Microwave-induced solvent-free synthesis of 2-arylbenzothiazoles using p-TsOH

Article abstract of DOI:10.1081/SCC-120014964

A simple and efficient procedure has been developed for the synthesis of 2-arylbenzothiazoles by a one-pot reaction of o-aminothiophenol with β-chlorocinnamaldehydes using p-TsOH under microwave irradiation.

Full text of DOI:10.1081/SCC-120014964

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MICROWAVE-INDUCED SOLVENT-FREE SYNTHESIS OF 2-
ARYLBENZOTHIAZOLES USING p-TsOH
a
a
b
Satya Paul , Mukta Gupta & Rajive Gupta
a
Department of Chemistry , University of Jammu , Jammu, 180 006, India
b
Department of Chemistry , University of Jammu , Jammu, 180 006, India
Published online: 16 Aug 2006.
To cite this article: Satya Paul , Mukta Gupta & Rajive Gupta (2002) MICROWAVE-INDUCED SOLVENT-FREE SYNTHESIS OF
-ARYLBENZOTHIAZOLES USING p-TsOH, Synthetic Communications: An International Journal for Rapid Communication of
2
Synthetic Organic Chemistry, 32:23, 3541-3547, DOI: 10.1081/SCC-120014964
To link to this article: http://dx.doi.org/10.1081/SCC-120014964
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 23, pp. 3541–3547, 2002
MICROWAVE-INDUCED
SOLVENT-FREE SYNTHESIS OF
2
-ARYLBENZOTHIAZOLES
USING p-TsOH
Satya Paul, Mukta Gupta, and Rajive Gupta*
Department of Chemistry,
University of Jammu, Jammu-180 006, India
ABSTRACT
A simple and efficient procedure has been developed for the
synthesis of 2-arylbenzothiazoles by a one-pot reaction of
o-aminothiophenol with b-chlorocinnamaldehydes using
p-TsOH under microwave irradiation.
Key Words: 2-Arylbenzothiazoles; p-TsOH; Microwave-
activation; Solvent-free conditions
The synthesis of benzothiazoles and their derivatives has been of con-
siderable interest to organicand medi ci nal ch emists for many years as large
[
1–5]
number of drugs
as optical brightners and dyes.
PBT) is rigid rod polymer with excellent thermal and oxidative stability
contain this heterocyclic nucleus. These have been used
[
6,7]
Poly (p-phenylene benzobisthiazole)
(
and good hydrolytic and chemical resistance.
Numerous methods are available for the synthesis of 2-arylbenzo-
thiazoles. The important ones include: the reaction of o-aminothiophenols
*
Corresponding author. Fax: 91-191-505086; E-mail: rajgupta@sancharnet.in
541
3
DOI: 10.1081/SCC-120014964
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3
542
PAUL, GUPTA, AND GUPTA
[
with benzoic acid or its derivative in polyphosphoric acid (PPA), poly-
8]
[9]
phosphate ester or a mixture of methanesulfonica ic d and phosphorus
[10]
[11]
pentoxide; the action of selenoamides on o-aminothiophenol; reaction
[
of copper(I)thiobenzoate and 2-iodoanilines; by palladium catalyzed con-
12]
densation of arylaldehydes with o-aminothiophenol followed by dehydrative
Most of these protocols, however, suffer from drawbacks,
[13,14]
cyclization.
namely longer reaction periods and the use of corrosive acids, toxic metallic
compounds that result in generation of waste streams.
In the wake of health and economic awareness, it is desirable to device a
[
15]
safe and metal free method with minimum disposable waste. Microwave-
assisted reactions in solvent-free conditions have gained popularity because
[
16]
of rapid reaction rates, cleaner reaction, and ease of manipulation.
need of clean synthesis,
The
and our involvement in the area of solvent-free
[15,17]
[
18]
microwave-assisted reactions, prompted us to search for an efficient and
eco-friendly protocol for the synthesis of 2-arylbenzothiazoles.
[
19]
In 1991, it has been reported
that when o-aminothiophenol is
treated with 2-chloro-1-formyl-2-trifluoromethyl-1-phenylethene, it leads
to the formation of 2-trifluoromethylbenzothiazole along with benzo-
thiazepine, which loses sulphur at room temperature to give quinoline.
However, if trifluoromethyl group is replaced with methyl group, then
exclusively benzothiazepine is formed. Based on this strategy, we have
carried out the reaction of o-aminothiophenol with b-chlorocinnamalde-
hydes without having electron-withdrawing group like trifluoromethyl
group in the presence of p-TsOH under microwave irradiation. It has
been found that 2-arylbenzothiazoles were obtained in moderate to good
yield (Sch. 1).
In order to be able to carry out synthesis of 2-arybenzothiazoles in a
faster and more efficient way, eliminating the use of solvent and reflux
conditions, we investigated the influence of microwave irradiation on a
[
20]
neat mixture of o-aminothiophenol 1 and b-chlorocinnamaldehyde 2 and
p-TsOH. After some experimentation with respect to molar ratios of reagents,
and the irradiation time and power level of microwave set-up, we have
found a set of conditions that generally provides 2-arylbenzothiazoles 3
in moderate to good yields. These conditions employed a 1.25 : 1 ratio
Scheme 1.

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2
-ARYLBENZOTHIAZOLES
3543
Scheme 2.
of o-aminothiophenol 1 and b-chlorocinnamaldehyde 2, using 100 mg of
p-TsOH. 2-Arylbenzothiazoles were purified by passing through column of
silica gel. The minor products may also be formed (TLC, cannot be isolated),
and we have reported only the major product i.e. 2-arylbenzothiazoles.
The proposed mechanism involves initial nucleophilic displacement
of chlorine by sulphur followed by nucleophilic addition of nitrogen to
conjugated C¼C leading to ring closure as shown in Sch. 2.
In order to see whether these conditions work under non-microwave
experiment, reactions under the similar conditions of time and temperature
as in microwave experiment, were carried out in a pre-heated oil-bath. It has
been found that though the reaction did takes place, but the yield was quite
low (Table 1). Further, if the reaction is continued for longer time period,
products obtained are still in lower yields (Table 1), which indicate that effect
of microwave irradiation is not purely thermal and a specific microwave
effect may be involved.
Microwaves interact with polar states and it has been suggested that
microwave effect may be higher in cases where transition state is more polar
than ground state. In the proposed mechanism, the transition state is
more polar and maximum rate enhancement has been observed in case of
2-(4-nitrophenyl) benzothiazole, where transition state (Sch. 3) is expected
to be most polar of all the cases studied (3 g, Á 1.5 min, 38%, 75 min, 68%;
MW 1.5 min, 85%).
In conclusion, the present procedure using p-TsOH provides an effi-
cient one-pot synthesis of 2-arylbenzothiazoles from o-aminothiophenol and
b-chlorocinnamaldehydes. The notable advantages of this procedure are: (a)
operational simplicity; (b) fast reaction; (c) environment friendly; (d) general
applicability accommodating a variety of substitution patterns.

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544
PAUL, GUPTA, AND GUPTA
Table 1. Synthesis of 2-Arylbenzothiazoles (3a–i) (2 mmol) Under Microwave
Irradiation and Pre-heated Oil-Bath Using p-TsOH (100 mg) (Power ¼ 300 W)
MW
Á (Oil-Bath)
Reaction
a
ꢁ
Temp.
ꢁ
Time Yield Time Yield
(%)
M.P. ( C)
Found/Reported
Product
Ar
( C)
(min) (%) (min)
b
[21]
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
4-OMeC
6
H
4
112–114 2.5
110–112 2.5
110–112 2.0
112–114 2.0
118–120 2.0
118–120 1.5
122–124 1.5
120–122 1.5
119–121 1.5
52
58
65
75
74
78
85
77
82
2.5
e
22
45
27
45
33
53
35
58
30
55
27
60
38
68
20
55
28
67
119–21/121.5–22
6
7
6
6
6
6
7
7
7
0
2.5
b
4
d
4-OEtC
6
H
97–98
e
0
2.0
b
5
[23]
6
C H
113/113–114
e
5
2.0
c
4
[21]
4-BrC
4-ClC
4-FC
4-NO
6
H
130–31/132–33
e
5
2.0
c
[21]
6
H
4
119–21/120–21
e
5
1.5
c
[21]
6
H
4
98–99/102.5–103.5
e
5
1.5
c
[22]
g
h
i
2
C
6
H
4
229–30/229–31
146–47/148–49
117–18/118–20
e
5
1.5
b
c
[23]
2,4-(Cl)
3,4-(Cl)
2
C
6
H
H
3
e
0
1.5
[23]
2
C
6
3
e
5
a
Final temperature is measured at the end of exposure during microwave experiment by
immersing glass thermometer in the reaction mixture (approximate temperature range).
b
Purified by column of silica gel using pet. ether: EtOAc (9.5 : 0.5) as eluant.
Purified by column of silica gel using pet. ether: EtOAc (9.8 : 0.2) as eluant.
c
d
À1
1
IR (KBr): 2957, 1577, 1462, 1365, 1262, 1042 cm . H NMR (CDCl
ÀOCH CH ), 4.06–4.13 (q, 2H, ÀOCH CH ), 6.90–7.10 (m, 2H, C
.27–7.55 (m, 2H, C -H and C -H), 7.75–7.90 (d, C
-H and C -H). m/z (%): 255 (97.01%). Elemental analysis: Found C, 70.52; H, 5.04;
N, 5.56. C15 13NOS requires C, 70.58; H, 5.09; N,5.49.
3
): ꢀ 1.37–1.48 (t, 3H,
0
0
2
3
2
3
3
-H and C
0
-H), 8.0–8.21 (d, 2H,
5
-H),
0
2 6
-H and C
7
5
6
C
4
7
H
e
Time which gives maximum yield in an oil-bath, after which no further increase in yield
has been observed, rather decomposition of products takes place.
EXPERIMENTAL
Melting points (uncorrected) were determined by Toshniwal melting
ꢀ
1
point apparatus. IR spectra (ꢀmax in cm ) were recorded on Shimadzu-435
1
spectrophotometer using KBr disc and H NMR spectra in CDCl (chemical
3
shifts in ꢁ, ppm) on Varian EM-390 (90 MHz) or Bruker AM-250 (250 MHz)

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2
-ARYLBENZOTHIAZOLES
3545
Scheme 3.
using TMS as an internal standard. The mass spectra were performed
on Delsi/NERMAG spectral 30 spectrometer. Microwave irradiation was
carried out using a BPL BMO 800T domestic oven having maximum power
output of 800 W.
General Procedure for the Synthesis of 2-Arylbenzothiazoles 3
To a mixture of o-aminothiophenol (2.5 mmol) and b-chlorocinnam-
aldehyde (2 mmol) in a borosil beaker (50 mL), p-TsOH (100 mg) was added
and the reaction mixture was mixed properly with the help of a glass rod.
The paste thus obtained was irradiated in a microwave oven at 300 W for the
appropriate time (Table 1). The reaction was monitored by TLC after every
30 s of irradiation. On cooling, the reaction mixture was extracted with
dichloromethane (3 ꢂ 15 mL) and washed with 5% aq. NaOH and finally
with water (2 ꢂ 20 mL). The extract was dried over anhydrous sodium

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546
PAUL, GUPTA, AND GUPTA
sulfate and on removal of the solvent under gentle vacuum, the residue was
purified by passing through column of silica gel to give 3a–g in 52–85%.
1
The structure of the products were confirmed by IR, H NMR, mass
spectral data, elemental analysis and comparison with authentic samples
prepared according to literature methods.
ACKNOWLEDGMENT
Financial support from UGC, New Delhi and JRF to one of the
authors (MG) is gratefully acknowledged.
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Received in the UK August 16, 2001

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