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Trapping and structure determination of an intermediate in the reaction between 2-methyl-5-t.butylpyrrole and dichlorocarbene
Tetrahedro~ Letters No. 27, PP 2439 - 2442, 1978. © Pergaplon Press Ltd. Printed in Great Britain.
0040-4039/78/0701-2439~02.00/0
TRAPPING AND STRUCTURE DETERMINATION OF AN INTERMEDIATE IN THE REACTION BETWEEN 2-METHYL-5-t. BUTYLPYRROLE AND DICHLOROCARBENE A. Gambacorta* and R. N i c o l e t t i I s t i t u t o di Chimica Organica - Universita di Roma - 00185 Roma - I t a l y S. C e r r i n i , W. Fedeli and E. Gavuzzo Laboratorio di S t r u t t u r i s t i c a Chimica "G. Giacomello", C.N.R., C . P . n . l O , 00016 Monterotondo Stazione, Roma, I t a l y . (Received in UK 30 ~larch 1978; accepted fo~ publication 12 Nay 1978)
2 , 5 - d i a l k y l pyrroles react in protic media with dichlorocarbene generated under basic conditions giving rise to ring expansion products ( 2 , 6 - d i a l k y l - 3 chloropyridines) and addition products ( 2 , 5 - d i a l k y l - 2 - d i c h l o r o m e t h y l - 2 H - p y r l roles or Plancher's pyrrolenines) . The l a t t e r are not intermediates for the 2 ring expansion reaction . 3 4 According to the mechanism generally accepted , these two product types are formed by d i f f e r e n t routes. Pyridines arise from the cycloaddition of d i chlorocarbene to the undissociated pyrrole, while 2H-pyrroles arise from an e l e c t r o p h i l i c attack of the reagent on the conjugate base of the substrate. In this way two d i f f e r e n t intermediates are supposed. The simplest hypothesis that both products were formed from a single intermediate has already been 5 6 suggested and recently reproposed . In order to c o l l e c t new data on this argument, we carried out a reaction between 2 - m e t h y l - 5 - t . b u t y l pyrrole (1) and dichlorocarbene, generated in neutral
and aprotic medium (dimethoxyethane, DME) from PhHgCCI3/Nal system7. Chromatographic separation of the reaction mixture gave - together with
the already-known compounds ( I I I - V ) - a c r y s t a l l i n e product ( I I )
containing
mercury (MP" I08-I09°C from CH3CN). °'
CHCI 2
(iv)
(v)
I r spectrum (in KBr; v max at 3070;3050;2980;2940;1610;1525;1030;1005 and -l 700 cm ) and NMR spectrum (in CCI4; 7.178,5H; 7.388 and 6.498, 2H,AB system, 2439
2440
2"(
No.
J=5 Hz; 1.586,3H, s i n g l e t ; 1.226,9H, s i n g l e t ) suggested for the mercurial the structure of
(II)
[l,l-dichloro-l-(2-methyl-5-t.butyl-2H-pyrril-2-)]phenylmer-
cury. CCI R Mi Ph
(i,)
Well-shaped colourless c r y s t a l s of ( I I )
were obtained by slow evaporation
from a c e t o n i t r i l e at room temperature. Crystal data are" CI6HI9NCI2Hg, M=496.83, monoclinic, a=6.261(2), b=15.400(4), c=17.594(B)A, 8=96.08(2) ° , V=IB86.BA3, -3 Space group P21/c, Z=4, Dc=l.79 gcm , F(000)=944, Mok~(>,=.71069), iJ=96.69 -l cm . The i n t e n s i t y data of 2514 non-zero ( I > 3 o ( I ) )
indipendent r e f l e c t i o n s we-
re collected on an automatic f o u r - c i r c l e d i f f r a c t o m e t e r , using monochromatized Mok~ r a d i a t i o n , 0-20 scan mode, from a c r y s t a l of O.25xO.30xO.30 mm, up to a 0 value of 30 ° . No correction for absorbtion or e x t i n c t i o n was applied. The crystal structure was solved by Patterson and Fourier methods and refined by block-diagonal least squares. The refinement of atomic parameters of a l l
the non-hydrogen atoms, as-
suming anisotropic thermal motion only for Hg and Cl atoms, led to an R=0.062. A final
difference Fourier synthesis showed no s i g n i f i c a n t residual electron
density maxima. Crystallographic evidence such as the analysis of the electron population of the Fourier peaks stereochemical considerations such as valence angles and bond distances allowed us to establish unambiguously the molecular structure of the c r i s t a l l i n e p r o d u c t ( I I ) . The f i g u r e shows the stereochemical features of the molecule in the c r i s t a l l i n e state.
N|
{:I
Ol
No. 27
It
2441
seems l i k e l y that compound ( I I )
arises from the trapping of an interme-
diate in the reaction between p y r r o l e (1) and dichlorocarbene. The chemical properties of ( I I ) (II)
are consistent with t h i s hypothesis (see t a b l e ) .
was stable when warmed (80°C) in EtOH or DME, but i t
mainly into 2H-pyrrole (V) and c h l o r o p y r i d i n e ( I I I )
was converted
by the action of acids or
bases in the same c o n d i t i o n s . Three other compounds were present in the reaction mixtures, and they were i d e n t i f i e d as pyrrole ( 1 ) ,
l - f o r m y l - 2 - m e t h y l - 5 - t . b u t y l pyrrole (Vl) and 2-chloro-
- 3 - m e t h y l - 6 - t . b u t y l p y r i d i n e ( V I I ) , on the basis of t h e i r chemical and physical p r o p e r t i e s . The presence of these compounds is a t t r i b u t a b l e to an a l t e r n a t i v e evolution of ( I I )
i n v o l v i n g a s h i f t of the -CCI2HgPh group from carbon to
n i t r o g e n , before the CCI2-Hg bond cleavage. This hypothesis is now under study. Results are summarized in the f o l l o w i n g table"
TABLE A c t i o n * of acids and bases on ( I I ) . Run
Reactant
Products (% GC area)
Sol vent (I)
l 2 3 4 5 6
KOH MeONa TsOH TsOH
EtOH DME EtOH DME EtOH DME
i ,I :
5 _ . lO
(Ill)
(V)
(Vl)
unreacted substrate unreacted substrate 95 lO0 40 40 70 20
(VII)
20 -
*) A l l reactions were carried out in duplicate in a sealed tube at 80°C f o r 18 hrs.
The conversion 2 H - p y r r o l e - e - 3 - c h l o r o p y r i d i n e , which is s i m i l a r to conversion ( I I ) - - - > ( I I I ) reported here, is already known, but involves a carbenoid 2 species . Results of runs l and 2 exclude the p o s s i b i l i t y of a carbene as intermediate, which could be formed through a thermic process. The c y c l i c expansion is the main process under a c i d i c c a t a . ] y s i s in aprotic
solvents (run 6),
chloropyridine ( I l l )
but the formation of 2H-pyrrole(V) in a d d i t i o n to the is observable in a p r o t i c solvent (run 5). This behaviour
p a r a l l e l s previous observations on the reaction between 2 , 5 - d i a l k y l p y r r o l e s
244P
No. 27
and dichlorocarbene 8. I t seems reasonable to assume that protic solvents favour the formation
of 2H-pyrroles, as previously observed6.
A mechanistic pathway on the formation of 3-chloropyridine ( I l l ) -pyrrole (V) from ( I I )
is outlined below"
® -
and 2H-
® >
>
,Bu
Q
N
, flu
/f~7
(It)
>
CCI 2-Hgph
11;Bu
>
2
I;llu I H
------->
> (111)
t Ilu I H
I H
The r e s u l t , that an unique "open" intermediate is able to produce either 2H-pyrrole (V) or 3-chloropyridine ( I l l ) ,
strongly suggests, that, in the reac-
tion between 2,5-dialkylpyrroles and dichlorocarbene, both types of products (expanded and addition) are formed by the same intermediate, as above depicted in the scheme. A more detailed work is in progress. REFERENCES l) H. Wynberg, Chem. Revs., 60, 169 (1960); W. Kirmse, "Carbene Chemistry", p. 396, Second Edition, Academic Press, N.Y., (1971). 2) A. Gambacorta, R. N i c o l e t t i and M.L. Forcellese, Tetrahedron, 27, 985(1971). 3) C.W. Rees and, C.E. Smithen, J. Chem. Soc., 928 (1964). 4) W. Kirmse, loc. c i t . 5) M. Nagazaki, J. Chem. Soc. Japan, 76, I169 (1955); B. Robinson, Tetrahedron - - . . - .
L.,
139 (1962).
6) M.L. Forcellese, A. Gambacorta and R. N i c o l e t t i , A t t i Accad. Naz. Lincei, 53, 569 (1972), C.A. 81-151202r. 7) D. Seyferth, J.Y. - P. Mui, M.E. Gordon and J.M B u r l i t c h , J. Am. Chem. Soc., 8__99, 959 (1967). 8) R.L. Jones and C.W. Rees, J. Chem. Soc. (C), 2255 (1969).
0040-4039/78/0701-2439~02.00/0
TRAPPING AND STRUCTURE DETERMINATION OF AN INTERMEDIATE IN THE REACTION BETWEEN 2-METHYL-5-t. BUTYLPYRROLE AND DICHLOROCARBENE A. Gambacorta* and R. N i c o l e t t i I s t i t u t o di Chimica Organica - Universita di Roma - 00185 Roma - I t a l y S. C e r r i n i , W. Fedeli and E. Gavuzzo Laboratorio di S t r u t t u r i s t i c a Chimica "G. Giacomello", C.N.R., C . P . n . l O , 00016 Monterotondo Stazione, Roma, I t a l y . (Received in UK 30 ~larch 1978; accepted fo~ publication 12 Nay 1978)
2 , 5 - d i a l k y l pyrroles react in protic media with dichlorocarbene generated under basic conditions giving rise to ring expansion products ( 2 , 6 - d i a l k y l - 3 chloropyridines) and addition products ( 2 , 5 - d i a l k y l - 2 - d i c h l o r o m e t h y l - 2 H - p y r l roles or Plancher's pyrrolenines) . The l a t t e r are not intermediates for the 2 ring expansion reaction . 3 4 According to the mechanism generally accepted , these two product types are formed by d i f f e r e n t routes. Pyridines arise from the cycloaddition of d i chlorocarbene to the undissociated pyrrole, while 2H-pyrroles arise from an e l e c t r o p h i l i c attack of the reagent on the conjugate base of the substrate. In this way two d i f f e r e n t intermediates are supposed. The simplest hypothesis that both products were formed from a single intermediate has already been 5 6 suggested and recently reproposed . In order to c o l l e c t new data on this argument, we carried out a reaction between 2 - m e t h y l - 5 - t . b u t y l pyrrole (1) and dichlorocarbene, generated in neutral
and aprotic medium (dimethoxyethane, DME) from PhHgCCI3/Nal system7. Chromatographic separation of the reaction mixture gave - together with
the already-known compounds ( I I I - V ) - a c r y s t a l l i n e product ( I I )
containing
mercury (MP" I08-I09°C from CH3CN). °'
CHCI 2
(iv)
(v)
I r spectrum (in KBr; v max at 3070;3050;2980;2940;1610;1525;1030;1005 and -l 700 cm ) and NMR spectrum (in CCI4; 7.178,5H; 7.388 and 6.498, 2H,AB system, 2439
2440
2"(
No.
J=5 Hz; 1.586,3H, s i n g l e t ; 1.226,9H, s i n g l e t ) suggested for the mercurial the structure of
(II)
[l,l-dichloro-l-(2-methyl-5-t.butyl-2H-pyrril-2-)]phenylmer-
cury. CCI R Mi Ph
(i,)
Well-shaped colourless c r y s t a l s of ( I I )
were obtained by slow evaporation
from a c e t o n i t r i l e at room temperature. Crystal data are" CI6HI9NCI2Hg, M=496.83, monoclinic, a=6.261(2), b=15.400(4), c=17.594(B)A, 8=96.08(2) ° , V=IB86.BA3, -3 Space group P21/c, Z=4, Dc=l.79 gcm , F(000)=944, Mok~(>,=.71069), iJ=96.69 -l cm . The i n t e n s i t y data of 2514 non-zero ( I > 3 o ( I ) )
indipendent r e f l e c t i o n s we-
re collected on an automatic f o u r - c i r c l e d i f f r a c t o m e t e r , using monochromatized Mok~ r a d i a t i o n , 0-20 scan mode, from a c r y s t a l of O.25xO.30xO.30 mm, up to a 0 value of 30 ° . No correction for absorbtion or e x t i n c t i o n was applied. The crystal structure was solved by Patterson and Fourier methods and refined by block-diagonal least squares. The refinement of atomic parameters of a l l
the non-hydrogen atoms, as-
suming anisotropic thermal motion only for Hg and Cl atoms, led to an R=0.062. A final
difference Fourier synthesis showed no s i g n i f i c a n t residual electron
density maxima. Crystallographic evidence such as the analysis of the electron population of the Fourier peaks stereochemical considerations such as valence angles and bond distances allowed us to establish unambiguously the molecular structure of the c r i s t a l l i n e p r o d u c t ( I I ) . The f i g u r e shows the stereochemical features of the molecule in the c r i s t a l l i n e state.
N|
{:I
Ol
No. 27
It
2441
seems l i k e l y that compound ( I I )
arises from the trapping of an interme-
diate in the reaction between p y r r o l e (1) and dichlorocarbene. The chemical properties of ( I I ) (II)
are consistent with t h i s hypothesis (see t a b l e ) .
was stable when warmed (80°C) in EtOH or DME, but i t
mainly into 2H-pyrrole (V) and c h l o r o p y r i d i n e ( I I I )
was converted
by the action of acids or
bases in the same c o n d i t i o n s . Three other compounds were present in the reaction mixtures, and they were i d e n t i f i e d as pyrrole ( 1 ) ,
l - f o r m y l - 2 - m e t h y l - 5 - t . b u t y l pyrrole (Vl) and 2-chloro-
- 3 - m e t h y l - 6 - t . b u t y l p y r i d i n e ( V I I ) , on the basis of t h e i r chemical and physical p r o p e r t i e s . The presence of these compounds is a t t r i b u t a b l e to an a l t e r n a t i v e evolution of ( I I )
i n v o l v i n g a s h i f t of the -CCI2HgPh group from carbon to
n i t r o g e n , before the CCI2-Hg bond cleavage. This hypothesis is now under study. Results are summarized in the f o l l o w i n g table"
TABLE A c t i o n * of acids and bases on ( I I ) . Run
Reactant
Products (% GC area)
Sol vent (I)
l 2 3 4 5 6
KOH MeONa TsOH TsOH
EtOH DME EtOH DME EtOH DME
i ,I :
5 _ . lO
(Ill)
(V)
(Vl)
unreacted substrate unreacted substrate 95 lO0 40 40 70 20
(VII)
20 -
*) A l l reactions were carried out in duplicate in a sealed tube at 80°C f o r 18 hrs.
The conversion 2 H - p y r r o l e - e - 3 - c h l o r o p y r i d i n e , which is s i m i l a r to conversion ( I I ) - - - > ( I I I ) reported here, is already known, but involves a carbenoid 2 species . Results of runs l and 2 exclude the p o s s i b i l i t y of a carbene as intermediate, which could be formed through a thermic process. The c y c l i c expansion is the main process under a c i d i c c a t a . ] y s i s in aprotic
solvents (run 6),
chloropyridine ( I l l )
but the formation of 2H-pyrrole(V) in a d d i t i o n to the is observable in a p r o t i c solvent (run 5). This behaviour
p a r a l l e l s previous observations on the reaction between 2 , 5 - d i a l k y l p y r r o l e s
244P
No. 27
and dichlorocarbene 8. I t seems reasonable to assume that protic solvents favour the formation
of 2H-pyrroles, as previously observed6.
A mechanistic pathway on the formation of 3-chloropyridine ( I l l ) -pyrrole (V) from ( I I )
is outlined below"
® -
and 2H-
® >
>
,Bu
Q
N
, flu
/f~7
(It)
>
CCI 2-Hgph
11;Bu
>
2
I;llu I H
------->
> (111)
t Ilu I H
I H
The r e s u l t , that an unique "open" intermediate is able to produce either 2H-pyrrole (V) or 3-chloropyridine ( I l l ) ,
strongly suggests, that, in the reac-
tion between 2,5-dialkylpyrroles and dichlorocarbene, both types of products (expanded and addition) are formed by the same intermediate, as above depicted in the scheme. A more detailed work is in progress. REFERENCES l) H. Wynberg, Chem. Revs., 60, 169 (1960); W. Kirmse, "Carbene Chemistry", p. 396, Second Edition, Academic Press, N.Y., (1971). 2) A. Gambacorta, R. N i c o l e t t i and M.L. Forcellese, Tetrahedron, 27, 985(1971). 3) C.W. Rees and, C.E. Smithen, J. Chem. Soc., 928 (1964). 4) W. Kirmse, loc. c i t . 5) M. Nagazaki, J. Chem. Soc. Japan, 76, I169 (1955); B. Robinson, Tetrahedron - - . . - .
L.,
139 (1962).
6) M.L. Forcellese, A. Gambacorta and R. N i c o l e t t i , A t t i Accad. Naz. Lincei, 53, 569 (1972), C.A. 81-151202r. 7) D. Seyferth, J.Y. - P. Mui, M.E. Gordon and J.M B u r l i t c h , J. Am. Chem. Soc., 8__99, 959 (1967). 8) R.L. Jones and C.W. Rees, J. Chem. Soc. (C), 2255 (1969).