Sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester a recyclable catalyst for the synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazole derivatives

Article abstract of DOI:10.1016/j.cclet.2011.04.012

A highly selective synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles from the reaction of o-phenylene-diamine and aromatic aldehydes in the presence of sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester (SASPSPE) in water and at 80 °C in good to

Full text of DOI:10.1016/j.cclet.2011.04.012

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1151–1154
www.elsevier.com/locate/cclet
Sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester
a recyclable catalyst for the synthesis of
2
-aryl-1-arylmethyl-1H-1,3-benzimidazole derivatives
*
Nasir Iravani , Negar Safikhani Mohammadzade, Khodabakhsh Niknam
*
Department of Chemistry, Islamic Azad University, Gachsaran Branch, Gachsaran, Iran
Received 10 January 2011
Available online 18 July 2011
Abstract
A highly selective synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles from the reaction of o-phenylene-diamine and
aromatic aldehydes in the presence of sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester (SASPSPE) in water and at 80 8C in
good to excellent yields.
#
2011 Nasir Iravani. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester; 2-Aryl-1-arylmethyl-1H-1,3-benzimidazoles; Aldehydes; o-Phenylenedia-
mine; Water
The benzimidazole nucleus is of significant importance to medicinal chemistry. Benzimidazoles are a component
of vitamin B12 and are related to the DNA base purine and the stimulant caffeine [1]. Interest in benzimidazole-
containing structures stems from their widespread occurrence in molecules that exhibit significant activity [2,3]. In
light of the affinity they display towards a variety of enzymes and protein receptors, medicinal chemists would
certainly classify them as ‘privileged sub-structures’ for drug design [4,5].
The traditional synthesis of benzimidazoles involves the reaction between an o-phenylenediamines and a carboxylic
acidoritsderivatives(nitriles, amidates, orthoesters)underharshdehydratingconditions[6,7]. Benzimidazoleshavealso
been prepared on solid-phase to provide a combinatorial approach [8]. The most popular strategies for their synthesis
utilizeo-nitroanilinesasintermediatesor resort to directN-alkylationof anunsubstitutedbenzimidazole[9]. A number of
synthetic protocols that involve intermediate o-nitroanilines have evolved to include the synthesis of benzimidazoles on
solid support [10]. Another method for the synthesis of these compounds is the reaction of o-phenylenediamines with
aldehydes in the presence of acidic catalysts under various reaction conditions [11–19].
Recently we prepared sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester (SASPSPE) and used as a catalyst for
the formylation and acetylation of hydroxyl groups [20] (Scheme 1).
During the course of our studies towards the development of new routes to the synthesis of highly substituted
heterocycles and using solid acid catalysts [21–26], herein we wish to report a valid and an efficient procedure for the
*
Corresponding authors.
E-mail addresses: iravani.nasir@yahoo.com (N. Iravani), khniknam@gmail.com (K. Niknam).
1001-8417/$ – see front matter # 2011 Nasir Iravani. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.04.012

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N. Iravani et al. / Chinese Chemical Letters 22 (2011) 1151–1154
Scheme 1. Preparation of sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester (SASPSPE).
Scheme 2. Condensation of o-phenylenediamine with aromatic aldehydes catalyzed by SASPSPE.
Table 1
The reaction of o-phenylenediamine with 4-methylbenzaldehyde in the presence of different amounts of SASPSPE at 80 8C in water.
a
b
Entry
The amount of catalyst (g)
Product
Time (min)
Yield (%)
1
2
3
3
4
–
–
3
3
3
3
180
50
40
30
30
–
70
80
90
90
0.01
0.03
0.05
0.1
a
The molar ratios of 1,2-phenylenediamine and aldehyde were used as followed 1:2 respectively at 80 8C in water (5 mL).
Isolated yield.
b
synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles via one-pot condensation of o-phenylenediamine and
aldehydes in the presence of SASPSPE as an inexpensive solid acid catalyst (Scheme 2).
To study the effect of catalyst loading on the condensation of o-phenylenediamine, aldehydes as the corresponding
2-aryl-1-arylmethyl-1H-1,3-benzimidazoles, the reaction of o-phenylenediamine and 4-methylbenzaldehyde was
chosen as a model reaction in water under reflux conditions (Table 1).
The results show clearly that SASPSPE is an effective catalyst for this transformation and in the absence of
SASPSPE, the reaction did not take place, even after 3 h (Table 1, entry 1). As indicated in Table 1, the best result has
been obtained with an amount of 0.05 g (1.7 mol%) SASPSPE in terms of reaction time and isolated yield.
Several aromatic aldehydes with different substituents on the aromatic ring were subjected to the condensation
reaction. As Table 2 shows, arylaldehydes without substituents gave the desired benzimidazoles in excellent yields
(3a, 3i). Aromatic aldehydes bearing electron-donating substituents gave the desired benzimidazoles (3b–3d) in a
short reaction times (20–25 min) and very good to excellent yields (Table 2). Arylaldehydes with electron-
withdrawing substituents such as 4-cyano- and 4-fluorobenzaldehyde gave the corresponding benzimidazoles 3g, and
3
h in very good yields. To extend the scope of this method, we also examined the condensation of alkyl aldehydes such
as butanal and octanal with o-phenylenediamine, but failed. In addition, the condensation reaction of cyclohexanone
with o-phenylenediamine failed (Table 2, entries 10–12).
The possibility of recycling the catalyst was examined. For this reason, the reaction of o-phenylenediamine with
4-methylbenzaldehyde in the presence of SASPSPE was studied at 80 8C in water. Upon completion, the reaction
mixture was filtered and washed with warm ethanol. The product was recrystallized from hot water–ethanol (1:1).

N. Iravani et al. / Chinese Chemical Letters 22 (2011) 1151–1154
1153
Table 2
Synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles catalyzed by SASPSPE at 80 8C in water.
a
b
Entry
Aldehyde
CHO
Product
Time (min)
Yield (%)
87
M
p
(8C)
1
2
3
4
5
6
7
8
9
C
6
H
5
3a
3b
3c
3d
3e
3f
25
130–132
128–130
129–131
150–151
135–137
161–163
82–84
190–192
92–94
–
c
c
4-CH
4-CH
2-CH
3
3
3
C
6
H
4
CHO
25, 25, 30, 35, 35
90, 88, 89, 86, 85
OC
OC
6
H
H
4
CHO
CHO
20
25
30
35
35
35
30
45
45
45
93
6
4
91
4-ClC
2-ClC
6
H
H
4
4
CHO
CHO
90
6
89
4-FC
4-NCC
2-Furyl-CHO
6
H
4
CHO
3g
3h
3i
85
6
H
4
CHO
93
75
10
11
12
CH
CH
3
(CH
(CH
2
)
)
2
–CHO
–CHO
3j
Trace
Trace
–
3
2
6
3k
3l
–
Cyclohexanone
–
a
b
c
The molar ratios of 1,2-phenylenediamine:aldehyde:SASPSPE were used as followed 1:2: and 0.05 (g) respectively at 80 8C in water (5 mL).
Isolated yield.
The recycled catalyst was used.
The recycled catalyst could be reused four times without any treatment. No observation of appreciable loss in its
catalytic activities was shown (Table 2, entry 2).
In conclusion, heterogeneous conditions, green solvent, easy and clean work-up, high yields and recovery of the
catalyst makes this method practical for the synthesis of benzimidazole derivatives.
General procedure, synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles
In a round bottomed flask to a mixture of o-phenylenediamine (1 mmol), aromatic aldehyde (2 mmol) in water
5 mL), SASPSPE (0.05 g, 1.7 mol%) were added and the reaction mixture stirred in an oil bath at 80 8C for the
(
appropriate time (see Table 2). The progress of the reaction was followed by TLC. After completion of the reaction, the
mixture was filtered and the precipitates were solved in hot ethanol (3Â 10 mL) and filtered to afford the desired
product. Finally the crude product was recrystallized from water–ethanol (1:1). The recovered catalyst was dried and
reused for subsequent runs.
1
Compound 3a: mp 130–132 8C, Lit. [11] 129–130 8C. H NMR (400 MHz, CDCl ): d 5.37 (s, 2H), 7.02 (dd, 2H,
3
J = 8.1 Hz, J = 1.5 Hz), 7.11–7.17 (m, 2H), 7.21–7.27 (m, 4H), 7.33–7.39 (m, 3H), 7.59–7.62 (m, 2H), 7.79 (dd, 1H,
1
2
1
J = 8.7 Hz, J = 1.0 Hz). C NMR (100 MHz, CDCl ): d 48.42, 110.59, 120.02, 122.73, 123.09, 126.01, 127.82,
3
1
2
3
1
28.80, 129.11, 129.30, 129.97, 130.09, 136.09, 136.42, 143.20, 154.22.
1
Compound 3b: mp 128–130 8C, Lit. [19] 128–130 8C. H NMR (500 MHz, CDCl ): d 2.33 (s, 3H), 2.40 (s, 3H),
3
5
J = 7.8 Hz), 7.86 (d, 1H, J = 8.0 Hz). C NMR (125 MHz, CDCl ): d 21.50, 21.85, 48.65, 110.96, 120.18, 123.06,
.41 (s, 2H), 6.99 (d, 2H, J = 7.8 Hz), 7.13 (d, 2H, J = 7.8 Hz), 7.19–7.26 (m, 4H), 7.30 (t, 1H, J = 7.3 Hz), 7.59 (d, 2H,
1
3
3
1
23.33, 126.32, 127.44, 129.61, 129.88, 130.13, 133.81, 136.45, 137.90, 140.55, 154.68.
1
Compound 3c: mp 129–131 8C, Lit. [19] 129–130 8C. H NMR (500 MHz, CDCl ): d 3.81 (s, 3H), 3.88 (s, 3H),
3
5
.41 (s, 2H), 6.89 (dt, 2H, J = 6.9 Hz, J = 2.4 Hz), 7.01 (dt, 2H, J = 8.8 Hz, J = 2.4 Hz), 7.06 (d, 2H, J = 8.7 Hz),
1
2
1
2
1
.24–7.26 (m, 2H), 7.31–7.34 (m, 1H), 7.68 (dt, 2H, J = 8.8 Hz, J = 2.4 Hz), 7.88 (d, 1H, J = 8.0 Hz). C NMR
3
7
1
2
(
125 MHz, CDCl ): d 48.33, 55.71, 55.80, 110.85, 114.63, 114.86, 120.09, 122.75, 123.00, 123.20, 127.64, 128.86,
3
1
31.15, 136.46, 154.47, 159.56, 161.37.
1
Compound 3d: mp 150–151 8C, Lit. [19] 149–152 8C. H NMR (500 MHz, CDCl ): d 3.59 (s, 3H), 3.77 (s, 3H),
3
5
.24 (s, 2H), 6.70 (d, 1H, J = 6.8 Hz), 6.76 (t, 1H, J = 7.4 Hz), 6.83 (d, 1H, J = 8.2 Hz), 6.96 (d, 1H, J = 8.3 Hz), 7.05
(
t, 1H, J = 7.5 Hz), 7.17–7.28 (m, 4H), 7.45 (dt, 1H, J = 7.9 Hz, J = 1.6 Hz), 7.54 (dd, 1H, J = 7.5 Hz, J = 1.6 Hz),
1 2 1 2
1
.86 (d, 1H, J = 8.0 Hz). C NMR (125 MHz, CDCl ): d 44.07, 55.59, 55.63, 110.40, 111.25, 111.31, 120.07, 120.83,
3
7
1
3
21.25, 122.56, 123.03, 124.83, 127.26, 128.23, 128.89, 131.98, 132.82, 156.96, 158.04.
Acknowledgment
We are thankful to the Islamic Azad University Research Council for the partial support of this work.

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N. Iravani et al. / Chinese Chemical Letters 22 (2011) 1151–1154
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