Simple and efficient method for the synthesis of benzimidazole derivatives using monoammonium salt of 12-tungstophosphoric acid

Article abstract of DOI:10.1080/00397910701410681

Benzimidazoles have been synthesized in very good yield from o-phenylenediamine and aromatic aldehydes in the presence of monoammonium salt of 12-tungstophosphoric acid [(NH4)H2PW12O40], an efficient heterogeneous catalyst. This catalyst has the advantage

Full text of DOI:10.1080/00397910701410681

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Simple and Efficient Method for the
Synthesis of Benzimidazole Derivatives using
Monoammonium Salt of 12‐Tungstophosphoric
Acid
B. Y. Giri a , B. L. A. Prabavathi Devi a , K. N. Gangadhar a , K. Vijaya
Lakshmi a , R. B. N. Prasad a , N. Lingaiah b & P. S. Sai Prasad b
a Lipid Science and Technology Division, Indian Institute of Chemical
Technology (CSIR), Hyderabad, India
b Inorganic and Physical Chemistry Division, Indian Institute of Chemical
Technology (CSIR), Hyderabad, India
Version of record first published: 11 Jul 2007
To cite this article: B. Y. Giri, B. L. A. Prabavathi Devi, K. N. Gangadhar, K. Vijaya Lakshmi, R. B. N. Prasad,
N. Lingaiah & P. S. Sai Prasad (2007): Simple and Efficient Method for the Synthesis of Benzimidazole
Derivatives using Monoammonium Salt of 12‐Tungstophosphoric Acid, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:14, 2331-2336
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Synthetic Communicationsw, 37: 2331–2336, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701410681
Simple and Efficient Method for the
Synthesis of Benzimidazole Derivatives
using Monoammonium Salt of
12-Tungstophosphoric Acid
B. Y. Giri, B. L. A. Prabavathi Devi, K. N. Gangadhar,
K. Vijaya Lakshmi, and R. B. N. Prasad
Lipid Science and Technology Division, Indian Institute of Chemical
Technology (CSIR), Hyderabad, India
N. Lingaiah and P. S. Sai Prasad
Inorganic and Physical Chemistry Division, Indian Institute of Chemical
Technology (CSIR), Hyderabad, India
Abstract: Benzimidazoles have been synthesized in very good yield from o-
phenylenediamine and aromatic aldehydes in the presence of monoammonium salt
of 12-tungstophosphoric acid [(NH4)H2PW12O40], an efficient heterogeneous
catalyst. This catalyst has the advantages of simple workup procedure, water insolubi-
lity, and good activity with high yield for the synthesis of benzimidazole derivatives.
Keywords: aldehydes, benzimidazole, monoammonium salt of 12-tungstophosphoric
acid, o-phenylenediamines
INTRODUCTION
The development of a simple, efficient, environmentally benign, and economi-
cally viable chemical process or methodologies for widely used organic
Received in India December 4, 2006
IICT Communication No. 061006.
Address correspondence to R. B. N. Prasad, Lipid Science and Technology
Division, Indian Institute of Chemical Technology (CSIR), Uppal Road, Hyderabad
500 007, India. E-mail: rbnprasad@iict.res.in
2331

2332
B. Y. Giri et al.
compounds are in great demand. Benzimidazole structures are classified under
several classes of drugs,[1] based on the possible substitutions at different
positions of the benzimidazole nucleus. The benzimidazole nucleus is found
in variety of pharmaceuticals as an cardiotonic,[2a] potential antitumor,
antiulcer, and antiviral agent.[3] In particular the triflouromethyl benzimida-
zoles[4] have important pesticidal and antibacterial activities. The importance
of benzimidazole units, especially in biochemistry, is increasing recently,
because they are found in many biological activity compounds.[5]
Hence, several methodologies for synthesizing benzimidazole deriva-
tives have already been optimized where azalactones, 2-aryl-1, 1-dibro-
moethanes, nitriles, and amino amides[6] are used as starting materials for
this synthesis. All these compounds contain the benzimidazole skeleton,
and hence it has been assumed that this is neccesarry for the therapeutic
effect. The condensations of o-aryldiamines with carboxylic acids or their
derivatives in the presence of strong acids such as polyphosphoric acid or
mineral acids[7] and other reagents such as I2/KI/K2CO3 N-halosuccini-
[8]
mide (X ¼ Cl, Br, I),[9] Yb(OTf)3,[10] and palladium, as well as using
microwave irradiation[11] and solid-phase reactions,[12] are reported in litera-
ture. However, many of the synthetic protocols reported so far suffer from
disadvantages, such as a requirement for anhydrous conditions, use of
organic solvents, harsh reaction conditions, prolonged reaction times,
expensive reagents, and low to moderate yields. Almost all the reported
methods make use of an acid catalyst, giving rise to tedious workup pro-
cedures. Therefore, the development of a cost-effective, safe, and environ-
mentally friendly reagent is still needed.
RESULTS AND DISCUSSION
Recently, we have employed monoammonium salt of 12-tungstophosphoric
acid catalyst,[13] in organic reactions for the selective esterification of
aliphatic carboxylic acids[14] and synthesis of 1, 5-benzodiazepines.[15] In
the present study, the versatility of this catalyst for the synthesis of benzimi-
dazole derivatives was attempted and found to be more efficient for the
condensation of o-phenylenediamine with aromatic aldehydes (Scheme 1).
Scheme 1. Synthesis of benzimidazole derivatives.

Table 1. Condensation of o-phenylenediamine with various aldehydes catalyzed by monoammonium salt of 12-
tungstophosphoric acid
Entry
1
Diamine
Aldehyde
Product
Yield (%)a
84
4-Methyl benzaldehyde
2
3
4
5
4-Methoxy benzaldehyde
Benzaldehyde
86
85
84
4-N,N-Dimethyl benzaldehyde
Benzaldehyde
92
(continued)

Table 1. Continued
Entry
6
Diamine
Aldehyde
Product
Yield (%)a
94
4-Methyl benzaldehyde
7
8
4-Methoxy benzaldehyde
4-N,N-Dimethyl benzaldehyde
4-Nitro benzaldehyde
94
91
90
91
94
89
9
10
11
12
4-Methyl benzaldehyde
4-Methoxy benzaldehyde
4-Flouro benzaldehyde
aIsolated yield.
Note. All the reactions were completed in 45–60 min.

Synthesis of Benzimidazole Derivatives
2335
The reactions were carried out by taking a 1:1 molar ratio mixture of
o-phenylenediamine and aldehyde in 1,2-dichloroethane (5 ml) as solvent in
the presence of 5 wt% of the catalyst of diamine with stirring at reflux con-
ditions for the appropriate time. In a specific experiment, the reaction is
mainly the condensation of 3-nitro-5-trifluoromethyl-o-phenylene diamine
and benzaldehyde in 1,2-dichloroethane as a solvent in the presence of a
catalyst. The reaction proceedes efficiently, giving 84 to 94% yields of benzi-
midazoles. The scope and efficiency of our method are summarized in Table 1.
Completion of the reaction was monitored by thin-layer chromatography
(TLC) using 30% EtOAc in hexane as the solvent system. The products
were characterized by spectroscopic methods such as NMR, IR, and gas
chromatography-mass spectroscopy (GC-MS). After completion of the
reaction, the organic layer was filtered from the catalyst and concentrated,
and the product was purified by silica-gel chromatography by gradient
elution of hexane and ethyl acetate. The monoammonium salt of 12-tungsto-
phosphoric acid catalyzed the condensation reactions and gave excellent
yields under reflux conditions in relatively short reaction times (45–60 min).
In conclusion, the use of monoammonium salt of 12-tungstophosphoric
acid catalyst for the synthesis of benzimidazoles from o-phenylenediamine
and aldehyde is an environmentally benign and economic process. The advan-
tages of the present protocol are mild, heterogeneous conditions, shorter
reaction times, easy workup, low toxicity, and inexpensive catalyst, which
make the procedure an attractive alternative to the existing methods for the
synthesis of benzimidazoles.
EXPERIMENTAL
1H NMR spectra were recorded a Varian 200- or Bruker 300-MHz
spectrometer. IR spectra were recorded on a Perkin Fourier transform-
infrared spectrometer (FT-IR) spectrometer. The reaction monitoring was
accomplished by TLC on silica-gel plates.
Typical Procedure for the Preparation of Benzimidazole
Derivatives
O-phenylenediamine (1 mmol), p-methoxybenzaldehyde (1 mmol), and mono-
ammonium salt of 12-tungstophosphoric acid catalyst (5 wt% of diamine) were
stirred rapidly at reflux temperature for an appropriate time. The reaction was
monitered by TLC (hexane–EtOAc v/v). The reaction mixture was taken in
chloroform and filtered to separate the catalyst. The filtrate was concentrated
under vacuum, and the product was purified on a silica-gel column eluting
with EtOAc–hexane to afford a pure product in 84–94% yield.

2336
B. Y. Giri et al.
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