l-Proline: an efficient catalyst for the one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles

Article abstract of DOI:10.1016/j.tet.2009.10.019

A simple highly versatile and efficient synthesis of 2,4,5-trisubstituted imidazoles is achieved by three-component cyclocondensation of 1,2-dicarbonyl compound, aldehyde and ammonium acetate using l-proline as a catalyst in methanol at moderate temperature. To explore the utility of this method 1,2,4,5-tetrasubstituted imidazoles were also synthesized. The key advantages of this process are high yields, cost effectiveness of catalyst, easy work-up and purification of products by non-chromatographic methods.

Full text of DOI:10.1016/j.tet.2009.10.019

Tetrahedron 65 (2009) 10155–10161
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Tetrahedron
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L
-Proline: an efficient catalyst for the one-pot synthesis of 2,4,5-trisubstituted
and 1,2,4,5-tetrasubstituted imidazoles
*
Subhasis Samai, Ganesh Chandra Nandi, Pallavi Singh, M.S. Singh
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple highly versatile and efficient synthesis of 2,4,5-trisubstituted imidazoles is achieved by three-
component cyclocondensation of 1,2-dicarbonyl compound, aldehyde and ammonium acetate using
Received 16 June 2009
Received in revised form
5 October 2009
Accepted 6 October 2009
Available online 12 October 2009
L-proline as a catalyst in methanol at moderate temperature. To explore the utility of this method 1,2,4,5-
tetrasubstituted imidazoles were also synthesized. The key advantages of this process are high yields, cost
effectiveness of catalyst, easy work-up and purification of products by non-chromatographic methods.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent reaction
One-pot synthesis
L-Proline
2,4,5-Trisubstituted imidazoles
1,2,4,5-Tetrasubstituted imidazoles
1. Introduction
A number of methods have been developed for the synthesis of
2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. Gen-
Multicomponent reactions (MCRs) have drawn great interest
enjoying an outstanding status in modern organic synthesis and
medicinal chemistry because they are one-pot processes bringing
together three or more components and show high atom economy
and high selectivity.1 MCRs have great contribution in convergent
synthesis of complex and important organic molecules from simple
and readily available starting materials, and have emerged as pow-
erful tools for drug discovery.2 Imidazoles are an important class of
heterocycles being the core fragment of different natural products
and biological systems. Compounds containing imidazole moiety
have many pharmacological properties and play important roles in
biochemical processes.3a The potency and wide applicability of the
imidazole pharmacophore can be attributed to its hydrogen bond
donor–acceptor capability as well as its high affinity for metals,
which are present in many protein active sites3b (e.g., Zn, Fe, Mg).
Various substituted imidazoles act as inhibitors of p38 MAP kinase,4a
B-Raf kinase,4b glucagon receptors,5 plant growth regulators,6 ther-
apeutic agents,7 antibacterial,8 antitumour,9 and also pesticides.10
Recent development of green chemistry and organometallic chem-
istry expands the utility of imidazoles as ionic liquids11 and N-het-
erocyclic carbenes.12 They also serve as useful building blocks for the
synthesis of other classes of compounds.
erally 2,4,5-trisubstituted imidazoles are synthesized by three-
component cyclocondensation of 1,2-diketone, -hydroxyketone or
a
a
-ketomonoxime with an aldehyde and ammonium acetate, which
comprise the use of ionic liquids,13 refluxing in acetic acid,14 silica
supported sulfuric acid,15 InCl3$3H2O,16a ceric ammonium nitrate
16c
(CAN),16b NiCl2$6H2O/Al2O3 and microwave irradiation.17
On the other hand, the synthesis of 1,2,4,5-tetrasubstituted
imidazoles have been carried out by four-component condensation of
a 1,2-diketone, a-hydroxyketone or a-ketomonoxime with an alde-
hyde, primary amine and ammonium acetate using microwaves,18a
18e
heteropolyacid,18b BF3$SiO2,18c silica gel/NaHSO418d or HClO4–SiO2
and ionic liquids.13 In addition, they can also be synthesized by the
cycloaddition reaction of mesoionic 1,3-oxazolium-5-olates with
N-(arylmethylene) benzenesulfonamides,19a hetero-Cope rearrange-
ment,19b condensation of a 1,2-diketone with an aryl nitrile and pri-
maryamine under microwave irradiation.19c Tri- and tetrasubstituted
imidazoles have been synthesized in high yields using 20 mol % of
ZrCl4 as catalyst at room temperature.19d
In recent years L-proline has drawn much interest in different
organic reactions due to its experimental simplicity, ease of handling,
cost effectiveness and excellent solubility in water and organic sol-
vents.
L-Proline has been found to be a very efficient catalyst in dif-
ferent transformations like enamine based direct catalytic
asymmetric aldol condensation,20 -amination reaction,21 Mannich
a
reaction,22 Diels–Alder reaction,23 Knoevenagel reaction,23a Michael
condensation24 and as excellent promoter for the copper-catalysed
* Corresponding author. Tel.: þ91 542 6702502; fax: þ91 542 2368127.
E-mail address: mssinghbhu@yahoo.co.in (M.S. Singh).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.019

10156
S. Samai et al. / Tetrahedron 65 (2009) 10155–10161
coupling reactions.25 More recently it has been used in solvent free
Biginelli reaction,26 in asymmetric Hantzsch reaction27 and for the
selective synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles from
a wide range of substituted o-phenylenediamines and aldehydes.28
Proline catalysis has emerged recently as an efficient means of
generating functionalized cyclohexanes and spirane products via
Barbas three-component cycloaddition.29 Proline has also been used
as catalyst for two-carbon homologation and in various multicom-
ponent reactions in one-pot.30
and toluene but none of the above solvent was found to be effective
than methanol for this reaction (Table 1). Since water exhibits
a unique reactivity and selectivity different from conventional
organic solvents, the reaction was also carried out in water.32
Nevertheless, the reaction at 60 ꢀC did not give the desired product
and the starting material was recovered, whereas, after a prolonged
reaction (>24 h) at 100 ꢀC only trace of the desired product was
identified by TLC in the crude (Table 1, entries 14 and 15). It was
found that methanol was a solvent of choice for the reaction and
the desired product was obtained in MeOH at 60 ꢀC in excellent
yield when 15 mol % of the catalyst was used (Table 1, entry 5). After
optimising the reaction condition, different 1,2-diketones and al-
dehydes were then evaluated for the reaction.
The developing of new MCRs31 and improving known multi-
component reactions are an area of considerable current interest.
Herein, we report a simple and facile multicomponent one-pot
synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imid-
azoles in highyields, using
L
-proline (15 mol %) as an organocatalyst.
We next examined a wide variety of aldehydes (both aromatic and
aliphatic) with various substituents to establish the catalytic impor-
tance of L-proline for this reaction. A wide range of ortho-, meta- and
para-substituted aromatic aldehydes undergo this one-pot multi-
component synthesis with 1,2-diketones and ammonium acetate to
afford 2,4,5-trisubstituted imidazoles (1) in good yields (Scheme 1).
Most of the above reported synthetic methods for the synthesis of
tri- and tetrasubstituted imidazoles suffer from one or more draw-
backs, such as hazardous reaction condition, complex work-up and
purification, strong acidic condition,15 high temperature,16,18 use of
toxic metal catalysts,17 poor yields, occurrence of side reactions and
expensive reagents. Therefore, the development of a mild general-
ised method to overcome these shortcomings still remains an
ongoing challenge for the synthesis of highly substituted imidazoles
for organic chemists.
Ar
Ar
O
+
N
15 mol % L-Proline
MeOH, 60 °C
R
CHO
NH4OAc
+
R
N
H
Ar'
Ar'
O
1
Scheme 1. L-Proline catalysed synthesis of 2,4,5-trisubstituted imidazoles.
2. Results and discussion
In all cases, we observed the almost same performance towards
this cyclocondensation to give the desired product (Table 2). Aliphatic
aldehydes gave the corresponding imidazoles in lower yield (42–51%)
than aromatic aldehydes (69–92%). Reaction profile is very clean and
no side products are formed. All the synthesized imidazoles have
been characterized on the basis of elemental and spectral studies.
Initially, we started the condensation of benzil (1 mmol),
benzaldehyde (1 mmol) and ammonium acetate (2 mmol) in
methanol at room temperature for 24 h in the absence of catalyst,
which led to very poor yield (12%) of 2,4,5-trisubstituted imidazole.
To enhance the yield of the desired product the temperature of the
reaction was increased to 60 ꢀC but no appreciable increment in the
product yield was observed. Then, it was thought worthwhile to
Table 2
Synthesis of 2,4,5-trisubstituted imidazoles (1a–1z)a
carry out the reaction in the presence of organocatalyst L-proline.
We also evaluated the amount of catalyst required for this trans-
formation and it was found that using 5 mol % and 10 mol % cata-
lyst, we obtained 56% and 78% yields, respectively. Maximum yield
was obtained (90%) when the reaction was loaded with 15 mol % of
the catalyst. A further increasing of catalyst loading does not affect
the yield, but slightly slow down the reaction (entry 6, Table 1). The
detail results obtained are given in Table 1.
Entry Ar
Ar0
R
Time (h) Product Yieldb (%)
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
9
1a
1b
1c
1d
1e
1f
90
89
92
87
88
86
70
82
80
73
85
79
85
75
69
84
42
46
51
84
89
82
88
80
78
90
2
Ph
4-OHC6H4
4-MeC6H4
4-NO2C6H4
4-ClC6H4
3-NO2C6H4
3-OHC6H4
4-OMeC6H4
2-ClC6H4
2-OHC6H4
2-NO2C6H4
2-OMeC6H4
4-NMe2C6H4
2,4-Cl2C6H3
9.5
8.5
9
3
Ph
4
Ph
5
Ph
9
6
Ph
10.5
12
11
11.5
12
7
Ph
1g
1h
1i
8
Ph
Table 1
9
Ph
Condensation of benzil, benzaldehyde and ammonium acetate in the presence of
different solvents and different catalyst percentagesa
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
1j
10.5
13
1k
1l
Entry
C catalyst (%)
Solvent
Temp (ꢀC)
Time (h)
Yield (%)
10
13
1m
1n
1o
1p
1q
1r
1
2
3
4
5
6
7
8
d
d
5
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
i-PrOH
t-BuOH
CHCl3
CH3CN
Toluene
CH2Cl2
H2O
H2O
1,4-Dioxane
30
60
60
60
60
60
60
60
60
60
60
60
60
60
100
60
24
24
12
12
9
12
12
12
13
18
24
24
24
24
24
24
12
25
56
78
90
88
70
55
35
25
40
30
Trace
N.R.b
Trace
Trace
5-Br-2-OHC6H3 12
2-OH-5-NO2C6H3 11.5
H
10
15
20
15
15
15
15
15
15
15
15
15
15
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
12
12
12
Me
CH(Me)2
4-NO2C6H4
4-MeC6H4
4-NMe2C6H4
1s
9.5
1t
9
10
9
10
9.5
13
1u
1v
1w
1x
1y
1z
9
10
11
12
13
14
15
16
4-CH3C6H4 4-CH3C6H4 4-OMeC6H4
Ph
Ph
2-ClC6H4
2-ClC6H4
4-MeC6H4
4-OMeC6H4
4-OMeC6H4 4-OMeC6H4 4-MeC6H4
a
1,2-Diketone/aldehyde/ammonium acetate (1:1:2).
Isolated yield.
b
a
Benzil/aldehyde/ammonium acetate (1:1:2).
No reaction.
b
In order to explore the applicability of this method, the same
reaction conditions were applied for the synthesis of 1,2,4,5-tet-
rasubstituted imidazoles (2) via the one-pot, four-component
condensation of 1,2-diketone (1 mmol), aldehyde (1 mmol), pri-
mary amine (1 mmol) and ammonium acetate (1 mmol) as depic-
ted in Scheme 2.
Choice of a solvent is also very crucial factor for multicomponent
reactions. We also looked into the solvent effect for this reaction.
The reaction was tested in a variety of protic and aprotic solvents
such as EtOH, i-PrOH, t-BuOH, CH3CN, CH2Cl2, CHCl3, 1,4-dioxane

S. Samai et al. / Tetrahedron 65 (2009) 10155–10161
10157
Ar
3. Conclusion
N
Ar
Ar
O
O
15 mol % L-Proline
MeOH, 60 °C
R1
R2NH2 NH4OAc
+
+
R1 CHO
+
N
R2
2
Ar
In conclusion, we have developed a simple and efficient one-pot
multicomponent methodology for the synthesis of 2,4,5-tri-
substituted and 1,2,4,5-tetrasubstituted imidazoles catalysed by
Scheme 2. L-Proline catalysed synthesis of 1,2,4,5-tetrasubstituted imidazoles.
15 mol % L-proline at moderate temperature. Simplicity of opera-
tion, high yields, easy work-up and purification of compounds by
non-chromatographic method (crystallization only) are the key
advantages of this method.
The substrate scope of the reaction was then evaluated using
a variety of structurally diverse 1,2-diketones, aldehydes and pri-
mary amines (Table 3). The strategy well tolerated the presence of
electron-donating and electron-withdrawing groups on the aryl-
aldehydic partner as well as on the 1,2-diarylketone. Both aromatic
and aliphatic primary amines have been successfully subjected to
this protocol. In each case, the reaction profile is clean and this
one-pot four-component procedure presents some improvements
and advantages over existing methods. One of the major advan-
tages of this protocol is the isolation and purification of the
products, which have been achieved by simple washing and
crystallization of the crude products.
4. Experimental
4.1. General
All reagents were purchased from Merck, Aldrich, CDH and
Fluka and used without further purification. NMR spectra were
recorded on JEOL AL 300 FT NMR spectrometer. The IR spectra were
recorded on Varian 3100 FT IR spectrophotometer. CHN analyses
were performed on Exeter Analytical Inc. ‘Model CE-400 CHN An-
alyzer’. Mass spectra were recorded at 70 eV ionizing voltage on
a JEOL SX-102. All the reactions were monitored by TLC using
0.25 mm silica gel plates (Merck 60F254) UV indicator. Melting
points were determined with Bu¨chi B-540 melting point apparatus
and are uncorrected.
Table 3
Synthesis of 1,2,4,5-tetrasubstituted imidazoles (2a–k)a
Entry Ar
R1
R2
Time (h) Product Yieldb (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
PhCH2
PhCH2
PhCH2
Ph
Ph
Me
8.5
9
8.5
9
8.5
9.5
9
9.5
8.5
2a
2b
2c
2d
2e
2f
2g
2h
2i
86
88
78
82
79
80
76
78
78
84
80
4-MeC6H4
4-ClC6H4
4-MeC6H4
4-NO2C6H4
4-MeC6H4
Ph
4-OHC6H4
4-OMeC6H4 PhCH2
4-MeC6H4
4.2. General procedure for the synthesis of 2,4,
5-trisubstituted imidazoles (1)
Me
Ph
In a 50 mL round bottom flask 1,2-diketone (1 mmol), aldehyde
(1 mmol) and ammonium acetate (2 mmol) were taken in presence
of 15 mol % of L-proline in methanol (5 mL). Then the reaction
mixture was stirred at 60 ꢀC for the stipulated period of time. The
progress of the reaction was monitored by TLC. After completion of
the reaction, volume of the reaction mixture was reduced, diluted
with water and extracted with ethyl acetate. Organic layer was
dried over anhydrous MgSO4 and then solvent was removed under
reduced pressure. Crude product was washed with n-hexane and
recrystallized from ethanol to obtain the pure product.
9
Ph
4-ClC6H4
10
11
PhCH2 10
2j
2k
4-MeC6H4 4-OMeC6H4 PhCH2 10
a
1,2-Diketone/aldehyde/primary amine/ammonium acetate (1:1:1:1).
Isolated yields.
b
Plausible mechanism for the L-proline catalysed synthesis of
substituted imidazoles (Scheme 3) has been proposed. In the case of
2,4,5-trisubstituted imidazole the reactionproceeds through diamine
intermediate A, which may form by two different pathways (pathway
I and/or pathway II). Path I involves the activation of the aldehydic
4.2.1. 2,4,5-Triphenyl-1H-imidazole (1a). Mp 267–269 ꢀC. FTIR (KBr,
cmꢁ1): 3451, 2856, 1636, 1490; 1H NMR (300 MHz, DMSO-d6):
carbonyl oxygen by the acid part of L-proline through intermolecular
hydrogen bonding,28 and subsequent condensation with two mole-
cules of ammonia to form diamine intermediate A. Path II provides
diamine intermediate A via iminium catalysis,33 which condenses
with the carbonyl carbons of the 1,2-diketone followed by de-
hydration to afford the imino intermediate B, which rearranges to the
required trisubstituted imidazoles (1). In the case of tetrasubstituted
imidazoles (2) reaction proceeds in the same fashion as above except
the intermediate B undergoes dehydration rather isomerization.
d
12.69 (s, 1H), 8.09 (d, J¼7.8 Hz, 2H), 7.56–7.22 (m, 13H); 13C NMR
(75 MHz, DMSO-d6):
d 145.6, 137.2, 135.2, 131.2, 130.4, 128.7, 128.5,
128.3, 128.2, 127.8, 127.2, 126.6, 125.3; ESI MS (m/z): 297.3 (Mþþ1);
Anal. Calcd for C21H16N2: C, 85.11; H, 5.44; N, 9.45. Found: C, 85.18;
H, 5.49; N, 9.33.
4.2.2. 4-(4,5-Diphenyl-1H-imidazol-2-yl)-phenol (1b). Mp 232–
233 ꢀC. FTIR (KBr, cmꢁ1): 3590, 3454, 3284, 3064, 1701, 1283; 1H
NMR (300 MHz, DMSO-d6):
d 12.40 (s, 1H), 9.70 (s, 1H), 7.90 (d,
J¼8.4 Hz, 2H), 7.54–7.21 (m, 10H), 6.86 (d, J¼8.4 Hz, 2H); 13C NMR
H
N
O
C
Ar
O
O
Pathway I
2 NH3
H2N
(75 MHz, DMSO-d6): d 157.7, 146.1, 136.6, 135.4, 131.3, 128.6, 128.3,
O
H
NH2
Ar
δ−
H
N
N
B
O
Ar'
127.5, 127.3, 127.0, 126.8, 126.3, 121.6, 115.4; ESI MS (m/z): 313.2
(Mþþ1); Anal. Calcd for C21H16N2O: C, 80.75; H, 5.16; N, 8.97.
Found: C, 80.79; H, 5.22; N, 8.91.
δ+
H
- 2H2O
Ar'
- H2O
H
A
H+ transfer
4.2.3. 4,5-Diphenyl-2-p-tolyl-1H-imidazole (1c). Mp 233–235 ꢀC.
-
2 NH3
COOH
FTIR (KBr, cmꢁ1): 3449, 3034, 1611, 1495, 1320; 1H NMR (300 MHz,
N
H
Ar
N
Pathway II
COOH
N
H
DMSO-d6):
d
12.59 (s, 1H), 7.98 (d, J¼7.8 Hz, 2H), 7.54–2.21 (m, 12H),
N
H
2.35 (s, 3H); 13C NMR (75 MHz, DMSO-d6):
d
145.6, 137.6, 136.9,
Ar'
O
COO
N
135.2, 131.1, 129.2, 128.6, 128.3, 128.1, 127.9, 127.6, 127.0, 126.4, 125.1,
20.8; ESI MS (m/z): 311.3 (Mþþ1); Anal. Calcd for C22H18N2: C,
85.13; H, 5.85; N, 9.03. Found: C, 85.23; H, 5.79; N, 8.97.
1
H
H
- H2O
C
4.2.4. 2-(4-Nitrophenyl)-4,5-diphenyl-1H-imidazole (1d). Mp 199–
Scheme 3. A plausible mechanism for the formation of imidazoles. Pathway Idacid
catalysis through intermolecular hydrogen bonding. Pathway IIdiminium catalysis.
201 ꢀC. FTIR (KBr, cmꢁ1): 3402, 2928,1598,1519,1346, 856; 1H NMR

10158
S. Samai et al. / Tetrahedron 65 (2009) 10155–10161
(300 MHz, DMSO-d6):
d
12.81 (s, 1H), 8.01–7.42 (m, 14H); 13C NMR
148.9, 143.7, 131.6, 130.6, 129.7, 128.4, 127.8,
(300 MHz, DMSO-d6):
d
11.82, (s, 1H), 8.02 (d, J¼7.5 Hz, 1H), 7.53–7.07
(75 MHz, DMSO-d6):
d
(m, 13H), 3.92 (s, 3H); 13C NMR (75 MHz, DMSO-d6):
d 158.2, 146.2,
127.4, 126.9, 126.1, 125.4, 124.3, 122.2, 118.5; ESI MS (m/z): 342.2
(Mþþ1); Anal. Calcd for C21H15N3O2: C, 73.89; H, 4.43; N, 12.31.
Found: C, 73.81; H, 4.44; N, 12.37.
128.3, 127.5, 125.4, 123.8, 115.4, 55.3; ESI MS (m/z): 327.2 (Mþþ1);
Anal. Calcd for C22H18N2O: C, 80.96; H, 5.56; N, 8.58. Found: C, 80.90;
H, 5.63; N, 8.51.
4.2.5. 2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole (1e). Mp 262–
4.2.13. [4-(4,5-Diphenyl-1H-imidazole-2-yl)-phenyl]-dimethylamine
264 ꢀC. FTIR (KBr, cmꢁ1): 3452, 3065, 1635, 1323; 1H NMR
(1m). Mp 256–259 ꢀC. FTIR (KBr, cmꢁ1): 3447, 3061, 1614, 1501;
(300 MHz, DMSO-d6):
d
12.78 (s, 1H), 8.11 (d, J¼8.1 Hz, 2H), 7.56–
1H NMR (300 MHz, DMSO-d6):
d
12.29 (s, 1H), 7.91 (d, J¼8.4 Hz,
7.23 (m, 12H); 13C (75 MHz, DMSO-d6):
d
146.3, 130.3, 129.9, 129.2,
2H), 7.54–7.19 (m, 10H), 6.80 (d, J¼8.4 Hz, 2H), 2.96 (s, 6H); 13C
128.5, 127.4, 127.0, 126.4, 125.5, 125.2, 123.3, 116.3; ESI MS (m/z):
331.2 (Mþþ1); Anal. Calcd for C21H15N2Cl: C, 76.24; H, 4.57; N, 8.47.
Found: C, 76.20; H, 4.61; N, 8.41.
NMR (75 MHz, DMSO-d6): d 150.2, 146.5, 128.2, 127.1, 126.3, 118.1,
111.9, 38.7; ESI MS (m/z): 400.2 (Mþþ1); Anal. Calcd for
C23H21N3: C, 81.38; H, 6.24; N, 12.38. Found: C, 81.46; H, 6.26; N,
12.28.
4.2.6. 2-(3-Nitrophenyl)-4,5-diphenyl-1H-imidazole (1f). Mp>300 ꢀC.
FTIR (KBr, cmꢁ1): 3448, 3068, 1526, 1350; 1H NMR (300 MHz,
4.2.14. 2-(2,4-Dichlorophenyl)-4,5-diphenyl-1H-imidazole (1n). Mp
DMSO-d6):
d
13.10 (s, 1H), 8.95 (s, 1H), 8.53 (d, J¼7.5 Hz, 1H), 8.23 (d,
175–178 ꢀC. FTIR (KBr, cmꢁ1): 3064, 2928, 1597, 1477; 1H NMR
J¼7.8 Hz, 1H), 7.81 (d, J¼7.8 Hz, 1H), 7.54–7.33 (m, 10H); 13C NMR
(300 MHz, DMSO-d6):
d
12.69 (s, 1H), 7.84 (s, 1H), 7.58–7.22 (m,
142.3, 137.1, 134.9, 133.8,
(75 MHz, DMSO-d6):
d
148.4, 143.4, 131.8, 131.2, 130.4, 128.7, 128.4,
12H); 13C NMR (75 MHz, DMSO-d6):
d
127.1, 122.6, 119.4; ESI MS (m/z): 342.3 (Mþþ1); Anal. Calcd for
C21H15N3O2: C, 73.89; H, 4.43; N, 12.31. Found: C, 73.84; H, 4.47; N,
12.39.
132.5, 132.4, 130.7, 129.7, 128.9, 128.6, 128.2, 127.8, 127.4, 127.1,
126.6; ESI MS (m/z): 365.0 (Mþþ1); Anal. Calcd for C21H14N2Cl2: C,
69.05; H, 3.86; N, 7.67. Found: C, 69.15; H, 3.82; N, 7.72.
4.2.7. 3-(4,5-Diphenyl-1H-imidazol-2-yl)-phenol(1g). Mp 258–260 ꢀC.
4.2.15. 5-Bromo-2-(4,5-diphenyl-1H-imidazol-2-yl)-phenol (1o). Mp
FTIR (KBr, cmꢁ1): 3388, 3064, 1592, 1476; 1H NMR (300 MHz, DMSO-
186–187 ꢀC. FTIR (KBr, cmꢁ1): 3585, 3422, 2927, 1643, 1486; 1H
d6):
d
12.60 (s, 1H), 9.54 (s, 1H), 7.51–7.21 (m, 14H); 13C NMR (75 MHz,
NMR (300 MHz, DMSO-d6):
d
13.18 (s, 1H), 12.74 (s, 1H), 8.24 (s,
166.3,
DMSO-d6):
d
157.6, 145.6, 136.9, 135.2, 131.6, 131.1, 129.7, 128.6, 128.5,
1H), 7.71–6.74 (m, 12H); 13C NMR (75 MHz, DMSO-d6):
d
128.2, 128.1, 127.7, 127.1, 126.5, 116.0, 115.4, 112.1; ESI MS (m/z): 313.1
(Mþþ1); Anal. Calcd for C21H16N2O: C, 80.75; H, 5.16; N, 8.97. Found: C,
80.71; H, 5.22; N, 9.05.
155.8, 153.9, 144.5, 132.4, 129.2, 128.7, 128.3, 127.2, 127.1, 119.1,
114.8; ESI MS (m/z): 391.1 (Mþþ1); Anal. Calcd for C21H15BrN2O:
C, 64.46; H, 3.86; N, 7.16. Found: C, 64.55; H, 3.89; N, 7.15.
4.2.8. 2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (1h). Mp 220–
4.2.16. 2-(4,5-Diphenyl-1H-imidazol-2-yl)-5-nitrophenol (1p). >Mp
223 ꢀC. FTIR (KBr, cmꢁ1): 3425, 3029, 2956, 1610, 1495, 1249; 1H NMR
219–220 ꢀC. FTIR (KBr, cmꢁ1): 3592, 3287, 3080, 1594, 1486; 1H
(300 MHz, DMSO-d6):
d
12.50 (s, 1H), 8.03 (d, J¼8.1 Hz, 2H), 7.50–7.33
NMR (300 MHz, DMSO-d6):
d
13.94 (s, 1H), 9.15 (s, 1H), 8.19 (s, 1H),
165.4, 157.3,
(m, 10H), 7.05 (d, J¼8.4 Hz, 2H), 3.82 (s, 3H); 13C NMR (75 MHz,
7.55–7.17 (m, 12H); 13C NMR (75 MHz, DMSO-d6):
d
DMSO-d6):
d
159.5, 145.7, 128.4, 127.7, 126.8, 123.1, 114.1, 55.2; ESI MS
154.4, 144.4, 133.2, 130.1, 128.9, 128.0, 127.6, 127.3, 126.9, 120.0,
114.5; ESI MS (m/z): 358.1 (Mþþ1); Anal. Calcd for C21H15N3O3: C,
70.58; H, 4.23; N, 11.76. Found: C, 70.49; H, 4.25; N, 11.77.
(m/z): 327.2 (Mþþ1); Anal. Calcd for C22H18N2O: C, 80.96; H, 5.56; N,
8.58. Found: C, 80.90; H, 5.51; N, 8.63.
4.2.9. 2-(2-Chlorophenyl)-4,5-diphenyl-1H-imidazole (1i). Mp 190–
4.2.17. 4,5-Diphenyl-1H-imidazole (1q). Mp 225–227 ꢀC. FTIR (KBr,
191 ꢀC. FTIR (KBr, cmꢁ1): 3445, 3060, 2954, 1600, 1445; 1H NMR
cmꢁ1): 3059, 2992, 1599, 1507; 1H NMR (300 MHz, DMSO-d6):
d 12.46
(300 MHz, DMSO-d6):
d
12.50 (s, 1H), 8.02 (d, J¼7.8 Hz, 2H), 7.55–
(s, 1H), 7.77 (s, 1H), 7.50–7.19 (m, 10H); 13C NMR (75 MHz, DMSO-d6):
7.21 (m, 10H), 7.05 (d, J¼7.8 Hz, 2H); 13C NMR (75 MHz, DMSO-d6):
d
135.6, 129.0, 128.4, 127.7, 127.3, 119.5; ESI MS (m/z): 221.2 (Mþþ1);
d
145.7, 128.4, 128.2, 128.1, 128.0, 127.7, 127.1, 127.0, 126.9, 126.7,
Anal. Calcd for C15H12N2: C, 81.79; H, 5.49; N,12.72. Found: C, 81.74; H,
5.43; N, 12.83.
123.1, 114.0; ESI MS (m/z): 331.1 (Mþþ1); Anal. Calcd for
C21H15N2Cl: C, 76.24; H, 4.57; N, 8.47. Found: C, 76.30; H, 4.68; N,
8.49.
4.2.18. 2-Methyl-4,5-diphenyl-1H-imidazole (1r). Mp 240–241 ꢀC.
FTIR (KBr, cmꢁ1): 3447, 1606, 1532; 1H NMR (300 MHz, DMSO-d6):
4.2.10. 2-(4,5-Diphenyl-1H-imidazol-2-yl)-phenol (1j). Mp 202–
d
12.07 (s, 1H), 8.11–7.25 (m, 10H), 2.34 (s, 3H); 13C NMR (75 MHz,
205 ꢀC. FTIR (KBr, cmꢁ1): 3595, 3450, 3060, 1595; 1H NMR
DMSO-d6): d 150.3, 133.2, 128.4, 128.0, 127.2, 127.1, 17.6; ESI MS
(300 MHz, DMSO-d6):
d
13.02 (s, 1H), 12.95 (s, 1H), 8.05 (d, J¼7.2 Hz,
(m/z): 235.1 (Mþþ1); Anal. Calcd for C16H14N2: C, 82.02; H, 6.02; N,
1H), 7.51–6.92 (m, 13H); 13C NMR (75 MHz, DMSO-d6):
d
157.0,
11.96. Found: C, 82.11; H, 6.09; N, 12.12.
145.3, 135.3, 131.7, 130.9, 128.7, 127.5, 126.3, 125.4, 123.3, 121.8,
116.4; ESI MS (m/z): 313.2 (Mþþ1); Anal. Calcd for C21H16N2O: C,
80.75; H, 5.16; N, 8.97. Found: C, 80.85; H, 5.14; N, 8.93.
4.2.19. 2-Isopropyl-4,5-diphenyl-1H-imidazole (1s). Mp 232–234 ꢀC.
FTIR (KBr, cmꢁ1): 3032, 2966,1600,1499; 1H NMR (300 MHz, DMSO-
d6):
d
11.93 (s, 1H), 7.47–7.16 (m, 10H), 3.03 (q, J¼6.9 Hz, 1H), 1.32 (d,
4.2.11. 2-(2-Nitrophenyl)-4,5-diphenyl-1H-imidazole (1k). Mp 230–
J¼7.2 Hz, 6H); 13C NMR (75 MHz, DMSO-d6):
d 153.1, 128.3, 128.3,
231 ꢀC. FTIR (KBr, cmꢁ1): 3451, 3062, 1525, 1354; 1H NMR
127.9, 127.8, 128.0, 127.7, 127.2, 127.1, 27.7, 21.63; ESI MS (m/z): 262.2
(Mþþ1); Anal. Calcd for C18H18N2: C, 82.41; H, 6.92; N, 10.67. Found:
C, 82.44; H, 6.84; N, 10.72.
(300 MHz, DMSO-d6):
(75 MHz, DMSO-d6):
d
12.95 (s, 1H), 7.99–7.22 (m, 14H); 13C NMR
148.3, 141.1, 132.1, 129.8, 129.6, 128.7, 128.3,
d
128.0, 127.0, 126.8, 124.0, 123.5; ESI MS (m/z): 342.32 (Mþþ1); Anal.
Calcd for C21H15N3O2: C, 73.89; H, 4.43; N, 12.31. Found: C, 73.85; H,
4.47; N, 12.37.
4.2.20. 4,5-Bis(4-chlorophenyl)-2-(4-nitrophenyl)-1H-imidazole
(1t). Mp 275–276 ꢀC. FTIR (KBr, cmꢁ1): 3400, 2925, 1591, 1511; 1H
NMR (300 MHz, DMSO-d6):
7.31 (m, 7H); 13C NMR (75 MHz, DMSO-d6):
129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 125.9, 124.3; ESI MS
d
13.24 (s, 1H), 8.38–8.30 (m, 5H), 7.54–
4.2.12. 2-(2-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (1l). Mp 210–
d
146.7, 143.9, 135.8,
211 ꢀC. FTIR (KBr, cmꢁ1): 3437, 3033, 2950, 1615, 1498; 1H NMR

S. Samai et al. / Tetrahedron 65 (2009) 10155–10161
10159
(m/z): 410.1 (Mþþ1); Anal. Calcd for C21H13Cl2N3O2: C, 61.48; H,
acetate. Organic layer was dried over anhydrous MgSO4 and then
solvent was removed under reduced pressure and an oily residue or
solid was obtained. The water/ethanol mixture (50:50) was added
to the oily residue, a milky to yellow solid was obtained. The solid
was then crystallized from ethanol to obtain the pure product.
3.19; N, 10.24. Found: C, 61.44; H, 3.27; N, 10.28.
4.2.21. 4,5-Bis(4-chlorophenyl)-2-p-tolyl-1H-imidazole
263–264 ꢀC. FTIR (KBr, cmꢁ1): 3448, 2924, 1636, 1492; 1H NMR
(300 MHz, DMSO-d6):
12.68 (s, 1H), 7.97 (d, J¼7.8 Hz, 2H), 7.55–
7.51 (m, 6H), 7.39 (d, J¼8.1 Hz, 2H), 7.30 (d, J¼7.8 Hz, 2H), 2.35
(s, 3H); 13C NMR (75 MHz, DMSO-d6):
146.2, 138.0, 136.2, 133.9,
(1u). Mp
d
4.3.1. 1-Benzyl-2,4,5-triphenyl-1H-imidazole (2a). Mp 163–165 ꢀC.
d
FTIR (KBr, cmꢁ1): 3056, 2926, 1600; 1H NMR (300 MHz, CDCl3):
132.4, 131.2, 130.1, 129.6, 129.3, 128.8, 128.3, 127.4, 127.1, 125.3,
20.9; ESI MS (m/z): 379.10 (Mþþ1); Anal. Calcd for C22H16Cl2N2: C,
69.67; H, 4.25; N, 7.39. Found: C, 69.72; H, 4.31; N, 7.33.
d
7.65–7.55 (m, 4H), 7.38–7.13 (m, 14H), 6.80 (d, J¼7.5 Hz, 2H), 5.11
(s, 2H); 13C NMR (75 MHz, CDCl3):
d
148.1, 137.9, 137.3, 134.1, 132.7,
131.0, 130.8, 130.5, 129.1, 128.9, 128.7, 128.6, 128.5, 128.2, 127.3,
126.9, 126.4, 126.0, 48.2; ESI MS (m/z): 387.2 (Mþþ1); Anal. Calcd
for C28H22N2: C, 87.01; H, 5.74; N, 7.25. Found: C, 87.11; H, 5.79; N,
7.40.
4.2.22. {4-[4,5-Bis-(4-chlorophenyl)-1H-imidazol-2-yl]-phenyl}-di-
methylamine (1v). Mp 248–250 ꢀC. FTIR (KBr, cmꢁ1): 3445, 2932,
1632, 1504; 1H NMR (300 MHz, DMSO-d6):
d
12.40 (s, 1H), 7.89
(d, J¼7.8 Hz, 2H), 7.49–7.38 (m, 10H), 6.80 (d, J¼8.4 Hz, 2H), 2.97
(s, 6H); 13C NMR (75 MHz, DMSO-d6):
150.4, 147.0, 131.6, 129.8,
4.3.2. 1-Benzyl-4,5-diphenyl-2-p-tolyl-1H-imidazole (2b). Mp 167–
d
168 ꢀC. FTIR (KBr, cmꢁ1): 3027, 2928, 1600; 1H NMR (300 MHz,
129.7, 129.6, 129.3, 129.2, 129.1, 129.0, 128.5, 126.4, 117.9, 111.9,
111.1; ESI MS (m/z): 408.2 (Mþþ1); Anal. Calcd for C23H19Cl2N3; C,
67.65; H, 4.69; N, 10.29. Found: C, 67.61; H, 4.62; 10.36.
CDCl3):
d
7.57 (d, J¼7.5 Hz, 4H), 7.33–7.12 (m,13H), 6.80 (d, J¼4.2 Hz,
2H), 5.09 (s, 2H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
148.2,
138.8, 137.9, 137.6, 134.5, 131.1, 131.0,129.8, 129.2, 128.9, 128.7, 128.5,
128.0, 127.2, 126.7, 126.2, 125.9, 48.2, 21.3; ESI MS (m/z): 401.3
(Mþþ1); Anal. Calcd for C29H24N2: C, 86.97; H, 6.04; N, 6.99. Found:
C, 86.91; H, 6.15; N, 6.94.
4.2.23. 2-(4-Methoxyphenyl)-4,5-di-p-tolyl-1H-imidazole (1w). Mp
250–251 ꢀC. FTIR (KBr, cmꢁ1): 3428, 2923, 1616, 1501; 1H NMR
(300 MHz, DMSO-d6):
(m, 10H), 3.81 (s, 3H), 2.34 (s, 3H), 2.28 (s, 3H); 13C NMR (75 MHz,
DMSO-d6): 159.3,145.3, 136.8, 136.5,135.4,132.6, 129.2,128.7, 128.4,
128.2, 127.3, 127.0, 126.6, 123.2, 114.1, 55.2, 20.8; ESI MS (m/z): 355.2
(Mþþ1);Anal. CalcdforC24H22N2O:C,81.33;H,6.26;N,7.90.Found:C,
81.39; H, 6.32; N, 7.98.
d
12.38 (s,1H), 8.00 (d, J¼8.1 Hz, 2H), 7.43–7.35
4.3.3. 1-Benzyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole
d
(2c). Mp 161–163 ꢀC. FTIR (KBr, cmꢁ1): 3058, 2936, 1598, 1448; 1H
NMR (300 MHz, CDCl3):
(75 MHz, CDCl3): 134.9, 133.8, 130.6, 130.4, 130.2, 130.1, 129.5,
d
7.98–6.97 (m, 19H), 5.11 (s, 2H); 13C NMR
d
128.9, 128.5, 128.4, 128.1, 127.2, 126.5, 126.0, 125.5, 48.1; ESI MS
(m/z): 421.2 (Mþþ1); Anal. Calcd for C28H21ClN2: C, 79.84; H, 5.03;
N, 6.66. Found: C, 79.91; H, 5.09; N, 6.62.
4.2.24. 4-(2-Chlorophenyl)-5-phenyl-2-p-tolyl-1H-imidazole
(1x). Mp 228–229 ꢀC. FTIR (KBr, cmꢁ1): 3447, 3028, 2926,1605,1485;
1H NMR (300 MHz, DMSO-d6):
d
12.82(s,1H), 7.98–7.91 (m, 2H), 7.67–
4.3.4. 1,4,5-Triphenyl-2-p-tolyl-1H-imidazole (2d). Mp 187–189 ꢀC.
7.17 (m,11H), 2.36(s, 3H);13C NMR (75 MHz, DMSO-d6):
d
145.8, 137.8,
FTIR (KBr, cmꢁ1): 3044, 2923, 1665, 1593; 1H NMR (300 MHz,
137.0, 134.8, 134.3, 133.8, 132.8, 132.3, 132.1, 130.6, 129.8, 129.6, 128.8,
127.6, 127.0, 126.0, 124.9, 20.9; ESI MS (m/z): 345.2 (Mþþ1); Anal.
Calcd for C22H17ClN2: C, 76.63; H, 4.97; N, 8.12. Found: C, 76.69; H,
5.06; N, 8.10.
CDCl3):
NMR (75 MHz, CDCl3):
d
7.60 (d, J¼7.2 Hz, 2H), 7.31–7.02 (m, 17H), 2.30 (s, 3H); 13
C
d 147.1, 138.1, 137.2, 134.5, 131.1, 130.7, 130.6,
128.9, 128.8, 128.4, 128.2, 128.1, 127.8, 127.6, 127.4, 126.5, 21.3; ESI
MS (m/z): 387.3 (Mþþ1); Anal. Calcd for C28H22N2: C, 87.01; H, 5.74;
N, 7.25. Found: C, 87.03; H, 5.81; N, 7.16.
4.2.25. 4-(2-Chlorophenyl)-2-(4-methoxyphenyl)-5-phenyl-1H-im-
idazole (1y). Mp 239–240 ꢀC. FTIR (KBr, cmꢁ1): 3428, 3057, 2934,
4.3.5. 2-(4-Nitrophenyl)-1,4,5-triphenyl-1H-imidazole (2e). Mp 191–
1612, 1491; 1H NMR (300 MHz, DMSO-d6):
d
12.72 (s, 1H), 8.00
193 ꢀC. FTIR (KBr, cmꢁ1): 3054, 1595, 1514, 1340; 1H NMR (300 MHz,
(d, J¼7.5 Hz, 2H), 7.65–7.03 (m, 11H); 13C NMR (75 MHz, DMSO-d6):
CDCl3):
d
8.10 (d, J¼8.7 Hz, 2H), 7.61–7.07 (m, 17H); 13C NMR
d
159.4, 145.7, 132.2, 129.8, 128.2, 126.8, 126.6, 123.1, 114.2, 55.2; ESI
(75 MHz, CDCl3): d 147.0, 144.3, 139.3, 136.6, 136.5, 133.8, 132.4, 131.0,
MS (m/z): 361.2 (Mþþ1); Anal. Calcd for C22H17ClN2O: C, 73.23; H,
129.9, 129.5, 129.4, 129.3, 129.2, 128.8, 128.6, 128.5, 128.4, 128.3,
128.2, 127.9, 127.0, 124.2, 124.0, 123.4; ESI MS (m/z): 418.2 (Mþþ1);
Anal. Calcd for C27H19N3O2: C, 77.68; H, 4.59; N, 10.07. Found: C,
77.60; H, 4.56; N, 10.11.
4.75; N, 7.76. Found: C, 73.28; H, 4.79; N, 7.68.
4.2.26. 4,5-Bis(4-methoxyphenyl)-2-p-tolyl-1H-imidazole (1z). Mp
213–214 ꢀC. FTIR (KBr, cmꢁ1): 3409, 2928, 1623, 1525; 1H NMR
(300 MHz, DMSO-d6):
d
12.76 (s, 1H), 8.05–7.93 (m, 5H), 7.73 (d,
4.3.6. 1-Methyl-4,5-diphenyl-2-p-tolyl-1H-imidazole (2f). Mp 222–
J¼8.4 Hz, 2H), 7.44–7.28 (m, 5H), 4.03 (s, 6H), 2.35 (s, 3H); 13C NMR
223 ꢀC. FTIR (KBr, cmꢁ1): 3063, 2927, 1667, 1597; 1H NMR
(75 MHz, DMSO-d6):
d
151.5, 150.9, 146.2, 139.3, 139.2, 138.2, 135.1,
(300 MHz, CDCl3):
NMR (75 MHz, CDCl3): d 148.0,138.6,137.6,134.7,131.3,130.8, 130.2,
d C
7.64–7.12 (m,14H), 3.49 (s, 3H), 2.42 (s, 3H); 13
134.2, 132.5, 129.3, 127.5, 127.2, 125.8, 125.3, 122.9, 114.8, 114.5, 59.8,
20.9; ESI MS (m/z): 371.2 (Mþþ1); Anal. Calcd for C24H22N2O2: C,
77.81; H, 5.99; N, 7.56. Found: C, 77.90; H, 5.97; N, 7.51.
129.2, 129.0, 128.9, 128.4, 126.9, 126.2, 33.1, 21.4; ESI MS (m/z):
325.2 (Mþþ1); Anal. Calcd for C23H20N2: C, 85.15; H, 6.21; N, 8.63.
Found: C, 85.21; H, 6.28; N, 8.50.
4.3. General procedure for the synthesis of 1,2,4,
5-tetrasubstituted imidazoles (2)
4.3.7. 1-Methyl-2,4,5-triphenyl-1H-imidazole (2g). Mp 146–147 ꢀC.
FTIR (KBr, cmꢁ1): 2926, 1600; 1H NMR (300 MHz, CDCl3):
d
7.99–
In a 50 mL round bottom flask 1,2-diketone (1 mmol), aldehyde
(1 mmol), primary amine (1 mmol) and ammonium acetate
(1 mmol) were taken in presence of 15 mol % of L-proline in
methanol (5 mL). Then the reaction mixture was stirred at 60 ꢀC for
the stipulated time. The progress of the reaction was monitored by
TLC. After completion of the reaction volume of the reaction mix-
ture was reduced, diluted with water and extracted with ethyl
7.14 (m, 15H), 3.51 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 148.3, 138.3,
137.8, 136.5, 131.3, 130.5, 129.9, 128.5, 127.3, 126.4, 126.0, 33.3; ESI
MS (m/z): 311.2 (Mþþ1); Anal. Calcd for C22H18N2: C, 85.13; H, 5.85;
N, 9.03. Found: C, 85.07, H, 5.78; N, 9.16.
4.3.8. 4-(1,4,5-Triphenyl-1H-imidazol-2-yl)-phenol (2h). Mp 284–
286 ꢀC. FTIR (KBr, cmꢁ1): 3448, 3057, 1582; 1H NMR (300 MHz,

10160
S. Samai et al. / Tetrahedron 65 (2009) 10155–10161
9. Wang, L.; Woods, K. W.; Li, Q.; Barr, K. J.; McCroskey, R. W.; Hannick, S. M.;
CDCl3):
d
8.37 (s, 1H), 7.76 (d, J¼8.4 Hz, 2H), 7.50–6.84 (m, 17H); 13
C
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.
10. Maier, T.; Schmierer, R.; Bauer, K.; Bieringer, H.; Buerstell, H.; Sachse, B. U.S.
Patent 4820335, 1989; Chem. Abstr. 1989, 111, 19494w.
11. (a) Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667; (b)
Nara, S. J.; Naik, P. U.; Harjani, J. R.; Salunkhe, M. M. Indian J. Chem. 2001, 45B,
2257; (c) Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63, 2363.
12. (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem. Rev. 2000, 100,
39; (b) Arnold, P. L.; Liddle, S. T. Chem. Commun. 2006, 3959; (c) Ku¨hl, O. Chem.
Soc. Rev. 2007, 36, 592.
NMR (75 MHz, CDCl3): d 158.1,144.4,139.2,136.9,136.2,134.0,132.1,
131.0, 130.1, 129.6, 129.4, 129.1, 128.8, 128.5, 128.1, 127.7, 127.4, 127.3,
127.1, 124.3, 123.9, 123.2; ESI MS (m/z): 389.3 (Mþþ1); Anal. Calcd
for C27H20N2O: C, 83.48; H, 5.19; N, 7.21. Found: C, 83.55; H, 5.11; N,
7.29.
4.3.9. 1-Benzyl-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole
(2i). Mp 164–165 ꢀC. FTIR (KBr, cmꢁ1): 3047, 1604; 1H NMR
13. Siddiqui, S. A.; Narkhede, U. C.; Palimkar, S. S.; Daniel, T.; Lahoti, R. J.; Srinivasan,
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(300 MHz, CDCl3):
6.80 (m, 4H), 5.08 (s, 2H), 3.81 (s, 3H); 13C NMR (75 MHz, CDCl3):
159.9, 147.9, 137.6, 134.5, 131.0, 130.9, 130.3, 129.7, 129.0, 128.7,
d
7.58 (d, J¼7.8 Hz, 4H), 7.31–7.12 (m, 11H), 6.92–
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J. M.; Hall, R. F.; Garigipati, R. S.; Bender, P. E.; Erhard, K. F.; Krog, A. J.; Hofmann,
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d
128.5, 127.9, 127.2, 126.7, 126.2, 125.9, 123.3, 113.9, 55.2, 48.1; ESI MS
(m/z): 417.3 (Mþþ1); Anal. Calcd for C29H24N2O: C, 83.63; H, 5.81;
N, 6.73. Found: C, 83.71; H, 5.80; N, 6.68.
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4.3.10. 1-Benzyl-4,5-bis(4-chlorophenyl)-2-p-tolyl-1H-imidazole
(2j). Mp 185–186 ꢀC. FTIR (KBr, cmꢁ1): 3033, 2932, 1604; 1H NMR
(300 MHz, CDCl3):
d
7.96 (d, J¼7.8 Hz, 4H), 7.54–7.18 (m, 11H), 6.77
(d, J¼6.6 Hz, 2H), 5.10 (s, 2H), 2.33 (s, 3H); 13C NMR (75 MHz,
CDCl3):
d 147.2, 137.9, 137.0, 134.4, 131.0, 130.9, 130.1, 129.3, 128.9,
128.6, 128.3, 128.0, 127.5, 126.5, 125.9, 125.8, 123.1, 114.0, 47.9, 20.8;
ESI MS (m/z): 469.2 (Mþþ1); Anal. Calcd for C29H22Cl2N2: C, 74.20;
H, 4.72; N, 5.97. Found: C, 74.31; H, 4.67; N, 6.01.
4.3.11. 1-Benzyl-2-(4-methoxyphenyl)-4,5-di-p-tolyl-1H-imidazole
(2k). Mp 183–184 ꢀC. FTIR (KBr, cmꢁ1): 3029, 2934, 1600; 1H NMR
(300 MHz, CDCl3):
(d, J¼6.3 Hz, 2H), 5.11 (s, 2H), 3.81 (s, 3H), 2.34 (s, 3H), 2.28 (s, 3H);
13C NMR (75 MHz, CDCl3):
159.8, 147.2, 137.2, 136.9, 134.5, 131.1,
d
7.61 (d, J¼8.1 Hz, 2H), 7.51–7.13 (m, 13H), 6.80
d
130.9, 130.3, 129.5, 129.0, 128.6, 128.4, 127.9, 127.2, 126.6,
126.0.125.8, 123.2, 113.9, 55.1, 48.0, 20.8, 20.7; ESI MS (m/z): 445.2
(Mþþ1); Anal. Calcd for C31H28N2O: C, 83.75; H, 6.35; N, 6.30.
Found: C, 83.79; H, 6.39; N, 6.41.
Acknowledgements
One of the authors S.S. is thankful to CSIR, New Delhi for the
financial support in the form of SRF. Financial assistance from the
Michigan Diagnostics L.L.C., Michigan, USA is gratefully
acknowledged.
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