One-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles in ionic liquid

Article abstract of DOI:10.1002/jhet.1751

The four-component condensation of benzil, aromatic aldehyde, primary amine, and ammonium acetate catalyzed by TFA in ionic liquid [Bpy]BF₄ at 80C provided 1,2,4,5-tetrasubstituted imidazoles in moderate to high yields.

Full text of DOI:10.1002/jhet.1751

May 2014
One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles in Ionic Liquid
713
*
Yu Wan,b Gui-xiang Liu,a Ling-ling Zhao,a Hai-ying Wang,a Shu-ying Huang,a Liang-feng Chen,a and Hui Wua,b
aSchool of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthesis of Functional Material,
Jiangsu Normal University, Xuzhou, 221116, People’s Republic of China
bJiangsu Key Laboratory of Biotechnology on Medical Plant, Xuzhou, 221116, People’s Republic of China
*
E-mail: wuhui72@126.com
Received March 10, 2012
DOI 10.1002/jhet.1751
Published online 3 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
Ph
N
Ph
Ph
O
O
15mol%TFA / 80oC
[Bpy]BF4
+
+
+
NH4OAC
4
Ph
Ar
Ar-CHO
2
RNH2
3
N
R
5
1
The four-component condensation of benzil, aromatic aldehyde, primary amine, and ammonium acetate
catalyzed by TFA in ionic liquid [Bpy]BF4 at 80ꢀC provided 1,2,4,5-tetrasubstituted imidazoles in moderate
to high yields.
J. Heterocyclic Chem., 51, 713 (2014).
INTRODUCTION
hazard organic solvents [27]. Hence, the development of
clean, high yielding, and environmental benign approaches
is still desirable and much in demand.
In this article, we report an efficient and simple strategy
to construct the framework of 1,2,4,5-tetrasubstituted
imidazole. The procedure involved the mixing of commer-
cially available benzil (1), aromatic aldehyde (2), primary
amine (3), and ammonium acetate (4) in ionic liquid [Bpy]
BF4 at 80ꢀC catalyzed by TFA (Scheme 1).
The development of a simple, efficient, and environmen-
tally synthetic method for widely used organic compounds
from readily available reagents is one of the major chal-
lenges for the chemists’ world [1]. With a wide range of
applications, imidazoles are receiving growing attention
in recent years [2]. Compounds containing imidazole
moiety have many pharmacological properties and play
important roles in biochemical processes [3]. In addition
with different substitutions, imidazoles have variable
biological activities such as anti-allergic activity [4],
anti-inflammatory activity [5], and analgesic activity [6].
Besides being known as inhibitors of p38MAP kinase
[7], various substituted imidazoles also act as therapeutic
agents [8], plant growth regulators [9], and glucagon
receptors [10]. Moreover, a recent report indicates that
synthetic imidazoles are potent inhibitors of protein–
protein interactions [11]. So, it is much in demand to find
simple and efficient methods for their synthesis.
In the last decades, many methods have been developed
for the synthesis of tetra-substituted imidazoles: (a) four-
component condensation of a 1,2-diketone, aldehyde, pri-
mary amine, and ammonium acetate using BF3–SiO2 [12],
silica gel–NaHSO4 [13], HClO4–SiO2 [14], K5CoW12-
O40Á3H2O [15], InCl3Á3H2O–MeOH [16], L–proline–MeOH
[17], I2–EtOH [18], HPA–EtOH [19], zeolite–HY–Cu(NO3)
2 [20], MCM-41 or p-TsOH [21], 1-butyl-3-methylimidazo-
lium bromide [22], and Brønsted acidic ionic liquid [23] as
catalyst; (b) hetero-Cope rearrangement [3]; (c) condensa-
tion of 1,2-diketone with an aryl nitrile and primary amine
under microwave irradiation [25]; and (d) reaction of
mesoionic 1,3-oxazolium-5-olates with N-(arylmethylene)
benzenesulfonamides [26].
RESULTS AND DISCUSSION
Initially, to optimize reaction condition, some catalysts
were screened first when benzil, p-fluorobenzaldehyde,
p-fluoraniline, and ammonium acetate were chosen as sub-
strates (Table 1). It was shown that 15 mol% of TFA is the
suitable one (entry 8), which may attribute to its suitable
acidity, for the ones with stronger or weaker acidity have
no advantages in this reaction. Consequently, all further
studies were conducted using 15 mol% of TFA as catalyst.
Having established the best catalyst, the effect of solvents
and temperature on the model reaction was subsequently
investigated (Table 2). Among the tested solvents such
as ethanol, THF, DMF, acetone, H2O, chloroform,
[Bmim]Br, [Bpy]Br, and [Bpy]BF4, [Bpy]BF4 gave the
highest yield (entry 11). It was observed that the suitable
temperature was 80ꢀC.
So, the mixture of benzil (1), aromatic aldehyde (2), amine
(3), ammonium acetate (4), and [Bpy]BF4 was stirred in the
presence of 15mol% of TFA at 80ꢀC for 1.5–3 h to give the
corresponding compounds (5) (Table 3). In all the cases,
1,2,4,5-tetrasubstituted imidazoles have been obtained in
moderate to high yields in short times (1.5–3 h). It was
important to note that the process tolerates both electron-
donating groups such as hydroxyl (entry 5k) and alkoxyl
However, some methods suffer disadvantages such as
tedious workup, low yields, longer reaction time, or using
© 2013 HeteroCorporation

714
Y. Wan, G.-x. Liu, L.-l. Zhao, H.-y. Wang, S.-y. Huang, L.-f. Chen, and H. Wu
Vol 51
Scheme 1. One-pot synthesis of 1,2,4,5-tetrasubstituted imidazole.
The probable mechanism was shown in Scheme 2. The
first step involved the acid-catalyzed reaction of amine (3)
with aromatic aldehyde (2), which acted as the source of
methylene to give imine (A) as the first key intermediate.
The addition of (A) to nucleophiles NH3 then gave the inter-
mediate (B). Subsequently, the intermediate (B) condensed
with the activated benzil to form the intermediate (D). Then,
the dehydration and rearranging of (D) and (E) via [1,5]
sigmatropic shift to give the final imidazoles (F).
Ph
N
Ph
Ph
O
O
15mol%TFA / 80oC
[Bpy]BF4
+
+
+
NH4OAC
4
Ph
Ar
Ar-CHO
2
RNH2
3
N
R
5
1
Table 1
The influence of catalysts on the yield of 5x.
In summary, we described a simple and convenient method
for the synthesis of 1,2,4,5-tetrasubstituted imidazoles in
[Bpy]BF4 at 80ꢀC in the presence of TFA. Both aromatic
aldehyde and aliphatic aldehyde can be used as substrates.
In addition, the method has many advantages such as facile
operations, the wide application of substrate, convenient
post-processing, and short reaction times (1.5–3 h).
Entry
Catalyst
Catalyst (mol%)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
HCl
H2SO4
HCOOH
SSA
CH3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
15
15
15
15
15
5
10
15
20
25
NP
NP
Nr
NP
Nr
30
55
87
87
86
EXPERIMENTAL
10
All reagents were purchased from commercial sources and used
without further purification. NMR spectra were recorded on a
Bruker Avance DMX400 (Hitachi, Japan) spectrometer in CDCl3
with TMS as an internal standard. Infrared spectra were recorded on
Bruker FTIR-Tensor 27 spectrometer expressed in cmÀ1 (KBr). Mass
was determined by using a Bruker Micro TOF-MS high-resolution
mass spectrometer. TLC analysis was performed with glass-backed
plates precoated with silica gel and examined under UV (254 nm).
Synthesis of 1,2,4,5-tetrasubstituted imidazoles. The mixture
of benzil (1 mmol), aromatic aldehyde (1 mmol), primary amine
(1 mmol), and ammonium acetate (5 mmol) was taken in a 50-mL
round-bottom flask containing 15 mol% of TFA and [Bpy]BF4
(2 mL) and stirred at 80ꢀC for the given time. After completion
of reaction (monitored by TLC), it was diluted with water
(15–20 mL); the precipitate was filtered, washed with water to
neutral and dried, then crystallized from 95% ethanol to give
the pure product.
Reaction condition: benzil (1 mmol), p-fluorobenzaldehyde (1 mmol),
p-fluoraniline (1 mmol), and ammonium acetate (5 mmol) in ionic liquid
[Bpy]BF4 (2 mL) at 80ꢀC for 2 h. NP, no desired products; Nr, no reac-
tion; SSA, silica sulfuric acid.
Table 2
The influence of solvents and temperature on the synthesis of 5x.
Entry
Solvent
T(ꢀC)
Isolated yield (%)
1
2
3
4
6
7
8
9
10
11
12
13
14
15
16
C2H5OH
THF
DMF
CH3COCH3
H2O
80
80
80
80
80
80
80
80
80
80
90
100
70
60
r.t.
10
Nr
Nr
Nr
Nr
Nr
56
61
74
87
87
86
65
54
0
CHCl3
[Bmim]Br
[Bpy]Br
[Bmim]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
We found that when more than one equivalent ammonium
acetate was used, the reaction will show better results. Thus, the
molar ratio of benzil to ammonium acetate was kept at 1:5.
Spectral data for new compounds.
1-(4-Chlorophenyl)-2,4,5-triphenyl-1H-imidazole (5a). mp
198–199ꢀC; IR (KBr) n: 3053, 2911, 1600, 1513, 1493, 1444, 1396,
1370, 1272, 1139, 1090, 1074, 1019, 959, 843, 770, 754,
705, 694 cmÀ1 1H NMR (400 MHz, CDCl3) (d, ppm): 7.19
;
(t, J= 7.2 Hz, 1H, Ar H), 7.24–7.35 (m, 12H, Ar H), 7.39–7.41 (m,
4H, Ar H), 7.50 (d, J= 7.6 Hz, 2H, Ar H); HRMS: Calcd for
C27H19Cl N2 [M + H]+; found (expected): 407.1548 (407.1316).
2-(4-Bromophenyl)-1-(4-chlorophenyl)-4,5-diphenyl-1H-
imidazole(5b). mp 210–212ꢀC; IR (KBr) n: 3063, 2954, 1601,
1564, 1491, 1441, 1411, 1370, 1319, 1272, 1180, 1169, 1137,
1089, 1073, 1017, 1006, 983, 960, 915, 841, 832, 786, 772,
Reaction condition: benzil (1 mmol), p-fluorobenzaldehyde (1 mmol),
p-fluoraniline (1 mmol), and ammonium acetate (5 mmol) in [Bpy]BF4
(2 mL) for 2 h catalyzed by 15 mol% of TFA. Nr, no reaction.
group (entry 5e) and electron-withdrawing substituents (such
as halide groups) on the aldehyde and amine. The groups on
the meta-position of the amine has produced low to moderate
yields of the corresponding imidazoles and took longer
reaction time, which illustrated that the steric hindrance
may have a certain impact on the reaction. On the other hand,
the cyclohexylamine gave the lower yield, which may be due
to its lower activity and bigger steric hindrance.
752, 726, 712, 676, 650 cmÀ1 1H NMR (400 MHz, CDCl3)
;
(d, ppm): 7.18 (t, J = 6.8 Hz, 1H, Ar H), 7.24–7.34 (m, 13H, Ar
H), 7.39–7.41 (m, 2H, Ar H), 7.51 (d, J = 7.6 Hz, 2H, Ar H);
HRMS: Calcd for C27H18BrClN2 [M + H]+; found (expected):
485.0640 (485.0421).
1-(4-Chlorophenyl)-2-(3,4,5-trimethoxyphenyl)-4,5-diphenyl-
1H-imidazole (5c). mp 192–194ꢀC; IR (KBr) n: 3029, 2927,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
Synthesis of Imidazoles in Ionic Liquid
715
Table 3
Synthesis of tetrasubstituted imidazoles 5 in ionic liquid.
Entry
Ar
R
t (h)
Isolated yield (%)
Lit. yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
5 t
5u
5v
5w
5x
C6H5
4-BrC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
PhCH2
PhCH2
PhCH2
PhCH2
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-BrC6H4
4-BrC6H4
4-CH3C6H4
4-FC6H4
3-ClC6H4
3-ClC6H4
3-ClC6H4
3-ClC6H4
3-BrC6H4
3-BrC6H4
3-CH3C6H4
CH3
2
2
2
1.5
2
2
2
1.5
2
2
2
2
2
1.5
2
2
2
2
2
2
2
1.5
1.5
2
2
2
3
3
3
3
3
2
2
3
87
89
86
90
85
88
87
88
89
87
81
85
87
88
87
82
86
84
82
85
83
85
86
87
78
83
80
75
70
65
62
86
85
56
3,4,5-(CH3O)2C6H3
4-IC6H4
4-CH3OC6H4
4-CH3OC6H4
4-FC6H4
4-IC6H4
4-ClC6H4
C6H5
4-OHC6H4
4-BrC6H4
4-BrC6H4
4-IC6H4
3,4,5-(CH3O)3C6H2
C6H5
4-FC6H4
4-CH3OC6H4
C6H5
3,4,5-(CH3O)3C6H2
C6H5
4-FC6H4
4-FC6H4
4-FC6H4
4-CH3OC6H4
4-IC6H4
4-FC6H4
C6H5
4-FC6H4
80 [28]
75 [28]
78 [17]
73 [28]
89 [27]
79 [16]
5y
5z
5aa
5bb
5cc
5dd
5ee
5ff
5gg
5hh
4-CH3OC6H4
4-FC6H4
3,4,5-(CH3O)3C6H2
4-FC6H4
CH3
cyclohexyl
4-ClC6H4
Reaction condition: benzil (1 mmol), aromatic aldehyde (1 mmol), amine (1 mmol), and ammonium acetate (5 mmol) in [Bpy]BF4 (2 mL) at 80ꢀC
catalyzed by TFA.
Scheme 2
Ph
OH
H
R
N
A
NH2
Ar NHR
O
Ph
O
H
NH3
+
RNH2
C
Ar
H
-H2O
Ar
H
B
Ph
OH
Ph
Ph Ph
O
N
H
HN
Ph
HO
Ph
Ar
N
Ar
Ar
NHR
R
R
-H2O
F
D
E
1600, 1523, 1514, 1479, 1446, 1420, 1387, 1369, 1222, 1158, 1139,
(d, J = 7.2 Hz, 2H, Ar H); 13C NMR (100 MHz, CDCl3): d
152.89, 146.69, 138.36, 135.96, 134.24, 134.16, 131.11, 130.63,
130.31, 129.77, 129.36, 128.27, 128.22, 127.40, 126.81, 125.47,
106.39, 60.91, 55.91, 30.93; HRMS: Calcd for C30H25ClN2 O3
[M+ H]+; found (expected): 497.1770 (497.1633).
1108, 1072, 1017, 959, 917, 839, 816, 772, 737, 720, 698, 660 cmÀ1
;
1H NMR (400 MHz, CDCl3) (d, ppm): 3.66 (s, 6H, 2 Â OCH3), 3.84
(s, 3H, OCH3), 6.63 (s, 2H, Ar H), 7.01 (d, J = 8.8 Hz, 2H, Ar H),
7.12–7.14 (m, 2H, Ar H), 7.20–7.30 (m, 8H, Ar H), 7.58
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Y. Wan, G.-x. Liu, L.-l. Zhao, H.-y. Wang, S.-y. Huang, L.-f. Chen, and H. Wu
Vol 51
1-(4-Chlorophenyl)-2-(4-iodophenyl)-4,5-diphenyl-1H-
imidazole (5d).
mp 221–223ꢀC; IR (KBr) n: 3062, 1590,
1524, 1511, 1501, 1479, 1444, 1419, 1370, 1234, 1179, 1157,
1140, 1097, 1074, 1027, 843, 788, 697 cmÀ1 1H NMR
(400 MHz, CDCl3) (d, ppm): 6.96 (d, J = 8.4 Hz, 2H, Ar H),
7.10–7.16 (m, 4H, Ar H), 7.20–7.29 (m, 8H, Ar H), 7.56 (d,
J = 7.2 Hz, 2H, Ar H), 7.61 (d, J = 8.4 Hz, 2H, Ar H).
J= 8.8 Hz, 2H, Ar H), 6.93–7.03 (m, 4H, Ar H), 7.10–7.13 (m,
2H, Ar H), 7.17–7.20 (m, 1H, Ar H), 7.22–7.26 (m, 5H, Ar H),
7.35 (d, J= 8.4 Hz, 2H, Ar H), 7.58 (d, J= 7.2 Hz, 2H, Ar H).
1,2-Bis(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole (5r).
mp 201–203ꢀC; IR (KBr) n: 3052, 2934, 2854, 1599, 1567, 1548,
1529, 1512, 1499, 1479, 1465, 1441, 1409, 1381, 1360, 1335, 1288,
;
1179, 1121, 1093, 1074, 1014, 993, 956, 929, 901, 839, 693 cmÀ1
;
1-(4-Chlorophenyl)-2-(4-methoxyphenyl)-4,5-diphenyl-1H-
imidazole (5e). mp 176–177ꢀC; IR (KBr) n: 3060, 1600, 1499,
1480, 1446, 1416, 1356, 1325, 1300, 1121, 1089, 1070, 1012, 974,
1H NMR (400 MHz, CDCl3) (d, ppm): 3.78 (s, 3H, OCH3), 3.79
(s, 3H, OCH3), 6.77 (t, J= 8.4 Hz, 4H, Ar H), 6.96 (d, J=8.8Hz,
2H, Ar H), 7.11–7.24 (m, 8H, Ar H), 7.39 (d, J= 8.4 Hz, 2H, Ar H),
7.59 (d, J= 7.2 Hz, 2H, Ar H).
1
953, 835, 758, 729, 720, 693 cmÀ1; H NMR (400 MHz, CDCl3)
(d, ppm): 3.80 (s, 3H, OCH3), 6.80 (d, J= 8.8 Hz, 2H, Ar H), 6.96
(d, J= 8.8 Hz, 2H, Ar H), 7.10–7.12 (m, 2H, Ar H), 7.19–7.26 (m,
8H, Ar H), 7.34 (d, J= 8.8 Hz, 2H, Ar H), 7.57 (d, J= 7.2 Hz, 2H,
Ar H); HRMS: Calcd for C28H21ClN2O [M+ H]+; found
(expected): 437.1652 (437.1421).
1-(4-Methoxyphenyl)-2,4,5-triphenyl-1H-imidazole (5s).
mp 175–177ꢀC; IR (KBr) n: 3051, 2961, 2836, 1602, 1510,
1479, 1462, 1444, 1398, 1294, 1247, 1178, 1169, 1106, 1072,
1029, 841, 771, 712, 695 cmÀ1 1H NMR (400 MHz, CDCl3)
;
(d, ppm): 3.77 (s, 3H, OCH3), 6.76 (d, J = 8.8 Hz, 2H, Ar H), 6.96
(d, J = 10.4 Hz, 2H, Ar H), 7.12–7.25 (m, 6H, Ar H), 7.30–7.36
(m, 2H, Ar H), 7.41–7.47 (m, 3H, Ar H), 7.55–7.60 (m, 3H, Ar
H), 7.98 (d, J = 7.6 Hz, 1H, Ar H).
2-(4-Methoxyphenyl)-1,4,5-triphenyl-1H-imidazole (5f).
mp 168–169ꢀC; IR (KBr) n: 3061, 2957, 2934, 2905, 2837,
1608, 1577, 1528,1495, 1481, 1441, 1421, 1387, 1368, 1307,
1294, 1252, 1182, 1154, 1113, 1071, 1025, 958, 916, 840, 781,
2-(3,4,5-Trimethoxyphenyl)-1-(4-methoxyphenyl)-4,5-diphenyl-
1H-imidazole (5t). mp 207–208ꢀC; IR (KBr) n: 3011, 2933, 2839,
1603, 1582, 1511, 1483, 1440, 1413, 1337, 1295, 1250, 1181, 1167,
1123, 1075, 1028, 1007, 965, 921, 869, 840, 778, 738,
1
764, 735, 720, 700, 657, 614 cmÀ1; H NMR (400 MHz, CDCl3)
(d, ppm): 3.73 (s, 3H, OCH3), 6.85 (d, J = 8.0 Hz, 2H, Ar H),
7.15–7.35 (m, 15H, Ar H), 7.49 (d, J = 8.0 Hz, 2H, Ar H).
2-(4-Fluorophenyl)-1,4,5-triphenyl-1H-imidazole (5g). mp
192–194ꢀC; IR (KBr) n: 3049, 1597, 1522, 1494, 1446, 1418,
1387, 1371, 1225, 1156, 1139, 1098, 1071, 1026, 1016, 959,
724, 702 cmÀ1 1H NMR (400 MHz, CDCl3) (d, ppm): 3.65
;
(s, 6H, 2 Â OCH3), 3.77 (s, 3H, OCH3), 3.83 (s, 3H, OCH3),
6.69 (s, 2H, Ar H), 6.79 (d, J = 8.8 Hz, 2H, Ar H), 7.01
(d, J = 8.8 Hz, 2H, Ar H), 7.13–7.26 (m, 8H, Ar H), 7.59
(d, J = 7.2 Hz, 2H, Ar H); 13C NMR (100 MHz, CDCl3): d
159.26, 155.47, 152.75, 146.74, 138.13, 136.78, 131.15, 130.71,
129.59, 128.38, 128.16, 127.40, 126.61, 114.30, 106.26, 60.88,
918, 839, 789, 777, 764, 734, 696, 659, 609 cmÀ1 1H NMR
;
(400 MHz, CDCl3) (d, ppm): 6.93 (t, J = 8.4 Hz, 2H, Ar H),
7.02–7.04 (m, 2H, Ar H), 7.11–7.13 (m, 2H, Ar H), 7.17–7.30
(m, 9H, Ar H), 7.39–7.42 (m, 2H, Ar H), 7.58 (d, J = 8.0 Hz,
2H, Ar H); HRMS: Calcd for C27H19Cl N2 [M + H]+; found
(expected): 391.1819 (391.1611).
55.91, 55.50, 30.93; HRMS: Calcd for C31H28N2
found (expected): 493.2349 (493.2128).
O
4[M+ H]+;
2-(4-Iodophenyl)-1,4,5-triphenyl-1H-imidazole (5h).
mp
1-(4-Bromophenyl)-2,4,5-triphenyl-1H-imidazole (5u). mp
218–220ꢀC; IR (KBr) n: 3049, 1596, 1523, 1494, 1446, 1419,
196–197ꢀC; IR (KBr) n: 3038, 1600, 1488, 1461, 1443, 1396, 1323,
1388, 1371, 1225, 1159, 1072, 960, 839, 789, 764, 735, 696 cmÀ1
;
1202, 1128, 1071, 1027, 1016, 965, 915, 840, 766, 734, 696 cmÀ1
;
1H NMR (400 MHz, CDCl3) (d, ppm): 7.03 (d, J= 7.2 Hz, 2H,
Ar H), 7.10–7.13 (m, 2H, Ar H), 7.16 (d, J= 8.4 Hz, 2H, Ar H),
7.20–7.25 (m, 5H, Ar H), 7.28–7.31 (m, 4H, Ar H), 7.57
(d, J= 8.4 Hz, 4H, Ar H); HRMS: Calcd for C27H19I N2 [M + H]+;
found (expected): 499.0871 (499.0672).
1H NMR (400 MHz, CDCl3) (d, ppm): 6.90 (d, J=8.4Hz, 1H,
Ar H), 7.12 (d, J= 8.0 Hz, 1H, Ar H), 7.20–7.23(m, 1H, Ar H),
7.31–7.49 (m, 13H, Ar H), 7.57(d, J= 8.0 Hz, 2H, Ar H), 7.93
(d, J = 8.4 Hz, 1H, Ar H).
1-(4-Bromophenyl)-2-(4-fluorophenyl)-4,5-diphenyl-1H-
imidazole (5v). mp 203–204ꢀC; IR (KBr) n: 3042, 2963, 2838,
1598, 1578, 1517, 1499, 1458, 1436, 1411, 1378, 1327, 1290,
1249, 1171, 1115, 1104, 1091, 1030, 1009, 901, 879, 854, 827,
1-Benzyl-2-(4-bromophenyl)-4,5-diphenyl-1H-imidazole (5m).
mp 171–172ꢀC; IR (KBr) n: 3057, 2925, 1592, 1573, 1517,
1500, 1458, 1435, 1381, 1327, 1276, 1238, 1208, 1171, 1117,
1103, 1028, 1011, 882, 856, 830, 755, 690 cmÀ1
;
1H NMR
794, 758, 693 cmÀ1; H NMR (400 MHz, CDCl3) (d, ppm): 6.89
1
(400 MHz, CDCl3) (d, ppm): 5.01 (s, 2H, CH2), 6.80–6.82 (m,
2H, Ar H), 7.15 (d, J = 6.8 Hz, 1H, Ar H), 7.19–7.23 (m, 7H, Ar
H), 7.30–7.36 (m, 3H, Ar H), 7.51 (s, 4H, Ar H), 7.55 (d,
J = 7.6 Hz, 2H, Ar H).
(d, J= 8.4 Hz, 2H, Ar H), 6.97 (t, J = 8.4 Hz, 2H, Ar H), 7.10–7.12
(m, 2H, Ar H), 7.18–7.25 (m, 4H, Ar H), 7.28–7.31 (m, 2H, Ar
H), 7.38–7.41 (m, 4H, Ar H), 7.57 (d, J= 7.2 Hz, 2H, Ar H).
2-(4-Fluorophenyl)-4,5-diphenyl-1-p-tolyl-1H-imidazole (5w).
mp 182–184ꢀC; IR (KBr) n: 3047, 2963, 2911, 1600, 1592, 1579,
1563, 1498, 1459, 1435, 1414, 1378, 1327, 1274, 1238, 1144,
1-Benzyl-2-(4-iodophenyl)-4,5-diphenyl-1H-imidazole (5n).
mp 182–183ꢀC; IR (KBr) n: 3059, 3025, 2939, 1599, 1557,
1478, 1446, 1410, 1359, 1324, 1299, 1256, 1120, 1070, 1061,
1029, 1004, 972, 952, 917, 828, 775, 760, 737, 724, 714, 694,
1
1089, 1028, 1007, 963, 868, 799, 788, 749, 731 cmÀ1; H NMR
(400 MHz, CDCl3) (d, ppm): 2.32 (s, 3H, CH3), 6.89–6.96
(m, 4H, Ar H), 7.05 (d, J = 8.0 Hz, 2H, Ar H), 7.12 (d, J = 7.2 Hz,
2H, Ar H), 7.17–7.26 (m, 6H, Ar H), 7.39–7.43 (m, 2H, Ar H),
7.57 (d, J = 7.6 Hz, 2H, Ar H).
1
666, 633, 617cmÀ1; H NMR (400 MHz, CDCl3) (d, ppm): 5.08
(s, 2H, CH2), 6.80–6.82 (m, 2H, Ar H), 7.13–7.22 (m, 8H, Ar H),
7.29–7.36 (m, 3H, Ar H), 7.38 (d, J = 8.0 Hz, 2H, Ar H), 7.55
(d, J = 8.0Hz, 2H, Ar H), 7.72 (d, J = 8.4 Hz, 2H, Ar H).
1,2-Bis(4-fluorophenyl)-4,5-diphenyl-1H-imidazole (5x).
mp 196–197ꢀC; IR (KBr) n: 3056, 1602, 1523 1509, 1480, 1446,
1414, 1387, 1370, 1325, 1223, 1154, 1128, 1096, 1073, 1026,
2-(4-Fluorophenyl)-1-(4-methoxyphenyl)-4,5-diphenyl-1H-
imidazole (5q).
mp 194–196ꢀC; IR (KBr) n: 3063, 2966,
2931, 2837, 1603, 1512, 1480, 1461, 1442, 1422, 1390, 1373,
1015, 959, 917, 839, 774, 737, 720, 697, 658, 623 cmÀ1 1H
;
1298, 1251, 1180, 1169, 1159, 1137, 1107, 1072, 1030, 960,
NMR (400 MHz, CDCl3) (d, ppm): 6.94–7.03 (m, 6H, Ar H),
7.11–7.13 (m, 2H, Ar H), 7.18–7.25 (m, 4H, Ar H), 7.27–7.28
(m, 2H, Ar H), 7.39–7.42 (m, 2H, Ar H), 7.57 (d, J = 7.2 Hz, 2H,
913, 840, 817, 776, 724, 714, 697, 656 cmÀ1
;
1H NMR
(400 MHz, CDCl3) (d, ppm): 3.79 (s, 3H, OCH3), 6.79 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
Synthesis of Imidazoles in Ionic Liquid
717
Ar H); HRMS: Calcd for C27H18F2 N2 [M+ H]+; found (expected):
409.1794 (409.1517).
1591, 1578, 1532, 1502, 1479, 1447, 1423, 1383, 1368, 1305,
1293, 1249, 1176, 1112, 1094, 1075, 1029, 993, 959, 888, 831,
1
1-(3-Chlorophenyl)-2-(4-methoxyphenyl)-4,5-diphenyl-1H-
788, 777, 736, 693cmÀ1; H NMR (400MHz, CDCl3) (d, ppm):
imidazole(5y).
1574, 1500, 1477, 1443, 1428, 1391, 1372, 1322, 1181, 1139,
1073, 1026, 961, 919, 802, 777, 721, 697 cmÀ1 1H NMR
mp 202–203ꢀC; IR (KBr) n: 3059, 1590,
2.21 (s, 3H, CH3), 6.84 (s, 2H, Ar H), 7.07–7.26 (m, 12H, Ar H),
7.43–7.46 (m, 2H, Ar H), 7.59 (d, J = 7.2 Hz, 2H, Ar H); 13C
NMR (100 MHz, CDCl3): d 163.91, 161.44, 145.96, 139.23,
138.19, 136.91, 134.46, 131.12, 130.93, 130.79, 130.70, 129.15,
128.95, 128.87, 128.31, 128.17, 127.98, 127.37, 126.62, 125.48,
115.24, 115.03, 30.93, 21.19.
;
(400 MHz, CDCl3) (d, ppm): 3.79 (s, 3H, OCH3), 6.80 (d,
J = 8.8 Hz, 2H, Ar H), 6.93(d, J = 8.0 Hz, 1H, Ar H), 7.04
(s, 1H, Ar H), 7.11–7.26 (m, 10H, Ar H), 7.36 (d, J = 8.8 Hz,
2H, Ar H), 7.58 (d, J = 7.6 Hz, 2H, Ar H); 13C NMR
(100 MHz, CDCl3): d 159.82, 146.89, 138.46, 138.26, 134.32,
131.14, 130.46, 130.34, 129.97, 128.69, 128.51, 128.17,
127.37, 126.85, 126.67, 122.78, 113.75, 55.27, 30.93.
2-(3,4,5-Trimethoxyphenyl)-1-methyl-4,5-diphenyl-1H-
imidazole (5ff). mp 218–219ꢀC; IR (KBr) n: 3032, 3011,
2957, 2936, 2903, 2827, 1584, 1526, 1487, 1427, 1412,
1386, 1328, 1238, 1181, 1168, 1074, 1022, 1002, 964, 937,
1
1-(3-Chlorophenyl)-2-(4-iodophenyl)-4,5-diphenyl-1H-
imidazole (5z). mp 193–194ꢀC; IR (KBr) n: 3061, 1589, 1499,
1478, 1443, 1432, 1406, 1300, 1183, 1140, 1095, 1074, 1058, 1028,
914, 882, 848, 837, 774, 732, 712, 699, 685, 650 cmÀ1; H
NMR (400 MHz, CDCl3) (d, ppm): 3.51 (s, 3H, CH3), 3.91
(s, 3H, OCH3), 3.94 (s, 6H, 2 Â OCH3), 6.93 (s, 2H, Ar H),
7.13–7.23 (m, 3H, Ar H), 7.41–7.50 (m, 5H, Ar H), 7.55
(d, J = 7.6 Hz, 2H, Ar H).
1
1007, 992, 960, 830, 806, 788, 774, 735, 720, 697, 655 cmÀ1; H
NMR (400 MHz, CDCl3) (d, ppm): 6.94 (d, J= 7.6 Hz, 1H, Ar
H), 7.05 (s, 1H, Ar H), 7.12 (d, J= 7.2 Hz, 2H, Ar H), 7.17
(d, J= 8.4 Hz, 2H, Ar H), 7.20–7.31 (m, 8H, Ar H), 7.57 (d,
J= 7.2 Hz, 2H, Ar H), 7.62 (d, J= 8.4 Hz, 2H, Ar H); 13C NMR
(100 MHz, CDCl3): d 145.87, 138.78, 137.48, 134.48, 134.03,
131.09, 130.47, 130.17, 129.76, 128.60, 128.35, 128.23, 127.34,
126.87, 94.72, 30.93.
2-(4-Fluorophenyl)-1-methyl-4,5-diphenyl-1H-imidazole(5gg).
mp 169–170ꢀC; IR (KBr) n: 3052, 2992, 2914, 1602, 1528,
1502, 1480, 1467, 1448, 1410, 1377, 1320, 1298, 1224, 1157,
1131, 1098, 1072, 1030, 1015, 1001, 958, 922, 839, 820, 777,
1
749, 733, 721, 704, 649, 604 cmÀ1; H NMR (400MHz, CDCl3)
(d, ppm): 3.49 (s, 3H, CH3), 7.15–7.23 (m, 5H, Ar H), 7.40–7.54
(m, 7H, Ar H), 7.71–7.75 (m, 2H, Ar H); HRMS: Calcd for
C22H17F N2 [M+ H]+; found (expected): 329.1650 (329.1455).
2-(4-Chlorophenyl)-1-cyclohexyl-4,5-diphenyl-1H-imidazole
(5hh). mp 193–195ꢀC; IR (KBr) n: 3052, 2934, 2853, 1599,
1512, 1499, 1479, 1465, 1441, 1381, 1359, 1335, 1288, 1221,
1-(3-Chlorophenyl)-2-(4-fluorophenyl)-4,5-diphenyl-1H-
imidazole (5aa).
1524, 1511, 1501, 1479, 1444, 1419, 1370, 1234, 1179, 1157,
1140, 1097, 1074, 1027, 843, 788, 697 cmÀ1 1H NMR
mp 193–194ꢀC; IR (KBr) n: 3062, 1590,
;
(400MHz, CDCl3) (d, ppm): 6.92–7.00 (m, 3H, Ar H), 7.04
(s, 1H, Ar H), 7.11–7.14 (m, 2H, Ar H), 7.21–7.30 (m, 8H, Ar
H), 7.40–7.44 (m, 2H, Ar H), 7.58 (d, J = 7.2 Hz, 2H, Ar H);
HRMS: Calcd for C27H18ClF N2 [M+ H]+; found (expected):
425.1440 (425.1222).
1093, 839, 693 cmÀ1 1H NMR (400 MHz, CDCl3) (d, ppm):
;
0.70–0.81 (m, 1H, CH2), 0.99–1.10 (m, 2H, CH2), 1.45–1.55
(m, 3H, CH2), 1.63–1.66 (m, 2H, CH2), 1.82–1.86 (m, 2H, CH2),
3.89–3.96 (m, 1H, CH), 7.09–7.16 (m, 3H, Ar H), 7.39–7.48
(m, 9H, Ar H), 7.56 (d, J = 7.6 Hz, 2H, Ar H).
1-(3-Chlorophenyl)-2,4,5-triphenyl-1H-imidazole (5bb). mp
214–215ꢀC; IR (KBr) n: 3062, 1590, 1499, 1478, 1443, 1391,
1372, 1140, 1095, 1074, 1026, 961, 919, 806, 789, 776, 763,
720, 697, 654 cmÀ1 1H NMR (400 MHz, CDCl3) (d, ppm):
;
Acknowledgments. We are grateful to the foundation of the
Priority Academic Program Development of Jiangsu Higher
Education Institutions, Qing Lan Project in Jiangsu Province
(no.08QL001T), Key Basic Research Project in Jiangsu University
(no. 10KJA430050), the Post-graduate Innovation Project in
Jiangsu Province (no. CXZZ11_0904), and the Natural Science
Foundation of Jiangsu Normal University (nos. 09XLA17 and
09XLB05) for financial support.
6.94 (d, J = 8.4 Hz, 1H, Ar H), 7.05 (s, 1H, Ar H), 7.12–7.14
(m, 2H, Ar H), 7.17–7.31 (m, 11H, Ar H), 7.44 (d, J = 6.4 Hz,
2H, Ar H), 7.60 (d, J = 7.6 Hz, 2H, Ar H).
1-(3-Bromophenyl)-2-(4-fluorophenyl)-4,5-diphenyl-1H-
imidazole (5cc).
mp 191–193ꢀC; IR (KBr) n: 3059, 1589,
1573, 1526, 1500, 1477, 1444, 1428, 1369, 1232, 1157, 1097,
1072, 844, 780, 696cmÀ1; 1H NMR (400 MHz, CDCl3) (d, ppm):
6.98 (t, J = 8.8 Hz, 3H, Ar H), 7.12–7.30 (m, 10H, Ar H),
7.39–7.45 (m, 3H, Ar H), 7.57 (d, J= 7.2 Hz, 2H, Ar H); HRMS:
Calcd for C27H18BrFN2 [M + H]+; found (expected): 469.0757
(469.0716).
REFERENCES AND NOTES
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1293, 1248, 1176, 1112, 1064, 1028, 959, 832, 780, 735,
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