One-pot synthesis of benzimidazoles from o-nitroanilines under microwaves via a reductive cyclization

Article abstract of DOI:10.1080/00397910701230170

An efficient microwave irradiation synthesis of 2-substituted benzimidazoles in one step via the Na2S2O4 reduction of o-nitroanilines in the presence of aldehydes is described. The method is simple and a good option to obtain the title compounds in a very short time. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701230170

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One‐Pot Synthesis of Benzimidazoles from
o‐Nitroanilines under Microwaves via a
Reductive Cyclization
Mandar P. Surpur a , Pankajkumar R. Singh a , Sachin B. Patil a & Shriniwas D.
Samant a
a Organic Chemistry Research Laboratory, University Institute of Chemical
Technology, Matunga, Mumbai, India
Version of record first published: 12 Apr 2007.
To cite this article: Mandar P. Surpur , Pankajkumar R. Singh , Sachin B. Patil & Shriniwas D. Samant (2007):
One‐Pot Synthesis of Benzimidazoles from o‐Nitroanilines under Microwaves via a Reductive Cyclization,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:8, 1375-1379
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Synthetic Communicationsw, 37: 1375–1379, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701230170
One-Pot Synthesis of Benzimidazoles from
o-Nitroanilines under Microwaves via a
Reductive Cyclization
Mandar P. Surpur, Pankajkumar R. Singh, Sachin B. Patil,
and Shriniwas D. Samant
Organic Chemistry Research Laboratory, University Institute of
Chemical Technology, Mumbai, India
Abstract: An efficient microwave irradiation synthesis of 2-substituted benzimida-
zoles in one step via the Na2S2O4 reduction of o-nitroanilines in the presence of
aldehydes is described. The method is simple and a good option to obtain the title
compounds in a very short time.
Keywords: benzimidazoles, microwaves, Na2S2O4, reductive cyclization
INTRODUCTION
Benzimidazole is a versatile core contained in several substances possessing a
broad spectrum of pharmacological activity such as anticancer, antimicrobial,
pesticide, and antithelmintic properties.[1] This class of molecules has also
found commercial applications in several therapeutic areas such as anti-
ulcerative, antiviral, and antihistaminic agents.[2] Hence, the development of
new synthetic methods for benzimidazoles, which are currently not easily
attainable by existing methods, is considered important by organic chemists.
Received in India September 15, 2006
Address correspondence to Shriniwas D. Samant, Organic Chemistry Research
Laboratory, University Institute of Chemical Technology, N. M. Parekh Marg,
Matunga, Mumbai 400 019, India. E-mail: samantsd@udct.org
1375

1376
M. P. Surpur et al.
The most popular synthetic approaches generally involve the condensation of
an arylenediamine with a carbonyl equivalent[3] or with organic acids,
employing hydrochloric acid,[4] polyphosphoric acid,[5] boric acid,[6] or
para-toluene sulphonic acid (p-TSA)[7] as catalyst. However, all these
reactions often require longer reaction times and tedious workup. Several
improved procedures for the preparation of benzimidazoles have been
reported either by fusion of 2-aminobenzamide and organic acid[8] or by
[9]
reaction of o-phenylenediamine and organic acid using FeCl3/O2 in a
catalytic Feþ2/Feþ3 redox cycling approach. Recently, benzimidazoles have
also been prepared from o-nitroanilines using sodium dithionite in the
presence of aldehydes,[10] by the condensation of orthoesters with o-phenyle-
nediamine in a dry medium under monomode microwave irradiation,[11]
and from phenylenediamines and organic acids in the presence of polypho-
sphoric acid (PPA) under microwaves.[12] In addition, the development of
novel but more complex solid-phase routes to benzimidazoles has been
advanced.[13]
Microwave irradiation of organic reactions has rapidly gained in
popularity because it accelerates a variety of synthetic transformations.[14]
The application of microwaves with certain catalysts or reagents provides
unique chemical processes with special attributes such as enhanced
reaction rates, higher yields, greater selectivity, and ease of manipulation.
Hence, microwave irradiation is becoming an increasing popular
technology.[11–15]
Here we report the direct synthesis of benzimidazoles from o-nitroani-
lines using sodium dithionite under microwaves. Sodium dithionite
(Na2S2O4) is a very inexpensive and efficient reducing reagent that acts as a
single-electron-transfer donor and has been reported to reduce aryl nitro
groups to aryl amines by a six-electron mechanism.[16] This observation,
coupled with mild reaction conditions of the method and a demonstrated
tolerance for other functional groups such as halogens, aldehydes, ketones,
and olefins, rendered Na2S2O4 a prime candidate for reductive cyclization
of o-nitroaniline.
The o-nitroaniline (1 mmol) and the aldehyde (1 mmol) were taken in
dimethyl formamide (DMF) (4 ml). To this solution, an aqueous solution
(1M) of Na2S2O4 (3 mmol) was added. This reaction mixture was then irra-
diated in a household microwave oven (Type: LG, Little Chef) for 60 s at a
power of 160 W. After the reaction was complete (as observed from thin-
layer chromatography, TLC), the reaction mixture was allowed to cool at
room temperature and was then treated with 5 N NH4OH. The solid
product that was formed was filtered and washed with water (2 ꢀ 15 ml)
and dried under suction. The product was purified using ethanol. To
extend the scope of the reaction, we tried the reaction of o-nitroaniline
with substituted aldehydes. The reactions went on smoothly, affording
complete conversion of the reactants in a short time. The results are sum-
marized in Scheme 1 and Table 1.

One-Pot Synthesis of Benzimidazoles
1377
Scheme 1.
EXPERIMENTAL
1
All products are known compounds and are well characterized by H NMR
and IR spectroscopy.
2-Phenylbenzimidazole (3a): A Typical Procedure
A mixture of o-nitroaniline (1 mmol) and benzaldehyde (1 mmol) was taken
in DMF (4.0 ml) in a 25-ml round-bottom flask. To this solution, an
aqueous solution (1M) of Na2S2O4 (3 mmol) was added. A funnel was kept
on the mouth of the flask, and this flask was kept in a 100-ml beaker. The
entire assembly was then placed in the microwave oven and the mixture
then irradiated with microwaves four times at a power of 160 W with pulse
15 s each and a 20-s cooling period between each pulse. After allowing the
Table 1. Microwave-assisted 2-substituted benzimida-
zoles using sodium dithionite
Entry
R
Yield (%)a
3a
3b
3c
3d
3e
3f
C6H5
4-ClC6H4
81
78
68
65
80
75
75
82
92
65
84
79
2-ClC6H4
2-BrC6H4
4-FC6H4
2-OHC6H4
3,4-(CH3O)2C6H4
4-OCH3C6H4
4-N,N-(CH3)2C6H4
2-Furyl
3g
3h
3i
3j
3k
3l
4-CH3C6H4
4-BrC6H4
aIsolated and unoptimized yields.

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M. P. Surpur et al.
reaction mixture to cool at room temperature, it was treated with 5 N NH4OH
dropwise to get the product. The product was filtered and washed with water
(2 ꢀ 15 ml) and dried under reduced pressure. The crude product was purified
from ethanol and gave 81% yield, mp 292–2938C.
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