PTSA catalyzed simple and green synthesis of benzothiazole derivatives in water

Article abstract of DOI:10.1007/s00706-009-0209-4

p-Toluenesulfonic acid (10 mol%) was found to be an effective and efficient catalyst for the synthesis of 2-substituted benzothiazoles from aromatic aldehydes and 2-aminothiophenol in moderate to excellent yields in water. This method provides a simple an

Full text of DOI:10.1007/s00706-009-0209-4

Monatsh Chem (2009) 140:1471–1473
DOI 10.1007/s00706-009-0209-4
ORIGINAL PAPER
PTSA catalyzed simple and green synthesis
of benzothiazole derivatives in water
Najmedin Azizi
Roya Baghi Mohammad Bolourtchian
Mohammad M. Hashemi
•
Alireza Khajeh Amiri
•
•
•
Received: 21 July 2009 / Accepted: 11 October 2009 / Published online: 11 November 2009
Ó Springer-Verlag 2009
Abstract p-Toluenesulfonic acid (10 mol%) was found
to be an effective and efficient catalyst for the synthesis of
using various oxidants [20–27]. However, these method-
ologies suffer from one or more disadvantages, such as
tedious workup, high temperature, prolonged reaction time,
and toxic organic solvents such as DMF and DMSO.
Carrying out organic reactions in water has become
highly desirable in recent years to meet environmental
considerations. The use of water as a sole medium of
organic reactions would greatly contribute to the develop-
ment of environmentally friendly processes. It would be
even more desirable to carry out catalytic organic reactions
in water, which normally require delicate reaction condi-
tions in order for the catalyst to be stable and yet reactive.
In this context, in recent years much attention has been
focused on Lewis acid-catalyzed organic reactions in
water, and several reactions of this type have been already
identified [28–30].
2
2
-substituted benzothiazoles from aromatic aldehydes and
-aminothiophenol in moderate to excellent yields in
water. This method provides a simple and efficient protocol
in terms of mild reaction conditions, clean reaction profiles,
small quantity of catalyst, and simple workup procedure.
Keywords Aldehydes Á Aminothiophenol Á Catalysis Á
Water chemistry Á Green chemistry
Introduction
Benzothiazole derivatives are an important class of
heterocyclic compounds that exhibit a wide range of bio-
logical properties in medicinal and agricultural chemistry
[
1–5]. Further industrial applications as antioxidants [6, 7],
vulcanization accelerators [8, 9], and a dopant in a light-
emitting organic electroluminescent devices [10] have also
been reported.
Results and discussion
As a continuation of our research into developing green
organic chemistry by using water as a reaction medium or
by performing organic transformations under solvent-free
conditions [31, 32], herein we report an efficient and
environmentally benign synthesis of benzothiazole under
mild conditions. Simple mixing of aromatic aldehydes and
o-aminothiophenol was carried out under clean reaction
conditions in the presence of a small amount of PTSA at
70 °C in water. This reduced the amount of waste by
omitting organic solvents. We succeeded in obtaining high
yields of the products with a very simple workup procedure
Many reports have appeared in the literature describing
the formation of benzothiazoles via one of the two major
routes. The most commonly used method involves the
condensation of o-aminothiophenols with substituted
nitriles, aldehydes, carboxylic acids, acyl chlorides, or
esters in the presence of a catalyst such as p-toluenesul-
fonic acid (PTSA) in an organic solvent [11–19]. Another
route is based on oxidative cyclization of thiobenzanilides
N. Azizi (&) Á A. K. Amiri Á R. Baghi Á M. Bolourtchian Á
M. M. Hashemi
Chemistry and Chemical Engineering Research Center of Iran,
P.O. Box 14335-186, Tehran, Iran
e-mail: azizi@ccerci.ac.ir
(
Scheme 1).
The literature survey reveals that there are so far few
papers on synthesizing benzothiazoles under solvent-free
conditions [33, 34] or in water [35–37]. Therefore, we were
123

1
472
N. Azizi et al.
Scheme 1
CHO
Cl
SH
PTSA (0.05 g)
water, 70°C, 1h
S
N
+
Cl
NH2
95%
Catalyst
Pd(OAc)2 NiCl2 Co(OAc)2 CuCl2 FeCl3 ZrCl4 H PW12O40 H PMo O
12 40
Bi(NO3)2
3
3
Yields (%)a
Catalyst
78
80
70
HCl
73
68
60
80
84
82
78
I2 CAN NBS
H SO H PO NaHSO4 NH MoO La O WO3 PTSA
2
4
3
4
4
4
2
3
Yields (%)a 60 80
75
72
78
80
80
88
92
95
a
NMR yields; NBS: N-bromosuccinimide, CAN: ceric ammonium nitrate, PTSA: p-toluenesulfonic acid
particularly interested in the use of simple starting mate-
rials such as aldehydes and o-aminothiophenol, which
are easily available and inexpensive (Table 1). Thus,
o-aminothiophenol was treated with 4-chlorobenzaldehyde
with various catalysts at various temperatures. The results
of this extensive catalyst screening and optimization of
several reaction conditions at room temperature are shown
in Scheme 1. It was found that both the yields and the rates
of the reactions were improved when various acids were
used under these conditions. Furthermore, a slight
improvement in yields was observed when the reaction was
carried out in the presence of a heteropoly acid, such as
H PMo O and H PW O , and metal oxides, such as
Table 1 Synthesis of benzothiazole in water
NH2
ArCHO
+
SH
PTSA
(10 mol%)
o
Water, 70 C
6
0-300 min
S
N
Ar
Entry Aldehydes
Products
Yields (%)a Ref.
1
2
3
4
5
6
7
8
9
X= H
X= Cl
X= Br
X= F
97
95
92
80
85
[32]
[32]
[32]
[32]
[32]
O
3
12 40
3
12 40
H
WO and La O , in water. After a survey of different
3
3
2
N
S
X= CH3
reaction conditions, the reaction was best carried out by
using one equivalent of o-aminothiophenol and one
equivalent of 4-chlorobenzaldehyde in the presence of
X
X= C H 82
X= OMe 70
X= NO2
[34]
2
5
[32]
[32]
82
1
0 mol% PTSA in water for 60 min at 70 °C. The crude
X= OH
74
[31]
X
O
product was isolated after washing with water and ethanol
and afforded the corresponding benzothiazoles in 95%
yield.
1
11
0
X= Cl
X= Br
X= F
X= OMe 80
X= NO2 84
80
82
78
[30]
[30]
[33]
[33]
[32]
H
S
1
2
3
1
N
Encouraged by the remarkable results obtained with these
conditions, to show the generality and scope of this new
protocol, we turned our attention to various aldehydes, and
the results (Table 1) clearly demonstrate that PTSA is an
excellent catalyst in water. Thus, a variety of aromatic
aldehydes, including electron-withdrawing and electron-
donating groups, were tested using the new method in water
in the presence of PTSA. The results are shown in Table 1.
Generally, excellent yields of benzothiazoles were obtained
under the optimized reaction conditions with aromatic
aldehydes. The reaction worked well with a variety of
aldehydes, including those bearing an electron-withdrawing
group as well as heterocyclic aldehydes. Several electron-
rich aromatic aldehydes led to the desired products in
good yields. However, under the same reaction conditions,
aliphatic aldehydes such as isobutyraldehyde and 3-phen-
ylpropionaldehyde did not give the desired products.
In summary, we have described a simple system that is
quite effective and an entirely green procedure for the
14
X
X
O
1
1
1
1
1
5
6
7
8
9
X= Cl
X= OMe 64
78
74
[31]
[31]
[31]
[31]
[31]
S
H
X= Me
N
X= OH 60
X= NO2 72
X
X
CHO
S
N
20
70
[33]
[33]
O
H
S
N
74
2
1
2
S
CHO
CHO
S
N
S
2
8
0
8
[33]
[33]
O
S
O
23
6
N
a NMR yields
1
23

PTSA catalyzed and synthesis of benzothiazole derivatives
1473
synthesis of benzothiazoles in water. Due to the mild
reaction conditions, enhanced reaction rates, clean reaction
profiles, operational and experimental simplicity, and with
options of further transformations of the resulting benzo-
thiazoles into synthetically interesting biologically active
compounds, this synthetic methodology is ideally suited for
automated applications in organic synthesis.
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To a mixture of an aromatic aldehyde (3 mmol) and
3
-aminothiophenol (3 mmol) in 2 cm water, PTSA
1
8. Chang W-C, Hu AT, Duan JP, Rayabarapu DK, Cheng CH
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2
(
10 mol%) was added and the reaction mixture stirred at
19. Rostamizadeh S, Housaini S (2005) Phosphorus Sulfur Silicon
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pure products were isolated by filtration and washing with
hot water and ethanol. In some examples the aqueous
3
mixture was extracted with 10 cm of diethyl ether or ethyl
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was removed under reduced pressure to give the desired
13
1
products. The crude product was analyzed by H and
C
NMR. Further purification was carried out by short column
chromatography on silica gel (hexane/diethyl ether) or
crystallization.
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Acknowledgments Financial support of this work by Chemistry
and Chemical Research Center of Iran is gratefully appreciated.
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