Facile one-pot synthesis of substituted dihydropyrrol-2-ones via four-component domino reaction of amines, Dialkyl Acetylenedicar boxylates and formaldehyde

Article abstract of DOI:10.1002/jccs.201300008

Amild and efficientmethod for the one-pot synthesis of substituted dihydropyrrol-2-one derivatives is described via four-component domino reaction of amines, dialkyl acetylenedicarboxyaltes and formaldehyde in the presence of 1-methyl-2-oxopyrrolidinium hydrogen sulfate ([Hpyro][HSO4]) as ionic liquid catalyst. This facile approach proceeded smoothly in good to high yields and pure products are separated from the reaction mixture by simple filtration.

Full text of DOI:10.1002/jccs.201300008

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Article
8-Hydroxyquinoline Functionalized PEG-1000 Bridged Dicationic Ionic Liquid as a
Novel Ligand for Copper-catalyzed N-Arylation of Imidazoles
Ying-Lei Wang, Jun Luo* and Zu-Liang Liu
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China
(Received: Jan. 4, 2013; Accepted: Mar. 12, 2013; Published Online: ??; DOI: 10.1002/jccs.201300008)
A novel 8-hydroxyquinoline functionalized PEG-1000 bridged dicationic ionic liquid ([HQ-PEG1000
-
DIL][BF4]) was synthesized and characterized. It was applied as an efficiently recyclable ligand for cop-
per-catalyzed N-arylation of nitrogen-containing heterocycles with aryl halides. The catalytic system
could be easily recovered and reused for at least five runs without obvious loss of catalytic activity.
Keywords: 8-Hydroxyquinoline; Poly(ethylene glycol); Ionic liquid; N-Arylation; Copper.
INTRODUCTION
vapor pressure, excellent thermal stability, remarkable sol-
ubility, and easy recyclability make them appealing for or-
ganic chemists.27 Large numbers of available cations and
anions allow a wide range of physical and chemical charac-
teristics to be achieved, and then the task-specific ionic liq-
uids (TSILs) or functionalized ionic liquids (FILs) have
been developed. Such ionic liquids can be applied in a wide
range of areas, including catalysts recycling, supports for
organic synthesis, catalysis, separation of specific metal
ions from aqueous solution, gas absorption and construc-
tion of nanostructures and ion conductive materials.28
Recently, poly(ethylene glycol) (PEG) polymers
have extensively been used as cheaply and easily function-
alized supports for the immobilization of reagents and the
recovery of catalysts, due to their distinctive properties,
such as inexpensive, nontoxic, nonvolatile, thermally sta-
ble, environmentally benign.29 The poly(ethylene glycol)
functionalized ionic liquids (PEG-ILs), which incorporate
the advantages of PEG and ILs, have demonstrated attrac-
tive physicochemical properties and application in various
areas.30 Peng and co-workers prepared mPEGBImPF6 and
used as a reaction medium for the hydrosilylation.31
Bhanage and co-workers reported a PEG-functionalized
phosphonium salt as catalyst for the synthesis 5-aryl-2-
oxazolidinones from CO2 and aziridines.32 Liu and co-
workers synthesized three PEG-functionalized imidazo-
lium salts and served as N-heterocyclic carbene precursors
for the palladium-catalyzed Suzuki reaction.33
N-Arylheterocycles find extensive applications in
medicinal, biological, agrochemical, material and N-het-
erocyclic carbene chemistry.1 Transition metal catalyzed
arylation of nitrogen-containing heterocycles with aryl
halides is one of the most efficient and powerful methodol-
ogies for the synthesis of N-arylheterocycles.2 However,
the current methods have some limitations because these
transformations usually require the application of expen-
sive transition metal catalysts such as palladium,3 rho-
dium,4 nickel,5 cobalt6 and lanthanum7 complexes. In re-
cent years, Buchwald and Hartwig8 have developed highly
economic and efficient methods for the N-arylation of ni-
trogen-containing heterocycles with aryl halides, by using
inexpensive copper catalysts. The ligands employed in the
Cu-catalyzed reactions include schiff bases,9 L-proline,10
N-hydroxyimides,11 benzotriazole,12 pyridine N-oxides,13
per-6-amino-b-cyclodextrin,14 (S)-pyrrolidinylmethylimi-
dazole,15 mannich bases,16 N,N¢-dioxide,17 and 6,7-dihy-
droquinolin-8(5H)-oneoxime.18
8-Hydroxyquinoline (HQ) is a versatile ligand in co-
ordination chemistry, which has been widely applied for
analytical purposes and separation techniques.19 More re-
cently, 8-hydroxyquinoline and its derivatives have been
used as an efficient N,O-ligand for the transition metal cat-
alyzed reactions, such as Ullmann reaction,20 Sonogashira
reaction,21 Suzuki reaction,22 Heck reaction,23 hydroxyl-
ation,24 hydroalkoxylation25 and hydroamination.26 How-
ever, one drawback in those reactions is that the catalyst
could not be efficiently recovered.
In continuous of our research on synthesis and appli-
cation of PEG bridged dicationic ionic liquid in synthetic
organic chemistry,34 herein, we report a novel 8-hydroxy-
quinoline functionalized PEG-1000 bridged dicationic
Ionic liquids (ILs) have received much attention in
the last decades. Their unique properties such as negligible
* Corresponding author. Tel: +86-25-84315514; Fax: +86-25-84315030; Email: luojun@njust.edu.cn
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Article
Wang et al.
ionic liquid ([HQ-PEG1000-DIL][BF4]) (Scheme I) and its
application as an efficient and recyclable ligand for the
copper-catalyzed N-arylation of imidazoles.
was performed with iodobenzene (1.0 equiv) and imida-
zole (1.5 equiv) in the presence of copper catalyst (10
mol%), [HQ-PEG1000-DIL][BF4] (10 mol%) and base (2
equiv) in different solvents. The results are listed in Table
1. Among the solvents screened, we found that DMSO pro-
vided the best result (Table 1, entries 1-6). However, the
control experiment with no [HQ-PEG1000-DIL][BF4] re-
sulted in low yield (Table 1, entry 7). As expected, no prod-
uct was detected in the absence of copper catalyst (Table 1,
entry 8). Some available copper catalysts were used to cata-
lyze this N-arylation and the results demonstrated that
Cu2O was the most superior (Table 1, entries 9-14). Base
affected the catalysis dramatically. Only trace 1-phenyl-
1H-imidazole was observed in the absence of base (Table
1, entry 15). Some inorganic bases like K2CO3, Cs2CO3,
K3PO4, NaOH and KOH facilitated this coupling reaction
and gave almost quantitative yields, while NaOAc, Na2CO3
and organic bases such as triethylamine and pyridine were
not so efficient and resulted in lower yields (Table 1, entries
16-23). Further investigation revealed that 6 h was enough
for the completion of the reaction (Table 1, entries 24-27).
In addition, reaction temperature showed surprising much
influence on the reaction since that the reaction under 110
Scheme I Synthesis of [HQ-PEG1000-DIL][BF4]
RESULTS AND DISCUSSION
The synthetic route of [HQ-PEG1000-DIL][BF4] is il-
lustrated in Scheme I. It was readily prepared through a
straightforward four-step procedure from commercially
available starting materials and reagents with good yields.
Firstly, compound 1 and compound 2 were synthesized by
modifying a synthetic procedure described in the litera-
ture.34a And then, the quaternization of compound 2 and
1-bromo-3-chloropropane was conducted in CH3CN to af-
ford the compound 3. Two methods for preparing [HQ-
PEG1000-DIL][BF4] were investigated. The first stragety
was the classical approach with the anion exchange at last.
However, this method suffered from tedious workup and it
was almost impossible to purify the ILs. Alternatively, the
bromide of compound 3 was exchanged with NaBF4 firstly,
and then reacted with 8-hydroxyquinoline in the presence
of K2CO3 in acetone, the target ionic liquid 4 could be ob-
tained in high purity, which was characterized by 1H NMR,
13C NMR, IR and MS. The thermal property was deter-
mined by thermal gravimetric analysis (TGA) and differen-
tial scanning calorimetry (DSC). The results indicate that
the [HQ-PEG1000-DIL][BF4] is highly thermal stable (Fig.
1) and has a glass transition temperature of -35 °C (Fig. 2).
In addition, the solubility of [HQ-PEG1000-DIL][BF4] was
determined at room temperature. In general, it is immisci-
ble with heptane, cyclohexane, diethyl ether, toluene and
water, but miscible with dichloromethane, acetone, metha-
nol, ethanol, N,N-dimethylformamide (DMF) and dimethyl
sulfoxide (DMSO).
Fig. 1. The TGA spectrum of [HQ-PEG1000-DIL]
[BF4].
Fig. 2. The DSC spectrum of [HQ-PEG1000-DIL][BF4].
To optimize the reaction conditions, the N-arylation
2
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Cu2O/[HQ-PEG1000-DIL][BF4] Catalyzed N-Arylation
Table 1. Screening reaction conditions for copper-catalyzed N-
arylation of imidazole with iodobenzene[a]
Table 2. Cu2O/[HQ-PEG1000-DIL][BF4] catalyzed N-arylation of
imidazole with various aryl halides [a]
copper catalyst, base
Cu2O, K3PO4, DMSO, 120 o
C
X
N
N
N
I
+
HN
N
N
R
+ HN
N
[HQ-PEG-DIL][BF4], solvent
R
[HQ-PEG1000-DIL][BF4]
X = I, Br, Cl
Copper
catalyst
t
T
Yield
Entry
Base
Solvent
(°C) (%)[b]
Entry
X
R
t (h)
Yield (%) [b]
(h)
1
CuI
CuI
CuI
CuI
CuI
CuI
CuI
-
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
H2O
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
18
12
6
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
110
100
13
37
10
70
25
29
36
0
1
I
4-H
4-CH3
4-NH2
4-Br
6
94
93
91
96
95
92
90
89
86
91
91
90
94
95
95
96
95
94
90
87
36
2
DMF
2
I
6
3
NMP
3
I
6
4
DMSO
Toluene
Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
4
I
6
5
5
I
4-NO2
4-H
6
6
7[c]
6
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
48
7
4-CH3
4-NH2
4-OH
8
8
9
CuBr
CuCl
Cu2O
84
80
97
87
81
74
trace
50
16
98
99
98
98
18
3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
10
11
12
13
14
15
16
17
18
19
20
21
4-CH3O
3-CH3O
2-CH3O
4-CH3CO
4-F
Cu(OAc)2 K2CO3
CuSO4
Cu
K2CO3
K2CO3
-
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
4-Cl
NaOAc
Na2CO3
Cs2CO3
K3PO4
NaOH
KOH
4-CN
4-CF3
4-NO2
2-Pyridyl
1-Naphthyl
4-NO2
Et3N
[a] Reaction conditions: aryl halide (1.0 mmol), imidazole (1.5
mmol), Cu2O (0.1 mmol), [HQ-PEG1000-DIL][BF4] (0.1 mmol),
K3PO4 (2.0 mmol), DMSO (2 mL), 120 °C.
[b] Isolated yield.
Pyridine
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
99
99
99
88
95
42
3
6
still obtained when the reaction time was prolonged to 24 h
(Table 2, entries 6-21). We could find the influence rule of
substitutents on coupling reaction from the relatively lower
reactivity of aryl bromides. The results indicated that aryl
bromides bearing electron-withdrawing groups (Table 2,
entries 13-18) exhibited higher reactivity than those bear-
ing electron-donating groups (Table 2, entries 7-12). One
6
[a] Reaction conditions: iodobenzene (1.0 mmol), imidazole (1.5
mmol), copper catalyst (0.1 mmol), [HQ-PEG1000-DIL][BF4] (0.1
mmol), base (2.0 mmol), solvent (2 mL).
[b] GC yield.
[c] Without [HQ-PEG1000-DIL][BF4].
typical example is that 4-bromobenzonitrile afforded a dis
tinguishable higher yield (Table 2, entry 16) than 4-bromo
phenol (Table 2, entry 9) after reacting under the same con
ditions. Notably, sterically demanding meta and ortho sub
-
-
-
-
°C could give an excellent yield of 95% but a little lower
temperature of 100 °C could only give a dramatically
reduced yield of only 42% (Table 1, entries 28-29).
The scope of aryl halide substrates was then investi-
gated by using this catalytic system under the optimized re-
action conditions, and the results were presented in Table 2.
It is clearly that all the aryl iodides, regardless of bearing
either electron-withdrawing groups or electron-donating
groups, afforded the corresponding products with excellent
yields (Table 2, entries 1-5). As expected, aryl bromides are
less reactive but fortunately, good to excellent yields were
stitutents did not hamper the arylation reaction (Table 2,
entries 10-11). This system was also successfully applied to
N-arylation of imidazole with heteroaryl bromide such as
2-bromopyridine (Table 2, entry 19). Unfortunately, aryl
chloride showed much lower reactivity even bearing strong
electron-withdrawing groups such as nitro, very low yield
was obtained even prolonged the reaction time to 48 h
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Article
Wang et al.
Table 3. Cu2O/[HQ-PEG1000-DIL][BF4] catalyzed N-arylation of
various nitrogen-containing heterocycles with aryl
halides [a]
yields.
CONCLUSION
Cu2O, K3PO4, DMSO, 120 o
C
X
N-Het
A novel 8-hydroxyquinoline functionalized PEG-
1000 bridged dicationic ionic liquid ([HQ-PEG1000-DIL]
[BF4]) was prepared and used as an efficiently recyclable
ligand for copper-catalyzed N-arylation of nitrogen-con-
taining heterocycles. Using the Cu2O/[HQ-PEG1000-DIL]
[BF4] system, a series of substituted aryl iodides and aryl
bromides could couple with nitrogen-containing hetero-
cycles to afford the corresponding products in good to ex-
cellent yields. Furthermore, this catalytic system could be
easily recycled for at least five times without obvious deac-
tivation.
Het-NH
+
[HQ-PEG1000-DIL][BF4]
X = I, Br
Entry
X
Het-NH
t (h)
Yield (%) [b]
1
2
3
4
5
6
I
Br
I
pyrrole
pyrrole
indole
indole
6
24
6
93
89
91
88
90
85
Br
I
24
6
benzimidazole
benzimidazole
Br
24
[a] Reaction conditions: aryl halide (1.0 mmol), Het-NH (1.5
mmol), Cu2O (0.1 mmol), [HQ-PEG1000-DIL][BF4] (0.1 mmol),
K3PO4 (2.0 mmol), DMSO (2 mL), 120 °C.
[b] Isolated yield.
EXPERIMENTAL
General. All chemicals were purchased from commercial
sources and used without further purification. The 1H NMR and
13C NMR spectra were recorded on a Bruker DRX spectrometer
(Table 2, entry 21).
In order to expand the scope of the methodology,
other nitrogen-containing heterocycles such as pyrrole,
indole and benzimidazole were applied in the catalytic sys-
tem. All the Het-NHs are coupled with iodobenzene or
bromobenzene to afford the corresponding N-arylated
products in excellent yields (Table 3, entries 1-6).
1
with H resonant frequency of 500 MHz and 13C resonant fre-
quency of 126 MHz. IR spectra were recorded in KBr disks with a
Shimazu Prestige-21 FT-IR spectrometer. Mass spectra were
taken on an Agilent LC-MS 1100 series instrument in the electro-
spray ionization mode. GC analyses were performed on an
Agilent 7890A instrument. The thermo gravimetric analysis
(TGA) was performed on a TGA/SDTA851e thermal analyzer
(Mettler Toledo). Samples were loaded into an aluminium oxide
crucible and heated at a rate of 20 °C·min-1 from 50 °C to 600 °C
under N2. The differential scanning calorimetry (DSC) was per-
formed on a DSC823e (Mettler Toledo), and heated at a rate of 10
°C·min-1 from -50 °C to 300 °C under N2.
One of the main aims of our study was to investigate
the recycling of the catalyst. The reusability of Cu2O/[HQ-
PEG1000-DIL][BF4] was examined using the above model
reaction under the optimized conditions. After completion
of the reaction, the final mixture was cooled to room tem-
perature and the product was extracted out with diethyl
ether. The catalyst left in the reaction vessel was dried un-
der vacuum for 2 h. Subsequently, the resultant residues
were reused directly without further treatment. As shown
in Fig. 3, we found that the catalytic system could be recy-
cled for at least five runs without significant decrease of the
Synthesis of 8-hydroxyquinoline functionalized PEG-
1000 bridged dicationic ionic liquid
Synthesis of compound 1.34a To a solution of PEG-1000
(25 g, 0.025 mol) and pyridine (4.0 mL, 0.05 mol) in CH2Cl2 (150
mL) was dropped SOCl2 (4.0 mL, 0.055 mol) at ambient tempera-
ture. The reaction mixture was stirred at ambient temperature for
12 h. After completion, the solvent was evaporated in vacuum.
The residue was then dissolved in ethyl acetate to allow the
pyridine hydrochloride to precipitate. After filtration and concen-
tration, the intermediate 1 was obtained and used directly for the
next reaction. 1H NMR (500 MHz, CDCl3, ppm) d 3.77 (t, J = 5.9
Hz, 4H), 3.73-3.60 (m, 78H).
Synthesis of compound 2.34a Imidazole (8.2 g, 0.12 mol)
was melted at around 100 °C and NaOH (4 g, 0.1 mol) was added.
After the solid NaOH thawed, toluene (50 mL) was added and
heated to remove water by azeotropy for 3 h. Then, the toluene
Fig. 3. The recycling of Cu2O/[HQ-PEG1000-DIL]
[BF4] system.
4
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Cu2O/[HQ-PEG1000-DIL][BF4] Catalyzed N-Arylation
was evaporated under reduced pressure. Subsequently, the solu-
tion of intermediate 1 in CH3CN (80 mL) was added. The mixture
was stirred under reflux for another 12 h. After completion, the
solvent was removed by distillation. The residue was dissolved in
CH2Cl2 and washed with water several times to remove inorganic
salts and excess imidazole. After removal of solvent, 20.5 g of the
mmol) were added to a tube and sealed. The reaction mixture was
stirred at 120 °C for a certain time, then cooled to room tempera-
ture and extracted with diethyl ether. The combined organic ex-
tracts were dried over anhydrous Na2SO4, filtered and concen-
trated to give the crude product, which was purified by column
chromatography on silica gel (200-300 mesh) using ethyl ace-
tate/petroleum ether as eluent to afford the desired product in high
1
desired compound 2 was obtained, yield 89%. H NMR (500
1
purity. The products were characterized by comparison of H
MHz, CDCl3, ppm) d 7.47 (s, 2H), 6.96 (d, J = 11.8 Hz, 4H), 4.05
(t, J = 5.2 Hz, 4H), 3.68 (t, J = 5.2 Hz, 4H), 3.65-3.48 (m, 87H).
Synthesis of compound 3. The Compound 2 (20.5 g) was
mixed with 1-bromo-3-chloropropane (6.5 g, 2.2 equiv) in
CH3CN and stirred at 50 °C for 48 h under nitrogen atmosphere.
After completion, the solvent was removed by distillation. The
residue was dissolved in deionized water and washed with ethyl
ether several times to remove traces of starting materials. After
evaporation under reduced pressure, the compound 3 was af-
NMR data with those in the literatures.
Characterization data of products
1-Phenyl-1H-imidazole.9b,14,15,16 Yellow oil; 1H NMR (500
MHz, CDCl3, ppm) d 7.48 (t, J = 7.6 Hz, 3H), 7.43-7.32 (m, 5H).
1
1-(p-tolyl)-1H-imidazole.9b,14,15,16 White solid; H NMR (500
MHz, CDCl3, ppm) d 7.82 (s, 1H), 7.27 (d, J = 2.1 Hz, 4H), 7.25
(s, 1H), 7.19 (s, 1H), 2.41 (s, 3H). 4-(1H-imidazol-1-yl)ani-
line.9b,15,16 Yellow solid; 1H NMR (500 MHz, CDCl3, ppm) d 7.73
(s, 1H), 7.20-7.09 (m, 4H), 6.78-6.70 (m, 2H), 3.82 (s, 2H).
1
forded and used directly for the next reaction. H NMR (500
1
MHz, D2O, ppm) d 8.86 (d, J = 12.5 Hz, 2H), 7.54 (dd, J = 7.4, 5.5
Hz, 4H), 4.42-4.25 (m, 10H), 3.86 (dd, J = 10.3, 5.5 Hz, 6H),
3.79-3.45 (m, 105H), 2.54-2.27 (m, 4H); 13C NMR (126 MHz,
d-DMSO, ppm) d 137.10, 123.46, 122.70, 70.24, 70.06, 70.00,
68.51, 49.35, 46.96, 42.17, 32.43; IR (KBr, cm-1): 3150, 2870,
1566, 1455, 1349, 1286, 1249, 1049, 947, 844, 763, 732, 641.
Synthesis of [HQ-PEG1000-DIL][BF4]. The compound 3
was mixed with NaBF4 (6.7 g, 2.4 equiv) in acetone (60 mL) and
stirred at room temperature for 48 h. After completion, the result-
ing mixture was filtered. After removal of solvent, the K2CO3 (5.8
g, 2.4 equiv), 8-hydroxyquinoline (6.2 g, 2.4 equiv) and acetone
(80 mL) were added. The reaction mixture was stirred at 50 °C for
72 h under nitrogen atmosphere. After acetone was removed in
vacuum, the residue was washed repeatedly with ethyl acetate to
remove excess 8-hydroxyquinoline, followed by evaporation un-
der reduced pressure, and the [HQ-PEG1000-DIL][BF4] was fi-
nally obtained (23.5 g, yield 81%). 1H NMR (500 MHz, CDCl3,
ppm) d 9.32 (s, 2H), 8.84 (d, J = 3.4 Hz, 2H), 8.10 (d, J = 8.3 Hz,
2H), 7.61 (s, 2H), 7.51 (s, 2H), 7.42-7.33 (m, 6H), 7.06 (d, J = 7.3
Hz, 2H), 4.55 (t, J = 6.5 Hz, 4H), 4.38-4.29 (m, 6H), 4.22 (t, J =
5.5 Hz, 4H), 3.82-3.71 (m, 6H), 3.65-3.42 (m, 122H), 2.56-2.45
(m, 4H); 13C NMR (126 MHz, CDCl3, ppm) d 153.90, 149.16,
140.04, 136.96, 136.18, 129.46, 126.90, 123.18, 122.66, 121.78,
120.41, 109.91, 70.42, 70.23, 70.14, 68.62, 65.39, 49.72, 47.18,
29.44; IR (KBr, cm-1): 2868, 1568, 1502, 1468, 1375, 1349, 1318,
1257, 1052, 946, 827, 796, 761, 730, 668, 643; ESI-MS, m/z:
612.9 (M++/2, n = 20), 635.0 (M++/2, n = 21), 657.3 (M++/2, n = 22).
General procedure for N-arylation reaction. In a typical
reaction, aryl halide (1.0 mmol), imidazole (1.5 mmol), K3PO4 (2
mmol), Cu2O (0.01 mmol) and [HQ-PEG1000-DIL][BF4] (0.1
1-(4-bromophenyl)-1H-imidazole.9b,15 White solid; H NMR
(500 MHz, CDCl3, ppm) d 7.84 (s, 1H), 7.65-7.59 (m, 2H), 7.31-
7.27 (m, 2H), 7.26 (t, J = 1.2 Hz, 1H), 7.23 (s, 1H). 1-(4-nitro-
phenyl)-1H-imidazole.9b,14,15,16 Yellow solid; 1H NMR (500
MHz, CDCl3, ppm) d 8.42-8.36 (m, 2H), 7.99 (s, 1H), 7.62-7.57
(m, 2H), 7.38 (t, J = 1.4 Hz, 1H), 7.29 (s, 1H). 4-(1H-imidazol-
1-yl)phenol.9b,15,16 White solid; H NMR (500 MHz, d-DMSO,
1
ppm) d 9.68 (s, 1H), 8.04 (s, 1H), 7.56 (s, 1H), 7.39 (d, J = 8.6 Hz,
2H), 7.04 (s, 1H), 6.86 (d, J = 8.6 Hz, 2H). 1-(4-methoxy-
phenyl)-1H-imidazole.9b,15,16 Yellow oil; H NMR (500 MHz,
1
CDCl3, ppm) d 7.74 (s, 1H), 7.30-7.25 (m, 2H), 7.17 (d, J = 11.4
Hz, 2H), 6.98-6.93 (m, 2H), 3.82 (s, 3H). 1-(3-methoxyphenyl)-
1H-imidazole.14 Yellow oil; 1H NMR (500 MHz, CDCl3, ppm) d
7.82 (s, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.25 (s, 1H), 7.17 (s, 1H),
6.94 (dd, J = 7.9, 1.4 Hz, 1H), 6.88 (dt, J = 8.5, 2.2 Hz, 2H,), 3.82
(s, 3H). 1-(2-methoxyphenyl)-1H-imidazole.15 Yellow oil; H
1
NMR (500 MHz, CDCl3, ppm) d 7.77 (s, 1H), 7.36-7.31 (m, 1H),
7.28-7.23 (m, 1H), 7.18 (s, 1H), 7.14 (s, 1H), 7.02 (dd, J = 15.4,
7.9 Hz, 2H), 3.82 (s, 3H). 1-(4-(1H-imidazol-1-yl)phenyl)-
ethanone.9b,14,15 White solid; 1H NMR (500 MHz, CDCl3, ppm) d
8.12-8.05 (m, 2H), 7.96 (s, 1H), 7.54-7.48 (m, 2H), 7.36 (d, J =
1.2 Hz, 1H), 7.25 (s, 1H), 2.65 (s, 3H). 1-(4-fluorophenyl)-
1H-imidazole.35 Yellow oil; 1H NMR (500 MHz, CDCl3, ppm) d
7.76 (s, 1H), 7.37-7.30 (m, 2H), 7.20 (s, 1H), 7.18-7.12 (m, 3H).
1
1-(4-chlorophenyl)-1H-imidazole.14, 16 White solid; H NMR
(500 MHz, CDCl3, ppm) d 7.83 (s, 1H), 7.46 (d, J = 8.6 Hz, 2H),
7.34 (d, J = 8.6 Hz, 2H), 7.25 (s, 1H), 7.22 (s, 1H). 4-(1H-
imidazol-1-yl)benzonitrile.9b,15 White solid; 1H NMR (500
MHz, CDCl3, ppm) d 7.95 (s, 1H), 7.84-7.77 (m, 2H), 7.57-7.50
(m, 2H), 7.35 (s, 1H), 7.27 (s, 1H). 1-(4-(trifluoromethyl)phen-
J. Chin. Chem. Soc. 2013, 60, 000-000
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
5

Article
Wang et al.
yl)-1H-imidazole.9b White solid; H NMR (500 MHz, CDCl3,
ppm) d 7.92 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.3 Hz,
2H), 7.33 (s, 1H), 7.25 (s, 1H). 2-(1H-imidazol-1-yl)pyri-
dine.9b,14,15,16 Yellow oil; 1H NMR (500 MHz, CDCl3, ppm) d 8.46
(dd, J = 4.8, 0.9 Hz, 1H), 8.33 (s, 1H), 7.80 (td, J = 8.2, 1.8 Hz,
1H), 7.62 (s, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.22 (ddd, J = 7.3, 4.9,
0.6 Hz, 1H), 7.17 (s, 1H). 1-(naphthalen-1-yl)-1H-imida-
zole.14,15 White solid; 1H NMR (500 MHz, CDCl3, ppm) d
7.94-7.88 (m, 2H), 7.74 (s, 1H), 7.60-7.46 (m, 4H), 7.42 (dd, J =
7.2, 1.0 Hz, 1H), 7.29 (s, 1H), 7.23 (t, J = 1.2 Hz, 1H).
1
9. (a) Henri, J. C.; Pascal, P. C.; Jean, F. S.; Marc, T. Chem. Eur.
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1-phenyl-1H-pyrrole.14,15,16 White solid; H NMR (500 MHz,
1
CDCl3, ppm) d 7.47-7.39 (m, 4H), 7.30-7.23 (m, 1H), 7.13-7.10
(m, 2H), 6.39-6.33 (m, 2H). 1-phenyl-1H-indole.9b,14,15,16 Yellow
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1
solid; H NMR (500 MHz, CDCl3, ppm) d 7.74 (d, J = 7.8 Hz,
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1H), 7.62 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 4.2 Hz, 4H), 7.42-7.36
(m, 2H), 7.27 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.4 Hz, 1H), 6.74 (d, J
= 3.1 Hz, 1H). 1-phenyl-1H-benzo[d]imidazole.14,15,16 White
solid; 1H NMR (500 MHz, CDCl3, ppm) d 8.14 (s, 1H), 7.90 (d, J
= 7.0 Hz, 1H), 7.60-7.53 (m, 3H), 7.51 (d, J = 7.5 Hz, 2H), 7.47 (t,
J = 7.4 Hz, 1H), 7.34 (p, J = 7.8 Hz, 2H).
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ACKNOWLEDGEMENTS
This project was financially sponsored and supported
by the National Natural Science Foundation of China (No.
21002050), the “Zijin Star Project” and the “Excellence
Initiative Project” of NUST.
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