Efficient microwave-assisted synthesis and antioxidant activity of 4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones

Article abstract of DOI:10.1002/jhet.766

The efficient synthesis of 4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones was achieved via microwaveassisted reactions of 4-arylmethylene-2-phenyloxazol-5(4H) -ones with urea in glycol. This approach provides a facile shortcut for the synthesis of this type

Full text of DOI:10.1002/jhet.766

January 2012
Efficient Microwave-Assisted Synthesis and Antioxidant Activity
of 4-Arylidene-2-phenyl-1H-imidazol-5(4H)-ones
59
Feng Shi,a,b† Xiao-Ning Zeng,c† Fei-Yue Wu,a Shu Yan,a Wei-Fa Zheng,a*
and Shu-Jiang Tua,b
*
aSchool of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou 221116,
People’s Republic of China
bCollege of Chemistry, Chemical Engineering and Materials Science, Soochow University,
Suzhou 215000, People’s Republic of China
cClinical Research Center, the First Affiliated Hospital of Nanjing Medical University,
Nanjing 210029, People’s Republic of China
*E-mail: laotu2001@263.net
†These authors contributed equally to the work.
Received August 17, 2010
DOI 10.1002/jhet.766
Published online 23 August 2011 in Wiley Online Library (wileyonlinelibrary.com).
The efficient synthesis of 4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones was achieved via microwave-
assisted reactions of 4-arylmethylene-2-phenyloxazol-5(4H)-ones with urea in glycol. This approach pro-
vides a facile shortcut for the synthesis of this type of compounds with short reaction time, high yields,
broad substrate scope and easy operation. Besides, the synthesized compounds were subject to the test
of antioxidant activity, which is represented by their capacities for scavenging 1,1-diphenyl-2-picrylhy-
drazyl, hydroxyl and superoxide anion free radicals. Bioassay of these compounds resulted in the find-
ing of several 4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones with significant antioxidant activity.
J. Heterocyclic Chem., 49, 59 (2012).
INTRODUCTION
substrate scope and operational complexity. On the other
hand, to the best of our knowledge, the antioxidant activ-
ity of 4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones has
not been investigated. Therefore, developing a synthetic
method of these target compounds with high efficiency,
broad substrate scope and easy operation as well as evalu-
ation of their antioxidant activity is of great significance.
As a continuation of our efforts on the efficient synthe-
sis and potential bioactivities of heterocyclic compounds
[11], we report the facile synthesis of 4-arylidene-2-phe-
nyl-1H-imidazol-5(4H)-ones 3 via condensations of 4-
arylmethylene-2-phenyloxazol-5(4H)-ones 1 with urea 2
in glycol under microwave irradiation (MW) (Scheme 1)
and the bioassay of their antioxidant activity.
4-Arylidene-2-phenyl-1H-imidazol-5(4H)-ones (Fig. 1),
one important kind of imidazole derivatives, have exhib-
ited various bioactivities including immunomodulatory [1],
anticancer [2], anti-inflammatory [3], leishmanicidal [4],
antibacterial and antifungal [5] activities besides their
actions as dual specificity tyrosine-regulated kinase-1A
inhibitors [6] and potential COX-2 inhibitors [7]. There-
fore, the synthesis and bioassay of this type of compounds
have absorbed great and persistent attention during half of
the century.
Survey of the literature reveals that there are mainly
three typical approaches to the synthesis of 4-arylidene-
2-phenyl-1H-imidazol-5(4H)-ones. One method is the
condensation of 4-arylmethylene-2-phenyloxazol-5(4H)-
ones with ammonium acetate, urea or thiourea under
various conditions [8]. Another method is the multicom-
ponent reactions of benzamidine or its hydrochloride, ar-
omatic aldehyde, and 2-haloacetate [9]. The other
method is the similar three-component condensations of
ethoxy substituted benzamidine, aromatic aldehyde, and
2-aminoacetate [10].
RESULTS AND DISCUSSION
Initially, the condensation of 4-(4-chlorobenzylidene)-
2-phenyloxazol-5(4H)-one 1c (1 mmol) with urea 2 (1.5
mmol) was employed to optimize the reaction condi-
tions. To find the best suitable solvent, we compared the
synthesis of 3c in different solvents including water,
glycol, DMF, glacial acetic acid, and ethanol at 160ꢀC
and 300 W. The results (Table 1) reveal that glycol as
However, these methods still have one or more limita-
tions such as long reaction time, moderate yields, narrow
C
V
2011 HeteroCorporation

60
F. Shi, X.-N. Zeng, F.-Y. Wu, S. Yan, W.-F. Zheng, S.-J. Tu
Vol 49
Table 1
Solvent optimization for the synthesis of 3c.
Entry
Solvent
Time (min)
Yield (%)
1
2
3
4
5
DMF
EtOH
HOAc
Water
Glycol
4
4
4
4
4
71
45
Figure 1. Structure of 4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones.
Trace
24
82
solvent can greatly improve the yield of this reaction.
Therefore, glycol was preferred as solvent for all further
microwave-assisted reactions.
To optimize the reaction temperature, the condensa-
tion of 1c (1 mmol) with urea 2 (1.5 mmol) was carried
out using glycol (2 mL) as solvent under MW (300 W)
at temperatures ranging from 100 to 190ꢀC, with an in-
crement of 10ꢀC each time. The results are shown in
Table 2. The yield of product 3c was increased when
the temperature was increased from 100 to 180ꢀC
(Entries 1ꢁ9, Table 2), whereas the yield leveled off
when the temperature was further increased to 190ꢀC
(Entry 10, Table 2). So, 180ꢀC is assigned as the most
suitable reaction temperature.
ones 3 were subject to the test of antioxidant activity, which
is represented by their capacities for scavenging 1,1-di-
phenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and
superoxide anion (Oꢁ2 ) free radicals using protocols
described in our previous works [11e,f], and the results are
summarized in Table 4. Compared with the positive control
(PC) L-Ascorbic acid, all the tested compounds showed
strong capacities for scavenging Oꢁ2 and OH, and most of
the tested compounds also showed strong capacities for
scavenging DPPH. The top three for scavenging DPPH and
OH radicals are compounds 3h, 3i, and 3j with two or three
methoxyl groups in the aromatic ring. Although the top
three for scavenging Oꢁ2 are compounds 3h, 3j, and 3c with
2,3-dimethoxylbenzyl, 3,4,5-trimethoxylbenzyl and 4-chlor-
obenzyl as Ar group, respectively. It is worthnoting that
compound 3h has the most extraordinary capacities for
scavenging all the three radicals, which are dozens of times
higher than those of the PC. Although there is no regular
relationship between the Ar group and the antioxidant activ-
ity of the tested compounds, it is obvious that the methoxyl
groups in the aromatic ring may contribute to the antioxi-
dant activity of the top three compounds 3h, 3i, and 3j.
In conclusion, this study has achieved the efficient
synthesis of 4-arylidene-2-phenyl-1H-imidazol-5(4H)-
ones and examined their in vitro antioxidant activity.
This microwave-assisted approach does provide a facile
shortcut for the synthesis of the target compounds with
short reaction time, high yields, broad substrate scope,
and easy operation. More importantly, bioassay of these
compounds resulted in the finding of several 4-aryli-
dene-2-phenyl-1H-imidazol-5(4H)-ones with significant
Under these optimized reaction conditions (2.0 mL of gly-
col, 180ꢀC), a series of 4-arylidene-2-phenyl-1H-imidazol-
5(4H)-ones 3 were synthesized under MW, and the results
were summarized in Table 3. Obviously, this protocol can
be applied not only to substrate 1 with either electron-with-
drawing or electron-donating group in aromatic ring, but
also to substrate 1 with heterocyclic aromatic ring in high
yields. Therefore, this efficient approach has wide scope of
applicability in synthesizing these type of compounds.
The structures of all the synthesized compounds were
established on the basis of their spectroscopic data and
high resolution mass spectrum (HRMS) [electrospray
ionization (ESI)]. The stereochemistry of the double
bond was designated as Z configuration by comparing
the 1H NMR data of compound 3a with that reported in
literature [12]. A plausible mechanism for the formation
of compounds 3 is suggested in Scheme 2. First, ammo-
nia acting as a nucleophilic reagent, which is obtained
from urea 2, attacks 4-arylmethylene-2-phenyloxazol-
5(4H)-ones 1 to generate the aminolysis of this starting
material and thereby performs the ring-opening reaction.
Second, the intramolecular nucleophilic addition and sub-
sequent elimination of water molecule affords final cyclic
4-arylidene-2-phenyl-1H-imidazol-5(4H)-ones 3.
Table 2
Temperature optimization for the synthesis of 3c.
Entry
T (ꢀC)
Time (min)
Yield (%)
To survey the possible biological activities of this class
of compounds, 4-arylidene-2-phenyl-1H-imidazol-5(4H)-
1
2
3
100
110
120
130
140
150
160
170
180
190
8
8
8
8
6
6
4
4
4
4
Trace
Trace
29
Scheme 1
4
5
48
61
6
7
75
82
8
87
90
90
9
10
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2012
Efficient Microwave-Assisted Synthesis and Antioxidant Activity of
4-Arylidene-2-phenyl-1H-imidazol-5(4H)-ones
61
Table 3
Table 4
Free radicals scavenging capacities of compounds 3.a
Scope for the synthesis of 3 under MW.
Time Yield
(min) (%)
3
DPPH (%/mg)
OH (%/mg)
Oꢁ2 (%/mg)
Entry
1
3
Ar
m.p. (ꢀC)
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
PCb
195.51 6 4.24
177.88 6 2.78
163.46 6 2.78
177.88 6 5.55
240.38 6 5.55
144.23 6 5.55
118.59 6 3.21
489.97 6 6.82
692.46 6 9.23
434.45 6 13.22
545.74 6 14.26
769.14 6 25.54
546.25 6 1.05
500.71 6 9.87
610.68 6 11.72
509.83 6 12.48
626.30 6 20.67
290.75 6 34.87
333.92 6 13.13
470.17 6 17.41
568.69 6 10.17
3a C6H5
4
83
>300
(272–273)8b
279–281
>300
(289–290)8b
282–283
>300
263–264
>300
260–261
282–284
>300
2
3
3b 2-ClC6H4
3c 4-ClC6H4
6
4
80
90
4
5
6
3d 3-BrC6H4
3e 4-BrC6H4
3f 3-NO2C6H4
4
4
4
4
6
6
6
4
4
84
86
85
83
77
76
73
85
80
2003.21 6 57.78 4131.61 6 97.15 3470.95 6 126.50
240.38 6 11.10 1269.46 6 3.12
561.52 6 17.41
973.80 6 15.14
531.60 6 6.17
576.21 6 5.48
577.38 6 3.20
104.17 6 1.10
7
8
3g 4-NO2C6H4
400.64 6 8.48
205.13 6 5.78
195.51 6 6.41
115.38 6 2.78
182.82 6 0.98
959.60 6 4.01
438.38 6 6.36
508.94 6 13.55
565.55 6 5.44
97.25 6 0.83
3h 2,3-(CH3O)2C6H3
3i 3,4-(CH3O)2C6H3
3j 3,4,5-(CH3O)3C6H2
3k 3,4-OCH2OC6H3
3l 4-(CH3)2NC6H4
9
10
11
12
>300
293-294
(268–269)8b
>300
(291–292)8b
a The scavenging capacities were represented as percentage inhibition
(mean 6 S.D., n ¼ 3) of the free radicals by 1 mg tested compound.
b L-Ascorbic acid was used as a positive control (PC).
13
3m Thiophen-2-yl
4
83
mmol) in ethylene glycol (2.0 mL) were mixed and then capped.
The mixture was irradiated by microwave at 300 W and 180ꢀ
for a given time. Upon completion, monitored by thin layer chro-
matography (TLC), the reaction mixture was cooled to room
temperature and then poured into cold water, filtered to give the
crude products, which were further purified by recrystallization
from 95% EtOH.
antioxidant activity, which gains some insights into the
possible application of these compounds for the treat-
ment of oxidative-induced diseases.
EXPERIMENTAL
(Z)-4-Benzylidene-2-phenyl-1H-imidazol-5(4H)-one (3a). IR
(KBr): 3124, 3067, 2989, 1698, 1639, 1539, 1496, 1452, 1419,
Microwave irradiation was carried out in a monomodal
EmrysTM Creator from Personal Chemistry, Uppsala, Sweden.
Melting points were determined in XT5 apparatus and are uncor-
rected. IR spectra were recorded on a FT-IR-Tensor 27 spec-
1322, 1266, 1187, 1031, 922, 775, 687 cmꢁ1 1H NMR (400
;
MHz, DMSO) (d, ppm): 12.12 (s, 1H, NH), 8.32 (d, J ¼ 7.2
Hz, 2H, ArH), 8.18 (d, J ¼ 7.6 Hz, 2H, ArH), 7.67–7.69 (m,
3H, ArH), 7.52–7.44 (m, 3H, ArH), 7.04 (s, 1H, ¼¼CH);
HRMS (ESI): m/z [MþH]þ calcd for C16H13N2O: 249.1023;
found: 249.1023.
1
trometer. H NMR spectra were measured on a DPX 400 spec-
trometer operating at 400 MHz, using DMSO-d6 as solvent and
TMS as internal standard. HRMS (ESI) was determined by using
micrOTOF-QII HRMS/MS instrument (BRUKER). All chemi-
cals except 4-arylidene-2-phenyl-1,3-oxazol-5(4H)-ones 1 were
purchased and used without further purification. 4-Arylidene-2-
phenyl-1,3-oxazol-5(4H)-ones 1 were synthesized according to a
previously reported approach [13].
General procedure for the synthesis of compounds
3. Typically, in a 10-mL EmrysTM reaction vial, 4-arylmethy-
lene-2-phenyloxazol-5(4H)-ones 1 (1.0 mmol) with urea 2 (1.5
(Z)-4-(2-Chlorobenzylidene)-2-phenyl-1H-imidazol-5(4H)-one
(3b). IR (KBr): 3151, 3125, 3061, 2990, 1707, 1638, 1499,
1456, 1216, 1033, 896, 755, 684 cmꢁ1 1H NMR (400 MHz,
.
DMSO) (d, ppm): 12.30 (s, 1H, NH), 9.05 (d, J ¼ 8.0 Hz, 1H,
ArH), 8.20 (d, J ¼ 8.4 Hz, 2H, ArH), 7.69–7.59 (m, 4H, ArH),
7.53–7.46 (m, 2H, ArH), 7.30 (s, 1H, ¼¼CH). HRMS (ESI): m/z
[MþH]þ calcd for C16H12ClN2O: 283.0633; found: 283.0641.
(Z)-4-(4-Chlorobenzylidene)-2-phenyl-1H-imidazol-5(4H)-one
(3c). IR (KBr): 3153, 3124, 3066, 2987, 1703, 1641, 1541,
1456, 1261, 1180, 1092, 923, 788, 691 cmꢁ1 1H NMR (400
.
Scheme 2
MHz, DMSO) (d, ppm): 12.18 (s, 1H, NH), 8.36 (d, J ¼ 8.4
Hz, 2H, ArH), 8.19 (d, J ¼ 8.4 Hz, 2H, ArH), 7.67–7.56 (m,
5H, ArH), 7.05 (s, 1H, ¼¼CH). HRMS (ESI): m/z [MþH]þ
calcd for C16H12ClN2O: 283.0633; found: 283.0636.
(Z)-4-(3-Bromobenzylidene)-2-phenyl-1H-imidazol-5(4H)-one
(3d). IR (KBr): 3127, 3068, 2982, 1711, 1647, 1536, 1454,
1419, 1356, 1262, 1193, 907, 782, 681 cmꢁ1 1H NMR (400
.
MHz, DMSO) (d, ppm): 12.20 (s, 1H, NH), 8.58 (s, 1H, ArH),
8.31 (d, J ¼ 8.0 Hz, 1H, ArH), 8.16 (d, J ¼ 6.8 Hz, 2H,
ArH), 7.67–7.61 (m, 4H, ArH), 7.46 (t, J ¼ 8.0 Hz, 1H, ArH),
7.02 (s, 1H, ¼¼CH). HRMS (ESI): m/z [MþH]þ calcd for
C16H12BrN2O: 327.0128; found: 327.0145.
(Z)-4-(4-Bromobenzylidene)-2-phenyl-1H-imidazol-5(4H)-one
(3e). IR (KBr): 3153, 3123, 3066, 2987, 2846, 1700, 1638,
1
1540, 1456, 1261, 1179, 1071, 922, 786 cmꢁ1. H NMR (400
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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F. Shi, X.-N. Zeng, F.-Y. Wu, S. Yan, W.-F. Zheng, S.-J. Tu
Vol 49
MHz, DMSO) (d, ppm): 12.19 (s, 1H, NH), 8.28 (d, J ¼ 8.4
Hz, 2H, ArH), 8.18 (d, J ¼ 8.4 Hz, 2H, ArH), 7.72–7.60 (m,
5H, ArH), 7.03 (s, 1H, ¼¼CH). HRMS (ESI): m/z [MþH]þ
calcd for C16H12BrN2O: 327.0128; found: 327.0138.
(d, J ¼ 6.8 Hz, 1H, ArH), 8.18 (d, J ¼ 6.8 Hz, 1H, ArH),
8.12 (dd, J1 ¼ 8.0 Hz, J2 ¼ 2.4 Hz, 1H, ArH), 8.02–8.01 (m,
1H, ArH), 7.58–7.56 (m, 2H, ArH), 7.53–7.51 (m, 1H, ArH),
6.94 (s, 1H, ¼¼CH), 6.82–6.76 (m, 2H, ArH), 3.31 (s, 6H,
2CH3). HRMS (ESI): m/z [MþH]þ calcd for C18H18N3O:
292.1445; found: 292,1439.
(Z)-4-(3-Nitrobenzylidene)-2-phenyl-1H-imidazol-5(4H)-one
(3f). IR (KBr): 3152, 3120, 3067, 2987, 1708, 1646, 1527,
1
1454, 1352, 1259, 1095, 920, 791 cmꢁ1. H NMR (400 MHz,
(Z)-2-Phenyl-4-((thiophen-2-yl)methylene)-1H-imidazol-5(4H)-
one (3m). IR (KBr): 3116, 3061, 2985, 1698, 1634, 1457, 1419,
DMSO) (d, ppm): 12.28 (s, 1H, NH), 9.34(s, 1H, ArH), 8.66
(d, J ¼ 8.0 Hz, 1H, ArH), 8.25 (d, J ¼ 8.0 Hz, 1H, ArH),
8.21 (d, J ¼ 8.0 Hz, 1H, ArH), 7.78 (q, J ¼ 8.0 Hz, 1H,
ArH), 7.70–7.64 (m, 4H, ArH), 7.20 (s, 1H, ¼¼CH). HRMS
(ESI): m/z [MþH]þ calcd for C16H12N3O3: 294.0874; found:
294.0876.
1320, 1256, 1200, 1121, 922, 891, 788, 692 cmꢁ1 1H NMR
.
(400 MHz, DMSO) (d, ppm): 12.06 (s, 1H, NH), 8.16 (dd, J1 ¼
8.0 Hz, J2 ¼ 1.2 Hz, 2H, ArH), 7.92 (d, J ¼ 5.2 Hz, 1H, ArH),
7.74 (d, J ¼ 2.7 Hz, 1H, ArH), 7.64–7.60 (m, 3H, ArH), 7.39 (s,
1H, ¼¼CH), 7.21–7.18 (m, 1H, ArH). HRMS (ESI): m/z
[MþH]þ calcd for C14H11N2OS: 255.0587; found: 255.0580.
Assay for DPPH scavenging potential. Potentials for scav-
enging DPPH radical was conducted as described in our previous
works [11e,f] with slight modification. Briefly, 2.0 mL of 0.1-mM
DPPH in methanol was added to 2.0 mL of each tested compound
solution (dissolved in DMSO at a concentration of 1mg/ mL).
The mixture was shaken vigorously and incubated at 30ꢀC for 30
min, followed by estimating its absorbance at 517 nm. Methanol
and L-Ascorbic acid was used as the blank and PC, respectively.
The scavenging activity was expressed as the percentage inhibi-
tion of the DPPH radicals by 1-mg tested compound, which was
calculated from [1 ꢁ (A1/A0)]ꢂ 100, where A1 and A0 are absor-
bencies of the tested compound and blank control, respectively.
Assay for OH scavenging potential. Potentials for scaveng-
ing hydroxyl radical was determined based on the theory of Fenton
reaction [14] and conducted according to the procedure detailed in
our previous work [11f] with slight modification. The tested com-
pounds were dissolved in DMSO at a concentration of 1 mg/ mL
and determining scavenging OH activity involved preparing the
following reagents (i) reagents for the blank control consisted of
1-mL phosphate buffer (150 mM), 0.2 mL 1,10-phenaproline (7.5
mM), 0.2 mL FeSO4 (7.5 mM), and 0.6 mL RO water; (ii) reagents
for the oxidized control were the same as above, except that 0.2-
mL RO water was substituted by 0.2-mL H2O2 (0.1%); (iii)
reagents for scavenging free radicals were the same as those for
the oxidized control except that 0.4-mL RO water was replaced by
0.4 mL of the tested compounds. All were incubated at 37ꢀC in a
water bath for 60 min followed by determining their absorption at
536 nm. Scavenging capacity for OH was calculated according to
(Z)-4-(4-Nitrobenzylidene)-2-phenyl-1H-imidazol-5(4H)-one
(3g). IR (KBr): 3127, 3066, 2986, 1711, 1594, 1511, 1416,
1341, 1256, 1056, 889, 684 cmꢁ1 1H NMR (400 MHz,
.
DMSO) (d, ppm): 12.31 (s, 1H, NH), 8.56 (d, J ¼ 8.4 Hz, 2H,
ArH), 8.31 (d, J ¼ 8.0 Hz, 2H, ArH), 8.23 (d, J ¼ 7.8 Hz,
2H, ArH), 7.71–7.61 (m, 3H, ArH), 7.12 (s, 1H, ¼¼CH).
HRMS (ESI): m/z [MþH]þ calcd for C16H12N3O3: 294.0874;
found: 294.0869.
(Z)-4-(2,3-Dimethoxybenzylidene)-2-phenyl-1H-imidazol-5(4H)-
one (3h). IR (KBr): 3126, 3068, 2988, 1704, 1637, 1573, 1458,
1
1263, 1074, 999, 786, 695 cmꢁ1. H NMR (400 MHz, DMSO)
(d, ppm): 12.17 (s, 1H, NH), 8.54 (d, J ¼ 6.8 Hz, 1H, ArH),
8.17 (d, J ¼ 6.8 Hz, 2H, ArH), 7.66–7.59 (m, 3H, ArH), 7.30
(s, 1H, ¼¼CH), 7.23 (t, J ¼ 8.0Hz, 1H, ArH), 7.16 (d, J ¼ 8.0
Hz, 1H, ArH), 3.86 (s, 3H, ꢀC H3), 3.84 (s, 3H, ꢀC H3).
HRMS (ESI): m/z [MþH]þ calcd for C18H17N2O3: 309.1234;
found: 309.1230.
(Z)-4-(3,4-Dimethoxybenzylidene)-2-phenyl-1H-imidazol-5(4H)-
one (3i). IR (KBr): 3122, 3069, 2936, 1700, 1639, 1593, 1519,
1
1458, 1335, 1232, 1136, 1018, 921, 787, 695 cmꢁ1. H NMR
(400 MHz, DMSO) (d, ppm): 12.02 (s, 1H, NH), 8.53 (s, 1H,
ArH), 8.15 (d, J ¼ 8.0 Hz, 1H, ArH), 8.05 (d, J ¼ 8.0 Hz,
1H, ArH), 7.76 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.2 Hz, 1H, ArH),
7.61–7.55 (m, 3H, ArH), 7.09–7.06 (m, 1H, ArH), 7.00 (s, 1H,
¼¼CH), 3.87 (s, 3H, OCH3), 3.84 (s, 3H, OCH3). HRMS (ESI):
m/z [MþH]þ calcd for C18H17N2O3: 309.1234; found:
309.1227.
(Z)-4-(3,4,5-Trimethoxybenzylidene)-2-phenyl-1H-imidazol-
5(4H)-one (3j). IR (KBr): 3153, 3063, 2991, 1703, 1637,
1575, 1499, 1456, 1332, 1246, 1135, 1000, 919, 786, 693
cmꢁ1 1H NMR (400 MHz, DMSO) (d, ppm): 12.09 (s, 1H,
.
NH), 8.16 (d, J ¼ 6.8 Hz, 2H, ArH), 7.78 (s, 2H, ArH), 7.66–
7.58 (m, 3H, ArH), 7.00 (s, 1H, ¼¼CH), 3.88 (s, 6H, 2OCH3),
3.75 (s, 3H, ꢀC H3). HRMS (ESI): m/z [MþH]þ calcd for
C19H19N2O4: 339.1340; found: 339.1350.
(Z)-4-((Benzo[d][1,3]dioxol-5-yl)methylene)-2-phenyl-1H-
imidazol-5(4H)-one (3k). IR (KBr): 3118, 3060, 2985, 1704,
1617, 1485, 1446, 1263, 1227, 1105, 1034, 920, 885, 785, 694
.
cmꢁ1 1H NMR (400 MHz, DMSO) (d, ppm): 12.05 (s, 1H,
scavenging
536
oxidized control
536
the formula: Scavenging rate (%) ¼ (A
–A
)/
blamk control oxidized control
536
(A
A536
)ꢂ100%. L-Ascorbic acid was used as a
PC. The scavenging capacities were represented as percentage in-
hibition of the OH by 1-mg tested compound.
Assay for Oꢁ2 scavenging potential. The scavenging
potential for superoxide radicals in samples was analyzed
using
a hypoxanthine/xanthine oxidase generating system
coupled with NBT reduction, as detailed previously [15]
with minor modification, where the reactions were carried out in
96-well plates. Briefly, each reaction mixture contained 134-lL
buffer (50-mM KH2PO4/KOH, pH 7.4), 2 lL of 100-mM
Na2EDTA, 20 lL of 3-mM hypoxanthine, 2 lL of 10-mM
NBT, and 10 lL of sample. Microplates were read 2.5 min after
adding 32 lL of xanthine oxidase (1 unit per 10-mL buffer) at
540 nm using a microplate reader (Bioreader 550, Bio-Rad, US).
L-Ascorbic acid was used as a PC. Superoxide scavenging activ-
ity was expressed as the percentage inhibition of superoxide
anion by 1-mg tested compound compared to the blank (i.e.,
buffer used in reaction).
NH), 8.15–8.13 (m, 3H, ArH), 7.70 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.2
Hz, 1H, ArH), 7.63–7.59 (m, 3H, ArH), 7.05 (d, J ¼ 8.0 Hz,
1H, ArH), 6.99 (s, 1H, ¼¼CH), 6.13 (s, 2H, CH2). HRMS
(ESI): m/z [MþH]þ calcd for C17H13N2O3: 293.0921; found:
293.0920.
(Z)-4-(4-(Dimethylamino)benzylidene)-2-phenyl-1H-imidazol-
5(4H)-one (3l). IR (KBr): 3126, 3059, 2985, 1695, 1590, 1522,
1
1455, 1364, 1316, 1165, 1120, 1029, 918, 798, 694 cmꢁ1. H
NMR (400 MHz, DMSO) (d, ppm): 11.91 (s, 1H, NH), 8.37
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2012
Efficient Microwave-Assisted Synthesis and Antioxidant Activity of
4-Arylidene-2-phenyl-1H-imidazol-5(4H)-ones
63
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Acknowledgments. We thank the Natural Science Foundation
of China (No. 21002083 and 21072163), the Natural Science
Foundation (09KJB150011) and Qing Lan Project (08QL001) of
Jiangsu Education Committee, and the Interdisciplinary Key Item
of Xuzhou Normal University (09XKXK01) for financial
supports.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet