CuI catalyzed C-N bond forming reactions between aryl/heteroaryl bromides and imidazoles in [Bmim]BF4

Article abstract of DOI:10.1016/j.tet.2006.03.026

By using CuI as the catalyst and l-Proline as the ligand, the Ullmann-type coupling reactions of aryl/heteroaryl bromides and imidazoles in [Bmim]BF₄ at 105-115 °C gave the corresponding N-arylimidazoles/N-heteroarylimidazoles in good yields. T

Full text of DOI:10.1016/j.tet.2006.03.026

Tetrahedron 62 (2006) 4756–4761
CuI catalyzed C–N bond forming reactions between
aryl/heteroaryl bromides and imidazoles in [Bmim]BF4
*
Xin Lv, Zhiming Wang and Weiliang Bao
Zhejiang University, Xi Xi Campus, Department of Chemistry, Hangzhou, Zhejiang 310028, P.R. China
Received 10 November 2005; revised 8 March 2006; accepted 9 March 2006
Available online 3 April 2006
Abstract—By using CuI as the catalyst and L-Proline as the ligand, the Ullmann-type coupling reactions of aryl/heteroaryl bromides and
ꢀ
imidazoles in [Bmim]BF4 at 105–115 C gave the corresponding N-arylimidazoles/N-heteroarylimidazoles in good yields. The system offers
a convenient, recyclable, and environmentally benign method for these coupling reactions.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Room temperature ionic liquids (RTILs) are one class of
non-molecular ionic solvents. They have special characteris-
tics such as low vapor pressure, high polarity, and etc.11
RTILs have been widely utilized in the area of organic chem-
istry as novel solvents.11 In recent years, metal catalyzed
coupling reactions have been studied in RTILs.12 Ullmann-
type reactions also have been tried in RTILs and many re-
sults revealed that they could proceed successfully in these
special solvents.13 Our laboratory reported a mild and effi-
cient method for Ullmann-type coupling of vinyl bromides
with imidazoles in ionic liquids, which was promoted by
L-proline.14
N-Arylimidazoles and N-heteroarylimidazoles have been
found useful for their biological effects and medicinal appli-
cations.1 Recently, these arylimidazole derivatives show
their important roles in the area of N-heterocyclic carbene
chemistry.2 Synthesis of these useful compounds becomes
a meaningful work. One common strategy is the Ullmann-
type C–N bond formations.3 However, the reactions usually
proceeds at high temperatures and their further applications
would be limited. N-Arylimidazoles could be obtained by
nucleophilic aromatic substitution,4 but the method is suit-
able only for the substrates with electron withdrawing sub-
stituents. In 1998, Chan and Lam reported cupric acetate
catalyzed coupling between aryl boronic acids and imidaz-
oles.5 The method could proceed at low temperatures, never-
theless the relatively expensive boronic reagents and the
strict optimization of the condition limits its scope in syn-
thetic areas.6 Palladium catalyzed C–N bond forming cou-
pling works effectively at mild temperatures, whereas the
catalysts used is expensive and sensitive to air and moisture.7
On the other hand, although synthesis of N-arylimidazoles
has been widely and intensively studied, researches on N-
heteroarylation of imidazoles are still rare. Relating to this
article, only two N-heteroarylimidazoles have been synthe-
sized by Ullmann coupling methods.15
Herein we reported a copper (I) catalyzed cross-coupling re-
action between aryl/heteroaryl bromides and imidazoles in
RTIL, which would be a milder, economical, and recover-
able way to obtain the N-arylimidazoles/N-heteroarylimida-
zoles. Considering the relatively rare reports on the latter and
their important applications, our research mainly focused on
the synthesis of N-heteroarylimidazoles.
Buchwald et al. firstly reported (CuOTf)$benzene/1,10-
phenanthroline/trans,trans-dibenzylideneacetone catalyzed
Ullmann-type reactions between aryl halides and imidazoles
8
ꢀ
at low temperatures (110–125 C), and latterly found the
diamines promoted CuI catalyzed coupling of aryl iodides
and imidazoles.9 However, Buchwald’s method requires
special catalysts or ligands. Recently, Ma and his co-workers
developed the first amino acids promoted CuI catalyzed sys-
tem in cross-coupling reactions, which were carried out in
mild conditions.10 Ma’s protocol uses economical and read-
ily available amino acids as promoters.
2. Results and discussion
2.1. Synthesis of N-arylimidazoles/N-heteroarylimidaz-
oles by Ullmann-type method in RTIL
Initially, CuI catalyzed coupling reactions between aromatic
heterocyclic bromides and imidazoles in ([Bmim]BF4) were
studied. It was found that in the presence of some weak bases
* Corresponding author. Tel./fax: +86 571 88911554; e-mail: wbao@
hzcnc.com
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.026

X. Lv et al. / Tetrahedron 62 (2006) 4756–4761
Table 2. Effect of the amount of CuI and liganda
4757
(such as K2CO3 and K3PO4), together with some a-amino
N
acids as ligands, CuI could facilitate this type of coupling re-
actions in [Bmim]BF4 under mild conditions. The coupling
between aryl (including substituted phenyl and naphthyl)
bromides and imidazoles under the similar conditions was
also tested, as a supplement for the arylation of the imidaz-
oles.
CuI/L-Proline
Br K2CO3
+
N
H
N
N
N
110°C
I.L.
N
Entry
CuI (L-Proline) (mol %)
Yield (%)b
1
2
3
4
10 (20)
20 (40)
30 (60)
40 (80)
56
78
87
89
By using a moderate base (K2CO3), we firstly altered the
ligand a-amino acids to search the most suitable promoter.
It was found that the type of ligands affected this reaction
significantly and L-proline seemed to be the best ligand
(Table 1, entries 1–4).
a
Reaction conditions: CuI (0.3–1.2 mmol), base (5.4 mmol), amino acid
(0.6–2.4 mmol), benzimidazole (3 mmol), 2-bromopyridine (5.4 mmol),
at about 110 ꢀC in [Bmim]BF4 (3 ml), 10 h.
b
Isolated yields.
Table 1. Effect of ligands and bases in one coupling reactiona
Table 3. CuI/a-amino acid catalyzed coupling reactions of heteroaryl/aryl
N
CuI/Ligand
Base
S
Br
bromides with imidazoles in RTILa
S
N
N
H
R
N
110°C
I.L.
N
X
X
Br
CuI/L-Proline
K2CO3
N
Y
Y
N
+
Entry
Ligand
L-Alanine
L-Arginine
L-Serine
L-Proline
L-Proline
L-Proline
L-Proline
Base
Yield (%)b
R
n
n
N
IL
105-115°C
Z
Z
H
1
2
3
4
5
6
7
K2CO3
K2CO3
K2CO3
K2CO3
KOH
73
51
65
76
52
71
26
X=CH, S, N; n=1, 2; Y=H, CH3, Br; Z=H, CH3, Cl, NO2; R=H, CH3
Entry
1
Substrates
Product
Time Yieldb
(h)
26
50
(%)
K3PO4
AcONa
S
N
N
Br
S
N
N
a
74
Reaction conditions: CuI (0.9 mmol), base (5.4 mmol), amino acid
(1.8 mmol), and benzimidazole (3 mmol), 2-bromothiophene (5.4 mmol),
at 110 ꢀC in [Bmim]BF4 (3 ml), 24 h.
N
H
Br
N
N
77c
b
S
S
Br
Isolated yields.
N
N
2
3
N
H
After the favorable ligand has been sought out, several dif-
ferent bases were tried (Table 1, entries 4–7). By comparing
the yields of these reactions, both K2CO3 and K3PO4 could
facilitate this coupling reaction and K2CO3 was the best
one. Although KOH was much stronger than the others,
the yield was lower, and more complex mixture was obtained
when the reaction was finished. In our opinion, when KOH
was used as a base, the reagents or solvent might decompose
and side reactions might exist. In contrast, AcONa was too
weak to facilitate the metal exchange process and so the
reactivity was lower.
S
H
N
Br
24
76
S
N
N
N
N
Br
Br
N
N
4
5
18
10
81
87
N
N
N
N
H
H
N
N
N
N
N
N
The reactions also seem to be sensitive to the amount of cat-
alyst and ligand. Different amount of the catalyst and ligand
were added into the reaction systems. The yield was signif-
icantly improved when the amount of CuI was increased
from 10 to 30 mol % gradually (Table 2). However, no obvi-
ous improvement was observed when the amount of CuI was
raised from 30 to 40 mol %. This results show that the reac-
tion might have been saturated when more than 40 mol %
CuI was used. In our opinion, 30 mol % CuI is sufficient
and optimum.
Br
N
N
N
6
7
8
48
36
36
71
72
75
N
N
N
H
S
N
N
S
N
H
Br
S
H
N
N
Br
Br
S
N
N
S
N
After optimizing the reaction conditions, we explored the
scope of the coupling reactions between heteroaryl bromides
and imidazoles. The results are listed in Table 3, entries 1–
13. The coupling reactions between aryl (including
substituted phenyl and naphthyl) bromides and imidazole
were also carried out under the above-mentioned conditions.
The reactions proceeded successfully and the yields were
satisfactory (Table 3, entries 14–19).
S
N
N
N
9
48
36
62
N
H
S
H
N
Br
10
73
S
N
N
(continued)

4758
X. Lv et al. / Tetrahedron 62 (2006) 4756–4761
Table 3. (continued)
effect on the product formation. Prolonging the reaction time
from 48 to 72 h did not substantially improve the yield. The
reactions between aryl bromides and imidazole could pro-
ceed successfully in the similar catalytic system (Table 3,
entries 14–17) in relatively short reaction time (24 h). It is
observed that these reactions tolerate both electron with-
drawing and electron donating substituents on the bromides
(Table 3, entries 14–19, yields 62–85%). The electron donat-
ing groups on the bromides are found to be more favorable
for these reactions than the electron withdrawing ones (Table
3, entries 14 and 18). 2-Bromo-6-methoxy-naphthalene is
found more reactive than phenyl bromides and the yield of
the corresponding product obtained is also better.
Entry
11
Substrates
Product
Time Yieldb
(h)
(%)
S
S
N
N
N
Br
Br
S
N
N
N
48
68
N
H
S
N
12
13
48
48
46
19
N
H
Cl
Cl
N
H
Br
N
N
S
S
2.2. Reusability and solvent effects of the coupling
reactions in RTIL
N
N
N
N
N
N
Br
N
N
14
15
16
17
18
24
24
24
24
24
24
82
75
70
80
62
85
N
H
One of the most attractive properties of ionic liquids is that
the catalyst system could be recycled. The recovery possibil-
ity of the reaction has also been investigated. To our satisfac-
tion, the results are rather good. After fourth runs, the system
still gave good yield (Table 4). The catalyst system, includ-
ing the solvent ionic liquids, the catalyst CuI and the ligand
could be favorably recycled. Because of the high polarity of
ionic liquid, the reaction mixture can be extracted directly by
lower polar solvents. Therefore the workup of these reac-
tions is simple. The recovered ionic liquid can be recycled
after proper treatment.
N
Br
N
H
N
Br
N
N
H
N
Cl
Br
Cl
N
N
N
H
O2N
Br
O2N
N
Table 4. Reuse of CuI/L-proline/IL reaction systema
N
N
H
N
CuI/L-Proline
Br
N
N
Br
K2CO3
110°C
N
N
N
N
H
I.L.
19
N
N
H
MeO
MeO
Cycle
Yield (%)
Cycle
Yield (%)b
a
Reaction conditions: CuI (0.9 mmol), base (5.4 mmol), amino acid
(1.8 mmol), imidazole (3 mmol), heteroaryl/aryl bromide (5.4 mmol), at
110 ꢀC in [Bmim]BF4 (3 ml).
1
2
87
82
3
4
80
76
b
c
Isolated yields.
a
Reaction conditions: CuI (0.9 mmol), K2CO3 (5.4 mmol), L-proline
(1.8 mmol), benzimidazole (3 mmol), 2-bromopyridine (5.4 mmol), at
110 ꢀC in [Bmim]BF4 (3 ml), 10 h. After reaction, the product was ex-
tracted with ether/ethyl acetate (v/v¼4/1, 3ꢁ5 ml). The remaining ionic
liquid was concentrated in vacuo (6.0 torr for 1 h at 110 ꢀC), further
amounts of base (5.4 mmol) and reactants were added and next turn began.
Isolated yields.
CuI (1.8 mmol), base (10.8 mmol), amino acid (3.6 mmol), imidazole
(6 mmol), 2,5-dibromothiophene (2 mmol), at 115 ꢀC in [Bmim]BF4
(5 ml).
b
2-Bromopyridine is found to be the most reactive heteroaryl
bromide in our experiment and benzimidazole seems to be
a little more reactive than imidazole and alkyl-substituted
imidazoles (Table 3, entries 4–6 and entries 7–9). We think
both electrophilicity of heteroaryl bromides and the nucleo-
philicity of imidazoles might affect these reactions.
Lastly, we have tried the reactions in traditional organic sol-
vents such as DMF and DMSO. The yields obtained in these
two solvents were also good but not as good as in the ionic
liquid (Table 5).
Table 5. Effect of different solventsa
As shown in Table 3, the reaction is hypersensitive to the ste-
ric environment of the heteroaryl/aryl bromides and imidaz-
oles, i.e., steric hindrance of the substrates obviously affects
these coupling reactions. As indicated in Table 3 (entries 1,
4, 11 and entries 6, 9, 12), the conversion declined when
imidazole is replaced by 2-methylimidazole. The effect of
the 2-position steric hindrance on the bromides seems to
be much stronger than on the imidazoles. As a result, the
o-substituted heterocycle bromides such as 2-bromo-4-
chloro-3-methylbenzo[b]thiophene are much more difficult
to react with imidazole (Table 3, entry 13) probably because
the methyl group on 3-position hinder the co-planarity of the
imidazole and the thiophene moieties, which gives a negative
N
CuI/L-Proline
110°C
S
S
Br
N
+
K2CO3
Solvent
N
H
N
Entry
Solvent
Yield (%)b
1
2
3
[Bmim]BF4
DMF
DMSO
76
66
71
a
Reaction conditions: CuI (0.9 mmol), K2CO3 (5.4 mmol), L-proline
(1.8 mmol), benzimidazole (3 mmol), 2-bromothiophene (5.4 mmol), at
110 ꢀC, Solvent (3 ml), 24 h.
b
Isolated yields.

X. Lv et al. / Tetrahedron 62 (2006) 4756–4761
4759
3. Conclusions
4.2.3. 1-(Thiophen-2-yl)-1H-benz[d]imidazole. Table 3,
entry 3, yield 76%. Viscous oil. 1H NMR (400 MHz,
CDCl3) d 7.07–7.09 (dd, J¼3.9, 5.5 Hz, 1H), 7.12–7.14
(dd, J¼1.4, 3.9 Hz, 1H), 7.26–7.28 (dd, J¼1.4, 5.5 Hz,
1H), 7.32–7.36 (m, 2H), 7.53–7.56 (m, 1H), 7.83–7.87 (m,
1H), 8.06 (s, 1H); 13C NMR (100 MHz, CDCl3) d 110.75,
120.76, 122.06, 123.40, 123.61, 124.33, 126.63, 143.87,
137.23, 143.36, 143.75; IR: 3077, 2925, 2860, 1611, 1550,
1488, 1327, 1231, 1196, 743, 699 cmꢂ1; HRMS (ESI) calcd
for C11H8N2SNa (M+Na)+, 223.0306; found: (M+Na)+,
223.0305.
In summary, we have developed an efficient and mild
method to synthesize N-arylimidazoles/N-heteroarylimidaz-
oles by Ullmann coupling strategy, in which ionic liquid was
used as a favorable solvent. The procedure is simple and can
be carried out under mild conditions, using comparatively
cheap CuI as the catalyst and natural amino acid as the
ligand. The conveniently recoverable and reusable catalytic
system makes the methodology environmentally benign and
economical.
4. Experimental
4.2.4. 2-(1H-Imidazol-1-yl) pyridine.15c,17 Table 3, entry 4,
17
1
ꢀ
ꢀ
yield 81%. Mp 38–40 C (lit. mp 38–40 C). H NMR
(400 MHz, CDCl3) d 7.12 (s, 1H), 7.29–7.32 (dd, J¼5.0,
7.4 Hz, 1H), 7.76–7.78 (d, J¼8.0 Hz, 1H), 7.92–7.96 (m,
2H), 8.44–8.46 (m, 1H), 8.54 (s, 1H); IR (KBr): 3078,
2926, 2865, 1611, 1601, 1488, 1328, 1231, 1196, 770,
4.1. General information
All reagents and solvents used were analytical grade mate-
rials purchased from commercial sources and were used
without further purification, if not stated otherwise. All the
NMR spectra were recorded in CDCl3 on a Bruker AMX-
400 (400 MHz) instrument with TMS as internal standard.
IR spectra were taken as liquid film or KBr plates. TLC
was carried out with 0.2 mm silica gel plates (GF254). Visu-
alization was accomplished by UV light or I2 staining. The
columns were hand packed with silica gel 60 (200–300
mesh). All reactions were carried out under atmosphere, if
not stated otherwise. The ionic liquid, [Bmimꢀ]BF4, was de-
humidified in vacuo by heating at about 110 C for 30 min
650 cmꢂ1
.
4.2.5. 1-(Pyridin-2-yl)-1H-benz[d]imidazole.15a,b Table 3,
18
1
ꢀ
ꢀ
entry 5, yield 87%. Mp 59–60 C (lit. mp 59–60 C). H
NMR (400 MHz, CDCl3) d 7.20–7.24 (m, 1H), 7.31–7.37
(m, 2H), 7.46–7.51 (m, 1H), 7.77–7.86 (m, 2H), 8.02–8.04
(m, 1H), 8.55 (s, 2H); IR (KBr): 3060, 3028, 2927, 2850,
1588, 1478, 1462, 1327, 1235, 1204, 773, 742 cmꢂ1
.
4.2.6. 2-(2-Methyl-1H-imidazol-1-yl) pyridine. Table 3,
entry 6, yield 71%. Viscous oil. 1H NMR (400 MHz,
CDCl3) d 2.55 (s, 3H), 6.98 (d, J¼1.0 Hz, 1H), 7.24 (d,
J¼1.0 Hz, 1H), 7.25–7.27 (m, 2H), 7.78–7.83 (td, J¼2.0,
8.0 Hz, 1H), 8.50–8.52 (d, J¼4.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 15.16, 117.13, 118.86, 122.26,
127.74, 138.58, 144.83, 149.06, 150.58; IR: 3101, 2931,
2860, 1588, 1499, 1475, 1442, 1312, 1283, 787, 741,
677 cmꢂ1; HRMS (ESI) calcd for C9H10N3 (M+H)+,
160.0875; found: (M+H)+, 160.0869.
prior to use. All products were confirmed by 1H NMR, 13
C
NMR, IR, and elemental/HRMS analysis (excepting the
known compounds and the N-arylimidazoles).
4.2. General procedure for N-heteroarylation/N-aryla-
tion of imidazoles under the catalysis of CuI and
a-amino acid in RTIL
4.2.1. Synthesis of 1-(thiophen-2-yl)-1H-imidazole in
[Bmim]BF4. Table 3, entry 1. CuI (1.71 g, 0.9 mmol), L-pro-
line (0.207 g, 1.8 mmol), K2CO3 (0.745 g, 5.4 mmol) and
dry [Bmim]BF4 (3.00 ml) were added to a 10 ml flask.
Stirred ꢀand humidified in vacuo by heating in an oil bath
at 110 C for 0.5 h. Imidazole (0.204 g, 3 mmol) was add
to the stirred mixture, then bromothiophene (0.880 g,
5.4 mmol, 1.8 equiv) was added by a syringe into the flask
(sealed). The reaction was monitored by TLC. After the re-
action was completed, the resulting mixture was cooled to
room temperature and was extracted by Et2O/EtOAc (v/v¼
4/1, 3ꢁ5 ml). The extracts were combined and washed by
water (2ꢁ10 ml), brine (15 ml), and dried (MgSO4). Evapo-
rating the solvent under reduced pressure gave a dark brown
oil, which was further purified by column chromatography
(v/v¼4/1, Et2O/EtOAc) to afford an viscous oil (0.316 g,
4.2.7. 1-(Thiophen-3-ylꢀ)-1H-imidazole. Table 3, entry 7,
yield 72%. Mp 82–83 C. 1H NMR (400 MHz, CDCl3)
d 7.14 (d, J¼1.2 Hz, 1H), 7.16 (d, J¼1.6 Hz, 1H), 7.18–
7.19 (dd, J¼1.2, 2.8 Hz, 1H), 7.21 (s, 1H), 7.39–7.41 (dd,
J¼2.8, 5.4 Hz, 1H), 7.79 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 113.19, 116.50, 121.37, 127.12, 129.87, 135.81,
136.14; IR (KBr): 3110, 2928, 2858, 1555, 1494, 1337,
1247, 856, 777, 736, 658 cmꢂ1; Anal. Calcd for C7H6N2S:
C 55.97, H 4.03, N 18.65; found: C 56.08, H 4.03, N 18.68.
4.2.8. 1-(Thiophen-3-yl)-1H-benz[d]imidazole.19 Table 3,
1
ꢀ
entry 8, yield 75%. Mp 90–91 C. H NMR (400 MHz,
CDCl3) d 7.23–7.25 (dd, J¼1.6, 5.2 Hz, 1H), 7.28–7.32
(m, 2H), 7.33–7.35 (dd, J¼1.6, 2.8 Hz, 1H), 7.46–7.48
(dd, J¼3.2, 5.2 Hz, 1H), 7.49–7.53 (m, 1H), 8.07 (s, 1H),
7.83–7.88 (m, 1H); IR (KBr): 3106, 2963, 2858, 1548,
74%). The H NMR is in accordance with literature.15,16
1
1H NMR (400 MHz, CDCl3) d 6.92–6.95 (m, 2H), 7.07–
7.10 (m, 1H), 7.11 (s, 1H), 7.14 (s, 1H), 7.72 (s, 1H); IR:
3079, 2920, 2858, 1611, 1565, 1502, 1450, 1331, 1228,
1491, 1226, 1194, 855, 789, 744, 642 cmꢂ1
.
1197, 1046, 800, 743 cmꢂ1
.
4.2.9. 2-Methyl-1-(thiophen-2-yl)-1H-imidazole. Table 3,
entry 9, yield 62%. Viscous oil. 1H NMR (400 MHz,
CDCl3) d 2.37 (s, 3H), 6.95–6.96 (dd, J¼1.6, 4.0 Hz, 1H),
6.98–6.99 (d, J¼1.6 Hz, 1H), 7.00–7.02 (m, 2H), 7.23–
7.26 (dd, J¼1.2, 5.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 13.32, 121.92, 123.16, 123.76, 125.84, 127.68,
138.60, 145.94; IR: 3107, 2927, 2850, 1553, 1496, 1451,
4.2.2. 2,5-Di(1H-imidazol-1-yl)thiophene. Table 3, entry 2,
16
1
ꢀ
ꢀ
yield 77%. Mp 71–72 C (lit. mp 71–72 C). H NMR
(400 MHz, CDCl3) d 6.92 (s, 2H), 7.18–7.19 (m, 4H), 7.75
(s, 2H); IR (KBr): 3103, 2925, 2870, 1649, 1575, 1481,
1310, 1251, 1047, 844, 808, 749 cmꢂ1
.

4760
X. Lv et al. / Tetrahedron 62 (2006) 4756–4761
1289, 984, 845, 703 cmꢂ1; HRMS (ESI) calcd for C8H9N2S
(M+H)+ 165.0486; found: (M+H)+, 165.0481.
(m, 1H), 7.18 (s, 1H), 7.19–7.21 (d, J¼8.0 Hz, 1H), 7.23
(s, 1H), 7.82 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 19.25, 19.84, 118.33, 118.75, 122.61, 129.71, 130.66,
135.02, 135.48, 136.11, 138.33; IR: 3113, 2922, 2850,
4.2.10. 1-(5-Methylthiophen-2-yl)-1H-benz[d]imidazole.
Table 3, entry 10, yield 73%. Viscous oil. 1H NMR
(400 MHz, CDCl3) d 2.52 (s, 3H), 6.72–6.73 (d, J¼3.6 Hz,
1H), 6.91–6.92 (d, J¼3.6 Hz, 1H), 7.31–7.36 (m, 2H),
7.51–7.55 (m, 1H), 7.82–7.87 (m, 1H), 8.02 (s, 1H); 13C
NMR (100 MHz, CDCl3) d 15.40, 110.37, 120.27, 121.96,
122.84, 123.78, 123.94, 133.80, 134.62, 138.06, 143.05,
143.27; IR: 3079, 2921, 2857, 1651, 1612, 1503, 1451,
1283, 919, 882, 800, 743, 676 cmꢂ1; HRMS (ESI) calcd
for C12H11N2S (M+H)+ 215.0643; found: (M+H)+,
215.0637.
2363, 1623, 1513, 1310, 814, 734 cmꢂ1
.
4.2.17. 1-(4-Chlorophenyl)-1H-imidazole.23 Table 3, entry
23a
1
ꢀ
ꢀ
17, yield 80%. Mp 84–86 C (lit. mp 85–87 C). H NMR
(400 MHz, d6-DMSO) d 7.13 (s, 1H), 7.58–7.60 (td, J¼2.0,
8.0 Hz, 2H), 7.70–7.72 (td, J¼2.0, 8.0 Hz, 2H), 7.78 (s, 1H),
8.30 (s, 1H). IR (KBr): 3110, 2926, 2854, 1635, 1508, 1303,
830 cmꢂ1
.
4.2.18. 1-(4-Nitrophenyl)-1H-imidazole.15c,20 Table 3,
20
ꢀ
entry 18, yield 62%. Mp 203–205 C (lit. mp 204.4–
1
ꢀ
4.2.11. 1-(5-Methylthiophen-2-yl)-1H-imidazole. Table 3,
entry 11, yield 68%. Viscous oil. 1H NMR (400 MHz,
CDCl3) d 2.50 (s, 3H), 6.64–6.65 (m, 1H), 6.79–6.80 (d,
J¼3.6 Hz, 1H), 7.16 (s, 2H), 7.72 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 15.30, 119.00, 120.21, 123.87,
129.80, 136.00, 136.54, 136.97; IR: 3112, 2921, 2859,
1644, 1568, 1510, 1474, 1302, 1215, 1038, 909, 801, 733,
657 cmꢂ1; HRMS (ESI) calcd for C8H9N2S (M+H)+
165.0486; found: (M+H)+, 165.0481.
205.2 C). H NMR (400 MHz, CDCl3) d 7.31–7.32 (m,
1H), 7.43 (s, 1H), 7.73–7.78 (t, J¼8.0 Hz, 1H), 7.81–7.83
(d, J¼8.0 Hz, 1H), 8.04 (s, 1H), 8.28–8.30 (d, J¼8.0 Hz,
1H), 8.33 (s, 1H); IR (KBr): 3100, 2924, 2853, 2363,
1621, 1529, 1358, 812 cmꢂ1
.
4.2.19. 1-(6-Methoxynaphthalen-2-yl)-1H-imidazole.24
24
ꢀ
85 C). H NMR (400 MHz, CDCl3) d 3.94 (s, 3H), 7.17
Table 3, entry 19, yield 85%. Mp 84–85 C (lit. mp
ꢀ
1
(d, J¼2.0 Hz, 1H), 7.22–7.25 (m, 2H), 7.36 (s, 1H), 7.46–
7.48 (dd, J¼2.0, 8.5 Hz, 1H), 7.73–7.74 (m, 1H), 7.75–
7.77 (m, 1H), 7.82–7.84 (d, J¼8.5 Hz, 1H), 7.93 (s, 1H);
IR (KBr): 3110, 2931, 2849, 2361, 1606, 1513, 1246,
4.2.12. 2-Methyl-1-(5-methylthiophen-2-yl)-1H-imidaz-
1
ꢀ
ole. Table 3, entry 12, yield 46%. Mp 40–41 C. H NMR
(400 MHz, CDCl3) d 2.33 (s, 3H), 2.45 (s, 3H), 6.61–6.62
(d, J¼3.6 Hz, 1H), 6.70–6.71 (d, J¼4.0 Hz, 1H), 6.94 (s,
2H); 13C NMR (100 MHz, CDCl3) d 13.33, 15.46, 122.08,
123.44, 123.72, 127.48, 135.72, 138.62, 146.25; IR: 3110,
2923, 2858, 1566, 1531, 1502, 1446, 1408, 1291, 1221,
1168, 1134, 985, 931, 802, 731, 671 cmꢂ1; Anal. Calcd for
C9H10N2S: C 60.64, H 5.65, N 15.72; found: C 60.74, H
5.80, N 15.70.
852 cmꢂ1
.
Acknowledgment
This work was financially supported by the Natural Science
Foundation of China (No. 20225309).
References and notes
4.2.13. 1-(4-Chloro-3-methylbenzo[b]thiophen-2-yl)-1H-
imidazole. Table 3, entry 13, yield 19%. Yellow needles.
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ꢀ
Mp 111–112 C. H NMR (400 MHz, CDCl3) d 2.29 (s,
3H), 7.19 (s, 1H), 7.25 (s, 1H), 7.37–7.40 (dd, J¼2.0,
8.4 Hz, 1H), 7.68–7.71 (m, 2H), 7.74 (s, 1H); 13C NMR
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20
82%. Mp 45–47 C (lit. mp 45–48 C). 1H NMR
(400 MHz, CDCl3) d 2.37 (s, 3H), 7.16–7.22 (m, 1H), 7.24
(s, 5H), 7.80 (s, 1H); IR (KBr): 3112, 2922, 2855, 1651,
ꢀ
ꢀ
1522, 815 cmꢂ1
.
4.2.15. 1-m-Tolyl-1H-imidazole.22 Table 3, entry 15, yield
75%. H NMR (400 MHz, CDCl3) d 2.40 (s, 3H), 7.15–
1
7.18 (m, 4H), 7.25 (s, 1H), 7.31–7.35 (m, 1H), 7.82 (s,
1H); IR: 3113, 2920, 2860, 1611, 1504, 1365, 785.13,
734.6, 691.2 cmꢂ1
.
4.2.16. 1-(3,4-Dimethylphenyl)-1H-imidazole. Table 3,
entry 16, yield 70%. H NMR (400 MHz, CDCl3) d 2.29
1
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