1
70
Chemistry Letters Vol.38, No.2 (2009)
Trichloroisocyanuric Acid (TCCA) as a Mild and Efficient Catalyst
for the Synthesis of 2-Arylbenzothiazoles
1
1
1
1
Ã1;2
Ã1
and Hua-Yue Wu
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325027, P. R. China
Hui-Long Xiao, Jiu-Xi Chen, Miao-Chang Liu, Dong-Jian Zhu, Jin-Chang Ding,
1
2
Wenzhou Vocational & Technical College, Wenzhou 325035, P. R. China
(Received November 9, 2008; CL-081089; E-mail: huayuewu@wzu.edu.cn)
The condensation reaction of 2-aminothiophenol with alde-
Table 1. The reaction of 2-aminothiophenol with benzaldehyde
a
hydes catalyzed by 1 mol % trichloroisocyanuric acid (TCCA)
was investigated. As a result, a set of diverse 2-arylbenzothia-
zoles were obtained in good to excellent yields at room temper-
ature.
under different reaction conditions
NH
2
N
S
+
CHO
SH
2
a
Reaction
medium
None
b
Entry TCCA/mol %
Time/h Yield /%
2
-Substituted benzothiazoles is becoming one of the most
important heterocyclic compounds in medicinal chemistry and
1
2
3
None
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
1
2
5
17
45
71
75
43
15
28
82
85
76
79
80
79
86
95
94
95
85
95
27
1
organic synthesis. Recently, Choo and co-workers reported that
2-arylbenzothiazoles exhibited topoisomerase II inhibitory ac-
tivities. One of the most practically and widely used routes
for the synthesis of these compounds is the direct condensation
of the 2-aminothiophenol with aldehydes, carboxylic acids, or its
derivatives in the presence of various promoting agents, such as
None
CH3OH
CH3CN
DMF
2
H O
PEG-400
Toluene
2
4
5
5
5
6
5
7
5
3
4
poly(phosphoric acid) (PPA), poly(phosphate ester), a mixture
5
8
5
of methanesulfonic acid and phosphorous pentoxide, acetic
6
9
5
(C H ) O
2 5 2
7
8
9
acid, FeCl3, Sc(OTf)3, molecular iodine, or ionic liquid un-
10
11
12
13
14
15
16
17
18
19
20
5
5
5
5
5
5
1
2
CH Cl
2
CHCl3
2
1
0
der microwave irradiation. Other general methods include pal-
ladium-catalyzed intramolecular cyclization of o-bromophen-
ylthioureas,11 the Suzuki biaryl coupling of 2-bromobenzothia-
zole with arylboronic acids, coupling of benzothiazoles with
aryl bromides,13 microwave-mediated reaction of 2-aminothio-
2 5
C H OH
EtOAc
THF
1
2
2-CH -THF
3
3
3
3
3
3
1
4
phenol with ꢀ-chlorocinnamaldehydes, the reaction between
2-CH -THF
1
5
thiophenols and aromatic nitriles, and the intramolecular cycli-
zation of thiobenzamides via aryl radical cations as reactive
intermediates.16 Recently, Bahrami and co-workers reported that
2-CH -THF
1
2-CH -THF
1
None
2-CH -THF
1
7
synthesis of 2-arylbenzothiazoles promoted by H2O2/CAN.
2-CH -THF
However, many of these methodologies suffer from one or more
disadvantages such as requirement of excess reagents or cata-
a
Reaction conditions: 2-aminothiophenol (1.1 mmol), benz-
aldehyde (1 mmol), reaction medium (1 mL), rt. Isolated
yield.
b
9,14
8
lysts,
prolonged reaction time, toxic or expensive metallic
compounds17 that result in waste streams. Therefore, the de-
velopment of mild, efficient, inexpensive, and facile methods
for the synthesis of benzothiazoles is necessary part of organic
synthesis.
3–5
C2H5OH, EtOAc, and THF), THF afforded good yield (86%,
Table 1, Entry 14).
2-Methyltetrahydrofuran (MeTHF) can be easily dried with
lower losses and lower recycle costs compared to THF and gives
cleaner phase separations compared to processes that use solvent
exchange of THF with toluene. Unlike THF, MeTHF has limited
solubility in water and this property makes it easier to isolate the
quenched reaction product and recycle dry MeTHF.
Trichloroisocyanuric acid (TCCA), an inexpensive, easily
available reagent, low toxicity and less corrosive, has been
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8
widely used in organic reactions, but it has not been carefully
studied as a catalyst in the synthesis of 2-arylbenzothiazoles
until now.
In continuation of our efforts to develop novel synthetic
routes for the formation of carbon–carbon and carbon–hetero-
atom bond.19 Herein, we report that a new and simple TCCA-
promoted synthesis of 2-arylbenzothiazole by condensation of
aldehydes with 2-aminothiophenol under mild conditions.
The model reaction of 2-aminothiophenol with benzalde-
hyde was conducted to screen the optimal reaction conditions
and the results were listed in Table 1. Initially, the effect of sol-
vents was tested. Among all the solvents screened (CH3OH,
DMF, H2O, PEG-400, toluene (C2H5)2O, CH2Cl2, CHCl3,
MeTHF’s distinct advantages over THF prompted us to fo-
cus on the synthesis of 2a using MeTHF as solvent. As expected,
the excellent yield was obtained in MeTHF in the presence of
TCCA (95%, Table 1, Entry 19). Moreover, we also studied
influence of the amount of TCCA on the reaction yields. One
mol % of TCCA was sufficient, excessive amount of catalyst
did not increase the yield remarkably (Table 1, Entries 15–20).
In light of these results, subsequent studies were carried out
under the following optimized conditions, that is, with 1 mol %
TCCA in 2-methytetrahydrofuran at room temperature.
Copyright Ó 2009 The Chemical Society of Japan