Microwave-assisted, solvent-free, parallel syntheses and elucidation of reaction mechanism for the formation of some novel tetraaryl imidazoles of biological interest

Article abstract of DOI:10.1002/jhet.68

The microwave assisted, solvent free, parallel syntheses of title compounds is described in this protocol. Twelve new tetraaryl imidazoles, which are incorporated with the chemotherapeutic pharmaco- phores, have been synthesized by adopting one pot multic

Full text of DOI:10.1002/jhet.68

278
Microwave-Assisted, Solvent-Free, Parallel Syntheses and
Elucidation of Reaction Mechanism for the Formation of Some
Novel Tetraaryl Imidazoles of Biological Interest
Vol 46
B. R. Prashantha Kumar,a* Gyanendra Kumar Sharma,a S. Srinath,a
Mohamed Noor,a B. Suresh,a and B. R. Srinivasab
aDepartment of Pharmaceutical Chemistry, J. S. S. College of Pharmacy, Ooty 643001,
Tamil Nadu, India
bSCIT, Astra Zeneca India Pvt. Ltd, Bangalore, Karnataka, India
*E-mail: brprashant@yahoo.com
Received March 10, 2008
DOI 10.1002/jhet.68
Published online 13 April 2009 in Wiley InterScience (www.interscience.wiley.com).
The microwave assisted, solvent free, parallel syntheses of title compounds is described in this proto-
col. Twelve new tetraaryl imidazoles, which are incorporated with the chemotherapeutic pharmaco-
phores, have been synthesized by adopting one pot multicomponent reaction. Attempt has been made to
investigate the mechanism behind the formation of tetraaryl imidazoles by product identification
method. The synthesized compounds were analyzed by physical and analytical data. The synthesized
compounds were evaluated for their antibacterial, antitubercular, and short-term anticancer activity.
Compound 13 was found to be the candidate compound to investigate further for its potential anticancer
activity.
J. Heterocyclic Chem., 46, 278 (2009).
INTRODUCTION
ber of articles have described the syntheses of various
imidazoles [11–19].
Syntheses of heterocyclic compounds from readily
available reagents by simple and efficient methods are
the major requirements of heterocyclic chemistry. A sur-
vey of the pertinent literature reveals that, tetraaryl imi-
dazoles possess diverse biological activities apart from
their synthetic interests [1–3]. They are reported to ex-
hibit pharmacological activities such as antirheumatoid
arthritis [4], antituberculosis [5], antiHIV [6], antiepilep-
tic [7], and anticancer activity [8,9]. Some of the best-
selling therapies today contain this versatile heterocycle
in their core structures. Therefore, it would be difficult
to underestimate the importance of imidazoles in the
pharmaceutical industry. Structurally, imidazole shows
all the typical properties of an aromatic ring system.
In 1858, Debus reported the reaction between glyoxal
and ammonia, ever since this reaction became a novel
route to the syntheses of imidazoles [10]. Later, a num-
On the basis of the above observations, we have
sought to synthesize novel tetraaryl imidazoles which
are incorporated with the chemotherapeutic pharmaco-
phores such as sulphanilamide, its bioisoster PABA (p-
aminobenzoic acid) and INH (isoniazid) as possible anti-
bacterial, antitubercular, or anticancer agents.
RESULTS AND DISCUSSION
Benzoin on oxidation gave Benzil 1 (Scheme 1). In
an attempt to search for oxidizing agent to oxidize a
mono ketone to diketone, we tried using oxidizing
agents such as aluminium nitrate, cerric ammonium sul-
phate, ferric ammonium sulphate, potassium nitrate, and
sodium nitrite. Among these oxidizing agents, only so-
dium nitrite was able to oxidize mono ketone to
C
V
2009 HeteroCorporation

March 2009
Microwave-Assisted, Solvent-Free, Parallel Syntheses and Elucidation of Reaction
Mechanism for the Formation of Some Novel Tetraaryl Imidazoles of Biological Interest
279
Scheme 1. Preparation of tetraaryl imidazoles. (a) NaNO2, AcOH, reflux
for 50 min. (b) Conv; AcOH, Reflux 5-6 h. MW; Activated silica gel,
1000 W, 8 min. (c) Conv; Ammonium acetate, Reflux 12-15 h. MW;
Ammonium acetate, 1000 W, 14–23 min.
irradiation, whereas tetraaryl imidazoles formed after
14–23 min of microwave irradiation.
We have an opinion that, the acidic nature of silica
gel would have enhanced this reaction particularly dur-
ing dehydration steps. All the synthesized compounds
1
were analyzed by TLC, mp, IR, H NMR, MASS, and
1
elemental analysis. The H NMR showed a characteris-
tic peak for NH between 8.77 and 8.86 d ppm for com-
pounds containing INH (2-4). A characteristic peak for
NH2 was observed between 6.57 and 6.82 d ppm for
compounds containing sulphanilamide (5-9). A charac-
teristic peak for COOH was observed between
12.94 and 13.04 d ppm for compounds containing
PABA (10-13).
Initially, we tried to synthesize the tetraaryl imida-
zoles by adopting a one-pot single-step multicomponent
reaction by both conventional and microwave method
[21–23], involving primary aromatic amine, aldehyde,
benzyl, and ammonium acetate as shown in Scheme 2.
However, the above reaction gave triaryl imidazole in
addition to the tetraaryl imidazole with incorporated aryl
amine in a yield ratio of 3:1, respectively. This result
indicated that, the formation of triaryl imidazole is rela-
tively easy when compared with tetraaryl imidazole. To
improve the yield of tetraaryl imidazoles and to synthe-
size them selectively, we have modified the procedure
according to the Scheme 1. Hence, for this reason we
prepared the Schiff’s bases first and then taken further
to the cyclization step involving equivalent amount of
diketone and excess of ammonium acetate. The list of
synthesized compounds and the comparative yield state-
ment between microwave and conventional method is as
shown in Table 1.
diketone efficiently in the presence of glacial acetic acid
as a solvent. In the literature [20], nitric acid and lead
nitrate were used to oxidize benzoin to benzil taking
1.5 h for completing reaction, involving a nasty brown
nitrogenous gas evolution. The same reaction using so-
dium nitrite just takes 50 min for completion. The yield
of benzil was better when compared with the existing
oxidizing agents and the brown nitrogenous gas evolu-
tion was also been reduced.
Scheme 2. (a) Multicomponent reaction, Conv; Glacial acetic acid,
reflux 12–15 h, MW; 1000 W, 14–23 min.
The primary aromatic or heteroarylamine was con-
densed with aryl or heteroaryl aldehydes to afford the
corresponding Schiff’s base. Schiff’s base was further
treated with ammonium acetate and benzil in the pres-
ence of glacial acetic acid as a solvent, gave the corre-
sponding tetraaryl imidazoles (2-13) according to
Scheme 1. The microwave assisted parallel syntheses
were performed under solvent-free conditions using acti-
vated silica gel at the full power of 1000 W. Schiff’s
base formation was completed after 8 min of microwave
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Vol 46
Table 1
Physical and analytical data of compounds 2-13
Reaction time
Yield (%)a
Conven
61
c
Compound
R
R0
MWb (min)
Conven (h)
13
MW
89
CTC50 (lg/mL)
2
14
16
190.26
3
13
83
58
>500
4
5
6
7
15
20
22
21
14
15
15
15
86
90
91
88
67
62
63
61
500
>500
>500
>500
8
9
19
17
15
14
93
81
72
77
>500
438.50
10
22
15
92
90
>500
11
12
13
21
20
23
15
13
15
86
97
84
86
88
71
>500
>500
94.63
a Isolated yield.
b Microwave irradiation (WhirlpoolTM domestic microwave oven).
c The cytotoxic concentration (which inhibited 50% growth of total cells).
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Microwave-Assisted, Solvent-Free, Parallel Syntheses and Elucidation of Reaction
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281
To understand the reaction mechanism, we per-
formed a couple of experiments to find out the possi-
ble intermediates formed during the formation of tet-
raaryl imidazoles [24]. The experiments were
designed to identify the intermediates under similar
reaction conditions as follows,
by both conventional and microwave method. Acetic
acid was used as a solvent in conventional method,
whereas activated silica gel was used in the microwave
method. By the conventional method all the above reac-
tion mixtures were refluxed for 10 h. The observations
were found to be same under both the methods.
In addition to the above experiments, we stopped the
reaction between benzil, anisaldehyde, PABA, and am-
monium acetate at the half way stage under both micro-
wave and conventional methods. The reaction mixtures
were directly fed to the mass spectromet. Presence of
triaryl imidazole, tetraaryl imidazole, and product of
experiment 1 and 3 was observed.
1. Benzil with ammonium acetate
2. Benzil with PABA
3. PABA with anisaldehyde
4. Ammonium acetate with anisaldehyde
5. Product of experiment 3 with benzil and excess of
ammonium acetate.
All the above experimental results revealed the possi-
ble intermediates formed during the formation of title
compounds. The possible motive or driving force for
this reaction would be the formation of relatively more
stable imidazole ring system. On the basis of these facts
the possible mechanism may be postulated as shown in
the Scheme 3.
The reaction mixtures were irradiated with micro-
waves for 8 min and directly fed to the mass spectrome-
try to find out the intermediates formed under APCI
(atmospheric pressure chemical ionization) technique.
The reaction mixture of experiment 1 showed a molecu-
lar ion peak at 209.0 confirming the formation of mono
imine and another molecular ion peak at 208.0 for a di
imine. TLC also showed one spot each for mono imine
and di imine. Further, isolated yield ratio was found to
be 7:1 for the mono imine and di imine, respectively.
This experiment indicated that, mono imine formation is
favored over the di imine. The reaction mixture of
experiment 2 showed the molecular ion peak at 329.1.
However, the isolated yield was found to be just 4%.
This result indicates that the formation of Schiffs base
from diketone is quite difficult in this reaction. Prob-
ably, the steric crowding around the diketone (benzil)
and less reactivity of aromatic amine may not have
favored the formation of Schiff’s base. The reaction
mixture of experiment 3 showed a molecular ion peak at
255.0 confirming the formation of Schiff’s base between
aldehyde and aromatic amine, the TLC showed a clear
single spot. The isolated yield was found to be about
98%. The reaction mixture of experiment 4 showed a
molecular ion peak at 135.0 indicating formation of
imine. But, we could not isolate the product, which may
be because of its instability or its being formed in very
low quantities. The reaction mixture of experiment 5
showed a molecular ion peak at 444.95 confirming the
formation of tetraaryl imidazole and no peak was
observed for triaryl imidazole. The TLC showed single
spot for the formation of tetraaryl imidazole and isolated
yield was found to be 99%. The experiment 5 clearly
indicates that the Schiffs base formation between alde-
hyde and aromatic amine is more likely during the for-
mation of tetraaryl imidazole. In contrast to this, the
experiment 2 results reveal that possibility of Schiffs
bases formation between aryl amine and diketone is less
likely under this set of reactants and provided reaction
conditions. All the above experiments were conducted
Even though, protocol and postulated mechanism for
the formation of triaryl imidazoles is reported by
Scheme 3. (a) Schiff’s base, (b) Imine, (c) Tetraaryl imidazole.
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B. R. P. Kumar, G. K. Sharma, S. Srinath, M. Noor, B. Suresh, and B. R. Srinivasa
Vol 46
expressed in ꢀC and are uncorrected. The IR spectra of com-
pounds were recorded on Perkin-Elmer infrared–283 FTIR
spectrometer by KBr pellet technique and are expressed in
Siddiqui [25] recently in the year 2005. The present pro-
tocol and postulated mechanism for the formation of tet-
raaryl imidazoles attempts to give the better insight
based on the experimental facts. We differ from their
postulated mechanism by saying; imine formation will
be favored between diketone and ammonia, rather
between aldehyde and ammonia. The reason for this as
already explained in the results of experiment 4. How-
ever, further studies are required to come to any hard
core conclusion.
cmꢁ1 1H NMR spectra were recorded on Bruker DRX-300
.
(300 MHZ, FT-NMR) spectrophotometer using TMS as an in-
ternal standard, CDCl3, or DMSO-d6 as a solvent. The chemi-
cal shifts are expressed in d ppm and following abbreviations
are used: s, singlet; d, doublet; t, triplet; q, quartlet; and m,
multiplet. Mass spectrum was obtained using LC-MS (Schi-
madzu-2010AT) under atmospheric pressure chemical ioniza-
tion technique (APCI) and elemental analysis was performed
using Elemental Vario EL III, Carlo-Erba 1108. TLC was per-
formed to monitor the reactions and to determine the purity of
the products on precoated aluminum plates using 10% metha-
nol in chloroform or 20% ethyl acetate in pet ether as a mobile
phase.
Procedure for the preparation of benzil (1). Crude ben-
zoin (10 g, 0.048 mole) and 15 g of sodium nitrite were trans-
ferred to a 250-mL round bottom flask containing 40 mL of
glacial acetic acid. The reaction mixture was refluxed using an
air condenser for about 50 min (till the evolution of white gas-
eous vapors ceases). Then the reaction mixture was cooled and
poured into a beaker containing 100 mL of ice-cold water. The
mixture was stirred well until the oil separates completely as a
yellow solid. The crude benzil was collected by filtration,
washed thoroughly with water, and recrystallized from ethanol.
The reaction was monitored through TLC. Yellow crystals
(97%); mp 95ꢀC, IR (cmꢁ1, KBr): 3047 (Ar CAH), 1707
(C¼¼O), 1601 (C¼¼C).
All the synthesized tetraaryl imidazoles incorporated
with chemotherapeutic pharmacophores were evaluated
for their in vitro antibacterial activity against two-gram
positive bacteriae such as B. subtilis and S. aureus and
two gram negative bacteriae E. coli and K. pneumoniae.
Only compound no 13 exhibited a moderate activity
with minimum inhibitory concentration (MIC) of 250 lg
against S. aureus. Surprisingly, no other compound
exhibited an antibacterial activity.
All the synthesized compounds were evaluated for
their possible antimycobacterial activity toward a strain
of M. tuberculosis H37Rv sensitive to isoniazid. Middle-
brook (MB) 7H10 agar medium was used for testing
antitubercular activity. The MIC determination was per-
formed from 1 to 50 lg/mL concentrations. But, no
compound exhibited MIC below 50 lg/mL concentra-
tion including the tetraaryl imidazoles containing isonia-
zid moiety (2, 3, and 4).
Anticancer activity of the synthesized compounds was
evaluated by determining the percentage growth inhibi-
tion of DLA (Dalton’s lymphoma ascites) cells by try-
phan blue dye exclusion technique. Compounds 2, 9,
and 13 showed good anticancer activity with CTC50 (cy-
totoxic concentration) at 190.26, 438.50, and 94.63 lg/
mL, respectively. The synthesized tetraaryl imidazoles
and their CTC50 values are as shown in Table 1.
In conclusion, we have developed a microwave
assisted, convenient, efficient, and environmentally be-
nign protocol for the syntheses of biologically active tet-
raaryl imidazoles. The present microwave method was
found to be better than conventional method in terms of
reaction time, yield, and relatively simple method to
perform parallel syntheses. Thus, this methodology
becomes an efficient strategy for the rapid syntheses of
tetraaryl imidazoles, selectively. From the point of bio-
logical interest, compound 13 was found to be the can-
didate compound to investigate further for its anticancer
activity.
General procedure for the preparation of Schiff’s bases
Conventional method. Equimolar amounts (0.01 mole) of
aromatic amine and aromatic aldehyde were transferred to a
250-mL flat bottom flask containing 15 mL of glacial acetic
acid to serve as a solvent, then refluxed with stirring for about
6 h. After completion of the reaction, the reaction mixture was
allowed to cool to give a corresponding product. The reactions
were monitored through TLC. The completed reactions were
taken directly for the preparation tetraaryl imidazoles.
Microwave method. This reaction was carried out in a par-
allel synthetic way as shown in Scheme 1. Equimolar amounts
(0.01 mole) of aromatic amine and aromatic aldehyde were
transferred to a clean and dry mortar containing 2 g of acti-
vated silica gel, triturate to become a uniform mixture. The
reaction mixture was then transferred to a 100 mL beaker.
Like this all other beakers containing different reaction mix-
tures were kept inside the microwave oven in a circle and then
microwave irradiation was carried out at 1000 W power for
about 8 min. Intermittent cooling was done after every 60 s of
microwave irradiation. During intermittent cooling, the reac-
tion mixtures were thoroughly mixed using a glass rod. The
reactions were monitored through TLC. The completed reac-
tions were taken directly for the preparation of tetraaryl imida-
zoles without any work up.
General procedures for the preparation of tetraaryl imi-
dazoles (2-13)
Conventional method. Benzil (0.01 mole) was transferred
along with excess of ammonium acetate (0.1 mole) into a flask
containing the Schiff’s base (0.01 mole) obtained in the previ-
ous conventional procedure. The reaction mixture was stirred
and refluxed on heating plate with magnetic stirrer for about
12–15 h. The reaction was monitored through TLC. When
EXPERIMENTAL
The laboratory grade chemicals and reagents were used to
synthesize all the reported compounds. The melting points
were determined in open capillaries. Temperatures are
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Microwave-Assisted, Solvent-Free, Parallel Syntheses and Elucidation of Reaction
Mechanism for the Formation of Some Novel Tetraaryl Imidazoles of Biological Interest
283
complete, the reaction mixture was poured into 250 mL of
water to remove ammonium acetate and acetic acid and the
product was collected by filtration dried in a hot air oven. The
crude product was washed with 2 ꢂ 10 mL of toluene to
remove traces of any unreacted benzil; further purification by
was by recrystallized using ethyl acetate.
ArH); MS (m/z): found 481.95, calcd, 482 (MþH)þ. 327.0,
329.10. Anal. Calcd for C28H23N3O3S: C, 69.84; H, 4.81; N,
8.73. Found: C, 69.49; H, 4.70; N, 8.54.
4-[2-(4-Chlorophenyl)-4,5-diphenylimidazole-1-yl]-benzene-
sulphonamide (6). Cream colored crystals; mp 280ꢀC; IR
(cmꢁ1, KBr): 3358 (NH), 3026 (Ar CAH), 1654 (C¼¼C), 1560
(C¼¼C), 1485 (C¼¼N), 1324 (SO, asym. stre), 1203 (CAN),
1139 (SO, sym. stre), 1014 (CAS), 697 (CACl); 1H NMR (d
ppm): 6.78 (s, 2H, NH2), 7.29-7.85 (m, 18H, ArH); MS (m/z):
found 485.85, calcd, 486 (MþH)þ. 327.0, 297.1, 330.0, 333.0,
373.0, 469.95. Anal. Calcd for C28H23N3O3S: C, 66.73; H,
4.15; N, 8.65. Found: C, 66.57; H, 4.37; N, 8.77.
4-[2-(3-Nitrophenyl)-4,5-diphenylimidazole-1-yl]-benzenesul-
phonamide (7). Yellow amorphous solid; mp 305ꢀC; IR
(cmꢁ1, KBr): 3400 (NH), 3056 (Ar CAH), 1598 (C¼¼C), 1522
(NO, asym. stre), 1479 (C¼¼N), 1348 (NO, sym. stre), 1328
(SO, asym. Stre), 1252 (CAN), 1132 (SO, sym. Stre), 1025
(CAS); 1H NMR (d ppm): 6.82 (s, 2H, NH2), 7.25-7.81 (m,
18H, ArH); MS (m/z): found 496.90, calcd 497 (MþH)þ.
297.05, 342.05, 344.0, 465.0. Anal. Calcd for C27H20N4O4S:
C, 65.31; H, 4.06; N, 11.28. Found: C, 65.1; H, 4.14; N,
11.42.
Microwave method. This reaction was carried out in a par-
allel synthetic way as shown in Scheme 1. Benzil (0.01 mole)
was transferred along with excess of ammonium acetate
(0.1 mole) into a dry mortar containing the Schiff’s base
(0.01 mole) obtained in the previous microwave procedure.
Triturate to become a uniform mixture. The reaction mixture
was then transferred to 100 mL beaker. Likewise, all other
beakers containing different reaction mixtures were kept inside
the microwave oven in a circle and then microwave irradiation
was carried out at 1000 W power for about 14–23 min. Inter-
mittent cooling was done after every 60 s of microwave irradi-
ation. During intermittent cooling, the reaction mixtures were
thoroughly mixed. The reactions were monitored through TLC.
The reaction mixtures were withdrawn from microwave oven
soon after the reactions were completed. The completed and
cooled reaction mixture was poured in to 250 mL of water to
remove ammonium acetate and acetic acid, filtered, and dried
it in hot air oven. The crude product along with silica gel was
washed with 2 ꢂ 10 mL of toluene to remove traces of any
unreacted benzil, further extracted with ethyl acetate. The ethyl
acetate was heated, filtered in hot condition, and allowed to
cool. The solid crystals formed were collected by filtration and
dried under vacuum.
4-[2-(4-Dimethylaminophenyl)-4,5-diphenylimidazole-1-yl]-
benzenesulphonamide (8). Bright yellow amorphous solid; mp
200ꢀC; IR (cmꢁ1, KBr): 3326 (NH), 3050 (Ar CAH), 2928
(Ali CAH), 1634 (C¼¼C), 1576 (C¼¼N), 1328(SO, asym. Stre),
1
1229 (CAN), 1128 (SO, sym. Stre), 1063 (CAS); H NMR (d
ppm): 1.56 (s, 6H, CH3), 6.68 (s, 2H, NH2), 6.9-7.75 (m, 18H,
ArH); MS (m/z): found 494.95, calcd 495 (MþH)þ. 149.9,
340.05. Anal. Calcd for C29H26N4O2S: C, 70.42; H, 5.30; N,
11.33. Found: C, 70.35; H, 5.25; N, 11.12.
The physical, analytical, and spectral data of final com-
pounds are given in the following text.
N-[2-(3-Nitrophenyl)-4,5-diphenylimidazol-1-yl]-pyridamide
(2). Pale yellow crystals; mp 45ꢀC; IR (cmꢁ1, KBr): 3250
(NH), 3032 (Ar C-H), 1654 (C¼¼O), 1621 (C¼¼C), 1595
(C¼¼N), 1528 (NO), 1368 (NO), 1275 (CAN); 1H NMR (d
ppm): 7.25-7.82 (m, 17H, ArH), 8.5 (s, 1H, ArH), 8.82 (bs,
1H, NH); MS (m/z): found 461.80, calcd 462 (MþH)þ.
311.05, 326.9, 342.0, 385.10. Anal. Calcd for C27H19N2O3: C,
70.27; H, 4.14; N, 15.18. Found: C, 70.20; H, 4.20; N, 15.30.
N-[2-(2-Hydroxyphenyl)-4,5-diphenylimidazol-1-yl]-pyridamide
(3). Yellow crystals; mp 48ꢀC; IR (cmꢁ1, KBr): 3401 (OH),
3260 (NH), 3052 (Ar CAH), 1669 (C¼¼O), 1623 (C¼¼C), 1595
(C¼¼N), 1255 (C¼¼O), 1132 (C¼¼N); 1H NMR (d ppm): 6.81-
8.49 (m, 18H, ArH), 8.80 (bs, 1H, NH), 8.91 (bs, 1H, OH);
MS (m/z): found 432.95, calcd 433 (MþH)þ. 266.0, 312.95,
352.10. Anal. Calcd for C27H20N4O2: C, 74.99; H, 4.66; N,
12.95. Found: C, 74.91; H, 4.52; N, 12.81.
N-[2-(4-Chlorophenyl)-4,5-diphenylimidazol-1-yl]-pyrida-
mide (4). Pale yellow crystals; mp 190ꢀC; IR (cmꢁ1, KBr):
3245 (NH), 3057 (Ar CAH), 1601 (C¼¼O), 1618 (C¼¼C), 1501
(C¼¼N), 1132 (CAN), 694 (CACl); 1H NMR (d ppm): 7.25-
7.94 (m, 18H, ArH), 8.77 (bs, 1H, NH); MS (m/z): found
449.15, calcd 449 (M-H)ꢁ. 110.95, 329.30. Anal. Calcd for
C27H19N4OCl: C, 71.92; H, 4.25; N, 12.42. Found: C, 72.27;
H, 4.23; N, 12.36.
4-[2-(2-Hydroxyphenyl)-4,5-diphenylimidazole-1-yl]-benzenꢁe-1
sulphonamide (9). White crystals; mp 203ꢀC; IR (cm
,
KBr): 3218 (OH), 3064 (Ar CAH), 1666 (C¼¼C), 1540
(C¼¼N), 1325 (asym. stre), 1262 (CAN), 1133 (SO, sym. Stre),
1
1025 (CAS); H NMR (d ppm): 6.57 (bs, 2H, NH2), 6.89-7.66
(m, 18H, ArH), 7.92 (bd, 1H, OH); MS (m/z): found 467.85,
calcd 468 (MþH)þ. 313.05. Anal. Calcd for C27H21N3O3S: C,
69.36; H, 4.53; N, 8.99. Found: C, 69.42; H, 4.39; N, 8.78.
4-[2-(p-Dimethylaminophenyl)-4,5-diphenylimidazole-1-yl]-
benzoic acid (10). Yellow amorphous solid; mp 250ꢀC; IR
(cmꢁ1, KBr): 3410 (OH), 3058 (Ar CAH), 2879 (Ali CAH),
1717 (C¼¼O), 1360 (C¼¼N), 1228 (C¼¼O), 1198 (C¼¼N); 1H
NMR (d ppm): 3.06 [s, 6H, (CH3)2], 6.72-7.8 (m, 18H, ArH);
12.94(bs, 1H, COOH) MS (m/z): found 460.0 calcd, 460
(MþH)þ. 340.05, 444.95, 427.90. Anal. Calcd for
C30H25N3O2: C, 78.41; H, 5.48; N, 9.14. Found: C, 78.55; H,
5.37; N, 9.30.
4-[2-(4-Chlorophenyl)-4,5-diphenylimidazole-1-yl]-benzoic
acid (11). White crystals; mp 272ꢀC; IR (cmꢁ1, KBr): 3390
(OH), 3058 (Ar CAH), 2852 (Ali CAH), 1709 (C¼¼O), 1654
1
(C¼¼C), 1485 (C¼¼N), 1292 (CAO), 1248 (CAN); H NMR (d
ppm): 7.32-7.87 (m, 18H, ArH); 13.01(bs, 1H, COOH) MS
(m/z): found 450.90, calcd 451(MþH)þ. 313.0. Anal. Calcd
for C28H19N2O2Cl: C, 74.58; H, 4.25; N, 6.21 Found: C,
74.51; H, 4.10; N, 6.02.
4-[2-(4-Methoxyphenyl)-4,5-diphenylimidazole-1-yl]-benzene-
sulphonamide (5). White amorphous solid; mp 222ꢀC; IR
(cmꢁ1, KBr): 3357 (NH), 3003 (Ar CAH), 1620 (CAC), 1612
(SO), 1578 (CAN), 1327 (SO, asym. Stre), 1291 (CAO), 1251
4-[2-(4-Methoxyphenyl)-4,5-diphenylimidazole-1-yl]-benz-
oic acid (12). White crystals; mp 255ꢀC; IR (cmꢁ1, KBr):
3398 (OH), 3042 (Ar CAH), 2958 (Ali CAH), 1710 (C¼¼O),
1667 (C¼¼C), 1493 (C¼¼N), 1292 (CAO), 1248 (CAN); 1H
NMR (d ppm): 3.78 (s, 3H, OCH3), 6.80-7.84 (m, 18H, ArH),
1
(CAN), 1143 (SO, sym. Stre), 1071 (CAS); H NMR (d ppm):
3.80 (s, 3H, CH3), 6.71 (d, 2H, NH2), 7.28-7.88 (m, 18H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

284
B. R. P. Kumar, G. K. Sharma, S. Srinath, M. Noor, B. Suresh, and B. R. Srinivasa
Vol 46
REFERENCES AND NOTES
12.98 (bs, 1H, COOH) MS (m/z): found 446.8, calcd 447
(MþH)þ. 313.0. Anal. Calcd for C29H22N2O3: C, 78.01; H,
4.97; N, 6.27 Found: C, 78.06; H, 4.79; N, 6.24.
4-[2-(2-Hydroxyphenyl)-4,5-diphenylimidazole-1-yl]-benzoic
acid (13). White crystals; mp 235ꢀC; IR (cmꢁ1, KBr): 3374
(OH), 3060 (Ar CAH), 1716 (C¼¼O), 1653 (C¼¼C), 1262
(CAO), 1202 (CAN); 1H NMR (d ppm): 6.8-8.1 (m, 18H,
ArH), 13.04 (bs, 1H, COOH); MS (m/z): found 432.95, calcd
433 (MþH)þ. 313.0. Anal. Calcd for C28H20N2O3: C, 77.76;
H, 4.66; N, 6.48 Found: C, 77.45; H, 4.36; N, 6.16.
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Anticancer activity screening procedure. Anticancer activ-
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phoma ascite) cells by tryphan blue dye exclusion technique
according to the standard procedure [33]. We checked anti-
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centration of 500, 250, 125, 62.5, 31.25 lg/mL. The percent-
age growth inhibition was calculated by using the following
formula: % Growth inhibition ¼ [(Total cells – Live cells) ꢂ
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The CTC50 values were calculated by plotting the graph
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synthesized tetraaryl imidazoles and their CTC50 values are as
shown in Table 1. Cyclophospamide was used as standard
drug (CTC50, 12 lg/mL).
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Acknowledgment. We thank Dr. A. K. Goel, assistant director,
CDRI, Lucknow, for providing elemental analysis and antituber-
cular activity data.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet