Efficient 2,4,6-trichloro-1,3,5-triazine-catalyzed synthesis of 2-arylbenzothiazoles and bisbenzothiazoles by condensation of 2-aminithiophenol with aldehydes under mild conditions

Article abstract of DOI:10.1002/jhet.462

2,4,6-Trichloro-1,3,5-triazine efficiently catalyzed the condensation reactions between 2-aminothiophenol and aromatic aldehydes to afford 2-arylbenzothiazolles in good-to-excellent yields. Simple and mild reaction conditions, the use of a cheap catalyst

Full text of DOI:10.1002/jhet.462

March 2011
Efficient 2,4,6-Trichloro-1,3,5-triazine-Catalyzed Synthesis of
-Arylbenzothiazoles and Bisbenzothiazoles by Condensation of
449
2
2
-Aminithiophenol with Aldehydes under Mild Conditions
a
a
Behrooz Maleki, * Davood Azarifar, Seyede Fateme Hojati,
b
c
Hojat Veisi, Mostafa Gholizadeh, Hafezeh Salehabadi,
d
a
a
and Mona Khodaverdian Moghadam
a
c
Department of Chemistry, Sabzevar Tarbiat Moallem University, Sabzevar, Iran
b
Department of Chemistry, Bu-Ali Sina University, Hamadan, Iran
Department of Chemistry, Payame Noor University, Songhor, Kermanshah, Iran
d
Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad
1775-1436, Iran
E-mail: maleki@sttu.ac.ir
9
*
Received October 21, 2009
DOI 10.1002/jhet.462
Published online 21 October 2010 in Wiley Online Library (wileyonlinelibrary.com).
2
,4,6-Trichloro-1,3,5-triazine efficiently catalyzed the condensation reactions between 2-aminothio-
phenol and aromatic aldehydes to afford 2-arylbenzothiazolles in good-to-excellent yields. Simple and
mild reaction conditions, the use of a cheap catalyst and easy work up, and isolation are notable fea-
tures of this method.
J. Heterocyclic Chem., 48, 449 (2011).
INTRODUCTION
-Arylbenzothiazoles have been investigated exten-
[17], and direct condensation of 2-aminothiophenol with
aromatic aldehydes under microwave irradiation [18].
2
sively by organic chemists due to their medicinal prop-
erties such as antitumor [1], antiviral, and antimicrobial
drugs [2]. Also, some benzothiazoles have been found
in some organisms [3]. Therefore, there is interest in
developing methods for their synthesis.
RESULTS AND DISCUSSION
In development of benzothiazoles synthetic metho-
dologies [19] and as a part of our research interest
toward the development of efficient and environmentally
benign synthetic methodologies using eco-friendly con-
ditions [20], we report here a facile synthesis of 2-aryl-
benzothiazoles in the presence of oxygen and a catalytic
amount of 2,4,6-trichloro-1,3,5-triazine (TCT, cyanuric
chloride) at room temperature (Scheme 1).
Numerous methods are available for the synthesis of
2
-arylbenzothiazoles and the important ones include the
reaction of o-aminothiophenols with carboxylic acids
4], the potassium ferricyanide cyclization of thioacyl-
[
bezanilides (Jacobson’s method) [5], the palladium-cata-
lyzed reaction of aryl halides with o-aminothiophenol in
the presence of carbon monoxide [6], the ceric ammo-
nium nitrate mediated reaction of thiophenols with aro-
matic nitriles [7], and flash vacuum pyrolysis and pho-
tolysis of 2-methylthio-N-(arenylidene)aniline [8].
On the other hand, the most general synthetic
approaches for synthesis of 2-arylbenzothiazoles involve
condensation of 2-aminothiophenols with aldehydes using
In recent years, 2,4,6-trichloro-1,3,5-triazine (TCT,
cyanuric chloride) has been used in organic synthesis
because it is stable, nonvolatile, inexpensive, commer-
cially available, and easy-to-handle reagent [21].
In the initial exploratory experiments, we optimized
the reaction condition by testing several parameters, such
as different amounts of TCT and different solvents. As a
test case, the reaction of 2-aminothiophenol (1.2 mmol)
with benzaldehyde (1 mmol) was carried out in the pres-
various oxidants such as MnO /SiO2 [9], p-TsOH or
2
graphite on the surface of solid mineral supports under
microwave irradiation [10], I /DMF [11], 1-phenyl-3-
2
methylimidazolium bromide by microwave irradiation
ence of TCT in CH CN to afford the 2-phenylbenzothia-
3
V
R
[
12], activated carbon (Shirasagi KL or Darco KB) under
oxygen atmosphere [13], O or H O in the presence of
zoles (2a). In the experiments carried out to establish the
optimal amount of TCT, the reaction with a 3 mol %
catalyst loading gave 87% yield after 3 h. Increasing the
amount of the catalyst (5, 7, and 10 mol %) did not
2
2 2
Sc(OTf) [14], tungstophosphoric acid impregnates zirco-
3
nium phosphate [15], electrooxidation [16], Dowex 50W
V
C
2010 HeteroCorporation

4
50
B. Maleki, D. Azarifar, S. F. Hojati, H. Veisi, M. Gholizadeh, H. Salehabadi, and M. K. Moghadam Vol 48
Scheme 1
H O, MeOH, CHCl , CH Cl , and EtOH solvents. Simi-
2
3
2
2
larly, by adopting optimized reaction conditions, the var-
ious 2-arylbenzothiazoles were prepared by condensation
of 2-aminothiophenol with aromatic aldehydes (1a–l) in
presence of 3 mol % TCT in CH CN (Table 1).
3
The present conversion did not precede under per-
fectly anhydrous reaction conditions. The proposed
mechanism for the TCT-catalyzed synthesis of 2-aryl-
benzothiazoles may tentatively be visualized to occur
via a tandem sequence of reactions as depicted in
change the isolated yield and the time reaction (3 h).
The solvent effect in this reaction was also studied, and
it was found that CH CN gave the best results among
3
Table 1
The results of the reaction of 2-aminothiophenol with various aldehydes by TCT (3 mol %) in CH
3
CN at room temperature.
a
ꢀ
Entry
1
Aldehyde (1a–l)
2-Arylbenzothiazole (2a–l)
Time (h)
3
Yield (%)
Observed mp ( C)
References
87
111–112
112–114 [17]
2
3
84
103–105
101–103 [17]
3
4
2.5
3.5
80
84
119–120
127–128
120–121 [17]
127–128 [22a]
5
6
4
78
80
82–84
52–54
85 [22a]
4.5
53–54 [22a]
7
8
2.5
3
86
84
132–133
82–83
132 [17]
83–84 [17]
b
9
30
80
80
90
86
157–159
116–118
161–162
179–180
160–161 [17]
115–117 [17]
162–164 [10]
181–182 [17]
1
1
1
0
1
2
2.5
2
3
a
1
13
The yields refer to those of isolated products characterized by spectroscopic (IR, H, C-NMR) data.
Reaction time is min.
b
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2011 Efficient 2,4,6-Trichloro-1,3,5-triazine-Catalyzed Synthesis of 2-Arylbenzothiazoles and
Bisbenzothiazoles by Condensation of 2-Aminithiophenol with Aldehydes under Mild Conditions
451
Scheme 2
(Scheme 2) involving TCT [20e], which reacts with ‘‘in-
generated from TCT as the active catalyst in the reac-
cipient’’ moisture and releases 3 mol of HCl and
cyanuric acid (removable by washing with water) as a
by-product. The in situ generated HCl acts as a protic
acid and activates the carbonyl oxygen to promote the
condensation of 2-aminothiophenol with aldehydes to
form adduct [A], which then undergoes cyclization to
give adduct [B], followed by oxidation with oxygen
tion medium. To confirm our assumption, we replaced
the TCT by 10 mol % of HCl. A test reaction was per-
formed between 4-chlorobenzaldehyde (1 mmol) and 2-
aminothiophenol (1.2 mmol) in the presence of HCl (10
ꢀ
mol %) at 70 C without solvent. It was found that the
generation of 2-(4-chlorophenyl) benzothiazole occurred
in 54% after 5 h. To show the accessibility of the pres-
ent work in comparison with the reported results with
TCT, we summarized some of the results for the prepa-
ration of 2-arylbenzothiazoles using HCl in Table 2.
It is important to mention that, when the reaction of
2-chlorobenzaldehyde (1 mmol) and 2-aminothiophenol
(1.2 mmol) was carried out in the presence of TCT (3
(air) to form 2-arylbenzothiazoles (2a–l).
On the basis of previously reported mechanism for
the synthesis of 2-arylbenzothiazoles in the presence of
various catalytic amounts [9,13,17,18,20a,21a], and
because of our observation in during the synthesis of
2-arylbenzothiazoles using TCT, we assume that HCl is
Table 2
Synthesis of 2-arylbenzothiazoles by HCl (10 mol %).
a
ꢀ
Entry
1
Aldehyde
2-Arylbenzothiazole
Time (h)
Yield (%)
Observed mp ( C)
References
b
5
54
115–116
115–117 [17]
c
2
3
20
52
48
84–86
83–84 [17]
c
15
120–121
120–121 [17]
a
1 13
The yields refer to those of isolated products characterized by spectroscopic (IR, H, C-NMR) data.
b
c
ꢀ
Reaction carried out under solvent-free condition at 70 C.
Reaction carried out in EtOH at room temperature.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

4
52
B. Maleki, D. Azarifar, S. F. Hojati, H. Veisi, M. Gholizadeh, H. Salehabadi, and M. K. Moghadam Vol 48
Scheme 3
mol %) under nitrogen atmosphere (in the absence of
oxygen), the reactions stopped at the 2-(2-chlorophenyl)-
benzothiazoline (mp 75–77 C, lit. 76 C [17]) stage,
which never proceeded to benzothiazoles. The isolated
FT NMR 90 MHz spectrometer in CDCl using TMS as an in-
3
ternal reference. Melting points were determined on a Stuart
SMP3 apparatus and are uncorrected.
Typical experimental procedure for the synthesis of 2-
arylbenzothiazoles by condensation 2-aminothiophenol with
aldehydes using 2,4,6-trichloro-1,3,5-triazine. To a stirred
ꢀ
ꢀ
2
-(2-chlorophenyl)benzothiazoline (1 mmol) reacted
with TCT (3 mol %) in the presence of O2 (air) to
afford the corresponding 2-(2-chlorophenyl)benzothia-
3
solution of 2-aminothiophenol (1.2 mmol) in CH CN (5 mL),
an aldehyde (1a–l, 1 mmol) and 3 mol % TCT were added.
The reaction mixture was stirred at room temperature until the
reaction was complete, as judged by TLC (eluent:hexane-
EtOAc ¼ 5:1) analysis. After completion, the solvent was
evaporated and the residue was washed with water to give the
crude products (2a–l). The residue was then recrystalized from
ꢀ
ꢀ
zole (mp 82–83 C, lit. 81–83 C [10]). This surely
proves that aerial oxygen is not essential for 2-arylben-
zothiazoline [B] formation, though it is absolutely essen-
tial for the oxidation step leading to the formation of
2
-arylbenzothiazoles (Scheme 3).
Having successfully performed the reactions of 2-ami-
(
EtOH, 5 mL) to afford the pure product.
Selected physical and spectroscopic data of isolated the
nothiophenol with a wide range of aldehydes, we
focused our attention on examining the reaction of 2-
aminothiophenol with 1,4-benzenedicarbaldehydes to
ꢀ
products. 2-Phenylbenzothiazole (2a). Mp 111–112 C (lit.
ꢀ
1
1
12–114 C [17]); H-NMR (90 MHz, CDCl
3
): d 7.41–8.08 (m,
): d 77.10 (CDCl ),
121.53, 123.23, 125.09, 126.22, 127.52, 128.91, 130.83,
13
HAAr); C-NMR (22.5 MHz, CDCl
3
3
TCT in CH CN at room temperature (Scheme 4).
3
Finally, we have developed this synthetic method for
the preparation of additional extended bisbenzothiazole
derivatives in a 2:1 molar ratio of 2-aminothiophenol to
133.64, 135.08, 154.19, 167.93; IR (KBr): 3064, 1588, 1555,
1509, 1478, 1433, 1244, 962, 766 cm
ꢁ1
.
2-(4-Methoxyphenyl)benzothiazole (2c). Mp 119–120 C (lit.
ꢀ
ꢀ
1
1
20–121 C [17]); H-NMR (90 MHz, CDCl ): d 3.82 (s, 3H,
3
1,4-benzenedicarbaldehyde with 10 mol % TCT in
CH CN. The reaction proceeded smoothly for 3 h at
13
OMe), 7.00–7.95 (m, 8H, HAAr); C-NMR (22.5 MHz, CDCl3):
d 77.10 (CDCl ), 55.45 (OCH ), 114.43, 121.53, 122.90, 124.81,
3
3
3
room temperature using the present protocol, and the
desired product 2m was obtained in 94% isolated yield,
1
2
26.21, 129.16, 134.91, 154.38, 162,02, 167.85; IR (KBr): 3023,
ꢁ
1
996, 2900, 2836, 1605, 1521, 1485, 1260, 832 cm
2
.
-(4-Methylphenyl)benzothiazole (2e). Mp 84–86 C (lit.
ꢀ
ꢀ
mp 258–260 C (lit. 258 C) [23].
In conclusion, we developed a new application for
ꢀ
ꢀ
1
8
5 C [22a]); H-NMR (90 MHz, CDCl ): d 2.38 (s, 3H, CH ),
3
3
2,4,6-trichloro-1,3,5-triazine. By using this catalyst, a se-
7
1484, 1456, 1434, 1384, 1312, 760 cm
.30–8.01 (m, 8H, HAAr); IR (KBr): 3024, 2905, 1609, 1521,
ꢁ
1
ries of 2-arylbenzothiazoles and bisbenzothiazoles were
obtained in high yields via condensation of 2-aminio-
thiophenol with aldehydes under mild condition. Simple
workup and easy isolation under mild reaction condi-
tions are the best features of the present methodology.
.
2-(4-Cyanophenyl)benzothiazole (2k). Mp 161–162 C (lit.
ꢀ
ꢀ
1
62–164 C [10]); H-NMR (90 MHz, CDCl
1
3
): d 7.37–7.96 (m,
13
HAAr); C-NMR (22.5 MHz, CDCl ): d 77.10 (CDCl ),
3
3
1
1
1
13.93, 118.08, 121.66, 123.68, 125.96, 126.69, 127.68,
32.50, 137.20, 153.88, 165.09; IR (KBr): 3061, 2226, 1606,
ꢁ
1
514, 1479, 1432, 1405, 764 cm
.
ꢀ
2
-(3-Nitrophenyl)benzothiazoles (2l). Mp 179–180 C (lit.
EXPERIMENTAL
ꢀ
81–182 C [17]); H-NMR (90 MHz, CDCl ): d 7.44–8.30 (m,
3
1
1
IR spectra were recorded on a Shimadzu 435-U-04 spectro-
1
photometer (KBr). H-NMR spectra were obtained using JEOL
7H, HAAr), 8.85 (s, 1H); IR (KBr): 3058, 1611, 1576, 1529,
ꢁ1
1459, 1433, 1347, 761 cm
.
Scheme 4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2011 Efficient 2,4,6-Trichloro-1,3,5-triazine-Catalyzed Synthesis of 2-Arylbenzothiazoles and
Bisbenzothiazoles by Condensation of 2-Aminithiophenol with Aldehydes under Mild Conditions
453
Acknowledgments. Financial support of this work by the
Tarbiat Moallem University of Sabzevar, Iran is gratefully
acknowledged.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet