Microwave-assisted preparation of 2-substituted benzothiazoles

Article abstract of DOI:10.1080/10426500590912268

2-Substituted benzothiazoles (3a-h) were prepared from the condensation reaction of 2-aminothiophenol 1 with aldehydes 2 in the presence of P-Ts-OH and graphite on the surface of solid mineral supports without using any oxidizing agent under microwave irr

Full text of DOI:10.1080/10426500590912268

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Phosphorus, Sulfur, and Silicon
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Microwave-Assisted
Preparation of 2-Substituted
Benzothiazoles
Shahnaz Rostamizadeh a & S. A. Gh. Housaini a
a Department of Chemistry, K. N. Toosi University of
Technology, Tehran, Iran
Version of record first published: 16 Aug 2006.
To cite this article: Shahnaz Rostamizadeh & S. A. Gh. Housaini (2005): Microwave-
Assisted Preparation of 2-Substituted Benzothiazoles, Phosphorus, Sulfur, and Silicon
and the Related Elements, 180:5-6, 1321-1326
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Phosphorus, Sulfur, and Silicon, 180:1321–1326, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500590912268
Microwave-Assisted Preparation of 2-Substituted
Benzothiazoles
Shahnaz Rostamizadeh
S. A. Gh. Housaini
Department of Chemistry, K. N. Toosi University of Technology,
Tehran, Iran
2-Substituted benzothiazoles (3a–h) were prepared from the condensation reaction
of 2-aminothiophenol 1 with aldehydes 2 in the presence of P-Ts-OH and graphite
on the surface of solid mineral supports without using any oxidizing agent under
microwave irradiation.
Keywords 2-Aminothiophenol; aldehyde; benzothiazole; microwave irradiation; solid
support
INTRODUCTION
The application of microwave energy in organic synthesis has attracted
a substantial amount of attention in the past few years.1,2 The main
benefits of performing reactions under microwave irradiation are the
significant rate enhancements and the higher product yields. Also,
apart from traditional solution phase chemistry, the use of solid sup-
ports such as clays, zeolites, silica gel, and alumina has gained increased
attention in organic synthesis.3 Furthermore, the most important ad-
vantages of these reagents are the simplification of reaction work-up
and product isolation.
Benzothiazoles have been found to exhibit a wide spectrum of biolog-
ical activities. They have shown antitumor,4−6 antimalarial,7 and fungi-
cide activity.8 They are also an important class of industrial chemicals.
Many kinds of 2-substituted benzothiazoles are utilized as vulcaniza-
tion accelators in the manufacture of rubber,9 as fluorescent brightening
agents in textile dyeing,10 and in the leather industry.11
These compounds have been prepared from the condensation reac-
tion of carboxylic acid, ester, amide, or nitrile with 2-aminothiophenol
Received July 9, 2004; accepted October 5, 2004.
Address correspondence to Shahnaz Rostamizadeh, Department of Chemistry,
K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran. E-mail:
rostamizadeh@hotmail.com
1321

1322
Sh. Rostamizadeh and S. A. Gh. Housaini
in the presence of polyphosphoric acid.12 They have also been pre-
pared from cyclization of thiobenzanilide by potassium ferricyanide
(Jacobson’s method)13 and other reagents.14 Tabakovic and Hoffman
prepared them from benzanalide.15 Formation of 2-aryl benzothiazoles
from the reaction of 2-aminothiophenol with carboxylic acids, aldehydes
in the presence of an oxidant16,17 and orthoesters18 were also reported
in the literature. Recently they have been prepared from oxidative cou-
pling between thiophenols and aromatic nitriles.19
RESULTS AND DISCUSSION
Previously we have reported formation of 2-substituted benzothiazoles
from the reaction of 2-aminothiophenols and S-methylisothioamide
hydroiodides.20 Under similar conditions, the reaction of 2-
aminothiophenol with aldehydes did not give any result. Inspired
by recent work on the Pechman reaction on graphite/montmorillonite
K-10 and pyrolysis of urea supported on graphite, in which the strong
thermal effect of graphite was reported in the literature,21 the mixture
of silica gel and graphite was used as solid support. Formation of
these compounds from aldehydes in the presence of an oxidant such as
nitrobenzene and MnO2 have been reported in the literature.17
In this research, we have prepared 2-substituted benzothiazoles 3a–
h from the reaction of 2-aminothiophenol 1 and aldehydes 2 in the pres-
ence of P-Ts-OH in two different methods without using any oxidant
(Scheme 1, Table I).
SCHEME 1
Method A: The reaction was carried out either on the surface of a
mixture of silica gel and graphite as well as montmorillonite K-10 and
graphite as solid support (Table I).
Method B: The reaction was performed on the surface of silica gel
without mixing it with graphite. To get the thermal effect of graphite,
the whole beaker and the reaction mixture was placed in a TeflonꢀR
vessel filled with graphite (Table II).
The data in Table II correspond to Method A in which the reaction
took place on the surface of both silica gel and montmorillonite together
with graphite. In this method we had difficulty extracting the product
from the fine powder of graphite. To bring about the thermal effect of

2-Substituted Benzothiazoles
1323
TABLE I Condensation of
2-Aminothiophenol 1 with Aldehydes 2
Aldehyde
R
Product
2a
2b
2c
2d
2e
2f
C6H5
3a
3b
3c
3d
3e
3f
4-NO2-C6H4
3-NO2-C6H4
4-Cl-C6H4
3-Cl-C6H4
MeOOC-C6H4
4-CN-C6H4
4-OH-C6H4
2g
2h
3g
3h
graphite, we used another technique in which the reaction mixture and
silica gel were mixed in a beaker, which was then placed in a Teflon,
vessel filled with graphite (Method B). It seems that the increase in
reaction rate, higher yield, and lower power are all because of the higher
temperatures caused by the use of graphite. The cleaner work-up in this
method also has a role in its higher yields. The results are summarized
in Table III.
High yield, short reaction time, and pure products are advantages
of both procedures in comparison to other methods. Easy work-up in
Method B makes the reaction even simpler in respect to Method A. The
data for the synthesis of benzothiazoles under different conditions are
shown in Table II and Table III.
EXPERIMENTAL
All products are known compounds and were characterized by com-
paring their spectral and physical data with those of known samples.
TABLE II Physical Characterization and Conditions for Preparation
of 2-Substituted Benzothiazoles (Method A)
Time (min)
K-10 SiO2
Yield (%)
Power
(watt)
M.p
(◦C)
Lit. M.p
(◦C)
Products
K-10
SiO2
Ref.
3a
3b
3c
3d
3e
3f
10
6
4
12
12
10
6
12
10
4
16
14
10
6
96
90
75
82
97
98
84
84
91
86
69
78
82
98
78
64
150
500
300
150
300
150
150
300
113.2
229.2
182.5
113
96.5
164
111–114
227–231
185
112–116
97–99
166
12
22
24
23
25
23
23
24
3g
3h
162
221
167
226
6
8

1324
Sh. Rostamizadeh and S. A. Gh. Housaini
TABLE III Physical Characterization and Conditions for
Preparation of 2-Substituted Benzothiazoles (Method B)
Products
Yield ( %)
Time (min)
Power (watt)
M.p (◦C)
3a
3b
3c
3d
3e
3f
97
96
93
94.5
98
98
96
92
6
6
4
8
8
6
6
6
150
150
150
150
150
150
150
150
113.2
229.2
182.5
113
96.5
164
3g
3h
162
221
Melting points were taken on an Electrothermal 9100 melting point
apparatus. IR spectra were recorded with a Shimadzu IR-408 spec-
trometer (KBr). The 1H NMR spectra were determined in chloroform-d
and DMSO-d6 solution on a Bruker DRX-500 Avance (500 MHz). Mi-
crowave irradiation was carried out using a commercial microwave
oven, Moulinex AET 5. Merck silica gel 60GF254 was used for ana-
lytical and preparative TLC.
General Procedure for the Synthesis of 2-Substituted
Benzothiazoles (Method A)
p-Toluen sulphonic acid (5 mmol) was added to the mixture of either
silica gel or montmorillonite (3gr), graphite (1gr), 2-aminothiophenol
(2 mmol), and aldehyde (2 mmol), and was well ground in a mortar.
The mixture was then subjected to microwave irradiation in an open
Pyrex beaker at appropriate power and time (Table II). The progress of
the reaction was monitored by TLC. After completion of the reaction,
the mixture was extracted with either ethyl acetate, and in some cases
dichloromethane, or methanol, (150 ml) by using Soxhilet apparatus.
The extracts were then combined and evaporated under vacuo. The re-
sulting oil or solid was washed with ether and crystallized from ethanol
to give the corresponding 2-substituted benzothiazoles.
General Procedure for the Synthesis of 2-Substituted
Benzothiazoles (Method B)
p-Toluen sulphonic acid (5 mmol) was added to the mixture of silica
gel (3gr), 2-aminothiophenol (2 mmol), and aldehyde (2 mmol), and was
well ground in a mortar. The mixture was poured in a Teflon vessel,

2-Substituted Benzothiazoles
1325
placed in a beaker filled with graphite, and then subjected to microwave
irradiation at appropriate power and time (Table III). 2-Substituted
benzothiazoles were obtained in the same way as mentioned in
Method A.
In conclusion the synthesis of a series of 2-substituted benzothiazoles
could be achieved from the reaction of 2-aminothiophenol and aldehydes
on the surface of either silica gel or montmorillonite by using graphite
to provide heat, without using any oxidant. These findings offer further
evidence that the coupling of microwave energy together with the mix-
ture of solid mineral support and graphite will bring a thermal effect
and therefore make the reaction easier.
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