Acidic ionic liquid… by S B Sapkal et al.

, Bulletin of the Catalysis Society of India, 2 (2009) 78-83

Acidic ionic liquid catalyzed environmentally friendly synthesis of

benzimidazole derivatives.
S.B. Sapkal, K.F. Shelke, S.S. Sonar, B.B. Shingate and M.S. Shingare*
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad (M.S.) 431 004, India
E-mail: msshingare_org@rediffmail.com

Abstract: An efficient synthesis of benzimidazole derivatives from o-phenylenediamine

and substituted aromatic aldehyde catalyzed by ionic liquids in high yield under
microwave irradiation is reported. The remarkable advantages offered by this method are
much faster reaction, excellent yields, environmentally benign catalyst and simple work-
up procedure.
Keywords: Benzimidazole derivatives; ionic liquids; high yield; microwave irradiation.
Introduction
The synthesis of benzimidazole
derivatives has been of considerable
interest to organic chemists because of
their wide rang of biological and
pharmaceutical properties [1] including
inhibition of phosphodiesterase IV [2],
neuropeptide Y [3], anti-arrhythmic and
antiviral indications[4]. 2-aryl
substituted and 1, 2-diaryl substituted
benzimidazole also exhibit activity
against HIV [5] and influenza [6].
Current clinical examples include the
antihistamine Astemizole [7], the anti-
ulcerative Esomeprazole [8] and
Albendazole [9] which is used to treat
parasitic diseases. Benzimidazoles are a
component of vitamin B12 and are
related to the DNA base purines.
Bisbenzimidazoles are being developed
as DNA minor-groove binding agents
with antitumor activity [10].
Due to their great importance,
many synthesis strategies have been
developed. The most popular synthesis
approaches generally involve the
condensation of an arylenediamine with
a carboxylic acid or its derivative under
harsh dehydrating reaction conditions.
[11]. Another method is the
condensation of an aldehyde with
arylenediamine [12]. Very recently,
literature survey reveal several methods
for synthesis of benzimidazole and its
derivatives using hypervalent iodine as
oxidant [13], oxalic acid [14], H2O2/HCl
[15], TiCl4 [16], PPA [17], SOCl2/SiO2
[18], L-Praline [19], Sulphamic acid
[20] and Zeolite [21].
However many of these methods
have several drawbacks such as low
yields, use of expensive reagents, long
reaction time, tedious work-up
procedure, and harsh reaction
conditions. Therefore, the search
continues for a better catalyst for
synthesis of Benzimidazole derivatives
in term of operational simplicity,
economic valiability and in particular
greater selectivity. The use of ionic
liquids as reaction media and catalyst
can offer a solution to solvent emission
and catalyst recycle problems. Ionic
liquids posses the advantages like
negligible vapour pressure, reasonable
thermal stability, recyclability, dissolves
many organic and inorganic substrates.
Recently ionic liquids have been
successfully employed as solvents as
well as catalyst for a variety of reactions
[22] but their use as catalyst under
solvent free conditions needs to be given
more attention. Ionic liquids with acidic
counterions like in 1-hexyl-3-methyl-
imidazolium hydrogen sulphate
([hmim][HSO4]), 1-butyl-3-methyl-
imidazolium dihydogen phosphate
([bmim][H2PO4]), and 1-[2-(2-hydroxy-
ethoxy)ethyl]-3-methyl-imidazolium
hydrogen sulphate ([heemim][HSO4])
[23] can be used as good acid catalysts.
Moreover their polar natures make them
ideal for use in microwave oven.
78
Acidic ionic liquid… by S B Sapkal et al., Bulletin of the Catalysis Society of India, 2 (2009) 78-83
Recently we have reported the use of 1-
benzyl-3-methyl-imidazolium hydrogen
sulphate [bnmim]HSO4 ionic liquid for
the synthesis of 2-substituted and 1, 2-
disubstituted benzimidazoles from o-
phenylenediamine and aromatic
aldehydes under solvent free condition.
2. Experimental
2.1. Materials and Methods
All products are known
compounds and their physical data; IR
and 1H NMR spectra were essentially
identical with those of authentic
samples. All the reagents and aldehydes
were obtained from commercial
suppliers and were not purified. Melting
points were determined in open capillary
apparatus and are uncorrected. The
reactions were monitored by TLC. IR
spectra were recorded on Perkin-Elmer
FT spectrophotometer in KBr disc. 1H
NMR spectra were recorded on Varian
300 MHz spectrophotometer in DMSO-
d6 as a solvent and TMS as an internal
standard.
2.2. Synthesis of 2-substituted
benzimidazoles
O-phenylenediamine (1 mmol),
substituted aromatic aldehydes (1 mmol)
NH2
H R
NH2
1 2
Scheme 1
NH2
2 Ar
H R
NH2
Scheme 2
and [bnmim] HSO4 (0.1 mmol) was
homogenized in a beaker and irradiated
in microwave oven for about 5-8 min. at
microwave power 450 Watts. The
progress of reaction was monitored by
TLC. After completion of reaction, the
reaction mixture was cooled to room
temperature and poured on crushed ice.
The solid was obtained, filtered and
washed with water. This was
recrystallized from ethanol to give the
pure product.
2.3. Synthesis of 1, 2-disubstituted
benzimidazoles
O-phenylenediamine (1 mmol),
substituted aromatic aldehydes (2 mmol)
and [bnmim]HSO4 (0.2 mmol) was
homogenized in a beaker and irradiated
in microwave oven for about 4-8 min. at
microwave power 450 Watts. The
progress of reaction was monitored by
TLC. After completion of reaction, the
reaction mixture was cooled to room
temperature and poured on crushed ice.
The solid was obtained, filtered and
washed with water. This was
recrystallized from ethanol to give the
pure product.
O N
[bnmim]HSO4
R
MW
N
H
3
O N
[bnmim]HSO4
MW
N
4 Ar
79
Acidic ionic liquid… by S B Sapkal et al., Bulletin of the Catalysis Society of India, 2 (2009) 78-83

3. Result and Discussion

2-molar amount of aromatic aldehydes
During our present work with with o-phenylenediamine in high yield
[bnmim]HSO4, we investigated the [Scheme 2].
synthesis of 2-substituted benzimidazole
derivatives (3) with equimolar amount To examine the catalytic activity of
of aromatic aldehydes(2)and o- ionic liquids we explored a modification
phenylenediamine (1) under microwave of reaction condition with o-
irradiation [Scheme1]. phenylenediamine and benzaldehyde
using equimolar as well as 1:2 molar
This method was also reported for the proportions respectively the results
synthesis of 1, 2-disubstituted using different ionic liquids are given in
benzimidazole derivatives (4) by using Table 1.

Table-1. Results of the reaction affected by different ionic liquids

Entry Ionic liquids Time(min) Yield (%)

1 b no catalyst 15 no reaction
c no catalyst 15 no reaction
2 b [bnmim]Cl 15 45
c [bnmim]Cl 15 39
3 b [bmim]Cl 15 40
c [bmim]Cl 15 41
4 b [bnmim]HSO4 a 05 92
c [bnmim]HSO4 05 90
a This ionic liquid were prepared using [bnmim]Cl and NaHSO4 in microwave oven
[24]. b- Equimolar proportion and c- 1:2 proportion of o-phenylenediamine and
benzaldehyde.

From above tabular data, we observed 4. Conclusion

that, an acidic ionic liquid
[bnmim]HSO4 gives high yield in
shorter reaction time entry-4a,4b, but
[bnmim]Cl and [bmim]Cl gives very
poor yield entry 2b-3c and no reaction
we observed in absence of ionic liquid.
The results disclosed in Table-2
and Table-3 shows the scope and
generality of the method with
[bnmim]HSO4 catalyst. One of the
salient feature of this method is that, an
electron withdrawing as well as electron
donating group substituted aromatic
aldehydes gives excellent yields and
purity.
While comparing the performance of
neutral and acidic ionic liquids for an
efficient synthesis of benzimidazole
derivatives from o-phenylenediamine
and aromatic aldehydes under solvent
free condition, some of the advantages
of this procedure are the very good
yield, shorter reaction time, use of
inexpensive, environmentally benign
catalyst and simple work-up procedure.
Acknowledgements
The authors are grateful to the Head,
Department of Chemistry, Dr. Babasaheb
Ambedkar Marathwada University,
Aurangabad for providing the laboratory
facility.

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Acidic ionic liquid… by S B Sapkal et al., Bulletin of the Catalysis Society of India, 2 (2009) 78-83

Table 2. [bnmim]HSO4 catalyzed synthesis of benzimidazole derivatives.

____________________________________________________________________
Productsa R Time (min) Yield (%) b M.P (°C)
____________________________________________________________________
3a
5 95 292-294
3b
Me 5 93 263-264
3c
Br 5 92 250-252
3d
NO2
8 90 201-202
3e
O2N 8 91 312-314
3f
Cl 5 96 230-232
3g
Cl 6 90 236-238
3h
Cl 5 94 289-290
3i
OMe 5 94 175-176
3j
OMe 5 89 207-209
3k
MeO 5 95 220-223
3l
(Me)2N
6 95 228-229
3m
Me 5 95 225-227
____________________________________________________________________
a
All compounds are known and their physical and spectroscopic data were in good
agreement with those of authentic samples. b Yields refer to isolated products.

81
 Acidic ionic liquid… by S B Sapkal et al., Bulletin of the Catalysis Society of India, 2 (2009) 78-83

Table 3. [bnmim]HSO4 catalyzed synthesis of 1,2-disubstituted benzimidazoles.

Productsa Ar Time(min) b
Yield(%) M.P(°C)

4a
5 90 132-134
4b
O2N
7 91 192-194
4c
NO2
7 85 118-120
4d
(Me)2N 5 95 252-254
4e
Cl 5 91 137-139
4f
Cl 5 92 155-157
4g
Me 5 89 126-128
4h
MeO 6 87 130-131
4i
OMe 6 92 151-153
4j
O 4 94 96-98
4k
NC 5 92 113-115

a
All compounds are known and their physical and spectroscopic data were in good
agreement with those of authentic samples. b-Yields refer to isolated products.

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