Antimicrobial screening of novel synthesized benzimidazole nucleus containing 4-oxo-thiazolidine derivatives

Article abstract of DOI:10.1007/s00044-011-9752-8

As a part of systematic investigation of synthesis, characterization and antimicrobial screening of some novel 3-(2-(6-methyl-1H-benzo[d]imidazol-2-yl) phenyl)-2-(aryl)thiazolidin-4-ones (3a-l), have been synthesized from Schiff bases of N-arylidene-2-(6-methyl-1H-benzo[d]imidazol-2-yl)anilines, (2a-l). The Schiff bases (2a-l) were prepared by condensation of different aldehydes with 2-(6-methyl-1H-benzo[d]imidazol-2-yl)aniline (1). The compound (1) was obtained from 2-amino benzoic acid and 4-methylbenzene-1,2-diamine. All the synthesized compounds were screened for in vitro antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger, and Aspergillus clavatus. The structures of the compounds synthesized were elucidated by IR, ¹H-NMR, ¹³C-NMR, and mass spectra. Springer Science+Business Media, LLC 2011.

Full text of DOI:10.1007/s00044-011-9752-8

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:2320–2328
DOI 10.1007/s00044-011-9752-8
ORIGINAL RESEARCH
Antimicrobial screening of novel synthesized benzimidazole
nucleus containing 4-oxo-thiazolidine derivatives
•
N. C. Desai Amit M. Dodiya Atul H. Makwana
•
Received: 30 May 2011 / Accepted: 18 July 2011 / Published online: 3 August 2011
Ó Springer Science+Business Media, LLC 2011
Abstract As a part of systematic investigation of synthe-
sis, characterization and antimicrobial screening of some
novel 3-(2-(6-methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-
(aryl)thiazolidin-4-ones (3a–l), have been synthesized from
Schiff bases of N-arylidene-2-(6-methyl-1H-benzo[d]imi-
dazol-2-yl)anilines, (2a–l). The Schiff bases (2a–l) were
prepared by condensation of different aldehydes with 2-(6-
methyl-1H-benzo[d]imidazol-2-yl)aniline (1). The com-
pound (1) was obtained from 2-amino benzoic acid and
4-methylbenzene-1,2-diamine. All the synthesized com-
pounds were screened for in vitro antibacterial and anti-
fungal activities on Escherichia coli, Staphylococcus
aureus, Pseudomonas aeruginosa, Staphylococcus pyoge-
nes, Candida albicans, Aspergillus niger, and Aspergillus
clavatus. The structures of the compounds synthesized were
elucidated by IR, 1H-NMR, 13C-NMR, and mass spectra.
reliably effective treatment for many infectious diseases
that had previously caused extensive mortality and mor-
bidity. The search of novel, effective, and suitable drugs
against human diseases is a continuous process. The
chemistry and pharmacology of benzimidazoles have been
of great interest to medicinal chemistry (Evstigneeva et al.,
1991), because its derivatives possess various biological
activities such as antioxidant (Kus et al., 2004), antimi-
crobial (Goker et al., 2002; Pawar et al., 2004), anthel-
mintic, fungicide (Mavrova et al., 2007), antihypertensive
(Starcevic et al., 2007), antifungal (Jat et al., 2006), anti-
inflammatory (Lazer et al., 1987), and antiprotozoal
activities (Navarette-Vazquez et al., 2001). Due to this
reason benzimidazole has been an important pharmaco-
phore and privileged structure in medicinal chemistry. The
benzimidazole scaffold is an useful structural motif for
displaying chemical functionality in biologically active
molecules (Desai et al., 2011a). Optimization of benz-
imidazole-based structures has resulted in marketed medi-
cines such as omeprazole (Lindberg et al., 1986) and lead
compounds in a wide range of therapeutic areas e.g., casein
kinase (Pagano et al., 2004), factor Xa (Ueno et al., 2004),
hepatitis C virus (Beaulieu et al., 2004) etc. From a com-
binatorial chemistry perspective, the benzimidazole scaf-
fold allows stepwise incorporation of diverse functionality
with control of regiochemistry, making it a suitable target
for library synthesis. Library synthesis has been reported
using solid and solution (Bendale and Sun, 2002) phase
approaches as well as parallel polymer-assisted synthesis
(Andrews et al., 2004).
Keywords Benzimidazole derivatives ꢀ
4-Thiazolidinone ꢀ Antimicrobial activity
Introduction
One of the most significant achievements of the 20th
century has been the discovery and commercial develop-
ment of numerous therapeutic agents that now provide
N. C. Desai (&) ꢀ A. M. Dodiya
Medicinal Chemistry Division, Department of Chemistry,
Bhavnagar University, Bhavnagar 364 002, India
e-mail: dnisheeth@rediffmail.com
For a long time, small heterocycle scaffold containing
nitrogen, sulfur, and oxygen have been under investigation
due to their important medicinal properties. The chemistry
of thiazolidinone ring system is of considerable interest as
it is a core structure in various synthetic pharmaceuticals
A. H. Makwana
XRF, St. Xavier’s College, Navrangpura,
Ahmedabad 380 009, India
123

Med Chem Res (2012) 21:2320–2328
2321
displaying a broad spectrum of biological activities (Liu
et al., 2011). The 4-thiazolidinone nucleus also appears
frequently in the structure of various natural products,
notably thiamine, compounds possessing cardiac and gly-
cemic benefits such as troglitazone (Ghazzi et al., 1997)
and many metabolic products of fungi and primitive marine
animals, including 2-(aminoalkyl)-thiazole-4-carboxylic
acids (Schmidt et al., 1987). Numerous thiazolidinone
derivatives have shown significant bioactivities such as
anticonvulsant (Ergene and Capan, 1994), antimicrobial
(Gouveia and de Oliveira, 2009), antidiabetic (Noboyoshi
and Heroaki, 2006), antihistaminic (Previtera et al., 1994),
anticancer (Wu et al., 2006), anti HIV (Rawal et al.,
2005) etc.
Mebendazole drug is a shining example of the impor-
tance of benzimidazole nucleus. This drug is a broad
spectrum anthelmintic agent producing high cure rates
in infections caused by threadworms, hookworms, and
whipworms (Roth et al., 1997). Rivoglitazone is the most
appropriate example of hybrid drug in which two
important moieties, benzimidazole and 4-thiazolidinone
are present together. In this article, we have adopted
hybrid approach for the search of novel antimicrobial
agents which is very popular in medicinal chemistry
(Desai et al., 2010; Desai and Dodiya, 2011; Goker et al.,
1995). In view of pharmacological significance of benz-
imidazole derivatives and 4-thiazolidinone derivatives
especially antimicrobial activity, it is planned to synthe-
size and screen for antimicrobial activity of some new
benzimidazole derivatives containing 4-thiazolidinone
moiety. The newly synthesized compounds were charac-
Currently, 4-thiazolidinones are considered as a new
class of antidiabetic (insulin-sensitizing) drugs and potent
aldose reductase inhibitors. In addition, they are potent for
the treatment of diabetes complications like cataract,
nephropathy, and neuropathy (Gerstein et al., 2006) .
1
terized on the basis of IR, H NMR, 13C NMR, and mass
spectral data. See Scheme 1.
O
NH
O
N
NH
OCH3
O
N
N
O
S
O
Mebendazole
NH
Rivoglitazone
O
HOOC
Scheme 1 Synthesis route for
the final compounds
NH
NH
N
2
PPA
o
160 C
+
H C
3
NH
H N
2
H C
3
2
1
H N
2
1,4-dioxane
ZnCl
OHC
2
R
N
N
H C
3
NH
NH
O
H C
3
SHCH COOH
2
N
N
1,4-dioxane
S
3a-l
2a-l
R
R = Different substituents
R
123

2322
Med Chem Res (2012) 21:2320–2328
Results and discussion
The proton of C-19 appeared as a singlet at d = 8.12 ppm
because C-19 has no hydrogen atom on either side at C-18
or at C-20. The proton of C-21 appeared as a doublet at
d = 8.07 ppm due to the presence of C–H at C-22 on one
side and nitro group containing carbon at C-20 position on
the other side. The hydrogen bonded to C-23 appeared as a
doublet at d = 7.75 ppm due to the presence of C-18 on
one side and C–H on the other side at C-22.
IR-data
IR spectra of the title compound 3j (molecular formula
C23H18N4O3S, m.w. 430.48 g/mol) has given vibration at
3005 cm-1 over the range which shows multiple weak
absorption peak corresponding to benzimidazole-H and
Ar–H stretching vibration absorption peaks. The high
frequency region of the IR spectra of this compound
contains –NH stretching vibration at 3482 cm-1. The
methylene group present in thiazolidinone nucleus
appeared in the range of 3025 cm-1, while the bending
13C-NMR-data
The final compound 3j contains two moieties like benz-
imidazole and 4-thiazolidinone. The chemical shift of
carbons of the final compound 3j varies from d = 171.2 to
21.3 ppm. The carbon nuclei under the influence of a
strong electronegative environment appeared downfield,
e.g., the C-15 carbonyl, which is directly linked to the ring
nitrogen has a chemical shift at d = 171.2 ppm, whereas
C-1 linked to nitrogen atoms on both sides, appeared at
d = 154.9 ppm. The carbon of the methyl group i.e., C-6
appeared at d = 21.3 ppm and the carbon where it is
attached, i.e., (C-5, aromatic, sp2) appeared at d =
132.7 ppm, while the other carbons (C-2, C-3, C-4, C-7,
and C-8) of the benzimidazole nucleus appeared between
d = 115.3 and 135.6 ppm. The carbons of the phenyl
ring (C-9 to C-14), which makes nucleus between benz-
imidazole and thiazolidinone rings appeared between
d = 114.4 and 136.9 ppm. The carbon of –CH2–, methy-
lene group present in thiazolidinone ring, i.e., C-16
appeared at d = 33.5 ppm. The carbon which is attached
on one side with nitrogen atom and on the other side with
sulfur atom, i.e., (C-17) appeared at d = 71.9 ppm. The
aromatic carbon C-20 which is directly attached with nitro
group appeared at d = 147.8 ppm due to strong electron-
withdrawing effect of nitro group, while the other carbons
(C-18, C-19, C-21, C-22, and C-23) of the nitro benzene
ring appeared between d = 122.3 and 140.1 ppm, respec-
tively. The numbering of carbons is described in Fig. 1.
vibration of the methylene group appeared at 1465 cm-1
.
The stretching vibrations of the methyl group appeared at
2950 cm-1, while bending vibration of the methyl group
appeared in the range of 1452 cm-1
. The strong
absorption at 1685 cm-1 is due to the C=O stretching
vibration and the moderate absorption at 1615 cm-1
corresponds to C=N stretching vibration while C=C
linkage absorption appeared at 1580 and 1460 cm-1 due
to stretching vibrations. The absorption at 1310 cm-1 is
due to the symmetric stretching of –NO2 group while
the absorption at 1520 cm-1 is due to the asymmetric
stretching of –NO2 group. The absorption peak at
755 cm-1 indicates that mono-substituted benzene ring is
present.
H-NMR-data
It has been observed from the chemical structure of com-
pound 3j that protons of the methyl group attached to C-6
position appeared as a singlet at d = 2.43 ppm. The pro-
tons attached with C-3 and C-4 appeared as doublet at
d = 7.12 and 7.54 ppm, respectively, while the proton of
C-7 appeared as a singlet at d = 7.43 ppm. A proton of the
secondary amine appeared as a singlet at d = 10.25 ppm.
The phenyl ring contains four protons which makes nucleus
between benzimidazole and 4-oxo-thiazolidine rings. The
proton attached with C-11 appeared as multiplet due to
mutual coupling with C-10 and C-12 at d = 7.49, while the
proton attached with C-12 appeared as a multiplet at
d = 7.46 due to mutual coupling with C-11 and C-13.
Other protons of the phenyl ring which are attached with
C-10 and C-13 appeared as a doublet at d = 7.84 and
7.33 ppm, respectively. The protons which are attached
with C-16 in 4-thiazolidinone ring appeared as bis-singlet
at d = 4.00; 3.90 ppm, while the other proton of 4-oxo-
thiazolidine which is attached with C-17 appeared as a
singlet at d = 6.44 ppm. The proton of the nitrobenzene
ring which is attached with C-22 appeared as a multiplet at
d = 7.59 due to mutual coupling with C-23 and C-21 ppm.
3
2
10
N
4
11
1
9
N
S
5
8
H3C
NH
12
7
6
14
O
13
15
16
23
17
18
22
21
19
20
NO2
Fig. 1 Carbon numbering of the final compound 3j
123

Med Chem Res (2012) 21:2320–2328
Antimicrobial activity
2323
Structure–activity relationship (SAR) study
For antibacterial activity, compounds 3b and 3f are con-
sidered to be moderately active against E. coli. Compounds
3g and 3l are considered as very good active against E. coli,
while compound 3j is considered as excellent active
against E. coli. Compound 3c is considered as good active
against P. aeruginosa. Compounds 3d, 3e, and 3k are
considered as good active against S. aureus, while com-
pounds 3b, 3g, and 3j are considered as very good active
against S. aureus, while compound 3l is considered as very
good active against S. aureus. Compound 3e is considered
as moderately active against S. pyogenes, while compounds
3b and 3j are considered as very good active against
S. pyogenes. For the antifungal activity, compounds, 3b,
3d, 3e, 3g, 3h, and 3k are considered as good active against
C. albicans, while compound 3c is considered as very good
active against C. albicans, while compound 3j considered
as excellent active against C. albicans. Compounds 3b, 3c,
and 3d are considered as good active while compound 3j is
considered as very good active against A. niger. Compound
3e is considered as good active against A. clavatus. The
data revealed that electron-withdrawing group like –NO2,
present on phenyl ring was found to increase the antimi-
crobial properties. The most of the synthesized compounds
exhibited significant antibacterial activity and moderate
antifungal activity. The discussion and comparison of
antibacterial and antifungal activities have been compared
with ampicillin and griseofulvin, respectively.
SAR studies revealed that different substitutions on the
benzimidazole and 4-thiazolidinone moieties exerted var-
ied biological activity. The electronic nature of the sub-
stituent groups at 2nd position in benzimidazole nucleus
and 2nd position in 4-thiazolidinone led to a significant
variation in antimicrobial activity. A series of compounds
when substituted by electron-withdrawing group like NO2
enhances the antimicrobial activity when present on aro-
matic ring.
Antibacterial activity
The newly synthesized compounds were screened for their
antibacterial activity against gram positive bacteria
S. aureus (MTCC-96) and S. pyogenes (MTCC-442) and
gram negative bacteria E. coli (MTCC-443) and P. aeru-
ginosa (MTCC-1688). Antibacterial activity was carried
out by serial broth dilution method (Ghalem and Mohamed,
2009; Desai et al., 2011b). The standard strains used for the
antimicrobial activity were procured from Institute of
Microbial Technology, Chandigarh. The compounds (3a–
l) were screened for their antibacterial activity in triplicate
sets against these bacteria at different concentrations of
1000, 500, 200, 100, 50, and 25 lg/ml as shown in Table 1.
The drugs which were found to be active in primary
screening were similarly diluted to obtain 100, 50, and
25 lg/ml concentrations. 10 lg/ml suspensions were
Table 1 Results of antibacterial and antifungal screening of the compounds 3a–l
Sr.no. Compd. -R
Minimum inhibitory concentration for bacteria(MIC)
lg/ml SD
Minimum inhibitory concentration for fungi
(MIC) lg/ml SD
Gram negative
Gram positive
P. aeruginosa S. aureus
MTCC-443 MTCC-1688 MTCC-96
E. coli
S. pyogenes
MTCC-442
C. albicans
MTCC-227
A. niger
MTCC-282
A. clavatus
MTCC-1323
1
3a
3b
3c
3d
3e
3f
-2-Cl
1000 2*
125 3.05* 250 1.95* 100 4*
62.5 3.45* 100 2* 1000 2.23* 5000 2.23* 250 3.54* 500 3*
250 3.20* 250 4.50* 250 3* 250 2* 500 2* 500 3.54* 1000 3*
500 4* 250 2* 250 2.22* 125 3.12* 500 4*
125 2.35* 250 3.24* 500 1.34* 500 2.4*
250 2*
-3,4,5-(OCH3)3 500 3.05* 250 3.12* 500 3*
1000 2.54* 500 3.64* 1000 3.54* 1000 4.36* 1000 2.21* 1000 4*
62.5 3* 500 3* 500 2.02* 1000 3.26*
500 3.23*
2
-4-Cl
3
-2,4-(Cl)2
-4-F
4
5
-3-OH
-4-OH
1000 3*
100 3.46*
1000 3.21*
6
1000 2.27* 1000 3*
7
3g
3h
3i
-3,4-(OCH3)2 100 3*
100 4.25* 1000 3.0* 500 3*
1000 2.25* 1000 2.36*
500 3.12* 1000 3.43* 1000 3.35*
1000 3.5* 1000 3.55* 1000 3.3*
8
250 2.3*
250 4.1*
9
-2-N02
500 3.12* 250 2.34* 1000 3*
25 4* 250 2*
500 2.22* 250 1.85* 250 3.53* 250 4*
62.5 4* 250 2* 62.5 3* 1000 3.5* 1000 2.26* 1000 3.53* 1000 4.12*
100 4.57* 100 4.12* 250 4.15* 100 3.55*
10
11
12
3j
-3-NO2
100 2.24* 62.5 3.2* 100 2.25* 100 3.54* 1000 3.47*
500 2.25* 1000 3.26* 1000 2*
3k
3l
-4-NO2
-2,4,-(N02)2
Ampicillin
–
–
Griseofulvin
–
–
–
–
500 2.64* 100 3*
100 3.46*
SD standard deviation, * P B 0.0001
123

2324
Med Chem Res (2012) 21:2320–2328
further inoculated on appropriate media and growth was
noted after 24 and 48 h. The lowest concentration, which
showed no growth after spot subculture was considered as
MIC for each drug. The highest dilution showing at least
99% inhibition is taken as minimum inhibitory concentra-
tions (MIC). The test mixture should contain 108 cells/ml.
The standard drug used in this study was ampicillin for
evaluating antibacterial activity which showed (100, 100,
250, and 100 lg/mL) MIC against E. coli, P. aeruginosa,
S. aureus, and S. pyogenes, respectively.
left uncorrected. Aluminum-coated TLC plates 60 F245
(E. Merck) were used for monitoring of reaction and purity
of compounds. In the conventional method, compounds
were synthesized by using Random synthesizer. Bookie
Rotavapour was used for distillation.
Procedure for the synthesis of 2-(6-methyl-1H-
benzo[d]imidazol-2-yl)aniline (1)
In a round bottom flask, a mixture of 4-methylbenzene-1,2-
diamine (0.01 mol), 2-amino benzoic acid (0.01 mol), and
polyphosphoric acid (15 ml) was heated at 160°C in an oil
bath for 4 h. The reaction mixture was cooled at room
temperature and poured into cold water (100 ml) and
neutralized with aqueous ammonia. The separated solid
was filtered, washed with water, and dried to obtain
product. The crude product was purified by dissolving in
10% HCl and re-precipitated by the addition of aqueous
ammonia solution. The intermediate product (1) was
recrystallized from ethyl acetate.
Antifungal activity
Similarly, the compounds (3a–l) were tested for antifungal
activity in triplicate sets against C. albicans, A. niger, and
A. clavatus at various concentrations of 1000, 500, 200,
and 100 lg/ml as shown in Table 1. The results were
recorded in the form of primary and secondary screening.
The synthesized compounds were diluted to 1000 lg/ml
concentration, as a stock solution. The compounds which
were found to be active in this primary screening were
further tested in a second set of dilution against all
microorganisms. The lowest concentration, which showed
no growth after spot subculture was considered as MIC for
each drug. The highest dilution showing at least 99%
inhibition was taken as MIC. The test mixture should
contain 108 spores/ml MIC. Griseofulvin was used as a
standard drug for antifungal activity, which showed (500,
100, and 100 lg/ml) MIC against C. albicans, A. niger, and
A. clavatus, respectively. The results of antimicrobial
evaluation of derivatives (3a–l) are shown in Table 1.
General preparation for the synthesis of N-arylidene-2-
(6-methyl-1H-benzo[d]imidazol-2-yl)anilines (2a–l)
In a round bottom flask, compound (1) (0.01 mol) was
taken in 1,4-dioxane (20 ml) and different aromatic alde-
hydes (0.01 mol) were added. To this mixture, a pinch of
anhydrous zinc chloride was added and refluxed for 6–8 h
and the product was poured onto crushed ice. The inter-
mediate products (2a–l) were filtered, washed with cold
water, dried, and recrystallized from methanol.
Statistical analysis
General method for the synthesis of 3-(2-(6-methyl-1H-
benzo[d]imidazol-2-yl)phenyl)-2-(aryl)thiazolidin-4-
ones (3a–l)
The standard deviation value is expressed in terms of SD.
On the basis of the calculated value by using ANOVA
method, it has been observed that differences below 0.0001
level (P B 0.001) were considered as statistically
significant.
In a round bottom flask, compounds (2a–l) (0.01 mol) in
1,4-dioxane (20 ml) and thioglycolic acid (0.01 mol) were
taken. The mixture was refluxed in an oil bath for about
8 h. The reaction mixture was cooled and neutralized with
saturated aqueous solution of NaHCO3. The product
obtained was recrystallized from rectified spirit.
Materials and methods
All the required chemicals were purchased from E. Merck.
IR spectra were recorded on Perkin-Elmer FT-IR Spec-
trophotometer. 1H-NMR and 13C-NMR spectra were
recorded on Bruker DPX-40C instrument at 400 MHz.
Chemical shifts were reported in ppm in reference to the
TMS signal. Mass spectra were recorded on JEOL SX-102
spectrophotometer. Elemental analysis was performed
by Perkin-Elmer 2400-CHN analyzer. Melting points
were recorded on Gallenkamp apparatus and were
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(2-
chlorophenyl)thiazolidin-4-one (3a)
Yield: 68%, m.p. 216–218°C; IR (KBr): m = 3487 (N–H
stretching), 3009 (aromatic–H), 3019 (C–H stretching,
–CH2 group), 2955 (C–H stretching, –CH3 group), 1682
(C=O stretching), 1618 (C=N stretching), 1582, 1464 (C=C
aromatic ring), 1461 (–CH2, bending), 1456 (CH3,
123

Med Chem Res (2012) 21:2320–2328
2325
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(4-
fluorophenyl)thiazolidin-4-one (3d)
bending), 758 (mono-substituted benzene), 742 (C–Cl
stretching) cm-1; 1H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H,
–CH3 group), 4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H,
S–CH–N group), 7.17–7.84 (m, 11H, benzimidazole-H,
and Ar–H), 10.25 (s, 1H, –NH group); 13C-NMR (ppm) : d
21.3, 33.5, 67.8, 102.5, 114.1, 115.1, 115.3, 115.5, 124.8,
124.9, 125.8, 126.7, 128.5, 128.7, 128.9, 130.7, 131.9,
132.7, 134.0, 135.6, 136.9, 154.9, 171.2; MS : m/z 419.04
(M?). Anal. calc. For C23H18ClN3OS: C, 65.78; H, 4.32; N,
10.01. Found: C, 65.84; H, 4.38; N, 10.09%.
Yield: 76%, m.p. 199–201°C; IR (KBr): m = 3488 (N–H
stretching), 3000 (aromatic–H), 3024 (C–H stretching,
–CH2 group), 2951 (C–H stretching, –CH3 group), 1683
(C=O stretching), 1619 (C=N stretching), 1582, 1458 (C=C
aromatic ring), 1467 (–CH2, bending), 1454 (CH3, bend-
ing), 1002 (C–F stretching), 755 (mono-substituted ben-
1
zene), cm-1; H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H,
–CH3 group), 4.00:3.90 (d, 2H, –CH2 group), 5.35 (s, 1H,
–OH group), 6.44 (s, 1H, S–CH–N group), 7.12–7.84 (m,
11H, benzimidazole-H, and Ar–H), 10.25 (s, 1H, –NH
group); 13C-NMR (ppm): d 21.3, 33.5, 72.9, 114.1, 115.1,
115.3, 115.5, 115.8, 124.8, 124.9, 125.8, 128.9, 130.3,
131.9, 132.7, 134.8, 135.6, 136.9, 154.9, 161.3, 171.2; MS:
m/z 403.12 (M?). Anal. calc. For C23H18FN3OS: C, 68.47;
H, 4.50; N, 10.41. Found: C, 68.54; H, 4.58; N, 10.49%.
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(4-
chlorophenyl)thiazolidin-4-one (3b)
Yield: 76%, m.p. 191–192°C; IR (KBr): m = 3485 (N–H
stretching), 3021 (C–H stretching, –CH2 group), 3006
(aromatic–H), 2951 (C–H stretching, –CH3 group), 1683
(C=O stretching), 1619 (C=N stretching), 1584, 1460 (C=C
aromatic ring), 1467 (–CH2, bending), 1454 (CH3, bend-
ing), 755 (mono-substituted benzene), 740 (C–Cl stretch-
ing) cm-1; 1H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H, –CH3
group), 4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H, S–CH–
N group), 7.17–7.84 (m, 11H, benzimidazole-H, and Ar–
H), 10.25 (s, 1H, –NH group); 13C-NMR (ppm): d 21.3,
33.5, 72.9, 114.1, 115.1, 115.3, 115.5, 124.8, 124.9, 125.8,
128.9, 130.2, 130.7, 131.9, 132.7, 135.6, 136.9, 137.3,
154.9, 171.2; MS : m/z 419.04 (M?). Anal. calc. For
C23H18ClN3OS: C, 65.78; H, 4.32; N, 10.01. Found: C,
65.86; H, 4.39; N, 10.07%.
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(3-
hydroxyphenyl)thiazolidin-4-one (3e)
Yield: 67%, m.p. 188–190°C; IR (KBr): m = 3478 (N–H
stretching), 3423 (–OH stretching), 3018 (C–H stretching,
–CH2 group), 3010 (aromatic–H), 2957 (C–H stretching,
–CH3 group), 1690 (C=O stretching), 1611 (C=N stretch-
ing), 1577, 1460 (C=C and aromatic ring), 1461 (–CH2,
bending), 1450 (CH3, bending), 751 (mono-substituted
1
benzene) cm-1; H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H,
–CH3 group), 4.00:3.90 (d, 2H, –CH2 group), 5.35 (s, 1H,
–OH group), 6.44 (s, 1H, S–CH–N group), 6.76–7.84 (m,
11H, benzimidazole-H, and Ar–H), 10.25 (s, 1H, –NH
group); 13C-NMR (ppm): d 21.3, 33.5, 73.2, 114.1, 114.3,
114.7, 115.1, 115.3, 115.5, 119.5, 124.8, 124.9, 125.8,
128.9, 130.0, 131.9, 132.7, 135.6, 136.9, 140.6, 154.9,
156.9, 171.2; MS: m/z 401.12 (M?). Anal. calc. For
C23H19N3O2S: C, 68.21; H, 4.77; N, 10.47. Found: C,
68.29; H, 4.82; N, 10.54%.
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(2,4-
dichlorophenyl)thiazolidin-4-one (3c)
Yield: 66%, m.p. 188–190°C; IR (KBr): m = 3480 (N–H
stretching), 3022 (C–H stretching, –CH2 group), 3007
(aromatic–H), 2952 (C–H stretching, –CH3 group), 1681
(C=O stretching), 1614 (C=N stretching), 1580, 1461
(C=C aromatic ring), 1463 (–CH2, bending), 1459 (CH3,
bending), 748 (ortho disubstituted benzene), 742, 746
(C–Cl stretching) cm-1 1H-NMR (DMSO-d6) ppm: d
;
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(4-
hydroxyphenyl)thiazolidin-4-one (3f)
2.43 (s, 3H, –CH3 group), 4.00:3.90 (d, 2H, –CH2 group),
6.44 (s, 1H, S–CH–N group), 7.11–7.84 (m, 10H, benz-
imidazole-H, and Ar–H), 10.25 (s, 1H, –NH group);
13C-NMR (ppm): d 21.3, 33.5, 67.8, 100.6, 114.1, 115.1,
115.3, 115.5, 124.8, 124.9, 125.8, 126.8, 128.9, 130.3,
131.5, 131.9, 132.7, 134.1, 135.4, 135.6, 136.9, 154.9,
171.2; MS: m/z 453.05 (M?). Anal. calc. For
C23H17Cl2N3OS: C, 60.80; H, 3.77; N, 9.25. Found: C,
60.87; H, 3.83; N, 9.32%.
Yield: 70%, m.p. 196–198°C; IR (KBr): m = 3476 (N–H
stretching), 3423 (–OH stretching), 3020 (C–H stretching,
–CH2 group), 3012 (aromatic–H), 2948 (C–H stretching,
–CH3 group), 1692 (C=O stretching), 1607 (C=N stretch-
ing), 1580, 1462 (C=C, aromatic ring), 1458 (–CH2,
bending), 1448 (CH3, bending), 751 (mono-substituted
123

2326
Med Chem Res (2012) 21:2320–2328
1
benzene) cm-1; H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H,
–CH3 group), 4.00:3.90 (d, 2H, –CH2 group), 5.35 (s, 1H,
–OH group), 6.44 (s, 1H, S–CH–N group), 6.63–7.54 (m,
11H, benzimidazole-H, and Ar–H), 10.25 (s, 1H, –NH
group); 13C-NMR (ppm): d 21.3, 33.5, 72.9, 114.1, 115.1,
115.3, 115.5, 115.8, 124.8, 124.9, 125.8, 128.9, 130.1,
131.9, 132.7, 135.6, 136.9, 154.9, 156.9, 171.2; MS: m/z
401.12 (M?). Anal. calc. For C23H19N3O2S: C, 68.21; H,
4.77; N, 10.47. Found: C, 68.28; H, 4.84; N, 10.56%.
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(2-
nitrophenyl)thiazolidin-4-one (3i)
Yield: 73%, m.p. 200–202°C; IR (KBr): m = 3476 (N–H
stretching), 3022 (C–H stretching, –CH2 group), 3014
(aromatic–H), 2943 (C–H stretching, –CH3 group), 1688
(C=O stretching), 1606 (C=N stretching), 1577, 1462
(C=C, aromatic ring), 1524 (–NO2 asymmetric stretching),
1454 (–CH2, bending), 1447 (CH3, bending), 1313 (–NO2
symmetric stretching), 751 (mono-substituted benzene)
1
cm-1; H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H, –CH3
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(3,4-
dimethoxyphenyl)thiazolidin-4-one (3g)
group), 4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H, S–CH–
N group), 7.12–8.12 (m, 11H, benzimidazole-H, and Ar–
H), 10.25 (s, 1H, –NH group); 13C-NMR (ppm): d 21.3,
33.5, 68.3, 114.1, 115.1, 115.3, 115.5, 124.5, 124.8, 124.9,
125.8, 128.0, 128.9, 129.6, 131.9, 132.7, 133.4, 134.7,
135.6, 136.9, 149.0, 154.9, 171.2; MS: m/z 430.48 (M?).
Anal. calc. For C23H18N4O3S: C, 64.17; H, 4.21; N, 13.01.
Found: C, 64.23; H, 4.28; N, 13.09%.
Yield: 76%, m.p. 206–208°C; IR (KBr): m = 3482 (N–H
stretching), 3025 (C–H stretching, –CH2 group), 3005
(aromatic–H), 2950 (C–H stretching, –CH3 group), 2828
(C–H stretching, –OCH3 group), 1685 (C=O stretching),
1615 (C=N stretching), 1580, 1460 (C=C, aromatic ring),
1470 (–CH2, bending), 1452 (CH3, bending), 1424 (–OCH3
bending), 745 (di-substituted benzene) cm-1 1H-NMR
;
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(3-
nitrophenyl)thiazolidin-4-one (3j)
(DMSO-d6) ppm: d 2.43 (s, 3H, –CH3 group), 4.00:3.90 (d,
2H, –CH2 group), 6.44 (s, 1H, S–CH–N group), 6.76–7.54
(m, 10H, benzimidazole-H, and Ar–H), 10.25 (s, 1H, –NH
group); 13C-NMR (ppm): d 21.3, 33.5, 56.1, 73.2, 112.3,
113.8, 114.1, 115.1, 115.3, 115.5, 122.0, 124.8, 124.9,
125.8, 128.9, 131.9, 132.4, 132.7, 135.6, 136.9, 148.2,
149.7, 154.9, 171.2; MS: m/z 445.53 (M?). Anal. calc. For
C25H23N3O3S: C, 67.40; H, 5.20; N, 9.43. Found: C, 67.48;
H, 5.28; N, 9.50%.
Yield: 68%, m.p. 221–222°C; IR (KBr): m = 3482 (N–H
stretching), 3021 (C–H stretching, –CH2 group), 3005
(aromatic–H), 2950 (C–H stretching, –CH3 group), 1685
(C=O stretching), 1615 (C=N stretching), 1580, 1460
(C=C, aromatic ring), 1465 (–CH2, bending), 1452 (CH3,
bending), 1520 (–NO2 asymmetric stretching), 1310 (–NO2
symmetric stretching), 755 (mono-substituted benzene)
1
cm-1; H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H, –CH3
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(3,4,5-
trimethoxyphenyl)thiazolidin-4-one (3h)
group), 4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H, S–CH–
N group), 7.12–8.12 (m, 11H, benzimidazole-H, and Ar–
H), 10.25 (s, 1H, –NH group); 13C-NMR (ppm): d 21.3,
33.5, 71.9, 114.4, 115.1, 115.3, 115.5, 122.3, 124.8, 124.9,
125.1, 125.8, 128.9, 129.5, 131.9, 132.7, 133.0, 135.6,
136.9, 140.1, 147.8, 154.9, 171.2; MS: m/z 430.48 (M?).
Anal. calc. For C23H18N4O3S: C, 64.17; H, 4.21; N, 13.01.
Found: C, 64.24; H, 4.29; N, 13.11%.
Yield: 66%, m.p. 202–204°C; IR (KBr): m = 3005 (aro-
matic–H), 3482 (N–H stretching), 3020 (C–H stretching,
–CH2 group), 2950 (C–H stretching, –CH3 group), 2835
(C–H stretching, –OCH3 group), 1685 (C=O stretching),
1615 (C=N stretching), 1580, 1460 (C=C, aromatic ring),
1473 (–CH2, bending), 1452 (CH3, bending), 1425 (–OCH3
bending), 740 (substituted benzene) cm-1
;
1H-NMR
(DMSO-d6) ppm: d 2.43 (s, 3H, –CH3 group), 3.83 (s, 9H,
–OCH3 group), 4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H,
S–CH–N group), 7.07–7.54 (m, 9H, benzimidazole-H, and
Ar–H), 10.25 (s, 1H, –NH group); 13C-NMR (ppm): d 21.3,
33.5, 56.1, 60.3, 60.8, 67.3, 104.6, 109.8, 114.1, 115.1,
115.3, 115.5, 123.0, 124.8, 124.9, 125.8, 128.9, 131.9,
132.7, 135.6, 136.9, 142.0, 151.1, 152.3, 154.9, 171.2; MS:
m/z 475.56 (M?). Anal. calc. For C26H25N3O4S: C, 65.67;
H, 5.30; N, 8.84. Found: C, 65.73; H, 5.37; N, 8.90%.
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(4-
nitrophenyl)thiazolidin-4-one (3k)
Yield: 70%, m.p. 238–240°C; IR (KBr): m = 3476 (N–H
stretching), 3025 (C–H stretching, –CH2 group), 3001
(aromatic–H), 2957 (C–H stretching, –CH3 group), 1677
(C=O stretching), 1604 (C=N stretching), 1583, 1463
(C=C, aromatic ring), 1458 (–CH2, bending), 1458 (CH3,
123

Med Chem Res (2012) 21:2320–2328
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bending), 1312 (–NO2 symmetric stretching), 1514 (–NO2
asymmetric stretching), 751 (mono-substituted benzene)
1
cm-1; H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H, –CH3
group), 4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H, S–CH–
N group), 7.12–8.14 (m, 11H, benzimidazole-H, and Ar–
H), 10.25 (s, 1H, –NH group); 13C-NMR (ppm): d 21.3,
33.5, 72.9, 114.1, 115.1, 115.3, 115.5, 123.8, 124.8, 124.9,
125.8, 128.9, 129.6, 131.9, 132.7, 135.6, 136.9, 145.3,
146.3, 154.9, 171.2; MS: m/z 430.48 (M?). Anal. calc. For
C23H18N4O3S: C, 64.17; H, 4.21; N, 13.01. Found: C,
64.25; H, 4.27; N, 13.10%.
Physical constants and characterization of 3-(2-(6-
methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-(2,4-
dinitrophenyl)thiazolidin-4-one (3l)
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Yield: 76%, m.p. 246–248°C; IR (KBr): m = 3476 (N–H
stretching), 3022 (C–H stretching, –CH2 group), 3017
(aromatic–H), 2954 (C–H stretching, –CH3 group), 1678
(C=O stretching), 1607 (C=N stretching), 1583, 1462
(C=C, aromatic ring), 1517 (–NO2 asymmetric stretching),
1314 (–NO2 symmetric stretching), 1461 (–CH2, bending),
1458 (CH3, bending), 738 (di-substituted benzene) cm-1
;
1H-NMR (DMSO-d6) ppm: d 2.43 (s, 3H, –CH3 group),
4.00:3.90 (d, 2H, –CH2 group), 6.44 (s, 1H, S–CH–N
group), 7.12–8.80 (m, 10H, benzimidazole-H, and Ar–H),
10.25 (s, 1H, –NH group); 13C-NMR (ppm): d 21.3, 33.5,
71.9, 114.1, 115.1, 115.3, 115.5, 124.2, 124.8, 124.9,
125.8, 126.0, 128.9, 131.9, 132.7, 135.6, 135.8, 136.9,
143.2, 146.2, 150.1, 154.9, 171.2; MS: m/z 430.48 (M?).
Anal. calc. For C23H17N5O5S: C, 68.10; H, 3.60; N, 14.73.
Found: C, 68.18; H, 3.68; N, 14.80%.
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Acknowledgments The authors are thankful to the Department of
Chemistry, Bhavnagar University, Bhavnagar and Xavier Research
Foundation, St. Xavier’s College, Ahmedabad for providing research
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