A clubbed quinazolinone and 4-thiazolidinone as potential antimicrobial agents

Article abstract of DOI:10.1007/s00044-011-9674-5

A series of N-{5-[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-oxo(1,3- thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl} carboxamides (6a-n) have been synthesized. 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 were elucidated by IR, ¹H NMR, ¹³C NMR, and Mass spectra. Springer Science+Business Media, LLC 2011.

Full text of DOI:10.1007/s00044-011-9674-5

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:1577–1586
DOI 10.1007/s00044-011-9674-5
ORIGINAL RESEARCH
A clubbed quinazolinone and 4-thiazolidinone as potential
antimicrobial agents
•
N. C. Desai Amit M. Dodiya Prashant N. Shihora
•
Received: 9 March 2011 / Accepted: 13 May 2011 / Published online: 28 May 2011
Ó Springer Science+Business Media, LLC 2011
Abstract A series of N-{5-[(2-chlorophenyl)methylene]-
2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}
carboxamides (6a–n) have been synthesized. All the syn-
thesized compounds were screened for in vitro antibacterial
and antifungal activities on Escherichia coli, Staphylo-
coccus aureus, Pseudomonas aeruginosa, Staphylococcus
pyogenes, Candida albicans, Aspergillus niger, and
Aspergillus clavatus. The structures of the compounds
were elucidated by IR, 1H NMR, 13C NMR, and Mass
spectra.
activities (Gursoy and Karali, 1995). They also work as
thymidyalate synthase (Baek et al., 1998), poly(ADP-
ribose) polymerase (PARP) (Griffin et al., 1998) and pro-
tein tyrosine kinase (Sumegi et al., 2007) inhibitors. These
compounds are also used as anti-HIV (Purohit et al., 2003)
and antiviral agents (Liu et al., 1999) such as TMV, CMV
inhibitors. With the inclining biological significance, syn-
thesis, and bioactivity of quinazoline derivatives have
gained momentum amongst the biologist and chemist in
recent past. Our group has reported that some of these
compounds showed antimicrobial activity (Desai and
Dodiya, 2011). Nanda and his co-workers synthesized
3-(arylideneamino)-2-phenylquinazoline-4(3H)-ones, which
were investigated for antibacterial activity against both
gram-positive (Staphylococcus aureus 6571 and Bacillus
subtilis) and gram-negative bacteria (Escherichia coli K12
and Shigella dysenteriae 6) using a turbidometric assay
method (Nanda et al., 2007). However, our group later
found that the incorporation of 3-arylideneamino sub-
stituent enhanced the antibacterial activity of quinazolone
system (Desai and Trivedi, 1993).
Keywords Quinazolinone ꢀ 4-Thiazolidinone ꢀ
Antimicrobial activity
Introduction
4(3H)-Quinazolinones and its derivatives constitute an
important class of heterocyclic compounds. In view of
wide range of bioactivities, this group of compounds dwell
an important role in medicinal and pesticide chemistry.
Having a broad spectrum of pharmacological activities,
they act as analgesic (Aly et al., 2010; Terashima et al.,
1995), antimicrobial (Jatav et al., 2006; Dahiya and
Kumar, 2008), antitumor (El-azab et al., 2010), anticancer
(Giri et al., 2010), antiinflammatory (Kumar and Rajput,
2009), anticonvulsant (Kashaw et al., 2010), antidepressant
(Ergenc et al., 1991), hypolipidemic (Bekhit and Khalil,
1998), antiulcer (Hamel et al., 1996), or immunotropic
For a long time small heterocycle scaffold containing
nitrogen, sulfur, and oxygen have been under investigation
due to their important medicinal properties. Among these
types of molecules, 4-thiazolidinones have displayed var-
ious important biological activities (Capan et al., 1999;
Vigorita et al., 2001; Kavitha et al., 2006; Ottana et al.,
2005; Kucukguzel et al., 2006). Currently 4-thiazolidones
are considered as a new class of antidiabetic (insulin-
sensitising) drugs and potent aldose reductase inhibitors. In
addition, they possess substantial potential for the treat-
ment of diabetes complications like cataract, nephropathy,
and neuropathy (Gerstein et al., 2006). Based on the
results, we have designed and synthesized a series of
N-{5-[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-
N. C. Desai (&) ꢀ A. M. Dodiya ꢀ P. N. Shihora
Medicinal Chemistry Division, Department of Chemistry,
Bhavnagar University, Bhavnagar 364 002, India
e-mail: dnisheeth@rediffmail.com
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Med Chem Res (2012) 21:1577–1586
oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-
hydroquinazolin-3-l)]phenyl}carboxamides (6a–n).
The condensation of 4-methylbenzoyl chloride and
anthranilic acid in the presence of pyridine below 10°C gives
2-(4-methylphenyl) benzo[d]1,3-oxazin-4-one (1), which
when reacted with benzocain gave ethyl 4-[2-(4-methyl-
phenyl)-4-oxo-3-hydroquinazolin-3-yl]benzoate (2) by the
removal of water molecule. Compound (2) on reaction with
hydrazine hydrate furnished N-amino{4-[2-(4-methyl-
phenyl)-4-oxo-(3-hydroquinazolin-3-yl)]phenyl}carboxam-
ide (3). Compound (3) on condensation with various
aromatic aldehydes yielded schiff bases N-[(1Z)-1-aza-2-(4-
hydroxyphenyl)vinyl]{4-[2-(4-methylphenyl)-4-oxo-(3-hy-
droquinazolin-3-yl)]phenyl} (4).
1520 cm-1 –NO2 group symmetric stretching vibration
while at 1345 cm-1 –NO2 group asymmetric stretching
vibration. The absorption peak at 860 cm-1 is due to the
bending vibration of methylene group. The absorption peak
at 774 cm-1 indicates that mono substituted benzene ring
is present.
1H NMR data
It has been observed from the chemical structure of com-
pound 6g that different pairs of carbons, e.g., C-10 and
C-15, C-11 and C-14, C-17 and C-21, C-18 and C-20, C-34
and C-38, C-35 and C-37 are attached to chemically
equivalent protons, which appeared at d = 7.71, 7.28, 7.35,
7.76, 7.78, 6.63 ppm, respectively. The protons attached at
C-13 position appeared as a singlet at d = 2.34 ppm due to
the –CH3 group. The proton of the hydroxy group appeared
as singlet at 5.0 ppm. The proton attached to C-5 appeared
as a multiplet at d = 7.63 ppm while the proton attached to
C-6 appeared as a multiplet at d = 7.70 ppm. The proton
attached to C-29 appeared as a multiplet at d = 7.66 ppm
due to mutual coupling with protons attached to C-28 and
C-30. The proton of the methylene group, which is attached
to C-26 appeared as a singlet at d = 4.6 ppm. The proton
of the secondary amine appeared as a singlet at d = 8.4
due to one side attachment with carbonyl group and
another side with nitrogen atom. The proton of the C-30
appeared as a doublet at d = 8.14 ppm and C-32 appeared
as a singlet at d = 8.31 ppm due to the influence of nitro
group on nearest position. The protons of the quinazolinone
ring which are attached to C-7 and C-8 appeared as a
doublet at d = 7.63 and 8.03 ppm, respectively.
Then, further it produced N-[2-(4-hydroxyphenyl)-4-
oxo-(1,3-thiazolidin-3-yl)]{4-[2-(4-methylphenyl)-4-oxo-
(3-hydroquinazolin-3-yl)] phenyl} carboxamide (5) by
cycloaddition with mercaptoacetic acid in the presence
of 1,4–dioxane which on condensation with different
aryl aldehydes furnished N-{5-[(2-chlorophenyl)methy-
lene]-2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}
{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]
phenyl}-carboxamides (6a–n).
The structures of compounds synthesized were assigned
1
on the basis of IR, H NMR, 13C NMR, and Mass spectra.
These compounds were evaluated for their antimicrobial
screening on different strains of bacteria and fungi
(Scheme 1).
Results and discussion
IR data
13C NMR data
The IR spectrum of the title compound 6g (molecular
formula C38H27N5O6S, m.w. 681.17) has given vibrations
at 3082 and 3061 cm-1 over the ranges which showed
multiple weak absorption peaks corresponding to Qu–H
and Ar–H stretching vibration. The absorption peak at
3315 cm-1 is due to the stretching vibration of secondary
amine which is part of amide linkage. The absorption peak
at 3230 cm-1 is due to the stretching vibration of hydroxyl
group. The absorption peak at 3050 cm-1 is due to the
stretching vibration of methylene group, while the
absorption at 2838 cm-1 is due to the stretching vibration
of aromatic –CH3 group, while the absorption at
1462 cm-1 is due to the bending vibration of aromatic
–CH3 group. The strong absorptions at 1719 and 1738 cm-1
are due to the C=O stretching vibration and amide group,
while the moderate intensity absorption at 1653 cm-1
corresponds to a C=N stretching vibration, and C=C link-
age stretching vibration appeared at 1608 cm-1. The
presence of nitro group gives two vibrations, at the range of
The chemical shifts of the final compound 6g carbons vary
from d = 164.8 to 24.3 ppm. The carbon nuclei under the
influence of a strong electronegative environment appeared
downfield, e.g., the C-2, C-22, and C-23 carbonyl, which
are directly linked to the ring nitrogen atom has a chemical
shift value of d = 160.8, 164.8, and 164.4 ppm, respec-
tively. The carbon C-1 which is attached on both sides to
nitrogen atoms appeared at the same high value of
d = 164.0 ppm. The chemical shift of the ring carbons at
C-3, C-19, and C-24 are affected by the presence of the
nearest carbonyl group, appeared at the same d = 120.8,
129.8, and 129.3 ppm, respectively. The C-31 appeared at
d = 147.8 ppm due to the strong electron withdrawing
influence of nitro group, while C-36 appeared at
d = 147.8 ppm due to the strong electron withdrawing
influence of hydroxy group. The methyl group attached
with the C-12 appeared at d = 139.8 ppm, while the car-
bon of the methyl group C-13 appeared at low value of
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Med Chem Res (2012) 21:1577–1586
1579
Scheme 1 Synthetic route of
the title compounds. (i) NH2-
NH2ꢀH2O. (ii) Methanol, 6 h
reflux. (iii) Methanol, 5 h reflux.
(iv) HSCH2COOH. (v) 1,4-
dioxane, 6 h reflux. (vi) 1,4-
dioxane, 8 h reflux
O
NH
2
COOC H
2
5
O
NH
O
N
N
(i)
N
(ii)
N
R
1
R
1
(3)
(2)
O
(iii)
R
2
H
O
O
O
NH
O
NH
R
2
N
R
2
N
N
(iv)
(v)
N
S
O
N
R
1
N
R
1
(4)
(5)
O
(vi)
(n-a)R
O
H
3
O
NH
R
2
Where,
N
N
S
R = C H -CH
3
1
6
4
O
R = C H -OH
2
6 4
N
R
1
R = Different substituents
3
R
3
(6a-n)
d = 24.3 ppm. The carbon of the methylene group C-26
appeared at d = 125.2 ppm. The carbon C-25 which is
present in thiazolidine ring and which is attached on one
side with nitrogen and on the other side with sulfur atom
appeared at d = 63.4 ppm. The carbons of the 4-methyl
phenyl ring which are attached to quinazolinone ring car-
bon at C-1 position having equivalent carbons like, C-10
and C-15 appeared at 126.0 ppm, while another equivalent
carbon of this ring are C-11 and C-14 appeared at
129.1 ppm, respectively. The carbons of the phenyl ring,
which is attached one side with amide group and another
side to quinazolinone nucleus having equivalent carbons
like, C-17 and C-21 appeared at 121.7 ppm, while C-18
and C-20 equivalent carbons appeared at 127.7 ppm. The
4-hydroxyphenyl ring with is attached with thiazoldine ring
at C-25 position having equivalent carbons like C-34 and
C-38 appeared at 129.1 ppm, while C-35 and C-37
appeared at 115.9 ppm. The carbons (C-27, C-28, C-29,
C-30, and C-32) of the 3-nitrophenyl ring which is attached
with methylene linkage appeared from 120.0 to 136.1 ppm,
respectively. The carbons (C-3, C-4, C-5, C-6, C-7, and
C-8) of the quinazolinone ring appeared from 120.8 to
151.2 ppm, respectively. The carbon numbering is descri-
bed in Fig. 1.
Antimicrobial activity
For antibacterial activity, compounds 6b, 6d, 6f, 6i, and 6j
are considered to be good active against E. coli, while
compounds 6m and 6n are considered as very good active
against E. coli, while compounds 6c and 6g are considered
as excellent active against E. coli. Compounds 6b, 6g, 6k,
and 6m are considered as good active against P.aerugin-
osa, while compounds 6d and 6e are considered as very
good active against P. aeruginosa. Compounds 6j and 6l
123

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Med Chem Res (2012) 21:1577–1586
OH
primary screening were similarly diluted to obtain 100, 50,
25, 12.5 lg/ml concentrations. 10 lg/ml suspensions were
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 (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.
37
36
O
38
25
18
35
19
22
17
O
NH
N
34
33
4
7
20
3
2
5
16
N
21
15
S
23
O
6
24
26
8
1
N
9
14
32
NO
2
10
27
31
12
11
28
CH
3
13
30
29
Fig. 1 Carbon numbering of the compound 6g
Antifungal activity
are considered as good active against S. aureus, while
compounds 6b, 6d, 6e, 6f, 6k, and 6m are considered as
very good active against S. aureus, while compound 6g is
considered as excellent active. Compounds 6a, 6c, 6d, 6h,
6l, and 6m are considered as good active against S. pyog-
enes, while compound 6f is considered as very good active
against S. pyogenes. For the antifungal activity, compounds
6d, 6e, 6g, and 6n are considered as good active against
C. albicans. Compounds 6b, 6c, 6g, 6i, and 6m are con-
sidered as good active against A. niger. Compounds 6d, 6f,
6i, and 6l are considered as good active against A. clavatus
The antibacterial and antifungal activities have been
enhanced due to the incorporation of 4-thiazolidine in
quinazoline ring followed by the substitution at 5th posi-
tion of 4-thiazolidine ring system due to the Knoevenagel
reaction of active methylene group present at 5th position.
The discussion and comparison of antibacterial and anti-
fungal activities have been compared with ampicillin and
griseofulvin, respectively.
While for the antifungal activity, same compounds were
tested for antifungal activity in triplicate against Candida
albicans, A. niger, and A. clavatus at various concentra-
tions 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 at 1000 lg/ml concentration, as a stock solution.
The synthesized 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 con-
centration, which showed no growth after spot subculture
was considered as (MIC) for each drug. The highest dilu-
tion showing at least 99% inhibition is taken as MIC. The
test mixture should contain 108 spores/ml MIC. ‘griseo-
fulvin’ 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 (6a–n) are
collected in (Table 1).
Antibacterial activity
Statistical analysis
For the antibacterial activity, the newly synthesized com-
pounds were screened for their antibacterial activity against
gram positive bacteria S. aureus (MTCC-96) and Strepto-
coccus pyogenes (MTCC-442) and gram negative E. coli
(MTCC-443) and Pseudomonas aeruginosa (MTCC-
1688)]. Antibacterial activity was carried out by serial
broth dilution method (Ghalem and Mohamed, 2009; Desai
and Trivedi, 1993; Al-Bayati and Al-Mola, 2008). The
standard strains used for the antimicrobial activity was
procured from Institute of Microbial Technology, Chan-
digarh. The compounds (6a–n) were screened for their
antibacterial activity in triplicate against E. coli, S. aureus,
P. aeruginosa, and S. pyogenes at different concentrations
of 1000, 500, 200, 100, 50, 25, 12.5 lg/ml as shown in
(Table 1). The drugs which were found to be active in
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 the differences below
0.0001 level (P B 0.0001) were considered as statistically
significant.
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
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Med Chem Res (2012) 21:1577–1586
1581
Table 1 Results of antibacterial and antifungal screening of the compounds (6a–n)
Sr. no. –R3
Minimum inhibitory concentration (MIC) in ug/ml SD Minimum inhibitory concentration (MIC) ug/ml SD
E. coli P. aeruginosa S. aureus
MTCC 443 MTCC 1688 MTCC 96
S. pyogenes C. albicans
MTCC 442 MTCC 227
A. niger
MTCC 282
A. clavatus
MTCC 1323
6a
6b
6c
6d
6e
6f
–H
–3,4,5-(OCH3)3 100 4.72* 100 3.05*
–N(CH3)2
–2–OH–naphthyl 100 4.04* 50 4.58
200 4.50* 500 3.78*
500 4.04* 100 4.04* 500 2.51*
100 3.05* 200 2.51* 1000 4.04*
1000 4.50*
100 3.51*
100 4.35*
1000 3.60*
500 4.50*
1000 4.58*
100 4.04*
1000 3.05*
100 3.51*
1000 3.51*
500 4.16*
1000 4*
100 3.60*
1000 3*
–
1000 3.05*
1000 4*
500 3.78*
100 3.05*
1000 3.60*
100 4.04*
500 4.04*
1000 4.16*
100 3*
25 4.93* 200 4.04* 1000 4.04* 100 4.50* 1000 4*
100 3.78* 100 4*
100 3.05* 250 1*
100 4.58*
100 4.04*
–4–F
500 3.78* 50 4*
100 4.04* 500 3.46*
25 4.93* 100 4.58*
–4–OH
–3–NO2
–2–Cl
100 2.51* 50 3.51* 1000 4.50*
50 3.51* 500 1* 100 2.30*
500 4.04* 100 1.32* 1000 3.21*
500 3* 500 4.04* 1000 3.51*
6g
6h
6i
200 4*
500 3.60*
–4–OCH3
100 3.78* 500 4.04*
6j
–2–OH–4–OCH3 100 3.21* 200 3.51*
250 3.21* 500 4.16* 500 3.46*
100 3.51* 500 2.08* 500 3.78*
250 3.05* 100 3.60* 500 3.05*
500 4.04*
500 3.05*
100 2.51*
1000 2*
1000 3*
–
6k
6l
–2–OCH3
–2–OH–5–Br
–2,6-(Cl)2
–4–Cl
500 3.21* 100 3.05*
500 4.58* 500 3.51*
50 4.04* 200 2*
6m
6n
100 3.53* 100 2*
500 3.78*
50 3*
100 3.21*
500 1.56* 500 3.45* 100 2.23*
Ampicillin
100 2.0* 100 1.0*
250 1.52* 100 2.08*
–
Griseofulvin
–
–
–
–
500 0.57*
100 1*
100 1.15*
SD standard deviation, * P B 0.0001
residual solvent signal. Mass spectra were recorded on
JEOL SX-102. Elemental analysis was performed by Per-
kin-Elmer 2400-CHN analyzer. Melting points were
recorded on Gallenkamp apparatus and were left uncor-
rected. Aluminum coated TLC plates 60 F245 (E. Merck)
were used for monitoring of reaction and purity of com-
pounds. In the conventional method, compounds were
synthesized by using Random synthesizer. Bookie Rotav-
apour was used for distillation.
for 6 h. After the reaction was completed, the reaction
mixture was poured into crushed ice to afford dark brown
precipitate. This was collected by filtration and washed
with cold water. The resulting solid was recrystallized from
ethanol (99%).
M.p.: 182°C, Yield 75%; IR (KBr): 3426 cm-1 (–N–H
stretching, primary amine), 3311 cm-1 (N–H stretching,
secondary amine), 3084, 3062 cm-1 (Qu–H and Ar–H
stretching, aromatic ring), 2837 cm-1 (C–H stretching,
–CH3 group), 1713 cm-1 (C=O stretching, amide group),
1648, 1605 cm-1 (C=N, C=C stretching, aromatic ring),
1341 cm-1 (C–N stretching, quinazoline ring), 771 cm-1
(para-substitution of aromatic ring); 1H NMR (CDCl3):
7.0–7.9 (m, 12H, Ar–H), 8.0 (s, 1H, –CONH–), 2.3 (s, 3H,
Ar–CH3), 2.0(s, 2H, –N–NH2); 13C NMR: 21.3, 120.8,
124.5, 125.6, 126.6, 126.7, 127.3, 127.6, 129.1, 129.6,
130.3, 133.4, 136.1, 139.8, 148.7, 156.2, 160.6, 167.2.
GCMS: m/z: 370.14 (M?). Anal. calcd. for C22H18N4O2: C,
71.33; H, 4.89; N, 15.12. Found: C, 71.52; H, 4.60; N,
15.26.
Experimental
Synthesis of 1 and 2
2-(4-methylphenyl)benzo[d]1,3-oxazin-4-one 1 and 2-(4-
methylphenyl)-3-(4-propanoylphenyl)-3-hydroquinazolin-
4-one 2 have been synthesized as described previously
(Pandey et al., 2005).
Preparation of N-amino{4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (3)
Preparation of N-[(1Z)-1-aza-2-(4-
hydroxyphenyl)vinyl]{4-[2-(4-methylphenyl)-4-oxo(3-
hydroquinazolin-3-yl)]phenyl}carboxamide (4)
The intermediate compound 3 has been achieved by a
mixture of 2-(4-methylphenyl)-3-(4-propanoylphenyl)-3-
hydroquinazolin-4-one 2 (0.01 mol) and excess of hydra-
zine hydrate (99%, 0.015 mol) in methanol (40 ml) was
added to a round bottom flask. The contents were refluxed
The intermediate compound 4 has been achieved by a
mixture of N-amino{4-[2-(4-methylphenyl)-4-oxo(3-hy-
droquinazolin-3-yl)]phenyl}carboxamides
3
(0.01 mol)
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Med Chem Res (2012) 21:1577–1586
General preparation of N-{5-[(aryl)methylene]-2-(4-
hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-
yl)]phenyl}carboxamides (6a–n)
and 4-hydroxybenzaldehyde (0.01 mol) (over a period of
10 min) in methanol (30 ml) was refluxed for 5 h. After the
reaction was completed, the light brown schiff base comes
out. This was collected by filtration. The resulting solid
was recrystallized from methanol.
M.p.: 222°C, Yield 78%; IR (KBr): 3312 cm-1 (N–H
stretching, secondary amine), 3233 cm-1 (O–H stretching,
–OH group), 3081, 3065 cm-1 (Qu–H and Ar–H stretch-
ing, aromatic ring), 2832 cm-1 (C–H stretching, –CH3
group), 1714 cm-1 (C=O stretching, amide group), 1644,
1603 cm-1 (C=N, C=C stretching, aromatic ring),
1344 cm-1 (C–N stretching, quinazoline ring), 774 cm-1
A mixture of a sodium methoxide solution of N-[2-
(4-hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)] {4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}car-
boxamide 5 (0.01 mol) and benzaldehyde (0.01 mol) in 1:4
dioxane (40 ml) was refluxed for 8 h. After the reaction
was completed, the reaction mixture was pour into crushed
ice to afford brown precipitate. This was collected by fil-
tration, and then washed with cold water. The resulting
solid was recrystallized from ethanol (99%).
1
(ortho substitution of aromatic ring); H NMR (CDCl3): d
6.8–7.9 (m, 16H, ArH), 8.1(s, 1H, –CONH–), 8.1 (s, 1H,
–N=CH–), 5.0 (s, 1H, ArOH); 13C NMR: 21.3, 116.0,
120.8, 124.5, 125.6, 126.3, 126.6, 126.7, 127.3, 128.4,
129.1, 129.6, 130.3, 130.6, 133.4, 136.1, 139.8, 146.8,
148.7, 156.2, 160.8, 163.2; GCMS: m/z: 474.17 (M?).
Anal. calcd. for C29H22N4O3:C, 76.09; H, 4.89; N, 8.87.
Found: C, 76.29; H, 4.60; N, 8.60.
Physical constants and characterization of N-{5-
[(phenyl)methylene]-2-(4-hydroxyphenyl)-4-oxo(1,3-
thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-
hydroquinazolin-3-yl)] phenyl}carboxamide (6a)
M.p.: 132°C, Yield 68%; IR (KBr): 3310 cm-1 (N–H
stretching, secondary amine), 3230 cm-1 (O–H stretching,
–OH group), 3120 cm-1 (C–H stretching, aromatic ring),
3052 (=CH stretching), 2900 cm-1 (C–H stretching, –CH3
group), 1710, 1725 cm-1 (C=O stretching, amide group),
1630, 1610 cm-1 (C=N, C=C stretching, aromatic ring),
1345 cm-1 (C–N stretching, quinazoline ring), 920 cm-1
(ortho-substitution of aromatic ring), 864 (=CH bending);
1H NMR (CDCl3): d 6.0–7.9 (m, 21H, Ar–H), 8.3 (s, 1H,
–CONH–), 4.7 (s, 1H, –C=CH–Ar), 5.9 (s, 1H, –N–CH–S),
5.0 (s, 1H, Ar–OH); 13C NMR (CDCl3): d 24.3, 63.4,
115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 126.4,
127.4, 127.7, 128.0, 128.7, 128.8, 129.1, 129.3, 129.8,
133.5, 134.5, 135.2, 136.1, 139.8, 151.2, 156.9, 160.8,
164.1, 164.3, 164.5; GCMS: m/z: 613.18 (M?). Anal.
calcd. for C38H28N4O4S: C-71.68%, H-4.43%, N-8.80%.
Found: C-71.74%, H-4.49%, N-8.85%.
Preparation of N-[2-(4-hydroxyphenyl)-4-oxo(1,3-
thiazolidin-3-yl)]{4-[2-(4-methylphenyl)-4-oxo(3-
hydroquinazolin-3-yl)]-phenyl}carboxamide (5)
The synthesis of intermediate compound 5 has been achieved
by a mixture of N-[(1Z)-1-aza-2-(4-hydroxyphenyl)vinyl]
{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]
phenyl}carboxamides 4 (0.01 mol) and mercaptoacetic acid
(0.011 mol) in 1:4 dioxane (40 ml) was refluxed for 6 h.
After the reaction completed, the solution was poured into
ice-cold aqueous solution of sodium bicarbonate to remove
unreacted mercaptoacetic acid. The yellow to brown pre-
cipitate was filtered, and then washed with cold water. The
resulting solid was recrystallized from ethanol (99%).
M.p.: 242°C, Yield 68%; IR (KBr): 3315 cm-1 (N–H
stretching, secondary amine), 3230 cm-1 (O–H stretching,
–OH group), 3081, 3065 cm-1 (Qu–H and Ar–H stretch-
ing, aromatic ring), 2835 cm-1 (C–H stretching, –CH3
group), 1738, 1717 cm-1 (C=O stretching, amide group),
1648, 1605 cm-1 (C=N, C=C stretching, aromatic ring),
1341 cm-1 (C–N stretching, quinazoline ring), 776 cm-1
Physical constants and characterization of N-{5-[(3,4,5-
trimethoxyphenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo- (1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6b)
1
M.p.: 125°C, Yield 71%; IR (KBr): 3311 cm-1 (N–H
stretching, secondary amine), 3231 cm-1 (O–H stretching,
–OH group), 3122 cm-1 (C–H stretching, aromatic ring),
3061 (=CH stretching), 2902 cm-1 (C–H stretching, –CH3
group), 1713, 1724 cm-1 (C=O stretching, amide group),
1632, 1611 cm-1 (C=N, C=C stretching, aromatic ring),
1346 cm-1 (C–N stretching, quinazoline ring), 1255 cm-1
(C–O stretching, ether group), 924 cm-1 (ortho-substitu-
tion of aromatic ring), 859 (=CH bending); 1H NMR
(ortho substitution of aromatic ring); H NMR (CDCl3): d
6.6–7.9 (m, 16H, Ar–H), 8.0 (s, 1H, –CONH–), 5.9 (s, 1H,
–N–CH–S), 4.9 (s, 1H, ArOH), 3.3 (s, 2H, –CO–CH–S).
13C NMR (CDCl3): d 21.3, 32.4, 62.2, 115.7, 120.8, 124.5,
125.6, 126.6, 126.7, 127.0, 127.3, 127.6, 129.1, 129.6,
130.3, 133.4, 136.1, 139.8, 148.7, 156.2, 156.5, 160.6,
163.7, 164.9; GCMS: m/z: 648.14 (M?). Anal. calcd. for
C31H24N4O4S: C, 67.86; H, 4.40; N, 10.21. Found: C,
67.27; H, 4.86; N, 10.52.
123

Med Chem Res (2012) 21:1577–1586
1583
(CDCl3): d 6.1–7.9 (m, 18H, Ar–H), 8.4 (s, 1H, –CONH–),
4.9 (s, 1H, –C = CH–Ar), 5.9 (s, 1H, –N–CH–S), 5.1 (s, 1H,
Ar–OH), 3.7 (s, 9H, Ar–OCH3); 13C NMR (CDCl3): d 24.3,
56.1, 56.4, 63.4, 103.8, 115.9, 120.8, 121.7, 122.4, 125.2,
125.6, 126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.5,
129.8, 133..5, 134.5, 136.1, 138.4, 139.8, 150.7, 151.2,
156.9, 160.8, 164.2, 164.5, 164.6; GCMS: m/z: 726.21 (M?).
Anal. calcd. for C41H34N4O7S: C-67.75%, H-4.72%,
N-7.71%. Found: C-67.81%, H-4.76%, N-7.75%.
(CDCl3): d 24.3, 63.4, 115.9, 117.7, 117.8, 120.8, 121.7,
122.3, 122.4, 123.6, 125.2, 125.6, 126.0, 126.8, 127.4,
127.7, 128.5, 128.8, 129.1, 129.3, 129.8, 130.1, 131.9,
133.5, 134.5, 136.1, 139.8, 151.2, 155.8, 156.9, 160.6,
164.2, 164.3, 164.6; GCMS: m/z: 702.19 (M?). Anal.
calcd. for C42H30N4O5S: C-71.78%, H-4.30%, N-7.97%.
Found: C-71.82%, H-4.34%, N-7.99%.
Physical constants and characterization of N-{5-[(4-
fluorophenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6e)
Physical constants and characterization of N-{5-[(4-
(dimethylamino)phenyl)methylene]-2-(4-
hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-
yl)]phenyl}carboxamide (6c)
M.p.: 175°C, Yield 74%; IR (KBr): 3313 cm-1 (N–H
stretching, secondary amine), 3231 cm-1 (O–H stretching,
–OH group), 3123 cm-1 (C–H stretching, aromatic ring),
3045 (=CH stretching), 2906 cm-1 (C–H stretching, –CH3
group), 1711, 1723 cm-1 (C=O stretching, amide group),
1634, 1616 cm-1 (C=N, C=C stretching, aromatic ring),
1344 cm-1 (C–N stretching, quinazoline ring), 1250 cm-1
(C–F stretching), 924 cm-1 (ortho substitution of aromatic
ring), 860 (=CH bending); 1H NMR (CDCl3): d 6.1–7.9 (m,
20H, Ar–H), 8.3 (s, 1H, –CONH–), 4.9 (s, 1H, –C = CH–
Ar), 5.9 (s, 1H, –N–CH–S), 5.1 (s, 1H, Ar–OH); 13C NMR
(CDCl3): d 24.3, 63.4, 115.4, 115.9, 120.8, 121.7, 122.4,
125.2, 125.6, 126.0, 127.4, 127.7, 128.0, 128.8, 129.1,
129.3, 129.8, 130.8, 133.5, 134.5, 136.1, 139.8, 151.2,
156.9, 162.1, 160.5, 164.0, 164.2, 164.8; GCMS: m/z:
654.17 (M?). Anal. calcd. for C38H27FN4O4S: C-69.71%,
H-4.16%, N-8.56%. Found: C-69.76%, H-4.21%,
N-8.60%.
M.p.: 100°C, Yield 70%; IR (KBr): 3314 cm-1 (N–H
stretching, secondary amine), 3232 cm-1 (O–H stretching,
–OH group), 3124 cm-1 (C–H stretching, aromatic ring),
3056 (=CH stretching), 2903 cm-1 (C–H stretching, –CH3
group), 1713 cm-1, 1723 cm-1 (C=O stretching, amide
group), 1632, 1612 cm-1 (C=N, C=C stretching, aromatic
ring), 1347 cm-1 (C–N stretching, quinazoline ring),
926 cm-1 (ortho-substitution of aromatic ring), 857 (=CH
1
bending); H-NMR (CDCl3): d 6.6–7.9 (m, 20H, Ar–H),
8.2 (s, 1H, –CONH–), 4.6 (s, 1H, –C=CH–Ar), 5.9 (s, 1H,
–N–CH–S), 5.0 (s, 1H, Ar–OH), 2.8 (s, 6H, Ar–N(CH3)2);
13C NMR (CDCl3): d 24.3, 40.2, 63.4, 114.2, 115.9, 120.8,
121.7, 122.4, 124.7, 125.2, 125.6, 126.0, 127.3, 127.4, 127.7,
128.8, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 148.8,
151.2, 156.9, 160.7, 164.2, 164.4, 164.7; GCMS: m/z: 679.23
(M?). Anal. calcd. for C40H53N5O4S: C-70.67%, H-4.89%,
N-10.30%. Found: C-70.72%, H-4.93%, N-10.35%.
Physical constants and characterization of N-{5-[(4-
hydroxyphenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6f)
Physical constants and characterization of N-{5-[(1-
hydroxy(2-naphthyl))methylene)]-2-(4-
hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}-
carboxamide (6d)
M.p.: 255°C, Yield 65%; IR (KBr): 3317 cm-1 (N–H
stretching, secondary amine), 3235 cm-1 (O–H stretching,
–OH group), 3120 cm-1 (C–H stretching, aromatic ring),
3055 (=CH stretching), 2900 cm-1 (C–H stretching, –CH3
group), 1715, 1727 cm-1 (C=O stretching, amide group),
1634, 1613 cm-1 (C=N, C=C stretching, aromatic ring),
1346 cm-1 (C–N stretching, quinazoline ring), 863 (=CH
bending), 927 cm-1 (ortho substitution of aromatic ring);
1H NMR (CDCl3): d 6.5–7.9 (m, 20H, Ar–H), 8.1 (s, 1H,
–CONH–), 4.8 (s, 1H, –C = CH–Ar), 5.8 (s, 1H, –N–CH–
S), 5.1 (s, 1H, Ar–OH), 5.0 (s, 1H, Ar–OH); 13C NMR
(CDCl3): d 24.3, 63.4, 115.8, 115.9, 120.8, 121.7, 122.4,
125.2, 125.6, 126.0, 127.4, 127.7, 127.8, 128.8, 129.1,
129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9,
M.p.: 160°C, Yield 55%; IR (KBr): 3313 cm-1 (N–H
stretching, secondary amine), 3233 cm-1 (O–H stretching,
–OH group), 3124 (C–H stretching, aromatic ring), 3051
(=CH stretching), 2904 cm-1 (C–H stretching, –CH3
group), 1713, 1725 cm-1 (C=O stretching, amide group),
1636, 1615 cm-1 (C=N, C=C stretching, aromatic ring),
1343 cm-1 (C–N stretching, quinazoline ring), 920 cm-1
(ortho substitution of aromatic ring), 863 (=CH bending);
1H NMR (CDCl3): d 6.6–7.9 (m, 20H, Ar–H), 8.5 (s, 1H,
–CONH–), 4.7 (s, 1H, –C=CH–Ar), 5.9 (s, 1H, –N–CH–S),
5.0 (s, 1H, Ar–OH), 5.1 (s, 1H, Ar–OH); 13C NMR
123

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Med Chem Res (2012) 21:1577–1586
157.7, 164.0, 160.8, 164.4, 164.8; GCMS: m/z: 652.18
(M?). Anal. calcd. for C38H28N4O5S: C-69.92%, H-4.32%,
N-8.58%. Found: C-69.96%, H-4.38%, N-8.64%.
164.3, 164.7; GCMS: m/z: 670.14 (M?). Anal. calcd. for
C38H27ClN4O4S: C-68.00%, H-4.05%, N-8.35%. Found:
C-68.05%, H-4.11%, N-8.39%.
Physical constants and characterization of N-{5-[(3-
nitrophenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6g)
Physical constants and characterization of N-{5-[(4-
methoxyphenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6i)
M.p.: 111°C, Yield 59%; IR (KBr): 3315 cm-1 (N–H
stretching, secondary amine), 3230 cm-1 (O–H stretching,
–OH group), 3083, 3061 cm-1 (Qu–H and Ar–H stretch-
ing, aromatic ring), 3050 (=CH stretching), 2838 cm-1 (C–
H stretching, –CH3 group), 1738, 1719 cm-1 (C=O
stretching, amide group), 1653, 1608 cm-1 (C=N, C=C
stretching, aromatic ring), 1520 cm-1 (–NO2 group
asymmetric stretching), 1345 cm-1 (C–N stretching, qui-
nazoline ring), 1345 (–NO2 group symmetric stretching),
860 (=CH bending), 774 cm-1 (ortho substitution of aro-
M.p.: 300°C, Yield 72%; IR (KBr): 3316 cm-1 (N–H
stretching, secondary amine), 3238 cm-1 (O–H stretching,
–OH group), 3120 cm-1 (C–H stretching, aromatic ring),
3048 (=CH stretching), 2903 cm-1 (C–H stretching, –CH3
group), 1715, 1728 cm-1 (C=O stretching, amide group),
1635, 1615 cm-1 (C=N, C=C stretching, aromatic ring),
1349 cm-1 (C–N stretching, quinazoline ring), 862 (=CH
bending), 926 cm-1 (ortho substitution of aromatic ring);
1H NMR (CDCl3): d 6.1–7.9 (m, 18H, Ar–H), 8.4 (s, 1H,
–CONH–), 4.7 (s, 1H, –C=CH–Ar), 5.8 (s, 1H, –N–CH–S),
5.0 (s, 1H, Ar–OH), 3.6 (s, 3H, Ar–OCH3); 13C NMR
(CDCl3): d 24.3, 55.8, 63.4, 114.2, 115.9, 120.8, 121.7,
122.4, 125.2, 125.6, 126.0, 127.4, 127.5, 127.7, 128.8,
129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 151.2,
156.9, 159.8, 160.3, 164.0, 164.1, 164.5; GCMS: m/z:
666.19 (M?). Anal. calcd. for C39H30N4O5S: C-70.25%,
H-4.54%, N-8.40%. Found: C-70.30%, H-4.59%, N-8.46%.
1
matic ring); H NMR (CDCl3): d 6.0–7.9 (m, 20H, Ar–H),
8.4 (s, 1H, –CONH–), 4.6 (s, 1H, –C=CH–Ar), 5.9 (s, 1H,
–N–CH–S), 5.0 (s, 1H, Ar–OH); 13C NMR (CDCl3): d 24.3,
63.4, 115.9, 120.0, 120.8, 123.1, 121.7, 122.4, 125.2, 125.6,
126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.6, 129.8,
132.5, 133.5, 134.5, 136.1, 139.8, 147.8, 151.2, 156.9,
160.8, 164.1, 164.3, 164.8; GCMS: m/z: 681.17 (M?). Anal.
calcd. for C38H27N5O6S: C-66.95%, H-3.99%, N-10.27%.
Found: C-66.99%, H-3.97%, N-10.32%.
Physical constants and characterization of N-{5-[(4-
methoxy-2-hydroxyphenyl)methylene]-2-(4-
hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-
yl)]phenyl}carboxamide (6j)
Physical constants and characterization of N-{5-[(2-
chlorophenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6h)
M.p.: 181°C, Yield 63%; IR (KBr): 3313 cm-1 (N–H
stretching, secondary amine), 3234 cm-1 (O–H stretching,
–OH group), 3120 cm-1 (C–H stretching, aromatic ring),
3059 (=CH stretching), 2903 cm-1 (C–H stretching, –CH3
group), 1712, 1723 cm-1 (C=O stretching, amide group),
1632, 1614 cm-1 (C=N, C=C stretching, aromatic ring),
1340 cm-1 (C–N stretching, quinazoline ring), 858 (=CH
bending), 923 cm-1 (ortho substitution of aromatic ring);
1H NMR (CDCl3): d 6.6–7.9 (m, 20H, Ar–H), 8.4 (s, 1H,
–CONH–), 4.8 (s, 1H, –C=CH–Ar), 5.9 (s, 1H, –N–CH–S);
5.1 (s, 1H, Ar–OH), 5.0 (s, 1H, Ar–OH), 3.7 (s, 3H, Ar–
OCH3). 13C NMR (CDCl3): d 24.3, 55.8, 63.4, 101.9,
106.8, 108.8, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6,
126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.8, 133.5,
134.5, 136.1, 139.8, 151.2, 156.9, 159.3, 161.2, 160.6,
164.3, 164.5, 164.5; GCMS: m/z: 682.18 (M?). Anal.
M.p.: 219°C, Yield 70%; IR (KBr): 3315 cm-1 (N–H
stretching, secondary amine), 3234 cm-1 (O–H stretching,
–OH group), 3120 cm-1 (C–H stretching, aromatic ring),
3053 (=CH stretching), 2909 cm-1 (C–H stretching, –CH3
group), 1716, 1729 cm-1 (C=O stretching, amide group),
1636, 1607 cm-1 (C=N, C=C stretching, aromatic ring),
1349 cm-1 (C–N stretching, quinazoline ring), 866 (=CH
bending), 920 cm-1 (ortho substitution of aromatic ring),
1
745 cm-1 (C–Cl stretching); H NMR (CDCl3): d 6.0–7.9
(m, 20H, Ar–H), 8.3 (s, 1H, –CONH–), 4.7 (s, 1H,
–C = CH–Ar), 5.8 (s, 1H, –N–CH–S), 5.1 (s, 1H, Ar–OH);
13C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7,
122.4, 125.2, 125.6, 126.0, 126.8, 127.4, 127.7, 127.8,
128.7, 128.8, 129.1, 129.3, 129.4, 129.8, 133.0, 31.1,
133..5, 134.5, 136.1, 139.8, 151.2, 156.9, 160.5, 164.2,
123

Med Chem Res (2012) 21:1577–1586
1585
Physical constants and characterization of N-{5-[(2,6-
dichlorophenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methyl- phenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide
(6m)
calcd. for C39H30N4O6S: C-68.61%, H-4.43%, N-8.21%.
Found: C-68.66%, H-4.49%, N-8.26%.
Physical constants and characterization of N-{5-[(2-
methoxyphenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6k)
M.p.: 183°C, Yield: 72%; IR (KBr): 3319 cm-1 (N–H
stretching, secondary amine), 3230 cm-1 (O–H stretching,
–OH group), 3123 cm-1 (C–H stretching, aromatic ring),
3048 (=CH stretching), 2903 cm-1 (C–H stretching, –CH3
group), 1716, 1728 cm-1 (C=O stretching, amide group),
1632, 1614 cm-1 (C=N, C=C stretching, aromatic ring),
1349 cm-1 (C–N stretching, quinazoline ring), 869 (=CH
bending), 925 cm-1 (ortho substitution of aromatic ring),
M.p.: 99°C. Yield 69%; IR (KBr): 3314 cm-1 (N–H
stretching, secondary amine), 3233 cm-1 (O–H stretching,
–OH group), 3122 cm-1 (C–H stretching, aromatic ring),
3051 (=CH stretching), 2903 cm-1 (C–H stretching, –CH3
group), 1713, 1725 cm-1 (C=O stretching, amide group),
1630, 1613 cm-1 (C=N, C=C stretching, aromatic ring),
1346 cm-1 (C–N stretching, quinazoline ring), 863 (=CH
bending), 921 cm-1 (ortho substitution of aromatic ring);
1H NMR (CDCl3): d 6.1–7.9 (m, 18H, Ar–H), 8.3 (s, 1H,
–CONH–), 4.7 (s, 1H, –C=CH–Ar), 5.9 (s, 1H, –N–CH–S),
5.1 (s, 1H, Ar–OH), 3.7 (s, 3H, Ar–OCH3); 13C NMR
(CDCl3): d 24.3, 56.2, 63.4, 114.2, 114.9, 115.9, 120.8,
121.0, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7,
128.8, 129.0, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1,
139.8, 151.2, 156.9, 157.6, 160.6, 164.2, 164.3, 164.6;
GCMS: m/z: 666.74 (M?). Anal. calcd. for C39H30N4O5S:
C-70.25%, H-4.54%, N-8.40%. Found: C-70.29%,
H-4.59%, N-8.46%.
1
752 cm-1 (C–Cl stretching); H NMR (CDCl3): d 6.2–7.7
(m, 19H, Ar–H), 8.4 (s, 1H, –CONH–), 4.9 (s, 1H,
–C=CH–Ar), 5.7 (s, 1H, –N–CH–S), 5.3 (s, 1H, Ar–OH);
13C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7,
122.4, 125.2, 125.6, 126.0, 126.8, 127.4, 127.7, 128.8,
129.1, 129.3, 129.8, 130.8, 132.5, 133.5, 134.5, 135.7,
136.1, 139.8, 151.2, 156.9, 160.8, 164.0,164.4, 164.8;
GCMS: m/z: 704.15 (M?). Anal. calcd. for C36H26Cl2
N4O4S: C-64.68%, H-3.71%, N-7.94%. Found: C-64.73%,
H-3.76%, N-7.99%.
Physical constants and characterization of N-{5-[(4-
chlorophenyl)methylene]-2-(4-hydroxyphenyl)-4-
oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-
oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6n)
Physical constants and characterization of N-{5-[(5-
bromo-2-hydroxyphenyl)methylene]-2-(4-
hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-
methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}-
carboxamide (6l)
M.p.: 209°C, Yield: 68%; IR (KBr): 3317 cm-1 (N–H
stretching, secondary amine), 3235 cm-1 (O–H stretching,
–OH group), 3125 cm-1 (C–H stretching, aromatic ring),
3055 (=CH stretching), 2905 cm-1 (C–H stretching, –CH3
group), 1716, 1728 cm-1 (C=O stretching, amide group),
1637, 1615 cm-1 (C=N, C=C stretching, aromatic ring),
1348 cm-1 (C–N stretching, quinazoline ring), 925 cm-1
(ortho substitution of aromatic ring), 859 (=CH bending),
M.p.: 150°C, Yield 71%; IR (KBr): 3313 cm-1 (N–H
stretching, secondary amine), 3234 cm-1 (O–H stretching,
–OH group), 3120 (C–H stretching, aromatic ring), 3057
(=CH stretching), 2907 cm-1 (C–H stretching, –CH3
group), 1718, 1727 cm-1 (C = O stretching, amide group),
1634, 1612 cm-1 (C=N, C=C stretching, aromatic ring),
1340 cm-1 (C–N stretching, quinazoline ring), 867 (=CH
bending), 926 cm-1 (ortho substitution of aromatic ring),
1
742 cm-1 (C–Cl stretching); H NMR (CDCl3): d 6.1–7.9
(m, 20H, Ar–H), 8.5 (s, 1H, –CONH–), 4.8 (s, 1H,
–C=CH–Ar), 5.8 (s, 1H, –N–CH–S), 5.0 (s, 1H, Ar–OH);
13C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7,
122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 127.8, 128.7,
128.8, 129.1, 129.3, 129.8, 133.3, 133.5, 134.5, 136.1,
139.8, 151.2, 156.9, 160.7, 164.2, 164.3, 164.7; GCMS: m/
z: 670.14 (M?). Anal. calcd. for C38H27ClN4O4S:
C-68.00%, H-4.05%, N-8.35%. Found: C-68.06%,
H-4.09%, N-8.41%.
1
556 cm-1 (C–Br stretching); H NMR (CDCl3): d 6.3–8.1
(m, 19H, Ar–H), 8.5 (s, 1H, –CONH–), 4.7 (s, 1H,
–C=CH–Ar), 5.8 (s, 1H, –N–CH–S), 5.1 (s, 1H, Ar–OH),
4.9 (s, 1H, Ar–OH); 13C NMR (CDCl3): d 24.3, 63.4, 115.9,
115.6, 118.0, 118.7, 120.8, 121.7, 122.4, 125.2, 125.6,
126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.8,131.3,
132.2, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 157.3,
160.9, 164.1, 164.3, 164.6; GCMS: m/z: 730.09 (M?). Anal.
calcd. for C38H27BrN4O5S: C-62.38%, H-3.72%, N-7.66%.
Found: C-62.42%, H-3.77%, N-7.71%.
Acknowledgment The authors express their sincere thanks to the
Department of Chemistry and to Bhavnagar University, Bhavnagar
for providing research facilities.
123

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Med Chem Res (2012) 21:1577–1586
Gursoy A, Karali N (1995) Synthesis and anticonvulsant activity of
new acylthiosemicarbazides and thiazolidones. Farmaco 50:857–
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