TMSCl/Fe(NO3)3-catalyzed synthesis of 2-arylbenzothiazoles and 2-arylbenzimidazoles under ultrasonic irradiation

Article abstract of DOI:10.1080/00397911.2010.501470

A convenient one-pot cyclocondensation method for benzothiazole and benzimidazole syntheses is described. A set of benzothiazoles and benzimidazoles were readily prepared from aromatic ortho-diamines or ortho-aminothiophenol and aldehydes using chlorotrim

Full text of DOI:10.1080/00397911.2010.501470

This article was downloaded by: [Fondren Library, Rice University ]
On: 02 August 2012, At: 08:54
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
TMSCl/Fe(NO3)3-Catalyzed Synthesis
of 2-Arylbenzothiazoles and 2-
Arylbenzimidazoles Under Ultrasonic
Irradiation
Yan-Qin Yuan a & Sheng-Rong Guo a
a Department of Chemistry, Lishui University, Lishui, Zhejiang, China
Version of record first published: 20 May 2011
To cite this article: Yan-Qin Yuan & Sheng-Rong Guo (2011): TMSCl/Fe(NO3)3-Catalyzed Synthesis of 2-
Arylbenzothiazoles and 2-Arylbenzimidazoles Under Ultrasonic Irradiation, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:14, 2169-2177
To link to this article: http://dx.doi.org/10.1080/00397911.2010.501470
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 2169–2177, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.501470
TMSCl/Fe(NO3)3-CATALYZED SYNTHESIS OF
2-ARYLBENZOTHIAZOLES AND
2-ARYLBENZIMIDAZOLES UNDER ULTRASONIC
IRRADIATION
Yan-qin Yuan and Sheng-rong Guo
Department of Chemistry, Lishui University, Lishui, Zhejiang, China
GRAPHICAL ABSTRACT
Abstract A convenient one-pot cyclocondensation method for benzothiazole and benzimida-
zole syntheses is described. A set of benzothiazoles and benzimidazoles were readily pre-
pared from aromatic ortho-diamines or ortho-aminothiophenol and aldehydes using
chlorotrimethylsilane in dimethylformamide as promoter and water scavenger under
ultrasonic irradiation in good yields (84–97%).
Keywords 2-Arylbenzimidazole; 2-arylbenzothiazole; Fe(NO3)3; TMSCl; ultrasonic
irradiation
INTRODUCTION
The development of simple, efficient, and environmentally benign chemical
processes or methodologies for widely used organic compounds from readily avail-
able reagents is one of the major challenges for chemists in organic synthesis. 2-Aryl-
benzothiazole derivatives are molecules that possess an interesting variety of
biological activities.[1–3] They are potent and selective antitumor agents that exhibit
nanomolar inhibitory activity against a range of human breast, ovarian, colon, and
renal cell lines in vitro.[4] In addition, 2-arylbenzimidazoles are also very important
intermediates in organic reactions,[5,6] and their derivatives exhibit significant activity
against several viruses such as HIV,[7] herpes (HSV-1),[8] RNA,[9] and influenza.[10]
Many synthetic methods for the syntheses of benzimidazoles and benzothia-
zoles are now available.[11–29] In general, the two kinds of compounds are synthesized
by condensation of 2-aminothiophenol (or 1,2-phenylenediamine) with aryl aldehyde
or carboxylic acid derivatives under different conditions. Despite their tremendous
success, however, some drawbacks still remain. For example, some of the catalysts
Received August 26, 2009.
Address correspondence to Sheng-rong Guo, Department of Chemistry, Lishui University, Lishui,
Zhejiang, China. E-mail: guosr9609@163.com
2169

2170
Y.-Q. YUAN AND S.-R. GUO
Scheme 1. Synthesis of 2-aryl benzothiazoles catalyzed by TMSCl=Fe(NO3)3 under ultrasound irradiation.
are expensive, complex, or not readily available, and organic solvents are always
used. As a consequence, the introduction of new methods and=or further work
on technical improvements to overcome the limitations is still an important
experimental challenge.
Examples of using aldehydes for a range of condensations in the presence of
trimethylsilyl halides as promoter and water scavenger have been recently
reported.[30] Continuing our research on such reactions,[31] we investigated the cyclo-
condensation of aromatic ortho-diamines or ortho-aminothiophenol with aldehydes
in the presence of chlorotrimethylsilane (TMSCl) and Fe(NO3)3. In this communi-
cation, we report a mediated, simple, efficient, and environmentally benign synthesis
of 2-arylbenzothiazole and 2-arylbenzimidazole derivatives using trimethylsilyl
chloride (TMSCl) as promoter and water scavenger and Fe(NO3)3 as catalyst. The
reaction conditions were studied by carrying out the condensation of 4-arylsulfanyl
benzaldehydes and 2-aminothiophenol as the reactants. The desired 2-arylbenzothia-
zole derivatives were obtained with good yield in the presence of TMSCl=Fe(NO3)3
with ultrasonic irradiation in dimethylformamide (DMF) solution at room tempera-
ture. The model reaction with 4-phenylsulfanyl-benzaldehyde (2a) gave the final
product 3a in 93% yield and 99% purity (Scheme 1).
RESULTS AND DISCUSSION
We
performed
a
set
of
preliminary
experiments
on
4-phenylsulfanyl-benzaldehyde (2a) and 2-aminothiophenol in the presence of differ-
ent amounts of TMSCl and Fe(NO3)3 at different reaction temperatures. The results
are depicted in Table 1. The best result was achieved by carrying out the reaction
with 2-aminothiophenol, aldehyde, TMSCl, and Fe(NO3)3 (1:1:4:1) at 60 ꢀC for
30 min under ultrasonic irradiation in DMF or without solvent.
The optimal reaction conditions were found to consist of N,N-
dimethylformamide solution, 30 min at 60 ꢀC under ultrasonic irradiation, and the
presence of 4 equivalents TMSCl and 1 equivalent Fe(NO3)3. To study the generality
of this procedure, the applicability of the TMSCl=Fe(NO3)3 system was then exam-
ined for the reactions of a series of aldehydes with 2-aminothiophenol under the opti-
mized reaction conditions (Table 2). As shown, a variety of substituted aromatic
aldehydes afforded the products in excellent yields and high purities.
In addition, increasing the amount of TMSCl (>5 equiv) did not improve the
product yield a considerable amount; only the presence of 2 equivalents of TMSCl
leads to a mixture of benzimidazoline and benzimidazole. The reaction was carried
out in an unsealed tube under ultrasonic irradiation at 60 ꢀC for 0.5–3 h, and the
iodotrimethylsilane generated in situ from chlorotrimethylsilane and sodium iodide

TMSCl/Fe(NO3)3-CATALYZED SYNTHESIS
2171
Table 1. Effects of increasing amounts of TMSCl and Fe(NO3)3 on the preparation of 2-aryl benzothia-
zoles at different reaction temperatures
Entrya
TMSCl (mmol)
Fe(NO3)3 (mmol)
Temp (ꢀC)
Yield (%)b
1
2
3
4
5
6
7
8
9
2
2
2
3
3
3
4
4
4
0.1
0.2
0.5
0.2
0.5
1
r.t.
r.t.
50
50
60
60
60
60
60
39
42
51
57
74
78
88
97
97
0.5
1
2
aReaction conditions: The reactions were performed with aldehyde (1 mmol) and 2-aminothiophenol
(1 mmol) in DMF for 30 min under ultrasonic irradiation.
bYields refer to pure isolated products.
in DMF solution also gave comparable results. After completing the reaction, the
reaction mixtures were subsequently diluted with 2 to 4 volumes of water, and the
amorphous precipitate that formed was triturated in an ultrasonic bath for 30 min,
providing the target product in high yield. The crude products were isolated by sim-
ple filtration, and the precipitates were washed on the filter with methanol or
acetonitrile to obtain pure products.
To determine whether the ultrasound irradiation was another essential factor
to realize the high conversions of this condensation, the same reaction was carried
Table 2. Results of the TMSCl- and Fe(NO3)3-promoted synthesis of 2-aryl benzothiazoles under ultra-
sound irradiation or without ultrasound irradiation at 60 ꢀC
Yield (%)c [Time (h)]
Product
R
Ia
IIb
Mp. (ꢀC)
3a
3b
3c
3d
3e
3f
H
4-F
97 [0.50]
91 [1.00]
92 [1.50]
92 [1.50]
90 [0.75]
86 [0.50]
96 [0.50]
84 [2.50]
88 [4.0]
82 [5.5]
84 [6.0]
88 [5.0]
82 [6.0]
90 [3.5]
90 [6.0]
78 [7.5]
152–153
99–101
79–81
3-F
2-F
118–119
136–138
112–114
152–154
108–110
4-CH3
4-CH3O
2-CH3, 6-Cl
3-CH3, 4-F
3g
3h
aReaction conditions: The reactions were performed with aldehyde (1 mmol) and 2-aminothiophenol
(1 mmol) in DMF for 30 min under ultrasonic irradiation.
bWithout using ultrasound irradiation.
cYields refer to pure isolated products.

2172
Y.-Q. YUAN AND S.-R. GUO
Scheme 2. Synthesis of 2-aryl benzimidazoles catalyzed by TMSCl=Fe(NO3)3 under ultrasound irradiation.
out in the same conditions without using ultrasound irradiation. When the reaction
mixture was irradiated with ultrasound, almost quantitative conversion was
observed by thin-layer chromatography (TLC). As a result (Table 2), the reaction
time was decreased by about 3–5 h. It is important to note that in the absence of
catalysis and without using ultrasound irradiation, the yield of the reactions
decreased to 4–8%.
We also investigated the effect of different solvents on the reaction rate and as
well as yields of the products (Table 3). In protic solvents such as water or EtOH, the
reaction was very slow and resulted in less product yield. Similar results were
obtained in coordinating solvents such as tetrahydrofuran (THF) and diethyl ether.
On the other hand, conducting the reactions in chlorinated solvents such as dichlor-
omethane and chloroform improved both the reaction rates as well as product yields.
Table 3. Investigation of the effect of various solvents on the synthesis of 2-arylbenzothiazole in the pres-
ence of TMSCl=Fe(NO3)3 at 60 ꢀC
Entrya
Solvent
Time (h)
Yield (%)b
1
2
EtOH
Water
THF
5
45
21
74
85
84
97
92
90
92
87
5
3
2
4
CH2Cl2
CHCl3
DMF
1
5
1.5
1
6
7
DMF-CH2Cl2
Dioxane
MeCN
1.5
1.5
1
8
9
10
DMF-MeCN
1
Table 4. Results of the TMSCl- and Fe(NO3)3-promoted synthesis of 2-arylbenzimidazoles under ultra-
sound irradiation at 60 ꢀC
Product
R
Yield (%)
Time (h)
Mp (ꢀC)
4a
4b
4c
4d
4e
4f
H
4-F
95
93
93
94
94
91
96
89
0.50
1.50
1.50
1.50
2.50
1.50
1.00
2.50
263–264
253–254
238–239
245–247
262–264
249–251
242–244
221–223
3-F
2-F
4-CH3
4-CH3O
2-CH3, 6-Cl
3-CH3, 4-F
4g
4h

TMSCl/Fe(NO3)3-CATALYZED SYNTHESIS
2173
After screening for different solvents, DMF came out as the solvent of choice; It not
only afforded the products in good yield, but the reaction needed only simple
isolation procedures.
1,2-Phenylenediamines also underwent the reaction, under conditions similar
to those used for 2-aminothiophenol, affording the corresponding 2-arylbenzimida-
zoles in excellent yields (Scheme 2, Table 4). Nevertheless, this protocol has its
limitations. Butyraldehyde, an aliphatic aldehyde, only provided 64% yield of the
desired product.
CONCLUSION
This method has been employed for the first time as a mild and efficient reagent
for the one-pot synthesis of benzimidazoles and benzothiazoles in excellent yields
from 1,2-phenylenediamines and 2-aminothiophenol. In addition, low cost, ready
availability of reagents, and simple procedures for conducting the reaction and iso-
lating the products make this methodology a useful contribution to the existing pro-
cedures available for the synthesis of benzimidazole and benzothiazole derivatives.
EXPERIMENTAL
Melting points are uncorrected. The NMR spectra were recorded on a Bruker
AV 300 spectrometer with dimethylsulfoxide (DMSO-d6) as solvent and tetramethyl-
silane (TMS) as internal reference. Chemical shifts are expressed as parts per million
(ppm). Elemental analyses were performed on a Perkin–Elmer-2400 elemental ana-
lyzer. Analytical TLC was performed with silica-gel plates using silica gel GF254.
General Procedure for the Synthesis of Benzothiazoles 3a–h and
Benzimidazoles 4a–h
A mixture of 2-aminothiophenol (1 mmol), aryl aldehyde (1 mmol), TMSCl
(4 mmol), and Fe(NO3)3 ꢁ 9 H2O (1 mmol, 0.4 g) was heated at 60 ꢀC in DMF
(5 mL) under ultrasonic irradiation for the appropriate time as mentioned in
Table 2. After completion of the reaction, the reaction mixture was poured into
ice water (30 mL). The pure solid product was filtered, washed with ice water, and
subsequently dried. An identical procedure was employed using 1,2-phenylenedi-
amine (1 mmol), arylaldehyde (1 mmol) in the presence of TMSCl (4 mmol), and
Fe(NO3)3 ꢁ 9 H2O (1 mmol) for the synthesis of benzothiazoles (Table 4).
Data
Compound 3a. Light yellow solid, mp 152–153 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.89–8.07 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.45–7.49 (m, 3H),
7.27–7.38 (m, 6H); 13C NMR (DMSO, 75 MHz) d: 166.9, 154.0, 141.0, 134.9,
133.2, 132.8, 131.4, 130.4, 129.6, 129.1, 128.5, 127.2, 126.0, 123.3, 122.8. Anal. calcd.
for C19H13NS2: C, 71.44; H, 4.10. Found: C, 71.47; H, 4.12.

2174
Y.-Q. YUAN AND S.-R. GUO
Compound 3b. Light yellow crystal, mp 99–101 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.88–8.06 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.46–7.52 (m, 3H),
7.36–7.40 (t, J ¼ 8.8 Hz, 1H), 7.25–7.29 (t, J ¼ 8.5 Hz, 2H), 7.07–7.13 (t, J ¼ 8.8 Hz,
2H); 13C NMR (DMSO, 75 MHz) d: 166.9, 164.6, 161.3, 154.0, 141.5, 136.4,
134.9, 131.2, 128.9, 128.5, 127.9, 127.2, 126.0, 123.3, 117.8. Anal. calcd. for
C19H12FNS2: C, 67.63; H, 3.58. Found: C, 67.67; H, 3.60.
Compound 3c. Light yellow crystal, mp 79–81 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.89–8.08 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.30–7.42 (m, 5H),
7.09–7.20 (dd, J ¼ 9.0 Hz, 2H), 6.98–7.02 (t, J ¼ 8.4 Hz, 1H); 13C NMR (DMSO,
75 MHz) d: 166.8, 164.5, 161.3, 154.0, 138.9, 136.2, 134.9, 132.2, 132.0, 131.1,
128.7, 128.0, 127.2, 126.1, 123.4, 118.6, 115.7. Anal. calcd. for C19H12FNS2: C,
67.63; H, 3.58. Found: C, 67.62; H, 3.59.
Compound 3d. Light yellow crystal, mp 118–119 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.86–8.06 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.32–7.50 (m, 6H),
7.12–7.17 (t, J ¼ 8.5 Hz, 2H), 13C NMR (DMSO, 75 MHz) d: 166.9, 163.5, 160.2,
154.0, 139.4, 136.0, 134.9, 132.4, 131.5, 129.0, 128.6, 127.2, 126.3, 126.1, 123.3,
119.3, 117.2. Anal. calcd. for C19H12FNS2: C, 67.63; H, 3.58. Found: C, 67.65; H,
3.54.
Compound 3e. Light yellow crystal, mp 136–138 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.87–8.05 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.37–7.50 (m, 4H),
7.20–7.27 (m, 4H), 2.39 (s, 3H); 13C NMR (DMSO, 75 MHz) d: 167.0, 154.0,
142.2, 139.4, 134.9, 134.1, 131.1, 130.9, 128.5, 128.4, 128.3, 127.2, 126.0, 123.2,
122.8, 21.2. Anal. calcd. for C20H15NS2: C, 72.03; H, 4.53. Found: C, 72.05; H, 4.52.
Compound 3f. Light yellow crystal, mp 112–114 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.89–8.08 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.42–7.55 (m, 4H),
7.29–7.41 (m, 4H), 3.24 (s, 3H); 13C NMR (DMSO, 75 MHz) d: 166.8, 159.2,
154.8, 138.9, 132.6, 133.8, 132.9, 131.1, 129.6, 129.5, 128.6, 128.4, 126.2, 123.8,
122.1, 61.6. Anal. calcd. for C20H15NOS2: C, 68.74; H, 4.33. Found: C, 68.75; H,
4.35.
Compound 3g. Light yellow crystal, mp 152–154 ꢀC; 1H NMR (DMSO,
300 MHz) d: 8.08–8.04 (m, 3H), 7.46–7.52 (m, 4H), 7.39–7.43 (m, 4H), 2.28 (s,
3H); 13C NMR (DMSO, 75 MHz) d: 168.1, 153.1, 141.1, 137.4, 135.0, 133.8,
132.9, 131.1, 130.0, 128.3, 127.6, 127.4, 126.5, 125.8, 125.1, 122.7, 122.1, 18.9. Anal.
calcd. for C20H14ClNS2: C, 65.29; H, 3.84. Found: C, 65.31; H, 3.86.
Compound 3h. Light yellow crystal, mp 108–110 ꢀC; 1H NMR (DMSO,
300 MHz) d: 7.86–8.06 (ddd, J ¼ 8.1 Hz, J ¼ 8.4 Hz, 4H), 7.30–7.42 (m, 4H),
6.89–7.02 (m, 3H); 13C NMR (DMSO, 75 MHz) d: 166.8, 161.3, 153.5, 135.0,
133.9, 133.3, 131.8, 131.5, 129.6, 128.7, 127.6, 127.3, 125.8, 125.3, 122.7, 122.1,
116.0, 15.8. Anal. calcd. for C20H14FNS2: C, 68.35; H, 4.02. Found: C, 68.34; H, 4.00.
Compound 4a. Yellow crystal, mp 263–264 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 12.45 (br, 1H), 8.49–8.51 (d, J ¼ 1.8 Hz, 1H), 8.08–8.24 (m, 3H), 7.84–7.88 (d, 1H),
7.43–7.52 (m, 4H), 7.18–7.23 (m, 3H); 13C NMR (DMSO, 75 MHz) d: 152.8, 142.7,

TMSCl/Fe(NO3)3-CATALYZED SYNTHESIS
2175
141.5, 138.7, 135.5, 131.8, 131.6, 131.0, 129.1, 127.6, 127.0, 118.0, 116.3, 110.5. Anal.
calcd. for C19H13N3O2S: C, 65.69; H, 3.77. Found: C, 65.71; H, 3.75.
Compound 4b. Yellow crystal, mp 253–254 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 12.15 (br, 1H), 7.49–7.50 (d, J ¼ 1.7 Hz, 1H), 8.21–8.25 (t, J ¼ 8.4 Hz, 3H),
7.73–7.75 (d, J ¼ 8.8 Hz, 1H), 7.54–7.58 (m, 2H), 7.31–7.37 (m, 4H); 13C NMR
(DMSO, 75 MHz) d: 165.8, 153.6, 144.0, 142.8, 138.9, 125.0, 132.6, 131.5, 131.1,
127.8, 127.5, 116.3, 116.1, 118.6, 110.5. Anal. calcd. for C19H12FN3O2S: C, 62.46;
H, 3.31. Found: C, 62.44; H, 3.35.
Compound 4c. Yellow crystal, mp 238–239 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 11.82 (br, 1H), 8.45–8.46 (d, J ¼ 1.8, 1H), 8.14–8.19 (m, 3H), 7.70–7.72 (d,
J ¼ 8.1 Hz, 1H), 7.38–7.48 (m, 7H); 13C NMR (DMSO, 75 MHz) d: 167.4, 165.1,
162.1, 156.1, 139.2, 136.8, 135.7, 133.3, 132.8, 132.5, 129.6, 128.6, 127.0, 126.2,
123.1, 119.8, 117.8. Anal. calcd. for C19H12FN3O2S: C, 62.46; H, 3.31. Found: C,
62.43; H, 3.27.
Compound 4d. Yellow crystal, mp 245–247 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 12.08 (br, 1H), 8.51–8.52 (d, J ¼ 1.8, 1H), 8.25–8.30 (m, 3H), 7.75–7.78 (d,
J ¼ 8.9 Hz, 1H), 7.52–7.58 (m, 2H), 7.25–7.42 (m, 4H); 13C NMR (DMSO,
75 MHz) d: 168.5, 164.2, 161.4, 156.8, 142.6, 138.3, 136.5, 134.8, 130.1, 129.8,
129.2, 128.1, 126.3, 126.1, 124.5, 118.9, 116.5. Anal. calcd. for C19H12FN3O2S: C,
62.46; H, 3.31. Found: C, 62.48; H, 3.29.
Compound 4e. Yellow crystal, mp 262–264 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 12.65 (br, 1H), 8.41–8.42 (d, J ¼ 1.6 Hz, 1H), 8.18–8.27 (m, 3H), 7.82–7.85 (d,
J ¼ 8.2 Hz, 1H), 7.21–7.39 (m, 6H); C NMR: 165.6, 152.0, 145.7, 138.6, 136.4,
135.8, 132.9, 130.1, 129.7, 129.1, 128.0, 127.9, 127.2, 124.8, 122.5, 20.6. Anal. calcd.
for C20H15N3O2S: C, 66.46; H, 4.18. Found: C, 66.42; H, 4.21.
Compound 4f. Yellow crystal, mp 249–251 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 11.75 (br, 1H), 8.23–8.28 (d, J ¼ 8.4 Hz, 2H), 7.52–7.55 (d, J ¼ 8.1 Hz, 1H),
7.31–7.34 (d, J ¼ 8.4 Hz, 2H), 7.31–7.34 (m, 6H), 3.04 (s, 3H); 13C NMR (DMSO,
75 MHz) d: 164.2, 158.2, 155.2, 141.4, 136.1, 134.2, 133.9, 132.8, 130.9, 130.2,
129.9, 129.6, 125.1, 123.4, 119.4, 59.8. Anal. calcd. for C20H15N3O3S: C, 63.65; H,
4.01. Found: C, 63.68; H, 4.02.
Compound 4g. Yellow crystal, mp 242–244 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 9.86 (br, 1H), 8.31–8.36 (m, 3H), 7.46–7.52 (dd, J ¼ 6.8 Hz, J ¼ 8.6 Hz, 4H),
7.19–7.23 (m, 3H), 2.23 (s, 3H); 13C NMR (DMSO, 75 MHz) d: 169.0, 157.2,
152.7, 143.0, 139.8, 136.4, 135.2, 134.0, 133.9, 133.6, 129.9, 128.9, 128.4, 127.0,
125.7, 125.5, 122.5, 122.0, 19.2. Anal. calcd. for C20H14ClN3O2S: C, 60.68; H,
3.56. Found: C, 60.70; H, 3.52.
Compound 4h. Yellow crystal, mp 221–223 ꢀC; 1H NMR (DMSO, 300 MHz)
d: 12.09 (br, 1H), 8.26–8.29 (d, J ¼ 8.2 Hz, 2H), 7.85–7.89 (s, 1H), 7.56–7.62 (m, 4H),
6.91–7.08 (m, 3H); 13C NMR (DMSO, 75 MHz) d: 172.1, 163.5, 161.6, 152.1, 143.2,
135.2, 134.5, 134.2, 132.6, 132.0, 129.1, 128.4, 124.4, 124.1, 123.5, 122.8, 116.8, 16.3.
Anal. calcd. for C20H14FN3O2S: C, 63.31; H, 3.72. Found: C, 63.35; H, 3.68.

2176
Y.-Q. YUAN AND S.-R. GUO
ACKNOWLEDGMENTS
This work was funded by the Natural Science Foundation of Zhejiang
Province, China (Project Y407240) and Key project of Lishui University.
REFERENCES
1. Xie, Y.; Deng, S.; Chen, Z.; Yan, S.; Landry, D. W. Identification of small-molecule inhi-
bitors of the AB-ABAD interaction. Bioorg. Med. Chem. Lett. 2006, 16, 4657–4660.
2. Hutchinson, I.; Chau, M. S.; Browne, H. L.; Trapani, V. Antitumor benzothiazoles,
part 14: Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)
benzothiazole. J. Med. Chem. 2001, 44, 1446–1455.
3. Hutchinson, I.; Jennings, S. A.; Vishnuvajjala, B. R.; Westwell, A. D.; Stevens, M. F. G.
Antitumor benzothiazole, part 16: Synthesis and pharmaceutical properties of antitumor
2-(4-aminophenyl) benzothiazole amino acid prodrugs. J. Med. Chem. 2002, 45, 744–747.
4. Kashiyama, E.; Hutchinson, I.; Chua, M.-S.; Stinson, S. F.; Phillipes, L. R.; Kaur, G.;
Sausville, E. A.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. Antitumor ben-
zothiazoles, 8: Synthesis, metabolic, and biological properties of the C- and N-oxidation
products of antitumor 2-(4-aminophenyl)-benzothiazoles. J. Med. Chem. 1999, 42,
4172–4184.
5. Kiumars, B.; Mohammad, M. K.; Fardin, N. H2O2=Fe(NO3)3-promoted synthesis of
2-arylbenzimidazoles and 2-arylbenzothiazoles. Synlett. 2009, 4, 569–572.
6. Hasegawa, E.; Yoneoka, A.; Suzuki, K.; Kato, T.; Kitazume, T.; Yangi, K. Reductive
transformation of a,b-epoxy ketones and other compounds promoted through photo-
induced electron transfer processes with 1,3-dimethyl-2-phenylbenzimidazoline (DMPBI).
Tetrahedron 1999, 55, 12957–12968.
7. Ma, H.; Wang, Y.; Wang, J. A simple KHSO4-promoted synthesis of 2-arylsubstituted
benzimidazoles by oxidative condensation of aldehydes with o-phenylenediamine. Hetero-
cycles 2006, 68(8), 1669–1673.
8. Chamberlain, S. D.; Migawa, M. T.; Girardet, J. L. Design, synthesis, and antiviral
activity of alpha-nucleosides: D- and L-isomers of lyxofuranosyl- and (5-deoxylyxofura-
nosyl) benzimidazoles. J. Med. Chem. 1998, 41(8), 1242–1251.
9. Varala, R.; Aayesha, N.; Enugala, R. L-Proline-catalyzed selective synthesis of 2-aryl-1-
arylmethyl-1H-benzimidazoles. Tetrahedron Lett. 2007, 48(1), 69–72.
10. Ma, H.; Han, X.; Wang, Y. A simple and efficient method for synthesis of benzimidazoles
using FeBr3 or Fe(NO3)3-9H2O as catalyst. Heterocycles 2007, 71(8), 1821–1825.
11. Razieh, F.; Hamid, A. A heterogeneous catalyst for efficient and green synthesis of 2-aryl-
benzothiazoles and 2-arylbenzimidazoles. Appl. Catal. A 2009, 353(1), 74–79.
12. Fawzia, A.-Q.; Ramadan, A. M.; Kamal, U. S. Cerium(IV) ammonium nitrate (CAN)
catalyzed one-pot synthesis of 2-arylbenzothiazoles. Molecules 2008, 13, 2908–2914.
13. Hutchinson, I.; Stevens, M. F. G.; Westwell, A. D. The regiospecific synthesis of 5- and
7-monosubstituted and 5,6-disubstituted 2-arylbenzothiazoles. Tetrahedron Lett. 2000,
41, 425–428.
14. Kiyofumi, I.; Hasegawa, C.; Hiroya, K.; Takayuki, D. Palladium-catalyzed synthesis of
2-substituted benzothiazoles via a CꢂH functionalization=intramolecular CꢂS bond
formation process. Org. Lett. 2008, 10(22), 5147–5150.
15. Majo, V. J.; Prabhakaran, J.; Mann, J. J.; Kumar, J. S. D. An efficient palladium-
catalysed synthesis of 2-arylbenzothiazoles. Tetrahedron Lett. 2003, 44, 8535–8537.
16. Chakraborti, A. K.; Selvam, C.; Kaur, G.; Bahagat, S. An efficient synthesis of benzothia-
zoles by direct condensation of carboxylic acids with 2-aminothiophenol under microwave
irradiation. Synlett 2004, 5, 851–855.

TMSCl/Fe(NO3)3-CATALYZED SYNTHESIS
2177
17. Mutsushita, H.; Lee, S. H.; Joung, M.; Clapham, B.; Janda, K. D. Smart cleavage reac-
tions: The synthesis of benzoimidazoles and benzothiazoles from polymer-bound esters.
Tetrahedron Lett. 2004, 45, 313–316.
18. Itoh, T. Nagata, K.; Ishikawa, H.; Ohsawa, A. synthesis of 2-arylbenzothiazoles and imi-
dazoles using scandium triflate as a catalyst for both a ring closing and an oxidation step.
Heterocycles 2004, 63, 2769–2783.
19. Kawashita, Y.; Meba, C.; Hayashi, A. A simple synthesis of 2-arylbenzothiazoles and its
application to palladium-catalyzed Mizoroki–Heck reaction. Tetrahedron Lett. 2006, 47,
4231–4233.
20. Praveen, C.; Kumar, K. H.; Muralidharan, D.; Perumal, P. T. Oxidative cyclization of
thiophenolic Schiff’s bases promoted by PCC: A new oxidant for 2-substituted benzothia-
zoles and benzoxazoles. Tetrahedron 2008, 64, 2369–2374.
21. Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.; Komata, M.; Tomozawa, K.; Chiba,
T. Electrooxidative cyclization of benzylideneaminothiophenols to the corresponding
2-arylbenzothiazoles. Heterocycles 2008, 75, 35–42.
22. Chou, C.-H.; Yu, P.-C.; Wang, B.-C. Synthesis of 2-arylbenzothiazoles from flash vacuum
pyrolysis and photolysis of 2-methylthio-N-(arenylidene) anilines. Tetrahedron Lett. 2008,
49, 4145–4146.
23. Chanada, M.; Arup, D. A green method for the synthesis of 2-arylbenzothiazoles. Hetero-
cycles 2007, 71, 1837–1842.
24. Sharghi, H.; Mohammad, H. B.; Mohammad, M. D. Reusable porphyrinatoiron(III)
complex supported on activated silica as an efficient heterogeneous catalyst for a facile,
one-pot, selective synthesis of 2-arylbenzimidazole derivatives in the presence of atmos-
pheric air as a green oxidant at ambient temperature. Eur. J. Org. Chem. 2008, 4126–4138.
25. Sharghi, H.; Asemani, O. Methanesulfonic acid = SiO2 as an efficient combination for the
synthesis of 2-substituted aromatic and aliphatic benzothiazoles from carboxylic acids.
Synth. Commun. 2009, 39(5), 860–867.
26. Raju, C. B.; Dharma, N. T.; Kumar, J. A. Efficient and inexpensive synthesis of benzimi-
dazoles and quinoxalines. Synth. Commun. 2009, 39(1), 175–188.
27. Gupta, S. D.; Hemendra, P. S.; Moorthy, N. S. Iodine-catalyzed, one-pot, solid-phase
synthesis of benzothiazole derivatives. Synth. Commun. 2007, 37(24), 4327–4329.
28. Bahrami, K.; Mohammad, M. K.; Kavianinia, I. A simple and efficient one-pot synthesis
of 2-substituted benzimidazoles. Synthesis 2007, 4, 547–550.
29. Bahrami, K.; Khodaei, M. M.; Naali, F. Mild and highly efficient method for the syn-
thesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles. J. Org. Chem. 2008, 73(17),
6835–6837.
30. Ryabukhin, B. V.; Plaskon, A. S.; Volochnyuk, D. M.; Andrey, A. T. Synthesis of fused
imidazoles and benzothiazoles from (hetero)aromatic ortho-diamines ortho-aminothio-
phenol, and aldehydes promoted by chlorotrimethylsilane. Synthesis 2006, 21, 3715–3726.
31. Guo, S. R.; Yuan, Y. Q. Convenient one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-
ones using TMSCl as a catalyst with ultrasonic irradiation in DMF. Synth. Commun.
2009, 39, 2205–2220.