Mild conditions for copper-catalyzed N-arylation of imidazoles

Article abstract of DOI:10.1055/s-0029-1218691

An efficient copper(I) bromide catalyzed N-arylation of azoles with a variety of aromatic bromides and iodides under mild conditions is reported. This reaction displayed great functional group compatibility and excellent reactive selectivity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218691

PAPER
1505
Mild Conditions for Copper-Catalyzed N-Arylation of Imidazoles
C
opper-Catalyzed
u
N
-Arylation
a
of Imidazo
m
les ing Chen,a Deping Wang,b,c Xianyang Wang,d Wenlong Huang,*a Qian Cai,b Ke Ding*b
a
China Pharmaceutical University, # 24 Tongjiaxiang, Nanjing 210009, P. R. of China
E-mail: ydhuangwenlong@126.com
Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health,
Chinese Academy of Sciences, Guangzhou International Business Incubator D-10,
Guangzhou Science Park, Guangzhou 510663, P. R. of China
b
Fax +86(20)32290606.; E-mail: ding_ke@gibh.ac.cn
Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, 19AYuquan Road, Beijing 100049, P. R. of China
Jiangsu Provincial Institute of Materia Medica, Nanjing University of Technology, 5 Xinmofan Road, Nanjing 210009, P. R. of China
c
d
Received 7 December 2009; revised 12 January 2010
Abstract: An efficient copper(I) bromide catalyzed N-arylation of
azoles with a variety of aromatic bromides and iodides under mild
conditions is reported. This reaction displayed great functional
group compatibility and excellent reactive selectivity.
Table 1 Optimization of the Reaction Conditions for the N-Aryla-
tion of 1H-Imidazole (2a) with Iodobenzene (1a)a
N
N
I
N
[Cu], ligand
Key words: copper, aryl halides, imidazoles, azoles, N-arylation
+
N
base, solvent
60 °C, 5 h
H
1a
2a
3a
N-Arylimidazoles represent an attractive class of chemi-
cals that are widely used in the preparation of agrochemi-
cals, pharmaceuticals, biological active compounds, and
N-heterocyclic carbene chemistry.1,2 Classical synthetic
methods for these compounds included nucleophilic aro-
matic substitution of active aryl halides with imidazole
and Ullmann-type coupling reactions etc.3 However, these
methods suffer from several drawbacks such as harsh re-
action conditions (>200 °C) and/or the use of stoichiomet-
ric amounts of copper.4 Much progress has been achieved
over the last few decades in copper-catalyzed C–N bond
formation.3 Employing different mono- and bidentate
chelators as effective ancillary ligands, N-arylimidazoles
were successfully produced under lower temperatures
(100–150 °C) in 24–40 hours.5 Most recently, a ligand-
free N-arylation of imidazoles from aryl iodides was also
reported at 35–40 °C in 40 hours.6 Nevertheless, a new
strategy for the assembly of N-arylimidazoles under mild
conditions, especially at lower temperatures and with
shorter reaction times, remains highly desirable.
N
O
N
O
ligand:
L1
L2
Entry
Base
Solvent
[Cu]
Yield (%)
<10b
<10
50c
95
1
2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
MeCN
i-PrOH
H2O
CuBr
–
3
CuBr
CuBr
CuBr
CuI
4
5
85d
95
6
7
CuCl
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
66
8
17
9
11
Recently, we identified pyridin-2-yl b-ketones as new ef-
ficient supporting ligands for copper-catalyzed coupling
reactions of aliphatic amines, ammonia, and phenols with
aryl halides under mild conditions.7 Herein we report the
efficient N-arylation of azoles with a variety of aromatic
bromides and iodides under the catalysis of a combination
of copper(I) bromide/pyridin-2-yl b-ketone.
10
11
12
13
14
15
0
DMF
93
Na2CO3
K2CO3
NaOH
Et3N
DMSO
DMSO
DMSO
DMSO
65
38
85
Initially, we chose the coupling of iodobenzene (1a) with
1H-imidazole (2a) as a model to optimize the reaction
conditions. As shown in Table 1, the yield of 3a was poor,
less than 10%, when the reaction was carried out in the ab-
8
a Reaction conditions: PhI (1a, 1.0 mmol), 1H-imidazole (2a, 1.2
mmol), [Cu] (5 mmol%), L1 (10 mmol%) (unless otherwise noted),
base (2.0 mmol), solvent (1.0 mL), 60 °C, N2, 5 h.
b Without ligand.
c L1 (5 mmol%) was used.
SYNTHESIS 2010, No. 9, pp 1505–1511
x
x
.
x
x
.2
0
1
0
d L2 (10 mmol%) was used.
Advanced online publication: 09.03.2010
DOI: 10.1055/s-0029-1218691; Art ID: F22909SS
© Georg Thieme Verlag Stuttgart · New York

1506
H. Chen et al.
PAPER
sence of ligand or copper at 60 °C (Table 1, entries 1 and logue, 1-pyridin-2-ylpropan-2-one (L2), also successfully
2). However, when 5 mmol% copper(I) bromide and promoted the coupling reaction with a slightly lower yield
5 mmol% 1-(5,6,7,8-tetrahydroquinolin-8-yl)ethanone (Table 1, entry 5). Other conditions, such as copper
(L1) were employed, 3a was produced in moderate yield sources, solvents, and bases, were also screened. The re-
(Table 1, entry 3). The isolated yield of 3a improved sig- sults indicated that optimal combination of 5 mmol% cop-
nificantly (~95%) when 10 mmol% of supporting ligand per(I) bromide, 10 mmol% L1, and 2.0 equivalents of
L1 was utilized. The results also revealed that the simplest cesium carbonate in dimethyl sulfoxide (1.0 mL).
and commercially available pyridin-2-yl b-ketone ana-
Table 2 Copper(I) Bromide/L1-Catalyzed N-Arylation of 1H-Imidazole (2a) with Aryl and Heteroaryl Halides 1a
CuBr/L1
Cs2CO3, DMSO
N
O
N
N
N
ArX
+
Ar
60 °C, 5 h
N
L1
H
1
2a
3
Entry
Ar-X
Product
Yield (%)
83
N
1
2
3b
I
N
OMe
OMe
I
3c
78
N
N
N
3
4
5
3d
3e
3a
91
89
86
Br
N
Br
I
N
I
N
N
N
Br
N
N
6
3f
82
Br
MeO
MeO
MeO
MeO
7
8
3g
3h
80
82
N
N
Br
N
Br
N
N
O
Br
O
N
9
3i
3j
86
95
F
F
F3C
F3C
10
N
Cl
Br
Cl
N
H2N
H2N
86b
N
11
3k
Br
N
F3C
F3C
O
N
12
13
3l
92
88
Br
N
O
N
3m
NC
Br
N
NC
Synthesis 2010, No. 9, 1505–1511 © Thieme Stuttgart · New York

PAPER
Copper-Catalyzed N-Arylation of Imidazoles
1507
Table 2 Copper(I) Bromide/L1-Catalyzed N-Arylation of 1H-Imidazole (2a) with Aryl and Heteroaryl Halides 1a (continued)
CuBr/L1
Cs2CO3, DMSO
N
O
N
N
N
ArX
+
Ar
60 °C, 5 h
N
L1
H
1
2a
3
Entry
Ar-X
Product
Yield (%)
72b
N
14
15
16
3n
HO
Br
N
HO
N
3o
3p
81b
80b
H2N
Br
N
H2N
N
Br
N
HO
HO
Br
N
17
18
19
3q
3a
3r
92
0
N
N
N
Cl
N
N
N
N
78
O
O
Br
N
N
N
N
N
N
N
20
21
22
3s
3t
76
77
80
Cl
Cl
Br
N
Br
N
N
N
N
N
3u
MeO
Br
MeO
N
N
N
N
Br
N
23
24
3v
73
N
N
N
N
3w
75c
Br
Br
N
N
N
N
a Reaction conditions: Ar-X 1 (1.0 mmol), 1H-imidazole (2a, 1.2 mmol), CuBr (5 mmol%), L1 (10 mmol%), Cs2CO3 (2.0 mmol), DMSO (1.0
mL), 60 °C, N2, 5 h.
b 120 °C, 12 h.
c Performed with 2.0 mmol of imidazole.
The scope of the copper(I) bromide/L1-catalyzed N-ary- coupling reactions were also successfully performed us-
lation of 1H-imidazole (2a) was explored by using a vari- ing electron-rich substrates, such as 3-bromotoluene, 3-
ety of aryl iodides and aryl bromides 1 under the bromoanisole, and 4-bromoanisole, giving 3f–h in good
optimized conditions. As summarized in Table 2, the re- yields (Table 2, entries 6–8). Furthermore, the copper(I)
sults showed that all the tested aryl iodides coupled with bromide/L1 system was well tolerated by multiple func-
1H-imidazole (2a) to afford the desired products 3b–e tional groups such as ketones, nitriles, free amines, and
with satisfactory yields (entries 1–4). For aryl bromides, free hydroxy groups (Table 2, entries 11–16). Although
the catalyst system efficiently promoted the coupling re- this protocol did not work well for electron-rich aryl chlo-
actions in most cases. The results also indicated that elec- rides (i.e., chlorobenzene, Table 2, entry 18) even if the
tron-withdrawing groups in the aryl bromide substrates reactions were carried out at high temperatures (120 °C)
benefited the coupling reaction to give the products 3j,l,m with longer reaction time, the catalyst system significantly
in excellent yields (Table 2, entries 10, 12, and 13). The improved the reaction efficiency of electron-deficient aryl
Synthesis 2010, No. 9, 1505–1511 © Thieme Stuttgart · New York

1508
H. Chen et al.
PAPER
chlorides with 1H-imidazole (2a). For example, coupling The N-arylation of imidazole with various halopyridines
of 1-chloro-4-nitrobenzene with 1H-imidazole (2a) at 100 and halopyrimidines was also performed with great suc-
°C in the absence of L1 gave 1-(4-nitrophenyl)-1H-imida- cess. Almost all the halopyridines and halopyrimidines
zole in only 41% yield, but addition of 10% L1 at 100 °C coupled with 1H-imidazole (2a) to give 3r–w in excellent
gave the product in a dramatically improved 81% yield or good yields under the optimized conditions (Table 2,
(results not shown). Utilizing 4-chlorobenzonitrile as the entries 19–24). In addition, the double-coupling product
substrate with 1H-imidazole (2a) gave 3m in 75% isolated 3w was obtained when 2,5-dibromopyridine was reacted
yield (results not shown).
with 1H-imidazole (2a) (Table 2, entry 24).
To further expand the scope of this methodology, the cat-
alytic system was applied to other nitrogen-containing
heterocycles 2. We were pleased to find that most of
azoles 2 coupled with aryl halides 1 to afford the corre-
sponding products 4 in good yields (Table 3), but that
slightly higher reaction temperatures (80 °C) and longer
reaction times (12 h) were required. It should be noted that
sterically hindered 2-methyl-1H-imidazole and 2-propyl-
1H-imidazole gave the desired coupling products 4d,e,h
in good yields (Table 3, entries 4, 5, and 8). Aryl bromides
bearing a free amino group could successfully undergo se-
lective N-arylation of 4-methyl-1H-imidazole and 4-
methyl-1H-pyrazole to assemble the corresponding prod-
ucts 4f,g in 81% and 88% yields, respectively (Table 3,
entries 6 and 7). In addition, excellent N1 regioselectivity
(19:1) for the coupling of 4-methyl-1H-imidazole was ob-
served (Table 3, entry 6).
Table 3 Copper(I) Bromide/L1-Catalyzed N-Arylation of Azoles
with Aryl Halidesa
N
O
CuBr/L1
Cs2CO3, DMSO
+ Het-NH
X
Ar N-Het
Ar
L1:
80 °C, 12 h
1
2
4
Entry Ar-X
Product
Yield
(%)
N
1
2
4a
4b
83b
83b
N
I
N
N
I
Ph
N
N
N
3
4c
N
86
78
NC
Br
In summary, we have successfully developed an efficient
copper(I) bromide/L1 catalyst system for the N-arylation
of azoles with a variety of aromatic bromides and iodides.
Employing this catalytic system, N-arylazoles can be syn-
thesized under much milder conditions (60–80 °C, 5–12
h). Also, this new protocol displays great functional
groups compatibility and excellent reactive selectivity.
Our effort may provide an attractive addition to the
copper-catalyzed synthesis of N-arylazoles.
NC
4
5
4d
N
N
Br
Br
N
N
4e
4f
65
H2N
H2N
All reactions were carried out in 5-mL sealed tubes, under a pure
and dry argon atmosphere. Solvents, base and all other materials
were used commercially without further purification. L1, L2 were
prepared as previously described.7a All new compounds are indicat-
ed as such: 3i, 3j, 3k, 3r, 3s, 3v, 3w, 4e, 4g, 4h; for all known com-
pounds, adequate characterization was obtained by 1H NMR
spectroscopy and mass spectrometry. NMR spectra were recorded
at 20 °C on a 300 or 400 MHz spectrometer working respectively at
300 or 400 MHz for 1H, at 75 or 100 MHz for 13C.
6
81c,d
Br
Br
N
N
F3C
H2N
F3C
H2N
7
4g
88c
N
N
F3C
F3C
Arylazoles 3 and 4; General Procedure
O
A sealed tube equipped with a Teflon valve was charged with a
magnetic stir bar, CuBr (7 mg, 0.05 mmol, 5 mol%), Cs2CO3 (650
mg, 2 mmol) and any remaining solids (azoles 2 and/or aryl halides
1). The tube was evacuated and backfilled with N2 (3 ×). Under a
counter flow of N2, azole 2 (1.2 mmol, if liquid), aryl halide 1 (1
mmol, if liquid), DMSO (1.0 mL), and L1 (18 mg, 0.10 mmol, 10
mol%) were added by syringe. The tube was evacuated and again
backfilled with N2 (3 ×) and sealed. The mixture was heated to the
indicated temperature for the required time period. After cooling to
r.t., the mixture was diluted with EtOAc (25 mL), passed through a
fritted glass filter to remove the inorganic salts and the filtrate was
washed by H2O, brine, then removed under vacuum. The residue
was purified by column chromatography (silica gel) and the product
was dried under high vacuum (at least 1 h).
Br
F
8
4h
78
F
N
O
N
a Reaction conditions: Ar-X 1 (1.0 mmol), Het-NH 2 (1.2 mmol),
CuBr (5 mmol%), L1 (10 mmol%), Cs2CO3 (2.0 mmol), DMSO (1.0
mL), 80 °C, N2, 12 h.
b 60 °C.
c 120 °C.
d The regioselectivity (19:1) was determined by GC-MS analysis and
the major pure product was isolated by recrystallization.
Synthesis 2010, No. 9, 1505–1511 © Thieme Stuttgart · New York

PAPER
Copper-Catalyzed N-Arylation of Imidazoles
1509
1-Phenyl-1H-imidazole (3a)5e
HRMS (EI): m/z [M]+ calcd for C10H7ClF3N2: 247.0244; found:
247.0240.
1H NMR (300 MHz, DMSO-d6): d = 8.28 (s, 1 H), 7.76 (t, 1 H), 7.67
(q, J = 5.8 Hz, 2 H), 7.53 (t, 2 H), 7.37 (t, 1 H), 7.14 (s, 1 H).
3-(1H-Imidazol-1-yl)-5-(trifluoromethyl)aniline (3k)
MS: m/z = 144.
1H NMR (300 MHz, DMSO-d6): d = 8.20 (br, 1 H), 7.72 (br, 1 H),
7.10 (s, 1 H), 7.01 (s, 1 H), 6.97 (s, 1 H), 6.84 (s, 1 H), 5.89 (s, 2 H).
1-(4-Tolyl)-1H-imidazole (3b)5t
1H NMR (300 MHz, CDCl3): d = 8.19 (s, 1 H), 7.69 (s, 1 H), 7.52
(d, J = 6.8 Hz, 2 H), 7.31 (d, J = 7.2 Hz, 2 H), 7.09 (s, 1 H), 2.34 (s,
3 H).
MS: m/z = 227.
HRMS (EI): m/z [M + H]+ calcd for C10H7ClF3N2: 228.0743; found:
228.0748.
MS: m/z = 158.
1-[4-(1H-Imidazol-1-yl)phenyl]ethanone (3l)5t
1H NMR (300 MHz, DMSO-d6): d = 8.48 (s, 1 H), 8.15 (d, J = 8.8
Hz, 2 H), 7.94 (s, 1 H), 7.90 (d, J = 8.8 Hz, 2 H), 7.22 (s, 1 H), 2.67
(s, 3 H).
1-(2-Methoxyphenyl)-1H-imidazole (3c)6
1H NMR (300 MHz, CDCl3): d = 7.89 (s, 1 H), 7.40 (t, J = 7.5 Hz,
3 H), 7.25 (d, J = 8.5 Hz, 1 H), 7.07 (t, J = 7.5 Hz, 2 H), 3.82 (s, 3
H).
MS: m/z = 186.
MS: m/z = 174.
4-(1H-Imidazol-1-yl)benzonitrile (3m)5t
1-(4-Bromophenyl)-1H-imidazole (3d)5e
1H NMR (400 MHz, DMSO-d6): d = 8.43 (s, 1 H), 7.97 (d, J = 8.8
Hz, 2 H), 7.88 (d, J = 8.8 Hz, 3 H), 7.15 (s, 1 H).
1H NMR (300 MHz, CDCl3): d = 8.28 (s, 1 H), 7.84 (s, 1 H), 7.72
(d, J = 9.0 Hz, 2 H), 7.63 (d, J = 9.0 Hz, 2 H), 7.11 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): d = 140.57, 136.25, 134.67,
130.99, 120.95, 118.81, 118.21, 109.53.
MS: m/z = 223.
MS: m/z = 169.
1-Biphenyl-4-yl-1H-imidazole (3e)5i
1H NMR (300 MHz, CDCl3): d = 8.33 (s, 1 H), 7.81 (m, 3 H), 7.74
(m, 4 H), 7.49 (m, 2 H), 7.39 (t, J = 7.3 Hz, 1 H), 7.13 (s, 1 H).
4-(1H-Imidazol-1-yl)phenol (3n)5t
1H NMR (400 MHz, DMSO-d6): d = 9.81 (br, 1 H), 8.15 (s, 1 H),
7.60 (s, 1 H), 7.39 (d, J = 8.8 Hz, 2 H), 7.11 (s, 1 H), 6.85 (d, J = 8.8
Hz, 2 H).
MS: m/z = 220.
1-(3-Tolyl)-1H-imidazole (3f)5r
13C NMR (100 MHz, DMSO-d6): d = 157.03, 143.02, 129.24,
129.06, 122.86, 119.21, 116.57.
1H NMR (300 MHz, CDCl3): d = 8.23 (s, 1 H), 7.73 (s, 1 H), 7.49
(s, 1 H), 7.39 (t, 2 H), 7.18 (t, J = 7.0 Hz, 1 H), 7.10 (s, 1 H), 2.38
(s, 3 H).
MS: m/z = 160.
MS: m/z = 158.
4-(1H-Imidazol-1-yl)aniline (3o)5t
1H NMR (400 MHz, DMSO-d6): d = 7.95 (br, 1 H), 7.47 (s, 1 H),
7.23–7.19 (m, 2 H), 7.01 (s, 1 H), 6.67–6.63 (m, 2 H), 5.24 (br, 2 H).
1-(3-Methoxyphenyl)-1H-imidazole (3g)5r
1H NMR (300 MHz, CDCl3): d = 8.29 (s, 1 H), 7.77 (s, 1 H), 7.42
(t, J = 8.5 Hz, 1 H), 7.22 (t, 2 H), 7.11 (s, 1 H), 6.94 (q, 1 H), 3.84
(s, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 148.42, 135.81, 129.47,
126.72, 122.45, 118.90, 114.73.
MS: m/z = 159.
MS: m/z = 174.
[4-(1H-Imidazol-1-yl)phenyl]methanol (3p)6
1-(4-Methoxyphenyl)-1H-imidazole (3h)6
1H NMR (400 MHz, DMSO-d6): d = 8.21 (s, 1 H), 7.70 (s, 1 H), 7.57
(d, J = 8.8 Hz, 2 H), 7.42 (d, J = 8.4 Hz, 2 H), 7.09 (s, 1 H), 5.32 (t,
J = 6.0 Hz, 1 H), 4.52 (d, J = 6.0 Hz, 2 H).
1H NMR (300 MHz, DMSO-d6): d = 8.12 (s, 1 H), 7.64 (s, 1 H), 7.55
(d, J = 8.8 Hz, 2 H), 7.06 (d, J = 8.8 Hz, 3 H), 3.80 (s, 3 H).
MS: m/z = 174.
13C NMR (100 MHz, DMSO-d6): d = 141.74, 135.95, 135.90,
130.17, 128.24, 120.55, 118.52, 115.48, 62.71.
1-[3-(4-Fluorophenoxy)phenyl]-1H-imidazole (3i)
1H NMR (300 MHz, DMSO-d6): d = 8.30 (s, 1 H), 7.78 (s, 1 H), 7.45
(m, 3 H), 7.28 (m, 2 H), 7.15 (m, 2 H), 7.10 (s, 1 H), 6.88 (t, 1 H).
MS: m/z = 174.
1-Naphthalen-1-yl-1H-imidazole (3q)5e
1H NMR (300 MHz, DMSO-d6): d = 8.15 (d, 2 H), 8.00 (s, 1 H),
7.66 (m, 1 H), 7.60 (m, 2 H), 7.56 (m, 2 H), 7.50 (m, 1 H), 7.20 (s,
1 H).
13C NMR (75 MHz, CDCl3): d = 161.0, 159.2, 157.8, 151.7, 138.6,
135.5, 131.0, 130.4, 123.4, 121.3, 121.2, 120.3, 118.1, 116.8, 116.5,
116.4, 115.6, 114.9, 111.0.
MS: m/z = 254.
MS: m/z = 194.
HRMS (EI): m/z [M + H]+ calcd for C15H12FN2O: 255.0928; found:
255.0936.
4-{[5-(1H-Imidazol-1-yl)pyridin-2-yl]methyl}morpholine (3r)
1H NMR (300 MHz, DMSO-d6): d = 8.85 (d, 1 H), 8.31 (s, 1 H),
8.07 (dd, J = 7.2, 3.6 Hz, 1 H), 7.81 (s, 1 H), 7.60 (m, 1 H), 7.15 (s,
1 H), 3.64 (s, 2 H), 3.60 (m, 4 H), 2.45 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 157.8, 142.2, 135.5, 132.6, 130.9,
129.4, 123.8, 118.1, 66.8, 64.2, 53.7.
1-[4-Chloro-3-(trifluoromethyl)phenyl]-1H-imidazole (3j)
1H NMR (300 MHz, DMSO-d6): d = 8.42 (s, 1 H), 8.12 (d, 1 H),
8.02 (m, 1 H), 7.90 (m, 2 H), 7.15 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 136.0, 135.5, 133.1, 131.4, 131.2,
130.4, 127.5, 125.4, 123.9, 120.75, 120.67, 120.61, 120.54, 120.29,
118.1.
MS: m/z = 244.
HRMS (EI): m/z [M + H]+ calcd for C13H17N4O: 245.1397; found:
245.1392.
MS: m/z = 246.
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1510
H. Chen et al.
PAPER
5-Chloro-2-(1H-imidazol-1-yl)pyrimidine (3s)
1H NMR (300 MHz, DMSO-d6): d = 9.00 (s, 2 H), 8.56 (s, 1 H), 7.93
(s, 1 H), 7.16 (s, 1 H).
2-Methyl-1-phenyl-1H-imidazole (4d)5r
1H NMR (300 MHz, DMSO-d6): d = 7.54 (m, 2 H), 7.45 (m, 3 H),
7.27 (s, 1 H), 6.92 (s, 1 H), 2.28 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 190.5, 157.1, 136.3, 131.0, 116.6,
106.3.
MS: m/z = 158.
1-Phenyl-2-propyl-1H-imidazole (4e)
MS: m/z = 180.
1H NMR (300 MHz, DMSO-d6): d = 7.51–7.56 (m, 3 H), 7.41–7.48
(m, 2 H), 7.23 (s, 1 H), 6.94 (s, 1 H), 2.50–2.58 (m, 2 H), 1.53–1.60
(m, 2 H), 0.78–0.81 (m, 3 H).
HRMS (EI): m/z [M + H]+ calcd for C7H6ClN4: 181.0276; found:
181.0279.
13C NMR (75 MHz, CDCl3): d = 148.5, 137.9, 129.3, 128.2, 127.5,
3-(1H-Imidazol-1-yl)pyridine (3t)5u
125.8, 120.6, 28.9, 21.4, 13.7.
1H NMR (300 MHz, DMSO-d6): d = 8.96 (d, J = 3.2 Hz, 1 H), 8.57
(q, 1 H), 8.35 (s, 1 H), 8.11 (m, 1 H), 7.84 (s, 1 H), 7.57 (m, 1 H),
7.16 (s, 1 H).
MS: m/z = 186.
HRMS (EI): m/z [M + H]+ calcd for C12H15N2: 187.1230; found:
MS: m/z = 145.
187.1233.
5-(1H-Imidazol-1-yl)-2-methoxypyridine (3u)5u
3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline (4f)8a
1H NMR (400 MHz, DMSO-d6): d = 8.06 (d, J = 0.8 Hz, 1 H), 7.35
(s, 1 H), 6.97 (s, 1 H), 6.94 (s, 1 H), 6.82 (s, 1 H), 5.87 (s, 2 H), 2.15
(s, 3 H).
1H NMR (300 MHz, DMSO-d6): d = 8.48 (d, J = 4.0 Hz, 1 H), 8.17
(s, 1 H), 8.01 (dd, J = 8.0, 4.0 Hz, 1 H), 7.68 (s, 1 H), 7.11 (s, 1 H),
6.98 (d, J = 11.6 Hz, 1 H), 3.90 (s, 3 H).
MS: m/z = 175.
13C NMR (100 MHz, DMSO-d6): d = 151.29, 138.89, 135.17,
135.81, 131.50, 125.81, 123.10, 114.62, 108.32, 103.69, 103.65,
13.97.
3-(1H-Imidazol-1-yl)-2-methylpyridine (3v)
1H NMR (300 MHz, DMSO-d6): d = 8.56 (m, 1 H), 7.90 (s, 1 H),
7.75 (m, 1 H), 7.67 (s, 1 H), 7.43 (m, 1 H), 7.13 (s, 1 H), 2.36 (s, 3
H).
13C NMR (75 MHz, CDCl3): d = 154.6, 149.4, 137.3, 133.9, 132.8,
130.0, 121.7, 120.3, 40.9.
MS: m/z = 241.
3-(4-Methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)aniline (4g)
1H NMR (400 MHz, DMSO-d6): d = 8.22 (s, 1 H), 7.54 (s, 1 H), 7.24
(s, 1 H), 7.14 (s, 1 H), 6.74 (s, 1 H), 5.82 (s, 2 H), 2.08 (s, 3 H).
MS: m/z = 159.
13C NMR (100 MHz, DMSO-d6): d = 151.05, 142.17, 141.58,
131.73, 131.42, 131.11, 130.80, 126.63, 125.98, 123.27, 118.30,
107.50, 107.46, 106.38, 101.55, 101.50, 9.13.
HRMS (EI): m/z [M + H]+ calcd for C9H10N3: 160.0869; found:
160.0871.
MS: m/z = 241.
2,5-Bis(1H-imidazol-1-yl)pyridine (3w)
HRMS (EI): m/z [M + H]+ calcd for C16H14FN2O: 242.0900; found:
242.0908.
1H NMR (300 MHz, DMSO-d6): d = 8.87 (d, J = 3.6 Hz, 1 H), 8.58
(s, 1 H), 8.38 (s, 1 H), 8.34 (d, J = 3.6 Hz, 1 H), 8.00 (m, 2 H), 7.88
(s, 1 H), 7.16 (d, J = 8.0 Hz, 2 H).
1-[3-(4-Fluorophenoxy)phenyl]-2-methyl-1H-imidazole (4h)
1H NMR (300 MHz, DMSO-d6): d = 7.48–7.54 (t, J = 7.8 Hz, 1 H),
7.26–7.30 (m, 3 H), 7.20–7.25 (m, 3 H), 7.14–7.19 (m, 1 H), 6.99–
7.06 (m, 1 H), 6.89 (s, 1 H), 2.28 (s, 3 H).
13C NMR (75 MHz, DMSO-d6): d = 161.0, 158.8, 157.8, 151.73,
151.7, 144.5, 139.3, 130.5, 127.8, 121.30, 121.25, 121.19, 120.5,
119.7, 117.1, 116.8, 116.5, 114.8, 13.8.
13C NMR (75 MHz, CDCl3): d = 148.1, 142.1, 135.5, 135.0, 132.4,
132.1, 131.4, 131.2, 118.1, 116.1, 112.8.
MS: m/z = 211.
HRMS (EI): m/z [M + H]+ calcd for C11H10N5: 212.0931; found:
212.0933.
1-Phenyl-1H-1,2,4-triazole (4a)5r
MS: m/z = 268.
H NMR (300 MHz, DMSO-d6): d = 9.30 (s, 1 H), 8.24 (s, 1 H), 7.88
(m, 2 H), 7.58 (m, 2 H), 7.43 (t, J = 7.2 Hz, 1 H).
HRMS (EI): m/z [M + H]+ calcd for C16H14FN2O: 269.1085; found:
269.1094.
MS: m/z = 145.
1-Biphenyl-4-yl-1H-1,2,4-triazole (4b)8b
Acknowledgment
1H NMR (300 MHz, DMSO-d6): d = 9.36 (s, 1 H), 8.27 (s, 1 H),
7.95–7.98 (d, J = 8.9 Hz, 2 H), 7.85–7.89 (d, J = 8.8 Hz, 2 H), 7.73–
7.76 (t, J = 7.2 Hz, 2 H), 7.47–7.53 (t, J = 7.8 Hz, 2 H), 7.38–7.43
(t, J = 7.3 Hz, 1 H).
We thank the 100-talent program of Chinese Academy of Sciences,
(CAS), National Natural Science Foundation (Grant # 20802077,
90813033) and National High Technology Research and Develop-
ment Program (Grant # 2008AA02Z420, 2009CB940904) for their
financial support.
MS: m/z = 221.
4-(1H-Benzoimidazol-1-yl)benzonitrile (4c)5s
1H NMR (400 MHz, DMSO-d6): d = 8.65 (s, 1 H), 8.06 (d, J = 8.4
Hz, 2 H), 7.90 (d, J = 8.8 Hz, 2 H), 7.79–7.77 (m, 1 H), 7.71–7.68
(m, 1 H), 7.36–7.31 (m, 2 H).
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