Mesoporous molecular sieve MCM-41 as a novel and efficient catalyst to synthesis of 2-substituted benzimidazoles

Article abstract of DOI:10.1002/jccs.200800166

o-Phenylenediamine derivatives readily react with benzoyl chloride derivatives in the presence of MCM-41 as catalyst to yield 2-substituted benzimidazoles in very good yields.

Full text of DOI:10.1002/jccs.200800166

Journal of the Chinese Chemical Society, 2008, 55, 1129-1132
1129
Mesoporous Molecular Sieve MCM-41 as a Novel and Efficient Catalyst to
Synthesis of 2-Substituted Benzimidazoles
Majid M. Heravi,* Bita Baghernejad, Hossein A. Oskooie and R. Malakooti
Department of Chemistry, School of Science, Azzahra University, Vanak, Tehran, Iran
o-Phenylenediamine derivatives readily react with benzoyl chloride derivatives in the presence of
MCM-41 as catalyst to yield 2-substituted benzimidazoles in very good yields.
Keywords: 2-Substituted benzimidazoles; MCM-41; Synthesis.
2
0-23
INTRODUCTION
The development of simple, efficient and environ-
lysts.
This is important because while some advantages
of homogeneous catalysts such as catalytic activities and
selectivities are retained, other properties like easier work-
up, recyclability and stability of heterogeneous systems
will be obtained. Different approaches like encapsulation
or immobilization of homogeneous catalysts in solid sup-
mentally benign chemical processes or methodologies for
widely used organic compounds from readily available re-
agents is one of the major challenges for chemists in or-
ganic synthesis.
2
4,25
The importance of benzimidazole units arises, be-
cause they are found in many biologically active com-
ports such as faujasite zeolites
homogeneous catalysts on reactive polymer surfaces or
and covalent grafting of
2
6
1
27,28
pounds. Several publications report benzimidazole-con-
inorganic solids
have been used. The latter is of great
taining compounds showing biological activities such as
importance especially after the discovery of a new class of
mesoporous molecular sieves such as MCM-41 containing
reactive silanol groups which offer large pores and great
surface area to accommodate the guest molecules. MCM-
41 have attracted the attention of many researchers. These
materials possess well-defined mesopores the diameters of
which can be tailored to the desired value (18-100 Å) by the
proper choice of surfactants, auxiliary organics and synthe-
2
selective neuropeptide YYI receptor antagonism, and as
5
-lipoxygenase inhibitors for use as novel antiallergic
3
4
agents, factor Xa (FXa) inhibitors, poly (ADP-ribose)
5
polymerase (PARP) inhibitors and as human cytomegalo-
6
virus (HCMV) inhibitors. In addition, benzimidazoles are
7
very important intermediates in organic reactions. There-
fore, the preparation of benzimidazoles has gained consid-
8
–10
29
erable attention in recent years.
2-Substituted benzimi-
sis parameter. Mesoporous silica of the MCM-41 type is
dazoles are widely used in medicinal chemistry because of
an important class of a hexagonal arrangement of cylindri-
11
their diverse biological activity and clinical applications.
cal pores between which an amorphous SiO
2
network is in-
3
0,31
The traditional synthesis of benzimidazoles involves the
terposed.
The most interesting feature of MCM-41 is its
reaction between a o-phenylenediamine and a carboxylic
regular pore system, which consists of a hexagonal array of
one-dimensional, hexagonally shaped pores. Other inter-
esting physical properties of MCM-41 include a highly
1
2
acid under harsh dehydrating reaction conditions. Anum-
ber of synthetic methods have been developed in recent
years to uncover a variety of new reagents for the synthesis
of 2-substituted benzimidazoles under milder conditions
2
specific surface area up to 1500 m /g, a specific pore vol-
ume up to 1.3 mL/g and a high thermal stability. All the
above properties make it suitable for many catalytic appli-
cations. Molecular sieves are widely used in acid catalyzed
reactions for the production of petrochemicals and fine
chemicals. In our attempts to develop new catalyst sys-
1
3
14
by the addition of Lewis acids, inorganic clays, and
1
5
mineral acids. Long reaction times for this reaction have
1
6,17,18
been mitigated by the use of microwave heating,
both
1
9
with and without polyphosphoric acid.
3
2
In recent years, great interest of many researchers has
tems, we selected MCM-41 as a new catalyst for the syn-
thesis of 2-substituted benzimidazoles (Scheme I).
been focused on the heterogenizing of homogeneous cata-
*
Corresponding author. Fax: +98-21-88047861; E-mail: mmh1331@yahoo.com

1
130 J. Chin. Chem. Soc., Vol. 55, No. 5, 2008
Heravi et al.
Table 1. Synthesis of benzimidazole derivatives catalyzed by
Scheme I
MCM-41
a
Entry
R’
R
Time (h) Product Yield (%)
1
2
3
4
5
6
7
8
9
C H -
H
H
H
CH3
CH3
CH3
NO2
2
2
2.5
2
2
2.5
2
2
2.5
2
2
2.5
3a
3b
3c
3d
3e
3f
3g
3h
3i
95
92
89
93
91
90
90
91
90
90
91
89
6
5
4-Me-C H -
6
4
CH3
C H -
6
5
4-Me-C H -
6
4
CH3
C H -
RESULTS AND DISCUSSION
6
5
4-Me-C H -
NO2
Since the discovery of mesoporous molecular sieves
6
4
2
9,31
CH3
C H -
NO2
MCM-41 by Mobile
in 1992, it has attracted consider-
1
0
Cl
Cl
Cl
3j
3k
3l
6
5
able attention for its potential use in catalytic reactions.
MCM-41 has a hexagonal array of cylindrical pores, cubic
ordered pores and lamellar structure, respectively. The
main characteristics of this material are large surface areas
1
1
4-Me-C H -
6
4
1
2
CH3
a
Isolated yields
3
3-37
and very narrow pore size distributions.
space enough to accommodate the guest molecules and are
In fact, it has
responding by-products.
2
8,38
We examined the reaction of o-phenylenediamines
and benzoyl chloride or acetyl chloride in the presence of
MCM-41 in different organic solvents (THF, acetonitrile,
ethanol, chloroform, ethyl acetate). The expected products
were obtained whose ratios depended on the nature of the
used in catalytic reactions.
During the course of our studies directed at the devel-
opment of practical and environmentally friendly proce-
3
2
dures for some important transformations, we developed
for the first time the applicability of a novel recyclable het-
erogeneous MCM-41 for efficient, convenient and facile
synthesis of 2-substituted benzimidazoles. 2-Substituted
benzimidazoles were obtained by the condensation of o-
phenylenediamine derivatives with various benzoyl chlo-
rides in the presence of MCM-41 as solid acid catalyst in
2 2
solvent and the best yields were obtained in CH Cl .
In summary, we have developed the use of MCM-41
as an inexpensive, easy to handle, non-corrosive and envi-
ronmentally benign catalyst for the synthesis of benzimida-
zole derivatives from o-phenylenediamine and benzoyl
chlorides. The advantages of the present procedure are us-
ing inexpensive and environmentally benign catalyst, rela-
tively short reaction time, simplicity of operation and work-
up, and high yields of products which makes it a useful al-
ternative to existing methods.
2 2
CH Cl (Scheme I) in good yields (Table 1). The effect of
temperature was studied by carrying out the reactions at
different temperatures. The yields of reactions increased as
the reaction temperature was raised. From these results, it
was decided that refluxing temperature would be the best
temperature for all reactions. In each reaction, the yield is a
function of the reaction time and the best time for all reac-
tions was completed after 2 h. The reaction proceeds very
cleanly under reflux conditions and is free of side products.
In the absence of the catalyst, the reaction did not complete
even after 24 h.
EXPERIMENTAL
All products are known compounds and were charac-
1
terized by mp, IR, H NMR and GC/MS. Melting points
were measured by using the capillary tube method with an
1
electro thermal 9200 apparatus. H NMR spectra were re-
We used acetyl chloride as a alkyl acid chloride; it is
noteworthy to mention that a slight amount of benzo [3,1,5]
oxadiazepine derivatives were obtained as by-products in
reactions including acetyl chloride. These by-products were
corded on a Bruker AQS AVANCE-300 MHz spectrometer
3
using TMS as an internal standard (CDCl solution). IR
spectra were recorded from KBr disks on the FT-IR Bruker
Tensor 27. GC/MS spectra were recorded on an Agilent
Technologies 6890 network GC system and an Agilent
5973 network mass selective detector. Thin layer chroma-
tography (TLC) on commercial aluminum-backed plates of
silica gel, 60 F254 was used to monitor the progress of re-
actions. All products were characterized by spectra and
1
detected using H NMR, IR spectroscopy and GC-Mass
analysis. Data were in accord with those reported for au-
thentic samples. In the case of benzoyl chloride, these
by-products were not observed. It may be due to the steric
effect of phenyl groups which prevent the formation of cor-

Mesoporous Molecular Sieve MCM-41
J. Chin. Chem. Soc., Vol. 55, No. 5, 2008 1131
physical data.
Table 2. Reuse of the MCM-41 for synthesis of 3a
Preparation of MCM-41
a
Entry
Time (h)
Yield (%)
MCM-41 was prepared according to a procedure de-
1
2
3
4
5
2
2
2
2.5
3
95
93
90
90
88
3
9
scribed previously. A typical procedure was as follows:
.8 g of fumed silica was added to a solution prepared from
1
dissolving 0.6 g of NaOH in 25 mL of water. The resultant
mixture was stirred for 2 h, and then 1.9 g of cetyltrimethyl
ammonium bromide (CTABr) in 20 mL of water was added
to this solution and stirred for one more hour. The resulting
reaction mixture which has the molar composition of 1
a
Isolated yields
MCM-41 in synthesis of 3a after five times is reported. As
is shown in Table 1 the first reaction using recovered
MCM-41 afforded a similar yield to those obtained in the
first run. In the second, third, fourth and fifth runs, the
yields were gradually decreased.
2 2 2
SiO , 7.5 Na O, 5.2 CTABr, 2500 H O was kept over night
and poured into a teflon lined stainless steel autoclave to
make crystallization under static conditions at 100 °C. The
product was filtered, washed with distilled water, dried at
7
0 °C and calcined in air at 540 °C for 4 h.
Typical procedure for the synthesis of 2-phenyl benz-
imidazole
Received May 7, 2008.
In this condensation reaction, to a stirred solution of
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