Synthesis of 1,2,4,5-Tetrasubstituted imidazoles using sulfuric acid ([3-(3-Silicapropyl)sulfanyl]propyl]ester as a recyclable solid acid

Article abstract of DOI:10.1002/jhet.847

Sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl]ester (SASPSPE) is used as a recyclable catalyst for the synthesis of 1,2,4,5-tetrasubstituted imidazoles. A range of various polysubstituted imidazoles was synthesized via four-component condensation of benzil, aldehydes, amines, and ammonium acetate in the presence of SASPSPE under solvent-free conditions at 140°C. The heterogeneous catalyst was recycled for five runs on the reaction of benzil, 4-methylbenzaldehyde, benzyl amine, and ammonium acetate without losing its catalytic activity.

Full text of DOI:10.1002/jhet.847

634
Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles Using Sulfuric
Acid ([3-(3-Silicapropyl)sulfanyl]propyl]ester as a Recyclable
Solid Acid
Vol 49
*
Ziba Tavakoli,* Mojtaba Bagherneghad, and Khodabakhsh Niknam
Department of Chemistry, Islamic Azad University, Gachsaran Branch, Gachsaran, Iran
*
E-mail: ziba.tavakoli@yahoo.com or khniknam@gmail.com
Received September 13, 2010
DOI 10.1002/jhet.847
View this article online at wileyonlinelibrary.com.
Sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl]ester (SASPSPE) is used as a recyclable catalyst for
the synthesis of 1,2,4,5-tetrasubstituted imidazoles. A range of various polysubstituted imidazoles was
synthesized via four-component condensation of benzil, aldehydes, amines, and ammonium acetate in the
presence of SASPSPE under solvent-free conditions at 140ꢀC. The heterogeneous catalyst was recycled
for five runs on the reaction of benzil, 4-methylbenzaldehyde, benzyl amine, and ammonium acetate
without losing its catalytic activity.
J. Heterocyclic Chem., 49, 634 (2012).
INTRODUCTION
[25], Bronsted acidic ionic liquid [26], and MCM-41 or
p-TsOH [27] under microwave-irradiated, solvent-free, or
classical conditions. However, most of these synthetic
methods suffer from some serious drawbacks, such as
laborious and complex workup and purification, significant
amounts of waste materials, strongly acidic conditions, and
occurrence of side reactions, poor yields, and the use of
expensive reagents. Therefore, the development of a new
catalytic system to overcome these shortcomings and fulfill
the criteria of a mild, efficient, and environmentally benign
protocol for the synthesis of highly substituted imidazoles
is an important task for organic chemists.
The imidazole ring system is one of the most important
substructure found in a large number of natural products
and pharmacologically active compounds [1,2]. The mem-
bers of this class of compounds are known to possess NO
synthase inhibition and antifungal, antimycotic, antibiotic,
antiulcerative, antibacterial, antitumor, and CB1 receptor
antagonistic activities [3]. Various substituted imidazoles
act as inhibitors of p38 MAP kinase [4a] and B-Raf kinase
[4b], glucagon receptors [5], plant growth regulators [6],
therapeutic agents [1], and pesticides [7].
Preparation of tetrasubstituted imidazoles has been the
subject of both the industrial and academic studies. As a
result, numerous solution-phase syntheses of these
compounds have been reported [8,9]. The most well-
known and classical method for the preparation of these
compounds involves four-component condensations of a
1,2-diketone derivative with an aldehyde, primary amine,
and ammonium acetate in refluxing HOAc, which is
known to have poor yields and long reaction times [10].
Improvements occurred using other acidic conditions, such
as heteropolyacid [11], silica gel [12], zeolite [12], alumnia
[13], NaHSO4-SiO2 [14], HClO4ÁSiO2 [15], molecular
iodine [16a,b], FeCl3Á6H2O [17a,b], BF3.SiO2 [18],
InCl3Á3H2O [19], K5CoW12O40Á 3H2O [20], copper acetate
[21], trifluroacetic acid [22], L-proline [23], zeolite-
supported reagents [24], mercaptopropylsilica (MPS)
Several types of solid sulfonic acid-functionalized silica
(both amorphous and ordered) have been synthesized and
applied as an alternative to traditional sulfonic acid resins
and homogeneous acids in catalyzing chemical transforma-
tions [28,29]. In continuation of our studies on the design
and application of solid acid catalysts in organic trans-
formations [30–32], herein, we describe the application
of sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl]ester
(SASPSPE) as recyclable catalyst for the synthesis of
1,2,4,5-tetrasubstituted imidazoles (Scheme 1).
RESULTS AND DISCUSSION
To study the effect of catalyst loading on the four-
component condensation reactions for the synthesize
of 1,2,4,5-tetrasubstituted imidazoles, the reaction of
© 2012 HeteroCorporation

May 2012
Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles Using Sulfuric Acid
([3-(3-Silicapropyl)sulfanyl]propyl]ester as a Recyclable Solid Acid
635
Scheme 1. Preparation of sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl)ester (SASPSPE).
4-methylbenzaldehyde, benzil, benzylamine, and ammo-
nium acetate was chosen as a model reaction (Table 1).
The results show clearly that SASPSPE is an effective
catalyst for this four-component condensation reaction.
The best catalytic loading of SASPSPE was 0.05 g in terms
of reaction time and isolated yield.
The model reaction was also examined in various
solvents as well as solvent-free conditions in the presence
of 0.05 g of SASPSPE (Table 2). The yield of the reaction
under solvent-free conditions was the highest, and the
reaction time was shortest. Therefore, the optimized condi-
tions was chosen as follows: benzil (1 mmol), aldehyde (1
mmol), amine (1 mmol), ammonium acetate (1 mmol), and
SASPSPE (0.05 g, 1.7 mol %) [30] and heated under
solvent-free conditions at 140ꢀC (Scheme 2).
Another important aspect is that various aliphatic and
aromatic amines such as aniline, benzyl, cyclohexyl, and
ethyl amine were used in this four-component condensa-
tion reaction under optimized conditions (Table 3). In
each case, no side product formation (for example, 2,4,5-
trisubstituted imidazoles) was observed, as is normally
the case in such reactions under the influence of strong
acids. This method not only affords the products in excel-
lent yields but also avoids the problems associated with
catalyst cost, handling, safety, and pollution. The results
illustrate the high ability of this method for the synthesis
of 1,2,4,5-tetrasubstituted imidazoles with different groups.
The practical synthetic efficiency of this reaction was
highlighted by the reaction of terephthaldehyde with
benzil, ethyl amine, and ammonium acetate in the presence
of SASPSPE to give structurally complex imidazole
derivative A (Scheme 3, and Table 3, entry 23).
The generality of this process was demonstrated by the
wide range of substituted and structurally diverse aromatic
aldehydes, aliphatic and aromatic amines, to synthesize
the corresponding products in high to excellent yields
(Table 3).
The possibility of recycling the catalyst was examined
using the reaction of benzil, 4-methylbenzaldehyde, benzyl
amine, and ammonium acetate under optimized conditions.
A wide range of aromatic aldehydes was used, and
all imidazoles were obtained in high to excellent yields
and were observed a general method that tolerates both
electron-withdrawing and electron-donating constituents.
Table 2
Condensation reaction of benzil, 4-methylbenzaldehyde, benzylamine,
and ammonium acetate using SASPSPE as catalyst in different solvents.a
Table 1
Time
Condensation reaction of benzil, 4-methylbenzaldehyde, benzylamine,
and ammonium acetate in the presence of different amounts of SASPSPE
as catalyst under solvent-free conditions at 140ꢀC.a
Entry
Solvent
Conditions
(min)
Conversion%b
1
2
3
4
5
EtOH
H2O
Reflux
Reflux
Reflux
Reflux
Reflux
200
380
350
480
180
45
15
20
Entry
Catalyst loading (g)
Time (min)
Conversion%b
CH2Cl2
CH3CN
H2O/EtOH
(1:1)
Solvent-free
Solvent-free
c
-
1
2
3
4
5
0.01
0.03
0.05
0.07
0.1
150
120
90
90
100
90
90
98
95
90
35
6
7
100ꢀC
140ꢀC
180
90
65
98
aReaction conditions: benzil (1 mmol), 4-methylbenzaldehyde (1 mmol),
benzylamine (1 mmol), ammonium acetate (2 mmol), and SASPSPE (0.05
aReaction conditions: benzil (1 mmol), 4-methylbenzaldehyde (1mmol),
benzylamine (1 mmol), and ammonium acetate (2 mmol) under solvent-
free conditions at 140ꢀC.
g) in solvent (5 mL).
bGC yield.
bGC yield.
cNo reaction.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

636
Z. Tavakoli, M. Bagherneghad, and K. Niknam
Vol 49
Scheme 2. Synthesis of 1,2,4,5-tetrasubstituted imidazoles catalyzed by SASPSPE.
On completion, the reaction mixture was filtered, and the
solid was washed with ethanol, and recycled catalyst was
saved for the next reaction. The recycled catalyst could
be reused five times without any further treatment. No ob-
servation of any appreciable loss in the catalytic activity of
SASPSPE was observed (Fig. 1).
the formation of diamine intermediate (3) by increasing
the electrophilicity of the carbonyl group of the aldehydes
and benzil. Intermediate (3), in the presence of SASPSPE,
condenses with benzil to form imidazol-5-ol intermediate
(6), which in turn changes to tetrasubstituted imidazoles
by elimination of water (Scheme 4).
To show the advantages of SASPSPE as a catalyst in
this reaction, our obtained results and used reaction condi-
tions for synthesis of 1-benzyl-2-(4-methylphenyl)-4,5-
diphenylimidazole (1b) were compared with previously
reported data in Table 4. The results show that our method
is quite comparable with the former methods in yields and
reaction times.
In conclusion, we have shown that sulfuric acid ([3-(3-
silicapropyl)sulfanyl]-propyl]ester SASPSPE, which can
be prepared from commercially available and cheap start-
ing materials, catalyzed efficiently this four-component
condensation reactions for the synthesis of 1,2,4,5-
tetrasubstituted imidazole derivatives. The simplicity of
the procedure, eco-friendly, nonvolatile, easy handling,
safety, and reusability of catalyst are the advantages of this
method.
In accordance with a delineated mechanism [22,23], it
may be proposed that the SASPSPE catalyst facilitates
Table 3
Preparation of various 1,2,4,5-tetrasubstituted imidazoles in the presence of SASPSPE under solvent-free conditions at 140ꢀC.a
Entry
Ar
R
Product
Time (min)
Yield (%)b
mp (ꢀC)
Lit. mp (ꢀC)
1
2
3
4
5
6
7
8
C6H5–
C6H5–CH2–
C6H5–CH2–
C6H5–CH2–
C6H5–CH2–
C6H5–CH2–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
1a
1b
1c
1d
1e
1f
1g
1h
1i
30
10
15
20
15
70
30
30
15
50
40
55
55
90
90
92
90
87
89
90
88
95
89
82
85
72
88
70
75
78
74
80
72
72
73
71
160–161
165–167
162–164
140–142
208–210
214–216
184–186
182–184
279–281
212–214
148–150
143–145
194–196
219–221
168–170
164–166
194–196
217–219
115–117
123–125
310–312
155–157
298–300
159–160 [18]
165–166 [17]
162–164 [18]
140–142 [18]
4-Me–C6H4–
4-Cl–C6H4–
2-Cl–C6H4–
4-NC–C6H4–
C6H5–
4-Me–C6H4–
4-MeO–C6H4–
4-HO–C6H4–
4-O2N–C6H4–
4-Cl–C6H4–
3-Br–C6H4–
4-NC–C6H4–
4-Me–C6H4–
C6H5–
4-Me–C6H4–
4-Cl–C6H4–
4-MeO–C6H4–
C6H5–
4-Me–C6H4–
4-Cl–C6H4–
4-NC–C6H4–
4-OHC–C6H4–
–
216–217 [18]
185–187 [18]
183–184 [22]
280–281 [15]
159–160 [22]
149–151 [17]
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1j
1k
1l
C6H5–
C6H5–
C6H5–
4-Br–C6H4–
–
–
–
1m
1n
1o
1p
1q
1r
1s
1t
55
C6H11
C6H11
C6H11
C6H11
Et–
–
–
–
–
210
130
170
120
40
15
20
20
70
167–169 [17]
162–164 [17]
–
–
116–118 [18]
122–124 [17]
Et–
Et–
Et–
Et–
1u
1v
A
–
–
–
aReaction conditions: benzil (1 mmol), aromatic aldehyde (1 mmol), amine (1 mmol), ammonium acetate (2 mmol), SASPSPE (0.05 g), solvent-free
at 140 ꢀC.
bIsolated yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2012
Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles Using Sulfuric Acid
([3-(3-Silicapropyl)sulfanyl]propyl]ester as a Recyclable Solid Acid
637
Scheme 3. Synthesis of bis-imidazole A.
EXPERIMENTAL
Chemicals were purchased from Fluka, Merck,
General.
and Aldrich chemical companies. All the products are known
compounds and were characterized by comparison of their IR,
1H–NMR, and 13C-NMR spectroscopic data and their melting
points with reported values [11–27]. SASPSPE was prepared
according to previously our reported procedures [30].
General procedure for the synthesis of 1,2,4,5-
tetrasubstituted imidazole derivatives.
To a mixture of
benzil (1 mmol), aldehyde (1 mmol), amine (1 mmol), and
ammonium acetate (2 mmol), 0.05 g of catalyst (SASPSPE, 1.7
mol %) was added [30] and heated at 140ꢀC. When the reaction
was complete as judged by TLC, ethanol (5 mL) was added, the
reaction mixture was filtered, and the remaining solid was
washed with warm ethanol (3 × 5 mL) to separate the catalyst.
The products were recrystallized from ethanol.
Figure 1. Recyclability of SASPSPE (0.05 g) in the reaction of p-
methylbenzaldehyde (1 mmol) and benzyl (1 mmol), benzyl amine
(1 mmol), ammonium acetate (2 mmol) under solvent-free conditions
at 140ꢀC. Reaction time = 10 min.
Spectral data for new compounds. 1-Benzyl-2-(4-
cyanophenyl)-4,5-diphenyl-1H-imidazole (1e).
IR (KBr):
3095, 3010, 2980, 2200, 1600, 1480, 1450, 840, 725, 695
1
cmÀ1. H-NMR (CDCl3, 500 MHz), d: 5.16 (s, 2H), 6.87–6.88
138.95, 145.67. Anal. Calcd for C27H19BrN2: C, 71.85; H, 4.24;
Br, 17.70; N, 6.21; found: C, 71.69; H, 4.90; N, 6.04.
(m, 2H), 7.19–7.44(m, 11H), 7.59–7.607(m, 2H), 7.69 (d, 2H,
J = 8.4 Hz), 7.83 (d, 2H, J = 8.4 Hz). 13C NMR (CDCl3, 125
MHz), d: 48.9, 112.6, 119.0, 127.2, 127.2, 128.2, 128.6, 129.3,
129.4, 129.5, 129.6, 130.8, 131.4, 131.9, 132.8, 134.4, 135.6,
137.4, 139.4. Anal. Calcd for C29H21N3: C, 84.65; H, 5.14; N,
10.21; found: C, 84.49; H, 5.18; N, 10.05.
2-(4-Cyanophenyl)-1,4,5-triphenyl-1H-imidazole (1m).
IR
.
(KBr): 3085, 3010, 2200, 1595, 1480, 840, 760, 690 cmÀ1
1H-NMR (CDCl3, 500 MHz), d: 7.1 (d, 2H, J = 7.8 Hz), 7.16
(d, 2H, J = 7.6 Hz), 7.23–7.40 (m, 9H), 7.54–7.63 (m, 6H).
13C-NMR (CDCl3, 125 MHz), d: 111.9, 119.1, 127.4, 127.7,
128.7, 128.8, 128.9, 129.3, 129.9, 130.5, 131.5, 132.3, 132.6,
134.4, 135.2, 137.1, 139.6, 145.0. Anal. Calcd for C28H19N3: C,
84.61; H, 4.82; N, 10.57; found: C, 84.44; H, 4.87; N, 10.41.
1-(4-Bromophenyl)-2-(4-methylphenyl)-4,5-diphenyl-1H-im-
idazole (1n). IR (KBr): 3085, 3034, 2987, 1478, 1055, 1015,
2-(3-Bromophenyl)-1,4,5-triphenyl-1H-imidazole (1l).
IR
(KBr): 3050, 1595, 1490, 1470, 1400, 1080, 830, 760, 690
1
cmÀ1. H-NMR (CDCl3, 500 MHz), d: 7.08–7.11 (m, 3H), 7.17
(dd, 2H, J1 = 8.1 Hz, J2 = 1.5 Hz), 7.24–7.34 (m, 10H), 7.42
(d, 1H, J = 8.0 Hz), 7.64 (d, 2H, J = 8.5 Hz), 7.77 (t, 1H, J =
1.7 Hz). 13C-NMR (CDCl3, 125 MHz), d: 122.73, 127.21,
127.60, 127.81, 128.57, 128.65, 128.79, 128.84, 129.03, 129.69,
129.91, 130.78, 131.52, 131.66, 131.76, 132.34, 134.60, 137.20,
1
835, 775, 695 cmÀ1. H-NMR (CDCl3, 500 MHz), d: 2.36 (s,
3H), 6.92–6.94 (m, 2H), 7.12 (d, 2H, J = 8 Hz), 7.15 (dd, 2H,
J1 = 7.8 Hz, J2 = 1.6 Hz), 7.21–7.41 (m, 10H), 7.61–7.63
Table 4
Synthesis of 1-benzyl-2-(4-methylphenyl)-4,5-diphenyl-imidazole 1b using different catalysts and reaction conditions.
Entry
Solvent and catalyst (loading)
Time (min)
Yield%a
Ref.
1
2
3
4
5
6
7
8
MW, solvent-free, zeolite HY (5 mol %)
Solvent-free, 140ꢀC, NaHSO4–SiO2 (18.6 g)
Solvent-free, 140ꢀC, HClO4.SiO2 (1 mol %)
MeOH, rt, InCl3.3H2O (10 mol %)
6
120
6
480
120
540
32
85
92
90
75
95
88
82
90
12
14
15
19
20
Solvent-free, 140ꢀC, K5CoW12O40.3H2O (0.1 mol %)
MeOH, 60ꢀC, L-proline (15 mol %)
23
27
Reflux in AcOH, MCM-41(0.04 g)
Solvent-free, 140ꢀC, SASPSPE (1.7 mol %)
10
This work
aIsolated yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

638
Z. Tavakoli, M. Bagherneghad, and K. Niknam
Vol 49
Scheme 4. Plausible mechanism for the formation of tetrasubstituted imidazoles.
(m, 2H). 13C-NMR (CDCl3, 125 MHz), d: 21.7, 122.5, 127.1,
127.8, 128.6, 129.0, 129.3, 129.4, 130.4, 130.8, 130.9, 131.6,
132.7, 134.7, 136.7, 138.9, 147.5. Anal. Calcd for C28H21BrN2:
C, 72.26; H, 4.55; Br, 17.17; N, 6.02; found: C, 72.07; H, 4.58;
N, 5.89.
146.5. Anal. Calcd for C23H19ClN2: C, 76.98; H, 5.33; Cl,
9.88; N, 7.81; found: C, 76.81; H, 5.37; N, 7.66.
1-Ethyl-2-(4-cyanophenyl)-4,5-diphenyl-1H-imidazole (1v).
IR (KBr): 3095, 3015, 2995, 2200, 1598, 1480, 840, 765, 695
cmÀ1 1H-NMR (CDCl3, 500 MHz), d: 1.09 (t, 3H, J = 6.8
.
1-Cyclohexyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole
(1q). IR (KBr): 3087, 3020, 2970, 1595, 1475, 1445, 1398,
Hz), 4.01–4.02 (m, 2H), 7.18–7.29 (m, 3H), 7.46–7.53
(m, 7H), 7.81 (d, 2H, J = 7.7 Hz), 7.91 (d, 2H, J = 7.7 Hz).
13C-NMR (CDCl3, 125 MHz), d: 16.7, 40.3, 112.6, 119.0,
127.0, 127.2, 128.6, 129.5, 129.6, 129.8, 131.1, 131.4, 132.9,
134.5, 136.2, 139.2, 145.4. Anal. Calcd for C24H19N3: C,
82.49; H, 5.48; N, 12.03; found: C, 82.31; H, 5.53; N, 11.87.
1-Ethyl-2-[(1-ethyl-4,5-diphenyl-1H-imidazol-2-yl)phenyl]-
4,5-diphenyl-1H-imidazole (A). IR (KBr): 3075, 3020, 2990,
1085, 965, 835 cmÀ1
.
1H-NMR (CDCl3, 500 MHz), d:
0.78–0.83 (m, 1H), 1.04–1.12 (m, 2H), 1.49–1.61 (m, 5H),
1.87 (d, 2H, J = 11.6 Hz), 3.96 (t, 1H, J = 12.2 Hz), 7.11–7.19
(m, 3H), 7.44–7.50 (m, 9H), 7.59 (d, 2H, J = 8.2 Hz).
13C-NMR (CDCl3, 125 MHz), d: 25.4, 25.6, 34.0, 58.9, 126.5,
127.1, 128.4, 129.0, 129.1, 129.3, 129.8, 131.4, 131.8, 132.6,
134.9, 135.4, 138.4, 146.9. Anal. Calcd for C27H25ClN2: C,
78.53; H, 6.10; Cl, 8.59; N, 6.78; found: C, 78.36; H, 6.14;
N, 6.59.
1590, 1460, 1320, 1085, 850, 775, 695 cmÀ1 1H-NMR
.
(CDCl3, 500 MHz), d: 1.08 (t, 6H, J = 7.1 Hz), 4.01–4.05
(m, 4H), 7.17 (t, 2H, J = 7.1 Hz), 7.24 (t, 4H, J = 7.5 Hz),
7.48–7.57 (m, 14H), 7.89 (s, 4H). 13C-NMR (CDCl3, 125
MHz), d: 16.70, 127.21, 128.49, 129.54, 129.84, 131.48. Anal.
Calcd for C40H34N4: C, 84.18; H, 6.00; N, 9.82; found: C,
84.01; H, 6.07; N, 9.65.
1-Cyclohexyl-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole
(1r). IR (KBr): 3095, 3010, 2980, 1600, 1475, 1440, 1375, 1280,
1
1245, 1180, 1020, 840, 780, 695 cmÀ1. H-NMR (CDCl3, 500
MHz), d: 0.77–0.82 (m, 1H), 1.04–1.11 (m, 2H), 1.47–1.67 (m,
5H), 1.87 (d, 2H, J = 11.7 Hz), 3.91 (s, 3H), 3.98 (t, 1H, J =
12.2 Hz), 7.03 (d, 2H, J = 8.4 Hz), 7.11 (t, 1H, J = 7.0 Hz), 7.17
(t, 2H, J = 7.5 Hz), 7.45–7.49 (m, 7H), 7.57 (d, 2H, J = 8.4 Hz).
13C-NMR (CDCl3, 125 MHz), d: 25.5, 26.6, 34.0, 55.8, 58.7,
114.2, 125.3, 126.3, 127.0, 128.3, 129.1, 129.1, 129.3, 131.7,
132.63, 133.1, 135.2, 138.0. Anal. Calcd for C28H28N2O: C,
82.32; H, 6.91; N, 6.86; found: C, 82.15; H, 6.89; N, 6.28.
Acknowledgments. Financial support for this work by the
Research Council of Islamic Azad University, Gachsaran Branch,
Iran, is gratefully acknowledged.
1-Ethyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole (1u).
IR (KBr): 3080, 3010, 2990, 1590, 1460, 1320, 1085, 835,
REFERENCES AND NOTES
775, 695 cmÀ1 1H-NMR (CDCl3, 500 MHz), d: 1.05 (t, 3H,
.
[1] Heers, J.; Backx, L. J. J.; Mostmans, J. H.; Van Cutsem, J. J
Med Chem 1979, 22, 1003.
[2] (a) Hunkeler, W.; Mohler, H.; Pieri, L.; Polc, P.; Bonetti, E. P.;
Cumin, R.; Schaffner, R.; Haefely, W. Nature 1981, 290, 514; (b)
Brimblecombe, R. W.; Duncan, W. A. M.; Durant, G. J.; Emmett, J. C.;
J = 7.1 Hz), 3.96 (q, 2H, J = 7.1 Hz), 7.15–7.24 (m, 3H),
7.45–7.55 (m, 9H), 7.69(d, 2H, J = 8.3 Hz). 13C-NMR (CDCl3,
125 MHz), d: 16.6, 40.1, 126.8, 127.2, 128.5, 129.2, 129.3,
129.5, 130.1, 130.2, 130.8, 131.5, 131.7, 134.7, 135.39, 138.4,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2012
Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles Using Sulfuric Acid
([3-(3-Silicapropyl)sulfanyl]propyl]ester as a Recyclable Solid Acid
639
[16] (a) Kidwai, M.; Mothsra, P.; Bansal, V.; Somvanshi, R. K.;
Ethayathulla, A. S.; Dey, S.; Singh, T. P. J Mol Catal A: Chem 2007,
265, 177; (b) Ren, Y. M.; Cai, C. J Chem Res (s) 2010, 133.
[17] Heravi, M. M.; Derikv, F.; Haghighi, M. Monatsh Chem 2008,
139, 31.
[18] Sadeghi, B.; Mirjalili, B. B. F.; Hashemi, M. M. Tetrahedron
Lett 2008, 49, 2575.
[19] Sharma, S. D.; Hazarika, P.; Konwar, D. Tetrahedron Lett
2008, 49, 2216.
Ganellin, C. R.; Parons, M. E. J Int Med Res 1975, 3, 86; (c) Tanigawara,
Y.; Aoyama, N.; Kita, T.; Shirakawa, K.; Komada, F.; Kasuga, M.;
Okumura, K. Clin Pharmacol Ther 1999, 66, 528; (d) Wauquier, A.;
Van Den Broeck, W. A. E.; Verheyen, J. L.; Janssen, P. A. J. Eur J
Pharmacol 1978, 47, 367.
[3] (a) Antolini, M.; Bozzoli, A.; Ghiron, C.; Kennedy, G.; Rossi,
T.; Ursini, A. Bioorg Med Chem Lett 1999, 9, 1023; (b) Wang, L.;
Woods, K. W.; Li, Q.; Barr, K. J.; McCroskey, R. W.; Hannick, S. M.;
Gherke, L.; Credo, R. B.; Hui, Y.-H.; Marsh, K.; Warner, R.; Lee, J. Y.;
Zielinsky-Mozng, N.; Frost, D.; Rosenberg, S. H.; Sham, H. L. J Med
Chem 2002, 45, 1697.
[20] Nagarapu, L.; Apuri, S.; Kantevari, S. J Mol Catal A: Chem
2007, 266, 104.
[21] Lipshutz, B. H.; Morey, M. C. J Org Chem 1983, 48, 3745.
[22] Mohammadizadeh, M. R.; Hasaninejad, A.; Bahramzadeh, M.
Synth Commun 2009, 39, 3232.
[23] (a) Samai, S.; Nandi, G. C.; Singh, P.; Singh, M. S. Tetrahedron
2009, 65, 10155; (b) Li, J. J.; Lin, S. W.; Dai, J. J.; Su, W. K.
J Chem Res (s) 2010, 196.
[4] (a) Lee, J. C.; Laydon, J. T.; McDonnell, P. C.; Gallagher, T.
F.; Kumar, S.; Green, D.; McNulty, D.; Blumenthal, M. J.; Keys, J. R.;
Vatter, S. W. L.; Strickler, J. E.; McLaughlin, M. M.; Siemens, I. R.;
Fisher, S. M.; Livi, G. P.; White, J. R.; Adams, J. L.; Young, P. R. Nature
1994, 372, 739; (b) Takle, A. K.; Brown, M. J. B.; Davies, S.; Dean,
D. K.; Francis, G.; Gaiba, A.; Hird, A. W.; King, F. D.; Lovell, P. J.; Naylor,
A.; Reith, A. D.; Steadman, J. G.; Wilson, D. M. Bioorg Med Chem Lett
2006, 16, 378.
[24] Sivakumar, K.; Kathirvel, A.; Lalitha, A. Tetrahedron Lett
2010, 51, 3018.
[5] de Laszlo, S. E.; Hacker, C.; Li, B.; Kim, D.; MacCoss, M.;
Mantalo, N.; Pivnichny, J. V.; Colwell, L.; Koch, G. E.; Cascieri, M. A.;
Hagmenn, W. K. Bioorg Med Chem Lett 1999, 9, 641.
[6] (a) Schmierer, R.; Mildenberger, H.; Buerstell, H. Ger. Pat.
3,61,464 (1987); (b) Schmierer, R.; Mildenberger, H.; Buerstell, H. Chem
Abstr 1988, 108, 37838.
[25] Mukhopadhyay, C.; Tapaswi, P. K.; Drew, M. G. B.
Tetrahedron Lett 2010, 51, 3944.
[26] Davoodnia, A.; Heravi, M. M.; Safavi-Rad, Z.; Tavakoli-
Hoseini, N. Synth Commun 2010, 40, 2588.
[27] Hekmat Shoar, R.; Rahimzadeh, G.; Derikvand, F.; Farzaneh,
M. Synth Commun 2010, 40, 1270.
[7] (a) Maier, T.; Schmierer, R.; Bauer, K.; Bieringer, H.;
Buerstell, H.; Sachse, B. U.S. Pat. 4,820,335 (1989); (b) Maier, T.;
Schmierer, R.; Bauer, K.; Bieringer, H.; Buerstell, H.; Sachse, B. Chem
Abstr 1989, 111, 19494w.
[8] (a) Siamaki, A. R.; Arndtsen, B. A. J Am Chem Soc 2006,
128, 6050; (b) Frantz, D. E.; Morency, L.; Soheili, A.; Murry, J. A.;
Grabowski, E. J. J.; Tillyer, R. D. Org Lett 2004, 6, 843–846.
[9] (a) Evans, D. A.; Lundy, K. M. J Am Chem Soc 1992, 114,
1495; (b) Davidson, D.; Weiss, M.; Jelling, M. J Org Chem 1937, 2,
319; (c) Claiborne, C. F.; Liverton, N. J.; Nguyen, K. T. Tetrahedron Lett
1998, 39, 8939.
[10] Schubert, H.; Stodolka, H. J Prakt Chem 1963, 22, 130.
[11] Heravi, M. M.; Derikvand, F.; Bamoharram, F. F. J Mol Catal
A Chem 2007, 263, 112.
[12] Balalaie, S.; Arabanian, A. Green Chem 2000, 2, 274.
[13] Usyatinsky, A. Y.; Khmelnitsky, Y. L. Tetrahedron Lett 2000,
41, 5031.
[28] (a) Karimi, B.; Ghoreishi-Nezhad, M. J Mol Catal A: Chem
2007, 277, 262; (b) Zareyee, D.; Karimi, B. Tetrahedron Lett 2007, 48,
1277.
[29] (a) Melero, J. A.; Grieken, R. V.; Morales, G. Chem Rev 2006,
106, 3790; (b) Shimizu, V; Hayashi, E.; Hatamachi, T.; Kodama, T.;
Higuch, T.; Satsuma, A.; Kitayama, Y. J Catal 2005, 231, 131.
[30] Niknam, K.; Saberi, D. Appl Catal A: Gen 2009, 366, 220.
[31] Niknam, K.; Saberi, D. Tetrahedron Lett 2009, 50, 5210.
[32] (a) Niknam, K.; Saberi, D.; Nouri Sefat, M. Tetrahedron Lett
2009, 50, 4058; (b) Niknam, K.; Saberi, D.; Mohagheghnejad, M.
Molecules 2009, 14, 1915; (c) Niknam, K.; Saberi, D.; Baghernejad, M.
Chin Chem Lett 2009, 20, 1444; (d) Niknam, K.; Saberi, D.; Sadegheyan,
M.; Deris, A. Tetrahedron Lett 2010, 51, 962; (e) Niknam, K.; Saberi, D.;
Molaee, H.; Zolfigol, M. A. Can J Chem 2010, 88, 164; (f) Niknam, K.;
Saberi, D.; Baghernejad, M. Phosphorus Sulfur Silicon 2010, 185, 875;
(g) Niknam, K.; Panahi, F.; Saberi, D.; Mohagheghnejad, M. J Heterocycl
Chem 2010, 47, 292.
[14] Karimi, A. R.; Alimohammadi, Z.; Azizian, J.; Mohammadi,
A. A.; Mohammadizadeh, M. R. Catal Commun 2006, 7, 728.
[15] Kantevari, S.; Vuppalapati, S. V. N.; Biradar, D. O.; Nagarapu,
L. J Mol Catal A: Chem 2007, 266, 109.
[33] (a) Gelens, E.; De Kanter, F. J. J.; Schmitz, R. F.; Sliedregt, L. A.;
Van Steen, B. J.; Kruse, C. G.; Leurs, R.; Groen, M. B.; Orru, R. V. Mol
Div 2006, 10, 17; (b) Siddiqui, S. A.; Narkhede, U. C.; Palimkar, S. S.;
Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. Tetrahedron 2005, 61, 3539.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet