'HRONICLES

EUROPEAN

CONFERENCE

HETEROCYCLIC

A.

ON

THE

CHEMISTRY

OF

COMPOUNDS

N. Kost

A c o n f e r e n c e on the c h e m i s t r y of h e t e r o c y c l i c compounds, o r g a n i z e d by the E u r o p e a n A s s o c i a t i o n of C h e m i s t s (EUCHEM), was held f r o m A p r i l 24 to April 27, 1973, in the L a Grande Metre health r e s o r t on the s e a c o a s t 9 km f r o m Montpelier. This a s s o c i a t i o n holds annual or biennial c o n f e r e n c e s on the various fields of c h e m i s t r y . T r a d i t i o n a l l y the c o n f e r e n c e s a r e functional in c h a r a c t e r , i.e., s p e a k e r s f r o m various countries a r e invited to s p e a k on a s e l e c t e d p r o b l e m in o r d e r to s e t f o r t h the status of the p r o b l e m and f o r m u l a t e the t h e m e s for d i s c u s s i o n . R e p r e s e n t a t i v e s of the s c i e n t i f i c - r e s e a r c h organizations, who pay for p a r t i c i p a t i o n in the c o n f e r e n c e but do not p r e s e n t p a p e r s or r e p o r t s , a r e invited to the c o n f e r e n c e . A c c o r d ing to tradition, the c o - w o r k e r s of the o r g a n i z e r institution, who c a r r y out the h e a v y o r g a n i z a t i o n a l work, a r e p r e s e n t at the c o n f e r e n c e f r e e of c h a r g e . Thus, the c o n f e r e n c e s a s s e m b l e about 100-150 participants and, in addition, 15-20 s p e a k e r s . No one p r e s e n t s any a b s t r a c t s w h a t s o e v e r , and the d i s c u s s i o n s a r e not p r i n t e d . The p a p e r s take up (at the d e s i r e of the s p e a k e r ) f r o m 20 minutes to 1 hour. Each p a p e r is followed by a d i s c u s s i o n , which s o m e t i m e s b e c o m e s quite prolonged. Thus these c o n f e r e n c e s r e c a l l o u r scientific schools with r e s p e c t to the s t y l e of their o p e r a t i o n . The 1973 c o n f e r e n c e was o r g a n i z e d by the U n i v e r s i t y of Montpelier and consequently was headed by the dean of the c h e m i s t r y faculty of this u n i v e r s i t y , P r o f e s s o r R. J a c q u i e r . T h e r e w e r e 18 s p e a k e r s , including six f r o m F r a n c e , t h r e e f r o m G r e a t Britain, one each f r o m D e n m a r k and Belgium, and two f r o m the F e d e r a l Republic of G e r m a n y . In addition, the o r g a n i z e r s invited s p e a k e r s f r o m the United States (three), the USSR {one), and the G e r m a n D e m o c r a t i c Republic (one). T h e r e w e r e about 60 p a r t i c i p a n t s with about another 30 c o - w o r k e r s of the U n i v e r s i t y of Montpelier. Thus t h e r e w e r e little m o r e than 100 p e r s o n s , and s i n c e not all of them w e r e p r e s e n t f o r each p a p e r (we note that the s p e a k e r s w e r e at all p l e n a r y s e s s i o n s ) , about 50 p e r s o n s w e r e p r e s e n t at one t i m e ; this made it e a s y to c a r r y out the d i s c u s s i o n s . Of the 60 p a r ticipants mentioned above, t h e r e w e r e r e p r e s e n t a t i v e s f r o m G r e a t B r i t a i n (four), the United States (three), Spain (two), Italy (two), Switzerland (three), Thailand (two), B u r m a (one), Holland (seven), and Belgium (one), while the r e s t w e r e f r o m F r a n c e . Most of the p a r t i c i p a n t s w e r e r e p r e s e n t a t i v e s of f i r m s . F o r e x a m p l e , the leading c h e m i s t s f r o m the f i r m s C i b a - G e i g y , Sandoz, and H o f f m a n - L a R o c h e c a m e f r o m Switzerland. The p r i m a r y group of p a p e r s was c o n c e n t r a t e d around two p r o b l e m s : h e t e r o c y c l i z a t i o n leading to nitrogen h e t e r o c y c l e s , and the p h o t o c h e m i s t r y of h e t e r o a r o m a t i c compounds. The g r e a t e r portion of the p a p e r s was linked with the i n t e r e s t s of m e d i c i n a l c h e m i s t r y , although the biological action of the s u b s t a n c e s obtained was not d i r e c t l y d i s c u s s e d in any of t h e m . The synthesis of i n t e r e s t i n g s t r u c t u r e s was of p r i m a r y concern. Professor A. Lattes (University of Toulouse) was the first speaker and reviewed his research on the u s e of a m i n o m e r c u r a t i o n and h y d r o x y m e r c u r a t i o n in the s y n t h e s i s of h e t e r o c y c l e s . It is known that m e r c u r y s a l t s add to olefins to give an active c a r b o n i u m ion that is c a p a b l e of attacking the u n s h a r e d p a i r of e l e c trons of the oxygen o r nitrogen atom to give, r e s p e c t i v e l y , fl - m e r c u r a t e d alcohols or a m i n e s . The m e r c u r o group is then r e a d i l y r e m o v e d by the action of s o d i u m b o r o h y d r i d e ; if the m e r c u r y a t o m is bonded to an a s y m m e t r i c a l c a r b o n atom, it is r e m o v e d with r e t e n t i o n of the configuration. Hg X2----~

.~--~-- Hg X

R2NH

BH~-

H e t e r o c y c l i z a t i o n is p o s s i b l e when a double bond and an amino group a r e p r e s e n t in the s a m e m o l e c u l e . Thus, the c o r r e s p o n d i n g p y r r o l i d i n e (II) is obtained f r o m 5 - a m i n o p e n t e n y l b e n z e n e (I), but up to 30~ of T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 277-285, F e b r u a r y , 1974. 9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

245

HgX2

BH Z

("liHsCH=CH(CH2)3NHR7 " ~ "

C6H5CH~ HgX R

T

" C6H5CH2~t ~" R

t

C6H5"~1 [~ R

piperidine d e r i v a t i v e III is f o r m e d s i m u l t a n e o u s l y with ring expansion. The ring expansion p r o c e e d s during d e m e r c u r a t i o n , since, judging f r o m the PMR s p e c t r u m , the i n t e r m e d i a t e m e r c u r o compound has a f i v e m e m b e r e d r i n g . The f o r m a t i o n of f i v e - and s i x - m e m b e r e d rings was also noted in the m e r c u r a t i o n and subsequent reduction of 6 - m e t h y l - 2 - p r o p y l a m i n o - 5 - h e p t e n e . However, if t h e r e a r e no substituents at the end of the double bond, the p r o c e s s takes place without i s o m e r i z a t i o n of the r a d i c a l . Thus 1 - p r o p y l a m i n o 3-butene and 1 - p r o p y l a m i n o - 5 - h e x e n e a r e cyc[ized to 1 - p r o p y l p y r r o l i d i n e and 2 - m e t h y l - l - p r o p y l p i p e r i d i n e , respectively. The r e a c t i o n depends substantially on s t e r i c f a c t o r s . Thus c y c l i z a t i o n of amine IV gives only i s o m e r V, while amine VI f o r m s a m i x t u r e of f i v e - and s i x - m e m b e r e d r i n g s .

HXNHR

9'

~.~//7-,,,, H --N\R

The s p e a k e r also examined the photochemical cyclization of u n s a t u r a t e d n i t r i t e s .

h'q ( R=CH3) R'

h"~ ( R=H )

O O

R

R'

If a triple bond r a t h e r than a double bond undergoes attack, the i n t e r m e d i a t e is cleaved as in the Beckmann rearrangement.

R-C=_C(CHz)3ONO R

S i m i l a r h e t e r o c y c l i z a t i o n s p r o c e e d during initiation with peroxides to give c a r b o n - c a r b o n o r c a r b o n h e t e r o a t o m bonds. The H o f m a n n - L S f f l e r r e a c t i o n , which is b a s e d on the decomposition of N - c h l o r o a m i n e s , is the m o s t developed r e a c t i o n in this direction. H e r e , the r a t i o of r e a c t i o n products depends s u b s t a n t i a l l y on the solvent.

Cl

R

R

R

NHR

H e t e r o c y c l i z a t i o n of u n s a t u r a t e d m e r c a p t a n s occurs s i m i l a r l y during photochemical initiation.

P r i m a r i l y a s e v e n - m e m b e r e d ring is f o r m e d f r o m 5-hexenethiol at -65~ while a s i x - m e m b e r e d ring is f o r m e d a l m o s t exclusively at +80 ~ . The synthesis of bicyclic s t r u c t u r e s could be c a r r i e d out similarly. P r o f e s s o r R. C a r r i e (University of Rennes} r e p o r t e d that aziridine d e r i v a t i v e s with s t r o n g e l e c t r o n a c c e p t e r groups attached to the c a r b o n atoms a r e capable of r e a d i l y undergoing c l e a v a g e at the C - C bond r a t h e r than at the C - N b o n d . Actually, such s t r u c t u r e s r e a c t as yUdes, interacting with both nucleophiles and e l e c t r o p h i l e s . F o r example, e s t e r VII is stabilized as ylide VIII by the action of benzoic acid. Ylide

246

VIII r e a d i l y r e a c t s with Wittig r e a g e n t s to give p y r r o l i n e s . Azetidines a r e obtained with ylides of t e t r a valent s u l f u r . RI

-COOCH3 ~ H

4-

? COOCH3 C6H5

A\ C"/ /COOCH3 B S = "R

Rj.

? COOCH3 C6H5

via

COOCH3

C H~/'IL--"N~cH 6 5 6 5

.

v.._A

P r o f e s s o r C. W. Rees (University of Liverpool) d i s c u s s e d a t t e m p t s to s y n t h e s i z e s u p e r a r o m a t i c s t r u c t u r e s of the benzoazetidine and cyclobutenopyridine type and the r e l a t e d c h e m i s t r y of 1 , 2 , 3 - t r i a z a n a p h thalene. Attempts to obtain a f o u r - m e m b e r e d ring in the benzene s e r i e s by p y r o l y s i s of o - a z i d o ketones led to opening of the benzene ring, while oxidation of the c o r r e s p o n d i n g h y d r a z o n e s gave t r i a z a n a p h t h a l e n e d e rivatives. The p a p e r p r e s e n t e d by O. Buchardt (Copenhagen) was devoted to the photochemical t r a n s f o r m a t i o n s of N-oxides of the pyridine and benzopyridine s e r i e s . He e x a m i n e d the m e c h a n i s m s of r e a c t i o n s with ring c o n t r a c t i o n (formation of acylindoles f r o m quinoline N-oxides) or ring expansion (formation of 1 , 3 - o x a z e p ines). In p a r a l l e l fashion, he e a s t a b l i s h e d the f o r m a t i o n of d i r e c t s , quinolone d e r i v a t i v e s , etc., for b e n z o pyridine d e r i v a t i v e s . He also e s t a b l i s h e d that the oxazepine model is an i n t e r m e d i a t e in the photochemical f o r m a t i o n of the p y r r o l e ring. S i m i l a r p r o c e s s e s w e r e followed in the p y r i d a z i n e s e r i e s .

--

Co

+

H

O

H

In a c o m p a r a t i v e l y b r i e f p a p e r , P r o f e s s o r N. Lozach (University of C aen) examined the instances of the ambiguous occurre'nce of r e a c t i o n s of s u l f u r analogs of i s o c o u m a r i n . As in the c a s e of the oxygen c o m pounds, t h e i r h y d r o l y s i s p r o c e e d s with p a r t i a l ring expansion.

Ar

N2H4

O X:O;S

[ ~ A r

NH2

~N/NH

4-

O

/N

An

O

The c o r r e s p o n d i n g thione (IX) undergoes r e p l a c e m e n t of the thione g r o u p on r e a c t i o n with aniline, but r e p l a c e m e n t of the ring sulfur a t o m o c c u r s during proton c a t a l y s i s , 9

N\

S C6H5

~

H5

A;~

C6H5 C6H~

The r e a c t i o n p r o c e e d s s i m i l a r l y but in a m o r e c o m p l e x m a n n e r if another h e t e r o a t o m is introduced into the r i n g . Surzur and M e t z g e r f r o m the U n i v e r s i t y of M a r s e i l l e s d i s c u s s e d the synthesis of f i v e - and s i x m e m b e r e d sulfur rings with two h e t e r o a t o m s (one of t h e m being a nitrogen atom) as a method for r a d i c a l cycloaddition and as a method for c h e m i c a l t r a n s f o r m a t i o n of an a l r e a d y existing r i n g . In p a r t i c u l a r , M e t z g e r focused attention on the s t e r i c r e q u i r e m e n t s of substituents during the alkylation of thiazolidonethiones, evaluating the s t r u c t u r e s of the molecules both f r o m the PMR s p e c t r a and by m e a n s of x - r a y diff r a c t i o n a n a l y s i s ; this m a d e it p o s s i b l e to have independent information r e g a r d i n g the s t r u c t u r e s in the solid s t a t e and in solution. H. Dorn f r o m the Institute of Organic C h e m i s t r y of the A c a d e m y of Sciences of the G e r m a n D e m o c r a t i c P epublic p r e s e n t e d a detailed p a p e r that s u m m a r i z e d his r e s e a r c h on the s y n t h e s i s of a m i n o p y r a z o l e s and their cyclization to p y r i d o - and p y r i m i d o p y r a z o l e s . He dealt s e p a r a t e l y with this method of a r o m a t i z a tion of p y r a z o l i n e s and pyrazolidones by c l e a v a g e of the c o r r e s p o n d i n g tosyl d e r i v a t i v e s . The alkylation routes f o r tion of the

A m e r i c a n s c i e n t i s t G, Stork p r e s e n t e d a s h o r t r e p o r t on a t t e m p t s to u s e the known method of of enamines (Stork alkylation) f o r the synthesis of yohimbine and its analogs. S t e r e o s p e c i f i c the s y n t h e s i s of two i s o m e r i c p e r h y d r o i s o q u i n o l i n e s , one of which is b a s e d on the p a r t i a l r e d u c b e n z e n e ring by the B i r c h method, w e r e found: 247

CH3OOC~CH~'-C"-O

9

CH30"--~CH~HR R I

CH3OOC--CH. =

CH30~C~.H

0 /

OH- O~ ' - - C H~-'N--R

o

The A m e r i c a n c h e m i s t L. A. Paquette found a quite g e n e r a l method for the synthesis of h o m o a r o m a t i c compounds in the h e t e r o c y c l i c s e r i e s . The ability to undergo p o l a r o g r a p h i c reduction was taken as the c r i t e r i o n of a r o m a t i c i t y . Dianion XI, which fulfills the r e q u i r e m e n t s of a r o m a t i c i t y , was obtained by the action of p o t a s s i u m m e t a l on a z a c y c l o o c t a t e t r a e n e (X). It displays a potential that c o r r e s p o n d s to t w o - e l e c t r o n reduction and r e a d i l y r e a c t s with acids (to give 3,4- and, in p a r t , 7,8-dihydro derivatives) and other electrophfles.

-

-

2. , -

"

"

OCH3

OCH 3

THF

,Q OCH 3

OCH 3

Ion XI r e a d i l y adds benzophenone and then undergoes spontaneous c o n v e r s i o n to cyclobutenopyridine {XII). C6H5C OC6H 5 C6H5'-CI - C6H5 -o

H o m o a r o m a t i c s t r u c t u r e XIII was s i m i l a r l y s y n t h e s i z e d and c h a r a c t e r i z e d .

OCH 3

xlt_~1

Doubly-charged ions condensed with the benzene ring can be s t a b i l i z e d with ring c o n t r a c t i o n .

H O

- OCP~3

H

A. K a t r i t z k y (University of g a s t Anglia), whose r e s e a r c h on t a u t o m e r i s m is well known to us in the Soviet Union, at this t i m e s e l e c t e d for his p a p e r the ability of 3 - h y d r o x y p y r i d i n e s and t h e i r benzo analogs to r e a c t in the dipolar ion f o r m . He was able to show the 3 - h y d r o x y p y r i d i n e methiodide, a f t e r d e p r o t o n a rich, f o r m s ylide XIV, which is capable of giving adducts with strong dienophiles (acrylic and m a l e i c acid d e r i v a t i v e s and dehydrobenzene). The subsequent t r a n s f o r m a t i o n s of the adducts p r o v e d to be a new method f o r the s y n t h e s i s of t r o p o l o n e s . The r e a c t i o n s p r o c e e d s i m i l a r l y for 3-hydroxyisoquinolines, 1 - p h e n y l - 3 hydroxypyridinium ions, etc.

N--CH3

O--

(CH3)2N ~

HO

O

CH~CHCN .c

I CH 3

o

2.o.-

.-

NC

•

In passing, it was a s c e r t a i n e d that the compound d e s c r i b e d in the l i t e r a t u r e as a 1 - ( d i n i t r o p h e n y l ) - 3 hydroxypyridinium s a l t (XV) has ether s t r u c t u r e XVI, into which this s a l t is v e r y rapidly c o n v e r t e d in the

248

NO2

0 NO2

O

(C2H5)3 N ~

NO2

C6H5

C6H5

xv__.j NO2

XV

p r e s e n c e of protic s o l v e n t s . P u r e XV gives adducts with, for example, s t y r e n e . quaternization of the pyridine ring is not n e c e s s a r y , for example:

In a number of c a s e s ,

N--CH2CH2CN ,~OH

(mixture of

CH{CHCN

isomers) I CH2CHzCN

CN

Similar reactions p r o c e e d for hydroxy compounds of the pyridazine, phthalazine, and cinnoline s e r i e s . §

(CH3)2 NCSCL + Ctz'--'~(CH3) 2 NCCt3~'r-~(CH3) 2 N=CC~z Cl,xvl--'T xg~u

The Belgian s c i e n t i s t H. Viehe examined the synthetic possibilities that are offered by the use of the s o - c a l l e d "phosgenimmonium s a l t s " as applied to h e t e r o c y c l i z a t i o n . In 1957, N. N. Yarovenko r e p o r t e d that unstable substance XVII is f o r m e d by the action of chlorine on c a r b a m o y l chloride. It was found that s u b stances of the XVII type actually have s a l t s t r u c t u r e XVIII, They spontaneously liberate CH3C1 on s t o r a g e , even at -180 ~ but one ,can work with them in situ just as easily as with o r d i n a r y r e a g e n t s . Salt XVIII proved to be a m o r e energetic r e a g e n t than the salt of B r o d e r i c k and V i l s m e i e r . It r e a c t s readily with various CHacid c o m p o u n d s . XVIII~ -r- CH2(CN)2

4 0 _ 6 0o (CH3)2NN /CN C---~C CL \CN

CH3NHNH2 H2N ._..~_/.~C N I N(CH3)2 CH3

Under more s e v e r e conditions, even the ~ - m e t h y l e n e group of acid d e r i v a t i v e s reacts to give an ion of the X I X type, f r o m which d i v e r s e heterocycles can be synthesized: R R X~ ~.. R'C(:NH) NH2 (CH3)2N "~,v~N(CH3)2

.RCH2CON(CH3)2~(CH3)2N-~C"~-"~%--N(CH3)z Cl

,~

CL

flN I"~T~N R'

Difunctional compounds f o r m h e t e r o c y c l e s with salt XVIII, for example. N--N

R_C~N--NH~

XV,,

R_JLXy__ N(C%)2

\XH X=O~S~NR' While Buchardt spoke on the photochemical transformations of N-oxides, A. Lablache-Combier (University of Lille) examined in detail the photochemical t r a n s f o r m a t i o n s of h e t e r o c y c l e s of the pyridine, quinoline, and p y r a z i n e type. It was found that i r r a d i a t i o n of acridine brings about its reduction with partial alkylation by solvent molecules and d i m e r i z a t i o n . When the solvent was ether, he was able to fix the i n t e r mediate f o r m a t i o n of free r a d i c a l s . It is a s s u m e d that an n ~ 1r * transition in the pyridine molecule (or its analogs) is o b s e r v e d initially, and an ion r a d i c a l is f o r m e d and is also attacked by a solvent r a d i c a l . This is in a g r e e m e n t with the q u a n t u m - c h e m i c a l calculations. OCH2CH3

~I,,~.,,,~L,.N.~J'-C '- H-- O 02H5

If the molecule is initially protonated, the p r o c e s s is facilitated, and alkylation proceeds even with methanol m o l e c u l e s .

249

The r e a c t i o n s of i s o p y r a z o l e s (i.e., pyrazolenines) w e r e examined in a p a p e r by M. F r a n k - N e u m a n n (University of S t r a s b o u r g ) . During the synthesis of these compounds by the usual method - r e a c t i o n of aliphatic diazo compounds with the c o r r e s p o n d i n g olefins or acetylenes - he was able to find e x p e r i m e n t a l l y convenient methods for the p r e p a r a t i o n of s t r u c t u r e s with functional groups in the side chain. Special a t t e n tion was d i r e c t e d to the synthesis of the c o r r e s p o n d i n g compounds with a s t e r o i d grouping. He was able to s y n t h e s i z e 1 H - p y r a z o l o [ 3 , 4 - d ] p y r i d a z i n e s (XXV) f r o m diketones of the i s o p y r a z o l e s e r i e s . C6H 5 C=H~C-- C~C-- CC~H= "ll II ~ ~ o o

(CH3)2 CN2

N--'---r-- CO C6H 5 II IJ N > ~ COC6H 5

~

CH 3

N2H/. ~

N~ N~ II I NX, K~N

CH 3

CH 3

CH3 C6H5 xxv

Migration of one of t h e geminal CH 3 groups to give p y r a z o l e s usually o c c u r s in the t h e r m o l y s i s of i s o p y r a z o l e s (it is i n t e r e s t i n g that the COOC2H ~ group m i g r a t e d when t h e r e was c o m p e t i t i o n between it and CH 3 groups). If this s o r t of s t r u c t u r e is subjected to i r r a d i a t i o n , nitrogen is p r e f e r a b l y eliminated to give c y c l o propene d e r i v a t i v e s . R

RJ,-F'~-FII R

.

:~20 ~

N

N'?/I'~CH3

R

~.x/CH3

X "R H3C COOC2H5

cOoC2H s

R/~

COOC2H 5

The A m e r i c a n A. I. M e y e r s d i s c u s s e d a new method f o r the synthesis (including the s t e r e o s p e c i f i c synthesis) of aliphatic aldehydes, ketones, and acids. Strictly speaking, this was not within the theme of the c o n f e r e n c e , but the r e s e a r c h was of i n t e r e s t to synthetic c h e m i s t s ; f o r m a l l y , the method is b a s e d on the use of h e t e r o c y c l e s , and it was t h e r e f o r e included in the p r o g r a m . 1,3-Oxazine d e r i v a t i v e s of the XXI type a r e alkylated r e l a t i v e l y r e a d i l y through the lithium d e r i v a t i v e s and f o r m aldehydes a f t e r reduction and h y d r o l y s i s . The yields with o r g a n o m a g n e s i u m compounds a r e s o m e w h a t l o w e r . However, the yield can be r a i s e d substantially if the nitrogen atom is quaternized and the r e a c t i o n is then c a r r i e d out in h e x a m e t a p o l (hexamethylphos phoric t r i a m i d e ) . O

RLI

"~O

R'X ,.

9 R,CH2CHO

THF,

-78=

XXI

CH2L~

CH2R'

Good results were also obtained in the synthesis of branched structures ; this made i t possible to develop a new method for the preparation of branched ketones. ., 1

H~

PCHO

R

The method p r o v e d to be suitable in the terpenoid and s t e r o i d s e r i e s . o ~::~/[--

CH2 2. H20/CH3OH

CH3OOCCH 2

I

A s e a r c h for methods for s t e r e o s p e c i f i c synthesis was made on the b a s i s of the s a m e p r i n c i p l e . Optically active norephedrine, f r o m which an active oxazolidine was s y n t h e s i z e d by reaction with propionic acid imino e s t e r , was u s e d initially. Subsequent alkylation and h y d r o l y s i s gave an optically active acid with an overall purity of only 29%. The use of optically active 2 - a m i n o - l - p h e n y l - l , 3 - p r o p a n e d i o l , which is a byproduct in the m a n u f a c t u r e of synthomycin, was c o n s i d e r a b l y m o r e s u c c e s s f u l . This made it possible to obtain 2-methylhexanoic acid with a high d e g r e e of optical purity. o

RXN~, N'h/R

CH30

250

o

R\N]J. N"~ .R CH 3

o

] ~Nl R-.

CH3

o

N4 R

The e s t a b l i s h m e n t of the s t r u c t u r e s of various N-oxides that a r e f o r m e d in the d i r e c t oxidation of pteridines was the s u b j e c t of the l e c t u r e b y W. P f l e i d e r e r (University of Konstanz). It was found that the nitrogen a t o m that is not shielded by a methyl group bonded to the nitrogen atom of the adjacent ring is oxidized p r e f e r a b l y . The joint application of the v a r i o u s s p e c t r a and a l t e r n a t i v e s y n t h e s i s made it p o s s i b l e to also e s t a b lish a n u m b e r of principles of alkylation f o r both p t e r i d i n e s and s i m p l e r model s t r u c t u r e s of the p y r i m i d i n e and pyridazine type. A s e r i e s of data on the d i r e c t i o n of r e a r r a n g e m e n t of s u c h N-oxides by the action of acetic anhydride was p r e s e n t e d . A long p a p e r by the English Nobel L a u r e a t e D. Barton was devoted to s y n t h e s e s by m e a n s of phenyls u l f e n a m i n e s . T r i s (phenylsulfenyl)-amine (XXII), which is r e l a t i v e l y r e a d i l y obtained by the action of C6HsSC1 on a m m o n i a , r e a d i l y t h e r m a l l y f o r m s r a d i c a l XXIII, which is c a p a b l e of undergoing n u m e r o u s r e a c t i o n s . Thus, it gives quinonimine d e r i v a t i v e s on r e a c t i o n with phenols o r a r o m a t i c a m i n e s .

~

--OH

4-

N(SC6H5) 3

.

~>::N--SC6H

5

+

tracesofthe 1,4-isomer

xxl--~

O

.to

N(SC6H5) 3

., . N(SC6H5) 3

-4-

(~

- SC6H 5

C6H55SC6H 5)

xx,__~J S t e r i c a l l y hindered phenols a r e attacked by this r e a g e n t with r e p l a c e m e n t of the group in the p a r a position r e l a t i v e to the hydroxyl group. The r e a c t i o n with 2,6-dialkylanilines p r o c e e d s s i m i l a r l y .

OH

O"

R

R

0

0

R

N(SC6H5)2

NSCsH5

The r e a c t i o n s with f i v e - m e m b e r e d h e t e r o c y c l e s a r e i n t e r e s t i n g . Reagent XXII (or, m o r e p r e c i s e l y , r a d i c a l XXIII) is a quite s t r o n g e l e c t r o p h i l e and attacks the G - c a r b o n a t o m of furan or p y r r o l e even if t h e r e is a s u b s t i t u e n t attached to it; r e p l a c e m e n t of the ring oxygen by nitrogen or ring expansion m a y o c c u r .

C6H5

C6H5 X-'~=~ C-'6HS'~N 5C'6H

C6Hs~'~C6H5 ~QO""C6H5~ CH6 H 5 C6H5 C6H5 C6Hs~_~C6H5 N(SC6Hw2

C6Hs~N~'~Cb.H~

C6H5

C6H5 "

HO

S i m i l a r l y , compounds of the indole s e r i e s undergo oxidative amination with e n t r y of the s u b s t i t u e n t into the 3 position.

C6~5

,,

-C6H5

C6 .~

In addition to r a d i c a l p r o c e s s e s , r e a g e n t XXII m a y r e a c t via the s c h e m e of ionic r e a c t i o n s with s t r u c t u r e s in which t h e r e is a p a i r of ~ e l e c t r o n s , and a bond is f o r m e d with the sulfur atom (enamines, f o r e x a m p l e , r e a c t t h i s way), o r in which t h e r e is an u n s h a r e d p a i r of p e l e c t r o n s , in which c a s e a bond is f o r m e d with the nitrogen a t o m .

o[ ~

1. XX.!.! , 20 = -~ 2o H30"I"

P (C6H5)3

20=

SCBH5

(C6H5~3P~NSC"6H5

251

Thus the unusual oxidative amination r e a c t i o n developed by Barton p r o c e e d s with a s o m e w h a t d i f f e r ent orientation (for e x a m p l e , p r e f e r r e d entry of substituents into the ortho position even in the naphthol s e r i e s ) than other r e a g e n t s give and is d e s e r v i n g of the s e r i o u s attention of c h e m i s t s doing r e s e a r c h in the synthesis of h e t e r o c y c l i c s t r u c t u r e s . A. N. Kost (Moscow University), on behalf of A. K. $heinkman (Donetsk University) and h i m s e l f , p r e sented a r e v i e w of h e t a r y l a t i o n r e a c t i o n s , i.e., a r e v i e w of methods for the d i r e c t introduction into an o r g a n ic molecule of the r e s i d u e of a h e t e r o a r o m a t i c compound of the pyridine type and its benzo d e r i v a t i v e s . The basic positions a s s o c i a t e d with the p r o b l e m of h e t a r y l a t i o n w e r e touched upon in a p a p e r by A. K. Sheinkman, which was published in Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii [Khim. G e t e r o t s i k l . Soedin., No. 1 (1974)]. It is also p r o p o s e d that the texts of s o m e other p a p e r s , which the authors have s e n t to the editorial s t a f f of this journal, be published in m o r e c o m p l e t e f o r m .

252