Highly chemoselective synthesis of benzimidazoles in Sc(OTf)3-catalyzed system

Article abstract of DOI:10.3987/COM-15-13326

The present researches elicit a simple, green and efficient method for the synthesis of substituted benzimidazoles through the coupling of o-phenylenediames with aldehydes catalyzed by Sc(OTf)₃ in ethanol, which obtains high chemoselectivity and excellent yield of many biologically active 1,2-disubstitued and 2-substituted benzimidazoles respectively and are also environment friendly.

Full text of DOI:10.3987/COM-15-13326

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HETEROCYCLES, Vol. 91, No. 12, 2015
HETEROCYCLES, Vol. 91, No. 12, 2015, pp. 2306 - 2314. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 17th September, 2015, Accepted, 2nd November, 2015, Published online, 25th November, 2015
DOI: 10.3987/COM-15-13326
HIGHLY CHEMOSELECTIVE SYNTHESIS OF BENZIMIDAZOLES IN
SC(OTF)3-CATALYZED SYSTEM
Liyan Fan,* Lulu Kong, and Wen Chen
Department of chemistry, Tongji University, 1239 Siping Road, Shanghai,
200092, China; E-mail: fanly@tongji.edu.cn
Abstract – The present researches elicit a simple, green and efficient method for
the synthesis of substituted benzimidazoles through the coupling of
o-phenylenediames with aldehydes catalyzed by Sc(OTf)3 in ethanol, which
obtains high chemoselectivity and excellent yield of many biologically active
1,2-disubstitued and 2-substituted benzimidazoles respectively and are also
environment friendly.
INTRODUCTION
Nitrogen-containing heterocyclic compounds have attracted considerable attention1 owing to their
potential involvement as key component for various pharmacological activities.2 Among the various
heteroaromatic compounds, benzimidazoles exhibit antiviral, antiseptic, antihypertensive and anticancer
properties.3 They are important intermediates in many pharmaceutical synthesis cases, such as drugs for
the treatment of obesity4 and hypertension.5
Diverse synthetic methodologies available for the synthesis of benzimidazoles have been developed,6ꢀ
with the most common method involving the treatment of o-phenylenediamines with either carboxylic
acids7 or their derivatives (nitriles,8 aldehydes9 or alcohols10) catalyzed by Lewis acids,11 ionic liquids,12
nanosized material13 and Zeolite.14 Although the reaction was efficiently promoted by the above
conditions, some of these methods suffer from some degree of disadvantages. One of the major limitation
to benzimidazoles is that some show poor selectivity, which results in the formation of two compounds
(the mixture of 2-substituted and 1,2-disubstituted benzimidazoles).15 In view of this drawback, Sasaki
and his group attempted the use of Co(OH)2 and CoO16 as catalyst to form 1,2-disubstitued
17
benzimidazoles. In 2013, Boroujeni developed PS-PyCl-xACl3 a heterogeneous catalyst to obtain
relatively high chemoselective 2-substitued benzimidazoles. To a certain extent, these methodologies
have made significant improvement in the formation of benzimidazoles with good chemoselectivity. At
present, a better reaction system to gain different substituted benzimidazoles with high chemoselectivity

HETEROCYCLES, Vol. 91, No. 12, 2015
2307
respectively in mild reaction conditions has not yet founded.
Herein, we report the Sc(OTf)3-catalyzed condensation of o-phenylenediamine with aldehydes in EtOH,
furnishing a practicable approaches for the formation of 1,2-disubstitued benzimidazoles with high
chemoselectivity and excellent yields in the presence of H2O2. Furthermore, the absence of H2O2 obtained
high reaction selectivity and productivity for the synthesis of 2-substitued benzimidazoles (Scheme 1).
R1
R1
NH2
NH2
R1
N
N
Sc(OTf)3
EtOH
N
Sc(OTf)3
R2
R2
R2 CHO
R2
+
H2O2, EtOH
N
H
3a-3j
up to 96%
4a-4k
up to 96%
Scheme 1. The process to 1,2-sustituted and 2-substituted benzimidazoles
RESULTS AND DISCUSSION
Reactions were started by examing the reaction of benzaldehyde (2 mmol) and 1, 2-phenylenediamines
(1.2 mmol) as model reaction. As is shown in Table 1, the use of Sc(OTf)3 allowed the direct conversion
of mixture into corresponding 1,2-disubstituted benzimidazole in a yield of 95% in EtOH (Table 1, Entry
1). Conversely, the use of other rare earth catalyst did not obviously enhance yields (Table 1, Entry 2-4).
Table 1. Catalyst-screen for the synthesis of 3aa
Entry
Catalyst (10 mol %)
none
Sc(OTf)3
ScCl3
Y(OTf)3
YCl3
Yieldb (%)
1
2
3
4
5
22
95
86
79
78
a 1, 2-phenylenediamine (1a, 1.2 mmol.), benzaldehyde (2a, 2.0 mmol.), Sc(OTf)3 (0.2 mmol.), 80 oC in
EtOH, reflux. b Isolated yield
To generalize the reagent system, the applicability of Sc(OTf)3-catalyzed system was then examined for
the reactions of series of aromatic aldehydes with 1,2-phenylenediamines under the optimized reaction
conditions (Table 2). As shown, a variety of benzaldehydes bearing electron-donating (Table 1, Entries 3,
4) or electron-withdrawing (Table 1, Entries 2, 5) were successfully employed to the corresponding
benzimidazole derivatives in good yields. And the formation of the corresponding benzimidazoles could
be realized with other diamines under the same conditions (Table 2, Entries 6–10).
Table 2. Sc(OTf)3-catalyzed synthesis of 1,2- benzimidazole 3a

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HETEROCYCLES, Vol. 91, No. 12, 2015
Entry
R1
R2
Product
Yieldb(%)
1
2
3
4
5
6
7
8
H 1a
H 1a
H 1a
H 1a
Ph 2a
90
92
95
93
96
84
91
88
85
88
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-ClC6H4 2b
4-MeOC6H4 2c
4-MeC6H4 2d
4-FC6H4 2e
Ph 2a
4-ClC6H4 2b
4-MeOC6H4 2c
4-MeC6H4 2d
4-FC6H4 2e
H 1a
NO2 1b
NO2 1b
NO2 1b
NO2 1b
NO2 1b
9
10
3j
a 1, 2-phenylenediamines (1a-1b, 1.2 mmol.), benzaldehydes (2a-2e, 2.0 mmol.), Sc(OTf)3 (0.2 mmol.),
80 oC in EtOH, reflux. b Isolated yield
Furthermore, the scope of this system has been successfully extended to the synthesis of 2-substituted
benzimidazoles, which represents the first synthesis of these compounds through adding the
oxidant.18During the research, we found that Sc(OTf)3 could catalyze the synthesis of 2-substituted
benzimidazoles in presence of H2O2 (Table 3, Entry 2). However, the yield was not satisfactory. The
direct reflux condensing of o-pheylenediamines and aldehydes was a competitive formation of the 1,
2-disubstituted and the 2-substituted benzimidazoles. So we change the reaction process, diluting the
aldehydes into EtOH and dropping them into the reaction mixture, the yield was improved. This reaction
also proceeded smoothly with morpholine, AATEMPO-BF4 and PhI(OAc)2, but with relatively lower
yields. With decreasing amounts of H2O2, the yield decreased.
Table 3. Effect of additives in the formation of 4aa
Entry
Oxidant (200 mol %)
none
H2O2
Yieldb (%)
Trace
60c
88
71
80
1
2
3
4
5
6
7
H2O2
H2O2 (100 mol%)
PhI(OAc)2
-
AATMPO·BF4
41
70
morpholine
a 1, 2-phenylenediamine (1a, 1.2 mmol), benzaldehyde (2b, 1.0 mmol.), Sc(OTf)3 (0.15 mmol.), H2O2
o
b
(2mmol.) was added into the mixture dropwise, 80 C in EtOH, reflux. Isolated yield.c benzaldehyde
was added into the mixture in one batch.
Aromatic aldehydes with electron-donating and electron-withdrawing groups both participated in this

HETEROCYCLES, Vol. 91, No. 12, 2015
2309
reaction equally well- apparently, the nature of substitution on the aryl ring does not make much
difference (Table 4, Entry 2-5). This procedure is also applicable to substituted 1, 2-phenylendiamines,
which produce the corresponding 2-arylbenzimidazoles smoothly in excellent yields (Table 4, Entry 6-10).
It is worthy to notice that the catalyst is also found to be active in the synthesis of benzidazoles using
furfuraldehyde (4k). And it is the main component of Fuberidazoles.19 Two reasonable mechanisms for
the condensation reaction of 1, 2-phenylenediamine and aldehydes are shown in Scheme 2.
Table 4. Sc(OTf)3-catalyzed synthesis of 2- benzimidazole 4a
Yieldb
Entry
R1
R2
Product
(%)
90
92
95
93
96
84
91
88
85
88
70
1
2
3
4
5
6
7
8
H 1a
H 1a
H 1a
H 1a
Ph 2a
4a
4b
4c
4d
4e
4f
4g
4h
4i
4-ClC6H4 2b
4-MeOC6H4 2c
4-MeC6H4 2d
4-FC6H4 2e
Ph 2a
4-ClC6H4 2b
4-MeOC6H4 2c
4-MeC6H4 2d
4-FC6H4 2e
2-Furyl 2f
H 1a
NO2 1b
NO2 1b
NO2 1b
NO2 1b
NO2 1b
H 1a
9
10
11
4j
4k
a
1, 2-phenylenediamine (1a-1b, 1.2 mmol.), benzaldehyde (2a-2f, 1.0 mmol.), Sc(OTf)3 (0.15 mmol.),
H2O2 (2 mmol.), 80 oC in EtOH, reflux. b Isolated yield
Sc3+
Sc3+
R1
R1
R1
R1
N
N
R2
R2
Sc3+
N
N
N
N
N
-Sc3+
R2
R2
H
N
3
5
4
2
R2
R2
R2
R2
O
R2
H
H
R1
NH2
NH2
1
O
R2
H
R1
NH2
N
H
N
R1
R1
N
H2O2
R2
R2
oxidation
Sc3+
R2
N
N
H
7
9
8
Scheme 2. Proposed mechanism for the synthesis of 1,2-sustituted and 2-substituted benzimidazoles
catalyzed by Sc(OTf)3

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EXPERIMENTAL
1H and 13C NMR spectrums were recored on Bruker ARX 400 for proton. For 13C NMR, chemical shifts
were reported in the scale relative to the solvent of CDCl3 (δ: 77.36 ppm), DMSO-d6 (δ: 40.45) and
1
(CD3)2CO (δ: 30.60, 205.87) used as an internal reference. And H NMR were reported downfield from
CDCl3 (δ: 7.27 ppm), DMSO-d6 (δ: 2.49), and (CD3)2CO (δ: 2.09) Column chromatographies were
performed with silica gel (200-300 mesh ASTM).
Starting Materials. All chemicals used in this study were commmercially available.
Typical experimental procedure of the preparation of products 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, and
3j.
1-Benzyl-2-phenyl-1H-benzo(d)imidazole (3a): A mixture of Sc(OTf)3 (98.4 mg, 0.2 mmol) and EtOH
(5 mL) were well stirred until the solid dissolved completely at reflux condition; then
o-phenylenediamine 1a (129.8 mg, 1.2 mmol) and benzaldehyde 2a (202 μL, 2.0 mmol) was added into
the above mixture. The reaction was monitored by TLC. The reaction mixture was cooled to rt, and then
evaporated in vacuum. The product purified by column chromatography (PE-EtOAc= 5:1) to give 3a
(269.6 mg, 95%); Light yellow solid; mp 131-133 °С. 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8 Hz, 1
H), 7.48-7.45 (m, 3 H), 7.34-7.30 (m, 4 H), 7.25-7.21 (m, 2 H), 7.11 (d, J = 7.2 Hz, 2 H), 5.47 (s, 2 H);
13C NMR (100 MHz, CDCl3) δ 154.22, 143.23, 136.44, 136.11, 130.12, 129.97, 129.30, 129.11, 128.81,
127.83, 126.01, 123.10, 122.74, 120.03, 110.61, 48.41.
1-(4-Chlorobenzyl)-2-(4-chlorophenyl)-1H-benzo(d)imidazole (3b): a light yellow solid (324.2 mg,
1
95%); mp 136-138 °С. H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8 Hz, 1 H), 7.60-7.58 (m, 2 H),
7.45-7.43 (m, 2 H), 7.36-7.27 (m, 4 H), 7.20 (d, J = 8 Hz, 1 H), 7.02 (d, J = 8.4 Hz, 2 H), 5.40 (s, 2 H);
13C NMR (100 MHz, CDCl3) δ 152.90, 143.14, 136.36, 135.96, 134.68, 133.87, 130.47, 129.41, 129.12,
128.41, 127.29, 123.50, 123.07, 120.22, 110.34, 47.82.
1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzo(d)imidazole (3c)˖˖a yellow solid (326.9 mg,
1
95%); mp 126-128 °С. H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8 Hz, 1 H), 7.65-7.63 (m, 2 H),
7.31-7.27 (m, 1 H), 7.24-7.21 (m, 2 H), 7.03 (d, J = 8.8 Hz, 2 H), 7.00-6.96 (m, 2 H), 6.86-6.84 (m, 2 H),
5.38 (s, 2 H), 3.85 (s, 3 H), 3.70(s, 3 H); 13C NMR (100 MHz, CDCl3) δ 160.90, 159.12, 154.14, 143.22,
136.13, 130.72, 128.51, 127.23, 122.74, 122.53, 122.49, 119.74, 114.44, 114.20, 110.45, 55.40, 55.32,
47.90.
1-(4-Methylbenzyl)-2-p-tolyl-1H-benzo(d)imidazole (3d): a yellow solid (290.3 mg, 93%); mp
128-130 °С. 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J=8 Hz, 1 H), 7.59 (d, J = 8 Hz, 2 H), 7.31-7.27 (m, 1
H), 7.25-7.24 (m, 2 H), 7.21-7.16 (m, 2 H), 7.13(d, J = 8 Hz, 2 H), 6.99 (d, J = 8 Hz, 2 H), 5.40 (s, 1 H),

HETEROCYCLES, Vol. 91, No. 12, 2015
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2.40 (s, 3 H), 2.33 (s, 3 H); 13C NMR (100 MHz, CDCl3, 25 °С, TMS) δ 154.38, 143.22, 140.05, 137.46,
136.14, 133.50, 129.73, 129.48, 129.19, 127.22, 125.93, 122.86, 122.58, 119.85 (s), 110.55 (s), 48.22,
21.48, 21.14.
1-(4-Fluorobenzyl)-2-(4-fluorophenyl)-1H-benzo(d)imidazole (3e): a yellow solid (307.1 mg, 96%);
1
mp 110-112 °С. H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 7.6 Hz, 1 H), 7.66-7.63 (m, 2 H), 7.34-7.28
(m, 2 H), 7.24-7.20 (m, 1 H), 7.17-7.13 (m, 2 H), 7.07-6.99 (m, 4 H), 5.40 (s, 2 H); 13C NMR (100 MHz,
CDCl3) δ 162.54, 161.08, 153.11, 143.07, 135.90, 131.95, 131.24, 127.64, 126.17, 123.33, 122.96, 120.11,
116.22 116.01 , 110.36, 47.74.
1-Benzyl-5-nitro-2-phenyl-1H-benzo(d)imidazole (3f): a yellow solid (277.4 mg, 84%); mp 163-169 °С.
1H NMR (400 MHz, CDCl3): δ 8.25 (dd, J = 8.8 Hz, J = 2.0 Hz, 1 H), 8.18 (d, J = 2 Hz, 2 H), 7.90 (d, J =
8.8 Hz, 1 H), 7.73-7.70 (m, 2 H), 7.55-7.48 (m, 3 H), 7.39-7.32 (m, 3 H), 7.10-7.07 (m, 2 H), 5.55 (s, 2 H);
13C NMR (100 MHz, CDCl3,): δ = 158.87, 147.65, 143.70, 135.45, 135.19, 130.94, 129.42, 129.36,
129.30, 129.09, 125.88, 120.03, 118.73, 107.47, 48.84.
1-(4-Chlorobenzyl)-2-(4-chlorophenyl)-5-nitro-1H-benzo(d)imidazole (3g): a yellow solid (362.4
mg,91%); mp 144-149 °С. 1H NMR (400 MHz, CDCl3) δ 8.27 (dd, J = 9.0 Hz, J = 2 Hz, 1 H), 8.17 (d, J =
1.6 Hz, 2 H), 7.65-7.60 (m, 2 H), 7.51-7.49 (m ,2 H), 7.37-7.34 (m, 2 H), 7.01 (d, J = 8.4 Hz, 2 H), 5.49 (s,
2 H); 13C NMR (100 MHz, CDCl3) δ 145.26, 140.50, 137.54, 134.42, 130.50, 129.74, 129.52, 129.15,
128.96, 127.15, 118.81, 103.82, 98.95, 82.60, 48.18.
1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-5-nitro-1H-benzo(d)imidazole (3h): a yellow solid (342.6
mg, 88%); mp 149-151 °С. 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 8.8 Hz, J = 2 Hz, 1 H), 8.17 (d, J
= 2 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 1 H), 7.69 (d, J = 8.4 Hz, 2 H), 7.02 (dd, J = 8.8 Hz, J = 4 Hz, 2 H),
6.88 (d, J = 8.4 Hz, 2 H), 5.48 (s, 2 H), 3.87 (s, 3 H), 3.80 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 160.87,
159.10, 158.97, 146.54, 140.74, 139.71, 129.77, 129.11, 128.91, 128.13, 127.59, 119.00, 114.25, 114.14,
114.06, 55.32, 47.93, 47.26.
1-(4-Methylbenzyl)-5-nitro-2-(p-tolyl)-1H-benzo(d)imidazole (3i): a yellow solid (303.7 mg, 85%); mp
154-156 oC. 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 8.8 Hz, J = 2 Hz, 1 H), 8.15 (d, J = 2 Hz, 1 H),
7.88 (d, J = 8.8 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.16 (d, J = 7.6 Hz, 2 H),
6.98 (d, J = 8.0 Hz, 2 H), 5.50 (s, 2 H), 2.43 (s, 3 H), 2.35 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 159.07,
147.73, 143.53, 141.31, 138.14, 135.49, 132.22, 130.04, 129.77, 129.22, 125.81, 119.79, 118.65, 107.45,
48.67, 27.38, 21.55, 21.14.
1-(4-Fluorobenzyl)-2-(4-fluorophenyl)-5-nitro-1H-benzo(d)imidazole (3j): a yellow solid (321.9 mg,
1
88%); mp 186-188 °С. H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 8.8 Hz, J = 2 Hz, 1 H), 8.18 (d, J =
2.0 Hz, 1 H), 7.90 (d, J = 9.2 Hz, 2 H), 7.70 (dd, J = 8.6 Hz, J = 5.6 Hz, 2 H), 7.24-7.19 (m, 2 H),
7.09-7.05 (m, 4 H), 5.50 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 165.57, 163.05, 157.75, 147.42 –

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147.29, 143.83 – 143.71, 135.32, 131.4, 130.76, 127.59, 125.03, 120.17, 118.92, 116.73 – 116.53, 116.50
– 116.30, 107.25, 48.19.
Typical experimental procedure of the preparation of products 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j,
and 4k.
2-Phenyl-1H-benzo(d)imidazole (4a): A mixture of o-phenylenediamine 1a (129.8 mg, 1.2 mmol),
Sc(OTf)3 (73.8 mg, 0.15 mmol) and EtOH (15 mL) wre well stirred until the solid dissolved completely at
reflux condition. Benzaldehyde 2b (101 μL, 1.0 mmol) and H2O2 (61 μL, 30 wt%, 2 mmol) was diluted to
20 mL EtOH, and dropwised into the preprocessed mixture. After TLC showed the reaction to be
complete, the reaction mixture was cooled to rt, and then evaporated in vacuum. The product purified by
column chromatography (PE-EtOAc= 4:1) to give 4a (160.6 mg, 90%); Light yellow solid; mp
1
289-291 °С. H NMR (400 MHz, DMSO-d6) δ 12.91(s, 1 H), 8.19-8.17(m, 2 H), 7.67-7.49 (m, 5 H),
7.21(s, br, 2H); 13C NMR (100 MHz, DMSO-d6,) δ 151.58, 143.38,135.50, 130.73, 130.29, 129.11,
126.87, 122.89, 121.20, 118.89, 111.84.
1
2-(4-Chlorophenyl)-1H-benzo(d)imidazole (4b): a yellow solid (208.8 mg, 92%); mp 289-291 °С. H
NMR (400 MHz, DMSO-d6) ߜ 12.90 (s, 1H), 8.21 (d, J =8.4Hz, 2H), 7.64 (d, J = 8.4Hz, 4H), 7.23–7.20
(m, 2H); 13C NMR (100 MHz, DMSO-d6) ߜ 150.56, 144.31, 135.02, 134.81, 129.50, 128.66, 128.22,
122.91, 122.50, 119.34, 111.69.
2-(4-Methoxyphenyl)-1H-benzo(d)imidazole (4c): a yellow solid (213.0 mg, 95%); mp 222-224 °С. 1H
NMR (400 MHz, DMSO-d6) ߜ 7.45 (d, J = 7.2Hz, 1H), 7.24–7.20 (m, 2H), 7.08 (d, J = 8.8Hz, 2H), 6.96
(d, J = 8.4Hz, 2H), 6.83 (d, J = 8.8Hz, 2H), 3.82 (s, 3H); 13C NMR (100 MHz, DMSO-d6) ߜ 160.80,
153.56, 143.27, 136.30, 129.27, 127.85, 122.47, 119.37, 114.68, 114.59, 111.48, 55.80.
2-(p-Tolyl)-1H-benzo(d)imidazole (4d): a yellow solid (193.7 mg, 93%); mp 274-276 °С. 1H NMR (400
MHz, DMSO-d6) ߜ 12.81 (s, 1H), 8.06 (d, J = 7.8Hz, 2H), 7.55 (s, 2H), 7.34 (d, J = 7.8Hz, 2H),
13
7.21–7.18 (m, 2H), 2.36 (s, 3H); C NMR (100 MHz, DMSO-d6) ߜ = 151.78, 144.28, 140.00, 135.36,
129.88, 127.86, 126.85, 122.69, 121.99, 119.12, 111.66, 21.33.
1
2-(4-Fluorophenyl)-1H-benzo(d)imidazole (4e): a brown solid (203.2 mg, 96%); mp 246-247 °С. H
NMR (400 MHz, DMSO-d6): δ12.92 (s, 1H), 8.25-8.21 (m, 2 H), 7.66-7.54 (m, 2 H), 7.43-7.38 (m, 2 H),
13
7.21-7.16 (m, 2 H); C NMR (100 MHz, DMSO-d6) δ 164.78, 162.23, 150.91, 129.72, 129.60, 129.22,
129.10, 127.33, 122.58,118.13, 116.88.
1
5-Nitro-2-phenyl-1H-benzo(d)imidazole (4f): a yellow solid (193.7 mg , 84%); mp 207-209 °С. H
NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 8.40 (s, 1H), 8.14–8.1 (m, 2H), 8.09–8.04 (m, 1H), 7.70 (d,
1H), 7.54 (s, 1H), 7.52 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 155.12, 143.10, 137.62, 131.37,
129.55, 129.42, 128.75, 127.37, 118.37, 110.71, 104.93.

HETEROCYCLES, Vol. 91, No. 12, 2015
2313
2-(4-Chlorophenyl)-5-nitro-1H-benzo(d)imidazole (4g): a yellow solid (249.6 mg , 91%); mp
305-306 °С. 1H NMR (400 MHz, DMSO-d6): δ 13.72 (s, 1 H), 8.51(s, br, 1 H), 8.24 (d, J = 8.8 Hz, 2 H),
13
8.16 (dd, J = 8.8 Hz, J = 2.0 Hz, 1 H), 7.80 (s, br, 1 H), 7.71 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz,
DMSO-d6) δ 155.13, 150.53, 143.50, 136.36, 131.46, 129.88, 129.32, 128.55, 118.92, 115.64, 112.65.
2-(4-Methoxyphenyl)-5-nitro-1H-benzo(d)imidazole (4h): a yellow solid (235.6 mg, 88%); mp
237-238 °С. 1H NMR (400 MHz, (CD3)2CO) δ 12.50 (s, 1H), 8.48 (s, 1H), 8.21 (t, J = 13.9 Hz, 2H), 8.16
(dd, J = 8.8, 2.1 Hz, 1H), 7.76 (t, J = 17.8 Hz, 1H), 7.15 (d, J = 8.6 Hz, 2H), 3.92 (s, 3H); 13C NMR (100
MHz, (CD3)2CO) δ 162.06, 143.71, 142.35, 128.70, 121.81, 117.76, 116.38, 114.35, 113.37, 100.35,
99.67 54.99.
1
5-Nitro-2-(p-tolyl)-1H-benzo(d)imidazole (4i): a yellow solid (216.3 mg, 85%); mp 209-211 °С. H
NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 8.10 (s, br, 1 H), 8.09 (dd, J1 = 8.8 Hz, J2 = 1 Hz, 1 H), 7.98
13
(d, J = 8.4 Hz, 2 H), 7.67 (s, br, 1 H), 7.36 (d, J = 8.4 Hz, 2 H), 2.45 (s, 3 H); C NMR (100 MHz,
DMSO-d6) δ 156.32, 136.37,130.12, 129.15, 127.77, 126.02, 118.67, 115.02, 112.81, 112.39, 109.91,
21.11.
2-(4-Fluorophenyl)-5-nitro-1H-benzo(d)imidazole (4j): a yellow solid (226.3 mg, 88%); mp 221-223
1
oC. H NMR (400 MHz, (CD3)2CO) δ 12.64 (s, 1H), 8.51 (s, 1H), 8.37 – 8.28 (m, 2H), 8.18 (dt, J = 8.9,
13
2.0 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 7.39 (td, J = 8.7, 1.7 Hz, 2H); C NMR (100 MHz, (CD3)2CO) δ
165.55, 163.07, 154.84, 143.52, 139.38, 129.43,129.40, 125.98, 118.05, 116.09, 116.03.
1
2-(Furan-2-yl)-1H-benzo(d)imidazole (4k): a yellow solid (129.4 mg, 70%); mp 285-286 °С. H NMR
(400 MHz, DMSO-d6) δ 12.91 (brs, 1H)㸪7.94 (s, 1 H), 7.62 (d, J = 8.4 Hz, 1 H), 7.50 (d, 1H, J = 8.0 Hz),
7.25-7.18 (m, 3H), 6.77-6.74 (m, 1 H); 13C NMR (100 MHz, DMSO-d6 ) δ 146.00, 143.45, 143.45,
137.12, 134.16, 122.43, 121.56, 118.66, 112.33, 111.23, 110.34.
ACKNOWLEDGEMENTS
This work was supported by the National Natural Science Foundation of China (No. 20802052). We also
thank the support from the Research Foundation of Tongji University.
REFERENCES
1. B. M. Savall and J. R. Fontimayor, Tetrahedron Lett., 2008, 49, 6667.
2. B. Prabal, S. Manisha, S. Ponmariappan, A. Sharma, P. Sharma, A. K. Srivastava, and M. P.
Kaushik, Bioorg. Med. Chem. Lett., 2011, 21, 7306.
3. (a) P. S. Chandrachood, D. R. Garud, T. V. Gadakari, R. C. Torane, N. R. Nirmala, and R. V.
Kashalkar, Acta Chim. Slov., 2011, 58, 367; (b) Y. S. Beheshtiha, M. M. Heravi, M. Saeedi, N.
Karimi, M. Zakeri, and N. Tavakoli-ahossieni, Synth. Commun., 2010, 40, 1216; (c) C. S. Radatz, R.

2314
HETEROCYCLES, Vol. 91, No. 12, 2015
B. Silva, and D. Alves, Tetrahedron Lett., 2011, 52, 4132; (d) Y. Kim, M. R. Kumar, M. J. Park, Y.
Heo, and S. Lee, J. Org. Chem., 2011, 76, 9577; (e) R. Shelkar, S. Sarode, and J. Nagakar,
Tetrahedron Lett., 2013, 54, 6986.
4. D.I. Shah, M. Sharma, Y. Bansal, G. Bansal, and M. Singh, Eur. J. Med. Chem., 2008, 43, 1808.
5. Y. Ogino, N. Ohtake, Y. Nagae, K. Matsuda, M. Kenji, M. Moriya, T. Suga, M. Ishikawa, M.
Kanesaka, Y. Mitobe, J. Ito, T. Kanno, A. Ishihara, H. Iwaasa, T. Ohe, A. Kanatani, and T. Fukami,
Bioorg. Med. Chem. Lett., 2008, 18, 5010.
6. Y. Riadi, R. Mamouni, R. Azzalou, M. E. Haddad, R. Sylvain, G. Gerald, and L. Sald, Tetrahedron
Lett., 2011, 52, 3492.
7. K. Bahrami, M. M. Khodaei, and I. Kavianinia, Synthesis, 2007, 547.
8. K. R. Hornberger, G. M. Adjabeng, H. D. Dickson, and G. D. Ronda, Tetrahedron Lett., 2006, 47,
5359.
9. (a) M. R. Mohammadizadeh and S. Z. Taghavi, Eur. J. Chem., 2011, 8, 01; (b) B. Kiumars, M.
Mehdi, and K. Iman, Synthesis, 2007, 547; (c) K. A. Shaikh and V. A. Patil, Org. Commun., 2012,
51, 12.
10. Y. Shiraishi, Y. Sugano, S. Tanaka, and T. Hirai, Angew. Chem. Int. Ed., 2010, 49, 1656.
11. M. M. Guru, M. A. Ali, and T. Punniyamurthy, J. Org. Chem., 2011, 76, 5295.
12. (a) R. N. Nadaf, S. A. Siddiqui, T. Daniel, R. J. Lahoti, and K. V. Srinivasan, J. Mol. Catal. A:
Chem., 2004, 214,155; (b) K. P. Boroujeni, A. Zhianinasb, and M. Jafarinasab, J. Serb. Chem. Soc.,
2013, 78, 155.
13. G. H. Mahdavlnla, S. Rostamlzadeh, A. M. Amant, and H. Sepehrlan, Heterocycl. Commun., 2012,
18, 33.
14. A. Hegedüüs, Z. Hell, and A. Potor, Synth. Commun., 2006, 36, 3625.
15. M. Chakrabarty, S. Karmakar, and A. Mukherji, Heterocycles, 2006, 68, 967.
16. M. A. Chari, D.Shobha, and T. Sasaki, Tetrahedron Lett., 2011, 52, 5575.
17. K. Boroujeni, A. Zhianinsab, and M. Jafarinasab, J. Serb. Chem. Soc., 2013, 78, 155.
18. (a) T. Yamashita, S. Yamada, and Y. Yamazaki, Synth. Commun., 2009, 39, 2982; (b) R. L.
Lombardy, F. A. Tanious, and K. Ramachandran, J. Med. Chem., 1996, 39, 1452.
19. J. T. Li, Y. X. Chen, and T. S. Li, J. Chem. Res., 2005, 6, 361.