Four-component, one-pot synthesis of tetra-substituted imidazoles using a catalytic amount of MCM-41 or p-TsOH

Article abstract of DOI:10.1080/00397910903068204

An improved and rapid one-pot synthesis of tetrasubstituted imidazoles by condensing benzil, ammonium acetate, amines, and aromatic aldehydes and using a catalytic amount of silica structure MCM-41 or p-toluenesulfonic acid (p-TsOH) as efficient, green, reusable catalysts in excellent yields is reported.

Full text of DOI:10.1080/00397910903068204

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Four-Component, One-Pot Synthesis of
Tetra-Substituted Imidazoles Using a
Catalytic Amount of MCM-41 or p-TsOH
Rahim Hekmat Shoar a , Golnaz Rahimzadeh a , Fatemeh Derikvand a
& Maryam Farzaneh a
a Department of Chemistry, School of Sciences , Alzahra University ,
Vanak, Tehran, Iran
Published online: 07 Apr 2010.
To cite this article: Rahim Hekmat Shoar , Golnaz Rahimzadeh , Fatemeh Derikvand & Maryam
Farzaneh (2010) Four-Component, One-Pot Synthesis of Tetra-Substituted Imidazoles Using a Catalytic
Amount of MCM-41 or p-TsOH, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:9, 1270-1275, DOI: 10.1080/00397910903068204
To link to this article: http://dx.doi.org/10.1080/00397910903068204
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Synthetic Communications1, 40: 1270–1275, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903068204
FOUR-COMPONENT, ONE-POT SYNTHESIS OF
TETRA-SUBSTITUTED IMIDAZOLES USING A
CATALYTIC AMOUNT OF MCM-41 OR p-TsOH
Rahim Hekmat Shoar, Golnaz Rahimzadeh,
Fatemeh Derikvand, and Maryam Farzaneh
Department of Chemistry, School of Sciences, Alzahra University, Vanak,
Tehran, Iran
An improved and rapid one-pot synthesis of tetrasubstituted imidazoles by condensing
benzil, ammonium acetate, amines, and aromatic aldehydes and using a catalytic amount
of silica structure MCM-41 or p-toluenesulfonic acid (p-TsOH) as efficient, green, reusa-
ble catalysts in excellent yields is reported.
Keywords: MCM-41; multicomponent one-pot reactions; p-TsOH; tetra-substituted imidazoles
Polysubstituted imidazoles have always played important roles in the pharmaceutical
and agrochemical industries because of their often potent physiological properties
and biological activities, which have resulted in numerous applications.[1,2] Many
methods have been reported for their synthesis, including condensation of diones,
aldehydes, primary amines, and ammonia;[3] N-alkylation of trisubstituted imida-
zoles;[4] condensation of benzoin or benzoin acetate with aldehydes, primary amines,
and ammonia in the presence of copper acetate;[5] cyclization of sulfonamides with
mesoionic 1,3-oxazolium-5-olates;[6] four-component condensations of diones,
aldehydes, primary amines, and ammonium acetate in refluxing acetic acid;[7] con-
densation of b-carbonyl-N-acyl-N-alkylamines with ammonium acetate in refluxing
HOAc;[8] and conversion of N-(2-oxo)amides with ammonium triflouroacetate under
neutral conditions.[9] In the classic approach for the synthesis of tetrasubstituted
imidazoles, in refluxing HOAc, the reaction progresses with poor yields after
long times.[7] Other methods need special and complex reagents. Therefore, the
development of clean, high-yielding, and environmentally friendly approaches is still
desirable and much in demand. Among the reported protocols, condensation of
diones, aldehydes, primary amines, and ammonium acetate is one of the most appro-
priate methods for the synthesis of tetra-substituted imidazoles.[10] This reaction was
performed in the presence zeolite HY or silica gel (1 g) under microwave irradiation.
Because of the numerous advantages associated with solid acid catalysts, they have
been explored as powerful, efficient, and ecofriendly catalysts in organic reactions.[11]
Received March 19, 2009.
Address correspondence to Rahim Hekmat Shoar, Department of Chemistry, Alzahra University,
Vanak, Tehran, Iran. E-mail: rhekmatus@yahoo.com
1270

SYNTHESIS OF TETRA-SUBSTITUTED IMIDAZOLES USING MCM-41 OR p-TsOH 1271
Scheme 1. One-pot synthesis of a series of tetra-substituted imidazoles.
MCM-41 is the most well-studied member of the M41S meso-structured silica
family.[12] It has a uniform hexagonal array of mesopores and very large surface area
(typically around 1,000 m2=g). MCM-41 was recently reported to be an efficient
agent in some important reactions such as hydrodesulfurization, hydrodenitrogena-
tion, and mild hydrocracking (MHC),[13] and it has been used as an acid catalyst for
Friedel–Crafts alkylation of 2,4-di-tert-butylphenol (bulky aromatic) with cinnamyl
alcohol and for the tetra-hydropyranylation of alcohol and phenol.[14] The mesopor-
ous materials showed more catalytic activity than amorphous silica, alumina, or
zeolites, because they facilitate the diffusion of bulky organic molecules in and out
of the porous structures.[15]
Herein, we report a highly efficient method for the four-component, one-pot
synthesis of a series of tetra-substituted imidazoles via the condensation of benzil,
benzaldehyde derivatives, primary amines, and ammonium acetate catalyzed by
MCM-41 or p-toluenesulfonic acid (p-TsOH), inexpensive and easy-to-handle
solid acid catalysts, under different conditions (Scheme 1). Using these catalysts
offered advantages including simplicity of operation, easy workup, and good
yields of products.
RESULTS AND DISCUSSION
To optimize the reaction conditions, synthesis of 2-(4-chlorophenyl)-
1,4,5-triphenylimidazole from the condensation of benzil (1 mmol), aniline (1 mmol),
4-Cl-benzaldehyde (1 mmol), ammonium acetate (5 mmol), and MCM-41 or p-TsOH
(0.04 g) was used as a model reaction. The model reaction was examined in different
solvents under heating conditions and also under solvent-free conditions. In the case
of MCM-41, the best results were obtained at 140 ꢀC under solvent-free conditions
or in refluxing acetic acid, but by using p-TsOH as catalyst, the best results were
obtained at 140 ꢀC under solvent-free conditions or in refluxing ethanol (Table 1).
Table 1. Optimization of the reaction conditions for the synthesis of 2-(4-chlorophenyl)-
1,4,5-triphenylimidazole
Entry
Catalyst (g)
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
MCM-41 (0.04)
MCM-41 (0.04)
MCM-41 (0.04)
MCM-41 (0.04)
p-TsOH (0.04)
p-TsOH (0.04)
—
120
20
72
78
38
52
75
82
HOAc
EtOH
CHCl3
—
115
150
125
22
EtOH
aYields refer to the isolated pure products.

1272
R. H. SHOAR ET AL.
Table 2. Synthesis of tetra-substituted imidazoles under different conditions
Mp (ꢀC)
Found Reported
Catalyst Time
(conditions) Solvent (min)
Yield
(%)a
Entry
Ar
R
1
2
4Cl-C6H5 C6H5
4MeO-C6H5 C6H5
MCM-41
MCM-41
MCM-41
MCM-41
MCM-41
MCM-41
MCM-41
—
—
120
135
115
25
78
74
82
75
78
79
84
82
85
81
75
79
82
78
81
83
77
73
82
81
83
157–159 158–160[16]
181–183 184–185[17]
188–190 185–188[18]
249–250 244–246[17]
157–159 158–160[16]
181–183 184–185[17]
188–190 185–188[18]
165–166 165–166[18]
3
4Me-C6H5
3NO2-C6H5
4-Cl-C6H5
C6H5
C6H5
C6H5
—
4
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
—
5
30
28
6
4MeO-C6H5 C6H5
7
4Me-C6H5
4Me-C6H5
C6H5
C6H5
35
32
8
C6H5-CH2 MCM-41
C6H5-CH2 MCM-41
C6H5-CH2 MCM-41
C6H5-CH2 p-TsOH
C6H5-CH2 p-TsOH
9
30
23
165
163–165 164–165[16]
166
165–166[18]
158–160 158–160[10]
187
185–188[18]
181–184 184–185[17]
165
164–165[16]
162–164 158–160[10]
163–165 165–166[18]
247–250 244–246[17]
157–159 158–160[16]
188–190 185–188[18]
216–218 216–218[10]
158–160[10]
10
11
12
13
14
15
16
17
18
19
20
21
4Cl-C6H5
4Me-C6H5
C6H5
125
115
130
15
—
—
4Me-C6H5 C6H5
4MeO-C6H5 C6H5
p-TsOH
p-TsOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
4Cl-C6H5
C6H5
C6H5-CH2 p-TsOH
C6H5-CH2 p-TsOH
C6H5-CH2 p-TsOH
20
20
4Me-C6H5
3NO2-C6H5
4Cl-C6H5
4Me-C6H5
C6H5
18
13
C6H5
C6H5
C6H5
C6H5
p-TsOH
p-TsOH
p-TsOH
p-TsOH
22
20
23
aYields refer to the isolated pure products.
The optimized conditions were used to construct a variety of tetra-substituted
imidazole derivatives. As shown in Table 2, these methods are effective with a variety
of substituted aromatic aldehydes and amines.
In comparison with silica gel (1 for 1 mmol aldehyde),[10] we used less of the
catalyst (0.04 g) without microwave irradiation. The obtained results confirmed that
MCM-41 had more catalytic activity than silica gel. It may be due to the more acidic
activity of MCM-41. In fact, MCM-41 can work as both Lewis and Brønsted acids.
In summary, in this work we report the synthesis of tetra-substituted imida-
zoles by condensing benzil, ammonium acetate, amines, and aldehyde derivatives
in excellent yields in the presence of MCM-41 or p-TsOH as solid acid catalysts.
Use of these catalysts offers advantages including simplicity of operation, easy
workup, and good yields of products.
EXPERIMENTAL
Melting points were measured by using the capillary tube method with an Elec-
trothermal 9200 apparatus. 1H NMR spectra were recorded on Bruker AQS Avance
500-MHz and Bruker AC-80 (80-MHz) spectrometers using tetramethylsilane
(TMS) as an internal standard [in dimethylsulfoxide (DMSO) solution]. Infrared
(IR) spectra were recorded from KBr discs on the Fourier transform (FT)–IR

SYNTHESIS OF TETRA-SUBSTITUTED IMIDAZOLES USING MCM-41 OR p-TsOH 1273
Bruker Tensor 27. The reactions were monitored by TLC. All solvents and reagents
were purchased from Aldrich and Merck in high-grade quality and used without any
purification. All products were known and characterized by comparison of their
physical and spectra data with those already reported.[10,16–18]
Preparation of Tetra-Substituted Imidazoles Using MCM-41 Under
Solvent-Free Conditions: General Procedure
A mixture of benzil (1 mmol), amine (1 mmol), aldehyde (1 mmol), ammonium
acetate (5 mmol), and catalyst (0.04 g) was stirred at 140 ꢀC for an appropriate time.
After completion of the reaction (monitored by TLC), the mixture was cooled to
room temperature and washed with water to separate the excess amount of
ammonium acetate. Diethyl ether (10 mL) was added to the obtained solid, and
the insoluble catalyst was separated by a simple filtration. The solvent was evapo-
rated, and pure products were obtained by recrystallization from ethanol. The
obtained results are summarized in Table 2.
Synthesis of Tetra-Substituted Imidazoles Using MCM-41 in AcOH:
General Procedure
A mixture of benzil (1 mmol), amine (1 mmol), aldehyde (1 mmol), ammonium
acetate (5 mmol), and catalyst (0.04 g) in AcOH (5 mL) was stirred under refluxing
conditions for an appropriate time. After completion of the reaction (monitored
by TLC), the mixture was poured into ice water, and the obtained solid was sepa-
rated by filtration. Diethyl ether (10 mL) was added to the solid, and the insoluble
catalyst was separated by simple filtration. The solvent was evaporated, and pure
products were obtained by recrystallization from ethanol. The obtained results are
summarized in Table 2.
Synthesis of Tetra-Substituted Imidazoles Using p-TsOH in
Refluxing Ethanol: General Procedure
A mixture of benzil (1 mmol), amine (1 mmol), aldehyde (1 mmol), ammonium
acetate (5 mmol), and catalyst (0.04 g) in ethanol (5 mL) was stirred under refluxing
conditions for an appropriate time. After completion of the reaction (monitored by
TLC), the mixture was poured into ice water, and the obtained solid was separated
by filtration. Pure products were obtained by recrystallization from ethanol. The
obtained results are summarized in Table 2.
Synthesis of Tetra-Substituted Imidazoles Using p-TsOH Under
Solvent-Free Conditions: General Procedure
A mixture of benzil (1 mmol), amine (1 mmol), aldehyde (1 mmol), ammonium
acetate (5 mmol), and catalyst (0.04 g) was stirred at 140 ꢀC for an appropriate time.
After completion of the reaction (monitored by TLC), the mixture was poured into
ice water, and the obtained solid was separated by filtration. Pure products were

1274
R. H. SHOAR ET AL.
obtained by recrystallization from ethanol. The obtained results are summarized in
Table 2.
Selected Spectroscopic Data
1-Benzyl-2-(4-methylphenyl)-4,5-diphenyl imidazole. Mp 165–166 ꢀC; IR
(KBr): 2925, 1600, 1575, 1495, 1485 cmꢁ1; 1H NMR (CDCl3): 3.00 (s, 3H, CH3), 5.07
(s, 2H, CH2), 6.68–7.65 (m, 19H, Ar).
1-Benzyl-2,4,5-triphenylimidazole. Mp 165 ꢀC; IR (KBr) nMax ¼ 3055,
2925, 1600, 1497, 1444 cmꢁ1
CH2), 6.80–7.7 (m, 20H, Ph) ppm.
;
1H NMR (CDCl3, 500 MHz): dH ¼ 5.16 (s, 2H,
ACKNOWLEDGMENT
The authors are thankful from Azzahra Research Council for the partial
financial support.
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