x
Foreword
This is the nineteenth annual volume of Progress in Heterocyclic Chemistry, and covers the literature published during 2006 on most of the important heterocyclic ring systems.
References are
incorporated into the text using the journal codes adopted by Comprehensive Heterocyclic Chemistry, and are listed in full at the end of each chapter. This volume opens with two specialized reviews. The first, by Xuechuan Hong and Michael Harmata, covers 'Recent progress in the chemistry of 2,1benzothiazines'. The second, by Ana Silva and Jose Cavaleiro, discusses 'Porphyrins in Diels-Alder and 1,3-dipolar cycloaddition reactions'. The remaining chapters examine the 2006 literature on the common heterocycles in order of increasing ring size and the heteroatoms present. In the previous volume, Vol. 18, it was not possible to include a chapter on 'Six-membered ring systems: diazines and benzo derivatives' so this volume has two chapters on this topic: chapter 5.4 (2005) covers the literature of 2005 and chapter 5.4 (2006) covers the publications of 2006. Due to unforeseen and unfortunate circum stances, 'Six-m embered ring system s: with 0 and/or S atom s' does not appear in this volume; Volume 20 will include a double chapter on this topic, covering the literature of 2006 and 2007. The Index is not fully comprehensive - it includes only systematic heterocyclic ring system names. Thus, wherever a pyrrole is discussed, that would be indexed under 'pyrroles'; wherever 'pyrido[3,4-b]indoles' are mentioned an indexed entry under that name will be found; similarly 'aceanthryleno[ I,2-e][ I,2,4]triazines', 'azirines', '2H-pyran-2-ones', 'I ,2,4-triazoles', etc., etc. are listed. But, subjects like '4-ethyl-5-methylpyrrole', '5-acylazirines', '6-alkyl-2H-pyran-2-ones', '3alkylamino-I,2,4-triazoles', are not listed as such in the Index. 'Diels-Alder reaction' or 'Heck coupling' etc., are also not indexed. However, again this year, the Contents pages list all the subheadings of the chapters which we hope will considerably improve accessibility for readers. We are delighted to welcome some new contributors to this volume and we continue to be indebted to the veteran cadre of authors for their expert and conscientious coverage. We are also grateful to Joan Anuels of Elsevier Science for supervising the publication of the volume. We hope that our readers find this series to be a useful guide to modern heterocyclic chemistry. As always, we encourage both suggestions for improvements and ideas for review topics.
Gordon W. Gribble John A. Joule
xi
436
Chapter 6.4Editorial Advisory Board Members
Progress in Heterocyclic Chemistry Six-membered ring systems" with 0 and/or S atoms 2006 - 2007 PROFESSOR M. BRIMBLE (CHAIRMAN) University of Auckland, New Zealand Unfortunately, due to unforeseen and unfortunate circumstances, the regular chapter on 'Six-membered ring systems: with O and/or S atoms' does not appear in this volume. We apologise for this anticipate that PHC 20 will include double chapter on this PROFESSOR D. omission. ST CLAIRWeBLACK PROFESSOR H. aHIEMSTRA area, covering the literature of 2006 and 2007.
University of New South Wales Australia
University of Amsterdam The Netherlands
PROFESSOR M.A. CIUFOLINI University of British Columbia Canada
PROFESSOR D.W.C. MAcMILLAN California Institute of Technology USA
PROFESSOR 1. FUKUYAMA University of Tokyo Japan
PROFESSOR M. SHIBASAKI University of Tokyo Japan
PROFESSOR A. FORSTNER Max Planck Institut Germany
PROFESSOR L. TIETZE University of Gottingen, Germany
PROFESSOR R. GRIGG University of Leeds UK
PROFESSOR P. WIPF University of Pittsburgh USA
Information about membership and activities of the International Society of Heterocyclic Chemistry (ISCH) can be found on the World Wide Web at http://webdb.uni-graz.aU-kappeco/ISHC/index.html
Chapter Chapter 1 Recent progress progress in the chemistry of of 2,1-benzothiazines 2,1-benzothiazines
Xuechuan Hong and Michael Hannata Harmata** Missouri 65211, Department ofChemistry, of Chem•try, University University ofMissouri-Columbia, of Missouri-Columbia, Columbia, Columbia, Missouri 65211, USA USA
[email protected] [email protected] 1.1 INTRODUCTION INTRODUCTION
. have been reported . In recent years, 2,I-benzothiazines 2,1-benzothiazines I, 1, have been of of enonnous enormous interest to synthetic chemists. The current review is intended to present the progress of synthetic procedures and applications of of 2,1-benzothiazines 2,1-benzothiazines 1 and related compounds. 5
4
6CO~ 6 ~ ~ N ~ S 33 /./ N/SZ 2
7 7
8
1 (1 (1))
I-benzothiazines 1 Figure 1. General structure of 2, 2,1-benzothiazines SYNTHESIS OF 2,1-BENZOTHIAZINES COMPOUNDS 1.2 THE SYNTHESIS 2,I-BENZOTHIAZINES AND RELATED RELATED COMPOUNDS 3,4-Dihydro-2,1-benzothiazine 2,2-dioxide 2,2-dioxide Derivatives 1.2.1 Synthesis of 3,4-Dihydro-2,I-benzothiazine
3,4-Dihydro-2,I-benzothiazine 3,4-Dihydro-2,1-benzothiazine 2,2-dioxide derivatives 2, a type of benzosultam, possess very strong biological activities and have been used as drugs for treating heart diseases and 92MI1; 94MIl; 94MI1; 98MIl; 98MI1; 02MIl; 02MI1; 02MI2; 04MIl> (Figure as lipoxygenase inhibitors '- Ph
30%
30%
(~H3 " ;02 Cl
)H Ph
8
9
-SO2CH21 NH3, EtOH= CI/'~~O
~
2
33%
I OH I Ph
Ph 8
10
Scheme Scheme 2
Abramovitch and co-workers also synthesized 3,4-dihydro-2,1benzothiazine 2,2-dioxide 4 by flash vacuum pyrolysis of ~-arylethanesulfonyl [3-arylethanesulfonyl azides 11. The 3,4-dihydro-2,I-benzothiazine 3,4-dihydro-2,1-benzothiazine 2,2-dioxide 4 was obtained in 13% yield at 300°C 300 ~ along with some side products, such as dihydropyrindine, indoline, indole, and styrene. Although the reaction yield was low, this new approach appeared very promising for the synthesis of 2,I-benzothiazenes 2,1-benzothiazenes (Scheme 3). After an extension of this work reported by the same group, OCH 3
~ _CH3 N
~
CI Nail, DMF DMF •.~ NaH, SO2CH3 60 60 DC, ~ 35% 35% N- 802CH lL
13 13
Ph Ph
ceo 16 16
1. BBr3' BBr3, CH CH2CI2, 77% • 1. 2CI 2, 77% y /80 2 2. H , Pd(OHh, 85% 02 2. H2, Pd(OH)2, 85% 2 N
~
14 14
OCH33 OCH
~I
&
OH OH
OCH3
L
lph Ph
NaH NailCDMF •=_ 25 DC, 47%
N~SO2CH3 25 80 CH
W
2
3
,47 Yo
CO
Lph
lph
~
02 N/ 802 H .
~
15 15
OCH3
CliO
60 OH OH
BBr3, CH CH2CI 650/0 • 1. BBr3' 2CI 22,, 65% /80 022 2. H2, H2, Pd(OH)2, Pd(OH)2, 82% =
N 17 17 lLph Ph
60 ~
02 N/ 802
15 15 H H
Scheme Scheme 4 An improved synthesis of 3,4-dihydro-2,I-benzothiazine 3,4-dihydro-2,1-benzothiazine 2,2-dioxide was reported by Togo and co-workers using photochemical conditions . Treatment of N-alkyI2-(aryl)ethanesulfonamides N-alkyl 2-(aryl)ethanesulfonamides 18 with (diacetoxyiodo)arenes under irradiation with a tungsten lamp at 20-30 DC ~ afforded 2,I-benzothiazines 2,1-benzothiazines 19 and 20. Chemical yields and selectivities were dependent upon the choice of solvents and the reactant's substituents 18 (Table 1). When THF and EtOH were used as solvents, the reactions failed to give the cyc1ized cyclized products, since their a-hydrogen was abstracted by the intermediate sulfonamidyl radical. Compound 20 was obtained as a major product when 1,2-dichloroethane was employed as a solvent. In contrast, in the case of EtOAc as solvent, compound 19 was obtained as the major product.
Table 1. Formation of l-benzothiazine 2,2-dioxides with N-alkyl 2of 3,4-dihydro-2, 3,4-dihydro-2,1-benzothiazine (aryl)ethanesulfonamides
~
SO2NHR Phl(OAc)2 Phl(OAc)2 (1.6 (1.6 eq.) ~802NHR 1 (1.0 eq), 12 (1.0 eq), 20-30 DC ~ 2 1.--:;:; R' X' X' W-hag, W-h'o, 2 h
ira,
X' X'
JC(l .--:;:;
R'
1
N/ 8022 + X'' + X
XXX
N/ 8022
.--:;:;
I
I
R
18
R'
R
20 20
19 19
Entry
Solvent
R R
R'
X'
Yield % of19 of 19
Yield %0f20 % of 20
1
THF
CH33 CH
H
H
0
0
2
EtOH
CH3 CH 3
H
H
0
0
3
AcOEt
CH3 CH3
H
H
81
10
4
CICH 2CH 2CI C1CH2CH2C1
CH 3 CH3
H
H
6
89
5
C1CHeCH2C1 CICH 2CH2CI
Et
H
H
0
89
6
CICH 2CH 2CI C1CH2CH2C1
CH 3 CH3
CH 3 CH3
H
0
97
7
C1CH2CH2C1 CICH 2CH 2CI
CH3 CH 3
H
CH 3 CH3
0
94
8
CICH 2CH 2CI C1CH2CH2C1
CH 3 CH3
H
CI C1
34
49
5
Recent progress in the chemistry of of 2,l-benzothiazines 2,1-benzothiazines
Table 2. Cyclization of N-methoxyl 2-(aryl)ethanesulfonamides
~I~
~S02NHOCH3 R" R
J:X) ~
SO2NHOCH3Arl(OH)OTs ArI(OH)OTs(1.1 (1.1eq.) eq.) ~ S O 2 o0 °C_ 20 min. ~ rt. rt. 20 min.
~
N/ S02
• R R
[I
OCH OCH 3 3
22 22
21
Entry
R
Solvent
~ E
Temp./°C Temp./o C
Time/min
Yield % of 22
1
H
CHC13 CHCh
4.7
20
18
2
H
AcOEt
6.0
20
29
3
H
ClCH C1CHzCHzC1 2CH 2 Cl
20
73
4
H
CH CH3CN 3CN
37.5
o0 °c ~ to rt o0 °c ~ to rt. o0 °c ~ to rt o0 °c ~ to rt
20
86
5
H
CH CH3CN 3CN
37.5
60-65
5
65
6
H
CH CH3CN 3CN
37.5
0
20
65
7
H
CH CH3CN 3CN
37.5
10-15
20
84
8
CH33 CH
CH CH3CN 3CN
37.5
20
85
9
C1 Cl
CH CH3CN 3CN
37.5
20
52
10
F
CH3CN
37.5
o0 °c ~ to rt o0 °c ~ to rt o0 °c ~ to rt
20
44
lOA 10.4
2,1-benzothiazines via Togo's group also reported the preparation of the 2,I-benzothiazines via an ionic pathway with hypervalent iodine compounds . . Using this method, it was found to be far easier to synthesize five- or seven-membered benzosultams and avoid the difficult deprotection of the N-alkyl group in the six-membered benzosultams to give the free NH group. The reaction of N-methoxy 2-(aryl)ethanesulfonamides 21 with various hypervalent iodine reagents produced the cyclization products in various yields, which were dependent on the dielectric constant (£) I-benzothiazines 22 (e) of solvents. The best yield of 2, 2,1-benzothiazines was 85% by treatment of N-methoxy 2-(aryl)ethanesulfonamides 21 with [hydroxy(tosyloxy)iodo] benzene in CH3CN CH3CN solvent from 0 °c ~ to room temperature for 20 [hydroxy(tosyloxy)iodo] minutes (Table 2). An electron-withdrawing group on the ppara a r a position of the aromatic ring in 21 (e.g., Cl, C1, F) reduced the yields of the cyclization reaction. In 2003, Togo and co-workers described a radical cyclization and ionic cyclization onto the aromatic rings of 2-(aryl)ethanesulfonamides 21 to produce 3,4-dihydro-2,1benzothiazine 2,2-dioxides with polymer-supported hypervalent iodine reagents in good yields . . 1.2.2 Synthesis Derivatives Synthesis of of Dibenzo[c,elIl,2]thiazine Dibenzo[c,e] [1,2]thiazine 5,5-dioxide 5,5-dioxide Derivatives
Dibenzo[c,e][1,2]thiazine 5,5-dioxide derivatives 23 are phannacologically Dibenzo[c,e][1,2]thiazine pharmacologically interesting . Various methods for the construction of these . general class of compounds is represented in Figure 4.
R R3 3
~R2
U
N
/$02
II
R R11= H, H, CH CH33 R = H, ester, acid, R2= H, ester, acid, ketone, ketone, arene arene 2 R R3= H, CH CH3, Phenyl 3=H, 3 , Phenyl
R1 R1 (31)
Figure 4. 1H-2,I-Benzothiazine 1H-2,1-Benzothiazine 2,2-dioxide derivatives Compound 34 can be synthesized by a Bamford-Stevens procedure from compound 33. Loer explored the cyclization of 32 with polyphosphoric acid (PPA), (PPA), followed by decomposition of the tosylhydrazone to form the desired IH-2,I-benzothiazine 1H-2,1-benzothiazine 2,2-dioxide 34 in good overall yield (Scheme 8) . . H
O~o,
N'.SO2 /O OH OH
32
H
PPA PPA
cy~
" 02
"
0O 33
Scheme 8
1)TosNHNH~ 1)TosNHNH~ 2) Base Base
H
i~/-~--.~N.so2
CO /-/
/-/
34
O2
8
X. X Hong and M. M Harmata
An improved synthesis IH-2,I-benzothiazine 4(3H)-one 2,2-dioxide 33 that results in synthesis of 1H-2,1-benzothiazine a relatively high overall yield was developed by Lombardino's group 1N • 3 ~
R3 R3-
v
NaOEt
COR2 -COR2
~4
42
2
3
CI R 1 R33 ==H, Cl R4 ==H, H, CH 3 R4 3
R
41
CO2Et
R 1 =ArCO, C02Et R1 = ArCO, R R2 = =CH CH 3,, Ph Ph
N "S,O2 R2
Scheme 12 Scheme
of Azathiabenzenes Azathiabenzenes and Azathiaphenanthrenes Azathiaphenanthrenes Synthesis of 1.2.4 Synthesis
Cyclic sulfilimines are considered useful reagents in organic synthesis . The chemistry of of cyclic sulfilimines has been studied extensively since the 1970s. of azathianaphthalene Hori and co-workers accomplished the first synthesis of azathianaphthalene and azathiaphenanthrene azathiaphenanthrene in 1979 . Their approach began with the formation of of an ortho-nitrobenzaldehyde 43, via a Wittig reaction with an ylide and a subsequent olefin from ortho-nitrobenzaldehyde ortho-aminostyryl methyl sulfide 45. The cisreduction with zinc to afford cis and trans ortho-aminostyryl olefin was then treated with NCS, AgC104 AgCI04 and KOH to yield 2-methyl-l-aza-2thianaphthalene 47 in 41% yield. 9-Methyl-IO-aza-9-thiaphenanthrene 9-Methyl- 10-aza-9-thiaphenanthrene 48a and 9-ethyl-lO9-ethyl- 10aza-9-thiaphenanthrene aza-9-thiaphenanthrene 48b were obtained in a similar fashion in almost quantitative yields, whereas 6-benzyl-6H-dibenzo[c,e][1,2]thiazines 6-benzyl-6H-dibenzo[c,e][1,2]thiazines 50 were isolated in moderate yields via a l,2-rearrangement 1,2-rearrangement (Scheme 13) . . CliO ~ N O
+ [~CH:CHSCH3 Ph3P-CHSCH3
2
89%
w:
43
1.NCS • [ ~ ~ N ~ S 2.AgCI0 ~ 2.AgCIO44~ 41%
I
~
o
~
-
NO2
+ ,S,+
1. NCS NCS 1.
2•2. KOH KOH H2R " CH2R
N
48a: =H, 100% 4 8 a : RR= H 100% '
48b: 48b: R R = = Me, Me, 90% 90%
~]~CH:CHSCH3
80%
NH2
44
+ CH 33 "CH H H CICI 46 46 I
Zn-CaCl2 >
45
KOH > ~ 57%
S
+ "CH3
47
~ I ~ _ . ~ ,,jSCH2R NH2
1. NCS
.~
1. NCS • 2. 2. n-BuLi n-BuLi
49 49
Scheme 13
~D 0.1 0
~,S
CH CH2Ar 2Ar 5 0 a RR = P= h Ph, 50% 50% 50a: '
50b: R R = = pTal, pTol, 57% 57%
10
X Hong and M. M Harmata x.
Moody and co-workers independently reported the synthesis of of azathiabenzenes by thermolysis . . Azides 51a and 51b were decomposed in boiling toluene to give the corresponding cyclic sulfimides 52a and 52b in 52% and 13% yields, respectively (Scheme 14). m
N3SR [ C():
f::,. roN';-R -_. I
N3sR
h
h
. f.rN
COzE! CO2Et
::::... h COzE!t ~[~~'L'~CO2E R= = Ph, Ph, 52% 52% 52a: R 52b: 52b: R R = Me, Me, 13% 13%
R= = Ph 51a: R 51b: R R = Me Me
Scheme 14
1.2.5 Synthesis of 1,2-Thiazine 1,2-Thiazine S-oxide by Cycloaddition Cycloaddition of N-Sulfinylaniline N-Sulfinylaniline
The reaction of aryl sulfinylamines as heterodienes has been well documented in the . A similar reaction was further reported high yield . 2,I-benzothiazine 150 was formed from acrylonitrile and 34 via via by the Loev group in which 2,1-benzothiazine . Electrophilic aromatic a Michael addition reaction, followed by a reduction . studied by Loev and Kormendy and by substitution reactions have been studied of 152 only afforded a 6 Sianesi and co-workers. Bromination and nitration of mono-brominated product product 153, 153, whereas bromination and nitration of 4 gave a mixture of mono-brominated 151, where the yields are dependent upon the reaction mono- and disubstituted products 151, 67MIl>. Another interesting reaction has been reported by Rossi conditions . and Pagani . Indole Indole 148 and N-methylaniline 149 were isolated from 2,I-benzothiazine 147 with copper powder at around 300 300°C treatment of 2,1-benzothiazine ~ (Scheme 38) . .
R' s
153: R =CH 3 R1 = Br, NO 2
H2
02
I R
A
CH 3
NBS or l
Me
HNO3
149
A CH3
H3~I
Cu
~~N~
S 02
02 ,
CH 3
I 148
152
l
l
R1 = CH3
Me2SO4
-
02
02 RI= H
H
33
Base, RX
H2 . ~
~ 02
R
147
H
H
4
34: R 1= H or CH 3
I NBS or R1 = H
1. CH2=CHCN 2. H2
HNO3
~~N~SO2
I
(CH3)3NH2
150 Scheme 38
- --SO2 R2
151:R1, R2 = Br, NO 2
26
X Hong and and M. M Harmata y.
Reactions of of Azathiabenzenes Azathiabenzenes and Azathiaphenanthrenes Azathiaphenanthrenes 1.3.2 Reactions
of azathiabenzenes azathiabenzenes and azathiaphenanthrenes azathiaphenanthrenes was reported by the Hori A further study of 87CC385> and the Moody group . 94JCS(PI)1709> was observed as their compounds possess an ylidic .
~ ?
~
~
O2Et C02Et
I + ~/k.N.S.p h ",::;
~CO2Et
PhH ~
" ~-P~N-S-ph
N/S'Ph
CO2Et
. ~N~S-Ph
52a ( f'I
MeO2C-CCO2Me Me02C==CC02Me 154
~
EtOH
155
156
CO2Et ~ C O 2 E t
~J'~ N~S+ph
CO2Et
~N.S+~ph
~N~CO2Me
CO2Me
CO2Me
158 158
CO2Et CO2Me "~SPh
CO2Et
~ ~N
157: 47%
S'ph
~
MeO2C .~.,~ N'~~/ ?+--k. MeO2C Pfi CO2Et
mhs
CO2Et
159
160: 65% 2:1
Scheme 39
27
Recent progress progress in in the the chemistry of of 2,1-benzothiazines
Azathiaphenanthrenes can be oxidized by KMn04 KMnO4 or m-chloroperbenzoic acid to the corresponding sulfoximines 163 in good yields. Azathiaphenanthrene 48a underwent a thermal ring expansion to afford 7H-dibenzo[dJ][1,3]thiazepine 7H-dibenzo[d,J][1,3]thiazepine 163 in 26% yield by a Stevens-type rearrangment 91JCS(P 1) 1733> while compound 48c furnish compound 165 by cycloelimination via 164 (Scheme 40). underwent dealkylation to furnish
"':::
, .0
~I -/s~ ~
+
CHzR H2R
N
r ~ l>.
xylene
H-
H,~__~
= =
48a R R=HH 48a: 48c R R = alkyl alkyl 48c:
KMnO4 KMoO,
~O C(~\S
-
N H H
=
H, 26% 162: R = H,26%
161
j Xy~ xy
ca ]- ce9 '-'::
r
+
H2R
0
163 163
'.0
~yHz2
~
N~
1
S
H
H Hq Ha-HC R' R' 164 164
165. R= R= alkyl, alkyl, -40% -40% 165.
Scheme 40 Scheme
+
+ .0 ~ ~ N~S'CHzR S +CH2R 48c 48c
i
=
RI(( R R = Me, Me, Et, et et al.) RI
--- r LDA
- S N~
48a 48a
+ 'CH 3
LOA
:-:; ·1~ TMSCl
CH z
N
+ +
166
Li
H
TMS 167
1RCO2Et RCOzEt
9-~
S
R
WOH
168
Scheme 41
28
x. X Hong and M. M Harmata
The methyl hydrogen of 9-methyl-IO-aza-9-thiaphenanthrene 9-methyl-10-aza-9-thiaphenanthrene 48a is acidic. It can be readily deprotonated by LDA in THF . . The corresponding anion can be quenched by alkyl iodides to give various 9-alkyl-1O-aza-9-thiaphenanthrenes 9-alkyl-10-aza-9-thiaphenanthrenes 48c in fair yields (Scheme 41). However, none of the expected products were found when the anion was quenched by TMSCI TMSC1 or esters. Ring expansion product 167 was obtained via sulfonium ylide intermediate intermediate 170 derived from the expected product 169 by a 1,2-shift (Scheme 42)
