Iron(III)-catalyzed synthesis of multi-substituted imidazoles via [3+2] cycloaddition reaction of nitroolefins and N-aryl benzamidines

Article abstract of DOI:10.1016/j.tet.2013.08.077

A novel and efficient iron(III)-catalyzed synthesis of multi-substituted imidazoles via [3+2] cycloaddition of nitroolefins and N-aryl benzamidines under the air atmosphere had been developed. This methodology is convenient, atom-economical, general, and eco-friendly in good yields and prefect regioselectivities.

Full text of DOI:10.1016/j.tet.2013.08.077

Tetrahedron 69 (2013) 9417e9421
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Iron(III)-catalyzed synthesis of multi-substituted imidazoles via
[3þ2] cycloaddition reaction of nitroolefins and N-aryl
benzamidines
,
,
,b,
Xiang Liu a b, Dong Wang a b, Baohua Chen a
*
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Gansu, PR China
b Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou 730000, Gansu, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2013
Received in revised form 28 August 2013
Accepted 30 August 2013
Available online 5 September 2013
A novel and efficient iron(III)-catalyzed synthesis of multi-substituted imidazoles via [3þ2] cycloaddition
of nitroolefins and N-aryl benzamidines under the air atmosphere had been developed. This method-
ology is convenient, atom-economical, general, and eco-friendly in good yields and prefect
regioselectivities.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Iron-catalyzed
Nitroolefins
Benzamidines
Multi-substituted imidazoles
Cycloaddition
1. Introduction
yields. Therefore, an efficient and simple way to construct multi-
substituted imidazoles is still necessary.
Imidazoles and their derivatives, a type of important N-con-
taining heteroaromatic compounds, were found in a large number
of pharmacologically active compounds and natural products.1
Among them, multi-substituted imidazoles are significant core
structures used in medicinal chemistry due to their remarkable
biological activities, such as antifungal, antiapoptotic, antibacterial,
antiviral and anti-inflammatory activities.2 In addition, they are
also used as fluorescence, agricultural products, dyes and chem-
sensing.3 Therefore, developing efficient methodologies for syn-
thesis of multi-substituted imidazoles has attracted numerous
attentions. Current methods for these syntheses focused mostly on
the less-substituted imidazoles, which commonly proceeded via
oxidative cyclization of 1,2-phenylenediamines with aldehydes.4
Only a handful of methodologies are reported for the synthesis of
multi-substituted imidazoles through reactions of 1,2-dike-tones/
a-hydroxy-ketones, aldehydes, primary amines and ammonium
acetates in one-pot.5 However, many of these procedures are as-
sociated with one or more disadvantages such as use of strong
bases or catalysts, use of toxic solvents, long reaction time and low
Recently, iron catalysts6 have been identified as important and
effective catalysts in various organic reactions because of their
low price, easy availability, sustainability, non-toxicity and envi-
ronmentally friendly characteristics. For example, Hajra7 and
co-workers described iron-catalyzed synthesis of imidazo[1,2-a]
pyridines via cascade reaction between nitroolefins and 2-
aminorpyridines. Our group has long term interest on developing
methodologies to construct imidazole rings.8 Earlier this year, we
have reported a novel and efficient strategy for the synthesis of tri-
or tetra-substituted imidazoles via copper-catalyzed [3þ2] cyclo-
addition reaction.9 However, the reactions required expensive li-
gands and an atmosphere of oxygen, thus, we are interested in
investigating a direct synthesis of multi-substituted imidazoles in
the absence of ligands under air. Herein, we report a novel and
efficient iron(III)-catalyzed synthesis of multi-substituted imidaz-
oles via [3þ2] cycloaddition of nitroolefins and N-aryl benzami-
dines under air. To the best of our knowledge, there is been no
report available on the synthesis of multi-substituted imidazoles
using iron catalyst in the open literature so far. It showed several
advantages comparing our previous method, such as an in-
expensive and less toxic catalyst, ligand-free conditions, easy op-
eration, environmental friendliness and no need of specific
atmosphere.
* Corresponding author. Fax: þ86 931 8912582; e-mail address: chbh@lzu.edu.cn
(B. Chen).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.077

9418
X. Liu et al. / Tetrahedron 69 (2013) 9417e9421
2. Results and discussion
the yields of the products. Generally, the aromatic ring with
electron-donating groups, such as methyl and methoxy group, gave
lower yields than those with electron-withdrawing groups, such as
fluoro, chloro and trifluoromethyl groups (Table 2, entries 1e8). The
reactions of N-p-tolylbenzamidine(1a) with different 2-
methylnitroolefins gave lower but still acceptable yields (Table 2,
entries 9e13). Similarly, the electron-withdrawing substituted 2-
methylnitroolefins produced better yields than the electron-
donating substituted ones. In addition, the 2-substituted nitro-
olefins showed slightly lower yields than the 4-substituted ones
(Table 2, entries 5 and 6) that was probably caused by steric effect.
We started from the reaction of N-p-tolylbenzamidine 1a
(0.2 mmol) and 1-(2-nitrovinyl)-benzene 2a (0.2 mmol). As shown
in Table 1, the reaction was carried out with 1a (0.2 mmol) and 2a
(0.2 mmol) in the presence of FeCl3 (20 mol %) and 1,10-phen
(20 mol %) in DMSO at 90 ꢀC under air for 4 h. The desired product
3aa was obtained in 60% yield (Table 1, entry 1). This impelled us to
investigate optimal conditions for the reaction in order to get better
yields. In this preliminary experiment, the reactions were carried
out with different ligands, such as 1,10-phen, bipy and L-proline,
and the cyclization reaction did not give higher yields (Table 1,
entries 1e3), but a good yield was obtained in the absence of ligand
(Table 1, entry 4). Then, the cyclization reactions were conducted in
different solvents, such as THF, toluene, DMF and 1,4-dioxane and
we found that DMF gave the best result (Table 1, entries 5e8). Next,
we investigated different loadings of FeCl3, in the amount of
10 mol % and 30 mol % and obtained 65% and 78% yields, re-
spectively (Table 1, entries 9 and 10). Other catalysts, such as FeBr3,
AlCl3, ZnCl2, TiCl4, Fe(OTf)3 and Fe(acac)3, showed little effective-
ness on promoting the reaction (Table 1, entries 11e13). Finally, we
investigated the reaction at different temperatures and found the
yield of 3aa was also influenced by the reaction temperature (Table
1, entries 14 and 15). Moreover, the yield of 3aa was little increased
under oxygen. Thus, 20 mmol % FeCl3 in DMF under air is chosen as
the optimal conditions for this reaction.
Table 2
Reactions of N-p-tolylbenzamidine with various nitroolefinsa
R3
NH
NH
NO2
R4
N
FeCl3(20%), DMF
90oC, 4h
R3
R4
+
Ph
N
Ph
1a
2
3
Entry
R3
H
4-CH3
4-CH3O
4-F
R4
Product
Yieldb (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
3aa
3ab
3ac
3ad
3ae
3af
82
60
51
61
68
55
50
53
47
35
41
45
56
4-Cl
2-Cl
4-CF3
2,4-DiCH3O
H
4-CH3O
4-Br
4-Cl
H
H
3ag
3ah
3ai
3aj
3ak
3al
Table 1
Optimization of the reaction conditiona
9
CH3
CH3
CH3
CH3
CH3
Ph
10
11
12
13
N
NH
catalyst, ligand
sovent, 90oC, 4h
NO2
+
N
Ph
Ph
Ph
NH
4-CN
3am
a
Reaction conditions: 1a (0.2 mmol), 2 (0.2 mmol), FeCl3(20 mmol %), DMF
(2 mL), 90 ꢀC, 4 h.
2a
1a
3aa
b
Isolated yield.
Entry
Catalyst
Ligand
Solvent
Yieldb (%)
The reactions of various benzamidines and 1-(2-nitrovinyl)-
benzene 2a also were investigated as shown in Table 3. A variety of
N-aryl benzamidines were found to be partners and the desired
products were formed in satisfactory to excellent yields. In general,
1
2
3
4
5
6
7
8
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (20%)
FeCl3 (10%)
FeCl3 (30%)
FeBr3 (20%)
Fe(OTf)3 (20%)
Fe(acac)3
ZnCl2
AlCl3
TiCl4
1,10-Phen
Bipy
DMSO
DMSO
DMSO
DMSO
THF
Toluene
DMF
Dioxane
DMF
DMF
DMF
DMF
DMF
60
61
58
77
12
23
L-Proline
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
82, 82c
44
65
78
53
47
55
Trace
5
Trace
79
67
Table 3
Reactions of 1-(2-nitrovinyl)-benzene with various benzamidinesa
9
Ph
10
11
12
13
14
15
16
17d
18e
NH
N
FeCl3(20%),DMF
90oC, 4h
NO2
+
Ph
R1
N R2
H
N
R1
DMF
DMF
DMF
DMF
R2
2a
3
1
Entry
R1
R2
Product
Yieldb (%)
FeCl3 (20%)
FeCl3 (20%)
DMF
1
2
3
4
5
6
7
8
C6H6
4-CH3C6H5
C6H6
C6H6
C6H6
4-CH3C6H5
4-CH3OC6H5
C6H6
4-CH3C6H5
C6H6
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
3ja
3ka
3la
3ma
3na
82
81
85
72
71
81
86
68
64
72
0
a
Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), catalyst (20% mmol), ligand
4-CH3OC6H5
3-CH3OC6H5
2-C2H5OC6H5
4-CH3C6H5
4-CH3C6H5
4-ClC6H5
3-ClC6H5
C6H6
C6H6
C6H6
C2H5
C6H6
(20%mmol), solvent (2 mL), 90 ꢀC, 4 h.
b
Isolated yield.
c
The reaction was carried out under an O2 atmosphere.
d
The reaction was carried out at 70 ꢀC.
e
The reaction was carried out at 110 ꢀC.
9
C6H6
10
11
12
13
14
4-CF3C6H5
4-NO2C6H5
3-Pyridinyl
C6H6
Under the optimized reaction conditions, we extended the study
with different nitroolefins and N-p-tolylbenzamidine(1a) for the
synthesis of various multi-substituted imidazoles. The results were
shown in Table 2. Various nitroolefins provided the desired prod-
ucts in moderate to good yields. It was obvious that the nature of
the substituent on the aromatic rings showed some influence on
67
0
0
tBu
a
Reaction conditions: 1 (0.2 mmol), 2a (0.2 mmol), FeCl3(20 mmol %), DMF
(2 mL), 90 ꢀC, 4 h.
b
Isolated yield.

X. Liu et al. / Tetrahedron 69 (2013) 9417e9421
9419
benzamidines with electron-donating substituents on R1 and/or R2
4. Experimental section
led to higher yields (Table 3, entries 1e6). On the contrary, elec-
tron-withdrawing substituted benzamidines gave lower yields
(Table 3, entries 8e10), some even (such as nitro) did not proceed
to the expected product (entry 11). Especially, when the
benzamidine bearing two electron-donating groups was
employed, the yield was enhanced to 86% (Table 3, entry 7).
However, the substrates with alkyl groups (such as N-phenyl-
pivalamidine and N-ethylbenzamidine) did not give the expected
product (Table 3, entries 13 and 14). Moreover, the substrate with
heterocycle group also gave the corresponding product 3la in 67%
yield (entry 12).
To probe the mechanism of the reaction, several control ex-
periments were performed. The reaction was carried out with 1a
(0.2 mmol), 2a (0.2 mmol), in the absence of FeCl3 in DMF at 90 ꢀC
under the air for 4 h and no product was obtained. Compound 3aa
was obtained in 82% yield even if reaction of 1a and 2a was
conducted under N2 protection. Thus, we speculated the NO2
group was the terminal oxidant in this process. Based on the
above observations and the analogous mechanisms discussed in
literature,10 a plausible mechanism for this reaction was proposed
as shown in Scheme 1. Firstly, the intermediate 4 was produced
from Michael addition of N-p-tolylbenzamidine (1a) to 1-(2-
nitrovinyl)-benzene (2a). With FeCl3 serving as Lewis acid, the
intermediate 5 was produced from the 4 via another intra-
molecular nucleophilic addition. Subsequently, the final product
3aa was obtained from intermediate 5 after elimination of
nitroxyl (HNO) and H2O.
4.1. The general procedure of the reaction between nitro-
olefins and benzamidines
4.1.1. Synthesis of 3aa (2,4-diphenyl-1-p-tolyl-1H-imidazole). All
reactions were performed on a 0.20 mmol scale of benzamidine.
The N-p-tolylbenzamidine 1a (0.20 mmol), 1-(2-nitrovinyl)-ben-
zene 2a (0.2 mmol), FeCl3 (0.040 mmol) and 2 mL DMF were taken
into a round bottom flask equipped with stirrer. The resulting
mixture was stirred for 4 h at 90 ꢀC. After cooling to room tem-
perature, to the reaction mixture was added water (2 mL), and
extracted with acetic ether (3ꢁ10 mL). The combined organic
phases were washed with brine (2ꢁ5 mL), dried over anhydrous
MgSO4 and concentrated under reduced pressure. The residue was
subjected to flash column chromatography with hexanes/EtOAc
(20:1) as eluent to obtain the desired 3aa as light yellow solid (90%
yield). The remaining multi-substituted imidazoles were
prepared in the similar manner and their characterization data are
as follows: 3aa was purified by flash chromatography (hexane/
EtOAc, v/v¼20:1) as light yellow oil (yield: 82%). 1H NMR (300 MHz,
CDCl3):
d
: 7.87e7.90 (d, J¼9 Hz, 2H), 7.39e7.48 (m, 5H), 7.10e7.36
(m, 8H). 13C NMR (100 MHz, CDCl3):
d
: 146.9, 141.4, 138.1, 135.9,
133.9, 130.3, 130.0, 128.5, 128.3, 128.1, 126.9, 125.5, 125.0, 118.1, 21.1.
ESI HRMS: calcd for C22H18N2 [MþH]þ: 311.1543, found: 311.1546.
4.1.2. 2-Phenyl-1,4-di-p-tolyl-1H-imidazole (3ab). 2-Phenyl-1,4-di-
p-tolyl-1H-imidazole (3ab) was purified by flash chromatography
(hexane/EtOAc, v/v¼20:1) as a light yellow solid (yield: 60%), mp:
134e136 ꢀC. 1H NMR (300 MHz, CDCl3):
d
: 7.76e7.79 (d, J¼9 Hz, 2H),
Ph
Ph
7.44e7.47 (m, 2H), 7.26 (s, 1H), 7.09e7.25 (m, 9H), 2.37 (s, 3H), 2.35
NH
NH
N
(s, 3H). 13C NMR (100 MHz, CDCl3):
d
: 146.7, 141.5, 138.0, 136.5,
H
Ph
FeCl3
OH
135.9, 129.9, 129.2, 128.7, 128.2, 128.1, 125.5, 124.9, 118.1, 21.2, 21.0.
N
NO2
Ph
Michael addition
O
ESI HRMS: calcd for C23H20N2 [MþH]þ: 325.1699, found: 325.1695.
NH
4.1.3. 4-(4-Methoxyphenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3ac). 4-(4-Methoxyphenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3ac) was purified by flash chromatography (hexane/EtOAc, v/
v¼20:1) as a light yellow solid (yield: 51%), mp: 146e148 ꢀC. 1H
4
2a
1a
NMR (300 MHz, CDCl3):
d
: 7.80e7.83 (d, J¼9 Hz, 2H), 7.45e7.48 (dd,
J¼3, 6 Hz, 2H), 7.10e7.7.31 (m, 8H), 6.93e6.96 (d, J¼9 Hz, 2H), 3.82
(s, 3H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3):
d: 158.7,146.6,141.3,
138.0, 135.9, 130.4, 129.9, 128.7, 128.2, 128.1, 126.7, 126.2, 125.5,
117.6, 113.8, 55.2, 21.1. ESI HRMS: calcd for C23H20N2O [MþH]þ:
341.1649, found: 341.1652.
Ph
H
N
N
- HNO
H2O
OH
OH
Ph
N
N
N
4.1.4. 4-(4-Fluorophenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3ad). 4-(4-Fluorophenyl)-2-phenyl-1-p-tolyl-1H-imidazole (3ad)
was purified by flash chromatography (hexane/EtOAc, v/v¼20:1) as
a light yellow oil (yield: 61%).1H NMR (300 MHz, CDCl3):
d: 7.82e7.86
3aa
5
(m, 2H), 7.46e7.47 (m, 2H), 7.04e7.45 (m,10H), 2.38 (s, 3H). 13C NMR
(100 MHz, CDCl3): : 163.6, 160.3, 146.9, 140.6, 138.2, 135.8, 129.9,
Scheme 1. A plausible reaction mechanism.
d
128.6, 128.3, 128.1, 126.6, 126.5, 125.5, 118.2, 115.5, 115.2, 21.0. ESI
HRMS: calcd for C22H17N2F[MþH]þ: 329.1449, found: 329.1452.
3. Conclusion
4.1.5. 4-(4-Chlorophenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3ae). 4-(4-Chlorophenyl)-2-phenyl-1-p-tolyl-1H-imidazole (3ae)
was purified by flash chromatography (hexane/EtOAc, v/v¼20:1) as
In conclusion, we have successfully developed an efficient and
novel catalytic approach for synthesis of multi-substituted im-
idazoles via nitroolefins and N-aryl benzamidines. This reaction
proceeds via stepwise [3þ2] cycloaddition in the presence of an
inexpensive iron catalyst under air. This methodology is conve-
nient, atom-economical, and eco-friendly in good yields and
prefect regioselectivities. This efficient strategy could signifi-
cantly direct further research of multi-substituted imidazoles
synthesis.
a light yellow oil (yield: 68%). 1H NMR (300 MHz, CDCl3):
d:
7.80e7.83 (d, J¼9 Hz, 2H), 7.09e7.47 (m, 12H), 2.38 (s, 3H). 13C NMR
(100 MHz, CDCl3): d: 147.0, 140.3, 138.2, 135.6, 132.4, 132.3, 130.1,
129.4, 128.9, 128.8, 128.3, 127.8, 126.2, 126.0, 125.6, 21.1. ESI HRMS:
calcd for C22H17N2Cl [MþH]þ: 345.1153, found: 345.1157.
4.1.6. 4-(2-Chlorophenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3af). 4-(2-Chlorophenyl)-2-phenyl-1-p-tolyl-1H-imidazole (3af)

9420
X. Liu et al. / Tetrahedron 69 (2013) 9417e9421
was purified by flash chromatography (hexane/EtOAc, v/v¼20:1) as
a light yellow solid (yield: 55%), mp: 107e109 ꢀC. 1H NMR
(dd, J¼3, 6 Hz, 4H), 7.20e7.25 (m, 5H), 7.07e7.19 (m, 2H), 2.40 (s,
3H), 2.22 (s, 3H). 13C NMR (100 MHz, CDCl3):
: 146.3, 138.8, 136.4,
d
(300 MHz, CDCl3):
7.47e7.88 (m, 4H), 7.13e7.45 (m, 8H), 2.38 (s, 3H). 13C NMR
(100 MHz, CDCl3): : 146.0, 138.2, 137.4, 135.8, 132.2, 130.7, 130.1,
d
: 8.35e8.38 (d, J¼9 Hz, 2H), 7.88 (s, 1H),
134.5, 133.7, 131.9, 130.6, 130.2, 128.4, 128.3, 128.2, 128.0, 127.9,
127.7, 126.5, 21.2, 11.1. ESI HRMS: calcd for C22H19N2Cl [MþH]þ:
359.1310, found: 359.1314.
d
130.09, 130.0, 129.7, 128.7, 128.4, 128.1, 127.5, 126.8, 125.6, 123.0,
21.1. ESI HRMS: calcd for C22H17N2Cl [MþH]þ: 345.1153, found:
345.1155.
4.1.13. 4-(5-Methyl-2-phenyl-1-p-tolyl-1H-imidazol-4-yl)benzoni-
trile
(3am). 4-(5-Methyl-2-phenyl-1-p-tolyl-1H-imidazol-4-yl)
benzonitrile (3am) was purified by flash chromatography (hexane/
4.1.7. 2-Phenyl-1-p-tolyl-4-(4-(trifluoromethyl)phenyl)-1H-imidaz-
ole (3ag). 2-Phenyl-1-p-tolyl-4-(4-(trifluoromethyl)phenyl)-1H-
imidazole (3ag) was purified by flash chromatography (hexane/
EtOAc, v/v¼20:1) as a light yellow oil (yield: 50%). 1H NMR
EtOAc, v/v¼20:1) as an off white solid (yield: 56%), mp: 178e180 ꢀC.
1H NMR (300 MHz, CDCl3):
d: 7.89e7.92 (d, J¼9 Hz, 2H), 7.64e7.67
(m, 2H), 7.39e7.40 (t, J¼3 Hz, 2H), 7.20e7.38 (m, 5H), 7.06e7.19 (m,
2H), 2.40 (s, 3H), 2.25 (s, 3H). 13C NMR (100 MHz, CDCl3):
d: 146.8,
(300 MHz, CDCl3):
d
: 7.96e7.99 (d, J¼9 Hz, 2H), 7.61e7.64 (d,
139.8, 139.0, 135.6, 134.1, 132.1, 130.3, 128.2, 128.18, 128.1, 128.0,
127.6, 127.0, 119.3, 109.0, 21.1, 11.3. ESI HRMS: calcd for C24H19N3
[MþH]þ: 350.1652, found: 350.1650.
J¼9 Hz, 2H), 7.45e7.47 (dd, J¼3, J¼6, 3H), 7.10e7.43 (m, 7H), 2.38 (s,
3H). 13C NMR (100 MHz, CDCl3):
d
: 147.4, 140.1, 138.5, 137.4, 135.6,
130.1,128.7,128.6,128.2,125.5,124.9,119.7, 21.1. ESI HRMS: calcd for
C23H17N2F3 [MþH]þ: 379.1417, found: 379.1413.
4.1.14. 1,4-Diphenyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazole
(3ja). 1,4-Diphenyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazole
(3ja) was purified by flash chromatography (hexane/EtOAc, v/
v¼20:1) as a light yellow oil (yield: 76%). 1H NMR (400 MHz,
4.1.8. 4-(2,4-Dimethoxyphenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3ah). 4-(2,4-Dimethoxyphenyl)-2-phenyl-1-p-tolyl-1H-imidazole
(3ah) was purified by flash chromatography (hexane/EtOAc, v/
v¼20:1) as an off white solid (yield: 53%), mp: 179e181 ꢀC. 1H NMR
CDCl3):
d
: 7.86e7.88 (d, J¼8 Hz, 2H), 7.21e7.57 (m, 13H). 13C NMR
(100 MHz, CDCl3): d: 145.3, 142.1, 138.9, 138.1, 129.7, 129.3, 129.1,
(300 MHz, CDCl3):
d
:8.01e8,02 (t, J¼3 Hz, 1H), 7.78e7.79 (t, J¼3 Hz,
128.7, 128.6, 127.2,125.8, 125.1, 125.07, 125.0, 119.6,119.3. ESI HRMS:
1H), 7.27e7.28 (t, J¼3 Hz,1H), 7.17e7.28 (m, 7H), 6.80e6.90 (m, 2H).
calcd for C22H15N2F3 [MþH]þ: 365.1260, found: 365.1262.
13C NMR (100 MHz, CDCl3):
d: 153.9, 150.4, 145.6, 137.9, 136.7, 136.1,
130.4, 129.9, 128.7, 128.2, 128.0, 125.7, 123.2, 123.1, 113.3, 112.1, 111.8,
55.8, 55.7, 21.0. ESI HRMS: calcd for C24H22N2O2 [MþH]þ: 371.1754,
found: 371.1758.
4.1.15. 2-(1,4-Diphenyl-1H-imidazol-2-yl)pyridine
(3la). 2-(1,4-
Diphenyl-1H-imidazol-2-yl)pyridine (3la) was purified by flash
chromatography (Hexane/EtOAc, v/v¼20:1) as a light yellow oil
(yield: 67%). 1H NMR (300 MHz, CDCl3):
d
: 8.65e8.66 (d, J¼3 Hz,
4.1.9. 5-Methyl-2,4-diphenyl-1-p-tolyl-1H-imidazole (3ai). 5-Methyl-
2,4-diphenyl-1-p-tolyl-1H-imidazole (3ai) was purified by flash
chromatography (hexane/EtOAc, v/v¼20:1) as an off white solid
1H), 8.50e8.52 (d, J¼6 Hz, 1H), 7.79e7.90 (m, 3H), 7.45e7.48 (m,
6H), 7.19e7.44 (m, 4H). 13C NMR (100 MHz, CDCl3):
d
: 149.2, 149.1,
143.9, 142.2, 137.8, 135.8, 133.4, 129.8, 128.7, 128.6, 127.2, 126.4,
125.8, 125.0, 123.0, 119.1. ESI HRMS: calcd for C20H15N3 [MþH]þ:
298.1339, found: 298.1342.
(yield: 47%), mp: 138e140 ꢀC. 1H NMR (300 MHz, CDCl3):
d:
7.78e7.81 (d. J¼9 Hz, 2H), 7.42e7.45 (dd, J¼3, 6 Hz, 4H), 7.08e7.41
(m, 8H), 2.40 (s, 3H), 2.24 (s, 3H). 13C NMR (100 MHz, CDCl3):
d: 146.1,
138.6, 134.7, 130.1, 129.4, 128.5, 128.3, 127.9, 127.8, 127.7, 127.2, 120.2,
21.2, 11.1. ESI HRMS: calcd for C23H20N2 [MþH]þ: 325.1699, found:
325.1671.
Acknowledgements
We are grateful for financial support from the National Science
Foundation of P.R. of China (No. 21372102) and the Project of
National Science Foundation of Gansu Province P.R. China
(No. 1208RJZA266).
4.1.10. 5-Methyl-2-phenyl-1,4-di-p-tolyl-1H-imidazole
(3aj). 5-
Methyl-2-phenyl-1,4-di-p-tolyl-1H-imidazole (3aj) was purified
by flash chromatography (hexane/EtOAc, v/v¼20:1) as an off white
solid (yield: 35%), mp: 172e174 ꢀC. 1H NMR (300 MHz, CDCl3):
d:
Supplementary data
7.67e7.70 (d, J¼9 Hz, 2H), 7.40e7.43 (dd, J¼3, 6 Hz, 2H), 7,09e7.25
(m, 9H). 2.41 (s, 3H), 2.38 (s, 3H), 2.23 (s, 3H). 13C NMR (100 MHz,
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.08.077.
CDCl3): d: 146.0, 138.6, 137.5, 135.8, 134.8, 132.3, 130.8, 130.1, 129.0,
128.3, 127.9, 127.8, 127.7, 127.1, 125.9, 21,2, 11.1. ESI HRMS: calcd for
C24H22N2 [MþH]þ: 339.1856, found: 339.1860.
References and notes
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4.1.11. 4-(4-Bromophenyl)-5-methyl-2-phenyl-1-p-tolyl-1H-imidaz-
ole (3ak). 4-(4-Bromophenyl)-5-methyl-2-phenyl-1-p-tolyl-1H-
imidazole (3ak) was purified by flash chromatography (hexane/
EtOAc, v/v¼20:1) as an off white solid (yield: 41%), mp: 158e160 ꢀC.
1H NMR (300 MHz, CDCl3):
d
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(m, 2H), 7.39e7.42 (m, 2H), 7.21e7.25 (m, 5H), 7.07e7.21 (m, 2H),
2.41 (s, 3H), 2.22 (s, 3H). 13C NMR (100 MHz, CDCl3):
d: 146.3, 138.8,
134.5, 134.2, 131.4, 130.6, 130.2, 128.7, 128.3, 128.0, 127.9, 127.7,
126.6, 120.1, 21.2, 11.1. ESI HRMS: calcd for C22H19N2Br [MþH]þ:
403.0805, found: 403.0801.
4.1.12. 4-(4-Chlorophenyl)-5-methyl-2-phenyl-1-p-tolyl-1H-imidaz-
ole
(3al). 4-(4-Chlorophenyl)-5-methyl-2-phenyl-1-p-tolyl-1H-
imidazole (3al) was purified by flash chromatography (hexane/
EtOAc, v/v¼20:1) as an off white solid (yield: 45%), mp: 160e162 ꢀC.
1H NMR (300 MHz, CDCl3):
d
: 7.72e7.75 (d, J¼9 Hz, 2H), 7.39e7.42

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