1,3,5-Trimethylpyrazolium chloride based ionogel as an efficient and reusable heterogeneous catalyst for the synthesis of benzimidazoles

Article abstract of DOI:10.1007/s12039-015-1000-1

A new approach for the synthesis of benzimidazoles using ionogel under solvent-free conditions is reported. Catalytic activity of ionogel was compared with silica coated with ionic liquid (silica-IL) and it was found that ionogel is highly active compared to silica-IL for the synthesis of benzimidazoles. Moreover, ionogel was recyclable for the synthesis of benzimidazoles. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-015-1000-1

c
J. Chem. Sci. Vol. 128, No. 1, January 2016, pp. 61–65. ꢀ Indian Academy of Sciences.
DOI 10.1007/s12039-015-1000-1
1,3,5-Trimethylpyrazolium chloride based ionogel as an efficient and
reusable heterogeneous catalyst for the synthesis of benzimidazoles
PANKAJ SHARMA and MONIKA GUPTA∗
Department of Chemistry, University of Jammu, Jammu 180 006, India
e-mail: monika.gupta77@rediffmail.com
MS received 7 August 2015; revised 14 September 2015; accepted 8 October 2015
Abstract. A new approach for the synthesis of benzimidazoles using ionogel under solvent-free conditions
is reported. Catalytic activity of ionogel was compared with silica coated with ionic liquid (silica-IL) and it
was found that ionogel is highly active compared to silica-IL for the synthesis of benzimidazoles. Moreover,
ionogel was recyclable for the synthesis of benzimidazoles.
Keywords. Ionogel; catalysis; ionic liquid; silica; benzimidazoles.
1. Introduction
of acids, long reaction times, difficult work-up or
may be less substrate versatility. Still, there remains a
demand to synthesize compounds via better methodol-
ogy. Herein, we describe a study on the catalytic activity
of ionogel prepared from tetrethylorthosilicate (TEOS)
and 1,3,5-trimethylpyrazolium chloride through sol-gel
process and comparison with silica coated with 1,3,5-
trimethylpyrazolium chloride for the synthesis of benz-
imidazoles. Our method involves simple work-up
procedure, solvent-free conditions, less reaction time,
tolerance to various functionalities and excellent yields,.
In our previous study, the ionogel was shown to be
highly active for the synthesis of benzothiazoles.16 Ear-
lier also, we reported the modification of catalyst with
ionic liquid to improve the catalytic behavior of the
catalyst for one-pot synthesis of 1,4-dihydropyridines.17
It is well known that ionic liquids are playing an impor-
tant role in synthetic chemistry and scientific interest in
these liquids continues to grow exponentially. However,
sometimes ionic liquids can cause problems in prod-
uct separation and recovery of ILs, especially when the
product is polar or somewhat soluble in water. Also,
from the environment and economic point of view, het-
erogenization of homogeneous catalytic reactions has
attracted much attention.1 Heterogenization of ionic liq-
uids is an area of current research, which enables easy
recovery and reuse of expensive catalysts.
Structures containing benzimidazole moiety are well
known to have a wide range of biological applications.
The properties of benzimidazole and its analogs have
been studied since over hundred years. However, the
main reason for greater interest of researchers towards
benzimidazole derivatives is due to the fact that 5,6-
dimethyl-1-(α-dribofuranosyl) benzimidazole is a basic
part of the structure of vitamine B12.2 Moreover, benz-
imidazole is also a structural unit of naturally occurring
nucleotide due to which it easily interacts with biopoly-
mers of living system. Due to this character, benzimi-
dazoles are regarded as a promising class of bioactive
heterocyclic compounds that exhibit a range of
biological activities such as antihelminthic,3 antifungal,4
antimicrobial,5–7 antiviral8 and antineoplastic agents.9
No doubt, there are various synthetic approaches for
the synthesis of benzimidazoles.10–15 Some of them
include green procedures but some methods have cer-
tain drawbacks such as harsh reaction conditions, use
2. Experimental
2.1 Materials and instrumentation
Silica gel was purchased from ACROS Organics and
other used chemicals were purchased from Sigma
Aldrich or Merck chemical companies and were used
without further purification. IR spectra of the catalyst
and the synthesized compounds were recorded in the
range of 4000–300 cm−1 on a Shimadzu Prestige-21
spectrophotometer. TGA of the catalyst was obtained
on a Linesis Thermal Analyser with heating of 10◦C
per minute. SEM was recorded on a SEM JS-7600F
and TEM was recorded on CM200 PHILIPS transmis-
1
sion electron microscope. H NMR and 13C NMR of
∗For correspondence
the compounds were obtained on a Bruker Avance III
61

62
Pankaj Sharma and Monika Gupta
H
N
NH2
NH2
O
C
Ionogel
80 o
R
H
R
CH3
C
N
Cl-
1
3 a-n (upto 95%)
2
NH
Ionic
N
H3C
liquid
Scheme 2. Ionogel catalyzed synthesis of benzimidazoles.
CH3
IL
l
C
H
stirrer under solvent-free conditions. After completion
of reaction (monitored through TLC), the reaction mix-
ture was treated with ethylacetate and then filtered at
pump under reduce pressure. The filtrate obtained was
concentrated and kept at room-temperature until solid
product was formed in crystalline form which was then
slightly washed with pet ether and ethylacetate in the
ratio of 10:1 to obtain the product in pure form.
-
l
S
O
o
n
a
E
h
t
T
E
Si
Si
O
60 O
C
Homogeneous mixture
(Liquid)
O
O
N
N
Cl
O
Si
Si
IONOGEL
Scheme 1. General scheme for the preparation of ionogel.
3. Results and Discussion
(400 MHz) spectrometer. Mass spectra of the prod-
ucts were obtained on a Bruker Daltonics Esquire 3000
spectrometer.
3.1 Catalyst testing and optimization of reaction
conditions
The preparation and characterization of iono-
gel has already been described.16 The ionogel
was synthesized from tetraethylorthosilicate and
1,3,5-trimethylpyrazolium through sol-gel process
(scheme 1). The characterization of ionogel was done
by SEM, TEM, FTIR and TGA. The SEM micrographs
of the catalyst revealed the fine nature of ionogel,
whereas TEM images revealed the formation of ionogel
in the form of nanorods (figure 1). TGA graph indica-
ted thermal stability of the ionogel and confirmed its
ability to carry out reactions at 80◦C.
In order to compare the activities of both synthe-
sized catalysts, viz. silica supported ionic liquid cata-
lyst (silica-IL) and ionogel, m-nitrobenzaldehyde and
o-pheneylenediamine were chosen as test substrates for
synthesizing 2-substituted benzimidazoles (scheme 2).
The reaction was carried out at 80◦C under solvent-free
conditions and it was found that for the synthesis of 2-
substituted benzimidazoles, ionogel gave best results as
compared to silica supported ionic liquid (table 1). The
ionogel is basically three dimensional network of solid
material encapsulating ionic liquid completely which
may be the reason for high yield associated with ionogel
compared to silica-IL.
2.2 General procedure for the synthesis of
In order to optimize the temperature for synthesis of
benzimidazole, a test reaction was carried out at 40, 60,
benzimidazoles using ionogel
A mixture of aldehyde (2 mmol), o-phenylenediamine 80 and 100◦C (table 1), it was found that the reactions
(2 mmol) and ionogel (0.1 g) were taken in a round bot- carried out at 40◦C and 60◦C were very slow, but reac-
tomed flask (100 mL) and stirred at 80◦C on magnetic tion at 80◦C was clean and excellent yield of product
SEM image
TEM image
Figure 1. SEM and TEM images of the ionogel.

Ionogel catalyzed synthesis of substituted benzimidazoles
63
Table 1. Effect of catalyst and temperature in the synthesis
of benzimidazolesa under solvent-free conditions.
Entry Catalyst Temperature (◦C) Time (min.) Yieldb (%)
1
2
3
4
5
6
Silica-IL
Ionogel
Ionogel
Ionogel
Ionogel
Ionogel
80
80
r.t.
40
60
100
20
20
20
20
20
20
50
95
trace
55
70
95
aReaction conditions; o-Phenelyenediamine (2 mmol), m-
nitrobenzaldehyde (2 mmol), catalyst (0.1 g).
bIsolated yield.
Figure 2. Recyclability graph of the ionogel in the synthe-
sis of benzimidazole (3d, table 3).
Table 2. Effect of solvents studied in the synthesis of
benzimidazoles.a
synthesis of benzimidazoles. Solvent effect was also
studied in the synthesis of benzimidazoles and among
various tried solvents, solvent-less condition gave sig-
nificant results (table 2).
To study the generality of this method, a variety of
substrates were tried (table 3) for the synthesis of benz-
imidazoles and it was observed that aromatic, aliphatic
and heterocyclic aldehydes all yielded good yield of
products. Moreover, the catalyst worked very well with
various functional groups including electron-releasing
and electron-withdrawing groups with excellent yields.
Entry
Solvent
Conditions Time (min.) Yieldb (%)
1
2
3
4
5
6
CH2Cl2
CH3OH
C2H5OH
H2O
CH3CN
No-solvent
Reflux
Reflux
Reflux
80◦C
40
20
20
20
20
20
30
50
65
50
70
95
80◦C
80◦C
aReaction conditions; o-Phenelyenediamine (2 mmol), m-
nitrobenzaldehyde (2 mmol), ionogel (0.1 g).
bIsolated yield.
was obtained. At 100◦C, the reaction was not clean, may
be due to multiple product formation, and also no
3.2 Recyclability of the Ionogel
significant increase in yield was observed above 80◦C. The important feature of ionogel was that it was reusable
So, 80◦C was chosen to be the best temperature for for several runs with very little loss in activity. To test
Table 3. Physical data of the synthesized benzimidazolesa catalyzed by ionogel.
Entry
Product
R
Time (min.)
Yieldb (%)
M.p./Lit. (◦C)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
H
CH3
C6H5
25
30
15
20
10
15
20
15
25
10
15
10
15
15
90
88
92
95
94
92
90
91
90
94
90
90
93
92
171-172/172-17318
175-177/177-17819
301-303/301-30320
187-188/185-18721
324-326/326-32720
261-263/261-26322
291-292/290-29220
270-272/272-27423
250-252/250-25224
296-297/297-29825
264-266/263-26520
234-235/234-23520
218-220/22026
3-NO2C6H4
4-NO2C6H4
2-NO2C6H4
4-ClC6H4
4-OHC6H4
4-FC6H4
9
10
11
12
13
14
4-BrC6H4
4-MeC6H4
4-MeOC6H4
4-OH-3-MeOC6H3
2-furyl
230-232/234-23527
aOptimized reaction Conditions; o-Phenelyenediamine (2 mmol), aldehyde (2 mmol), ionogel (0.1 g), stirred at 80◦C under
solvent-free conditions.
bIsolated yield.

64
Pankaj Sharma and Monika Gupta
Si
O
Si
O
Si
O
N
N
Cl
O
Si
IONOGEL
O
C
H
NH2
OH
NH2
NH2
NH2
-H2O
H
C
H
C
N
H
N
1
Si
O
Si
O
Si
O
H
N
2
H
N
N
Cl
O
N
N
Si
N
H
Product
IONOGEL
Si
Si
O
O
IONOGEL
Si
Si
O
O
O
N
N
Cl
O
O
N
Si
N
Si
Cl
O
IONOGEL
Si
Si
Figure 3. Proposed mechanism for the synthesis of benzimidazoles.
the recyclability of ionogel for the synthesis of benzimi- zolium chloride based ionogel is a new and attractive
dazoles, a series of seven consecutive runs in the case of solid support which can contribute to the develop-
m-nitrobenzaldehyde (entry 4, table 3) were carried out ment of catalytic processes and minimal environmen-
and the results are represented in figure 2. These results tal problems (reusable catalyst, non-toxicity of the
demonstrated that ionogel is recyclable upto seven con- catalyst, reduced amount of solvent, etc.). The recy-
secutive runs without significant loss of activity. The clability of the catalyst makes the process greener and
very little loss in activity may be attributed to reduction cost-effective.
of some active sites of ionogel after each use.
3.3 Proposed mechanism for the synthesis of
benzimidazoles
Supplementary Information
Supplementary file contains details on preparation of
the ionic liquid and its characterization, preparation of
the ionogel and silica-supported catalyst, characteriza-
tion of the ionogel including SEM, TEM, FTIR and
TGA. It also contains spectral data of the synthesized
compounds.
Ionogel as a heterogeneous catalyst provides active sites
and large surface area for the reaction. Moreover, the
presence of ionic liquid has a strong influence on the
structural and textural properties of the catalyst. In the
proposed mechanism (figure 3), ionogel provides sur-
face area to both the reactants and facilitates the nucle-
ophilic attack of o-phenlyenediamine on the carbonyl
centre of aldehyde resulting in the formation of inter-
mediate 1 which gets converted into the product by the
loss of a H2.
Supplementary Information is available at www.ias.
ac.in/chemsci.
Acknowledgements
4. Conclusions
We are sincerely thankful to the Director, IIIM Jammu
In conclusion, we have developed a new kind of an and SAIF Chandigarh for facilities for spectra; Head,
efficient and selective procedure for the synthesis of Central Research facility section, IIT Roorkee for SEM
benzimidazoles from o−phenylenediamine with aliphatic/ and TEM. We also thank the Department of Chem-
heterocyclic/aromatic aldehydes catalyzed by ionogel istry, University of Jammu, for NMR, FTIR and TGA
under solvent free conditions. 1,3,5-Trimethylpyra- analysis.

Ionogel catalyzed synthesis of substituted benzimidazoles
65
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