Synthesis and antimicrobial activity of quinazolin-4(3H)-ones incorporating sulfonamido-4-thiazolidinone

Article abstract of DOI:10.1002/cjoc.201090332

Some new derivatives 7-chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-[4-(2-substituted phenyl-4-oxothiazolidin-3-yl)phenyl]sulfonamido-quinazolin-4(3H)-ones 5a-5l were synthesized from 2-[2-(2,6-dichlorophenyl) amino]phenyl acetic acid via acid chloride,

Full text of DOI:10.1002/cjoc.201090332

FULL PAPER
Synthesis and Antimicrobial Activity of Quinazolin-4(3H)-ones
Incorporating Sulfonamido-4-thiazolidinone
Patel, Navin B.*
Patel, Jaymin C.
Patel, Virendra N.
Department of Chemistry, Veer Narmad South Gujarat University, Surat 395007, Gujarat, India
Some new derivatives 7-chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-[4-(2-substituted phenyl-4-oxo-
thiazolidin-3-yl)phenyl]sulfonamido-quinazolin-4(3H)-ones 5a — 5l were synthesized from 2-[2-(2,6-dichloro-
phenyl)amino]phenyl acetic acid via acid chloride, benzoxazinone, amino quinazolin-4(3H)-one and Schiff base
formation. The synthesized compounds were screened for in vitro antibacterial and antifungal activities by broth
micro dilution method. Some of the Schiff base as well as 4-thiazolidinone derivatives showed promising antibacte-
rial activity while pronounced antifungal activity was observed against C. albicans.
Keywords biological activity, quinazolin-4(3H)-one, sulfonamide, 4-thiazolidinone
Introduction
rectly. Melting points were determined in PMP-DM
scientific melting point apparatus and are uncorrected.
The purity of compound was confirmed by TLC using
Merck silica gel 60 F254 plates using toluene ∶
ethylacetate∶methanol (7∶2∶1, volume ratio) as a
mobile phase and spots were visualized under UV radia-
tion. IR spectra were recorded on a Perkin-Elmer RX 1
The heterocyclic compounds are important part of
medicinal chemistry due to its rapid and diverse me-
dicinal applications. It was reported that quinazolines
have an interesting antimicrobial activity against differ-
ent species of pathogenic gram positive bacteria, gram
negative bacteria and fungi.1-4 Quinazolin-4(3H)-one
have emerged as an important class of nitrogenated het-
erocycle that have attracted synthetic interest because
they possess pharmacological and therapeutic properties.
A number of quinazolin-4(3H)-one derivatives have a
wide range of biological applications including antibac-
terial, antifungal, antiviral, anticonvulsant, analgesic,
antiinflammatory, antitubercular, anticancer and CNS
depressant.5-10 Schiff base has good biological impor-
tance and possesses variety of activities i.e. anticonvul-
sant, antimicrobial, antitubercular, anticancer, antitumor
and antimalarial.11-17 4-Thiazolidinone is a sulfur atom
containing 5-member heterocycle possessing antibacterial,
antifungal, anti-HIV, anticonvulsant, anti-inflammatory
and hypnotic activities.18-24 Sulfonamide also showed
broad spectrum of pharmacological properties such as
antibacterial, antifungal, anticandidal, antinociceptive,
anticancer and anti-inflammatory activities.25-30
FTIR spectrophotometer, using potassium bromide pel-
－
1
1
lets and the frequencies are expressed in cm . The H
NMR and 13C NMR spectra were recorded with a
Bruker Avance II 400 NMR spectrometer, using
tetramethylsilane as the internal reference, with deutero
chloroform (CDCl3) as a solvent. Elemental analyses
were performed on a Heraeus Carlo Erba 1180 CHN
analyzer. 2-[(2,6-Dichlorophenyl)amino]phenyl acetyl
chloride (1) was synthesized by literature procedure.31
Synthesis of 7-chloro-2-[2-(2,6-dichlorophenyl)amino]-
benzyl-4H-3,1-benzoxazin-4-one (2)
A mixture of acid chloride 1 (15 mmol) and 4-chloro-
anthranilic acid (15 mmol) in 20 mL pyridine were
stirred at 0—5 ℃ for 1 h, further stirred for 1 h at room
temperature. After completion of reaction, a pasty mass
obtained was washed thoroughly with sodium bicarbon-
ate (5% w/v) to remove unreacted acid. A solid sepa-
rated was filtered, dried and recrystallized from metha-
The quinazolin-4(3H)-one incorporated with differ-
ent type of aryl as well as heteryl linkers, showed wide
range of pharmacological applications. In the present
work we have synthesized quinazolin-4(3H)-one incor-
porated with 4-thiazolidinone and evaluated its in vitro
antimicrobial activity.
1
nol. Yield 53%, m.p. 183—188 ℃; H NMR (CDCl3,
400 MHz) δ: 3.58 (s, 2H, CH2), 6.37—8.18 (m, 10H,
Ar-H), 9.25 (bs, 1H, NH); 13C NMR (CDCl3, 100 MHz)
δ: 32.26, 112.73, 116.12, 120.43, 121.42, 124.25, 126.47,
126.63, 127.28, 127.61, 129.32, 131.18, 134.24, 137.38,
－
1
141.72, 142.17, 149.86, 159.34, 164.29 cm ; IR (KBr)
ν: 3440 (NH), 2921, 2848 (CH2), 1735 (C＝O), 1620
(C＝N), 1145 (C—O), 754 (C—Cl). Anal. calcd for
C21H13Cl3N2O2 (Mr＝431.7): C 58.43, H 3.04, N 6.49;
Experimental
All chemicals were of analytical grade and used di-
*
E-mail: drnavin@satyam.net.in(N. B. Patel), drjaymin@yahoo.in (J. C. Patel)
Received March 16, 2010; revised April 23, 2010; accepted June 3, 2010.
Chin. J. Chem. 2010, 28, 1989— 1997
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1989

Patel, Patel & Patel
FULL PAPER
found C 58.52, H 3.08, N 6.39.
157.64, 160.53, 162.89; IR (KBr) ν: 3425 (NH), 2925,
2843 (CH2), 1677 (C＝O), 1637 (N＝CH), 1608 (C＝
－
1
Synthesis of 7-chloro-2-[2-(2,6-dichlorophenyl)amino]-
benzyl-3-(4-aminophenyl)sulfonamido-quinazolin-
4(3H)-one (3)
N), 1342, 1159 (SO2), 743 (C—Cl) cm . Anal. calcd
for C34H23Cl4N5O3S (Mr＝723.46): C 56.45, H 3.20, N
9.68; found C 56.34, H 3.25, N 9.61.
A mixture of benzoxazinone 2 (10 mmol) and
4-aminophenylsulfonyl hydrazide (10 mmol) was dis-
solve in 50 mL pyridine. The reaction mixture was re-
fluxed for 5—6 h, cooled and poured into ice-cold water
containing concentrated HCl. The separated solid was
filtered, washed and recrystallised from ethanol. Yield
65%, m.p. 170—173 ℃; 1H NMR (CDCl3, 400 MHz) δ:
3.62 (s, 2H, CH2), 5.71 (bs, 2H, NH2), 6.37—8.17 (m,
14H, Ar-H), 9.22 (bs, 1H, NH), 11.82 (bs, 1H, SO2NH);
13C NMR (CDCl3, 100 MHz) δ: 31.23, 116.19, 117.15,
120.54, 121.57, 123.26, 124.35, 124.61, 126.82, 127.27,
127.52, 128.44, 129.44, 130.21, 131.04, 132.29, 136.43,
137.32, 141.84, 146.28, 150.74, 160.69, 162.76; IR
(KBr) ν: 3512—3386 (NH and NH2), 2930, 2842 (CH2),
1678 (C＝O), 1618 (C＝N), 1362, 1149 (SO2), 750 (C
—Cl) cm－ 1. Anal. calcd for C27H20Cl3N5O3S (Mr＝
600.9): C 53.97, H 3.35, N 11.65; found C 54.16, H 3.28,
N 11.77.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(2-hydroxybenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4c) Yield 66%, m.p. 153—155
1
℃; H NMR (CDCl3, 400 MHz) δ: 3.57 (s, 2H, CH2),
4.92 (bs, 1H, OH), 6.35—8.17 (m, 18H, Ar-H), 8.57 (s,
1H, N＝CH), 9.24 (bs, 1H, NH), 10.77 (bs, 1H, SO2NH);
13C NMR (CDCl3, 100 MHz) δ: 30.86, 109.23, 116.07,
116.56, 119.75, 120.29, 121.32, 122.53, 123.48, 124.12,
124.45, 125.39, 127.04, 127.16, 127.43, 128.60, 129.58,
130.96, 131.28, 132.36, 136.11, 137.63, 139.27, 141.54,
146.46, 155.68, 156.73, 157.85, 160.62, 162.98; IR (KBr)
ν: 3434 (NH), 3252 (OH), 2927, 2850 (CH2), 1678 (C＝
O), 1635 (N＝CH), 1612 (C＝N), 1340, 1155 (SO2), 760
－
1
(C—Cl) cm . Anal. calcd for C34H24Cl3N5O4S (Mr＝
705.01): C 57.92, H 3.43, N 9.93; found C 58.14, H 3.55,
N 10.08.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(4-hydroxybenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4d) Yield 69%, m.p. 135—
General procedure for the synthesis of Schiff base
4a— 4l
1
138 ℃; H NMR (CDCl3, 400 MHz) δ: 3.62 (s, 2H,
CH2), 4.98 (bs, 1H, OH), 6.36—8.18 (m, 18H, Ar-H),
8.63 (s, 1H, N＝CH), 9.27 (bs, 1H, NH), 10.74 (bs, 1H,
SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.06, 115.96,
116.73, 118.27, 120.44, 121.25, 122.49, 123.57, 124.18,
124.37, 126.98, 127.24, 127.32, 128.42, 128.66, 129.64,
131.14, 132.47, 136.36, 137.59, 139.45, 141.76, 146.33,
155.83, 157.58, 159.86, 160.40, 163.13; IR (KBr) ν: 3438
(NH), 3246 (OH), 2930, 2846 (CH2), 1685 (C＝O), 1632
(N＝CH), 1614 (C＝N), 1353, 1152 (SO2), 753 (C—Cl)
A mixture of compound 3 (5 mmol) and substituted
aromatic aldehyde (5 mmol) with catalytic amount of
glacial acetic acid was refluxed in 40 mL absolute etha-
nol for 4—6 h on water bath. The excess solvent was
distilled off, poured into ice cold water. The separated
solid was filtered, washed and recrystallized from etha-
nol.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-
3-[4-(2-chlorobenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4a) Yield 75%, m.p. 147—
－
1
cm . Anal. calcd for C34H24Cl3N5O4S (Mr＝705.01): C
57.92, H 3.43, N 9.93; found C 57.78, H 3.46, N 9.87.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(2-nitrobenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4e) Yield 79%, m.p. 140—
1
149 ℃; H NMR (CDCl3, 400 MHz) δ: 3.60 (s, 2H,
CH2), 6.36—8.16 (m, 18H, Ar-H), 8.60 (s, 1H, N＝CH),
9.25 (bs, 1H, NH), 10.80 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 31.28, 116.05, 120.48, 121.53,
122.38, 123.33, 124.29, 124.57, 126.76, 127.32, 127.55,
127.77, 128.18, 128.62, 128.83, 129.39, 129.87, 131.23,
131.42, 132.36, 135.16, 136.41, 137.45, 139.17, 141.82,
146.25, 155.53, 157.73, 160.72, 162.86; IR (KBr) ν:
3424 (NH), 2920, 2845 (CH2), 1680 (C＝O), 1635 (N＝
1
142 ℃; H NMR (CDCl3, 400 MHz) δ: 3.59 (s, 2H,
CH2), 6.37—8.17 (m, 18H, Ar-H), 8.57 (s, 1H, N＝CH),
9.23 (bs, 1H, NH), 10.76 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 30.76, 115.85, 120.16, 121.38,
122.23, 123.34, 123.67, 124.03, 124.22, 126.82, 126.94,
127.18, 128.76, 129.17, 129.76, 130.53, 131.42, 132.24,
133.46, 134.14, 136.51, 137.28, 139.64, 142.12, 146.25,
149.86, 155.35, 157.66, 160.27, 163.26; IR (KBr) ν: 3437
(NH), 2920, 2845 (CH2), 1679 (C＝O), 1635 (N＝CH),
1615 (C＝N), 1540, 1362 (NO2), 1342, 1154 (SO2), 747
－
1
CH), 1610 (C＝N), 1355, 1152 (SO2), 750 (C—Cl) cm .
Anal. calcd for C34H23Cl4N5O3S (Mr＝723.46): C 56.45,
H 3.20, N 9.68; found C 56.27, H 3.16, N 9.74.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-
3-[4-(4-chlorobenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4b) Yield 70%, m.p. 169—
－
1
(C—Cl) cm . Anal. calcd for C34H23Cl3N6O5S (Mr＝
734.01): C 55.63, H 3.16, N 11.45; found C 55.48, H
3.11, N 11.37.
1
173 ℃; H NMR (CDCl3, 400 MHz) δ: 3.55 (s, 2H,
CH2), 6.37—8.16 (m, 18H, Ar-H), 8.55 (s, 1H, N＝CH),
9.21 (bs, 1H, NH), 10.75 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 31.15, 116.24, 120.63, 121.46,
122.32, 123.33, 123.55, 124.26, 124.57, 126.91, 127.39,
127.58, 128.76, 129.31, 131.28, 131.76, 132.12, 133.38,
135.52, 136.25, 137.48, 139.36, 141.66, 146.42, 155.72,
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(3-nitrobenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4f) Yield 71%, m.p. 155—157
1
℃; H NMR (CDCl3, 400 MHz) δ: 3.60 (s, 2H, CH2),
6.36—8.38 (m, 18H, Ar-H), 8.63 (s, 1H, N＝CH), 9.27
(bs, 1H, NH), 10.78 (bs, 1H, SO2NH); 13C NMR (CDCl3,
1990
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1989—1997

Synthesis and Antimicrobial Activity of Quinazolin-4(3H)-ones
100 MHz) δ: 30.81, 115.73, 120.02, 120.23, 121.19,
122.34, 123.42, 124.16, 124.38, 124.54, 125.65, 126.73,
126.96, 127.25, 129.04, 129.88, 130.62, 131.27, 132.15,
133.36, 136.43, 136.89, 139.23, 141.84, 146.37, 148.47,
155.52, 157.78, 160.41, 163.09; IR (KBr) ν: 3435 (NH),
2927, 2842 (CH2), 1680 (C＝O), 1628 (N＝CH), 1602
(C＝N), 1548, 1365 (NO2), 1338, 1161 (SO2), 742 (C—
found C 57.04, H 3.51, N 9.45.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(4-hydroxy-3-methoxybenzylideneamino)phenyl]-
sulfonamido-quinazolin-4(3H)-one (4j) Yield 62%,
m.p. 146—148 ℃; 1H NMR (CDCl3, 400 MHz) δ: 3.36
(s, 3H, OCH3), 3.58 (s, 2H, CH2), 4.92 (bs, 1H, OH),
6.36—8.16 (m, 17H, Ar-H), 8.61 (s, 1H, N＝CH), 9.27
(bs, 1H, NH), 10.76 (bs, 1H, SO2NH); 13C NMR (CDCl3,
100 MHz) δ: 31.22, 54.98, 112.87, 116.25, 119.29,
120.61, 121.48, 122.33, 123.39, 123.67, 124.23, 124.62,
126.76, 126.93, 127.40, 127.72, 128.85, 129.32, 131.30,
132.23, 136.27, 137.52, 139.50, 141.68, 146.38, 147.56,
149.79, 155.86, 157.69, 160.55, 163.19; IR (KBr) ν:
3442 (NH), 3254 (OH), 2930, 2856 (CH2), 1677 (C＝O),
1634 (N＝CH), 1612 (C＝N), 1353, 1147 (SO2), 1210,
－
1
Cl) cm . Anal. calcd for C34H23Cl3N6O5S (Mr＝734.01):
C 55.63, H 3.16, N 11.45; found C 55.74, H 3.18, N
11.41.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(4-methoxybenzylideneamino)phenyl]sulfonamido-
quinazolin-4(3H)-one (4g) Yield 75%, m.p. 172—
1
175 ℃; H NMR (CDCl3, 400 MHz) δ: 3.30 (s, 3H,
OCH3), 3.55 (s, 2H, CH2), 6.38—8.17 (m, 18H, Ar-H),
8.59 (s, 1H, N＝CH), 9.23 (bs, 1H, NH), 10.73 (bs, 1H,
SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.14, 55.16,
114.43, 116.11, 116.84, 120.23, 121.38, 122.16, 123.54,
123.87, 124.22, 126.32, 126.54, 126.78, 127.21, 129.23,
130.12, 131.15, 132.35, 136.67, 137.03, 139.39, 141.73,
146.48, 155.74, 157.82, 159.93, 160.65, 163.17; IR
(KBr) ν: 3440 (NH), 2929, 2850 (CH2), 1675 (C＝O),
1635 (N＝CH), 1607 (C＝N), 1352, 1158 (SO2), 1206,
－
1
1106 (C—O—C), 742 (C—Cl) cm . Anal. calcd for
C35H26Cl3N5O5S (Mr＝735.04): C 57.19, H 3.57, N 9.53;
found C 57.08, H 3.62, N 9.59.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(4-dimethylaminobenzylideneamino)phenyl]sulfon-
amido-quinazolin-4(3H)-one (4k) Yield 60%, m.p.
1
141—143 ℃; H NMR (CDCl3, 400 MHz) δ: 3.10 [s,
23H, N(CH3)2], 3.56 (s, 2H, CH2), 6.37—8.18 (m, 18H,
Ar-H), 8.66 (s, 1H, N＝CH), 9.20 (bs, 1H, NH), 10.75
(bs, 1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 30.84,
38.24, 112.72, 116.09, 120.32, 121.33, 122.56, 122.88,
123.49, 124.13, 124.58, 126.89, 127.22, 127.61, 128.73,
128.97, 129.56, 131.11, 132.42, 136.13, 137.49, 139.25,
141.56, 146.34, 150.65, 156.05, 157.74, 160.29, 163.32;
IR (KBr) ν: 3433 (NH), 2918, 2830 (CH2), 1680 (C＝O),
1632 (N＝CH), 1610 (C＝N), 1355, 1164 (SO2), 756
－
1
1110 (C—O—C), 755 (C—Cl) cm . Anal. calcd for
C35H26Cl3N5O4S (Mr＝719.04): C 58.46, H 3.64, N 9.74;
found C 58.34, H 3.58, N 9.83.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(3,4,5-trimethoxybenzylideneamino)phenyl]sulfon-
amido-quinazolin-4(3H)-one (4h) Yield 65%, m.p.
1
164—166 ℃; H NMR (CDCl3, 400 MHz) δ: 3.32 (s,
33H, OCH3), 3.58 (s, 2H, CH2), 6.36—8.18 (m, 16H,
Ar-H), 8.54 (s, 1H, N＝CH), 9.22 (bs, 1H, NH), 10.76
(bs, 1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.26,
54.76, 55.23, 104.96, 116.32, 120.11, 121.29, 122.35,
123.47, 123.93, 124.19, 126.62, 126.81, 127.34, 127.87,
129.16, 130.25, 131.26, 132.54, 136.78, 137.15, 139.43,
140.68, 141.91, 146.32, 148.83, 156.12, 157.63, 160.18,
162.92; IR (KBr) ν: 3438 (NH), 2927, 2842 (CH2), 1673
(C＝O), 1630 (N＝CH), 1610 (C＝N), 1350, 1162
－
1
(C—Cl) cm . Anal. calcd for C36H29Cl3N6O3S (Mr＝
732.08): C 59.06, H 3.99, N 11.48; found C 59.23, H
4.07, N 11.42.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-
3-[4-(2-hydroxy-4-diethylaminobenzylideneamino)-
phenyl]sulfonamido-quinazolin-4(3H)-one (4l) Yield
78%, m.p. 143—146 ℃; 1H NMR (CDCl3, 400 MHz) δ:
1.35 [t, J＝7.56 Hz, 23H, N(CH2CH3)2], 2.82 [q, J＝7.56
Hz, 22H, N(CH2CH3)2], 3.54 (s, 2H, CH2), 4.96 (bs, 1H,
OH), 6.38—8.18 (m, 17H, Ar-H), 8.60 (s, 1H, N＝CH),
9.29 (bs, 1H, NH), 10.69 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 14.86, 31.17, 43.27, 102.03, 108.34,
110.18, 115.92, 120.65, 121.63, 122.19, 123.31, 124.39,
124.50, 126.95, 127.36, 127.48, 129.11, 129.66, 130.46,
131.20, 132.14, 136.55, 137.43, 139.46, 142.14, 146.12,
151.69, 155.92, 157.92, 159.74, 160.32, 163.04; IR (KBr)
ν: 3442 (NH), 3258 (OH), 2925, 2849 (CH2), 1679 (C＝
O), 1636 (N＝CH), 1605 (C＝N), 1358, 1165 (SO2), 744
－
1
(SO2), 1210, 1114 (C—O—C), 746 (C—Cl) cm . Anal.
calcd for C37H30Cl3N5O6S (Mr＝779.09): C 57.04, H
3.88, N 8.99; found C 56.87, H 3.96, N 8.92.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
[4-(2-hydroxy-4-methoxybenzylideneamino)phenyl]-
sulfonamido-quinazolin-4(3H)-one (4i) Yield 66%,
m.p. 153—156 ℃; 1H NMR (CDCl3, 400 MHz) δ: 3.35
(s, 3H, OCH3), 3.56 (s, 2H, CH2), 4.95 (bs, 1H, OH),
6.38—8.17 (m, 17H, Ar-H), 8.62 (s, 1H, N＝CH), 9.25
(bs, 1H, NH), 10.79 (bs, 1H, SO2NH); 13C NMR (CDCl3,
100 MHz) δ: 30.92, 55.37, 104.19, 106.53, 108.74,
116.02, 119.97, 121.41, 122.54, 123.58, 123.88, 124.26,
126.89, 127.11, 127.15, 129.08, 129.85, 131.17, 131.83,
132.39, 136.44, 137.62, 139.71, 142.23, 146.29, 155.95,
157.52, 158.49, 160.22, 160.36, 163.24; IR (KBr) ν:
3435 (NH), 3249 (OH), 2920, 2842 (CH2), 1675 (C＝O),
1629 (N＝CH), 1608 (C＝N), 1347, 1156 (SO2), 1200,
－
1
(C—Cl) cm . Anal. calcd for C38H33Cl3N6O4S (Mr＝
776.13): C 58.81, H 4.29, N 10.83; found C 58.59, H
4.23, N 10.91.
General procedure for the synthesis of 4-thiazolidi-
nonyl-quinazolin-4(3H)-ones 5a— 5l
Thioglycolic acid (4 mmol) was added to a stirred
solution of 4a—4l (2 mmol) in 50 mL dry DMF, con-
taining a pinch of anhydrous ZnCl2 and refluxed for 8—
－
1
1104 (C—O—C), 735 (C—Cl) cm . Anal. calcd for
C35H26Cl3N5O5S (Mr＝735.04): C 57.19, H 3.57, N 9.53;
Chin. J. Chem. 2010, 28, 1989—1997
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1991

Patel, Patel & Patel
FULL PAPER
9 h. Excess of solvent was distilled off and the residual
reaction mixture was cooled and poured into ice-cold
water. The separated solid was filtered, washed and
recrystallised from ethanol.
3.65 (s, 2H, CH2), 3.94 (s, 2H, CH2-S), 5.14 (s, 1H,
CH-S), 4.97 (bs, 1H, OH), 6.36—8.19 (m, 18H, Ar-H),
9.25 (bs, 1H, NH), 10.78 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 30.89, 36.43, 64.26, 116.09,
116.48, 120.58, 121.23, 121.34, 122.16, 123.45, 124.22,
124.46, 126.86, 126.98, 127.19, 127.38, 128.14, 129.78,
131.12, 132.51, 134.29, 136.29, 137.69, 141.62, 145.51,
146.44, 156.75, 160.53, 163.25, 172.85; IR (KBr) ν:
3434 (NH), 3256 (OH), 2927, 2844 (CH2), 1748 (C＝O,
thiazolidinone), 1680 (C＝O, quinazolinone), 1611 (C＝
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(2-chlorophenyl)-4-oxo-thiazolidin-3-yl]phenyl}-
sulfonamido-quinazolin-4(3H)-one (5a) Yield 78%,
m.p. 156—158 ℃; 1H NMR (CDCl3, 400 MHz) δ: 3.61
(s, 2H, CH2), 3.95 (s, 2H, CH2-S), 5.22 (s, 1H, CH-S),
6.37—8.16 (m, 18H, Ar-H), 9.26 (bs, 1H, NH), 10.84
(bs, 1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.34,
35.75, 58.81, 105.87, 116.23, 120.47, 121.27, 121.64,
123.37, 124.41, 124.68, 125.74, 126.72, 127.01, 127.33,
127.45, 127.62, 127.94, 128.25, 129.59, 131.12, 132.36,
134.23, 135.32, 136.32, 137.53, 141.96, 145.47, 146.17,
160.51, 162.89, 173.38; IR (KBr) ν: 3436 (NH), 2925,
2839 (CH2), 1758 (C＝O, thiazolidinone), 1682 (C＝O,
quinazolinone), 1610 (C＝N), 1362, 1150 (SO2), 755
－
1
N), 1339, 1153 (SO2), 742 (C—Cl) cm . Anal. calcd
for C36H26Cl3N5O5S2 (Mr＝779.11): C 55.50, H 3.36, N
8.99; found C 55.38, H 3.41, N 9.07.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(2-nitrophenyl)-4-oxo-thiazolidin-3-yl]phenyl}-
sulfonamido-quinazolin-4(3H)-one (5e) Yield 82%,
m.p. 151—154 ℃; 1H NMR (CDCl3, 400 MHz) δ: 3.58
(s, 2H, CH2), 3.96 (s, 2H, CH2-S), 5.23 (s, 1H, CH-S),
6.38—8.18 (m, 18H, Ar-H), 9.26 (bs, 1H, NH), 10.73
(bs, 1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 30.89,
35.42, 59.61, 115.78, 120.11, 121.19, 121.45, 122.92,
123.76, 124.13, 124.34, 126.69, 126.88, 127.10, 127.23,
128.36, 129.54, 129.73, 131.36, 132.29, 132.64, 134.18,
135.21, 136.59, 137.18, 142.15, 145.56, 146.26, 150.25,
160.36, 163.12, 172.67; IR (KBr) ν: 3447 (NH), 2915,
2840 (CH2), 1746 (C＝O, thiazolidinone), 1675 (C＝O,
quinazolinone), 1616 (C＝N), 1545, 1365 (NO2), 1342,
1157 (SO2), 754 (C — Cl) cm － 1. Anal. calcd for
C36H25Cl3N6O6S2 (Mr＝808.11): C 53.51, H 3.12, N
10.40; found C 53.38, H 3.14, N 10.48.
－
1
(C—Cl) cm . Anal. calcd for C36H25Cl4N5O4S2 (Mr＝
797.56): C 54.21, H 3.16, N 8.78; found C 54.03, H 3.24,
N 7.89.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(4-chlorophenyl)-4-oxo-thiazolidin-3-yl]phenyl}-
sulfonamido-quinazolin-4(3H)-one (5b) Yield 75%,
m.p. 172—176 ℃; 1H NMR (CDCl3, 400 MHz) δ: 3.56
(s, 2H, CH2), 3.93 (s, 2H, CH2-S), 5.20 (s, 1H, CH-S),
6.37—8.17 (m, 18H, Ar-H), 9.20 (bs, 1H, NH), 10.70
(bs, 1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.22,
36.18, 63.77, 116.34, 120.54, 121.36, 121.58, 123.21,
123.49, 124.19, 124.67, 127.03, 127.13, 127.32, 127.71,
129.28, 130.68, 131.35, 131.53, 132.25, 133.97, 136.17,
137.53, 138.46, 141.76, 145.76, 146.38, 160.39, 163.06,
173.12; IR (KBr) ν: 3428 (NH), 2927, 2843 (CH2), 1745
(C＝O, thiazolidinone), 1672 (C＝O, quinazolinone),
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(3-nitrophenyl)-4-oxo-thiazolidin-3-yl]phenyl}-
sulfonamido-quinazolin-4(3H)-one (5f) Yield 85%,
m.p. 162—166 ℃; 1H NMR (CDCl3, 400 MHz) δ: 3.62
(s, 2H, CH2), 3.97 (s, 2H, CH2-S), 5.22 (s, 1H, CH-S),
6.37—8.40 (m, 18H, Ar-H), 9.28 (bs, 1H, NH), 10.77
(bs, 1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 30.95,
35.75, 66.28, 115.86, 120.14, 120.94, 121.10, 121.48,
122.74, 123.49, 124.22, 124.44, 125.28, 126.67, 126.87,
127.02, 127.31, 129.76, 131.32, 132.24, 133.12, 133.87,
135.53, 136.58, 136.92, 142.11, 145.64, 146.43, 148.30,
160.47, 162.93, 173.23; IR (KBr) ν: 3432 (NH), 2930,
2857 (CH2), 1765 (C＝O, thiazolidinone), 1682 (C＝O,
quinazolinone), 1605 (C＝N), 1541, 1357 (NO2), 1333,
1150 (SO2), 750 (C — Cl) cm － 1. Anal. calcd for
C36H25Cl3N6O6S2 (Mr＝808.11): C 53.51, H 3.12, N
10.40; found C 53.36, H 3.07, N 10.34.
－
1
1606 (C＝N), 1345, 1156 (SO2), 746 (C—Cl) cm .
Anal. calcd for C36H25Cl4N5O4S2 (Mr＝797.56): C 54.21,
H 3.16, N 8.78; found C 54.32, H 3.19, N 8.72.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-
3-{4-[2-(2-hydroxyphenyl)-4-oxo-thiazolidin-3-yl]-
phenyl}sulfonamido-quinazolin-4(3H)-one (5c) Yield
76%, m.p. 160—162 ℃; 1H NMR (CDCl3, 400 MHz) δ:
3.60 (s, 2H, CH2), 3.97 (s, 2H, CH2-S), 5.22 (s, 1H,
CH-S), 4.94 (bs, 1H, OH), 3.36—8.18 (m, 18H, Ar-H),
9.26 (bs, 1H, NH), 10.75 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 30.69, 35.92, 58.63, 108.96, 115.87,
116.15, 119.46, 120.35, 121.17, 121.23, 123.54, 124.26,
124.62, 124.83, 127.12, 127.19, 127.29, 127.56, 128.32,
129.42, 131.11, 132.53, 134.11, 136.19, 137.77, 141.65,
145.57, 146.37, 152.81, 160.59, 163.14, 172.78; IR (KBr)
ν: 3440 (NH), 3252 (OH), 2924, 2847 (CH2), 1750 (C＝
O, thiazolidinone), 1674 (C＝O, quinazolinone), 1613
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-
3-{4-[2-(4-methoxyphenyl)-4-oxo-thiazolidin-3-yl]-
phenyl}sulfonamido-quinazolin-4(3H)-one (5g) Yield
81%, m.p. 179—181 ℃; 1H NMR (CDCl3, 400 MHz) δ:
3.28 (s, 3H, OCH3), 3.57 (s, 2H, CH2), 3.96 (s, 2H,
CH2-S), 5.13 (s, 1H, CH-S), 6.37—8.18 (m, 18H, Ar-H),
9.20 (bs, 1H, NH), 10.71 (bs, 1H, SO2NH); 13C NMR
(CDCl3, 100 MHz) δ: 31.25, 36.48, 55.33, 64.12, 114.19,
116.28, 120.17, 121.25, 121.52, 122.62, 123.68, 124.06,
124.42, 125.64, 126.46, 126.83, 126.95, 127.15, 129.94,
131.05, 132.40, 134.04, 136.75, 137.12, 141.88, 145.69,
－
1
(C＝N), 1340, 1155 (SO2), 750 (C—Cl) cm . Anal.
calcd for C36H26Cl3N5O5S2 (Mr＝779.11): C 55.50, H
3.36, N 8.99; found C 55.32, H 3.28, N 8.86.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-
3-{4-[2-(4-hydroxyphenyl)-4-oxo-thiazolidin-3-yl]-
phenyl}sulfonamido-quinazolin-4(3H)-one (5d) Yield
70%, m.p. 145—148 ℃; 1H NMR (CDCl3, 400 MHz) δ:
1992
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Chin. J. Chem. 2010, 28, 1989—1997

Synthesis and Antimicrobial Activity of Quinazolin-4(3H)-ones
146.59, 158.37, 160.56, 163.26, 173.46; IR (KBr) ν:
3435 (NH), 2932, 2858 (CH2), 1752 (C＝O, thiazolidi-
none), 1674 (C＝O, quinazolinone), 1610 (C＝N), 1345,
Anal. calcd for C37H28Cl3N5O6S2 (Mr＝809.14): C 54.92,
H 3.49, N 8.66; found C 54.78, H 3.43, N 8.58.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(4-dimethylaminophenyl)-4-oxo-thiazolidin-3-
－
1
1152 (SO2), 1205, 1106 (C—O—C), 741 (C—Cl) cm .
Anal. calcd for C37H28Cl3N5O5S2 (Mr＝793.14): C 56.03,
H 3.56, N 8.83; found C 56.17, H 3.60, N 8.76.
yl]phenyl}sulfonamido-quinazolin-4(3H)-one
(5k)
1
Yield 70%, m.p. 150—152 ℃; H NMR (CDCl3, 400
MHz) δ: 3.12 [s, 23H, N(CH3)2], 3.57 (s, 2H, CH2), 3.96
(s, 2H, CH2-S), 5.18 (s, 1H, CH-S), 6.36—8.19 (m, 18H,
Ar-H), 9.21 (bs, 1H, NH), 10.78 (bs, 1H, SO2NH); 13C
NMR (CDCl3, 100 MHz) δ: 30.71, 36.14, 65.24, 38.37,
112.59, 116.11, 120.27, 121.32, 121.44, 123.56, 123.97,
124.39, 127.06, 127.22, 127.29, 127.78, 128.12, 129.04,
129.37, 130.89, 132.57, 133.84, 136.22, 137.66, 141.63,
145.76, 146.43, 149.28, 160.33, 163.28, 173.18; IR
(KBr) ν: 3430 (NH), 2915, 2836 (CH2), 1743 (C＝O,
thiazolidinone), 1672 (C＝O, quinazolinone), 1614 (C＝
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(3,4,5-trimethoxyphenyl)-4-oxo-thiazolidin-3-
yl]phenyl}sulfonamido-quinazolin-4(3H)-one
(5h)
1
Yield 69%, m.p. 172—175 ℃; H NMR (CDCl3, 400
MHz) δ: 3.34 (s, 33H, OCH3), 3.61 (s, 2H, CH2), 3.95 (s,
2H, CH2-S), 5.16 (s, 1H, CH-S), 6.36—8.17 (m, 16H,
Ar-H), 9.24 (bs, 1H, NH), 10.78 (bs, 1H, SO2NH); 13C
NMR (CDCl3, 100 MHz) δ: 31.34, 36.29, 54.65, 55.46,
64.32, 104.57, 116.37, 120.01, 121.12, 121.34, 123.53,
123.83, 124.25, 126.69, 126.92, 127.24, 127.41, 130.16,
131.22, 132.61, 133.92, 134.72, 135.86, 136.89, 137.22,
141.96, 145.48, 146.28, 148.59, 160.29, 163.07, 173.35;
IR (KBr) ν: 3431 (NH), 2927, 2846 (CH2), 1755 (C＝O,
thiazolidinone), 1670 (C＝O, quinazolinone), 1613 (C＝
N), 1348, 1152 (SO2), 1210, 1108 (C—O—C), 736 (C—
Cl) cm－ 1. Anal. calcd for C39H32Cl3N5O7S2 (Mr ＝
853.19): C 54.90, H 3.78, N 8.21; found C 54.82, H 3.76,
N 8.25.
－
1
N), 1352, 1156 (SO2), 759 (C—Cl) cm . Anal. calcd
for C38H31Cl3N6O4S2 (Mr＝806.18): C 56.61, H 3.88, N
10.42; found C 56.46, H 3.93, N 10.34.
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(2-hydroxy-4-diethylaminophenyl)-4-oxo-thia-
zolidin-3-yl]phenyl}sulfonamido-quinazolin-4(3H)-
1
one (5l) Yield 80%, m.p. 153—155 ℃; H NMR
(CDCl3, 400 MHz) δ: 1.34 [t, J＝7.52 Hz, 23H, N(CH2-
CH3)2], 2.83 [q, J＝7.52 Hz, 22H, N(CH2CH3)2], 3.56 (s,
2H, CH2), 3.97 (s, 2H, CH2-S), 5.25 (s, 1H, CH-S), 4.95
(bs, 1H, OH), 6.37—8.19 (m, 17H, Ar-H), 9.27 (bs, 1H,
NH), 10.71 (bs, 1H, SO2NH); 13C NMR (CDCl3, 100
MHz) δ: 15.13, 35.89, 31.24, 43.38, 58.42, 101.64,
106.92, 108.83, 115.85, 120.49, 121.28, 121.55, 123.48,
124.19, 124.65, 126.82, 127.28, 127.46, 127.67, 129.73,
130.06, 131.15, 132.26, 134.17, 136.69, 137.34, 141.98,
145.62, 146.23, 150.22, 158.53, 160.14, 163.16, 172.73;
IR (KBr) ν: 3438 (NH), 3248 (OH), 2928, 2853 (CH2),
1750 (C＝O, thiazolidinone), 1676 (C＝O, quinazoli-
none), 1608 (C＝N), 1353, 1159 (SO2), 756 (C—Cl)
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(2-hydroxy-4-methoxyphenyl)-4-oxo-thiazolidin-
3-yl]phenyl}sulfonamido-quinazolin-4(3H)-one (5i)
1
Yield 79%, m.p. 163—167 ℃; H NMR (CDCl3, 400
MHz) δ: 3.32 (s, 3H, OCH3), 3.55 (s, 2H, CH2), 3.94 (s,
2H, CH2-S), 5.19 (s, 1H, CH-S), 4.97 (bs, 1H, OH), 6.38
—8.18 (m, 17H, Ar-H), 9.22 (bs, 1H, NH), 10.82 (bs,
1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.13,
35.74, 55.43, 58.56, 102.31, 105.42, 108.29, 116.10,
119.86, 121.38, 121.49, 123.64, 124.03, 124.33, 126.77,
126.97, 127.18, 127.35, 129.98, 131.37, 131.58, 132.45,
133.78, 136.54, 137.66, 142.17, 145.37, 146.38, 154.67,
159.15, 160.41, 163.35, 172.88; IR (KBr) ν: 3442 (NH),
3255 (OH), 2924, 2845 (CH2), 1753 (C＝O, thiazolidi-
none), 1674 (C＝O, quinazolinone), 1612 (C＝N), 1347,
－
1
cm . Anal. calcd for C40H35Cl3N6O5S2 (Mr＝850.23): C
56.51, H 4.15, N 9.88; found C 56.38, H 4.11, N 9.95.
－
1
Antimicrobial activity
1154 (SO2), 1218, 1097 (C—O—C), 748 (C—Cl) cm .
Anal. calcd for C37H28Cl3N5O6S2 (Mr＝809.14): C 54.92,
H 3.49, N 8.66; found C 55.14, H 3.57, N 8.62.
The MICs of synthesized compounds were carried
out by broth micro dilution method as described by Rat-
tan.32 Antibacterial activity was screened against two
gram positive bacteria (S. aureus MTCC 96, S. pyo-
genes MTCC 442) and two gram negative bacteria (E.
coli MTCC 443, P. aeruginosa MTCC 1688). Ampicil-
lin was used as a standard antibacterial agent. Antifun-
gal activity was screened against three fungal species C.
albicans MTCC 227, A. niger MTCC 282 and A. clava-
tus MTCC 1323. Griseofulvin was used as a standard
antifungal agent. All MTCC cultures were collected
from Institute of Microbial Technology, Chandigarh and
tested against above mentioned known drugs. Mueller
hinton broth was used as nutrient medium to grow and
dilute the drug suspension for the test. Inoculum size for
test strain was adjusted to 108 CFU (Colony Forming
Unit) per milliliter by comparing the turbidity. DMSO
7-Chloro-2-[2-(2,6-dichlorophenyl)amino]benzyl-3-
{4-[2-(4-hydroxy-3-methoxyphenyl)-4-oxo-thiazolidin-
3-yl]phenyl}sulfonamido-quinazolin-4(3H)-one (5j)
1
Yield 68%, m.p. 154—158 ℃; H NMR (CDCl3, 400
MHz) δ: 3.35 (s, 3H, OCH3), 3.59 (s, 2H, CH2), 3.97 (s,
2H, CH2-S), 5.16 (s, 1H, CH-S), 4.94 (bs, 1H, OH), 6.35
—8.17 (m, 17H, Ar-H), 9.26 (bs, 1H, NH), 10.77 (bs,
1H, SO2NH); 13C NMR (CDCl3, 100 MHz) δ: 31.32,
35.66, 54.85, 63.96, 112.38, 116.39, 118.94, 120.43,
121.44, 121.65, 122.86, 123.47, 124.15, 124.57, 126.83,
127.06, 127.32, 127.64, 129.55, 130.72, 131.22, 132.31,
134.25, 136.40, 137.48, 141.45, 143.53, 145.45, 146.52,
149.30, 160.67, 163.24, 173.06; IR (KBr) ν: 3435 (NH),
3246 (OH), 2920, 2842 (CH2), 1750 (C＝O, thiazolidi-
none), 1678 (C＝O, quinazolinone), 1610 (C＝N), 1350,
－
1
1144 (SO2), 1228, 1087 (C—O—C), 745 (C—Cl) cm .
Chin. J. Chem. 2010, 28, 1989—1997
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1993

Patel, Patel & Patel
FULL PAPER
Results and discussion
was used as diluents to get desired concentration of
drugs to test upon standard bacterial strains. Serial dilu-
tions were prepared in primary and secondary screening.
The control tube containing no antibiotic was imme-
diately sub cultured (before inoculation) by spreading a
loopful evenly over a quarter of plate of medium suit-
able for the growth of the test organism and put for in-
cubation at 37 ℃ overnight. The tubes were then in-
cubated overnight. The MIC of the control organism
was read to check the accuracy of the drug concentra-
tions. The lowest concentration inhibiting growth of the
organism was recorded as the MIC. All the tubes not
showing visible growth (in the same manner as control
tube described above) was sub cultured and incubated
overnight at 37 ℃. The amount of growth from the
control tube before incubation (which represents the
original inoculum) was compared. Subcultures might
show: similar number of colonies indicating bacterio-
static; a reduced number of colonies indicating a partial
or slow bactericidal activity and no growth if the whole
inoculum has been killed. The test must include a sec-
ond set of the same dilutions inoculated with an organ-
ism of known sensitivity. Each synthesized drug was
diluted obtaining 2000 µg/mL concentration, as a stock
solution. In primary screening 500, 250 and 125 µg/mL
concentrations of the synthesized drugs were taken. The
active synthesized drugs found in this primary screening
were further tested in a second set of dilution against all
microorganisms. The drugs found active in primary
screening were similarly diluted to obtain 100, 50, 25,
12.5, 6.250, 3.125 and 1.5625 µg/mL concentrations.
The highest dilution showing at least 99% inhibition is
taken as MIC.
Chemistry
The compounds 7-chloro-2-[2-(2,6-dichlorophenyl)-
amino]benzyl-3-[4-(2-substituted phenyl-4-oxo-thia-
zolidin-3-yl)phenyl]sulfonamido-quinazolin-4(3H)-ones
5a—5l were synthesized from 2-[2-(2,6-dichlorophenyl)-
amino]phenyl acetic acid by using efficient methods as
described in Scheme 1. The benzoxazinone 2 was
conveniently synthesized by the cyclization reaction of
acid chloride 1 with 4-chloroanthranilic acid. The IR
spectra showed strong C＝O and C＝N stretching
vibration of benzoxazinone at 1735 and 1620 cm－
1
respectively which was further confirmed by 13C NMR
spectra, showing C＝O and C＝N signals at δ 159.34
and 164.29, respectively. The condensation reaction of
benzoxazinone 2 with 4-aminophenylsulfonyl hydrazide
yielded amino-quinazolin-4(3H)-one (3), which showed
－
1
strong C＝O stretching vibration at 1678 cm , indicating
the formation of quinazolinone moiety. The acid
catalyzed condensation of amine 3 with substituted
aromatic aldehydes afforded the Schiff base 4a—4l. The
Schiff base (N＝CH) showed C＝N stretching at around
1630 cm －
in IR spectrum whereas in 1H NMR
1
spectrum the singlet equivalent to one proton was
observed at around δ 8.6. The cyclization reaction of
Schiff base with thioglycolic acid yielded the desired
compounds thiazolidinonyl-quinazolin-4(3H)-ones 5a—
5l. The 4-thiazolidinone showed strong C＝O stretching
－
1
at around 1750 cm . 1H NMR spectra showed singlet at
around δ 3.95 and 5.20, confirming the presence of
CH2-S and CH-S of 4-thiazolidinone respectively. 13C
NMR spectra displayed the signals at around δ 36, 60
and 173 regarding CH2-S, CH-S and C ＝ O of
4-thiazolidiones.
Scheme 1 Synthesis of 4-thiazolidinonyl-quinazolin-4(3H)-ones 5a— 5l
R = 2-Cl, 4-Cl, 2-OH, 4-OH, 2-NO2, 3-NO2, 4-OCH3, 3,4,5-(OCH3)3, 2-OH-4-OCH3, 4-OH-3-OCH3, 4-N(CH3)2, 2-OH-4-N(C2H5)2
Reagents and conditions: (a) 4-Chloro anthranilic acid, pyridine, 0 ℃ to r.t.; (b) 4-Aminophenylsulfonyl hydrazide, pyridine, 5 to 6 h; (c) Aromatic
aldehyde, absolute ethanol, glacial acetic acid, 4 to 6 h; (d) Thioglycolic acid, DMF, ZnCl2, 8 to 9 h.
1994
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Chin. J. Chem. 2010, 28, 1989—1997

Synthesis and Antimicrobial Activity of Quinazolin-4(3H)-ones
Antimicrobial activity
(MIC: 500 and 250 µg/mL, respectively) against gram
positive bacteria S. pyogenes. On the other hand Schiff
bases 4h [R＝3,4,5-(OCH3)3] and 4j (R＝4-OH-3-
OCH3) displayed poor activities (MIC: 250 and 500
µg/mL, respectively) while its 4-thiazolidinone deriva-
tives showed good activities (MIC: 100 and 125 µg/mL,
respectively) against gram positive bacterial S. pyogenes.
The Schiff base derivatives 4b (R＝4-Cl), 4c (R＝
2-OH), 4d (R＝4-OH) and 4g (R＝4-OCH3) as well as
4-thiazolidinone derivatives 5a (R＝2-Cl) and 5b (R＝
4-Cl) possessed very good activities (MIC: 50—125
µg/mL) against gram negative bacteria E. coli. The
Schiff base derivatives 4a (R＝2-Cl), 4b (R＝4-Cl), 4c
(R＝2-OH), 4d (R＝4-OH) and 4g (R＝4-OCH3) exhib-
ited very good activities (MIC: 62.5—125 µg/mL) while
its 4-thiazolidinone derivatives showed poor activities
except compound 5a (R＝2-Cl) which showed good ac-
tivity at 125 µg/mL against gram negative bacteria
P. aeruginosa. The antifungal activity result reveals
The results of antibacterial and antifungal activity
are summarized in Table 1. The result shows that some
of the compounds showed very good antibacterial as
well as antifungal activity. Schiff base derivatives 4a (R
＝2-Cl), 4b (R＝4-Cl), 4c (R＝2-OH), 4d (R＝4-OH)
and 4g (R＝4-OCH3) showed excellent activities (MIC:
50—125 µg/mL) against gram positive bacteria S.
aureus. The results were found different when Schiff
bases are converted to 4-thiazolidinone. The 4-thia-
zolidinone derivatives 5b (R＝4-Cl) and 5h [R＝
3,4,5-(OCH3)3] exhibited excellent activities (MIC: 50
and 100 µg/mL, respectively) while 5a (R＝2-Cl), 5c
(R＝2-OH), 5d (R＝4-OH) and 5g (R＝4-OCH3)
showed poor activity (MIC: 500 µg/mL) against gram
positive bacteria S. aureus. Schiff bases 4g (R＝4-OCH3)
and 4i (R＝2-OH-4-OCH3) showed good activities
(MIC: 100 and 125 µg/mL, respectively) while its
4-thiazolidinone derivatives possessed poor activities
Table 1 Antibacterial and antifungal activity of compounds 4a— 4l and 5a— 5l
Antibacterial activitya
Antifungal activity
Fungal species
Gram positive bacteria
Gram negative bacteria
Compod.
R
S. aureus S. pyogenes
E. coli
P. aeruginosa C. albicans
A. niger
A. clavatus
MTCC96 MTCC 442
MTCC443 MTCC 1688
MTCC 227 MTCC 282 MTCC 1323
4a
4b
4c
4d
4e
4f
2-Cl
4-Cl
125
125
62.5
125
500
500
50
200
250
500
500
500
500
100
250
125
500
500
500
500
250
250
500
250
500
500
100
250
125
500
500
100
NT
500
125
62.5
50
125
62.5
100
100
1000
500
125
250
500
500
500
500
125
200
250
500
500
250
500
500
500
1000
500
500
100
NT
＞
＞
＞
＞
＞
＞
＞
1000
1000
1000
1000
1000
1000
1000
200
＞
＞
＞
＞
＞
＞
＞
1000
1000
1000
1000
1000
1000
1000
200
＞
＞
＞
＞
＞
＞
＞
1000
1000
1000
1000
1000
1000
1000
500
2-OH
4-OH
2-NO2
500
250
100
250
500
500
500
500
62.5
125
250
200
500
250
500
1000
500
250
500
500
100
NT
3-NO2
4g
4h
4i
4-OCH3
3,4,5-(OCH3)3
2-OH-4-OCH3
4-OH-3-OCH3
4-N(CH3)2
2-OH-4-N(C2H5)2
2-Cl
250
500
1000
250
500
500
50
500
＞
＞
＞
＞
1000
1000
1000
1000
250
＞
＞
＞
＞
1000
1000
1000
1000
500
4j
500
4k
4l
＞
1000
500
5a
5b
5c
5d
5e
5f
500
4-Cl
200
250
500
2-OH
250
500
250
500
500
100
500
2850
500
500
250
NT
100
250
500
4-OH
250
500
1000
1000
1000
1000
1000
1000
1000
1000
1000
NT
2-NO2
1000
1000
500
＞
＞
1000
1000
500
＞
＞
3-NO2
5g
5h
5i
4-OCH3
3,4,5-(OCH3)3
2-OH-4-OCH3
4-OH-3-OCH3
4-N(CH3)2
2-OH-4-N(C2H5)2
Ampicillin
Griseofulvin
125
＞
＞
＞
＞
＞
1000
1000
1000
1000
1000
NT
＞
＞
＞
＞
＞
500
5j
1000
1000
100
5k
5l
NT
500
100
100
a Minimum inhibitory concentration (MIC, µg/mL): the lowest test concentration that completely inhibits microorganism growth; NT: not
tested.
Chin. J. Chem. 2010, 28, 1989—1997
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1995

Patel, Patel & Patel
FULL PAPER
that some of the compounds showed excellent activity
against C. albicans while moderate activities were ob-
served against A. niger. All of the Schiff bases as well
as 4-thiazolidinone derivatives displayed poor activities
against A. clavatus compared to griseofulvin. Schiff
bases 4h [R＝3,4,5-(OCH3)3], 4i (R＝2-OH-4-OCH3),
4j (R＝4-OH-3-OCH3) and 4l [R＝2-OH-4-N(C2H5)2]
as well as 4-thiazolidinones 5a (R＝2-Cl), 5b (R＝4-Cl),
5c (R＝2-OH), 5d (R＝4-OH), 5g (R＝4-OCH3), 5h [R
＝3,4,5-(OCH3)3], 5i (R＝2-OH-4-OCH3) and 5l [R＝
2-OH-4-N(C2H5)2] showed very good activities (MIC:
100—500 µg/mL) against C. albicans. All Schiff base
derivatives possessed poor activities against A. niger
except compound 4h [R＝3,4,5-(OCH3)3] which was
found active at 200 µg/mL against A. niger. The
4-thiazolidinone derivatives 5a (R＝2-Cl), 5b (R＝4-Cl)
and 5c (R＝2-OH) exhibited moderate activity (MIC:
250 µg/mL) against A. niger compared to griseofulvin.
The remaining compounds showed poor activities
against A. niger.
4
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Conclusion
The title compounds 5a—5l were comprehensively
synthesized using efficient methods and showed satis-
factory analytical results. Furthermore some of the com-
pounds showed good antimicrobial activity. The Schiff
base derivative containing chloro and hydroxyl group
showed good activity against gram positive bacteria S.
aureus and gram negative bacteria P. aeruginosa. The
Schiff base derivative containing 4-methoxy group was
found active against all gram positive as well as gram
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derivative containing 3,4,5-trimethoxy and 4-hydroxy-3-
methoxy group possessed good activity against gram
positive bacteria while 2-chloro group containing
4-thiazolidinone was found active against gram negative
bacteria. The 4-thiazolidinone derivatives exhibited very
good activity against C. albicans than that of Schiff base
derivatives. Hence, the overall result was found satis-
factory and will guide to enhance these work with
structural modification to improve biological activity.
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Acknowledgements
The authors are thankful to Veer Narmad South Gu-
jarat University for providing necessary facilities. We
also thank SAIF Lucknow for elemental analysis and
SAIF Chandigarh for spectral analysis of the com-
pounds. Thank to Dhanji Rajani for antimicrobial activ-
ity screening.
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www.cjc.wiley-vch.de
1997