Novel one-pot synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles in water and tauto-isomerization study using NMR

Article abstract of DOI:10.1016/j.tet.2009.06.082

A simple and green route to synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles is described. Two isomers can tautomerize to each other by the heat absorption. The tauto-isomerization process was studied by NMR technique. Acidity and stability of products were studied using B3LYP method.

Full text of DOI:10.1016/j.tet.2009.06.082

Tetrahedron 65 (2009) 6882–6887
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Novel one-pot synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles in water
and tauto-isomerization study using NMR
*
Behzad Khalili, Tahereh Tondro, Mohammed M. Hashemi
Department of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and green route to synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles is described. Two iso-
mers can tautomerize to each other by the heat absorption. The tauto-isomerization process was studied
by NMR technique. Acidity and stability of products were studied using B3LYP method.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 13 January 2009
Received in revised form 2 June 2009
Accepted 19 June 2009
Available online 25 June 2009
1. Introduction
in the literature on the formation of (4 or 5)-aryl-2-aryloyl-(1H)-imi-
dazole derivatives via condensation of arylglyoxals with ammonium
As an important member of the five-membered ring heterocycles,
the imidazole moiety is present in a wide range of naturally occurring
molecules.1 Itis a common scaffoldinhighlysignificant biomolecules,
including biotin, the essential amino acid histidine, histamine, and
the pilocarpine alkaloids.2 Imidazolesalsohaveanability to behaveas
ligands in metalloenzymes and non-natural metal complexes.3 The
use of imidazoles and their derivatives in chemical processes, espe-
cially in pharmaceuticals, is becoming increasingly important, be-
cause of the possibility of hydrogen bond formation.4 Compounds
with an imidazole moiety have many pharmaceutical activities, sev-
eral of which have been incorporated in marketed drugs such as ci-
metidine and losartan.5 The biological importance of the imidazole
ring system has made it a common structure in numerous synthetic
compounds, such as fungicides,6 herbicides,6 plant growth regula-
tors7 and therapeutic agents.8 Recently, advances in green chemistry
and organometallic chemistry have extended the boundary of imid-
azoles to the synthesis and application of a large class of imidazoles
such as ionic liquid and imidazole9 related N-heterocyclic carbenes.10
Due to their wide range of biological, industrial and synthetic appli-
cations, these compounds have recently received a great deal of at-
tention. There are several methods reported in the literature for the
synthesis of imidazoles, such as hetero-cope rearrangement,11 four
component condensation of aryl glyoxals, primaryamines, carboxylic
acids and isocyanides on Wang resin,12 reaction of N-(2-oxo)amides
with ammonium trifluroacetate,13 1,2-aminoalcohols in the presence
acetate. In this paper, we describe the one-pot reaction between
arylglyoxals 2 and excess amount of ammonium acetate in water to
give (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles (1a or 1b) (Scheme 1).
Ar
O
N
N
NH4OAc
H
Ar
Ar
Ar
+
Ar
N
H
Water, rt
N
H
O
O
O
2
1a
1b
Scheme 1. Synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazole.
2. Results and discussion
During our latest work describing the synthesis of new pyrole
derivatives,20 we found that in some cases 1,3-dicarbonyl com-
pounds did not react and were recovered. Therefore the reactions
were repeated without using 1,3-dicarbonyl compounds to give
new compounds which were characterized as imidazole de-
rivatives. For example, the reaction of 4-methoxyphenylglyoxal in
the presence of an excess amount of ammonium acetate in ethanol
at room temperature was carried out. 1H NMR gave two signals for
NH with different intensities (13.4 ppm with high intensity and
13.5 ppm with low intensity), two singlet signals for the CH of
imidazole ring (7.90 ppm with high intensity and 7.64 ppm with
low intensity), two different signals for phenyl groups, and two
different signals for both methyl groups (Figs. 1a–c in Supple-
mentary data). These results show that there are two isomeric
2-aryloylimidazoles. The signal for NH of 4-aryl-2-aryloyl-
(1H)-imidazole (isomer 1a) has a lower chemical shift (ppm) than
5-aryl-2-aryloyl-(1H)-imidazole (isomer 1b). The a/b ratio was
determined by 1H NMR, using the intensities of the NH of the im-
idazole rings of two isomers. Two isomers (a and b) can be gen-
erated via a [1,5]-hydrogen shift as shown in Scheme 2. According
of PCl5,14 diketones, aldehydes, amine and ammonium acetate15
;
from a
-aminonitriles,16 Palladium-catalysed17 cyclisation of o-pen-
tafluorobenzoylamidoximes,18 from keto-oxime, aldehydes and am-
monium acetate.19 To the best of our knowledge, there are no reports
* Corresponding author. Tel.: þ98 2166165313; fax: þ98 2166165718.
E-mail address: mhashemi@sharif.edu (M.M. Hashemi).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.082

B. Khalili et al. / Tetrahedron 65 (2009) 6882–6887
6883
Table 2
O
HN
NH
N
O
HN
O
Synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles in water
O
Ph
NH4OAc
Ph
H
Ph
OH
Ph
Ph
N
Ph
N
H
Ph
Entry
Imidazole
Yield (%)
a/b Ratio
O
O
13
12
11
N
N
N
N
Path B
1
69
3.7
H
[1,5]-hydrogen shift
N
N
N
3
4
5
H
O
O
H
O
O
O
O
O
3b
Br
Cl
F
Br
Cl
F
HN
O
N
N
N
Path A
H
2
3
4
5
59
75
55
48
5.6
6.5
4.8
7.5
[1,5]-hydrogen shift
N
H
3a
O
Scheme 2. Plausible mechanism for imidazole synthesis.
N
the path A and B in which a and b isomers can be generated re-
spectively. In path A hydrogen shift begins through No.1 nitrogen
atom while in path B it begins through No.3 nitrogen atom. To
examine the solvent effect on [1,5]-hydrogen shift regioselectivity
(a/b ratio), different solvents were used. Results are summarized in
Table 1.
N
H
N
N
H
6
Table 1
Solvent effect on yield (%) and a/b ratio of products
Ph
Ph
Solvent
a/b ratio for compd (3), (4), (6)
N
Yield (%) for compd (3), (4), (6)
H2O
EtOH
EtOAC
CH3CN
CHCl3
DMSO
69, 59, 71
71, 87, 83
56, 68, 80
48, 63, 62
65, 77, 83
67, 65, 84
3.70, 5.90, 4.80
3.90, 6.00, 4.30
1.10, 1.85, 4.16
1.00, 6.25, 2.87
1.13, 2.00, 2.93
1.94, 6.60, 2.92
N
H
7
OMe
MeO
N
6
7
79
86
3.0
2.8
N
H
8
O
O
Based on the data from Table 1 and the friendly environmental
nature of water, it was chosen as solvent for these reactions. From
experimental and theoretical data we found that aryl groups in-
cluding electron withdrawing substituents show higher [1,5]-hy-
drogen shift regioselectivity. The results are summarized in Table 2.
The proposed mechanism involves an attack of (in situ) generated
aldimine 11 onto another aldimine molecule with the elimination of
one H2O molecule from 12 to give compound 13 (Scheme 2).
According to paths A and B with a [1,5]-hydrogen shift, 3a and
3b can be generated respectively. we tried to isolate these two
isomers (a and b) but since the isomers are converting rapidly to
each other therefore we could not isolate them. For the de-
termination of product percentage and spectral data assignment,
theoretical methods were used which optimized stabilization en-
ergy for two isomers using the B3LYP method on the basis set of (6-
311þþG d,p) and GAMESS program package.21 The equilibrium
constant from theoretical data was calculate using Eq. 1. Data from
this calculation for compounds 3, 4, 5, 6 and 8 are shown in Table 3.
OMe
OMe
MeO
MeO
N
N
H
9
O
O
O
O
8
76
2.9
N
N
10
H
O
Table 3
Calculated optimized stabilization energy and equilibrium constant for compounds
3, 4, 5, 6 and 8 [
E¼EaꢀEb (kcal)]
D
Compd
Ea (kcal)
Eb (kcal)
D
E(kcal)
K
3
4
5
6
8
ꢀ503,188.2520
ꢀ3,733,035.6128
ꢀ1,080,024.2923
ꢀ627,772.8164
ꢀ646,960.6730
ꢀ503,187.8446
ꢀ3,733,034.7928
ꢀ1,080,023.5374
ꢀ627,772.0698
ꢀ646,960.5844
ꢀ0.4074
ꢀ0.8199
ꢀ0.7549
ꢀ0.7466
ꢀ0.0886
0.0594
0.2506
0.0256
0.3206
0.5659
D
D
G ¼ G ꢀ Ga
G ¼ ꢀbRT ln K
(1)
K ¼ ½bꢁ=½aꢁ
D
G=RT
K ¼ eꢀ
The position of the NH signal of imidazole ring in 1H NMR
spectra verified our initial suposition that intra molecular hydrogen
bonding may be formed between the NH and the carbonyl group of
the aryloyl substitution. The obtained data from IR spectroscopy in
KBr and CCl4 showed no differences in the position of NH peaks.
Comparison of the 1H NMR spectra in methanol proved hydrogen
bonding with imidazole derivatives which was not observed in
acetone. This intra molecular hydrogen bonding limited the free
rotation of carbon-carbon single bond within the carbonyl group
and imidazole ring, that led to existence of two isomeric 2-aryloyl
imidazole structures. Two isomers can be tautomerized to each
other with [1,3]-hydrogen shifts which was investigated by NMR
method. We found that these two isomers can be interchanged
with thermal energy. We obtained thermodynamic data for this
interchange process with NMR technique.
Variable-temperature 1H NMR spectroscopy was used to in-
vestigate the barrier of H–N tauto-isomerization in the case of
compound 8 (Scheme 3).

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B. Khalili et al. / Tetrahedron 65 (2009) 6882–6887
OMe
OMe
MeO
MeO
MeO
N
Heat
HN
N
Tauto-isomerization
[1,3]-Hydrogen Shift
N
H
O
O
8a
8b
N
N
H
O
OMe
8b
Scheme 3.
1H NMR study of compound 8 in DMSO solvent showed four
distinct singlet signals for the hydrogens of the two methyl groups
at 298 K. 1H NMR study of these protons shows two distinct singlet
signals at 376 K. Figure 1 shows the temperature-dependent 1H
NMR spectra of these compounds exhibiting exchange broadening
of the two inner short peaks. Four separate signals can be observed
for hydrogens of two methyl groups below 320 K, while above
376 K, only two signals can be observed.
Figure 2. Eyring plot for tauto-isomerization study of compd 8.
Figure 3. Arrhenius plot for tauto-isomerization study of compd 8.
Table 5 shows the values of the experimental kinetic parameters
for compound 8 obtained from its rate constants.
The B3LYP method with the basis set of (6-311þþG d,p) for
calculating acidity (DHacidity) of these compounds in the gas and
solution phase with the use of compound 4 and an imaginary re-
action (Scheme 4) was used.
Table 5
Kinetic experimental parameters for compd 8
Kinetic parameter
Experimental value
D
D
D
D
G#
H#
S#
(kJ/mol)
(kJ/mol)
(J/mol)
81.13
75.86
298
298
ꢀ17.72
298
298
E#
(kJ/mol)
78.83
Figure. 1. Temperature-dependent 500 MHz 1H NMR spectra of compd 8. Only protons
attached to methyl groups represented.
Br
Br
Table 4 lists the experimental rate constants characterizing
tauto-isomerization of compound 8.
Eyring and Arrhenius plot from the rate constants extracted
using total line-shape analysis of compound 8, is presented in
Figures 2 and 3 respectively.
Br
Br
N
N
Gas Phase
H
+
N
N
H
O
4'a
O
4a
Scheme 4.
Table 4
Experimental rate constants
Based on this imaginary reaction the acidity of this compound
was calculated using Eq. 2:
T (K)
k
1/T
k/T
ln(k/T)
ln(k)
340.2
348.3
353.0
357.4
361.9
367.7
375.4
1.90
3.50
5.10
7.10
0.002939
0.002871
0.002833
0.002798
0.002763
0.002720
0.002664
0.005585
0.010049
0.014448
0.019866
0.030119
0.043514
0.064198
ꢀ5.18768
ꢀ4.60030
ꢀ4.23723
ꢀ3.91876
ꢀ3.50261
ꢀ3.13468
ꢀ2.74578
0.64185
1.25276
1.62924
1.96009
2.38876
2.77258
3.18221
ꢀ
ꢁ
h
i
ꢂ
ꢃ
D
Hacidity
¼
D
U þ
D
ðPVÞ ¼ U 40a þ U Hþ ꢀ U½4aꢁ þ 2:5RT
(2)
10.9
16.0
24.1
In Eq. 2, U is thecalculated absolute energyand2.5RT is thekinetic
energy contribution from Hþ at 298 K. U[Hþ]¼0 because Hþ has no

B. Khalili et al. / Tetrahedron 65 (2009) 6882–6887
6885
electron. This contribution is zero at 0 K. In progress for comparison
3.3. NMR measurements for tauto-isomerization study
of acidity in gas and solutionphase we calculate acidity of compound
4 in water using PCM model. The resulets are given in Table 6. From
these data the acidity in water phase is higher than gas phase. We
think that this difference resulted from water solvation which is
higher in the case of ionic than nutral parts and absend in gas phase.
1H NMR measurements were performed on a Bruker AMX500
using 5 mm variable temperatures (VT) probe with proton obser-
vation at 500.13 MHz. All measurements were made on spinning
samples in the locked mode. In all measurements, acquisition time
was 1.58 s/scan, (with a) pulse length of 9.65 ls, and pulse delay
time of 10 s. Typically 16 scans were collected at each temperature
and stored in 32k of memory. Sweep width was 10,330.58 Hz for all
spectra, giving a digital resolution of 0.316 Hz/point. The resulting
solution spectra for all compounds had typical S/N ratios greater
than 500:1. The spectra line-width parameter, T2nat, was de-
termined for each spectrum by measuring the line width of the
TMS. Probe temperatures (ꢄ0.5) were measured with a calibrated,
digital thermocouple.
Table 6
Data for acidity of compd 4
Parameter
Value (kcal/mol)
DH
DH
DH
*
¼
D
H(acidity) in gas phase
326.16
302.73
23.43
**
¼DH(acidity) in water phase
***
¼
DH
ꢀDH
* **
Finally, Figure 4 shows the optimized geometry for the ground
state of compounds 8a (lower) and 8b (upper) by B3LYP method in
(6-311þþG d,p) basis set.
3.4. Computational methods
All computations were carried out with the GAMESS program
package. The energies and geometries were calculated with B3LYP
method and 6-311þþG(d,p) basis set. Harmonic vibrational fre-
quencies were computed to confirm an optimized geometry cor-
responds to local minimum that has only real frequencies. Rate
constants were calculated for exchange spectra using the MEXICO23
program, which uses an iterative nonlinear least squares regression
analysis to obtain the best fit of the experimental spectrum.
4. Characterization of compounds 3–10
4.1. Phenyl-(5-phenyl-1H-imidazol-2-yl)ketone (3a) and
phenyl-(4-phenyl-1H-imidazol-2-yl)ketone (3b)
A yellow solid, 1H NMR (500 MHz, DMSO-d6):
d 13.80 (0.25H, s,
NH), 13.63 (1H, s, NH), 8.60 (2H, d, J 7.76 Hz), 8.47 (0.5H, d, J 7.7 Hz),
8.08 (1H, s), 7.97 (0.5H, d, J 7.95 Hz), 7.94 (2H, d, J 7.64 Hz), 7.79
(0.25H, s), 7.69 (1H, t, J 7.1 Hz), 7.66 (0.25H, t, J 7.6 Hz), 7.60 (2H, t, J
7.6 Hz), 7.57 (0.5H, t, J 8.1 Hz), 7.47 (0.5H, t, J 7.55 Hz), 7.42 (2H, t, J
7.7 Hz), 7.37 (0.25H, t, J 7.1 Hz), 7.28 (1H, t, J 7.3 Hz). 13C NMR
(125 MHz, DMSO-d6): d 181.6, 179.2, 146.6, 145.5, 143.7, 137.0, 136.8,
136.6, 134.5, 133.9, 133.7, 131.5, 131.4, 129.8, 129.5, 129.1, 129.0,
128.0, 126.5, 125.7, 119.5. IR (neat, cmꢀ1): 3270, 1621, 1454, 1280,
1164, 906, 771, 687. Anal. Calcd for C16H12N2O: C, 77.40; H, 4.87; N,
11.28. Found: C, 77.39; H, 4.73; N, 11.17.
Figure 4. Optimized geometry of compounds 8a and 8b.
In conclusion, we report an efficient, novel, and entirely green
procedure for the synthesis of new imidazole derivatives in water
without using any catalyst at room temperature. In addition, a very
easy workup, short reaction time and obtaining pure products di-
rectly by filtration, washing the filtrate with water and crystaliza-
tion from ethanol are some advantages of this new method.
4.2. 4-Fluorophenyl-[5-(4-fluorophenyl)-1H-imidazol-2-
yl]ketone (6a) and 4-fluorophenyl-[4-(4-fluorophenyl)-1H-
imidazol-2-yl]ketone (6b)
A yellow solid, 1H NMR (500 MHz, DMSO-d6):
d 13.81 (0.2H, s,
3. Experimental section
NH), 13.64 (1H, s, NH), 8.70 (2H, dd, J 5.89, 8.64 Hz), 8.58 (0.4H, dd, J
5.15, 8.07 Hz), 8.07 (1H, s), 8.01 (0.4H, dd, J¼5.01, 8.16 Hz), 7.95 (2H,
dd, J 5.74, 8.31 Hz), 7.76 (0.2H, s), 7.43 (2H, t, J 8.82 Hz), 7.39 (0.4H, t,
J 8.83 Hz), 7.31 (0.4H, t, J 8.74 Hz), 7.25 (2H, t, J 8.8 Hz). 13C NMR
3.1. General procedure for synthesis of (4 or 5)-aryl-2-aryloyl-
(1H)-Imidazole derivatives
(125 MHz, DMSO-d6): d 179.9, 179.8, 166.9, 164.9, 163.3, 161.4, 145.3,
To arylglyoxal22 compound (1 mmol) in water (10 ml), was added
ammonium acetate (5 mmol), successively at room temperature
(20–25 ꢂC) and stirred at the same temperature for the 30–45 min.
After appropriate time the reaction mixture was concentrated, then
the obtained solid was filtrated, washed with water (3ꢃ15 mL), and
the crude was purified by crystallization from ethanol.
145.2,142.8,134.5,134.5,133.3,131.0,131.0,128.7,128.7,127.6,127.6,
119.4, 116.7, 116.4, 116.3, 116.2, 116.2. IR (neat, cmꢀ1): 3282, 3129,
3096, 1623, 1595, 1514, 1450, 1245, 1160, 906, 838, 774, 649. Anal.
Calcd for C16H10F2N2O: C, 67.60; H, 3.55; N, 9.85. Found: C, 67.59; H,
3.68; N, 10.02.
4.3. 4-Chlorophenyl-[5-(4-chlorophenyl)-1H-imidazol-2-
yl]ketone (5a) and 4-chlorophenyl-[4-(4-chlorophenyl)-1H-
imidazol-2-yl]ketone (5b)
3.2. Sample preparation for tauto-isomerization study
Solution-phase NMR samples for 1H NMR was prepared with
0.1 M concentration. Deuteriated solvent was obtained from Merck.
DMSO-d6 were 99.5 atoms% D and contained 1% of TMS.
An orange solid, 1H NMR (500 MHz, DMSO-d6):
NH), 13.73 (1H, s, NH), 8.60 (2H, d, J 8.5 Hz), 8.50 (0.3H, d, J 8.2 Hz),
d 13.91 (0.15H, s,

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B. Khalili et al. / Tetrahedron 65 (2009) 6882–6887
8.15 (1H, s), 7.99 (0.3H, d, J 8.7 Hz), 7.95 (2H, d, J 8.4 Hz), 7.84(0.15H,
s), 7.68 (2H, d, J 8.5 Hz), 7.65 (0.3H, d, J 8.25 Hz), 7.54 (0.3H, d, J
7.55 Hz), 7.49 (2H, d, J 8.4 Hz). 13C NMR (125 MHz, DMSO-d6):
(0.3H, s), 7.48–7.44 (2.3H, m), 7.14 (1H, d, J 8.24 Hz), 7.10 (0.3H, d, J
8.22 Hz), 7.01–6.97 (1.3H, m), 6.18 (2H, s), 6.17 (0.6H, s), 6.07 (0.6H,
s), 6.04 (2H, s). 13C NMR (125 MHz, DMSO-d6):
d 182.2, 179.2, 152.4,
d
181.6, 179.7, 147.9, 146.3, 143.7, 137.0, 136.8, 136.6, 134.5, 133.9,
148.53, 148.25, 148.1, 147.2, 145.2, 143.4, 130.9, 128.8, 128.4, 128.1,
120.6, 119.2, 118.4, 110.7, 109.6, 109.4, 108.9, 108.7, 106.9, 106.2,
102.8, 102.1, 101.8. IR (neat, cmꢀ1): 3444, 3285, 1622, 1500, 1460,
1245, 1099, 1039, 935, 812, 770, 457. Anal. Calcd for C18H12N2O5: C,
64.29; H, 3.60; N, 8.33. Found: C, 64.10; H, 3.65; N, 8.40.
133.7,131.5,131.4,129.8,129.5,129.1,129.0,128.0,126.5,125.7,119.5.
IR (neat, cmꢀ1): 3277, 3112, 3096, 1619, 1539, 1514, 1445, 1293, 1172,
1100, 1019, 906, 834, 770. Anal. Calcd for C16H10Cl2N2O: C, 60.59; H,
3.18; N, 8.83. Found: C, 60.58; H, 3.10; N, 8.61.
4.4. 4-Bromophenyl-[5-(4-bromophenyl)-1H-imidazol-2-
yl]ketone (4a)and 4-bromophenyl-[4-(4-bromophenyl)-1H-
imidazol-2-yl]ketone (4b)
4.8. Biphenyl-4-yl-[5-(biphenyl-4-yl)-1H-imidazol-2-
yl]ketone (11a) and biphenyl-4-yl-[4-(biphenyl-4-yl)-1H-
imidazol-2-yl]ketone (11b)
A yellowish brown solid, 1H NMR (500 MHz, DMSO-d6):
d 13.91
A yellow solid, 1H NMR (500 MHz, DMSO-d6):
d 13.81 (0.3H, s,
(0.16H, s, NH),13.73 (1H, s, NH), 8.51 (2H, d, J 8.4 Hz), 8.42 (0.32H, d, J
8.3 Hz), 8.16 (1H, s), 7.93 (0.32H, d, J 8.15 Hz), 7.89 (2H, d, J 8.35 Hz),
7.83 (2H, d, J 8.45 Hz), 7.80 (0.32H, d, J 8.4 Hz), 7.79 (0.16H, s), 7.67
(0.32H, d, J 8.05 Hz), 7.62 (2H, d, J 8.35 Hz). 13C NMR (125 MHz,
NH), 13.69 (1H, s, NH), 8.74 (2H, d, J 7.95 Hz), 8.60 (0.6H, d, J
7.95 Hz), 8.16 (1H, s), 8.08 (0.6H, d, J 7.2 Hz), 8.05 (2H, d, J 7.8 Hz),
7.94 (2.3H, m), 7.88 (0.6H, d, J 7.9 Hz), 7.82 (2H, d, J 7.55 Hz), 7.79
(0.6H, d, J 6.35 Hz), 7.74 (5.2H, m), 7.52 (3H, m), 7.48 (3H, m), 7.45
(0.9H, m), 7.37 (0.9H, m). 13C NMR (125 MHz, DMSO-d6):
d 180.9,
DMSO-d6): d 181.6,179.7,145.8,144.3,143.7,137.0,136.8,136.6,134.5,
133.9, 133.7, 131.5, 131.4, 129.8, 129.5, 129.1, 129.0, 128.0, 126.5, 125.7,
119.5. IR (neat, cmꢀ1): 3269, 3025, 1612, 1579, 1557, 1451, 1292, 1171,
1073,1012, 901, 833, 767, 707, 644, 513. Anal. Calcd for C16H10Br2N2O:
C, 47.32; H, 2.48; N, 6.90. Found: C, 47.30; H, 2.56; N, 6.82.
179.8, 145.7, 145.3, 144.5, 143.4, 140.6, 139.8, 139.6, 135.6, 133.7,
133.0, 132.3, 132.2, 130.0, 129.9, 129.9, 129.9, 129.8, 129.8, 129.8,
129.7, 129.3, 129.2, 129.1, 128.2, 127.9, 127.9, 127.8, 127.7, 127.7, 127.4,
127.3, 127.3, 126.3, 119.8, 119.7. IR (neat, cmꢀ1): 3270, 3055, 3032,
1615, 1453, 1286, 1169, 906, 839, 755. Anal. Calcd for C28H20N2O: C,
83.98; H, 5.03; N, 7.00. Found: C, 83.99; H, 5.00; N, 6.00.
4.5. 4-Methoxyphenyl-[5-(4-methoxyphenyl)-1H-imidazol-2-
yl]ketone (8a) and 4-methoxy phenyl-[4-(4-methoxyphenyl)-
1H-imidazol-2-yl]ketone (8b)
Acknowledgements
A yellow solid, 1H NMR (500 MHz, DMSO-d6):
d 13.52 (0.37H, s,
We thank the Research Office of the Sharif University of Tech-
nology for financial support, Dr. S. Taheri and Mrs. A. Karimnia for
taking NMR Spectra and Dr. N. Hadi, Dr. A. Fattahi, Dr. A. Ziyaei, Dr.
B. Eftekhari-sis and Dr. Z. Tehrani (Sharif University of Technology)
for to their valuable advice and suggestions. We also offer special
thank Mr. M.A. Frozaneh for his valuable helps about tauto-isom-
erization study.
NH), 13.40 (1H, s, NH), 8.67 (2H, d, J 9 Hz), 8.54 (0.74H, d, J 8.9 Hz),
7.90 (1H, s), 7.89 (0.74H, d, J 8.16 Hz), 7.84 (2H, d, J 8.65 Hz), 7.64
(0.37H, s), 7.13 (2H, d, J 8.9 Hz), 7.09 (0.74H, d, J 8.85 Hz), 7.01 (0.74H,
d, J 8.9 Hz), 6.99 (2H, d, J 8.75 Hz), 3.88 (3H, s), 3.87 (1.11H, s), 3.80
(1.11H, s), 3.78 (3H, s). 13C NMR (125 MHz, DMSO-d6):
d 179.9, 179.8,
164.1, 163.9, 161.0, 159.4, 146.4, 145.5, 143.5, 136.2, 133.9, 133.8,
129.7, 129.5, 128.5, 128.0, 127.3, 127.0, 122.1, 117.8, 115.2, 114.9, 114.5,
114.4, 56.4, 56.3, 56.0, 55.9. IR (neat, cmꢀ1): 3266, 1611, 1598, 1455,
1289, 1250, 1163, 1028, 905, 832, 774, 643. Anal. Calcd for
C18H16N2O3: C, 70.12; H, 5.23; N, 9.09. Found: C, 70.12; H, 5.27; N,
8.91.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.06.082.
4.6. 3,4-Dimethoxyphenyl-[5-(3,4-dimethoxyphenyl)-1H-
imidazol-2-yl]ketone (9a) and 3,4-dimethoxyphenyl-[4-(3,4-
dimethoxyphenyl)-1H-imidazol-2-yl]ketone (9b)
References and notes
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A yellow solid, 1H NMR (500 MHz, DMSO-d6):
d 13.57 (0.35H, s,
NH), 13.41 (1H, s, NH), 8.47 (1H, d, J 1.5 Hz), 8.38 (1.35H, m), 8.07
(0.35H, d, J 1.61 Hz), 7.97 (1H, s), 7.70 (0.35H, s), 7.62 (0.35H, s), 7.51
(1H, s), 7.48 (1.35H, m), 7.18 (1H, d, J 8.55 Hz), 7.14 (0.35H, d, J
8.59 Hz), 7.01 (1.35H, m), 3.91 (3H, s), 3.90 (3H, s), 3.88 (1.05H, s),
3.86 (1.05H, s), 3.85 (1.05H, s), 3.83 (3H, s), 3.79 (1.05H, s), 3.76 (3H,
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d 179.6, 179.4, 154.0 153.9, 149.9,
7. (a) Schmierer, R.; Mildenberger, H.; Buerstell, H. German Patent 3614364, 1987;
(b) Schmierer, R.; Mildenberger, H.; Buerstell, H. Chem. Abstr. 1988, 108, 37838.
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149.8, 149.0, 148.9, 145.5, 143.5, 129.6, 129.3, 128.7, 127.6, 126.6,
126.2, 119.1, 118.1, 117.9, 114.4, 113.8, 112.9, 111.8, 111.6, 110.2, 109.5,
56.61, 56.58, 56.43, 56.40, 56.30, 56.28, 56.17, 56.14. IR (neat, cmꢀ1):
3431, 2922, 1627, 1513, 1469, 1378, 1270, 1137, 1022, 853, 768, 608,
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4.7. Benzo[d][1,3]dioxol-5-yl-[5-(benzo[d][1,3]dioxol-5-yl)-
1H-imidazol-2-yl]ketone (10a)and benzo[d][1,3]dioxol-5-yl-
[4-(benzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl]ketone (10b)
A yellowish green solid, 1H NMR (500 MHz, DMSO-d6):
d 13.52.
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