Nanocrystalline magnesium oxide: A novel and efficient catalyst for facile synthesis of 2,4,5-trisubstituted imidazole derivatives

Article abstract of DOI:10.1007/s00706-010-0397-y

Nanocrystalline magnesium oxide with high specific surface area has been used as a novel and efficient catalyst for an improved and rapid synthesis of biologically active 2,4,5-trisubstituted imidazoles, by three-component, one-pot condensation of 1,2-dik

Full text of DOI:10.1007/s00706-010-0397-y

Monatsh Chem (2010) 141:1339–1345
DOI 10.1007/s00706-010-0397-y
ORIGINAL PAPER
Nanocrystalline magnesium oxide: a novel and efficient catalyst
for facile synthesis of 2,4,5-trisubstituted imidazole derivatives
•
Javad Safari Shiva Dehghan Khalili
•
•
•
Mehran Rezaei Sayed Hossein Banitaba
Fereshteh Meshkani
Received: 18 February 2010 / Accepted: 6 September 2010 / Published online: 7 October 2010
Ó Springer-Verlag 2010
Abstract Nanocrystalline magnesium oxide with high
specific surface area has been used as a novel and efficient
catalyst for an improved and rapid synthesis of biologically
active 2,4,5-trisubstituted imidazoles, by three-component,
one-pot condensation of 1,2-diketones and aryl aldehydes,
in excellent yields under solvent-free and conventional
heating conditions. The method has several advantages, for
example excellent yields, shorter reaction time, and use of
a non-toxic and recyclable catalyst.
active backbone in drugs such as losartan, eprosartan [6],
and trifenagrel [7]. They also have a variety of bioactive
effects, for example fungicidal [8, 9], herbicidal [10],
antitumor [11], anti-inflammatory [12], anti-allergic [13],
analgesic [14], and antibacterial [15]. Some substituted
imidazoles are selective antagonists of the glucagons
receptor [16], inhibitors of p38 MAP kinase [17], B-Raf
kinase [18], transforming growth factor b1 (TGF-b1)
type 1 activin receptor-like kinase (ALK5) [19], cycloox-
ygenase-2 (COX-2) [20], and biosynthesis of interleukin-1
(IL-1) [21].
Keywords Nanocrystalline magnesium oxide ꢀ
2,4,5-Trisubstituted imidazoles ꢀ One-pot condensation ꢀ
Solvent-free conditions
Several methods are used for synthesis of multi-substi-
tuted imidazoles [22–33]. Recently, one-pot condensations
of an aldehyde and ammonium acetate with an a-hydroxy
ketone, an a-keto oxime, or a 1,2-diketone have been
achieved by using a variety catalysts, for example Zr(acac)4
[34], Yb(OTf)3 [35], Yb(OPf)3 [36], InCl3ꢀ3H2O [37], I2
[38], NiCl2ꢀ6H2O/Al2O3 [39], ZrCl4 [40], silica sulfuric
acid (SSA) [41, 42], boric acid [43], ionic liquids [44–47],
heteropolyacid [48], ceric ammonium nitrate (CAN) [49,
50], sodium bisulfite [51], potassium aluminum sulfate
(alum) [52], polymer-supported ZnCl2 [53], phosphomo-
lybdic acid [54], ZrOCl2ꢀ8H2O [55], L-proline [56], PEG-
400 medium [57], and scolecite [58]. Despite their potential
utility, some of these methods are not environmentally
friendly and suffer from one or more disadvantages, for
example hazardous reaction conditions, complex work-up
and purification, strongly acidic conditions, high tempera-
ture, use of toxic metal catalysts, poor yields, occurrence of
side reactions, and long reaction time. Therefore, the
development of a mild general method to overcome these
shortcomings remains a challenge for organic chemists in
the synthesis of highly substituted imidazoles. Magnesium
oxide (MgO) has many applications as catalyst [59, 60],
refractory materials [61], optically transparent ceramic
Introduction
The synthesis, reactions, and biological properties of
substituted imidazoles constitute a significant part of
modern heterocyclic chemistry. Multi-substituted imida-
zoles, an important class of pharmaceutical compounds,
have a wide spectrum of biological activity [1–3]. They
have emerged as an integral part of many biological sys-
tems [4], viz. histidine, histamine, and biotin [5], and an
J. Safari (&) ꢀ S. D. Khalili ꢀ S. H. Banitaba
Laboratory of Organic Chemistry Research,
Department of Organic Chemistry, College of Chemistry,
University of Kashan, 87317-51167 Kashan, I.R. Iran
e-mail: Safari@kashanu.ac.ir
M. Rezaei ꢀ F. Meshkani
Catalyst and Advanced Materials Research Laboratory,
Chemical Engineering Department, Faculty of Engineering,
University of Kashan, 87317-51167 Kashan, I.R. Iran
123

1340
S. D. Khalili et al.
Ar1
Ar2
MgO with a high specific surface area as a catalyst with
higher activity and better controlled selectivity.
Ar2
Ar1
O
Nanocrystalline MgO
100 o C, 30 min
Ar3-CHO
N
2NH4OAc
+
+
N
H
The crystallite sizes determined by XRD were between
12.8 and 17.5 nm (determined by use of the Scherrer
equation), indicative of the nanocrystalline structure of the
prepared MgO. In addition the surface area was approxi-
mately 116 m2 g-1. The pore volume and pore size were
also calculated from the N2 adsorption result; the pore size
was approximately 21.1 nm and the pore volume approx-
imately 0.69 cm3 g-1. The theoretical particle size was
also calculated from surface area, assuming spherical par-
ticles, from the equation:
O
Ar3
4a-4v
1a-1b
2
3a-3r
Scheme 1
windows [62, 63], etc. Magnesium oxide with large spe-
cific surface area is also a potential catalyst support for
various reactions and a promising sorbent for chemi-
sorption and destructive adsorption of a variety of
pollutants. In the field of catalysis, MgO has strongly
basic properties, which are associated with catalysis by
bases in many organic reactions [64]. Nanoscale supports
create catalysts with more edges and corners, which can
lead to higher performance of the catalyst. Herein, we
report convenient and facile multi-component, one-pot
synthesis of 2,4,5-trisubstituted imidazoles in high yields
by using nanocrystalline magnesium oxide with high
specific surface area of approximately 116 m2 g-1 and a
crystallite size of approximately 12 nm as a novel and
efficient catalyst (Scheme 1).
ꢀ
ꢁ
6; 000
q ꢁ S
DBET
¼
ð1Þ
where DBET is the equivalent particle diameter in nano-
meters, q is the density of the material in g cm-3, and S is
the specific surface area in m2 g-1. The particle size cal-
culated from Eq. 1 was 14.4 nm, which confirmed the
nanostructure of the MgO sample [66]. The TEM image of
MgO is shown in Fig. 1. As can be seen, the sample has a
nanocrystalline structure with a plate-like shape.
Subsequent efforts were focused on optimizing condi-
tions for formation of 2,4,5-triphenylimidazole by using
different amounts of nanocrystalline MgO and different
temperatures to determine their effects on the reaction
(Table 2). As indicated, the best result was obtained at
100 °C with 5 mol% nanocrystalline MgO. The reaction
yield with increasing amount of nanocrystalline MgO and
temperature was not substantially increased.
Results and discussion
In an initial study, for examination of catalytic activity of
different catalysts such as CaO, BaO, and MgO in this
condensation reaction, 1 mmol benzaldehyde was first
reacted with 1 mmol benzil and 2 mmol ammonium ace-
tate for 30 min at 100 °C in the presence of each catalyst
(2 mol%) separately. In the course of this study we found
that MgO was the most effective catalyst (Table 1). In the
absence of catalyst, yield of the product was found to be
very low. Therefore, we decided to use nanocrystalline
Results from nanocrystalline magnesium oxide-cata-
lyzed condensation reaction of 1,2-diketones (benzil, 1a,
4,40-difluorobenzil, 1b) with different aromatic aldehydes
and ammonium acetate at 100 °C under solvent-free con-
ditions are given in Table 3. As shown, these conditions
proved to be general for the reacting aldehyde. Aldehydes
bearing either electron-withdrawing or electron-donating
Table 1 Synthesis of 2,4,5-triphenyl-1H-imidazole in the presence
of metal oxide catalysts
O
O
N
H
Catalyst (2 mol %)
2 NH4OAc
+
+
Solvent-free, 100o C
N
H
O
Entry Catalyst
Time (min) Temperature (°C) Yield (%)
1
2
3
4
5
None
MgO
CaO
BaO
30
30
30
30
100
100
100
100
100
15
55
20
50
80
Nano-MgO 30
Fig. 1 TEM image of nanocrystalline MgO
123

Synthesis of 2,4,5-trisubstituted imidazole derivatives
1341
magnesium oxide with high surface area as a novel, effi-
cient, and recyclable catalyst under solvent-free and
conventional heating conditions. The approach has several
benefits, for example low waste, easy work up, short
reaction time, and high yields.
Table 2 Optimization of reaction conditions for synthesis of 2,4,5-
triphenyl-1H-imidazole
O
O
H
N
2 NH OAc
Conditions
+
+
4
O
N
H
Experimental
Entry
Nanocrystalline
MgO (mol%)
Temperature
(°C)
Time
(min)
Yield
(%)
Materials
1
2
5
60
60
30
30
30
30
30
30
30
30
30
30
30
30
35
50
55
55
80
94
93
92
80
95
92
92
Chemical reagents in high purity were purchased from the
Merck Chemical Company. All materials were of com-
mercial reagent grade.
2
3
7
60
4
11
2
60
5
100
100
100
100
130
130
130
130
Apparatus
6
5
7
7
Melting points were determined in open capillaries using
an Electrothermal Mk3 apparatus. Infrared spectra were
recorded using a Perkin–Elmer FTIR 550 spectrometer. 1H
NMR and 13C NMR spectra were recorded with a Bruker
DRX-400 spectrometer at 400 and 100 MHz, respectively.
NMR spectra were obtained in DMSO-d6 solutions and are
reported as parts per million (ppm) downfield from tetra-
methylsilane as internal standard. The abbreviations used
are: singlet (s), doublet (d), triplet (t), and multiplet (m).
Elemental analysis (C, H, N) was performed with a Carlo
Erba model EA 1108 analyzer or a Perkin–Elmer 240c
analyzer, and results agreed favorably with calculated
values. UV spectra were recorded on a Hitachi 200-20
spectrophotometer using spectrophotometric grade chloro-
form (Baker). The N2 adsorption/desorption analysis (BET)
was performed at -196 °C using an automated gas
adsorption analyzer (Tristar 3000, Micromeritics). XRD
analysis was performed with an X-ray diffractometer
(PANalytical X’Pert-Pro) using a Cu-Ka monochromatic
radiation source and an Ni filter. Transmission electron
microscopy (TEM) was performed with a Jeol JEM-
2100UHR, operated at 200 kV.
8
11
2
9
10
11
12
5
7
11
groups perform equally well in the reaction and all imi-
dazoles were obtained in high yields.
The high efficiency of the nanoparticle oxides is caused
not only by their high surface area but also by the high
concentration of low-coordinated sites and structural
defects on their surface. As the particle size is scaled down
to a few nanometers, the constituting atoms have highly
defective coordination environments. Most of the atoms
have unsatisfied valencies and reside at the surface [65].
Nanocrystalline MgO also acts as a mild Lewis acid that
catalyzes three-component, one-pot synthesis of 2,4,5-tri-
substituted imidazoles.
The structure of compounds 4a–4v was deduced from their
high-field1HNMR, 13CNMR, IR, andUVspectraldata. Also,
their melting points were compared with literature reports.
The 1H NMR spectra of all the products contained a singlet at
approximately d = 12.50–12.80 ppm. IR spectra contained a
distinguishing peak at 3,400–3,440 cm-1 for NH. In 13C
NMR spectra of fluorinated derivatives, C–F couplings were
Preparation of nanocrystalline MgO
Nanocrystalline MgO was prepared by means of a procedure
reported elsewhere [66]. In short, poly(vinyl alcohol) (PVA,
MW 70,000) was dissolved in water at 90 °C under vigorous
stirring to form a transparent solution. Mg(NO3)2ꢀ6H2O was
dissolved in water containing PVA. The metal ion-to-PVA
monomer unit molar ratio (M/PVA) was chosen as 1:3.
Aqueous ammonia (25% w/w) was added dropwise at room
temperature to the resulting viscous liquid mixture, with
rapid stirring, to achieve careful pH adjustment to 10.5. After
precipitation, the slurry was stirred for another 30 min and
then heated under reflux at 80 °C for 20 h under continuous
1
observed with coupling constants of JC–F = 241–244 Hz,
2JC–F = 21–22 Hz, 3JC–F = 7–8 Hz, and 4JC–F = 2 Hz. For
example, the 13C NMR spectrum of compound 4t is indicated
in Fig. 2.
In summary, we describe a facile, eco-friendly, and
green procedure for synthesis of biologically active 2,4,5-
trisubstituted imidazoles via condensation of representative
1,2-diketones with a variety of aromatic aldehydes and
ammonium acetate in the presence of nanocrystalline
123

1342
S. D. Khalili et al.
Table 3 Nanocrystalline MgO-catalyzed synthesis of 2,4,5-trisubstituted imidazoles at 100 °C under solvent-free conditions
Ar1
Ar2
Ar2
O
Nanocrystalline MgO (5 mol %)
Ar3-CHO
N
2NH4OAc
N
H
+
+
100o
C, 30 min
Ar1
O
Ar3
Entry
Benzil
Ar1, Ar2
Aldehyde
Ar3
Product
Yield (%)a
Time (min)
M.p. (°C)
Found
Reported
1
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
C6H5
3a
3b
3c
3d
3e
3f
C6H5
4a
4b
4c
4d
4e
4f
94 (30)
96 (30)
97 (30)
94 (30)
93 (30)
93 (30)
91 (30)
90 (30)
91 (30)
92 (30)
95 (30)
94 (30)
94 (30)
92 (30)
93 (30)
94 (30)
94 (30)
96 (30)
94 (30)
95 (30)
96 (30)
97 (30)
270–272
230–233
228–231
260–261
263–265
259–262
198–201
269–271
282–283
301–303
259–260
273–276
261–264
170–172
255–257
213–216
254–256
215–216
251–253
287–290
207–208
218–220
272–273 [38]
2
C6H5
p-MeC6H4
232–235 [12]
3
C6H5
p-MeOC6H4
p-ClC6H4
230–232 [12]
4
C6H5
262–264 [12]
5
C6H5
p-BrC6H4
261.5–263.5 [12]
6
C6H5
m-MeOC6H4
O-HOC4H6
m-O2NC4H6
m-ClC6H4
–
7
C6H5
3g
3h
3i
4g
4h
4i
203–205 [38]
8
C6H5
265–267 [38]
9
C6H5
285–287 [12]
10
11
12
13
14
15
16
17
18
19
20
21
22
a
C6H5
3j
m-BrC6H4
4j
303–304 [12]
C6H5
3k
3l
p-HOC4H6
4k
4l
260–261 [38]
C6H5
2-Naphthyl
–
C6H5
3m
3n
3o
3p
3q
3r
3f
2-Thienyl
4m
4n
4o
4p
4q
4r
4s
262–266 [12]
C6H5
2,4-Cl2C6H3
p-(Me)2NC6H4
3,4-(MeO)2C6H3
3,5-(MeO)2C6H3
3-HO-4-MeOC6H4
m-MeOC6H4
m-BrC6H4
174–176 [12]
C6H5
257–258 [35]
C6H5
215–219 [12]
C6H5
–
–
–
–
–
–
C6H5
4-F C6H5
4-F C6H5
4-F C6H5
4-F C6H5
3j
4t
3p
3r
3,4-(MeO)2C6H3
3-HO-4-MeOC6H4
4u
4v
Isolated yield based on aldehyde
Preparation of 2,4,5-trisubstituted imidazoles by use
of nanocrystalline magnesium oxide
A mixture of 1,2-diketone (1 mmol), 0.15 g ammonium
acetate (2 mmol), aldehyde (1 mmol), and 0.008 g nano-
crystalline magnesium oxide (5 mol%) was stirred at
100 °C for 30 min. The progress of the reaction was
monitored by TLC (petroleum ether–ethyl acetate 7:3).
After cooling, the reaction mixture was dissolved in ace-
tone and filtered. The filtrate was concentrated on a rotary
evaporator under reduced pressure and the solid product
obtained was washed with water and recrystallized from
acetone–water 9:1 (v/v). Pure products were obtained in
excellent yields, as summarized in Table 3. Most of the
products are known and were identified by comparison of
their physical and spectral data with those of authentic
samples.
Fig. 2 13C NMR spectrum of compound 4t
stirring. The mixture was cooled to room temperature, fil-
tered, and washed with hot deionized water for effective
removal of the poly(vinyl alcohol). The final product was
dried at 80 °C for 24 h and calcined at 700 °C.
123

Synthesis of 2,4,5-trisubstituted imidazole derivatives
1343
2-(3-Methoxyphenyl)-4,5-diphenyl-1H-imidazole
(4f, C22H18N2O)
2-(3-Methoxyphenyl)-4,5-bis(4-fluorophenyl)-1H-imidaz-
ole (4s, C22H16F2N2O)
Colorless powder; yield 93%; m.p.: 259–262 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.70 (s, 1H, NH), 6.80–7.80
(m, 14H, Ar–H), 3.80 (s, 3H, OMe) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 160.00, 145.86, 137.63,
135.60, 132.15, 130.27, 129.20, 128.86, 127.70, 118.13,
Off-white powder; yield 94%; m.p.: 251–253 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.71 (s, 1H, NH), 7.65 (d,
1H, 3J = 7.6 Hz, Ar–H), 7.62 (s, 1H, Ar–H), 7.50–7.55 (m,
3
4H, Ar–H), 7.38 (t, 1H, J = 8.0 Hz, Ar–H), 7.30 (t, 2H,
3J = 8.8 Hz, Ar–H), 7.15 (t, 2H, 3J = 8.8 Hz, Ar–H), 6.94
3
114.70, 110.70, 55.70 ppm; IR (KBr): m = 3,432 (N–H),
(d, 1H, J = 8.0 Hz, Ar–H), 3.82 (s, 3H, OMe) ppm; 13C
ꢀ
1,591 (C=C), 1,513 (C=N) cm-1
;
UV (CDCl3):
NMR (100 MHz, DMSO-d6): d = 162.20 (C–F, d,
1J = 243.0 Hz), 161.57 (C–F, d, 1J = 243.0 Hz), 160.05,
145.90, 136.74, 132.04, 131.94, 131.09 (d, 3J = 7.0 Hz),
130.26, 129.37 (d, 3J = 7.0 Hz), 127.83, 127.58, 118.11,
116.15 (d, 2J = 21.0 Hz), 115.56 (d, 2J = 22.0 Hz), 114.68,
kmax = 314, 240 nm.
2-(2-Naphthyl)-4,5-diphenyl-1H-imidazole
(4l, C25H18N2)
Colorless powder; yield 94%; m.p.: 273–276 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.80 (s, 1H, NH), 8.61 (s,
1H, Ar–H), 8.25 (d, 1H, J = 8.0 Hz, Ar–H), 7.92–8.02
ꢀ
110.74, 55.61 ppm; IR (KBr): m = 3,441 (N–H), 1,600 (C=C),
1,520 (C=N) cm-1; UV (CDCl3): kmax = 315, 245 nm.
3
(m, 3H, Ar–H), 7.53–7.61 (m, 6H, Ar–H), 7.46 (t, 2H,
3J = 7.9 Hz, Ar–H), 7.39 (t, 1H, 3J = 7.6 Hz, Ar–H), 7.32
2-(3-Bromophenyl)-4,5-bis(4-fluorophenyl)-1H-imidazole
(4t, C21H13BrF2N2)
3
3
(t, 2H, J = 7.9 Hz, Ar–H), 7.24 (t, 1H, J = 7.6 Hz, Ar–
H) ppm; 13C NMR (100 MHz, DMSO-d6): d = 146.00,
137.90, 135.60, 133.50, 132.20, 131.50, 129.10, 129.00,
128.90, 128.70, 128.60, 128.30, 128.20, 127.60, 127.10,
Colorless powder; yield 95%; m.p.: 287–290 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.70 (s, 1H, NH), 8.26 (s,
1H, Ar–H), 8.06 (d, 1H, J = 8.0 Hz, Ar–H), 7.52–7.55
3
3
(m, 5H, Ar–H), 7.44 (t, 1H, J = 8.0 Hz, Ar–H), 7.30 (t,
3
3
ꢀ
127.00, 126.80, 124.10, 123.90 ppm; IR (KBr): m = 3,429
2H, J = 8.4 Hz, Ar–H), 7.15 (t, 2H, J = 8.4 Hz, Ar–H)
ppm; 13C NMR (100 MHz, DMSO-d6): d = 162.25 (C–F,
d, 1J = 244.0 Hz), 161.62 (C–F, d, 1J = 242.0 Hz),
(N–H), 1,601 (C=C), 1,510 (C=N) cm-1; UV (CDCl3):
kmax = 330, 288 nm.
4
144.34, 137.01, 132.85, 131.69 (d, J = 2.0 Hz), 131.37
(d, 3J = 8.0 Hz), 131.09, 131.01, 129.42 (d, 3J = 8.0 Hz),
2-(3,5-Dimethoxyphenyl)-4,5-diphenyl-1H-imidazole
(4q, C23H20N2O2)
4
128.09, 127.98, 127.56 (d, J = 2.0 Hz), 124.50, 122.62,
Colorless powder; yield 94%; m.p.: 254–256 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.70 (s, 1H, NH), 7.30–7.54
(m, 9H, Ar–H), 7.28 (d, 2H, J = 2.0 Hz, Ar–H), 7.22 (t,
2
116.22 (d, J = 22.0 Hz), 115.64 (d, J = 21.0 Hz) ppm;
2
ꢀ
IR (KBr): m = 3,437 (N–H), 1,604 (C=C), 1,516 (C=N)
4
cm-1; UV (CDCl3): kmax = 310, 245 nm.
3
1H, J = 7.8 Hz, Ar–H), 6.52 (t, 1H, 4J = 2.0 Hz, Ar–H),
3.81 (s, 6H, OMe) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 161.21, 145.76, 137.51, 135.56, 132.59, 131.52,
129.14, 128.98, 128.65, 128.30, 127.56, 127.01, 103.54,
2-(3,4-Dimethoxyphenyl)-4,5-bis(4-fluorophenyl)-1H-
imidazole (4u, C23H18F2N2O2)
Off-white powder; yield 96%; m.p.: 207–208 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.50 (s, 1H, NH), 7.48–7.63
(m, 6H, Ar–H), 7.30 (t, 2H, J = 8.0 Hz, Ar–H), 7.14 (t,
ꢀ
101.10, 55.83 ppm; IR (KBr): m = 3,429 (N–H), 1,601
(C=C), 1,533 (C=N) cm-1; UV (CDCl3): kmax = 310,
245 nm.
3
2H, 3J = 8.0 Hz, Ar–H), 7.05 (d, 1H, 3J = 8.0 Hz, Ar–H),
3.80 (s, 3H, OMe), 3.83 (s, 3H, OMe) ppm; 13C NMR
5-(4,5-Diphenyl-1H-imidazol-2-yl)-2-methoxyphenol
(4r, C22H18N2O2)
1
(100 MHz, DMSO-d6): d = 162.11 (C–F, d, J = 243.0
Hz), 161.47 (C–F, d, 1J = 241.0 Hz), 149.59, 149.27,
1
Ash-gray powder; yield 96%; m.p.: 215–216 °C; H NMR
3
146.17, 136.36, 132.04, 131.06 (d, J = 8.0 Hz), 129.30
(400 MHz, DMSO-d6): d = 12.50 (s, 1H, NH), 9.11 (s,
1H, OH), 7.46–7.55 (m, 6H, Ar–H), 7.42 (t, 2H,
3J = 7.6 Hz, Ar–H), 7.34 (t, 1H, 3J = 7.2 Hz, Ar–H),
7.28 (t, 2H, 3J = 7.6 Hz, Ar–H), 7.20 (t, 1H, 3J = 7.2 Hz,
Ar–H), 7.00 (d, 1H, 3J = 8.4 Hz, Ar–H), 3.81 (s, 3H,
OMe) ppm; 13C NMR (100 MHz, DMSO-d6): d = 148.58,
146.99, 146.31, 137.17, 135.86, 131.71, 129.05, 128.82,
128.62, 128.02, 127.51, 126.84, 123.94, 117.01, 113.31,
3
(d, J = 8.0 Hz), 128.02, 127.00, 123.55, 118.38, 116.18
(d, 2J = 21.0 Hz), 115.56 (d, 2J = 21.0 Hz), 112.27,
ꢀ
109.26, 56.03, 55.98 ppm; IR (KBr): m = 3,424 (N–H),
1,599 (C=C), 1,524 (C=N) cm-1; UV (CDCl3): kmax
310, 243 nm.
=
5-[4,5-Bis(4-fluorophenyl)-1H-imidazol-2-yl]-2-
methoxyphenol (4v, C22H16F2N2O2)
Silver powder; yield 97%; m.p.: 218–220 °C; 1H NMR
(400 MHz, DMSO-d6): d = 12.50 (s, 1H, NH), 9.13 (s,
1H, OH), 7.40–7.60 (m, 6H, Ar–H), 7.27 (t, 2H,
ꢀ
112.55, 56.09 ppm; IR (KBr): m = 3,409 (N–H), 3,260
(O–H), 1,596 (C=C), 1,510 (C=N) cm-1; UV (CDCl3):
kmax = 310, 244 nm.
123

1344
S. D. Khalili et al.
3J = 8.8 Hz, Ar–H), 7.13 (t, 2H, 3J = 8.8 Hz, Ar–H), 7.00
20. Lange JHM, Van Stuivenberg HH, Coolen HKAC, Adolfs TJP,
McCreary AC, Keizer HG, Wals HC, Veerman W, Borst AJM, de
Looff W, Verveer PC, Kruse CG (2005) J Med Chem 48:1823
21. Gallagher TH, Fier-Thompson SM, Garigipati RS, Sorenson ME,
Smietana JM, Lee D, Bender PE, Lee JC, Laydon JT, Griswold
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24. Tsuji J, Sakai K, Nemoto H, Nagashima H (1983) J Mol Catal
18:169
3
(d, 1H, J = 8.4 Hz, Ar–H), 3.81 (s, 3H, OMe) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 162.06 (C–F, d,
1
1J = 244.0 Hz), 161.47 (C–F, d, J = 242.0 Hz), 148.66,
3
147.02, 146.34, 136.32, 132.17, 130.96 (d, J = 8.0 Hz),
3
129.31 (d, J = 8.0 Hz), 128.00, 126.91, 123.84, 117.05,
116.08 (d, 2J = 21.0 Hz), 115.53 (d, 2J = 21.0 Hz),
ꢀ
113.32, 112.56, 56.08 ppm; IR (KBr): m = 3,437 (N–H),
3,298 (O–H), 1,594 (C=C), 1,521 (C=N) cm-1; UV
25. Evans DA, Lundy KM (1992) J Am Chem Soc 114:1495
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(CDCl3): kmax = 310, 242 nm.
Acknowledgments We gratefully acknowledge the financial sup-
port from the Research Council of the University of Kashan.
30. Lantos I, Zhang WY, Shui Y, Eggleston DS (1993) J Org Chem
58:7092
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