Synthesis and antimicrobial activity of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives

Article abstract of DOI:10.1016/j.ejmech.2009.09.028

A series of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives have been synthesized by reaction of 7-amino-4-methyl-benzopyran-2-one (1) with an appropriate substituted aldehydes to obtain various Schiff bases (3a-k) which on treatment with thioglycolic acid afforded the title compounds (4a-k). Purity of the compounds has been confirmed by TLC. Structure of these compounds were established on the bases IR, ¹H NMR, ¹³C NMR and Mass spectral data. Schiff bases and title compounds were evaluated for antibacterial and antifungal activities against various bacterial and fungal strains. The results showed that compounds 3d, 3f, 4d, 4f and 4i (100 μg/ml) exhibited good antibacterial and antifungal activity as that of standard antibiotics Ciprofloxacin and Griseofulvin.

Full text of DOI:10.1016/j.ejmech.2009.09.028

European Journal of Medicinal Chemistry 45 (2010) 85–89
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis and antimicrobial activity of 7-(2-substituted
phenylthiazolidinyl)-benzopyran-2-one derivatives
,
b
a
Pradeepkumar M. Ronad a , Malleshappa N. Noolvi , Sheetal Sapkal ,
*
Satyanarayana Dharbhamulla c, Veeresh S. Maddi a
a Department of Pharmaceutical chemistry, KLE’s College of Pharmacy, Vidyanagar, Hubli -580031, Karnataka, India
b Department of Pharmaceutical Chemistry, ASBASJSM College of Pharmacy, Bela, Ropar, Punjab, India
c Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Science, Paneer, Deralkatte, Mangalore - 574 160, Karnataka, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives have been synthesized
by reaction of 7-amino-4-methyl-benzopyran-2-one (1) with an appropriate substituted aldehydes to
obtain various Schiff bases (3a–k) which on treatment with thioglycolic acid afforded the title
compounds (4a–k). Purity of the compounds has been confirmed by TLC. Structure of these compounds
were established on the bases IR, 1H NMR, 13C NMR and Mass spectral data. Schiff bases and title
compounds were evaluated for antibacterial and antifungal activities against various bacterial and fungal
Received 24 July 2008
Received in revised form
4 August 2009
Accepted 17 September 2009
Available online 23 September 2009
strains. The results showed that compounds 3d, 3f, 4d, 4f and 4i (100
and antifungal activity as that of standard antibiotics Ciprofloxacin and Griseofulvin.
Ó 2009 Elsevier Masson SAS. All rights reserved.
mg/ml) exhibited good antibacterial
Keywords:
7-Amino-4-methyl-benzopyran-2-one
Thiazolidinones
Antimicrobial
7-Amino coumarin
1. Introduction
biological activity. As reported earlier the thiazolidinone ring
present in a large number of biologically active molecules of
different pharmacological classes exhibited different activities. The
historical importance of thiazolidine derivative was emphasized
during the period 1941–1945, i.e. the development of penicillin
which shows the presence of thiazoline ring.
The development of novel 7-amino-4-methylcoumarin is one of
the most fascinating and useful areas in medicinal chemistry. The
discovery of coumarin as therapeutic agents in early 1820’s was the
beginning of the coumarin drug development. The coumarin have
a relatively broad spectrum with high activity profile against
various bacteria and fungi [8,9].
Due to the diversified nature of coumarin and thiazolidinone
which render them useful substances in drug research. In contin-
uation of our search for novel biologically active coumarinyl
heterocycles[1–3], in this paper we report the synthesis and
antibacterial activity of a novel series of Schiff bases of 7-amino-4-
methylcoumarin and its derivatives 3-(4-methyl-2-oxo-2H-chro-
men-7-yl)-2-phenylthiazolidin-4-one.
Coumarin derivatives reported with diverse structural features
and versatile biological properties such as anti-inflammatory [1–3],
antioxidant [4], vasorelaxant [5], cytotoxic [6], anti-HIV [7], antitu-
bercular [8] and antimicrobial [9]. The literature survey revealed that
compounds with thiazolidinone ring have been reported to demon-
strate a wide range of pharmacological activities; which include
antibacterial [10], antifungal [11,12], anticonvulsant [13]. The emer-
gence of multidrug-resistant gram-positive bacteria, such as methi-
cillin-resistant Staphylococcus aureus (MRSA) have made treatment of
infectious diseases difficult and over the last decades, became
a serious medical problem. As pathogenic bacteria continuously
evolve resistance to currently used antibacterial agents, so the
discovery of novel and potent antibacterial agents is the best way to
overcome bacterial resistance and develop effective therapies [14].
The molecular manipulation of promising lead compounds is
still a major line of approach to develop new drugs. It involves an
effort to combine the separate pharmacophoric groups of similar
activity into one compound, thus making structural changes in the
2. Chemistry
* Corresponding author. Department of Pharmaceutical Chemistry, KLE’ S College
of Pharmacy, Vidyanagar, Hubli-580 031, Karnataka, India. Tel.: þ91 836 2373174;
fax: þ91 836 2371694.
The synthesis of 7-amino-4-methylcoumarin (1) was carried out
by the condensation of 3-amino phenol with ethylchloroformate
E-mail address: ronad_p@rediffmail.com (P.M. Ronad).
0223-5234/$ – see front matter Ó 2009 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2009.09.028

86
P.M. Ronad et al. / European Journal of Medicinal Chemistry 45 (2010) 85–89
by earlier reported methods [15,16]. The various substituted
schiff’s base of 7-amino-4-methylcoumarin (3a–k) was prepared
by reacting 7-amino-4-methylcoumarin with substituted aromatic
aldehydes (2a–k). Thus obtained Schiff base was further con-
verted into thiazolidinyl coumarin derivatives (4a–k) on treat-
ment with thioglycolic acid as shown in scheme-1. The purity of
compounds was confirmed by TLC using precoated silica gel as
staitionary phase, using appropriate solvent system as mobile
phase and iodine vapors as visualizing agent. Structure of the title
compounds were confirmed by IR, NMR and Mass spectral
studies.
The results showed that compounds 3d, 3f, 4d, 4f and 4i
exhibited good antibacterial and antifungal activity at a concentra-
tion of 100
Grisofulvin.
mg/ml as that of standard antibiotics Ciprofloxacin and
The activity is considerably affected by substituents of para
position of phenyl ring of thiazolidinone. It has been observed that
having furan group instead of phenyl showed moderate activity. It
was also noted that the effect of imine and thiazolidinone ring on
the antibacterial and antifungal activity. It was observed that the
Schiff bases are less active than thiazolidinone derivatives.
4. Conclusion
3. Result and discussion
In this paper we report the synthesis and antimicrobial activity
of novel series of Schiff base (3a–k) and 7-(2-substituted-phenyl-
thiazolidinyl)-coumarin derivatives (4a–k). The derivatives were
prepared by condensation between 7-amino-4-methylcoumarin
with various substituted aromatic aldehydes to obtain schiff bases,
further it was condensed with thioglycolic acid to obtain title
compounds (4a–k).
The preliminary in vitro antimicrobial activity of these novel
series of derivative has evidenced that thiazolidinone derivatives
are more active than that of schiff bases. Further studies are
required for the detailed mechanism of action of these derivatives.
Eleven derivatives of both Schiff bases and its phenyl-
thiazolidinyl coumarin derivatives were reported. Structure of the
synthesized compounds was established on the basis of IR, 1H NMR,
13C NMR and Mass spectral data. The general spectral characters of
3a–k showed absorption bands ranging from 1555–1610 cmꢀ1 for
imine (pC]N–) formation and 1680–1710 cmꢀ1 for (pC]O) of
coumarin. Similarly compounds 4a–k have showed absence of
absorption band at 1555–1610 cmꢀ1 and two sharp bands at 1680–
1730 cmꢀ1 gave conformation of pC]O in both thiazolidinone and
coumarin ring in their respective spectra.
In particular, it must be pointed out that 1H NMR of compounds
5. Experimental section
3a–k showed presence of a singlet between
cated the formation of imine (pCH]N–) by simple condensation
process. Further characteristic peaks at 2.4 ppm indicated the
presence of 4-CH3 group of coumarin ring in their structure. The
compounds 3a–k showed prominent singlet at 6.2–6.3 ppm for
6.9–8.3 ppm for aromatic
d 8.4–8.9 ppm indi-
Melting points were determined in Thermonik melting point
apparatus and are uncorrected. IR spectrum was recorded on
Thermonicolet FTIR 200 spectrophotometer by using KBr pellet
values are expressed in cmꢀ1. NMR spectra were recorded in
DMSO-d6 using Varian 400 mz mercury plus and chemical shift are
d
d
3rd proton of coumarin and multiplet at
protons.
d
reported in
d (ppm). Mass spectra were recorded on Shimaduzu
Title compound 4a–k has shown singlet at
of thiazolidinone) and the absence of peak at
confirmed the formation of thiazolidinone. 13C NMR spectral data
for the title compounds most characteristic peak around 53.0 and
63.0 ppm (–CH2) indicated the formation thiazolidinone ring.
Electron impact mass spectra showed an accurate molecular ion
peak at m/z 337.4, 353.4, 367.4, 382.4, 406.2, 367.4, 327.6, 380.4,
355.3, 351.4 and 353.4 for title compounds 4a–k respectively.
The synthesized compounds were evaluated for in vitro anti-
bacterial and antifungal activity against various gram-positive,
gram-negative bacteria and fungal strains using agar cup plate
method. The results are shown in table-1 and 2.
d
3.7–4.0 ppm (–CH2
2010 and mass values are reported in m/z.
d
8.4–8.9 ppm
Microbial strains obtained from NCL Pune, Maharastra, India-
S aureus NCIM 2602; Bacillus subtillis NCIM 2613; Escherichia coil
NCIM 2666; Pseudomonas desmolyticum NCIM 2028; Penicillium
roquefortii NCIM 712; Aspergillus niger NCIM 813.
d
5.1. General procedure for the preparation of schiff’s bases
of coumarin: (3a–k)
A mixture of 7-amino-4-methylcoumarin (I) (1.5 g, 0085 mmol)
and substituted aromatic aldehyde (a–k) (0.017 mmol) in 25 ml of
CH3
O
CH3
O
O
H
a
O
N
b
O
H
H2N
O
3 a-k
a-k
R
O
R
g
1
2a-k
a, R= H
b, R= 2-OH
c, R= 3-OCH3
d, R= 3-NO2
e, R= 2,4-Cl
f, R= 4-OCH3
CH3
O
H
S
h, R= 4-N(CH3)2
i, R= 4-F
O
N
R
j, R= 4-CH3
k, R= 4-OH
O
4 a-k
Scheme 1. Synthesis of 7-(2-substituted-phenylthiazolidinyl)-benzopyran-2-one derivatives (4a-k). Reagents and Reaction Conditions. (a) Acetic anhydride, Ethanol, Reflux, 6 h. (b)
Thioglycolic acid, Dioxan, anhydrous ZnCl2, Reflux 4–6 h.

P.M. Ronad et al. / European Journal of Medicinal Chemistry 45 (2010) 85–89
87
Table 1
Antibacterial and antifungal activity of synthesized novel series of 7-(substituted benzylideneamino)-4-methylcoumarin derivatives (3a–k)*.
Zone of inhibition in mm
Compound
R
B. subtillis
S. aureus
E. coli.
P. desmolyticum
P. roquefortii
A. niger
3a
3b
3c
3d
3e
3f
H
10(ꢁ0.89)
7(ꢁ1.32)
11(ꢁ1.07)
3(ꢁ0.58)
9(ꢁ1.29)
15(ꢁ1.81)
5(ꢁ1.07)
13(ꢁ1.32)
13(ꢁ1.31)
NA
11(ꢁ1.16)
9(ꢁ1.24)
14(ꢁ0.97)
7(ꢁ1.07)
10(ꢁ1.37)
NA
8(ꢁ0.97)
10(ꢁ0.89)
13(ꢁ1.24)
NA
11(ꢁ1.07)
10(ꢁ0.89)
13(ꢁ1.32)
4(ꢁ0.73)
9(ꢁ1.29)
14(ꢁ0.97)
9(ꢁ1.29)
6(ꢁ0.89)
2-OH
3-OCH3
3-NO2
2,4-Cl
4-OCH3
13(ꢁ0.97)
20(ꢁ0.72)
12(ꢁ0.58)
21(ꢁ0.52)
11(ꢁ1.06)
NA
7(ꢁ1.07)
9(ꢁ0.97)
3g
11(ꢁ1.07)
7(ꢁ1.07)
12(ꢁ0.58)
7(ꢁ1.32)
6(ꢁ0.89)
NA
O
3h
3i
3j
3k
4-N(CH3)2
4-F
14(ꢁ0.97)
17(ꢁ1.07)
9(ꢁ1.65)
10(ꢁ1.37)
25( 0.87)
–
6(ꢁ0.89)
16(ꢁ0.68)
7(ꢁ1.07)
4(ꢁ1.03)
18( 0.63)
–
8(ꢁ0.97)
14(ꢁ0.97)
10(ꢁ1.37)
NA
30( 0.58)
–
8(ꢁ0.97)
12(ꢁ0.73)
11(ꢁ1.16)
NA
18( 0.73)
–
NA
NA
NA
3(ꢁ0.58)
6(ꢁ0.89)
–
5(ꢁ1.07)
7(ꢁ1.07)
8(ꢁ1.16)
–
4-CH3
4-OH
Ciprofloxacin
Gresiofulvin
2( 0.78)
17( 0.86)
Gram-positive bacterial strains: B. subtillis-Bacillus subtillis; S. aureus-Staphylococcus aureus Gram-negative bacterial strains: E coli-Escherichia coli; P.aeruginosa–Pseudomonas
desmolyticum. Fungal strains P. roquefortii-Penicillium roquefortii; A. niger-Aspergillus niger. The concentration of test compounds was 100
active. * mean value (SEM).
m
g/ml. Solvent used DMF. NA ¼ Not
absolute alcohol and 0.5 ml of acetic anhydride were refluxed for
6 h and the solvent was removed under reduced pressure. The
resulting crude compound was washed with cold water and
recrystallized by using appropriate solvents. The purity of the
compounds was confirmed by TLC using silica gel G as stationary
phase, ethylacetate: cyclohexane (1:2) as mobile phase and iodine
vapors as visualizing agent. The structure of the compounds was
confirmed by spectroscopic data1.
by TLC using silica gel G as stationary phase, ethylacetate: cyclo-
hexane (1:2) as mobile phase and iodine vapors as visualizing agent
5.2.1. 7-(2-phenyl thiazolidinyl)-4-methyl-benzopyran-2-one (4a)
m.p.: 270–272; % yield: 75; IR (KBr) cmꢀ1: 1717 (pC]O of
a
-pyrone and thiazolidone), 1631 (C]C stretching), 1377 (C–N
stretching), 1253 (pC]O stretching, 1135(pC–O)), 651 (C–S–C);
1HNMR (400 Mz, CDCl3)
ppm: 7.7–7.4 (m, 8H, Ar–H), 6.2 (s, 1H,
2-CH), 3.4, 3.3 (s, 2H, CH2–S), 2.4 (s, 3H, CH3); 13CNMR (400 Mz,
CDCl3), ppm: 170.3 (pC]O of thiazolidone), 160.9 (pC]O of
-pyrone), 153.6–116.5 (12C, Ar), 112.5 (C3 of -pyrone), 63.7 (C2 of
d
d
5.2. General procedure for the preparation of 7-(2-substituted-
phenylthiazolidinyl)-benzopyran-2-one derivatives: (4a–k)
a
a
thiazolidone), 32.7 (C4 of thiazolidone), 21.3 (C4–CH3 of a-pyrone).
DIPMS m/z: 336.03 Mþ and HRMS calcd for C19H15NO3S: 337.0773
found 337.0769
Schiff’s bases (3a–k) (0.001 mmol) treated with mercaptoacetic
acid (0.001 mmol) in dioxan (25 ml) in presence of anhydrous ZnCl2
and reaction mixture was refluxed for 4–6 h (monitored by TLC),
after cooling the reaction mixture was poured on crushed ice with
stirring. Thus separated solid was then filtered, washed with sodium
bicarbonate to remove the unreacted thioglycolic acid and recrys-
tallized from ethanol. The purity of the compounds was confirmed
5.2.2. 7-(2-(p-hydroxy)phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4b)
m.p.: 276–278; % yield: 70; IR (KBr) cmꢀ1: 3348 (–OH
stretching), 2922 (pC–H), 1719 (pC]O of
a
-pyrone and
Table 2
Antibacterial and antifungal activity of synthesized novel series of 7-(2-substituted phenyl thiazolidinyl)-benzopyran-2-one derivatives (4a–k)*
Zone of inhibition in mm
Compound
R
B. subtillis
S. sureus
E. coli.
P. desmolyticum
P. roquefortii
A. niger
4a
4b
4c
4d
4e
4f
H
19(ꢁ0.97)
8(ꢁ0.86)
12(ꢁ0.73)
4(ꢁ0.73)
10(ꢁ0.89)
19(ꢁ1.03)
7(ꢁ0.93)
16(ꢁ0.68)
2(ꢁ1.07)
NA
12(ꢁ0.58)
10(ꢁ0.73)
15(ꢁ1.07)
8(ꢁ0.97)
14(ꢁ0.97)
NA
9(ꢁ1.07)
9(ꢁ1.24)
11(ꢁ1.16)
NA
13(ꢁ0.97)
11(ꢁ1.07)
20(ꢁ1.16)
3(ꢁ0.87)
8(ꢁ0.96)
17(ꢁ0.73)
8(ꢁ1.16)
7(ꢁ1.07)
13(ꢁ1.07)
NA
2-OH
3-OCH3
3-NO2
2,4-Cl
4-OCH3
17(ꢁ1.07)
27(ꢁ0.58)
10(ꢁ0.89)
21(ꢁ0.52)
6(ꢁ0.89)
11(ꢁ1.06)
4g
10(ꢁ1.37)
8(ꢁ1.16)
13(ꢁ1.32)
6(ꢁ0.89)
5(ꢁ1.07)
NA
O
4h
4i
4j
4k
4-N(CH3)2
4-F
13(ꢁ1.24)
28(ꢁ0.73)
8(ꢁ0.97)
9(ꢁ1.65)
25(ꢁ0.87)
–
5(ꢁ0.93)
20(ꢁ0.82)
6(ꢁ1.07)
4(ꢁ1.03)
18(ꢁ0.63)
–
10(ꢁ0.73)
18(ꢁ0.58
20(ꢁ0.71)
NA
7(ꢁ1.32)
13(ꢁ0.97)
15(ꢁ1.81)
NA
NA
NA
19(ꢁ0.73)
6(ꢁ0.89)
9(ꢁ1.29)
–
13(ꢁ0.58)
3(ꢁ0.58)
5(ꢁ1.07)
–
4-CH3
4-OH
Ciprofloxacin
Gresiofulvin
30(ꢁ0.58)
18(ꢁ0.73)
–
–
2(ꢁ0.78)
17(ꢁ0.86)
Gram-positive bacterial strains: B. subtillis-Bacillus subtillis; S. aureus-Staphylococcus aureus Gram-negative bacterial strains: E coli-Escherichia coli; P.aeruginosa–Pseu-
domonas desmolyticum. Fungal strains P. roquefortii-Penicillium roquefortii; A. niger-Aspergillus niger. The concentration of test compounds was 100 mg/ml. Solvent used
DMF. NA ¼ Not active. * mean value(SEM).

88
P.M. Ronad et al. / European Journal of Medicinal Chemistry 45 (2010) 85–89
thiazolidone), 1611 (C]C stretching), 1396 (C–N stretching), 1263
(pC]O stretching, 1155(pC–O), 701 (C–S–C)); 1HNMR (400 Mz,
stretching), 1253 (pC]O stretching), 635 (C–S–C); 13CNMR
(400 Mz, CDCl3), ppm: 171.3 (pC]O of thiazolidone), 160.9
(<C]O of -pyrone), 155.1–115.7 (12C, Ar), 112.5 (C3 of -pyrone),
59.7 (C2 of thiazolidone), 33.7 (C4 of thiazolidone), 19.7 (C4–CH3 of
a
-pyrone). DIPMS m/z: 327.06 Mþ and HRMS calcd for C17H13NO4S:
d
CDCl3)
CH), 3.3 (s, 2H, CH2–S), 2.4 (s, 3H, CH3). 13CNMR (400 Mz, CDCl3),
ppm: 171.3 (pC]O of thiazolidone), 160.9 (pC]O of -pyrone),
153.1–115.9 (12C, Ar), 112.7 (C3 of -pyrone), 55.7 (C2 of thiazo-
d
ppm: 10.7 (s, 1H, OH), 7.8–7.3 (m, 7H, Ar–H), 6.2 (s, 1H, 3–
a
a
d
a
a
327.0565 found 327.0560.
lidone), 33.7 (C4 of thiazolidone), 21.3 (C4–CH3 of
a-pyrone).
DIPMS m/z: 353.07 Mþ and HRMS calcd for C19H15NO4S: 353.0722
5.2.8. 7-(2-(N,N-dimethyl)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4h)
found 353.0700.
m.p.: 268–270; % yield: 48; IR (KBr) cmꢀ1: 1723 (pC]O of
5.2.3. 7-(2-(m-methoxy)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4c)
a
-pyrone and thiazolidone), 1600 (C]C stretching), 1385 (C–N
stretching), 1262 (pC]O stretching), 695 (C–S–C); 1HNMR
(400 Mz, CDCl3) ppm: 7.3–6.5 (m, 8H, Ar–H), 6.2 (s, 1H, 2-CH), 5.9
(s, 1H, CH–S), 3.5 (s, 2H, CH2–S), 2.9 (s, 6H, N(CH3)2), 2.4 (s, 3H,
CH3). 13CNMR (400 Mz, CDCl3),
ppm: 171.1 (pC]O of thiazoli-
done), 160.7 (<C]O of -pyrone), 153.9–115.9 (12C, Ar), 112.3 (C3
of -pyrone), 65.7 (C2 of thiazolidone), 41.3 2C of N(CH3)2, 33.7 (C4
of thiazolidone), 19.5 (C4–CH3 of
-pyrone). DIPMS m/z: 380.10 Mþ
m.p.: 258–260; % yield: 55; IR (KBr) cmꢀ1: 2927 (pC–H), 1727
d
(pC]O of
(C–N stretching), 1260 (pC]O stretching, 1145(pC–O), 697
(C–S–C)); 1HNMR (CDCl3)
ppm: 8.3 –7.4 (m, 7H, Ar–H), 6.23 (s, 1H,
2-CH), 3.8 (s, 2H, CH2–S), 3.6 (s, 3H, OCH3), 2.4 (s, 3H, CH3). 13CNMR
(400 Mz, CDCl3), ppm: 171.3 (pC]O of thiazolidone), 160.9
(<C]O of -pyrone), 160.5–115.9 (12C, Ar), 112.7 (C3 of -pyrone),
65.7 (C2 of thiazolidone), 33.7 (C4 of thiazolidone), 21.1 (C4–CH3 of
-pyrone). DIPMS m/z: 367.09 Mþ and HRMS calcd for C20H17NO4S:
a-pyrone and thiazolidone), 1610 (C]C stretching), 1356
d
d
a
a
d
a
a
a
and HRMS calcd for C21H20N2O3S: 380.1196 found 380.1190.
a
5.2.9. 7-(2-(p-fluoro)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4i)
367.0878 found 367.0870.
m.p.: 257–259; % yield: 68; IR (KBr) cmꢀ1: 1727 (pC]O of
5.2.4. 7-(2-(m-nitro)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4d)
a
-pyrone and thiazolidone), 1597 (C]C stretching), 1385 (C–N
stretching), 1143 (pC]O stretching), 659 (C–S–C); 1HNMR (400 Mz,
CDCl3) ppm: 7.3–6.8 (m, 8H, Ar–H), 6.2 (s, 1H, 2-CH), 5.9 (s, 1H, CH–
S), 3.5 (s, 2H, CH2–S), 2.4 (s, 3H, CH3).13CNMR (400 Mz, CDCl3),
ppm:
171.3 (pC]O of thiazolidone),160.9 (<C]O of -pyrone),152.9–115.1
(12C, Ar), 112.5 (C3 of -pyrone), 65.7 (C2 of thiazolidone), 33.7 (C4 of
thiazolidone), 19.3 (C4–CH3 of
-pyrone). DIPMS m/z: 355.01 Mþ and
m.p.: 249–251; % yield: 48; IR (KBr) cmꢀ1: 1728 (pC]O of
d
a
-pyrone and thiazolidone), 1613 (C]C stretching), 1359 (C–N
stretching), 1250 (pC]O stretching), 631(C–S–C); 1HNMR (400 Mz,
CDCl3) ppm: 7.8–7.3 (m, 7H, Ar–H), 6.2 (s, 1H, 2-CH), 3.8 (s, 2H,
CH2–S), 2.4 (s, 3H, CH3). 13CNMR (400 Mz, CDCl3),
ppm: 171.1
(pC]O of thiazolidone), 160.9 (<C]O of -pyrone), 153.1–116.9
(12C, Ar), 112.1 (C3 of -pyrone), 64.7 (C2 of thiazolidone), 33.7
d
a
d
a
d
a
a
HRMS calcd for C19H14FNO3S: 355.0678 found 355.0671.
a
(C4 of thiazolidone), 21.3 (C4–CH3 of
a
-pyrone). DIPMS m/z: 382.06
5.2.10. 7-(2-(p-methyl)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4j)
Mþ and HRMS calcd for C19H14N2O5S: 382.0623 found 382.0619.
m.p.: 254–256; % yield: 58; IR (KBr) cmꢀ1: 1735 (pC]O of
5.2.5. 7-(2-(o,p-dichloro)-phenyl thiazolidinyl)-4-methyl-
a
-pyrone and thiazolidone), 1596 (C]C stretching), 1383 (C–N
stretching), 1257 (pC]O stretching), 709 (C–S–C); 1HNMR (400 Mz,
CDCl3) ppm: 8.1–7.2 (m, 8H, Ar–H), 6.5 (s, 2H, CH2), 6.2 (s, 1H, 2-
CH), 3.5 (s, 2H, CH2–S), 2.4 (s, 3H, CH3). 13CNMR (400 Mz, CDCl3),
ppm: 171.3 (pC]O of thiazolidone), 160.9 (<C]O of -pyrone),
154.9–115.3 (12C, Ar), 112.5 (C3 of -pyrone), 65.7 (C2 of thiazoli-
benzopyran-2one (4e)
m.p.: 277–279; % yield: 60; IR (KBr) cmꢀ1: 1730 (pC]O of
a
-
d
pyrone and thiazolidone), 1602 (C]C stretching), 1342 (C–N
stretching), 1265 (pC]O stretching), 625(C–S–C); 1HNMR (400 Mz,
d
a
CDCl3)
CH–S), 3.5 (s, 2H, CH2–S), 2.4 (s, 3H, CH3). 13CNMR (400 Mz, CDCl3),
ppm: 171.3 (pC]O of thiazolidone), 160.9 (<C]O of -pyrone),
152.9–116.9 (12C, Ar), 112.5 (C3 of -pyrone), 56.7 (C2 of thiazoli-
d
ppm: 7.4–6.8 (m, 8H, Ar–H), 6.2 (s, 1H, 2-CH), 5.8 (s, 1H,
a
done), 33.3 (C4 of thiazolidone), 21.3 (p-CH3), 19.3 (C4–CH3 of a-
d
a
pyrone). DIPMS m/z: 351.10 Mþ and HRMS calcd for C20H17NO3S:
a
351.0929 found 351.0920.
done), 33.7 (C4 of thiazolidone), 21.3 (C4–CH3 of a-pyrone). DIPMS
m/z: 405.01 Mþ and HRMS calcd for C19H13Cl2NO3S: 404.9993
found 404.9990.
5.2.11. 7-(2-(p-hydroxy)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4k)
m.p.: 277–278; % yield: 42; IR (KBr) cmꢀ1: 3400 (–OH stretching),
5.2.6. 7 -(2-(p-methoxy)-phenyl thiazolidinyl)-4-methyl-
benzopyran-2-one (4f)
1723 (
(pC]O stretching), 635 (C–S–C); 1HNMR (400 Mz, CDCl3)
(b, 1H, OH), 7.3–6.6 (m, 8H, Ar–H), 6.2 (s, 1H, 2-CH), 5.9 (s, 1H, CH–S),
3.5 (s, 2H, CH2–S), 2.4 (s, 3H, CH3). 13CNMR (400 Mz, CDCl3),
ppm:
171.3 (pC]Oof thiazolidone),160.7 (<C]O of -pyrone),156.9–115.9
(12C, Ar), 112.5 (C3 of -pyrone), 65.7 (C2 of thiazolidone), 33.5 (C4 of
thiazolidone), 19.5 (C4–CH3 of
-pyrone). DIPMS m/z: 353.07 Mþ and
a
-pyrone), 1600 (C]C stretching), 1375 (C–N stretching), 1255
d
ppm: 11.5
m.p.: 267–269; % yield: 45; IR (KBr) cmꢀ1: 1735 (pC]O of
a
-pyrone and thiazolidone), 1596 (C]C stretching), 1362 (C–N
stretching),1257 (pC]O stretching), 639 (C–S–C); 1HNMR (400 Mz,
CDCl3) ppm: 8.1–6.8 (m, 8H, Ar–H), 6.2 (s, 1H, 2-CH), 5.9 (s, 1H,
CH–S), 3.5 (s, 2H, CH2–S), 3.7 (s, 3H, OCH3), 2.4 (s, 3H, CH3). 13CNMR
(400 Mz, CDCl3), ppm: 171.1 (pC]O of thiazolidone), 160.9
(<C]O of -pyrone), 152.9–116.9 (12C, Ar), 112.5 (C3 of -pyrone),
65.7 (C2 of thiazolidone), 58.5(4-OCH3) 33.7 (C4 of thiazolidone),
21.3 (C4–CH3 of
-pyrone). DIPMS m/z: 367.06 Mþ and HRMS calcd
d
a
d
a
a
d
HRMS calcd for C19H15NO4S: 353.0722 found 353.0719.
a
a
6. Biological activity
a
for C20H17NO4S: 367.0878 found 367.0870.
The synthesized compounds were screened for antibacterial and
antifungal activity using agar cup plate method [17–19]. Cipro-
floxacin and Grisofulvin were used as standard drug for the anti-
bacterial and antifungal activity respectively at a concentration of
5.2.7. 7-(2-(o-furan)-phenyl thiazolidinyl)-4-methyl-benzopyran-
2-one (4g)
m.p.: 280–282; % yield: 44; IR (KBr) cmꢀ1: 1723 (pC]O of
50
mg/ml and zone of inhibition of all newly synthesized
a
-pyrone and thiazolidone), 1580 (C]C stretching), 1378 (C–N
compounds 3a–k and 4a–k was measured against various strains

P.M. Ronad et al. / European Journal of Medicinal Chemistry 45 (2010) 85–89
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Acknowledgement
Authors are thankful to Dr. B. M. Patil, Principal, K.L.E.s College of
Pharmacy, Hubli for providing necessary facilities. Mrs. Geena
Malhotra, Manager R&D and Dr. Manish, Head ADL Dept. Cipla Ltd.,
Mumbai, Director, SIAF, Punjab University, Chandigarh for providing
spectral data and Ms. Manjusha Bartakke, Lecturer, T. K. C. P. College
Warananagar, for antimicrobial studies. We are thankful to Prof.
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