Eco-friendly synthesis of benzimidazole derivatives using solid acid scolecite catalyst

Article abstract of DOI:10.1016/j.cclet.2010.03.038

A series of benzimidazole derivatives were synthesized expeditiously in good yields by condensation of 1,2-diaminobenzene and aromatic aldehydes in the presence of modified scolecite catalyst. The world wide availability, easy handling and reusability of catalyst, higher yields and shorter reaction times are the advantages of the present method.

Full text of DOI:10.1016/j.cclet.2010.03.038

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 1053–1056
www.elsevier.com/locate/cclet
Eco-friendly synthesis of benzimidazole derivatives
using solid acid scolecite catalyst
*
Lakshman S. Gadekar, Balasaheb R. Arbad, Machhindra K. Lande
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad (MS) 431004, India
Received 6 January 2010
Abstract
A series of benzimidazole derivatives were synthesized expeditiously in good yields by condensation of 1,2-diaminobenzene
and aromatic aldehydes in the presence of modified scolecite catalyst. The world wide availability, easy handling and reusability of
catalyst, higher yields and shorter reaction times are the advantages of the present method.
# 2010 Machhindra K. Lande. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Benzimidazole; Ethanol; Natural zeolite–scolecite
Benzimidazole and their derivatives display a wide range of biological properties, and they have commercial
applications in various realms of therapy, including ulcerative, anti-hypertensive, antiviral, antibacterial, anti-tumor,
antihistaminic and antihelminthic agents in veterinary medicine [1]. Benzimidazole derivatives exhibit significant
activity against several viruses such as HIV [2,3], influenza [4] and human cytomegalovirus (HCMV) [2], it also act as
topoisomerase inhibitors [5], selective neuropeptide YY1 receptor antagonists [6], angiotensin II inhibitors [7],
smooth muscle cell proliferation inhibitors [8] and have much more importance in organic synthesis.
As a result of their importance from industrial, pharmacological and synthetic point of view, several synthetic
routes of benzimidazoles have been reported, which includes the condensation of 1,2-diaminobenzene and aldehydes
[9,10], the condensation of 1,2-diaminobenzene and carboxylic acids or their derivatives in the presence of acids such
as polyphosphoric acid [11] or mineral acids [12], boric acid [13], p-toluene sulphonic acid [14], cerric ammonium
nitrate [15] as a catalyst.
Few recent protocols reported for the synthesis of benzimidazole derivatives include solvent-free synthesis of
benzimidazoles under microwave-irradiation using Yb(OTf)3 [16], KSF clay [17], PPA [18] Na2SO4 [19], metal halide
supported alumina [20] and solid support [21]. As many of these processes have limitations, such as use of some toxic
acids as a catalyst, drastic reaction conditions, low yields, high temperature, tedious workup procedures, there is need
to develop new route for the synthesis of benzimidazole derivatives to overcome these limitations.
In the recent years, the use of heterogeneous catalysts has received considerable interest in various disciplines
including organic synthesis. Synthetic organic routes followed by using heterogeneous catalysts have advantages over
their counterparts in which, used-catalyst can be easily recycled.
* Corresponding author.
E-mail address: mkl_chem@yahoo.com (M.K. Lande).
1001-8417/$ – see front matter # 2010 Machhindra K. Lande. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.03.038

[(Scheme_1)TD$FIG]
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L.S. Gadekar et al. / Chinese Chemical Letters 21 (2010) 1053–1056
Scheme 1.
Since last decade, there has been increased improvement in the synthetic methodology due to the use of solid acid
catalysts, such as clays and zeolites [22–24]. Zeolite catalyst has a Bronsted and Lewis acidic sites, which are
responsible for their reactivity. An extensive application of heterogeneous catalysts in synthetic organic chemistry can
make the synthetic process more efficient from both environmental and economic point of view [25].
We have previously reported the use of scolecite as a solid acid catalyst for the synthesis of 3,4-
dihydropyrimidones, 2,4,5-triarylimidazoles and polyhydroquinoline [26]. Herein, we report the synthesis of
benzimidazole derivatives by the condensation of 1,2-diaminobenzene and substituted aldehydes in ethanol using
modified scolecite as a catalyst (Scheme 1).
1. Experimental
All the reagents and aromatic aldehydes were obtained from S.D. Fine-Chem. Ltd. (Mumbai) and were used as
such. Melting points were determined in open capillaries apparatus and are uncorrected. The reactions were monitored
by TLC and visualized with UV light. IR spectra were recorded on a matrix of KBr with FTIR-4100 (Jasco, Japan)
spectrometer. 1H NMR spectra were recorded on Varian NMR spectrometer, Model Mercury Plus (200 MHz) and the
chemical shifts are given in ppm relative to TMS as an internal standard.
The naturally occurring scolecite zeolite is a calcium zeolite with NAT topology and an ordered (Si:Al) distribution.
The chemical compositions of natural scolecite (atom %) were Si, Al, Fe, Na, Ca and O in the ratio 16.03, 10.34, 0.03,
0.20, 7.05, 66.34 respectively. It was collected from the Ellora valley, Aurangabad (MS), Deccan traps of India. It was
subsequently washed with distilled water and acetone for several times, dried and crushed into fine powder which was
further washed with distilled water 3–4 times and dried at 110 8C in an oven. The resulting sample was heated at
500 8C in high temperature muffle furnace for 1 h at rate 3 8C per minute. The sample was naturally cooled and used in
organic synthesis. The surface area, pore volume, pore diameter of the catalyst was determined by the nitrogen
adsorption on Quantachrome Autosorb Instrument and Acidity of the sample measured by temperature programmed
desorption (TPD) of ammonia on Quantachrome TPR.
Aldehydes (0.5 mmol) and 1,2-diaminobenzene (0.5 mmol) were thoroughly mixed in ethanol (5 mL) then
scolecite (3 wt% with respective initial concentration of reactants) was added, and the solution was refluxed for
appropriate time (Table 2). The progress of the reaction was monitored by TLC. After completion of the reaction, the
reaction mixture was cooled to room temperature and the resulting solid was collected by filtration and dissolved in
20 mL ethyl acetate. The catalyst was recovered by filtration and the solution was washed with NaOH (5%, w/w).
After evaporation of the solvent, the resulting solid product was recrystallized from ethanol to obtain pure product.
Spectral data of typical compounds
2-(3-Chlorophenyl)benzimidazole (5): 1H NMR (200 MHz, DMSO-d6): d 7.18–7.22 (m, 2H), 7.52–7.59 (m, 4H),
8.11 (dd, 1H), 8.20 (s, 1H), 13.01 (s, 1H): IR (KBr, cmÀ1): 1618 (C N), 3458 (NH). m/z 229 (M+H)+.
2-(4-Methylphenyl)benzimidazole (11): 1H NMR (200 MHz, DMSO-d6): d 2.37 (s, 3H), 7.19 (d, 2H), 7.34–7.39 (m,
2H), 7.45–7.50 (m, 1H), 7.60–7.63 (m, 1H), 8.06 (d, 2H), 12.80 (s, 1H): IR (KBr, cmÀ1): 1622 (C N), 3432 (NH). m/z
209 (M+H)+.
2. Results and discussion
The cumulative desorption surface area of catalyst from adsorption–desorption isotherm of nitrogen
2
3
˚
(SBJH = 26.39 m /g), pore volume at p/po = 0.993 (PV = 0.0344 cm /g) and pore diameter (Pd = 11.08 A) was
determined by BJH method. Temperature programmed desorption (TPD) method was used to determine the acidic
properties of solid catalyst. This provides information about the total concentration and strength of acidic sites
(Bronsted and Lewis). It was found that the total ammonia desorbed is 0.376 mmol/g of the catalyst.
In order to find the optimum reaction conditions for eco-friendly synthesis of benzimidazole derivatives, we have
selected model reaction by refluxing 1:1 molar ratio of 1,2-diaminobenzene and 4-chlorobenzaldehyde in presence of

L.S. Gadekar et al. / Chinese Chemical Letters 21 (2010) 1053–1056
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Table 1
Effect of catalyst quantity in the synthesis of 2-(4-chlorophenyl)-1H-benzo[d]imidazole.
Weight of catalyst (%)
Time (min)
Yield (%)a
No catalyst
60
60
60
60
60
29
71
82
94
94
1
2
3
4
a
Yield refer to isolated products.
Table 2
Scolecite catalyzed synthesis of benzimidazole derivatives.
Entry
R
Time (min)
Yield (%)a,b
M.P. (8C) Found reported
1
2
C6H5
55
60
55
60
65
55
70
45
75
50
65
60
75
60
60
65
65
89
92
93
94
85
90
87
91
79
86
87
84
81
82
78
75
85
292–293
261–263
234–235
291–292
236–238
179–180
205–206
>300
290–293 [27]
264–265 [27]
234 [28]
2-NO2C6H4
2-ClC6H4
3
4
4-ClC6H4
288–291 [14]
238 [28]
5
3-ClC6H4
6
2-OCH3C6H4
3-OCH3C6H4
4-NO2C6H4
3-NO2C6H4
2-BrC6H4
179–180 [29]
205 [29]
7
8
322–323 [27]
204–206 [30]
246 [28]
9
204–205
247–248
263–265
200–201
239–240
224–225
284–285
>300
10
11
12
13
14
15
16
17
4-CH3C6H4
C6H5CH CH
2-OHC6H4
264–265 [27]
199–201 [14]
242 [10]
4-OCH3C6H4
C4H3O(2-furyl)
C4H3S(2-thiophene)
C6H5N(2-pyridine)
223–226 [15]
284–286 [31]
330 [15]
214–216
216–219 [15]
a
Yield refers to isolated products.
b
All compounds are known and their physical and spectroscopic data consistent with those of authentic samples.
various amount of modified scolecite in ethanol medium and the results are summarized in Table 1. It was observed
that the reaction completed in 60 min giving maximum yield (94%) of the product when 3 wt% catalyst was used. This
synthetic route is found to be inspiring. In a similar fashion, a variety of benzimidazole derivatives were synthesized
using different reactants and in each case it is observed that the time period for condensation was reduced considerably
and the yield of the products changed to excellent yields (Table 2). Aldehyde compounds which have electron donating
or electron withdrawing groups were used and as expected it gives good yield of products, only meta substituted
compound require comparatively more time. This indicates that the present catalyst efficiently makes the condensation
reaction much faster with increased yields.
In this reaction the catalyst can be recovered by filtration and washing with n-hexane and subjected to further reaction
after heating it at 110 8C in oven for an hour. The reusability of recovered catalyst was tested by performing condensation
reactions using the same amount of catalyst again and again and observed that the percentage yield remains almost same
as depicted in Table 3. This indicates that the catalyst could be recycled without much loss of catalytic activity.
Table 3
Recovery and reusability studies of modified scolecite catalyst for the synthesis of 2-(4-chlorophenyl)-1H-benzo[d]imidazole in ethanol solvent.
Entry
Cycle
Yield (%)a
1
2
3
4
Fresh
First
94
93
93
92
Second
Third
a
Yield refers to isolated product.

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L.S. Gadekar et al. / Chinese Chemical Letters 21 (2010) 1053–1056
3. Conclusion
The present synthetic protocol for the synthesis of benzimidazole derivatives is advantageous over the earlier
reported methods as (i) the reaction could be performed with an environmentally benign zeolite catalyst, (ii) it provides
a good yield of product (iii) the reaction occurs more rapidly, (iv) the catalyst was easily separated from the reaction
mixture and (v) efficiency of catalyst remains almost same in recycling process.
Acknowledgments
The authors are thankful to Head, Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad for providing necessary laboratory facilities, and one of the author (L.S. Gadekar) is thankful to
University for awarding Golden Jubilee J.R.F.
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