SbCl5.SiO2: An efficient alternative for one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles in solvent or under solvent-free condition

Article abstract of DOI:10.1007/BF03245896

In a one-pot four-component reaction, an aldehyde, an amine, benzil and ammonium acetate were condensed for the synthesis of 1,2,4,5-tetrasubstituted imidazoles in the presence of silica supported antimony pentachloride (SbCl ₅.SiO₂) in improved yields. The catalyst is recoverable by simple filtration and can be used in the subsequent reactions.

Full text of DOI:10.1007/BF03245896

J. Iran. Chem. Soc., Vol. 8, No. 3, September 2011, pp. 648-652.
JOURNAL OF THE
Iranian
Chemical Society
SbCl .SiO : an Efficient Alternative for One-Pot Synthesis of 1,2,4,5-Tetrasubstituted
5
2
Imidazoles in Solvent or under Solvent-Free Condition
a,
b
a
a
B. Sadeghi *, B.B.F. Mirjalili , S. Bidaki and M. Ghasemkhani
a
Department of Chemistry, Islamic Azad University, Yazd Branch, P.O. Box 89195-155, Yazd, Iran
Department of Chemistry, College of Science, Yazd University, P.O. Box 89195-741, Yazd, Iran
b
(
Received 4 July 2009, Accepted 29 July 2010)
In a one-pot four-component reaction, an aldehyde, an amine, benzil and ammonium acetate were condensed for the synthesis
of 1,2,4,5-tetrasubstituted imidazoles in the presence of silica supported antimony pentachloride (SbCl
The catalyst is recoverable by simple filtration and can be used in the subsequent reactions.
5
.SiO ) in improved yields.
2
Keywords: 1,2,4,5-Tetrasubstituted imidazoles, SbCl .SiO , Benzil, One-pot synthesis, Aldehyde
5
2
INTRODUCTION
since its handling and usability in the liquid form is laborious,
the supported form is indeed preferable. It has been claimed
The tetrasubstituted imidazole core exists in many
biological systems such as Losartan, Olmesartan and in some
natural products and pharmacologically active compounds [1].
The best protocol for the construction of tetrasubstituted
imidazoles is the condensation of a benzil, a primary amine, an
aldehyde and ammonium acetate in the presence of an acidic
catalyst. Previously, silica gel or Zeolite HY [2], silica
that the supported SbCl
5
is a solid superacid. SbCl is used
5
extensively in organic synthesis as a Lewis acid for enhancing
a variety of organic reactions such as the Friedel-Craft
alkylation [12], electrophilic additions to alkenes and 1,3-
dienes [13] and aromatization of enamines [14]. In the present
research, we wish to describe a mild and efficient approach for
the synthesis of tetrasubstituted imidazoles using a catalytic
gel/NaHSO
hetropolyacids [6], HClO
9] and L-proline [10] were applied as catalysts in this
technique.
Solid-supported reagents have improved the activity and
4
[3], molecular iodine [4], K
5
CoW12
O
40.3H
2
O [5],
amount of SbCl as a Lewis acid catalyst (Scheme 1).
5
4
-SiO [7], InCl
2
3
.3H
2
O [8], BF
3
/SiO
2
[
EXPERIMENTAL
SbCl .SiO , benzil, ammonium acetate, aldehydes, amines
5
2
selectivity more than can individual reagents, because the
surface area of the reagent is increased manifold [11].
and other necessary chemical compounds were purchased
from Fluka and Merck companies. The products were known
and characterized by IR and H NMR and by comparing their
1
Antimony pentachloride (SbCl ), a thin, colored and
5
fuming liquid, is used in industry and organic synthesis. Since
Antimony pentachloride is a liquid with a high specific gravity
that fumes in air and reacts with the moisture to form HCl, and
physical properties with those reported in the literature. IR
spectra were run on a Shimadzu IR-470 spectrometer. H
NMR was obtained using a Bruker Avans 300 MHz
1
spectrometer. Melting points were determined with
Barnstead Electrothermal melting point apparatus.
a
*Corresponding author. E-mail: bsadeghia@gmail.com

Sadeghi et al.
Scheme 1. Synthesis of tetrasubstituted imidazoles using a catalytic amount of SbCl
5
/SiO
2
Preparation of Silica-Supported SbCl5
ethanol. All products were known and were identified by
comparing their physical or spectral data with those of
authentic samples.
The reagent was prepared by stirring a mixture of SbCl5
(
0.7 ml) and 1 g of silica gel in 5 ml of chloroform for 1 h at
room temperature. The slurry was filtered and washed with
chloroform. The obtained solid (62% SbCl .SiO ) was dried at
5
2
RESULTS AND DISCUSSION
an ambient temperature for 2 h and then stored in a dry
container.
In continuation of our investigation into the application of
solid acids in organic synthesis [9,15], we studied the
synthesis of tetrasubstituted imidazoles in the presence of
SbCl .SiO as an inorganic polymeric solid Lewis acid. The
General Procedure for the Synthesis of 1,2,4,5-
Tetrasubstituted Imidazoles
5
2
Method A. A solution of benzil (3 mmol), amine (3
mmol), aldehyde (3 mmol), ammonium acetate (3 mmol) and
efficiency of this acid is comparable with some other catalysts
such as O, HClO -SiO SiO .NaHSO
BF .SiO and L-proline. To optimize the reaction conditions,
K
5
CoW12
O40.3H
2
4
2
,
2
4
,
SbCl
5
.SiO
2
(62% w/w) (0.15 g) in 10 ml of EtOH was heated
3
2
at reflux for 45 min (Table 2). The progress of the reaction
was traced by TLC (n-hexane:EtOAc 70:30). After the
completion of the reaction, the solvent was evaporated under
reduced pressure. Dichloromethane was added to the mixture
and filtered to remove the catalyst. By evaporation of the
solvent, an oily residue or an impure solid was obtained. By
adding ethanol and water to the residue, a milky-to-yellow
solid was obtained. The solid was then crystallized with
ethanol. All products were known and were identified by
comparing their physical or spectral data with those of
authentic samples.
the reaction of 4-methyl benzaldehyde, benzyl amine, benzil
and ammonium acetate was used as a model (Table 1).
According to the obtained data, the adoption of the 62%
SbCl .SiO (10 mol%) at reflux in EtOH seems to be the best
5
2
condition for the tetrasubstituted imidazoles formation (Table
1,entry 19). Accordingly, some aldehydes and amines were
subjected to condensation to give their tetrasubstituted
imidazoles (Scheme 1 and Table 2). It is interesting to note
that this transformation can also be carried out with the said
catalyst under solvent-free conditions at 140 °C (Table 2).
To identify the structure of SbCl /SiO , we studied IR
5
2
Method B. A mixture of benzil (3 mmol), amine (3
mmol), aldehyde (3 mmol), ammonium acetate (3 mmol) and
SbCl /SiO (62% w/w) (0.15 g) was placed in a round bottom
spectra of SbCl , SbCl .SiO and SiO (Fig. 1). In all of the
5 5 2 2
spectra, OH stretching band was observed and strong
intermolecular hydrogen bonding occurred in the hydroxyl
groups. Therefore, the resulting O-H absorption was broad.
5
2
flask. The materials were mixed and heated at 140 ºC for 2 h
Table 2). The progress of the reaction was monitored by TLC.
(
The moisture in SbCl caused the presence of OH stretching
5
After the completion of the reaction, the mixture was cooled to
room temperature. Dichloromethan was added to the mixture
and filtered to remove the catalyst. By evaporation of the
solvent, an oily residue or an impure solid was obtained. By
adding ethanol and water to the residue, a milky-to-yellow
solid was obtained. The solid was then crystallized with
bond in its infrared spectra. Infrared spectra of SbCl
5
.SiO
2
and
SiO were similar. In both of them, the absorption band of Si-
2
-1
-1
OH and Si-O-Si appeared in ~800 cm and ~1065 cm ,
respectively. In SbCl spectrum, the absorbtion of Sb-Cl is
5
-
1
observed in 1567 cm . In the IR spectrum of SbCl .SiO the
5
2,
Sb-Cl, Sb-O, Si-OH and Si-O-Si were observed in 1567, 560,
6
49

SbCl .SiO : an Efficient Alternative for One-Pot Synthesis of
5
2
a
Table 1. Acid-Catalyzed Synthesis of 1-Benzyl-4,5-diphenyl-2-p-tolyl-1H-imidazole
CHO
NH
2
NH4OA c
C atalyst
N
N
+
+
CH3
O
O
C H3
Entry
Catalyst
[PMo11VO40] (1 mol%)
Temp. (°C)/
Time (min)
78/14
140/120
MW/2
140/120
MW/12
140/6
Yield
Ref.
b
(%)
1
2
H
4
90
95
97
92
96
90
85
92
88
65
57
50
50
60
30
47
78
82
86
88
94
88
82
[6]
K CoW O .3H O (0.1 mol%)
5
[5]
12 40
2
[5]
3
SiO /NaHSO (0.4 g)
[3]
2
4
[3]
4
5
6
7
8
9
SiO
2
/HClO
4
(1 mol%)
[7]
Zeolite HY (1 g)
MW/6
140/120
60/120
80/45
[2]
(37%) BF
L-Proline (15 mol%)
ZnCl (21 mol%)
3
/SiO
2
(0.08 g)
[9]
[10]
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
SnCl .2H O (21mol%)
80/45
2
2
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
AlCl (21 mol%)
80/45
3
MgCl (21 mol%)
80/45
2
SnCl (21 mol%)
80/45
4
31% SbCl
5
.SiO
2
(5 mol%)
80/45
48% SbCl .SiO (8 mol%)
25/300
70/240
140/120
80/45
5
2
48% SbCl
5
.SiO
2
(8 mol%)
48% SbCl .SiO (8 mol%)
5
2
48% SbCl
5
.SiO
2
(8 mol%)
48% SbCl .SiO (11 mol%)
80/45
5
2
62% SbCl .SiO (10 mol%)
80/45
5
2
nd
62% SbCl .SiO (21 mol%)2 run
80/45
5
2
nd
62% SbCl .SiO (21 mol%)3 run
80/45
5
2
a
b
The molar ratio of 4-methyl benzaldehyde, benzylamine, benzil and ammonium acetate is 1:1:1:1. Isolated yield.
a
Table 2. SbCl .SiO Catalyzed Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles
5
2
Entry R2
R3
Time (min)/Yield (%)b
Time (min)/Yield (%)c Ref.d M.P. (°C)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
C H
6
C H
6
45/92
45/87
45/89
45/96
45/94
45/85
45/94
45/94
45/90
45/83
45/95
45/87
45/91
45/57
45/64
120/90
120/82
120/87
120/96
120/93
120/83
120/92
120/93
120/90
120/84
120/94
120/87
120/85
-
[7]
[5]
[2]
[4]
[7]
[4]
[6]
[2]
[2]
[7]
[7]
[5]
[7]
[8]
[7]
216-218
163-165
115-117
149-151
140-142
280-281
185-188
165-166
122-124
128-130
152-155
170-172
182-184
115-117
6
5
6
5
C H
C H CH
5
5
5
2
2
2
C
6
H
CH
3
CH
5
2
4-ClC H
C H
6
4
4
6
2-ClC
6
H
C
6
H
5
5
5
CH
4-OHC H
C H
6
6
4
4-CH
3
C
6
H
4
4
4
C H
6
4-CH C H
C H CH
3
6
6
5
4-CH C H
CH CH
3 2
3
6
0
1
2
3
4
5
3-OMeC H
C H CH
6 5
6
4
2
2
2
2
2
2
2-NO C H
C H CH
2
6
4
6
5
4-BrC
6
H
4
C
6
H
5
CH
4-NMe C H
C H CH
6
2
6
4
5
CH
(CH ) CH
3
C
6
H
5
CH
1
C H CH
6
-
132-135
3
2
5
a
b
Molar ratio of aldehyde:amine:benzil:ammonium acetate: SbCl
5
.SiO
2
(62% w/w) (g) was 1:1:1:1:0.05. Isolated yield
c
d
under reflux in ethanol. Isolated yield under solvent free condition at 140 °C. All products are known and were
1
identified by their melting points, IR and H NMR spectra.
6
50

Sadeghi et al.
Fig. 1. FT-IR (ATR) spectrum of (a) SbCl
5
, (b) SbCl
5
.SiO
2
and (c) SiO .
2
Cl Sb-O
O-SbCl4
4
Wang, Z. Zhao, C.W. Lindsley, Org. Lett. 6 (2004)
453.
S. Balalaei, A. Arabanian, Green Chem. 2 (2000) 274.
A.R. Karimi, Z. Alimohammadi, J. Azizian, A.A.
Mohammadi, M.R. Mohmmadizadeh, Catal. Commun.
1
Si
Si
O
O
[2]
[3]
n
Scheme 2. Proposed structure for SbCl
5
.SiO
2
7
(2006) 728.
-
1
3
340 and 1065 cm , respectively [16,17]. Based on these
[
4]
M. Kidwai, P. Mothsra, V. Bansal, R.K. Somvanshi,
A.S. Ethayathulla, S. Dey, T.P. Singh, J. Mol. Catal. A:
Chem. 265 (2007) 177.
5
results, we suggest the following structure for SbCl .SiO2
(
Scheme 2).
[5]
[6]
[7]
[8]
[9]
L. Nagarapu, S. Apuri, S. Kantevari, J. Mol. Catal. A:
Chem. 266 (2007) 104.
M.M. Heravi, F. Derikvand, F.F. Bamoharram, J. Mol.
Catal. A: Chem. 263 (2007) 112.
S. Kantevari, S.V.N. Vuppalapati, D.O. Biradar, L.
Nagarapu, J. Mol. Catal. A: Chem. 266 (2007) 109.
S. Das Sharma, P. Hazarika, D. Konwar, Tetrahedron
Lett. 49 (2008) 2216.
ACKNOWLEDGMENTS
We gratefully thank the Islamic Azad University of Yazd
for their financial support of this piece of research.
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SbCl .SiO : an Efficient Alternative for One-Pot Synthesis of
5
2
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5
6
52