Wolak, Polish J. Chem., 1984, 58, 1035). Me

H2N ~

Me

NH2 (6)

Me

H2N ~

NH2 (7)

(b) Rearrangements The mechanism of the Wallach rearrangement has been reviewed (G.G.Furin, Usp. Khim., 1987, 56, 911). Generally the acid promoted rearrangements of 4,4'-disubstituted azoxybenzenes give 2-hydroxyarylazo compounds, however, when 4,4'-dimethylazoxybenzene is heated with aluminium trichloride in nitromethane for four hours at 100 ~ it yields 3-chloro-4,4'-dimethylazobenzene (14%), 4-chloromethyl-4'-methylazobenzene (21%), and 4,4'-dimethylazobenzene (30%). 4-Methylazoxybenzene (a mixture of N~(O) and N(O)~ isomers) affords 3-chloro-4-methylazobenzene, 4-chloromethylazobenzene, 4-chloro-4'-methylazobenzene, and 4-methylazobenzene. Similar chemistry is noted for other azoxyarenes (I.Shimao, Nippon Kaguku Kaishi, 1984, 2009; 1985, 1556; see also J.Yamamoto et al., ibid., 1987, 851). Azoxybenzenes give a 1:1 addition complexes when treated with antimony pentachloride in carbon tetrachloride. These complexes also undergo ortho-Wallach rearrangements when heated in an inert solvent to form o-hydroxyazobenzenes (J.Yamamoto, Y.Nishigaki and M.Umezu, Tetrahedron, 1980, 36, 3177). (c) Uses in heterocyclic synthesis The cyclisation reactions of N~l,(O)-o-(propanoyl)azoxybenzene (1) has been studied. In the presence of sodium methoxide and methanol a mixture of 1,2,3,4-tetrahydro-3-methoxy-3-methyl-2-phenylbenzopyridazin-4-one (2), bis(2-methylindolin-3(1H)-on-2-yl) (3), and azoxybenzene are formed (S.S.Mochalov, A.N.Fedotov and Yu.S.Shabarov, Khim. Geterot. Soedin., 1983, 688; 743).

236 O COEt

NaOMe/MeOH ~1'~...i'~ N .. N -. ph

II

I

H

o--N+ph

(2)

(1) O

~ _ ~ M

e

H N

(3)

8. Arenediazonium salts (i) Synthesis 1-Aryl-2-(piperid-l-yl)diazenes can be used as a source of diazonium salts. On treatment with methanesulphonic acid in organic solvents these compounds dissociate into the corresponding arenediazonium methanesulphonates and piperidine (T.J.Tewson and M.J.Welch, J. Chem. Soc., Chem. Commum., 1979, 1149). Similarly, 1-aryl-3-(tetrazol-5-yl)triazenes cleave when reacted with trifluoroacetic acid giving arenediazonium salts and 5-aminotetrazole. As such the parent compounds act as bench stable arenediazonium synthons and, for example, may be used to couple with phenols affording azo compounds. Alternatively they may be reacted with ammonium halides and trifluoroacetic acid to give halogenoarenes. It seems that radicals are not involved in these reactions (R.N.Butler and P.D.O'Shea, J. Chem. Soc., Perkin Trans. 1, 1987, 1039). Another convenient source of the benzenediazonium cation is from azobenzene-t~-hydroperoxide (T.Tezuka, S.Ando and T.Wada, Chem. Letters, 1986, 1667). Nitrodiazophenols (3) are prepared by the nitration of suitable anilines and the rearrangement of the product N,C-nitroamines (1). The rearrangement reactions are considered to involve 1,2,3-benzoxadiazoles (2) as intermediates (R.L.Atkins and W.S.Wilson, J. Org. Chem., 1986, 51,

237 2572).

O

H

_

H tO "N +. N

I

"N"

N+

=o

Ph

N

Ph ~

I

II

N(Ph)2

,,,~O

>=o

S N

" N(Ph)2 (6)

(5)

formed when 2-benzyl-4-methoxy-l,2,5-thiadiazol-3-one 1-oxide (1) is reacted with phenylhydrazine (S.Karady et al., Tetrahedron Letters, 1985, 26, 6155).

MeO

H ~

S -N (1)

CONHCH2Ph

S-N ~CH2Ph

00

Ph ~N" ~ N/ ~

O'

(2)

7. Pyridazines Diethyl 2-c yano-3-methylpent-2-en- 1,5-dioate ( 1) couples with arenediazonium chlorides to yield intermediate hydrazones (2) which cyclise to 2-aryl-6-ethoxycarbonyl-4-cyano-5-methylpyridazin-3-(1H)-ones (3) (N.S.Ibrahim et al., Heterocycles, 1986, 24, 1219). 3-(N-Arylhydrazono)pentan-2,4-diones (4) when reacted with acetyl chloride, or acetic anhydride, in the presence of either concentrated sulphuric acid, or p-toluenesulphonic acid, form the corresponding N-acetyl derivatives (5), together with 3-acetyl-l-aryl-6-methyl-1H-pyridazin-4-ones (6) (H.V.Patel et al., Indian J. Chem. Sect. B., 1991, 30B, 932). 2-Aryl-2,3,5,6-tetrahydro-3,6-diphenylpyranopyridazin-8-ones (8) are obtained in two steps from the 2-(N-arylhydrazones) (7) of pentane-2,3,4-triones. First the benzylidene derivatives are formed through reactions with benzaldehyde in the presence of sodium hydroxide, and these products are then cyclised by heating them with acetic acid (H.V.Patel and P.S.Fernandes, Indian J. Chem. Soc. Sect. B., 1989, 28B, 167). Pentane-2,3,4-trione 3-(N-arylhydrazones) are deprotonated by sodium hydride and then N-acylated by chloroacetyl chloride to afford the

288 derivatives (9). In the presence of excess sodium hydride these cyclise to 3-acetyl- 1-aryl-5-chloro-4,5-dihydro-4-methylpyridazin-(5(1H)-ones (10). The same products are also formed if the starting hydrazones are reacted with chloroacetyl chloride in the presence of sulphuric acid, or 4-toluenesulphonic acid (H.V.Patel, Indian J. Chem. Sect. B, 1992, 31B, 273). 2,3,4,4a-Tetrahydro-2-phenylcyclopentano(c)pyridazine (11) is formed when the phenylhydrazone of 2-(2-chloroethyl)cyclopentanone is heated (B.Robinson and D.G.Hawkins, Chem. Ind., 1985, 697)

O NCi ' ~ CO2Et Me

ArN2CI,.~ ---9

CH2CO2Et

NC~ I I

OEt N"H" Ar N

Me~

O

(1) NC

N"

Ar

CO2Et (2)

v

Me

C02Et

(3) NNHAr O

O (4)

0

O Ac20 Aci ~ M e N Ac "N" H2SO4 I Ar (5)

A N~N~C

Me I

Ar (6)

289

MemO

Ph

PhCHO

Ar"~ "N / " ~ M 0

O

Ph

NaOH/H20 H

O

(7) HOAc

A

Ph.

~

O

Ar N ~ ~N~/~~,~

.,,Ph "*

O

(8)

~

H I

N"

N

"Ar

NaH

~176 Me

CICH2COCI

Me

N

~176 N"

Me

"Ar

Me (9)

Ar i

Nail

O,.

N,, N

Me

Me

(10)

Benzopyranopyridazinones (13) are synthesised through the cyclisation of the phenylhydrazones (12) of O-substituted 2-hydroxybenzaldehydes (K.Hajela and R.S.Kapil, Indian J. Chem., Sect. B., 1990, 29B, 683).

290

r

H,. Ph"

Ph" (11) OMe

O

' / " t ' ~ ~ " ~ ' ~ - - N ~ N ~ Ph

"N

"H

0

I (13) Ph

(12)

3-Acetyl-3,4-dihydro-4-hydroxycinnoline (15) is synthesised from ethyl 2-(N-phenylhydrazono)but-3-onoate (14) by treatment with aluminium trichloride (M.S.K.Youssef et al., Commun. Czech. Chem. Soc., 1991, 56, 1768).

~

EtO2C /~.COMe AICI3.~"~

OH

COMe

NSN I

H

8. Benzoxazines Thermolysis of ethyl 2-{N-[2-(allyloxy)phenyl]hydrazono}-2-azido acetate (1) in boiling benzene gives 1-ethoxycarbonyl-3,4,4a,5-tetrahydro-pyrimidino[4,5-c]-l,4-benzoxazine (2). The reaction involves initial formation of a nitrene intermediate, followed by intramolecular 1,4-cycloaddition (L.Geranti and G.Zecchi, Tetrahedron Letters, 1980, 21, 559).

291

CO2Et

CO2Et

N~N3

H i "N

N~N " I

-N 2 v

(2)

(i) 9. Triazoles and benzotriazoles

Oxidative cyclisation of the bis(N-arylhydrazones) of cyclohexan-l,2-dione leads to 2,4-diaryl-4,5,6,7-tetrahydrobenzotriazoles (R.N.Butler and J.P.James, J. Chem. Soc., Chem. Commun., 1983, 627).

~

NNHAr Pb(OAc)4 ~NN .,._ NNHAr

DCM

- Ar

N Ar

Related chemistry shows that tris(N-arylhydrazones) of cyclohexane-l,2,3-triones are also oxidised by lead tetraacetate to give fused cyclohexanotriazoles, but the products now retain one hydrazono unit (S.Lefpopoulou, S.Stephanidou and N.E.Alexandrou, J. Chem. Res. Synop., 1985, 82). 5-Dialkylamino-2-aryl-4-cyano-l,2,3-triazoles are obtained by the oxidative cyclisation of the amidines (1). The starting materials are themselves formed by treating the arylhydrazones of malononitrile with secondary amines. The related chloroimides (2) are converted into 4-amino-5-(N-arylhydrazono)- 1,2,5,6-tetrahydro-3-(pyridin- 1-yl)pyrid-2,6-dione chlorides by treatment with pyridine and Thorpe cyclisation (H.Sch~ifer et al., Monatsh. Chem., 1991, 122, 195).

292

NNHAr

N

Ar

NNHAr DCM/25~

NNHAr

NNHAr

(R = H, or Me;Ar = C6H4-CI-4,or CsH4-Me-4) ArN,,N ~CN R2NH H"

Ar N HN,,H~N (1)

ArNH,.N ~ CN~ CI O

C

CuSO 4pyridinAr.. ell~N,,CN~~ NIN

NC

N I H

NR2

pyridine ArNH"N ~

O

NR2

"H2

O

O CII

H

(2) Diazomethane adds to the N-acetylphenylhydrazone (3) to give 1- [(N-acetyl-N-phenyl)amino]-5,5-di(methoxycarbonyl)- 1,2,3-triazol-2-ine (4) in 92% yield. Treatment of this compound with trifluoroacetic acid generates 1- [(N-acetyl-N-phenyl)amino]-2,2-di(methoxycarbonyl)aziridine (5) (A.V.Prosyanik et al., Zh. Org. Khim., 1985, 21, 911).

Ac C.O2Me Ac CO2Me CH2N2 I N,,,~ CO2Me --------tI~ Ph ,, N~ Ph" N.. N-N (3)

(4)

CO2Me ~ /

N-N d" CO2Me

Ph

(5)

293 1,2,4-Triazoles are synthesised from N-benzyloxycarbonyl a-aminoacids by first esterification with methyl choroformate and triethylamine, and then reaction of the esters (6) with methyl 2-(N-phenylhydrazono)-2-[(triphenylphosphoranylidene)amino]acetate (7). Deprotection of the products (8) is achieved through successive hydrogenolysis and treatment with hydrogen chloride gas (L.Bruch6, L.Garanti and G.Zecchi, Synthesis, 1989, 399).

MeO2C /~ +

R MeO2C

NHZ

N

N - PPh3

-----t~

~N

' "Ph H

(6) MeO2C

(7)

..z N-,N~ =

R

Ph (8) (Z = benzyloxycarbonyl) 1,3-Diphenyl-5-vinyl-l,2,4-triazole (9) is synthesised in an excellent yield by the oxidation of the cycloadduct formed between the radical cation of 1-benzyl-2-phenylhydrazine and acrylonitrile. Electron transfer from the parent hydrazine is achieved by addition of the radical perchlorate salt of thianthrene, or the radical antimonyhexachloride of tris(2,4-dibromophenyl)amine. Evidence is presented to show that the radical cation of the hydrazine undergoes cycloaddition with the C~N bond of the nitrile and further oxidation leads to the triazoles. An alternative route, in which a nitrilimine is considered to be the reaction intermediate, is discounted because when 1,3-diphenylnitrilimine, generated from N-phenylbenzohydrazonoyl chloride and triethylamine (see next section), was reacted with acrylonitrile the product was not 1,3-diphenyl-5-vinyltriazole, but 5-cyano-l,3-diphenylcyanopyrazoline (10). This result complies with the accepted view that the dienophilic activity of the cyanide group is less than that of the vinyl group (H.J.Shine and A.K.M.Hoque, J. Org. Chem., 1988, 53, 4349).

294

Ph V +

N ,, NHPh +

N--

IO]

i,,,= r

~. Ph

f

N

N--

" N " Ph

(9)

+

Ph ~ N .

NHPh

-I.-

Ph " ~~N'N'/Ph \

CN

CN

(lo)

Arylhydrazines react with methyl 2,2,2-trifluoroethylimino ether to afford arylhydrazinylimines (11), which cyclise to 1,5-diaryl-3-trifluoromethyl-1,2,4-triazoles (12) when treated with aroyl chlorides (L.Czollner et al., Monatsh., 1988, 119, 349). 1,5-Diaryl-3-tbuty1-1,2,4-triazoles (14) arise when 1-(arylhydrazin-2-yl)-l-imino-2,2-dimethylpropanes (13) are reacted with araldehydes in boiling xylene during the course of 20 hours [J.P., 60 209 573 (1985); C.A., 1985, 104, 148884c].

295 Ar - NHNHC(CF3)=NH

ArNHNH2 + F3CC(OMe)=NH

(11)

Ar ArCOCI

N-N

v

(12) Ar H / N-N ,

H

Ar "

ArCHO ,

C(Me)3

z~

A

N -N C(Me)3

HN

(12) (13) Similarly, 5-amino-3-methylthio-l-phenyl-l,2,4-triazole (15) is formed when phenylhydrazine is reacted with the substituted guanidine (14) (R.Evers and E.Fisher, J. Prakt. Chem., 1985, 327, 609).

H2NyN~

O2N,,N

"sMe

SMe (14)

PhNHNH2

N-N t

Ph

MeS ~ ' ~ N/ ' ~ NH2 (15)

1,3,5-Trisubstituted 1,2,4-triazoles are available through the oxidation of N-alkylamide arylhydrazones (amidrazones) with either hydrogen peroxide, or potassium permanganate (B.I.Busykin and Z.A.Bredikhina, Synthesis, 1993, 59). The reaction of acetone phenylhydrazone with phenylisocyanate at 60 ~ for 15 hours gives an oil from which three compounds may be isolated: 2-[ 1-phenyl- 1-(N-phenylaminocarbonyl)hydrazono-2-yl] propane (16), 5,5-dimethyl-2,4-diphenyltriazolidin-3-one (17) and 5,5-dimethyl-2,4-diphenyl- 1-(N-phenylaminocarbonyl)triazolidin-3-one (18) (M.Heitmann and G.Zinner, Chem. Ztg., 1980, 104, 239). Presumably the hydrazone (16) is

296 formed first and cyclises to the triazolidinone (17), this then reacts with a second molecule of phenylisocyanate to furnish the third product (18).

Ar

H / "N - N

R~N

Ar [O ]

'~N - N

Ph

Ph

R~

I

H

Ar

H "N'- N\

Ar

AF

"N-N

~

N-N Ph

I

H

H

Me

Ph N-N

Me N - Ph J PhNHCO

Me

o I

Ph

(16)

(17) PhNHCO

Ph N-N

PhNCO

%

t=.=

M

N I

Ph (18)

Acetone arylhydrazones [ArNHN=C(Me).z] combine with acetyl isocyanate in toluene solution to gwe 4-acetyl-l-aryl-5,5-dimethyl-l,2,4-triazolidin-3-ones (19). These on acid hydrolysis ring open,

297 expel acetone, and cyclise again to give 2-aryl-5-methyl-l,2,4-triazolin-3(4H)-ones (20) (P.S.Ray and R.F.Hanh, J. Het. Chem., 1990, 27, 2017).

Ar _~,O Ar"N .! " ~ OH Ar O N H+/H20 .Me20 xN H-N N. ~ N ~ N N Me%e COMe H"'~ - H --N~COMe 2 OH O M e " ~ "H Me

Me

(19)

(20)

Semicarbazones (21) react with aqueous potassium hydroxide to give 1-aryl-3-hydroxy-l,2,4-triazoles (22), but thermal cyclisation in boiling xylene affords the isomeric 2-aryl-2,3-dihydro-l,2,4-triazol-3(H)-ones (23) (O.Tsuge, T.Hatta and R.Mizuguchi, Heterocycles, 1994, 38, 235).

Hx

~

,"%

Ar ..N

'~ O

(23)

N

A

ArNH

~O

,

,,N N xylene H ' ~ "H O (21)

KOH / H20

-~

Ar \N - ~k~:::: N,~I/N /

OH (22)

Heating N-(benzyl)benzenesulphonamide (C6H5SO2NHCH2C6Hs) with phosphorus trichloride at 170~ gives N-(0t-chlorobenzylidene)benzenesulphonimide [C6H.sSOEN=C(C1)Ph]. This reacts with ammonium thioisocyanate to gwe N-((z-isothiocyanatobenzylidene)benzenesulphonamide [C6HsSO2N=C(NCS)Ph], which is cyclised with phenylhydrazine in diethyl ether to yield 1,5-diphenyl-l,2,4-triazoline-3-thione (24) (G.Barnikow and R.Dieter, Z. Chem., 1980, 20, 97). Cyclohexanone phenylhydrazone, in dimethylformamide, is deprotonated by sodium hydride and the anion so formed can then be reacted with phenylthiocyanate to afford 5-spiro-cyclohexyl-2,4-diphenyl-l,2,4-triazolidine-3-thione (25) (G.L'abb6 and K.Allewaert, Bull. Soc. Chim., Belg., 1987, 96, 825).

298 S // Ph "'"~N ,,N ~ H I

Ph (24)

NNHPh

H Ph N .. N"

(i) Nail y

~ ~

(ii) PhCNS

Ph (25)

6-(2-Aminophenyl)-2,3,4,5-tetrahydro-l,2,4-triazine-3,5-dione (26) can be diazotized and coupled with ethylcyanoacetyl carbamate to give the hydrazone (27) (91%). When heated with concentrated hydrochloric acid this product cyclises to 2,3,4,6-tetrahydro-l,2,4-triazino[5,6-c]cinnolin-3one (28), whereas heating in aqueous base leads to 1-[1,2,4-triazine- (2H,4H)- 3,5- dione-5- yl]-2- [6-cyano- 1,2,4-triazine- (4H)- 3,5- dione-2-yl]benzene (29) (J.Slouka, Collect. Czech. Chem. Commun., 1979, 44, 2438). H

H

I

I

Ns

I

N

N"H

~

N,, H NHN=C(CN)CONHCO2Et

(26)

(27)

299 H

O

/

I N

N-H

N

O

"H

,.N

,

_CN

oJ--. i o

H

H

(28)

(29)

10. Benzotriazines 2-Acetylbenzenediazonium chloride combines with alkylamines (RCH2NH2; R=H, CN, or CO2Et) to give 3-(2-acetylphenyl)-l-alkyltriazenes (1) which tautomerise to 3-alkyl-4-hydroxymethyl-3,4-dihydrobenzotriazines (2). The latter easily dehydrate affording the corresponding 3-alkyl-4-methylene-3H-benzotriazines (3) (K.Vaughan et al., Can. J. Chem., 1985, 63, 2455). Me

Me

0

~ "~----

N . NHCH2R

OH

N"

(1)

N

(2)

-H20 ~

N~

"-

R

N

(3) Cyclohexanone 2-aminophenylhydrazone (4) is in tautomeric equilibrium with cyclohexane-3-spiro-l,2,3,4-tetrahydro-l,2,4-benzotriazine (5). The cyclic tautomer is oxidised in air to cyclohexane-3-spiro-3,4-di-

300 hydro-l,2,4-benzotriazine (6). The reverse reaction is achieved through catalytic hydrogenation over palladium on carbon (F.Sparatore and R.Cerri, J. Het. Chem., 1989, 16, 1001).

H I N N--

HI [~N,,N,.

NH2

H

(4)

O'

c N'N >

~'H2/Pd

N H

H

(5)

(6)

This is one example of a wider investigation which reveals that the 2-aminophenylhydrazones of aldehydes are easily oxidised in air to afford 3-substituted 1,2,4-benzotriazines (8). In the absence of oxygen, acids catalyse the formation of 2-substituted benzimidazoles (9) with loss of ammonia. It is suggested that both reactions proceed via 1,2,3,4tetrahydro-l,2,4-benzotriazines (7) (R.Cerri, A.Boido and F.Sparatore, ibid., 1979, 16, 1005).

[~

H I N"N~CHR NH2

H i [~N"N"H N I H (7)

02

~Nr

N

H (8)

301 H

H

I

N

I

H

(7)

H H

N I H

I

"NH 2 C+R " ~H

H

+ NH3 I

R

H

H

(9)

10. N-Arylhydrazonoyl halides and arylnitrilimines (arylnitrile imides)

(i) Synthesis (hydrazonoyl halides) Arylhydrazones of c~-ketoaldehydes (ArNHN=CHCOR), react with N-bromosuccinimide to afford (N-aryl)acetohydrazonoyl bromides [ArNHN=C(Br)COR]. The corresponding chlorides are formed if N-chlorosuccinimide is the reagent. Similarly nitration with nitric acid sulphuric acid mixtures affords the nitro analogues [ArNHN=C(NO2)COR] (K.C.Joshi, V.N.Pathak and S.Sharma, Org. Prep. Proced. Int., 1985, 17, 146). Nitrosobenzene and ethyl N,N-dibromoaminoacetate combine together to afford 2-(ethoxycarbonylmethyl)-l-phenyldiazene 1-oxide. This when treated with concentrated sulphuric acid rearranges to give a mixture of the phenylhydrazone (1) and its tautomer the phenylhydrazine (2). If the azoxy compound is reacted with hydrogen chloride then the product is ethyl 2-chloro-2-(phenylhydrazono)acetate (3) (O.A.Luk'yanov et al., Ivz. Akad. Nauk. SSSR., Ser. Khim., 1990, 352). O Ph NO

+

~ Br- N\

CO2Et

DCM

Ph

/--- COzEt

~N+~N ' I

Br

20~

O-

302

H2SO4

0 Ph ~ CO2Et N-N H H

OH Ph />--- CO2Et N-N / H (1)

(2)

CI Ph / ~ - CO2Et N-N / H (3) (ii) Reactions Hydrazonoyl halides readily afford nitrilimines under basic conditions and many of the reactions of hydrazonyl halides probably involve the initial formation of nitrilimines which then act as 1,3-dipolar species (see below). The spectra and kinetic behaviour of nitrilimines, generated photochemically from tetrazoles and from sydnones, have been studied (K.Bhattacharyya et al., J. Photochem., 1987, 36, 63; see also A.S.Shawali et al., Spectrochim. Acta, 1992, 42A, 1165). Diphenylnitrilimine (Ph CN+N-Ph), the ground state structure of which has a localized triple bond and a linear, or almost linear, array of CNN atoms, can be prepared by the photochemical irradiation of 2,5-diphenyltetrazole in polyvinylchloride (H.N.Toubro and A.Holm, J. Amer. Chem. Soc., 1980, 102, 2093). Alternatively, the nitrilimine can be obtained from the same substrate by thermolysis at 180 ~ It reacts with benzaldehyde phenylhydrazone to give 1,3,4,6-tetraphenyl- 1,2,4,5-tetraaza-2,5-hexadiene (1). This compound is said to isomerise to the bis(N-phenylhydrazone) (2) of benzil (B.I.Buzykin, and N.G.Gazetdinova, Izv. Akad. Nauk. SSSR, Ser. Khim., 1980, 1616).

PhN'N=C+Ph +

H,

PhCH=N" N,, Ph

PhNHN

Ph

---.

PhNHN ,.

Ph

PhNHN

Ph

---*

PhCH=N" " Ph (1)

(2)

303 Arylnitrilimines are implicated as reactive intermediates in many reactions which lead to heterocyclic products. Thus N-acylated phenylhydrazines can be used to generate 1,3-dipolar intermediates, which are trapped by alkenes and alkynes to produce pyrazolines and pyrazoles respectively (H.Wamhoff and M.Zahran, Synthesis, 1987, 876). The reactions employ a phosphorylating-dehydrophosphorylating reagent system comprising of triphenylphosphine-perchloroethene (a source of Ph3PC12), and triethylamine.

AF

Ar

Ph3PCI2

RC--CR

C"

R

Ar

I/

N

H"

"N" H I

Ph

N

",N+

Et3N

I

__

Ph_~

I

Ph

Another source of pyrazoles (4) is provided by the cycloaddition of 2,2-dicyanostyrene and the nitrilimine from the triethylamine promoted dehydrochlorination of the N-aryl-C-(phenylaminocarbonyl)formohydrazonoyl chlorides (3). Other compounds, such as deoxybenzoins, may be used in place of the styrene (H.M.Hassaneen et al., Org. Prep. Proced. Int., 1989, 119). The reaction of 1-[N-(2-nitrophenyl)hydrazono]-l-chloropropan-2-one (5, Ar = 2-O2NC6H4) with sodium ethoxide and ethylcyanocyanate yields 3-acetyl-5-amino-4-ethoxycarbonyl-l-(2-nitrophenyl)pyrazole (6). The hydrazononyl chloride (5) also reacts with acetylacetone, or with dibenzoylmethane, to give the corresponding 3-acetyl-4-acyl-l-(nitrophenyl)pyrazoles (7), which upon hydrazinolysis yield 7-methyl-2-(2-nitrophenyl)pyrazolo[3,4-d]pyridazines (8) (H.M.Hassaneen, A.O.Abdelhamid and A.S.Shawali, Heterocycles, 1982, 19, 319). Nitrilimines are also probably implicated in the formation of pyrazolo[3,4-b]pyridines and pyrrolo[3,4-c]pyrazoles when N-aryl-C-(chloroformyl)formohydrazonoyl chlorides are reacted with suitable precursors in the presence of bases (M.K.A.Ibrahim et al., J. Indian Chem. Soc., 1987, 64, 345).

304

PhNHCO

Et3N

N

~ "N"

Ar

PhNHCO + ~-=-- N - N

v

I

CI

Ar

H (3) PhNHCO

PhCH=C(CN) 2

Ph

-HCN I

Ar (4)

CI

NCCH2CO2Et

Ac ~ ' N N H A r NaOEt

EtO2C .

/

NH 2

~~~"XtN - Ar Ac ~

(5)

N

(6)

(ROC)2CH 2 ~ NaOEt R RCO

NH2NH2 ~ N N - Ar

N

-

Ar

N

Ac Me

(7)

(8) (Ar = 2-NO2C6H4; R = Me, or Ph)

A procedure which affords 4-acyl-2-aryl-5-(arylsulphonyl)pyrazoles (11) initially involves bromination of the hydrazones (9), to give N-aryl-C-(arylsulphonyl)formohydrazonoyl bromides (10). These are then reacted with 1,3-dicarbonyl compounds. Should potassium isothiocyanate

305 be used in place of the dicarbonyl reactants then the final products are thiadiazines (12) (H.M.Hassaneen et al., J. Het. Chem., 1985, 22, 395; see also A.S.Shawali et al., ibid., 1982, 19, 73). Ac

H

Br2/NaOAc

Br

H

RCOCH2CoRRCOx/~R

ArSO2..~ N,I~I ., Ar ------I~ ArSO2-'~N,, ~ "- Ar HOAc/Ac20 (9) (10)

~

"" ArSO2..~N, ~1.. Ar (11)

KSCN

NH

ArSO2"~N -N " Ar (12)

Again it seems probable that the reactions involve cycloadditions between the corresponding nitrilimines and the isothiocyanate ion, or the enolates. Similarly, other nitrilimines undergo cycloaddition reactions with 1,4-benzoquinones to produce both mono- and bis-adducts (13) and (14), respectively (N.G.Argyropoulos, D.Mentzafos and A.Terzis, J. Het. Chem., 1990, 27, 1983). N-Arylbenzohydrazonoyl bromides react with phenylethynecopper(I) to gwe the corresponding hydrazines (15, R = C-CPh), however, if 3-hydroxypropynecopper(I) is employed then 1-aryl-5-hydroxymethyl-3-phenylpyrazoles (16) are produced (L.Yu.Okhin, Zh.I.Orlova and L.V.Belousova, Khim. Gerot. Soedin., 1986, 856). 1,2,4-Triazoles (18) are synthesised through the oxidative cyclisation of C-aminohydrazones (17). The latter are themselves formed from N-arylbenzohydrazonoyl chlorides by reactions with alkylamines (B.I.Buzykin, Z.A.Bredikina and N.G.Gazetinova, Zh. Obshch. Khim., 1991, 61, 1034).

306

O 4-

R

O

-

PhN=N=CR +

N

v p

a

R' Ph

O

O (13)

R

O H

R

(14) H

p,_(

Ar N-N

R

t

'.

PhC=CCu Ph

Ph .Ar HOCH2C=CCu ~ N ,N- N H ~ I N

Br

"~Ar

HOCH2

(15)

(16)

CI NHCH2R ,~ RCH2NH 2,.,~ [O] ,._ ArNHN Ph v ArNHN Ph v (17)

R ~_N /~

Ar ~'N- N

Ph

(18)

Oxalodihydrazonyl dichlorides combine with sodium azide to afford the corresponding diazides, which upon reduction with lithium aluminiumhydride yield the diamines. When these are treated with acyl halides (RCOC1) cyclisation to bis(1,2,4-triazoles) occurs. The same products arise if the diazides are converted first into phosphinimes by reaction with triphenylphosphine, then hydrolysis to the diamines and, finally, treatment with acyl halides (A.S.Shawali et al., Tetrahedron, 1993,

307 49,2761).

ArNHN

CI

ArNHN ~

NaN3

/

N3

LAH y

CI ArNHN H2N

\\

NNHAr NH2

,v

N3

.coc,

"NNHAr

NHAr

Ar ,,_ ,, N

N ~.e,'R " Ar

R

Examples where nitrilimines add across the imine (C=N) bond are known, thus diphenylnitrilimine reacts with isoquinoline to form 3a,9b-dihydro-l,3-diphenyl-lH-naphtho[ 1,2-c][1,2,4]triazole (19). Similar additions of diarylnitrilimines to substituted pyridines yield 1,3-diaryl-3a,7b-dihydro-lH-benzo[c][1,2,4]triazoles (20) (L.Grubert et al., Liebig's Ann. Chem., 1992, 885). Ph N-N

N

PhC--N+N-Phv'= [~~~~N~

Ph

(19) Ar

N--N

C

ArC-N+NAr ,..-"-

i ~ j ~ N~

Ar

(2o) Diphenylnitrilimine, generated in situ from N-phenylbenzohydrazonoyl

308 49,2761).

ArNHN CI

CI \\

ArNHN ~/~ H2N

NNHAr

/

ArNHN ~

NaN3

NH2

~NHAr

"-

,/

N3

RCOCl ~--

N3

LAH

NHAr

Ar ,, . ,, N N \\ /~ R--

/

N ~.e/R "l

N / - - - ' ~ N " N " Ar

Examples where nitrilimnes add across the imine (C=N) bond are known, thus diphenylnitrilimine reacts with isoquinoline to form 3a,9b-dihydro-l,3-diphenyl-lH-naphtho[ 1,2-c][1,2,4]triazole (19). Similar additions of diarylnitrilimines to substituted pyfidines yield 1,3-diaryl-3a,7b-dihydro-lH-benzo[c][1,2,4]triazoles (20) (L.Grubert et al., Liebig's Ann. Chem., 1992, 885). Ph N--N N

Ph

PhC-N+N-Ph

(19) AF

N--N

N

ArC-=N+N-Ar

(20)

Diphenylnitrilimine, generated in situ from N-phenylbenzohydrazonoyl

309 chloride, adds to benzenesulphonyl isocyanate to produce a mixture of the oxadiazole (21) and the triazolinone (22) (M.Hedayatullah and M.Benji, Phosphorus Sulphur, 1987, 32, 163).

O

PhSO2-N

~ Ph

PhC-=N+=NPh + PhSO2NCO Ph

/

0

PhSO2 ~ N ~ N

(21) ~ Ph

Ph

(22) Benzaldehyde hydrazone and methyl 2-chloro-2-(phenylhydrazono)acetate condense together in the presence of triethylamine at 50 ~ to give the formazan (23). This reacts with phosgene to yield 4-benzylidenamino-5-methoxycarbonyl-2-phenyl-l,2,4-triazolin-3-one (24) (H.Ehrhardt, G.Heubach and M.Mildenberg, Liebig's Ann. Chem., 1982, 994). O PhSO2 -N ~~--~N-/~ ~Ph

PhC'=N+=NPh + PhSO2NCO Ph O

/ (23)

PhSO2 ~ N~,,N ~ Ph Ph

(24) N-Aryl-C-(ethoxycarbonyl)formohydrazonoyl chlorides cyclise on treatment with sodium ethoxide to produce a mixture of 2,5-diaryl-3,6-di(ethoxycarbonyl)-l,4-dihydro-l,2,4,5-tetrazines (25) and 2-aryl-5-ethoxycarbonyl-4-(arylhydrazono)pyrazol-3(4H)-ones (26) (M.O.Lozinskii et al., lzv. Akad. Nauk. SSSR., Ser. Khim., 1990, 2635).

310 CO2Et

Ar\ N-N

H/

NaOEt

N ~ N --Ar

N, N Ar ~"

\~--CI

I

CO2Et

I

+

I

CO2Et (25)

NNHAr

O~

II

CO2Et

N-N J Ar (26)

N-Phenyl-2,2,2-trifluoroacetohydrazonoyl bromide (27) reacts with potassium isothiocyanate, or with sodium isocyanate, to afford 2-imino-3-phenyl-5-trifluoromethyl- 1,3,4-thiadiazoline (28), or 2-phenyl-5-trifluoromethyl-l,2,4-triazolin-3-one (29), respectively. The first product is readily hydrolysed to the corresponding carbonyl compound: 3-phenyl-5-trifluoromethyl-l,3,4-thiadiazolin-2-one (K.Tanaka et al., J. Het. Chem., 1987, 24, 1391).

CF3

Ph tN-H

Br KNCS~// (27) ~ a N C O CF3N~_ ~

CF3

Nil

O

(28)

(29)

311 Cycloaddition of diphenylnitrilimine and tetrazol-5-yl-N-sulphonylimines leads to 2,4-diphenyl-5-(tetrazol-5-yl)-l,2,3,5-thiatriazole S-oxides (30) (R.N.Butler and G.A.O'Halloran, Chem. Ind., 1986, 750).

N', N .

Ph

N -N

N-N NSO

+ PhC=N+N-Ph

..-

N', N, I

R

I

R

N I

N I

S.--N (~' ~Ph (30)

5-Alkoxycarbonyl-l-arylamino-lH-tetrazoles (33) can be synthesised by the electrocyclisation of hydrazonylazides (32, Y = N 3) in contact with thionyl chloride. The starting materials are themselves formed by treating hydrazonyl chlorides (31, Y = C1) with sodium azide (L.Bruche, L.Garanti and G.Zecchi, Syn. Commun., 1992, 22, 309).

N ,-H 'N

X

CO2R

SOCI2 ~

N" 'N ~ CO2R N H ,bN ..N

X

Y = N3 (31)

Y (33)

(32)

R = Me or Et X = H, 4-NO 2, 2-COMe, 4-CI etc.

11. Substituted arylhydrazines and 1,2-diarylhydrazines (hydrazobenzenes)

(i) Synthesis tButyl arylhydroxamates (ArN(OH)COtBu) are used to synthesise 2-methyl-2-phenyl-l-arylhydrazines, by reacting them with N-methyl-

312 phenylamine at 80 ~ (G.Boche, F.Ferdinand and S.Schroeder, Ger. Often. D.E., 3,803,580 (1989); CA., 1990, 112, 55216m]. Alternatively, N-arylcarbamates (ArNHO2CR) can be used (G.Boche,. F.Bosold and S.Schroexler, Angew. Chem., 1988, 100, 965). 1,2-Diphenylhydrazines (ArNHNHAr) are conveniently prepared by the reduction of nitrobenzenes with formaldehyde/glucose in the presence of 1,4-naphthoquinone in 50% aqueous methanol at 50-55 ~ Sodium dodecylbenzenesulphonate is added as a phase-transfer catalyst [S.Yuan and S.Liu, CN 1,032,657 (1989); C.A., 1990, 113, 114802v]. Another system uses silica supported polyvinylpyridine polymer-palladium complexes as catalysts for the hydrogenation of azo, or nitro compounds, to hydrazoarenes (J.P.Mathew and M.Srinvasan, Polymer Internat., 1992, 29, 179). Tributyltin hydride is also an effective reagent for the reduction of azobenzenes to hydrazobenzenes (A.Alberti et al., J. Org. Chem., 1992, 57, 607). 2,4,6-Tricyano, or pentacyanoaryl halides (C1, or Br), undergo nucleophilic aromatic substitution by phenylhydrazine to give the corresponding polycyanoarylhydrazobenzenes. In related cases where two halogen atoms are present bishydrazo compounds are produced and if three halogen atoms are present in the starting materials these may all be replaced when the conditions are severe enough (e.g. 130 ~ 2 atm.). All the hydrazo compounds formed by these reactions, on oxidation with lead peroxide, give the corresponding azo derivatives (J.Rieser et al., Liebig's Ann. Chem., 1981, 1586). The phenylhydrazone of 2-oxomalonic acid adds hydroxylamine to give the hydroxyamino derivative (1, R - NHOH). This upon hydrogenation over a palladium catalyst yields 2-amino(2-phenylhydrazinyl)propanedioic acid (1, R = NH2) (A.A.Siddiqui, K.H.Khan, and Basheeruddin, Indian J. Chem. Sect. B, 1981, 20B, 1003).

CO2H PhNH.N.~-.~ CO2H

NH2OH ~

CO2H PhNHNH R--~

R=NHOH

CO2H (I)

Benzil and acetophenone undergo selective reduction by titanium(HI) chloride in aqueous solution to produce semidione radicals. These add to p-substituted arenediazonium tetrafluoroborates to yield azo derivatives (2), which in turn can be reduced to the corresponding hydrazines (3). Other

313 products are 1,1-diacyl-2-arylhydrazines (4) arising through rearrangement of the semidione-arylazo radical cations, prior to reduction (A.Clerici and O.Porta, J. Org. Chem., 1991, 56, 6813). Ph

k

o/I

/

R

Ti3+

Ph

R

0

ArN2BF4

O-H

~9

7g Ph \

//

0

R

Ph \

.+

Ti3+

\

R N=NAr OH

Ti3+

---~"

Ph \

R

/\ NHNHAr

II

0

OH

(3)

(2)

\/ N=N Ar OH

/

Ph

NHAr

0

COR

(4) (ii) Reactions

A mild oxidising agent for the conversion of hydrazobenzenes into azobenzenes is tetrabutylammoniumcerium(IV) nitrate (H.A.Muathen, Indian J. Chem. Sect. B, 1991, 30B, 522). Heating hydrazobenzene with potassium ethoxide at 300 ~ gives N-ethylaniline in 76% yield, however, if 1-phenyl-2-(4-pyridyl)hydrazine is reacted in this way, at the slightly lower temperature of 260 ~ 4-(N-ethylamino)pyridine is the only product (M.F.Marshalkin, V.A.Azimov and L.N.Yakhontov, Zh. Org. Khim., 1979, 15, 1781). Rhodium and ruthenium triphenylphosphine complexes [Rh(PPh3)3C1 and Ru(PPh3)3C12] catalyse hydrogen transfer from propan-2-ol to hydrazobenzene at 90-180 ~ to give acetone and aniline (90% yield) (B.M.Savchenko et al., lzv. Akad. Nauk. SSR., Ser. Khim., 1979, 2632). Hydrazobenzene reacts with diethoxy disulphide to give azobenzene in quantitative yield. The first step seems to be the formation of a N-ethoxy disulphide derivative (1) of hydrazobenzene which eliminates ethanol to

314 give an intermediate dithiadiazetine (2). This then expels sulphur releasing azobenzene (H.Kagani and S.Motoki, Bull. Chem. Soc. Jpn., 1979, 52, 3463). Ph~

IPh

H

H

EtOSSOEt

N-N

"--

Ph,, N _ N ,'Ph I

I

H S . SOEt

(1)

-EtOH h,,N_;,,Ph -Sn Ph~N Ph (2)

2-(2-Arylhydrazinyl)tropolones undergo benzidine-type rearrangements when heated with hydrochloric acid in ethanol at 50-60 ~ The products are 2-amino-5-(4-aminoaryl)tropolones (3), which on hydrolysis give 5-aryltropolones (4) (T.Nozoe et al., Chem. Letters, 1986, 1577).

0

0

ArNHNH.~~

H2N"~NHAr

(3)

(4) 12. Formazans

(i) Synthesis

3-Acetyl-5-aryl-l-(thiazol-2-yl)formazans (1) are formed when the arylhydrazones of pyruvaldehyde are reacted with 2-thiazolediazonium sulphate (L.V.Shmelev et al., Zh. Obsch. Khim., 1986, 56, 2393).

315

Ar,N,,H

N

I

+

(

Ar-N,,H ,,,J~S ~ N2)2SO4

,~

NI

COMe

II N

COMe (1)

5-Aryl-l-(2-methyltetrazol-5-yl)-3-phenylformazans (3) are prepared in 50-100% yields by the reactions of the 2-(2-methyltetrazol-5-yl)hydrazone (2) of benzaldehyde with arenediazonium chlorides (V.P.Shchipanov et al., Zh. Org. Khim., 1979, 15, 2207).

N=NAr Me

"

H (2)

Me ~

N

"N

,~ H

(3)

1,1",5,5'-Tetraphenyl-3,3"-biformazan (5) is prepared by reacting 3-formyl-l,5-diphenylformazan (4) with phenylhydrazine, followed by treatment of the product with benzenediazonium chloride. Dehydrogenation of the biformazan also causes rearrangement affording the tetrazol-5-yl betaine (6) (F.A.Neugebaur and H.Fischer, Chem. Ber., 1980, 113, 1226). Treating the biformazan (7) with paraformaldehyde and boron trifluoride diethyletherate in dichloromethane gives the bis(verdazylium) ion (8) which can be reduced by formaldehyde and ammonia in dimethylformamide to give the biradical 1,1',l,5,5'-tetraphenyl-3,3'-biverdazyl (9) (F.A.Neugebauer, H.Fischer and P.Meier, Chem. Ber., 1980, 113, 2049).

316 Ph Ph

"N"

H PhNHNH 2

i

N~N.~N~,Ph

i

Ph

(4) ~N"

,N

"H

H

I

N~N,~N." Ph

PhN2CI

Ph

-N..N

N'~N" Ph

N-N

Ph

N

i

N

"H

~N"

N-N % Ph

"N"

H

I

H PhNHNH 2

i

Ph

(6)

(5) Ph

Ph

t

x>- C'-

,+ N Ph"

Ph

Wr

CHO Ph

H "N" i N~ N

NN~y N .. N

N,~N.~NS Ph CHO

~

Ph

i

N

Ph J "H (4) Ph

"N"

H

I

N,~N~NsPh

PhN2CI

Ph

"N..N ,+

N , ~ N~,,N-- ph i

Ph"

N

Ph

N

N-N N -

/

Ph

Nx Ph

"H

(5)

(6)

A betaine (12) can be formed through the O-demethylation of 5-(4-methoxyphenyl)-2,3-diphenyltetrazolium tetrafluoroborate (11) and

317

Ph

Ph

Ph N-N

H/ N-N

Ph

HCHO

N--N

\>__

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