Synthesis of multisubstituted imidazoles via copper-catalyzed [3 + 2] cycloadditions

Article abstract of DOI:10.1021/jo302555z

A simple route for the synthesis of imidazole derivatives via copper-catalyzed [3 + 2] cycloaddition reaction is described. This strategy has achieved high regioselectivity and used oxygen as an oxidant without the addition of expensive catalysts to provide moderate to good yields.

Full text of DOI:10.1021/jo302555z

Note
pubs.acs.org/joc
Synthesis of Multisubstituted Imidazoles via Copper-Catalyzed [3 +
2] Cycloadditions
Dong Tang, Ping Wu, Xiang Liu, Yong-Xin Chen, Shuai-Bo Guo, Wen-Lin Chen, Jia-Gen Li,
and Bao-Hua Chen*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Gansu Lanzhou, 730000, P. R. China, and Key Laboratory
of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou, 730000, P. R. China
S
* Supporting Information
ABSTRACT: A simple route for the synthesis of imidazole
derivatives via copper-catalyzed [3 + 2] cycloaddition reaction
is described. This strategy has achieved high regioselectivity
and used oxygen as an oxidant without the addition of
expensive catalysts to provide moderate to good yields.
a
Table 1. Optimization of the Reaction Conditions
he imidazole ring represents an important class of
1
Theterocycles frequently found in many natural products.
In addition, imidazole derivatives have been reported to possess
pharmacological properties2 such as antiplasmodium,3 anti-
tumor,4 and antifunga.5 Consequently, many efforts in the past
decade have been focused on the preparation of those
privileged scaffolds. For example, the synthesis of 1,2,4,5-
tetrasubstituted imidazoles have been developed by using
various catalytic systems including I2,6a BF3−SiO2,6b SBPPSA,6c
alumina,6d FeCl3·6H2O,6e Cu(OAc)2,6f and DABCO.6g Tran-
sition-metal-catalyzed direct C−H or N−H functionalization
provides a powerful tool for the formation of multisubstituted
imidazoles.7 Many reported methods, though very efficient for
obtaining imidazole derivatives, suffer from one or more
drawbacks such as requiring harsh reaction conditions, usage of
expensive catalysts and long reaction time. Therefore, new
synthetic methods are still needed to synthesize imidazoles
under much milder conditions and with a simpler catalytic
system.
b
entry
catalyst
CuI
ligand
bipy
solvent
yield (%)
1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
Dioxane
Toluene
DCE
68
27
65
52
58
66
trace
trace
59
41
55
31
72
77
0
2
Cu(acac)2
CuBr
Cu(OAc)2
CuBr2
CuI
bipy
3
bipy
4
bipy
5
bipy
6
1,10-Phen
L-proline
Ph3P
bipy
7
CuI
8
CuI
9
CuI
10
11
12
13
14
15
16
17
18
CuI
bipy
CuI
bipy
CuI
bipy
c
c
c
c
c
c
Nitroolefins, as easily available and versatile substrates, have
been ubiquitously employed in many synthetic strategies.8 In
particular, they have drawn great attention because of their
interesting properties in applying cycloaddition reactions. To
the best of our knowledge, nitroolefins can easily lead to
electrophilic cycloaddition because of the nitro that significantly
withdraws the electron. Recently, Yan and co-workers reported
copper-catalyzed aminopyridines and nitroolefins to synthesize
imidazo[1,2-a]pyridines.9 As part of our further investigations,
this paper will report a novel and efficient strategy for the
synthesis of tri- or tetrasubstituted imidazoles via copper-
catalyzed [3 + 2] cycloaddition reaction.
CuI
bipy
DMF
DMF
DMF
DMF
DMF
DMF
,
,
,
,
,
d
d
d
d
d
CuI
bipy
,
e
CuI
bipy
bipy
0
,
,
f
CuI
CuI
bipy
71
67
g
bipy
a
Reaction conditions: 1a (0.1 mmol), 2a (0.1 mmol), catalyst (10%),
ligand (20%), solvent (2 mL), 90 °C, 5 h. Isolated yield based on 2a.
The reaction was carried out under an O2 atmosphere. The ratio of
1a (0.1 mmol)/2a = 1.2:1. In the presence of t-BuOK. 60 °C. 110
b
c
d
e
f
g
°C.
including catalysts, ligands, solvents, and temperature were
examined (Table 1, entries 2−12, 17, and 18), but with only
inferior results. To our delight, the yield was increased to 72%
when the reaction was conducted under an O2 atmosphere
We started with an investigation into the reaction of 4-
methyl-N-phenylbenzamidine (1a) and 1-(2-nitrovinyl)-
benzene (2a) (Table 1). The desired product 3a was isolated
in a 68% yield by the use of CuI as the catalyst and 2,2-bipyridyl
(bipy) as the ligand in DMF at 90 °C under air conditions
(Table 1, entry1). Encouraged by this result, we continued to
explore the optimal conditions. Different reaction parameters
Received: December 12, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo302555z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
(Table 1, entry 13). Enhancing the ratio of 1a/2a to 1.2:1
afforded a product with a 77% yield (Table 1, entry 14).
Notably, the control experiment showed that no reaction
occurred if no catalyst was added or if it was performed in the
presence of the base (Table 1, entries 15 and 16).
Table 3. Substrate Scope of Nitroolefins
With the optimized conditions in hand, we continued our
investigation by exploring the substrate scope of this trans-
formation. At the outset, a series of substituted arylamidines
were tested with 2a under the optimized conditions (Table 2).
a
Table 2. Substrate Scope of Amidine
a
Reaction conditions: 1l (0.24 mmol), 2 (0.2 mmol), CuI (10%), bipy
b
(20%), DMF (2 mL), 90 °C, 5 h, under an O2 atmosphere. Isolated
yield based on 2.
corresponding products in moderate to good yields, and the
functional groups had no significant impact on the yields
(Table 3, entries 1−7). Somewhat disappointingly, when the R4
was substituted by the methyl group, the steric effect of methyl
lowered the yields significantly (Table 3, entries 8−10).
However, we were pleased to note that substrates with bulky
aromatic groups such as 2-(2-nitrovinyl)naphthalene (2l) could
perform smoothly, and a 75% yield of the desired imidazole 3w
was obtained (Table 3, entry 11).
This reaction system was also applicable for a larger scale
under the optimized condition. A mixture of 1f (1.2 mmol), 2a
(1 mmol), CuI (10%), bipy (20%), and DMF (3 mL) was
stirred at 90 °C for 5 h and afforded the desired product (3f)
with a 59% yield.
a
Reaction conditions: 1 (0.24 mmol), 2a (0.2 mmol), CuI (10%),
bipy (20%), DMF (2 mL), the ratio of 1:2a = 1.2:1, 90 °C, 5 h, under
an O2 atmosphere. Isolated yield based on 2a.
b
On the basis of the analogous mechanisms discussed in
literature,10 a plausible mechanism for this transformation was
depicted in Scheme 1. Generally, CuI was initially oxidized to
CuII under oxygen atmosphere. Compound 1l lost one
electron, and H+ generated the monoradical intermediate A
by CuII, which was further oxidized by CuII to give the diradical
intermediate B. Subsequently, a molecular nitroolefin reacted
with the intermediate B via [3 + 2] cycloaddition with a high
regioselectivity through the transition status C, which was
favored because of its steric hindrance of the aromatic groups
on subsrates. In the end, the transition status C was converted
into a stable intermediate D followed by the elimination of one
molecule of HNO2 to afford the desired product 3.
Generally, the reactions showed good functional group
tolerance and afforded the desired products in moderate to
good yields. In regard to the electronic effects, we found that
electron-rich-substituted arylamidines showed better reactivities
and gave higher yields than electron-deficient ones (Table 2,
entries 1, 2, 5−7, and 10). In addition, the functional groups at
the para-position showed slightly better reactivities than those
at the meta-position (Table 2, entries 1, 2, 5, and 9). Notably,
N-phenylnicotinamidine (1e) could also be well tolerated,
providing the corresponding product 3e with a 59% yield
(Table 2, entry 4). Nevertheless, the substrates with alkyl
groups such as N-phenylpivalamidine (1m) were not effective
for this kind of transformation (Table 2, entry 12).
In summary, a novel and facile copper-catalyzed [3 + 2]
cycloaddition reaction has been developed, and this method-
ology could be applied to the construction of a diverse range of
multisubstituted imidazole derivatives starting from readily
available reactants. Moreover, the reaction, using oxygen as an
The reaction scope was also investigated with respect to the
other coupling partners 2 (Table 3), which include methyl-,
methoxy-, chloro-, or trifluoromethyl-substituted aryl nitro-
olefins. Most of the substrates proceeded smoothly to afford the
B
dx.doi.org/10.1021/jo302555z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 1. Plausible Reaction Pathway
7.22−7.16 (m, 3H), 2.40−2.26 (dq, J = 19.5, 7.3 Hz, 2H), 0.99−0.94
(t, J = 7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 147.2, 140.6, 133.8,
129.5, 129.3, 128.5, 1289.2, 128.1, 127.7, 127.6, 126.8, 124.8, 118.9,
23.6, 13.9; HRMS (ESI) calcd for C23H21N2 (M + H)+ 325.1699,
found 325.1694.
3-(1,4-diphenyl-1H-imidazol-2-yl)pyridine (3e): 0.2 mmol, 35 mg,
59%; yellow oil; 1H NMR (300 MHz, CDCl3) δ 8.66−8.67 (d, J = 2.0
Hz, 1H), 8.51−8.50 (d, J = 4.8 Hz,1H), 7.90−7.87 (m, 2H), 7.82−
7.79 (dd, J = 8.0, 1.8 Hz, 1H), 7.48−7.38 (m, 6H), 7.30−7.18 (m,
4H); 13C NMR (75 MHz, CDCl3) δ 150.1, 149.9, 144.8, 143.1, 138.7,
136.6, 134.2, 130.6, 129.5, 129.5, 128.0, 127.2, 126.6, 125.8, 123.8,
119.9; HRMS (ESI) calcd for C20H16N3 (M + H)+ 298.1339, found
298.1336.
oxidant, is experimentally simple and environmentally benign.
In particular, the strategy could proceed smoothly with a high
regioselectivity resulting in moderate to good yields, and it can
provide a potential pathway to afford valuable scaffolds of
complex molecules in biochemistry and medicinal chemistry.
EXPERIMENTAL SECTION
General Methods Used for Preparing Starting Materials 1a−
l and 2a−k. Starting materials 1a−l and 2a−k were prepared
according to the procedure in literature.11
■
Typical Procedure for the Preparation of Multisubstituted
Imidazole. The reactions were carried out in a round-bottom side
arm flask (10 mL), and 1 (0.24 mmol), 2 (0.2 mmol), CuI (0.02
mmol), bipy (0.04 mmol), and DMF (2 mL) were added to the flask
with magnetic stirring bar under the O2 atmosphere. The mixture was
stirred at 90 °C for 5 h. After being cooled to room temperature, the
mixture was filtered and extracted with ethyl acetate. Then the filtrate
was concentrated under reduced pressure in order to get the crude
product, which was further purified by silica gel chromatography
(petroleum/ethyl acetate = 10/1 as eluent) to obtain product 3.
1H NMR spectra were recorded at 300 MHz in CDCl3, and 13C
NMR spectra were recorded on 75 MHz in CDCl3. The structures of
the products (3k,l) were identified according to the literature.12,13 All
of the products were further characterized by HRMS (ESI-TOF), and
the melting points of solid products were determined on a microscopic
apparatus.
1, 4-Diphenyl-2-p-tolyl-1H-imidazole (3a): 0.2 mmol, 35 mg, 67%;
yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.93−7.84 (m, 2H), 7.42−
7.31 (m, 8H), 7.27−7.19 (m, 3H), 7.06−7.03 (dd, J = 8.5 Hz, 0.6 Hz,
2H), 2.29 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 147.0, 141.4, 138.5,
138.2, 133.8, 129.3, 128.8, 128.5, 128.0, 127.3, 126.8, 125.7, 124.9,
118.2, 21.2; HRMS (ESI) calcd for C22H19N2 (M + H)+ 311.1543,
found 311.1539.
1-(3-Chlorophenyl)-2,4-diphenyl-1H-imidazole(3f): 0.2 mmol, 38
1
mg, 58%; yellow oil; H NMR (300 MHz, CDCl3) δ 7.89−7.86 (m,
2H), 7.46−7.42 (m, 2H), 7.41−7.39 (d, J = 3.1 Hz, 2H), 7.37−7.36
(m, 1H), 7.34−7.33 (dd, J = 1.9, 1.2 Hz,1H), 7.31−7.25 (m, 6H),
7.09−7.06 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 146.9, 141.9,
139.4, 135.0, 133.5, 130.4, 129.8, 128.8, 128.8, 128.6, 128.3, 127.1,
125.8, 125.0 124.1, 118.1; HRMS (ESI) calcd for C21H16ClN2 (M +
H)+ 311.0997, found 311.0994.
4-Phenyl-1,2-di-p-tolyl-1H-imidazole (3g): 0.2 mmol, 46 mg, 71%;
yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.89−7.86 (m, 2H), 7.40−
7.33 (m, 5H), 7.26−7.23 (d, J = 7.2 Hz, 1H), 7.18−7.15 (d, J = 8.3 Hz,
2H), 7.12−7.09 (d, J = 8.4 Hz, 2H), 7.07−7.04 (d, J = 8.0 Hz, 2H),
2.36 (s, 3H), 2.29 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 147.0,
138.1, 137.9, 136.0, 129.9, 128.8, 128.6, 128.5, 126.8, 125.5, 124.9,
118.4, 21.2, 21.0; HRMS (ESI) calcd for C23H21N2 (M + H)+
325.1699, found 325.1695.
1-(4-Methoxyphenyl)-2,4-diphenyl-1H-imidazole (3h): 0.2 mmol,
1
49 mg, 75%; yellow oil; H NMR (300 MHz, CDCl3) δ 7.90−7.86
(dd, 2H), 7.48−7.44 (m, 2H), 7.41−7.35 (m, 3H), 7.27−7.15 (m,
4H), 7.14−7.12 (d, 2H), 6.89−6.85 (d, 2H), 3.78 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 146.9, 138.1, 135.9, 130.3, 129.9, 128.7, 128.5,
128.3, 128.1, 126.8, 125.5, 124.9, 118.6, 21.1; HRMS (ESI) calcd for
C22H19N2O (M + H)+ 327.1492, found 327.1496.
2,4-Diphenyl-1-p-tolyl-1H-imidazole (3b): 0.2 mmol, 43 mg, 70%;
1
yellow oil; H NMR (300 MHz, CDCl3) δ 7.90−7.87(d, 2H), 7.48−
2-(2-Chlorophenyl)-1,4-diphenyl-1H-imidazole (3i): 0.2 mmol, 43
mg, 65%; yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.91−7.88 (dd, J
= 8.3, 1.2 Hz, 2H), 7.58 −7.54 (m, 2H), 7.42−7.37 (m, 2H), 7.33 -
7.22 (m, 7H), 7.17−7.13 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
144.6, 141.6, 137.7, 134.3, 133.6, 132.6, 130.6, 130.4, 129.6, 129.1,
128.5, 127.6, 127.0, 126.7, 124.9, 124.4, 116.9; HRMS (ESI) calcd for
C21H16ClN2 (M + H)+ 331.0997, found 331.0993.
7.40 (m, 2H), 7.39−7.25 (m, 3H), 7.26−7.18 (m, 3H), 7.16−7.09 (m,
5H), 2.37 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 146.9, 141.4, 138.1,
135.9, 133.8, 130.3, 129.9, 128.7, 128.5, 128.3, 128.1, 126.8, 125.5,
124.9, 118.6, 21.1; HRMS (ESI) calcd for C22H19N2 (M + H)+
311.1543, found 311.1540.
1-(4-Chlorophenyl)-2,4-diphenyl-1H-imidazole (3c): 0.2 mmol, 40
1
mg, 61%; yellow oil; H NMR (300 MHz, CDCl3) δ 7.90−7.86 (m,
2H), 7.46−7.29 (m, 7H), 7.28−7.18 (m, 4H), 7.18−7.15 (t, 2H); 13C
NMR (75 MHz, CDCl3) δ 146.9, 141.6, 138.4, 133.8, 130.2, 129.4,
128.7, 128.5, 128.4, 128.1, 128.1, 126.9, 125.8, 124.9, 118.5; HRMS
(ESI) calcd for C21H16ClN2 (M + H)+ 331.0997, found 331.0993.
1-(2-Ethylphenyl)-2,4-diphenyl-1H-imidazole (3d): 0.2 mmol, 41
mg, 63%; yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.92−7.90 (d, J =
7.9 Hz, 2H), 7.49−7.45 (dd, J = 6.6, 3.1 Hz, 2H), 7.41−7.36 (dd, J =
10.3, 4.7 Hz, 3H), 7.33−7.30 (d, J = 7.8 Hz, 2H), 7.26−7.23 (m, 3H),
2,4-Diphenyl-1-m-tolyl-1H-imidazole (3j): 0.2 mmol, 38 mg, 62%;
1
yellow oil; H NMR (300 MHz, CDCl3) δ 7.87−7.90 (d, J = 7.4 Hz,
2H), 7.48−7.44 (dd, J = 6.7, 3.0 Hz, 2H), 7.39−7.34 (m, 3H), 7.25−
7.18 (m, 5H), 7.13−7.06 (d, J = 7.7 Hz, 1H), 7.06 (s, 1H), 6.98−6.95
(d, J = 7.6 Hz, 1H), 2.30 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
146.7, 141.4, 139.4, 138.2, 133.8, 130.2, 129.0, 128.8, 128.6, 128.4,
128.2, 128.0, 126.8, 126.1, 124.9, 122.8, 118.5, 21.1; HRMS (ESI)
calcd for C22H19N2 (M + H)+ 311.1543, found 311.1538.
C
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The Journal of Organic Chemistry
Note
2-(4-Methoxyphenyl)-4-phenyl-1-p-tolyl-1H-imidazole (3k):12 0.2
mmol, 53 mg, 78%; white solid, mp: 128−132 °C; H NMR (300
135.4, 130.9, 129.8, 129.0, 128.6, 128.4, 128.3, 128.1, 127.5, 126.7,
126.5, 11.4; HRMS (ESI) calcd for C22H19N2 (M + H)+ 311.1543,
found 311.1547.
1
MHz, CDCl3) δ 7.89−7.86 (dd, J = 8.3, 1.0 Hz, 2H), 7.40−7.35 (m,
5H), 7.25−7.20 (t, J = 7.4 Hz, 1H), 7.18−7.09 (dd, J = 19.0, 8.3 Hz,
4H), 6.80−6.76 (t, J = 5.7 Hz, 2H), 3.73 (s, 3H), 2.36 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 159.5, 146.8, 141.1, 137.9, 135.9, 133.9,
130.0, 129.9, 128.4, 126.7, 125.5, 124.8, 122.9, 118.2, 113.5, 55.0, 21.0;
HRMS (ESI) calcd for C23H21N2O (M + H)+ 341.1648, found
341.1643.
4-(4-Chlorophenyl)-5-methyl-1,2-diphenyl-1H-imidazole (3u): 0.2
1
mmol, 30 mg, 43%; white solid; mp 193−196 °C; H NMR (300
MHz, CDCl3) δ 7.75−7.72 (m, 2H), 7.47−7.43 (dd, J = 4.9, 1.8 Hz,
3H), 7.42−7.37 (m, 4H), 7.25−7.19 (m, 5H), 2.24 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 146.6, 137.5, 136.9, 134.0, 132.3, 130.8, 129.9,
129.1, 128.8, 128.7, 128.6, 128.4, 126.7, 11.5; HRMS (ESI) calcd for
C22H18ClN2 (M + H)+ 345.1153, found 345.1158.
1,2,4-Triphenyl-1H-imidazole(3l):13 0.2 mmol, 41 mg, 69%; yellow
oil; 1H NMR (300 MHz, CDCl3) δ 7.94−7.91 (d, 2H), 7.51−7.46 (m,
4H), 7.47−7.42 (m, 4H), 7.31−7.26 (m, 6H); 13C NMR (75 MHz,
CDCl3) δ 146.9, 141.9, 136.8, 133.9, 133.5, 129.9, 129.6, 128.7, 128.6,
128.6, 128.3, 127.1, 126.9, 125.0, 118.1; HRMS (ESI) calcd for
C21H17N2 (M + H)+ 297.1386, found 297.1383.
4-(4-Methoxyphenyl)-5-methyl-1,2-diphenyl-1H-imidazole (3v):
1
0.2 mmol, 23 mg, 34%; yellow oil; H NMR (300 MHz, CDCl3) δ
7.74−7.71 (d, J = 8.7 Hz, 2H), 7.46−7.44 (d, J = 5.2 Hz, 3H), 7.40−
7.37(m, 2H), 7.26−7.15 (m, 5H), 7.00−6.97(d, J = 8.7 Hz, 2H), 3.85
(s, 3H), 2.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 158.3, 146.0,
137.5, 130.8, 129.6, 128.6, 128.5, 128.3, 128.1, 128.1, 128.0, 127.8,
125.4, 113.8, 55.2, 11.06; HRMS (ESI) calcd for C23H21N2O (M +
H)+ 341.1649, found 341.1644.
1,2-Diphenyl-4-(4-(trifluoromethyl)phenyl)-1H-imidazole (3m):
1
0.2 mmol, 45 mg, 62%; yellow oil; H NMR (300 MHz, CDCl3) δ
8.00−7.97 (d, J = 8.6 Hz, 2H), 7.65−7.62 (d, J = 8.6 Hz, 2H), 7.51 (s,
1H), 7.47−7.37 (m, 5H), 7.30−7.21 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 147.4, 140.2, 138.1, 137.3, 129.9, 129.5, 128.7, 128.7, 128.4,
128.3, 125.7, 125.6, 125.6, 125.5, 125.5, 124.9, 119.6; HRMS (ESI)
calcd for C22H16F3N2 (M + H)+ 365.126, found 365.1255.
4-(Naphthalen-2-yl)-1,2-diphenyl-1H-imidazole (3w): 0.2 mmol,
1
52 mg, 75%; white solid; mp 144−146 °C; H NMR (300 MHz,
CDCl3) δ 8.75−8.67 (m, 1H), 7.91−7.77 (m, 3H), 7.51 (ddd, J = 12.9,
5.1, 2.7 Hz, 5H), 7.45−7.36 (m, 4H), 7.35−7.23 (m, 5H); 13C NMR
(75 MHz, CDCl3) δ 146.4, 140.8, 138.3, 133.9, 131.5, 131.2, 130.1,
129.4, 128.7, 128.3, 128.2, 128.1, 127.7, 126.6, 126.0, 125.9, 125.7,
125.5, 125.4, 121.3; HRMS (ESI) calcd for C25H19N2 (M + H)+
347.1543, found 347.1539.
4-(2-Chlorophenyl)-1,2-diphenyl-1H-imidazole (3n): 0.2 mmol, 44
1
mg, 66%; yellow oil; H NMR (300 MHz, CDCl3) δ 8.39−8.36 (m,
1H), 7.92 (s, 1H), 7.48−7.44 (m, 2H), 7.43−7.34 (m, 5H), 7.29−7.25
(m, 5H), 7.20−7.17 (dd, J = 7.4, 1.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ 146.0, 138.3, 137.6, 132.1, 130.7, 130.1, 130.0, 129.7, 129.4,
128.7, 128.4, 128.1, 127.5, 126.8, 125.8, 122.8; HRMS (ESI) calcd for
C21H16ClN2 (M + H)+ 331.0997, found 331.0993.
ASSOCIATED CONTENT
■
S
* Supporting Information
4-(2,4-Dimethoxyphenyl)-1,2-diphenyl-1H-imidazole (3o): 0.2
1H NMR and 13C NMR spectra data for all the products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
1
mmol, 48 mg, 68%; yellow solid; mp 182−185 °C; H NMR (300
MHz, CDCl3) δ 8.01−8.00 (d, J = 3.1 Hz, 1H), 7.80 (s, 1H), 7.50−
7.46 (m, 2H), 7.41−7.38 (d, J = 6.7 Hz, 3H), 7.3−7.24 (m, 5H),
6.91−6.88 (d, J = 8.9 Hz, 1H), 6.81−6.77 (dd, J = 8.9, 3.1 Hz, 1H),
3.89−3.88 (d, 6H); 13C NMR (75 MHz, CDCl3) δ 153.9, 150.5, 145.7,
138.6, 136.9, 130.3, 129.3, 128.6, 128.3, 128.1, 128.0, 125.9, 123.2,
123.0, 113.39, 112.1, 111.8, 55.9, 55.8; HRMS (ESI) calcd for
C23H21N2O2 (M + H)+ 357.1598, found 357.1593.
AUTHOR INFORMATION
Corresponding Author
*E-mail: chbh@lzu.edu.cn.
■
Notes
4-(4-Chlorophenyl)-1,2-diphenyl-1H-imidazole (3p): 0.2 mmol, 38
1
The authors declare no competing financial interest.
mg, 57%; yellow oil; H NMR (300 MHz, CDCl3) δ 7.82−7.78 (m,
2H), 7.44−7.32 (m, 8H), 7.26−7.19 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 147.0, 140.5, 138.2, 132.4, 132.3, 129.4, 132.3, 130.0, 129.4,
128.7, 128.5, 128.2, 128.1, 126.2, 125.7, 118.6; HRMS (ESI) calcd for
C21H16ClN2 (M + H)+ 331.0997, found 331.0993.
ACKNOWLEDGMENTS
We are grateful to the project sponsored by the National
Science Foundation of P. R. China (No. J11003307).
■
4-(4-Fluorophenyl)-1,2-diphenyl-1H-imidazole (3q): 0.2 mmol, 40
1
mg, 64%; yellow oil; H NMR (300 MHz, CDCl3) δ 7.87−7.82 (m,
REFERENCES
■
2H), 7.45−7.42 (m, 2H), 7.39−7.36 (m, 4H), 7.28−7.21 (m, 5H),
7.10−7.05 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 163.9, 160.6,
147.2, 141.0, 138.5, 129.7, 128.9, 128.7, 128.4, 126.9, 126.7, 126.0,
118.3, 115.8, 115.5; HRMS (ESI) calcd for C21H16FN2 (M + H)+
315.1292, found 315.1289.
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4-(4-Methoxyphenyl)-1,2-diphenyl-1H-imidazole (3r): 0.2 mmol,
43 mg, 66%; yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.83−7.79 (m,
2H), 7.45−7.41 (m, 2H), 7.37−7.31 (m, 4H), 7.26−7.18 (m, 5H),
6.97−6.88 (m, 2H), 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
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1,2-Diphenyl-4-p-tolyl-1H-imidazole (3s): 0.2 mmol, 41 mg, 66%;
1
yellow oil; H NMR (300 MHz, CDCl3) δ 7.79−7.77 (d, J = 8.1 Hz,
2H), 7.46−7.42 (m, 2H), 7.37−7.34 (m, 4H), 7.25−7.18 (ddd, J = 8.2,
6.0, 3.2 Hz, 7H), 2.35 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 146.7,
141.6, 138.4, 136.5, 130.9, 130.2, 129.3, 129.2, 128.7, 128.3, 128.1,
128.0, 125.7, 124.8, 118.0, 21.2; HRMS (ESI) calcd for C21H16ClN2
(M + H)+ 311.1543, found 311.1538.
5-Methyl-1,2,4-triphenyl-1H-imidazole (3t): 0.2 mmol, 24 mg,
1
39%; yellow solid; mp 148−152 °C; H NMR (300 MHz, CDCl3) δ
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2.27 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 146.4, 137.9, 137.7,
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