Synthesis of 2,5-disubstitued benzimidazole using SnCl2- catalyzed reduction system at room temperature

Article abstract of DOI:10.1016/j.cclet.2013.10.014

Stannous chloride dihydrate is used as an efficient catalyst in reductive cyclization of 2-nitro-5-substituted aniline Schiff base leading to stable 2,5-disubstitued benzimidazole derivatives in excellent yields with good purity. It provides a novel method of synthesis of 2,5-disubstitued benzimidazole under reductive system at room temperature.

Full text of DOI:10.1016/j.cclet.2013.10.014

G Model
CCLET-2727; No. of Pages 4
Chinese Chemical Letters xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Synthesis of 2,5-disubstitued benzimidazole using SnCl2-catalyzed
reduction system at room temperature
Li-Ping Duan a, , Qiang Li a,b, Ning-Bo Wu a, Dong-Fang Xu b, Hao-Bing Zhang a
*
a National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis,
and Filariasis, Key laboratory of Parasitology and Vector Biology at National Institute of Parasitic Diseases, Shanghai 200025, China
b Shanghai Normal University, Shanghai 200005, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Stannous chloride dihydrate is used as an efficient catalyst in reductive cyclization of 2-nitro-5-
substituted aniline Schiff base leading to stable 2,5-disubstitued benzimidazole derivatives in excellent
yields with good purity. It provides a novel method of synthesis of 2,5-disubstitued benzimidazole under
reductive system at room temperature.
Received 2 September 2013
Received in revised form 6 September 2013
Accepted 13 September 2013
Available online xxx
ß 2013 Li-Ping Duan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Stannous chloride dihydrate
Reductive cyclization
Benzimidazole derivatives
1. Introduction
conditions, elimination of toxic oxide reagents, operational
simplicity, and high yields of products.
The benzimidazole structural motif plays very important roles
in numerous pharmaceutical molecules with a wide range of
biological properties including anticancer, antihistaminic, antihy-
pertensive, antifungal, and antiviral effects [1–3]. Consequently,
the synthesis of the heterocyclic nucleus has gained great
importance. Many methods for the synthesis of benzimidazoles
have been discovered and reported. There are two general methods
for the synthesis of benzimidazoles. One is oxidative cyclo-
dehydrogenation of aniline Schiff base with various oxidative
reagents [4–6]. The other method is the coupling of a carboxylic
acid with phenylenediamine under high temperature [7,8].
However, these synthetic protocols suffer from one or more
disadvantages such as the use of dangerous or toxic oxide reagents,
high temperature, strong acid conditions, prolonged reaction
times, cumbersome multi-step processes, or the formation of side
products. As a consequence, the introduction of new methods with
technical improvements to overcome the limitations is still an
important experimental challenge [9,10]. To the best of our
knowledge, few studies have related to the synthesis of
benzimidazole derivatives under reductive atmosphere [11]. The
advantages of using the reduction system include mild reaction
In the last decade, stannous chloride dihydrate has gained
special attention as a mild and highly chemoselective reducing
agent for various organic transformations. For example,
SnCl2ꢀ2H2O is still popularly used to selectively reduce aromatic
nitro group to amino for its eco-friendly nature, affordability, high
reactivity, and safety profile. A significant breakthrough in the field
of reductive cylization heterocyclic compounds was based on
stannous chloride dihydrate. In 2002, Bates and Li reported
cyclization products produced for nitroarene reduction to ami-
noarene using SnCl2ꢀ2H2O [12]. In 2006, Roy and co-workers
reported that a one-step reductive transformation of 2-(2-nitro-
phenyl)-3H-quinazolin-4-one in various alcohols furnished the
desired tetracyclic product with SnCl2ꢀ2H2O [13]. Recently, the
method of reductive cyclization of 2-nitrobenzamides with
haloketones or keto acids mediated by SnCl2ꢀ2H2O was reported
by Shi [14]. In this paper, we wish to describe a new route to
synthesize benzimidazole derivatives via novel reductive cycliza-
tion of 2-nitro-5-substituted aniline Schiff base by SnCl2ꢀ2H2O at
room temperature.
2. Experimental
From the starting material 2-nitro-5-substituted anilines (1),
through the intermediate 2-nitro-5-substituted aniline Schiff
bases (2), the target compounds 2,5-disubstitued benzimidazoles
(3a–i) were obtained with stannous chloride dehydrate [15]. The
*
Corresponding author.
E-mail address: lipingduan@yahoo.com (L.-P. Duan).
1001-8417/$ – see front matter ß 2013 Li-Ping Duan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.10.014
Please cite this article in press as: L.-P. Duan, et al., Synthesis of 2,5-disubstitued benzimidazole using SnCl2-catalyzed reduction system
at room temperature, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.10.014

G Model
CCLET-2727; No. of Pages 4
2
L.-P. Duan et al. / Chinese Chemical Letters xxx (2013) xxx–xxx
3.5
N
N
R
NH
NO
N
1
2
R
R
1
1
(a)
3.0
(b)
R
2
R
2
N
H
NO
2
2
2.5
2.0
1.5
1.0
0.5
0.0
1
C
2
3
D
Scheme 1. Synthesis of 3. Reaction conditions: (a) POCl3, R2CON(CH3)2, toluene,
reflux; (b) SnCl2ꢀ2H2O, ethanol, 25 8C.
E
B
N,N-dimethyl-N'-(2-nitrophenyl)acetimidamide
A
F
2-methylbenzimidazole
200
250
300
350
400
450
500
Wavethlength (nm)
Fig. 3. The reaction process of N,N-dimethyl-N0-(2-nitrophenyl)acetimidamide with
the addition of SnCl2ꢀ2H2O in ethanol at 25 8C was monitored using UV–vis
spectroscopy in 1 h (the time interval is 15 min each trace in 1 h).
(1.5 mmol) and phosphorus oxychloride (2.5 mL) in toluene
(10 mL) was refluxed for 4 h at 120 8C. The mixture was cooled
and poured onto crushed ice, then made basic with sodium
bicarbonate solution. The organic layer was washed with water,
then dried over sodium sulfate and evaporated under vacuo. The
crude material was purified by chromatography on silica gel
column using ethyl acetate and petroleum ether (1:1 by volume)
as the eluent. The solvent was removed under reduced pressure to
afford the different substituted N,N-dimethyl-N0-(2-nitropheny-
l)imidamide intermediates (2). Next, a mixture of 2 (1 mmol) and
stannous chloride dihydrate (4 mmol) in ethanol (10 mL) was
stirred at room temperature for 1 h. The solvent was removed
under vacuo and the mixture was dissolved in dichloromethane
and washed with sodium bicarbonate solution. The organic layer
was then dried over sodium sulfate and evaporated in vacuo. The
crude material was purified by chromatography on silica gel
column using ethyl acetate and petroleum ether (1:2 by volume) as
eluent. The solvent was removed under reduced pressure to give
2,5-disubstitued benzimidazoles 3.
Fig. 1. Molecular structure of 2-methyl-5-phenylthio-benzimidazole.
details for the syntheses are shown in Scheme 1. The structures of
3a–i were characterized by mass spectrometry and NMR. The
molecular structure of 2-methyl-5-phenylthio-benzimidazole was
confirmed by X-ray analysis (Fig. 1). The crystallographic data have
been assigned the deposition numbers at the Cambridge crystal-
lographic data Centre (CCDC945241).
Typical experimental procedure for synthesis 2,5-disubstitued
benzimidazole derivatives: A solution of 2-nitro-5-substituted
aniline (1 mmol), difference substituted N,N-dimethylamine
Ethanol
Acetonitnile
Acetic acid
Acetone
100
90
80
70
60
50
40
30
20
0.5
1.0
1.5
Time (h)
2.0
2.5
3.0
1
Fig. 2. Solvent effect for synthesis of 2-methylbenzimidazole using SnCl2ꢀ2H2O
Fig. 4. H NMR spectra of N,N-dimethyl-N0-(2-nitrophenyl)acetimidamide (a) and
catalysts by HPLC.
2-methylbenzimidazole (b) in CDCl3.
Please cite this article in press as: L.-P. Duan, et al., Synthesis of 2,5-disubstitued benzimidazole using SnCl2-catalyzed reduction system
at room temperature, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.10.014

G Model
CCLET-2727; No. of Pages 4
L.-P. Duan et al. / Chinese Chemical Letters xxx (2013) xxx–xxx
3
R
2
R
2
H
N
SnCl . 2H O
N
+
2
2
R
+
H
R
2
1
N
C
N
R
- NH(CH )
1
3 2
N
C N
R
1
R
R
2
1
N
H
N
N
H
NO
2
NH
2
CH CH
2
,CH
3
Cl
R =
3,
H,
SH,
R =
2
1
Scheme 2. Potential mechanism for benzimidazole formation.
Table 1
Synthesis of 2,5-disubstitued benzimidazole (3a–3i).
Entry
R1
R2
Product
Time (h)
Yield (%)
Mp (oC)
1
2
3
4
5
6
7
8
9
C6H4–SH
CH3
3a
3b
3c
3d
3e
3f
1
92.1
90.3
89.6
95.6
95.0
92.3
90.8
90.2
88.7
159.6–162.6
C6H4–SH
CH3CH2
Ph
1
135.3–137.8
C6H4–SH
1.5
1.5
1.5
1.5
2
146.3–148.4
H
CH3
164.3–165.4 [16]
122.7–125.6 [17]
293.3–296.4 [18]
205.1–207.4 [19]
185.1–186.2 [17]
212.1–213.0 [20]
H
CH3CH2
Ph
H
Cl
Cl
Cl
CH3
3g
3h
3i
CH3 CH2
Ph
2
2
3. Results and discussion
Furthermore, the process works well for the synthesis of various
substituted benzimidazoles. As the results shown in Table 1, SnCl2
alcohol solution catalyst with various o-nitro anilines successfully
afforded the corresponding benzimidazoles. Both 2-alkyl- and 2-
aryl-substitued benzimidazoles were successfully produced in
very high yields. In addition, 5-substituted derivatives were also
produced successfully. 2-Nitroaniline containing electron donat-
ing substitution (such as phenylthio) shows a fast reaction time,
because it increases amino nucleophilic character of 2-amino-5-
substituted aniline Schiff base intermediate. In this protocol, all
synthesized products were obtained in excellent yield.
The reaction can usually be carried out effectively in various
solvents such as ethanol, acetonitrile, acetic acid and acetone. So,
we selected o-nitro aniline and N,N-dimethylacetamine as model
substrates to optimize the experimental conditions for the
proposed reductive cyclization reaction. The results showed that
at room temperature in 1 h the best solvent was ethanol, and the
reaction preceded smoothly in high yield (92.1%). Acetonitrile
(76%) and acetic acid (75%) exhibited almost the same activity, and
acetone showed poor activity (48%) in 1 h (Fig. 2). Additionally, the
relationship between the molecules and spectral changes was
discussed, and the reaction process was monitored using UV–vis
spectroscopy. The resulting absorption is shown in Fig. 3. The
addition of 4 equiv. of stannous chloride dihydrate to the solution
of N,N-dimethyl-N0-(2-nitrophenyl)acetimidamide intermediate
that is generated from the condensation of o-nitro aniline and
N,N-dimethylacetamine caused a decrease in the absorbance at
275 nm. The absorption peak at 375 nm disappeared, which can be
4. Conclusion
In conclusion, treatment of 2-nitro-5-substituted aniline with
difference substituted N,N-dimethylamine gives 2-nitro-5-substi-
tuted aniline Schiff base, and the adducts are readily converted into
benzimidazoles by stannous chloride dihydrate in ethanol condi-
tion. It will possibly find wide application in organic synthesis.
assigned to p–p* transition due to C55N bonds in conjugation with
phenyl group. Meanwhile, a new increased absorption peak at
280 nm can be attributed to the 2-methylbenzimidazole. 1H NMR
experiments were also carried out to confirm the formation of
benzimidazole derivative (Fig. 4). The N,N-dimethyl resonance
peak (3.01 ppm) of N,N-dimethyl-N0-(2-nitrophenyl)acetimida-
mide disappeared, and a new equal peak centered at 2.67 ppm
appeared, which could be assigned to the NH protons of the
benzimidazole. This result indicated that benzimidazole was
formed.
Acknowledgments
This project is supported by Shanghai Municipal Natural
Science Foundation (No. 12ZR1434900), International Collabora-
tion on Drugs and Diagnostics Innovation of Tropical Diseases in
China (International S&T Cooperation 2010DFB73280).
References
Regarding the mechanism of the reductive cyclization reaction
process, we speculated that 2-amino-5-substituted aniline Schiff
base intermediate formed first through SnCl2ꢀ2H2O-assisted
reduction (Scheme 2), followed by a very rapid elimination of
HN(CH3)2 thus resulting in a stable imidazole ring. Finally, the
generated base HN(CH3)2 is scavenged by the acid to produce salt
in water. This catalyst SnCl2ꢀ2H2O promotes two different
transformations in one pot: the conversion of nitro into amino
through reduction, and catalytic 2-amino-5-substituted aniline
Schiff base of benzimidazole intermediates leading to 2,5-
disubstitued benzimidazole derivatives.
[1] (a) S. Lin, L. Yang, A simple and efficient procedure for the synthesis of benzi-
midazoles using air as the oxidant, Tetrahedron Lett. 46 (2005) 4315–4319;
(b) G.L. Gravatt, B.C. Baguley, W.R. Wilson, W.A. Denny, DNA-directed alkylating
agents. 6. Synthesis and antitumor activity of DNA minor groove-targeted aniline
mustard analogs of pibenzimol (Hoechst 33258), J. Med. Chem. 37 (1994) 4338–
4345.
[2] (a) J.S. Kim, B. Gatto, C. Yu, et al., Substituted 2,50-bi-1H-benzimidazoles: topo-
isomerase I inhibition and cytotoxicity, J. Med. Chem. 39 (1996) 992–998;
(b) T. Roth, M.L. Morningstar, P.L. Boyer, et al., Synthesis and biological activity of
novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 2-Aryl-substituted
benzimidazoles, J. Med. Chem. 40 (1997) 4199–4207;
(c) P.S. Charifson, A.L. Grillot, T.H. Grossman, et al., Novel dual-targeting benz-
imidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent
antibacterial activity: intelligent design and evolution through the judicious use
Please cite this article in press as: L.-P. Duan, et al., Synthesis of 2,5-disubstitued benzimidazole using SnCl2-catalyzed reduction system
at room temperature, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.10.014

G Model
CCLET-2727; No. of Pages 4
4
L.-P. Duan et al. / Chinese Chemical Letters xxx (2013) xxx–xxx
of structure-guided design and structure–activity relationships, J. Med. Chem. 51
(2008) 5243–5263.
[13] A.D. Roy, A. Subramanian, R.J. Roy, Auto-redox reaction: tin(II) chloride-mediated
one-step reductive cyclization leading to the synthesis of novel biheterocyclic
5,6-dihydro-quinazolino[4,3-b]quinazolin-8-ones with three-point diversity,
Org. Chem. 71 (2006) 382–385.
[14] M. Wang, G. Dou, D. Shi, Efficient and convenient synthesis of pyrrolo[1,2-
a]quinazoline derivatives with the aid of tin(II) chloride, J. Comb. Chem. 12
(2010) 582–586.
[3] (a) D.A. Horton, G.T. Bourne, M.L. Smythe, The combinatorial synthesis of bicyclic
privileged structures or privileged substructures, Chem. Rev. 103 (2003) 893–930;
(b) M. Alamgir, D.S.C. Black, N. Kumar, Synthesis, Reactivity and Biological Activity
of Benzimidazoles, Topics in Heterocyclic Chemistry, vol. 9, Springer, Berlin,
Heidelberg, 2007, pp. 87–118.
[4] (a) G.M. Coppola, N-Hydroxyphthalimide/cobalt acetate, a new catalytic oxida-
tive system for the synthesis of benzimidazoles, Synth. Commun. 38 (2008)
3500–3507;
(b) K. Bahrami, M.M. Khodaei, I. Kavianinia, A simple and efficient one-pot
synthesis of 2-substituted benzimidazoles, Synthesis (2007) 547–550.
[5] (a) K. Bahrami, M.M. Khodaei, F. Nejati, Synthesis of 1,2-disubstituted benzimi-
dazoles, 2-substituted benzimidazoles and 2-substituted benzothiazoles in SDS
micelles, Green Chem. 12 (2010) 1237–1241;
[15] 2-Methyl-5-phenylthio-benzimidazole (3a): white solid, mp: 159.6–162.6 8C, IR
(KBr, cmꢁ1): v 3260, 3165, 2981, 1482, 1361. 1H NMR (400 MHz, CDCl3): d7.490
(d, 2H, J = 8.0 Hz), 7.305–7.284 (m, 1H), 7.222 (d, 1H, J = 8.0 Hz), 7175–7.109 (m,
4H), 2.620 (s, 3H); 13C NMR (100 MHz, CDCl3): d154.6, 139.8, 122.4, 115.8, 14.1;
LC–MS [M+H+]: 241.23. 2-Ethyl-5-phenylthio-benzimidazole (3b): white solid,
mp: 135.3–137.8 8C, IR (KBr, cmꢁ1): v 3245, 3163, 3054, 2982, 1481, 1420. 1H
NMR (400 MHz, CDCl3): d7.280 (s, 1H), 7.236–7.109 (m, 5H), 7.087 (d, 1H,
J = 8.0 Hz), 6.748 (d, 1H, J = 8.0 Hz), 2.426–2.370 (m, 2H), 1.243–1.206 (t, 3H);
13C NMR (100 MHz, CDCl3): d151.6, 137.8, 122.4, 116.1, 22.4, 13.9; LC–MS
[M+H+]: 255.25. 2-Phenyl-5-phenylthio-benzimidazole (3c): white solid, mp:
146.3–148.4 8C. IR (KBr, cmꢁ1): v 3268, 3174, 3054, 1452, 1420. 1H NMR
(400 MHz, CDCl3): d7.823 (d, 2H, J = 8.00 Hz), 7.645 (s, 1H), 7.512–7.254 (m,
9H), 7.131 (d, 1H, J = 8.00 Hz); 13C NMR (100 MHz, CDCl3): d151.8, 138.8, 123.4,
115.8; LC–MS [M+H+]: 303.29. 2-Methyl-benzimidazole (3d): pale yellow solid,
mp: 164.3–165.4 8C, IR (KBr, cmꢁ1): v 3260, 3174, 3054, 1452, 1420. 1H NMR
(400 MHz, CDCl3): d7.523 (d, 2H, J = 9.20 Hz), 7.222–7.178 (m, 2H), 2.671 (s, 1H),
2.612 (s, 3H); 13C NMR (100 MHz, CDCl3): d151.6, 137.8, 122.4, 115.8, 13.9; LC–
MS [M+H+]: 133.22. 2-Ethyl-benzimidazole (3e): pale yellow solid, mp: 122.7–
125.6 8C, IR (KBr, cmꢁ1): v 3264, 3187, 3008, 1434, 1425, 1120. 1H NMR (400 MHz,
CDCl3): d7.527 (d, 2H, J = 9.20 Hz), 7.222–7.164 (m, 2H), 2.964–2.907 (m, 2H),
1.432–1.389 (t, 3H); 13C NMR (100 MHz, CDCl3): d151.9, 139.8, 125.4, 119.8, 20.8,
15.1; LC–MS [M+H+]: 147.24. 2-Phenyl-benzimida-zole (3f): pale yellow solid,
mp 293.3–296.4 8C. IR (KBr, cmꢁ1): v 3256, 3174, 1452, 1444. 1H NMR (400 MHz,
(b) K.D. Parghi, R.V. Jayaram, Sequential oxidation and condensation of alcohols
to benzimidazoles/benzodiazepines by MoO3–SiO2 as a heterogeneous bifunc-
tional catalyst, Catal. Commun. 11 (2010) 1205–1210;
(c) C.J. Zhu, Y.Y. Wei, An inorganic iodine-catalyzed oxidative system for the
synthesis of benzimidazoles using hydrogen peroxide under ambient conditions,
Chem. Sus. Chem. 4 (2011) 1082–1086.
[6] (a) R.V. Shingalapur, K.M. Hosaman, An efficient and eco-friendly tungstate
promoted zirconia (WOx/ZrO2) solid acid catalyst for the synthesis of 2-arylben-
zimidazoles, Catal. Lett. 137 (2010) 63–68;
(b) K. Bahrami, M.M. Khodaei, F. Naali, H2O2/Fe(NO3)3promoted synthesis of 2-
arylbenzimidazoles and 2-arylbenzothiazoles, Synlett 39 (2009) 569–572;
(c) K. Bahrami, M.M. Khodaei, F. Naali, Mild and highly efficient method for the
synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles, J. Org. Chem. 73
(2008) 6835–6837.
[7] P.L. Beaulieu, B. Hache, E. Von Moos, A practical oxone1-mediated, high-through-
put, solution-phase synthesis of benzimidazoles from 1,2-phenylenediamines
and aldehydes and its application to preparative scale synthesis, Synthesis 11
(2003) 1683–1693.
[8] (a) K.J. Lee, K.D. Janda, Traceless solid-phase synthesis of 5-benzoylbenzimida-
zoles, Can. J. Chem. 79 (2001) 1556–1561;
CDCl3): d7.609 (d, 2H, J = 9.20 Hz), 7.481–7.438 (m, 2H), 7.397–6.958 (m, 5H); 13
C
NMR (100 MHz, CDCl3): d150.6, 139.3, 130.8, 129.3, 128.8, 123.9, 115.7; LC–MS
[M+H+]: 195.30. 2-Methyl-5-chloro-benzimidazole (3g): white solid, mp 205.1–
207.4 8C. IR (KBr, cmꢁ1): v 3420, 3000, 2987, 2931, 1465, 1399. 1H NMR (400 MHz,
CDCl3): d7.621 (d, 1H, J = 2.4 Hz), 7.552 (d, 1H, J = 8.6 Hz), 7.25 (dd, 1H, J = 8.6,
2.4 Hz), 2.604 (s, 3H); 13C NMR (100 MHz, CDCl3): d151.3, 139.2, 138.6, 128.7,
123.4, 115.0, 114.8, 15.2; LC–MS [M+H+]: 167.24. 2-Ethyl-5-chloro-benzimid-
azole (3h): white solid, mp 185.1–186.2 8C. IR (KBr, cmꢁ1): v 3425, 3020, 2990,
1465, 1399. 1H NMR (400 MHz, CDCl3): d7.622 (d, 1H, J = 2.4 Hz), 7.562 (d, 1H,
J = 8.6 Hz), 7.23 (dd, 1H, J = 8.6, 2.4 Hz), 2.446–2.380 (m, 2H), 1.263–1.256 (t, 3H);
13C NMR (100 MHz, CDCl3): d151.3, 139.2, 138.6, 128.7, 123.4, 115.0, 114.8, 24.6,
15.2; LC–MS [M+H+]: 181.55. 2-Phenyl-5-chloro-benzimidazole (3i): white solid,
mp 212.1–213.0 8C, IR (KBr, cmꢁ1): v 3418, 3062, 3054, 1463, 1438, 1400. 1H NMR
(400 MHz, CDCl3): d 8.192 (d, 2H, J = 8.0 Hz), 7.653–7.492 (m, 5H), 7.22 (dd, 1H,
J = 8.0, 2.4 Hz); 13C NMR (100 MHz, CDCl3): d 154.2, 143.5, 139.1, 132.4, 130.1,
128.9, 128.1, 127.5, 123.3, 115.6; LC–MS [M+H+]: 244.65.
(b) Y.X. Chen, L.F. Qian, W. Zhang, B. Han, Efficient aerobic oxidative synthesis of
2-substituted benzoxazoles, benzothiazoles, and benzimidazoles catalyzed by 4-
methoxy-TEMPO, Angew. Chem. 120 (2008) 9470–9473;
(c) G.A. Molander, K. Ajayi, Oxidative condensations to form benzimidazole-
substituted potassium organotrifluoroborates, Org. Lett. 14 (2012) 4242–4245.
[9] (a) M. Shen, T.G. Driver, Iron(II) bromide-catalyzed synthesis of benzimidazoles
from aryl azides, Org. Lett. 10 (2008) 3367–3370;
(b) Z.H. Zhang, J.J. Li, Y.Z. Cao, Y.H. Liu, Synthesis of 2-substituted benzimidazoles
by iodine-mediated condensation of orthoesters with 1, 2-phenylenediamines, J.
Heterocycl. Chem. 44 (2007) 1509–1512;
(c) D. Yang, H. Fu, L. Hu, Y. Jiang, Y. Zhao, Copper-catalyzed synthesis of benzi-
midazoles via cascade reactions of o-haloacetanilide derivatives with amidine
hydrochlorides, J. Org. Chem. 73 (2008) 7841–7844.
[16] M. Damm, T.N. Glasnov, C.O. Kappe, Translating high-temperature microwave
chemistry to scalable continuous flow processes, Org. Process Res. Develop. 14
(2010) 215–224.
[17] Z.H. Zhang, J.J. Li, Y.Z. Gao, Y.H. Liu, Synthesis of 2-substituted benzimidazoles by
iodine-mediated condensation of orthoesters with 1,2-phenylenediamines, J.
Heterocyclic. Chem. 44 (2007) 1509–1512.
[18] M.A. Chari, D. Shobha, T. Sasaki, Room temperature synthesis of benzimidazole
derivatives using reusable cobalt hydroxide (II) and cobalt oxide (II) as efficient
solid catalysts, Tetrahedron Lett. 52 (2011) 5575–5580.
[19] J. Kim, J. Kim, B.H. Kim, Indium-mediated one-pot benzimidazole synthesis from
2-nitroanilines or 1,2-dinitroarenes with orthoesters, Tetrahedron 67 (2011)
8027–8033.
[10] (a) R. Trivedi, S.K. De, R.A. Gibbs, A convenient one-pot synthesis of 2-substituted
benzimidazoles, J. Mol. Catal. A: Chem. 245 (2006) 8–11;
(b) D.S. VanViet, P. Gillespie, J.J. Scicinski, Rapid one-pot preparation of 2-substi-
tuted benzimidaziles from 2-nitroamilines using microwave conditions, Tetra-
hedron Lett. 46 (2005) 6741–6743;
(c) J. Kim, J.H. Kim, H.S. Lee, B.M. Lee, B.H. Kim, Indium-mediated one-pot
benzimidazole synthesis from 2-nitroanilines or 1,2-dinitroarenes with orthoe-
sters, Tetrahedron 67 (2011) 8027–8033.
[11] Z.M. Wu, P. Rea, G. Wickham, ‘‘One-pot’’ nitro reduction–cyclisation solid phase
route to benzimidazoles, Tetrahedron Lett. 41 (2000) 9871–9874.
[12] D.K. Bates, K. Li, Stannous chloride-mediated reductive cyclization-rearrange-
ment of nitroarenyl ketones, J. Org. Chem. 24 (2002) 8662–8665.
[20] M. Shen, T.G. Driver, Iron(II) bromide-catalyzed synthesis of benzimidazoles from
aryl azides, Org. Lett. 10 (2008) 3367–3370.
Please cite this article in press as: L.-P. Duan, et al., Synthesis of 2,5-disubstitued benzimidazole using SnCl2-catalyzed reduction system
at room temperature, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.10.014