586 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 586±587$
Rapid Side-chain Chlorination of Heterocyclic
Compounds using Focused Microwave Irradiation$
Mazaahir Kidwai,* Seema Kohli and Parven Kumar
Department of Chemistry, University of Delhi, Delhi-110007, India
Rapid chlorination of side-chain Me groups of substituted quinolines and 2-mercapto-5-methyl 1,3,4-oxadiazole/
thiadiazole is reported using sodium hypochlorite under microwave irradiation.
Presently there is considerable interest in the rapid synthesis
of
a variety of heterocyclic compounds under micro-
wave irradiation in domestic microwave ovens1 owing to
substantial reduction in reaction times. Halogenoarenes are
useful intermediate for industrial as well as laboratory
purposes.2 In continuation of our earlier work on micro-
wave reactions3±6 we report herein sodium hypochlorite as a
selective and cheap reagent for chlorination of side-chain
Me groups of 2-hydroxy-4-methyl-2-chloro-4-methyl- and
2-¯uoro-4-methyl-quinoline, 2-chloro-4-methylquinoline-3-
carbaldehyde and 2-mercapto-5-methyl-1,3,4-oxadiazole/
thiadiazole.
2-Hydroxy-4-methylquinoline was prepared7 by the
cyclisation of acetoacetanilide using sulfuric acid; this on
treatment with PCl5±POCl3 aorded 2-chloro-4-methyl-
quinoline which on reaction with potassium ¯uoride in
acetonitrile as a solvent gave 2-¯uoro-4-methylquinoline.
2-Chloro-4-methylquinoline-3-carbaldehyde and 2-mercapto-
5-methyl-1,3,4-oxadiazole/thiadiazole were prepared accord-
ing to literature methods.8,9
Scheme 1
The chlorination of side-chain Me groups of substi-
tuted quinolines and 2-mercapto-5-methyl-1,3,4-oxadiazole/
thiadiazole has been carried out using microwave irradiation
(Scheme 1). The reaction involves free radical mono-
halogenation10 without aecting other substituents. All the
synthesized compounds except 2b11 are new and are char-
acterised by physical and spectral data. 1H NMR of com-
pounds 1e,f showed a signal at d 13.25 due to SH which
was exchangeable with D2O indicating that the compounds
are not dehydrodimerised at sulfur. Quinoline 1a and its
chlorination product 2a exist in the hydroxy tautomeric
form and a peak at d 5.00 con®rms the presence of OH.
The domestic multimode microwave oven con®nes the
microwaves to the reaction vessel only and excess micro-
waves are absorbed by a dummy load,12 hence leading to
focused microwaves.
Experimental
Physical data for the new compounds are listed in Table 1.
Mps (uncorrected) were recorded on an electrothermal apparatus.
IR (KBr) were recorded on a Model 599 Perkin-Elmer spectro-
photometer and 1H NMR were recorded on a Hitachi R-600 FT
spectrophotometer using SiMe4 as internal standard. Mass spectra
were recorded on a JEOL-JMS-DX 303 mass spectrophotometer.
Spectral data for the new compounds are listed in Table 2. The
purities of the compounds were checked on silica coated A1 plates
(Merck).
General procedure for the chlorination of side-chain methyl groups
of various substituted quinolines and 2-mercapto-5-methyl-1,3,4-
oxadiazole/thiadiazole.ÐTo
chlorite (0.03 mol) in a 100 ml conical ¯ask were added appropriate
substituted quinolines or 2-mercapto-5-methyl-1,3,4-oxadiazole/
thiadiazole (0.01 mol). The reaction mixture was placed under
focused microwaves in an unmodi®ed domestic microwave oven at
a solution of 5±8 ml sodium hypo-
Table 1 Physical data for the new compounds
Elemental analysis [Found (calc.) %]
Compound
Formula
10H8ClNO
C10H7Cl2N
10H7ClFN
% Yield (time/min)
92 (2.0)
C
H
N
Mp
2a
C
62.04
(62.01)
56.63
(56.60)
61.40
(61.38)
54.80
(55.00)
23.94
4.18
(4.13)
3.28
(3.30)
3.54
(3.58)
2.93
(2.91)
2.00
7.26
(7.23)
6.57
(6.60)
7.20
150
2b
2c
2d
2e
2f
93 (2.5)
96 (2.3)
90 (2.5)
95 (1.3)
89 (1.5)
83
60
C
(7.16)
5.81
C11H7Cl2NO
C3H3ClN2SO
C3H3ClN2S2
120
230
220
(5.83)
18.57
(18.60)
16.80
(16.81)
(23.92)
21.60
(21.62)
(1.99)
1.76
(1.80)
2450 MHz. A dummy load of water was also introduced. TLC was
run every 30 s to check the progress of the reaction. Once the reac-
tion was complete the reaction mixture was poured into water. The
solid obtained was ®ltered o, washed with water and dried to give
the product.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Kidwai, Mazaahir
