J. CHEM. RESEARCH (S), 1999 245
�
1
Table 1 AM1 calculated heat of formation in kcalmol for the
species given in Fig. 1.
Our experimental observations reveal that the Vilsmeier
reaction on 9-methylcarbazole results in 3-formyl-9-
methylcarbazole as well as 3,6-diformyl-9-methylcarbazole.
It is quite expected that the mechanism of formation of
the diformyl derivative is similar to that for the monoformyl
derivative. As the diformyl derivative is formed along with
monoformyl derivative it is logical that another nucleophilic
attack at the 6-position of intermediate 4 occurs before
hydrolysis of the group at 3-position takes place.
Configuration
1
TS-I
2
3
TS-II
4
0
3
3
R; 3 S
97.0
97.0
104.6 94.8
104.6 94.5
98.2
98.4
110.7 60.7
110.9 60.7
0
S; 3 S
Cl
Cl
P
Experimental
O
O
3,6-Diformyl-9-methylcarbazole.öA mixture of 3.6 g (0.02 mol) of
9-methylcarbazole (prepared by shaking carbazole with dimethyl
sulfate and conc. potassium hydroxide solution in acetone medium)6
3.7 ml (0.04 mol) of phosphorus oxychloride, 4.9 ml (0.04 mol) of
N-methylformanilide and 20 ml ofo-dichlorobenzene was boiled under
re£ux for 6 h. The solution was then cooled and a viscous mass was
obtained. To this mass was added a 30% sodium acetate solution
and the solvent, o-dichlorobenzene, was removed from the mixture
by steam distillation. The resulting gummy mass, after washing with
water, was dissolved in glacial acetic acid. The whole solution was then
poured into water and extracted with di-ethyl ether. The ether layer,
on evaporation, furnished white crystals of 3,6-diformyl-9-methyl
carbazole. This product was puri¢ed by crystallization from methanol
•
•
•
H C
3
CH3
H
H
+
N
Fig. 2 Antiperiplanar arrangement of the leaving groups and lone
pair of nitrogen in Æap conformation (along the 3 C ! 3 N bond)
0
0
�
1
of TS-II
(m.p. 230 8C, yield 10%). nmax/cm
(KBr) 1675, 1620, 1590; dH
(
1
90 MHz, CDCl3) 3.77 (3 H, s, N-CH3), 7.17 (2 H, d, J 7:5 Hz,
-H, 8-H), 7.74 (2 H, d, J 7:5 Hz, 2-H, 7-H), 8.25 (2 H, s, 4-H,
-H), 9.73 (2 H, s, ±CHO).
5
3
-Formyl-9-methylcarbazole.öThe mother liquor, after separation
0
0
staggered conformations along the 3 C^3 N bond in TS-II
owing to the orientation of the N,N-dimethyl group) only
of the 3,6-diformylcarbazole crystals, was evaporated to dryness
and the resulting gummy mass was chromatographed over silica gel.
On elution with a mixture of light petroleum (60^80 8C) and benzene
1:1) a yellow mass of 3-formyl-9-methycarbazole was obtained
m.p. 74 8C, yield 20%), and its structure was con®rmed by
(
Æ ap results in a true saddle point (Fig. 2), which is capable
of forming the product by a concerted syn elimination pro-
cess (as indicated by the mode of vibration corresponding
to the negative force constant in the transition structure).
It is interesting to note that in this conformation the per-
(
(
2
comparison of its properties with literature data.
Thanks are due to Dr D. N. Chowdhury, Reader in
Chemistry, Visva-Bharati, Santiniketan, and Dr D.
Bhattacharyya, Reader, Biophysics Division, Saha Institute
of Nuclear Physics (SINP), Belgachia, Calcutta, for their
kind help. GKD is thankful to CSIR, New Delhi for the
award of a Research Associate.
0
iplanarity of the lone pair of the adjacent atom (3 N) is main-
tained along with the periplanar orientation of the two
leaving groups (phosphoryl and hydrogen). The other two
conformations, sc and � sc of TS-II are not able to form
the product by a concerted process due to the lack of per-
iplanarity of the lone pair, though the conformation in
�
sc su¡ers less steric strain. Owing to the presence of
Received, 8th September 1998; Accepted, 2nd December 1998
Paper E/8/07020B
0
two chiral carbon, 3C and 3 C, in this transition state,
the Æ ap conformation may exist in two diastereomeric
forms. H.O.F (Table 1) reveals that both these diastereomers
are equally favourable. Reactant 3 and product 4 correspond-
ing to TS-II were obtained by running IRC calculation.
From Table 1 it is evident that the H.O.F. of the second step
References
1
D. P. Chakraborty, in The Alkaloids, ed. G. A. Cordell, Aca-
demic Press, New York, 1993, vol. 44, p. 257.
�
1
1
2
3
N. P. Buu-Hoi and N. Hoan, J. Am. Chem. Soc., 1951, 73, 98.
¨
M. J. S. Dewar, E. G. Zoebisch, E. F. Healy and J. J. P.
Stewart, J. Am. Chem. Soc., 1985, 107, 3902.
(
12.5 kcal mol ) is much higher than that of the ¢rst step
�
(7.6 kcal mol ). This suggests that the elimination step is
the rate-determining step. As this step involves the transfer
of a proton (Fig. 1), a primary kinetic isotope e¡ect is
expected for this reaction.
The observation of the assistance of the lone pair of an
adjacent atom in the elimination step may help a chemist
to develop a synthetic route where an elimination process
may be assisted by the antiperiplanar arrangement of the
electron pair of an adjacent group that is not directly involved
in the elimination step. This may help to reduce the activation
energy required for the elimination step.
4
5
J. J. P. Stewart, J. Comput. Aided Mol. Design, 1990, 4, 1.
For example, see D. Reid, R. Webster and S. Mckenzie, J.
Chem. Soc., Perkin Trans. 1, 1979, 2334; C. P. Traas, H. J.
Takken and H. Boelens, Tetrahedron Lett., 1977, 18, 2129;
E. M. Becalli, A. Marchesini and H. Molinari, Tetrahedron
Lett., 1986, 27, 627; G. F. Smith, J. Chem. Soc., 1954, 3842;
T. Shono, Y. Matsumura, K. Tsubata and Y. Sugihara,
Tetrahedron Lett., 1975, 16, 3391.
6
R. Livingstone, in Rodd's Chemistry of Carbon Compounds, ed.
S. Co¡ey, Elsevier, Amsterdam, 2nd edn., 1973, vol.
(Part A), p. 486.
4