Synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles catalyzed by br?nsted acidic ionic liquid under ultrasonic irradiation

Article abstract of DOI:10.14233/ajchem.2014.15606

A series of 2-aryl-1-arylmethyl-1H-benzimidazoles were synthesized through the condensation reactions of aromatic aldehydes and ophenylenediamine using Br?nsted acidic ionic liquid, 3-methyl-1-(3-sulfopropyl)-imidazolium trifluoro acetate, as catalyst under ultrasonic irradiation condition. The yields of the products were in the range from 85 % to 97 %. The Br?nsted acidic ionic liquid can be recovered and reused at least five consecutive cycles without significant loss of its catalytic activity. The results indicated that the proposed method is easy, efficient and environmental friendly for the preparation of 2-aryl-1-arylmethyl-1H-benzimidazoles.

Full text of DOI:10.14233/ajchem.2014.15606

Asian Journal of Chemistry; Vol. 26, No. 7 (2014), 1980-1982
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.15606
Synthesis of 2-Aryl-1-arylmethyl-1H-benzimidazoles Catalyzed by
Brønsted Acidic Ionic Liquid under Ultrasonic Irradiation
1
1
2
1
1,*
WEI-HUA LIU , SHU-TAO GAO , PENG-HUI ZHANG , XIN ZHOU and CHUN WANG
1College of Science, Agricultural University of Hebei, Baoding 071001, China
2Personnel Division, Agricultural University of Hebei, Baoding 071001, China
*Corresponding author: Tel/Fax: +86 312 7528292; E-mail: chunwang69@126.com
Received: 8 April 2013;
Accepted: 20 August 2013;
Published online: 22 March 2014;
AJC-14941
A series of 2-aryl-1-arylmethyl-1H-benzimidazoles were synthesized through the condensation reactions of aromatic aldehydes and o-
phenylenediamine using Brønsted acidic ionic liquid, 3-methyl-1-(3-sulfopropyl)-imidazolium trifluoro acetate, as catalyst under ultra-
sonic irradiation condition. The yields of the products were in the range from 85 % to 97 %. The Brønsted acidic ionic liquid can be
recovered and reused at least five consecutive cycles without significant loss of its catalytic activity. The results indicated that the pro-
posed method is easy, efficient and environmental friendly for the preparation of 2-aryl-1-arylmethyl-1H-benzimidazoles.
Keywords: Brønsted acidic ionic liquid, 2-Aryl-1-arylmethyl-1H-benzimidazoles, Synthesis.
Synthesis of benzimidazoles in aqueous media using Zn-
proline17, silica sulfuric acid18 and glyoxylic acid19 as catalyst
and high temperature in water20 have been reported in the
documents.
INTRODUCTION
Benzimidazole and their derivatives have diverse appli-
cations in medicinal chemistry because of their unique biolo-
gical and pharmacological activities. Many members of this
family have commercial applications in various realms of
therapy, including antiulcerative, antihypertensive, antiviral,
antifungal, antitumor and antihistaminic agents and antihel-
minthic agents in veterinary medicine1-7. Due to their affinity
towards enzymes and protein receptors, they have been appro-
priately classified as ‘privileged sub-structures’for drug design.
Moreover, benzimidazoles are very important intermediates
in various organic reactions8. Therefore, the preparation of benzi-
midazoles has received considerable attention in recent years.
Until now, many synthetic strategies for the preparation
of benzimidazoles have been reported in the literature. Gene-
rally, they are synthesized through the condensation reaction
of o-phenylenediamines and carboxylic acids or their deriva-
tives (nitriles, amidates, orthoesters)9 in the presence of strong
acids such as polyphosphoric acid10 or mineral acids11. Benzi-
midazoles have also been prepared by the condensation
reaction of aldehyde and arylenediamine under oxidative
conditions12-15. However, each of these methodologies suffer
from one or more shortcomings, such as low yields, long
reaction times, using toxic catalyst and solvents, tedious work-
up procedures and co-occurrence of several side reactions.
Organic reactions in aqueous media have attracted great
interest due to its safety, low cost and environmental friendly16.
Recently ionic liquids have been successful employed as
Brønsted acidic catalysts for a variety of reactions21-23 due to
their unique properties, such as extremely low vapor pressure,
excellent thermal stability, reusability, ability to dissolves many
organic and inorganic substrates and their potential to enhance
reaction rates and selectivity24.
In continuation of our research in developing environ-
mental benign synthetic methodlogies25, we report here a simple
and efficient method for the preparation of 2-aryl-1-aryl-
methyl-1H-benzimidazoles using Brønsted acidic ionic
liquid 3-methyl-1-(3-sulfopropyl)-imidazolium trifluoro
acetate ([HSO3-pmim][CF3COOH]) as catalyst under ultrasonic
irradiation condition (Fig. 1).
EXPERIMENTAL
Melting points were recorded on an electrothermal apparatus
and are uncorrected. 1H NMR (400 MHz) spectra were deter-
mined with Brucker AVANCE 400 spectrometer (CDCl3-d6)
using TMS as internal standard. IR spectra (cm-1) were measured
with a WQF-510 spectrometer.All of the Brønsted acidic ionic
liquids, [HSO3-pmim][CF3COOH], [HSO3-pmim][p-
toluenesulfonic acid] and [HSO3-pmim] [CHH3SO3H]
(Scheme-I), were synthesized according to the procedures
described in the literature26.

Vol. 26, No. 7 (2014)
Synthesis of 2-Aryl-1-arylmethyl-1H-benzimidazoles Catalyzed by Brønsted Acidic Ionic Liquid 1981
N
[HSO3pmim]
[CF3COOH]
Ar
N
N
NH2
NH2
N
H
2 ArCHO +
+
Ultrasound
Irradiation
H2O, r.t.
1
2
3
4
Ar
not formed
Ar = C6H5, 2-O2NC6H4, 4-O2NCH4, 2-Cl C6H4, 4-Cl C6H4, 2-CH3OC6H4,
4-CH3OC6H4, 4-CH3C6H4, 4-(CH3)2NC6H4
Fig. 1. Condensation reaction of aromatic aldehydes with o-phenylenediamine
3f: 1H NMR: δ 7.82 (d, J = 8 Hz, 1H): 7.54 (dd, J = 8 and
2 Hz, 1H): 7.40 (td, J = 8 and 2 Hz, 1H): 7.26 - 7.12 (m, 4H):
7.05 (t, J = 8 Hz, 1H): 6.90 (d, J = 8 Hz, 1H): 6.85 (d, J = 8
Hz, 1H): 6.77 (t, J = 7 Hz, 1H): 6.66 (dd, J = 7 and 1 Hz, 1H):
5.25 (s, 2H): 3.78 (s, 3H); 3.58 (s, 3H); IR (KBr, νmax, cm–1):
3176, 2954, 2930, 1564, 1476, 1243.
3g: 1H NMR: δ 7.85 (d, J = 8 Hz, 1H): 7.64 (d, J = 9 Hz,
2H): 7.32-7.23 (m, 1H): 7.22 (m, 2H): 7.02 (d, J = 9 Hz, 2H):
6.94 (d, J = 9 Hz, 2H): 6.80 (d, J = 8 Hz, 2H): 5.38 (s, 2H):
3.83 (s, 3H): 3.79 (s, 3H): IR (KBr, νmax, cm–1): 3163, 2956,
2932, 1554, 1476, 1240.
3h: 1H NMR: δ 7.87 (m, 1H): 7.59 (d, J = 8 Hz, 2H): 7.26
(m, 1H): 7.26 (d, J = 8 Hz, 2H): 7.22 (m, 2H): 7.13 (d, J = 8
Hz, 2H): 6.99 (d, J = 8 Hz, 2H): 5.41 (s, 2H): 2.40 (s, 3H):
2.33 (s, 3H): IR (KBr, νmax, cm–1): 3034, 2937, 2865, 1431, 1269.
3i: 1H NMR: δ 7.72 (d, J = 8 Hz, 1H): 7.56 (d, J = 9 and
2 Hz, 2H): 7.72-7.15 (m, 3H): 6.98 (d, J = 9 Hz, 2H), 6.72-
6.50 (m, 4H): 2.90 (s, 3H): 2.82 (s, 3H); IR (KBr, νmax, cm–1):
3043, 2969, 2919, 2780, 1592, 1440 cm-1.
An–
N
+
N
SO3H
H3C
An = CH3COOH, CH3SO3H,
p
-toluenesulfonic acid
Scheme-I: Structure of acidic ionic liquid
General procedure: A mixture of 10 mmol aldehyde 1,
5 mmol o-phenylenediamine 2, 0.25 mmol (5 mmol %) [HSO3-
pmim][CF3COOH] and 10 mL water were placed in a 50 mL
round-bottomed flask. Then, the reaction mixture was sub-
mitted to ultrasound irradiation at room temperature for a
desired period of time (monitored by thin-layer chromato-
graphy, TLC). Upon completion of the reaction, the mixture
was filtered and the obtained solid was washed with water.
The crude product was recrystallized from 95 % ethanol and
then dried to afford 2-aryl-1-arylmethyl-1H-benzimidazole 3
(Table-1). The products were identified by IR and 1H NMR.
The filtrate was extracted with ether (10 mL × 2) and evapo-
rated under reduced pressure to recover the catalyst.
RESULTS AND DISCUSSION
3a: 1H NMR: δ 7.80 (d, J = 8 Hz, 1H): 7.60 (dd, J = 8 and
2 Hz, 2H): 7.41-7.30 (m, 3H): 7.24-7.11 (m, 6H): 7.08 (dd,
J = 8 and 2 Hz, 2H): 5.30 (s, 2H); IR (KBr, νmax, cm-1): 3038,
2958, 1508,1473, 1235, 1196.
In our initial study, the condensation reaction of o-phenyl-
enediamine and benzaldehyde was chosen as the model reactant
in order to examine the efficiency of different catalysts. As
shown in Table-2, no product was obtained in the absence of
the catalyst, indicating that the catalyst was necessary for the
reaction.Among the catalysts tested, [HSO3-pmim][CF3COOH]
was found to be the most effective catalyst since it gave the
highest yield of product. Meanwhile, the effect of ultrasound
irradiation on the condensation reaction of o-phenylenedi-
amine and benzaldehyde was also investigated. To complete
the reaction, the reaction time was 120 min under the ultra-
sound irradiation condition and 180 min under stirring
condition without ultrasound irradiation.
3b: 1H NMR: δ 8.18-8.12 (m, 2H): 7.80 (dd, J = 8 and 1
Hz, 1H); 7.70-7.60 (m, 2H): 7.52-7.43 (m, 3H): 7.40 (td, J = 8
and 1 Hz,1H): 7.32 (td, J = 8 and 1 Hz, 1H): 7.12 (dd, J = 8
and 1 Hz, 1H): 6.90 (dd, J = 7 and 1 Hz, 1H): 5.72 (s, 2H); IR
(KBr, νmax, cm-1) : 3063, 1608, 1526, 1446, 1278, 1078.
3c: 1H NMR: δ 8.30 (d, J = 9 Hz, 2H): 8.20 (d, J = 8 Hz,
2H): 7.90 (dd, J = 8 and 1 Hz, 1H): 7.80 (d, J = 9 Hz, 2H):
7.40 (td, J = 7 and 1 Hz, 1H): 7.30 (td, J = 9 and 1 Hz, 1H);
7.25 (d, J = 9 Hz, 2H): 7.22 (dd, J = 8 and 1 Hz, 1H): 5.55 (s,
2H): IR (KBr, δmax, cm–1) : 3060, 1608, 1562, 1417, 1226, 1078.
3d: 1H NMR: δ 7.86 (d, J = 8 Hz,1H): 7.50-7.38 (m, 3H):
7.38-7.12 (m, 6H); 7.06 (td, J = 8 and 1 Hz, 1H): 6.60 (dd, J =
8 and 1 Hz, 1H): 5.34 (s, 2H): IR (KBr, νmax, cm-1): 3029,
2980, 2926, 1632, 1447, 1390, 1358, 1270, 1171, 1040.
3e: 1H NMR: δ 7.84 (d, J = 8 Hz, 1H): 7.54 (m, 2H): 7.40
(m, 2H): 7.38-7.24 (m, 4H): 7.18 (d, J = 8 Hz, 1H): 7.04 (d,
J = 9 Hz, 2H): 5.42 (s, 2H): IR (KBr, νmax, cm–1): 3038, 2928,
2863, 1470, 1449, 1071.
To generalize the proposed method, a series of aromatic
aldehydes were subjected to react with o-phenylenediamine
for the preparation of 1,2-disubstituted benzimidazoles. The
results were shown in Table-1, which indicated that a wide
range of structural varied aromatic aldehydes reacted smoothly
to give the 1,2-disubstituted benzimidazoles in good yields.
The reusability of the recycled catalyst was also investigated.
The recycled catalyst could be resued for at least five cycles
without loss catalytic activity.

1982 Liu et al.
Asian J. Chem.
TABLE-1
SYNTHESIS OF 1,2-DISUBSTITUTED BENZIMIDAZOLES CATALYZED BY [HSO3-pmim][CH3COOH]a
Entry
3a
3b
3c
Ar
Time (min)
120
Yield (%)
m.p. (°C)
129.1-132.5
118-120
m.p. lit. (°C)
133-134 [Ref. 27]
118[Ref. 27]
C6H5
85
95
97
88
92
89
88
89
90
2-O2NC6H4
4-O2NC6H4
2-ClC6H4
60
189-191 [Ref. 27]
158-159 [Ref. 27]
137-139 [Ref. 27]
151 [Ref. 27]
60
189.6-192.6
157-159.7
136-139.3
150-152
100
3d
3e
4-ClC6H4
100
2-CH3OC6H4
4-CH3OC6H4
4-CH3C6H4
4-(CH3)2NC6H4
150
3f
127.129 [Ref. 27]
126 [Ref. 27]
150
125.5-127.9
125-127
3g
3h
3i
120
252 [Ref. 27]
110
251-252
aReaction condition: molar ratio of aldehyde to o-phenylenediamine is 2:1, amount of catalyst is 5 mmol %
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TABLE-2
CONDENSATION REACTION OF BENZALDEHYDE
AND o-PHENYLENEDIAMINE
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Catalyst
Yield (%)
No catalyst
–
[HSO3-pmim][CF3 COOH]
85
60
10
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[HSO3-pmim][p-Toluenesulfonic acid]
[HSO3-pmim][CH3SO3H]
aReaction condition C6H5CHO: 10 mmol, o-phenylenediamine: 5
mmol, H2O: 10 mL, catalyst: 0.25 mmol reaction time: 120 min
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Conclusion
In conclusion, we have developed a mild, reliable
and environmentally benign procedure for the synthesis of
1,2-disubstituted benzimidazole derivatives using [HSO3-
pmim][CF3COOH] as catalyst in water media. The advantages
of this protocol are good yields, low catalyst loading and mild
reaction conditions. We believe that this method can be a useful
contribution to the present methodologies for the synthesis of
1,2-disubstituted benzimidazoles.
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ACKNOWLEDGEMENTS
This work was financially supported by the Natural Science
Foundation of Hebei Province (No. B2011204051) and the
Natural Science Foundation of the Agricultural University of
Hebei (LG201107).
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