Synthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinones

Article abstract of DOI:10.1080/10426500701555801

A series of new thiazolidinonyl -4-aryloxymethylcoumarins (4a-h) have been synthesized from 4-Bromomethylcoumarins (1a-b) and 4-aryliminomethyl-phenols (2a-d). Structures of all the new compounds are elucidated by elemental analyses, IR, 1 H NMR, and mass spectral data. All these compounds have been subjected to in-vitro antimicrobial and in-vivo anti-inflammatory screening.

Full text of DOI:10.1080/10426500701555801

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Phosphorus, Sulfur, and Silicon
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Synthetic and Biological Studies
on 4-Aryloxymethyl Coumarinyl
Thiazolidinones
K. Shivashankar a , Lokesh A. Shastri a , Manohar
V. Kulkarni a , Vijaykumar P. Rasal b & Sandur V.
Rajendra b
a Department of Postgraduate Studies in Chemistry ,
Karnatak University , Dharwad, India
b Department of Pharmacology , Karnataka Liberal
Education Society's College of Pharmacy , Hubli,
India
Published online: 20 Feb 2008.
To cite this article: K. Shivashankar , Lokesh A. Shastri , Manohar V. Kulkarni ,
Vijaykumar P. Rasal & Sandur V. Rajendra (2007) Synthetic and Biological Studies on
4-Aryloxymethyl Coumarinyl Thiazolidinones, Phosphorus, Sulfur, and Silicon and the
Related Elements, 183:1, 56-68, DOI: 10.1080/10426500701555801
To link to this article: http://dx.doi.org/10.1080/10426500701555801
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Phosphorus, Sulfur, and Silicon, 183:56–68, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701555801
Synthetic and Biological Studies on 4-Aryloxymethyl
Coumarinyl Thiazolidinones
K. Shivashankar,1 Lokesh A. Shastri,1
Manohar V. Kulkarni,1 Vijaykumar P. Rasal,2
and Sandur V. Rajendra2
1Department of Postgraduate Studies in Chemistry, Karnatak
University, Dharwad, India
2Department of Pharmacology, Karnataka Liberal Education Society’s
College of Pharmacy, Hubli, India
A series of new thiazolidinonyl-4-aryloxymethylcoumarins (4a–h) have been syn-
thesized from 4-Bromomethylcoumarins (1a–b) and 4-aryliminomethyl-phenols
(2a–d). Structures of all the new compounds are elucidated by elemental analyses,
IR, 1 H NMR, and mass spectral data. All these compounds have been subjected to
in-vitro antimicrobial and in-vivo anti-inflammatory screening.
Keywords Coumarins; thiazolidinone; 4-bromomethylcoumarins; antimicrobial; anti-
inflammatory
INTRODUCTION
Thiazolidinones possessing aryl groups at C-2 and N-3 positions have
been found to exhibit anti-tubercular1 and HIV protease inhibiting2
activities. Their potential to inhibit inflammation caused by phlogistic
agents has been well supported by in-vivo studies in animal models.3–5
The ability of coumarins to prevent the formation of 5-HETE and
5-HHE in the Arachidonic acid metabolism and their role in inhibiting
inflammation has been well established.6,7 Our earlier work has
revealed that linking biocompatible fragments like Vanillin8 and
Received 5 May 2007; accepted 5 June 2007.
We thank the University Scientific Instrumentation Center–Karnatak University
Dharwad and Indian Institute of Chemical Technology–Hyderabad, for providing
spectral data. K. Shivashankar thanks University Grants Commission, New Delhi, for
providing the FIP fellowship.
Address correspondence to Manohar V. Kulkarni, Karnatak University,
Dept. of Post Graduate Studies in Chemistry, Dharwad 580003, India. E-mail:
profmvk@rediffmail.com
56

Aryloxymethyl Coumarinyl Thiazolidinones
57
Paracetamol9 at the allylic position, with respect to the C3-C4 dou-
ble bond, results in 4-aryloxymethylcoumarins with significant inflam-
mation inhibiting and interesting photophysical properties. The in-
troduction of pyrazole ring in the phenoxy moiety was accomplished
by using pre-functionalized phenols, leading to a library of pyrazole
linked 4-aryloxymethyl coumarins, which were found to be potential
anti-inflammatory agents.10 In view of these reports, it was thought
of interest to introduce the thiazolidinone ring at para position in the
phenoxy moiety of 4-aryloxymethylcoumarins, by nucleophilic addition
and N-heterocyclization route (Scheme 1).
CHEMISTRY
The present synthetic strategy begins with the generation of the re-
quired 4-bromomethylcoumarins11 (1a–b) by the Pechmann cyclisation
of meta and para cresols with 4-bromoethylacetoacetate12 (Scheme 1).
In view of the poor reactivity of the p-carbonyl group observed
in 4-aryloxymethyl coumarins,10 pre-functionalized phenols (2a–d)
(obtained by the reaction of p-formyl phenol and aromatic amines) were
used for a room temperature allylic SN reaction under standard acetone-
potassium carbonate conditions generating the required precursors
(3a–h) in high yields. The azomethine group in (3a–h) underwent nu-
cleophilic addition with thioglycollic acid followed by dehydration due
to N-CO bond formation. The reaction was carried out in dimethyl for-
mamide under refluxing conditions. The products (4a–h) were isolated
by decomposing the cooled reaction mixture with ice followed by treat-
ment with 10% NaHCO3 to remove excess of thioglycollic acid. The
resulting solids were found to be high melting solids and were purified
by crystallization from DMF.
RESULTS AND DISCUSSION
The IR spectrum of 4-{4-[(4-chloro-phenylimino)-methyl]-phenoxyme-
thyl}-6-methyl-chromen-2-one (3c) (R = 6-CH3, R1 = Cl) showed lac-
tone carbonyl stretching frequency at 1699 cm−1 and stretching
frequency for C N group at 1624 cm−1. The PMR spectrum of (3c)
exhibited a singlet due to CH3 protons at 2.37 δ ppm, C4-CH2 at 5.29
δ ppm and C3-H at 6.56 δ ppm. The aromatic protons resonated in the
range of 6.96–8.33 δ ppm. The azomethine proton appeared downfield
as a singlet at 9.84 δ ppm. The observed chemical shifts of C4-CH2
and C3-H are in agreement with our earlier work on 4-aryloxymethyl
coumarins.11

58

Aryloxymethyl Coumarinyl Thiazolidinones
59
The IR spectrum of 2-[4-(7-methyl-2-oxo-2H-chromen-4-ylmethoxy)-
phenyl]-3-phenyl-thiazolidin-4-one (4e) (R = 7-CH3, R1 = H) showed
lactone carbonyl stretching at 1715 cm−1 and carbonyl of thiazolidinone
stretching at 1680 cm−1. The PMR spectrum of 2-[4-(6-methyl-2-oxo-
2H-chromen-4-ylmethoxy)-phenyl]-3-phenyl-thiazolidin-4-one (4a) (R
= 6-CH3, R1 = H) showed a singlet at 2.45 δ ppm due to C6-CH3
protons. A singlet appeared at δ 3.56 was due to methylene protons
(S-CH2) of thiazolidinone ring. Singlets observed at 4.3, 5.24, and 6.64
δ ppm are due to S-CH-N, C4-CH2 and C3-H protons, respectively.
The aromatic protons resonated as multiplet in the range of 6.98–
7.93 δ ppm. The disappearance of the low field singlet observed in
compounds (3) and the appearance of an upfield singlet at 4.3 δ ppm,
characteristic of thiazolidinones13 confirmed the addition of thioglycol-
lic acid across the azomethine linkage in compounds (3). The EI Mass
spectrum of 2-[4-(6-methyl-2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-3-
phenyl-thiazolidin-4-one (4a) (R = 6-CH3, R1 = H) showed no molecular
ion peak but base peak appeared at m/z 145 (100%) due to homolytic
cleavage of the allylic CH2-O bond with the subsequent loss of carbon
monoxide, which is in agreement with literature reports.14
PHARMACOLOGY
Albino rats of Wister strain of either sex weighing between 150–230 g
were selected. The animals were kept on a standard diet and allowed
food and water ad libitum. Ibuprofen was used as standard for anti-
inflammatory activity administered orally at a dose of 45 mg kg−1 body
weight in a suspension of 5% gum acacia. Carrageenin (0.1 mL; 1%)
suspended in 0.5% carboxymethyl cellulose (CMC). Data were analyzed
by one-way ANOVA (F-test) followed by Dunnet multiple comparison
test. Differences below the 0.01 level (P < 0.01) were considered as
statistically significant.
ACUTE TOXICITY STUDIES
For testing the acute toxicity potential of the test compounds, albino
mice of either sex weighing 25–50 g were selected, separated in to 10
groups each containing six mice. The dosage was varied from 100 up to
3000 mg kg−1 body weight. The mice were continuously observed for 24
h for any signs of increased or decreased motor activity, ataxia, tremors,
convulsions, sedation, lacrimation, and so on. After 24 h, the mice were
sacrificed; stomach, intestine and liver were inspected under the mag-
nifying lens for any ulcer hemorrhagic spots. The whole experiment
on animals was cleared from Institutional Animal Ethics Committee

60
K. Shivashankar et al.
(IAEC). All the compounds showed good safety profile until the highest
dose of 3000 mg kg−1 in albino rats. Amongst the behavioral changes
no sedation, convulsions and tremors were observed. Post-mortem ex-
amination of the stomach and intestine did not reveal any ulcer and
hemorrhagic spots. Liver was also examined and showed no necrosis.
ANTI-INFLAMMATORY ACTIVITY (CARRAGEENAN INDUCED
RAT PAW OEDEMA METHOD)
Carrageenan induced rat paw oedema inhibition method according to
Winter et al.15 was employed during the present study. Ten groups
of rats (six in each group) received Carrageenan (0.1 mL of 1% Car-
rageenan in 0.5 mL of carboxy methyl cellulose) sub plantarly in the
left hind paw. One group was kept as control. Other nine groups re-
ceived standard and test compounds at a dose of 300 mg kg−1 body
weight in 0.2 mL of 5% gum acacia only 1 h prior to the sub plantar
injection of Carrageenan. The paw edema volume was measured with
the help of plethysmograph by mercury displacement method at zero
hour immediately after injecting Carrageenan. Then, the edema vol-
ume was measured at 1 h interval for 5 h. Control groups received 0.2
mL of 5% gum acacia. Ibuprofen 45 mg kg−1 body weight in 0.2 mL of
5% gum acacia was used as the standard. The results indicated that,
when compared with the control, compounds (4b), (4d), and (4g) showed
significant reduction in edema volume. The results depicting edema vol-
umeand percentage inhibition of inflammation at various time intervals
have been summarized in Table I. It can be seen from Table I that all
the compounds exhibited a delayed on set of action, which achieved a
significant level only at the end of 2 h. Further a steady increase was
observed even at the end of 5 h. Compounds (4d) and (4g) were the best
in the present series. Compounds (4a), (4c), (4e), (4f), and (4h) have
not shown significant activity to warrant further investigation.
ANTIMICROBIAL ACTIVITY
The antimicrobial screening for all the compounds was carried out
against Gram positive and Gram-negative species with B. subtilis andE.
coli respectively. A. niger and C. albicans were employed as fungal
strains. DMF was used as solvent control. The reference drugs used
were Ciprofloxacin and Gresiofulvin. The tests were carried out by cup
plate method16 at a concentration of 100 µg mL−1. After 48 h of in-
cubation at 37◦C, the zone of inhibition was measured in mm. The
percent inhibition of the test compounds was related to the standard

61

62
K. Shivashankar et al.
whose zone of inhibition was taken as 100%. Among ethers (3a–d)
and (3f–h) showed growth inhibition in the range of 78–94% (Table II)
against B. subtilis and E. coli and the fungal strain A. niger. Compound
(3e) has shown growth inhibition of 78% against E. coli. Compound
(3c), (3g), and (3h) showed growth inhibition in the range of 78–89%
against the C. albicans. In the case of thiazolidinonyl coumarins (4c),
(4d), (4g) and (4h) showed growth inhibition in the range of 78–94%
against the bacteria E. coli, the fungal strain A. niger, and C. albicans.
Compound (4b) showed 78% inhibition against B. subtilis. Remaining
compounds have been found to be moderately active. Upon (1:1) dilu-
tion, the activity observed was reduced and did not warrant further
dilution.
EXPERIMENTAL
Melting points were determined using an electric melting point appa-
ratus and are uncorrected. IR spectra were run in KBr pellets on a
1
Nicolet-Impact-410 FT-IR spectrometer (νmax in cm−1). H NMR spec-
tra were recorded in DMSO-d6 with TMS as an internal standard
(Chemical shift in δ, ppm) on a Bruker 300 MHz FT-NMR spectrom-
eter. Mass spectra (EI) were recorded from Indian Institute of Chem-
ical Technology, Hyderabad. Purity of the compounds was checked by
TLC. Nomenclature was made using Chem. Draw Ultra version 6.0. All
the reagents were of laboratory reagent quality and were purchased
from Sd.fine-chem.limited and used after purification. All the new com-
pounds gave satisfactory elemental analyses.
Preparation of 4-(4-Phenyliminomethyl-phenoxymethyl)-
chromen-2-ones 3(a–h)—General Procedure
4-Phenyliminomethyl-phenols (2a–d) (10 mmol) and anhydrous K2CO3
(1.38 g, 10 mmol) were stirred in dry acetone (25 mL) for 30 min. 4-
Bromomethylcoumarins (1a–b) (2.52 g, 10 mmol) was added and stir-
ring was continued for 24 h. The reaction mixture was concentrated
and poured into crushed ice (100 g). The solid separated was filtered
and washed with 5% HCl (10 mL) to neutralize excess of potassium car-
bonate. Then, it was washed with 100 mL of cold water and with dilute
ethanol. The crude product was dried and recrystallized from DMF.
6-Methyl-4-(4-phenyliminomethyl-phenoxymethyl)-
chromen-2-one (3a)
Colorless crystals from DMF. Yield 72%, m.p. 215–217◦C; (found; C,
77.89; H, 5.09; N, 3.68. C24H19O3N (369) requires C, 78.04; H, 5.14;

63

64
K. Shivashankar et al.
1
N, 3.79%); IR (KBr): ν = 1712 (C O, lactone), 1604 (C N) cm–1; H
NMR (300 MHz, DMSO-d6): δ = 2.37 (s, 3H, C6-CH3), 5.35 (s, 2H, CH2-
O), 6.54 (s, 1H, C3-H), 7.14–8.36 (m, 12H, Ar-H), 9.83(s, 1H, –CH N)
ppm.
6-Methyl-4-[4-(p-tolylimino-methyl)-phenoxymethyl]-
chromen-2-one (3b)
Colorless crystals from DMF. Yield 70%, m.p. 209–211◦C; (found: C,
78.12; H, 5.26; N 3.49. C25H21O3N (383) requires C, 78.32; H, 5.48;
N, 3.65%); IR (KBr): ν = 1709 (C O, lactone), 1610 (C N) cm–1; H
1
NMR (300 MHz, DMSO-d6): δ = 2.37 (s, 3H, C6-CH3), 2.45 (s, 3H, -CH3),
5.30 (s, 2H, CH2-O), 6.68 (s, 1H, C3-H), 6.98–8.42 (m, 11H, Ar-H), 9.93
(s, 1H, –CH N) ppm.
4-{4-[(4-Chloro-phenylimino)-methyl]-phenoxymethyl}-
6-methyl-chromen-2-one (3c)
Colorless crystals from DMF. Yield 62%, m.p. 244–246◦C; (found; C,
71.11; H, 4.27; N, 3.31. C24H18O3NCl (403) requires C, 71.37; H, 4.46;
1
N, 3.46%); IR (KBr): ν = 1699 (C O, lactone), 1624 (C N) cm–1; H
NMR (300 MHz, DMSO-d6): δ = 2.37 (s, 3H, C6-CH3), 5.29 (s, 2H, CH2-
O), 6.56 (s, 1H, C3-H), 6.96–8.33 (m, 11H, Ar-H), 9.84 (s, 1H, –CH N)
ppm.
4-{4-[(4-Bromo-phenylimino)-methyl]-phenoxymethyl}-
6-methyl-chromen-2-one (3d)
Colorless crystals from DMF. Yield 66%, m.p. 242–244◦C; (found; C,
64.12; H, 3.83; N, 3.01. C24H18O3NBr (447) requires C, 64.28; H, 4.01;
1
N, 3.12%); IR (KBr): ν = 1738 (C O, lactone), 1617 (C N) cm–1; H
NMR (300 MHz, DMSO-d6): δ = 2.46 (s, 3H, C6-CH3), 5.34 (s, 2H, CH2-
O), 6.66 (s, 1H, C3-H), 7.13–7.93 (m, 11H, Ar-H), 9.94 (s, 1H, –CH N)
ppm.
7-Methyl-4-(4-phenyliminomethyl-phenoxymethyl)-
chromen-2-one (3e)
Colorless crystals from DMF. Yield 70%, m.p. 252–254◦C; (found; C,
77.88; H, 5.01; N, 3.63. C24H19O3N (369) requires C, 78.04; H, 5.14; N,
3.79%); IR (KBr): ν = 1727 (C O, lactone), 1604 (C N) cm–1; 1H NMR
(300 MHz, DMSO-d6): δ = 2.39 (s, 3H, C7-CH3), 5.27 (s, 2H, CH2-O),
6.50 (s, 1H, C3-H), 7.06–7.82 (m, 12H, Ar-H), 9.83 (s, 1H, –CH N) ppm.

Aryloxymethyl Coumarinyl Thiazolidinones
65
7-Methyl-4-[4-(p-tolylimino-methyl)-phenoxymethyl]-
chromen-2-one (3f)
Colorless crystals from DMF. Yield 68%, m.p. 262–264◦C; (found; C,
78.17; H, 5.29; N, 3.51. C25H21O3N (383) requires C, 78.32; H, 5.48;
1
N, 3.65%); IR (KBr): ν = 1736 (C O, lactone), 1611 (C N) cm–1; H
NMR (300 MHz, DMSO-d6): δ = 2.40 (s, 3H, C7-CH3), 2.50 (s, 3H, -CH3),
5.32 (s, 2H, CH2-O), 6.49 (s, 1H, C3-H), 7.10–7.91 (m, 11H, Ar-H), 9.83
(s, 1H, –CH N) ppm.
4-{4-[(4-Chloro-phenylimino)-methyl]-phenoxymethyl}-
7-methyl-chromen-2-one (3g)
Colorless crystals from DMF. Yield 60%, m.p. 260–262◦C; (found; C,
71.19; H, 4.31; N, 3.29. C24H18O3NCl (403) requires C, 71.37; H, 4.46;
1
N, 3.46%); IR (KBr): ν = 1724 (C O, lactone), 1621 (C N) cm–1; H
NMR (300 MHz, DMSO-d6): δ = 2.40 (s, 3H, C7-CH3), 5.21 (s, 2H, CH2-
O), 6.49 (s, 1H, C3-H), 7.11–7.83 (m, 11H, Ar-H), 9.83 (s, 1H, –CH N)
ppm.
4-{4-[(4-Bromo-phenylimino)-methyl]-phenoxymethyl}-
7-methyl-chromen-2-one (3h)
Colorless crystals from DMF. Yield 63%, m.p. 244–246 ◦C; (found; C,
64.10; H, 3.87; N, 3.03. C24H18O3NBr (447) requires C, 64.28; H, 4.01; N,
3.12%); IR (KBr): ν = 1722 (C O, lactone), 1609 (C N) cm–1; 1H NMR
(300 MHz, DMSO-d6): δ = 2.49 (s, 3H, C7-CH3), 5.30 (s, 2H, CH2-O),
6.56 (s, 1H, C3-H), 7.08–8.38 (m, 11H, Ar-H), 9.94 (s, 1H, –CH N) ppm.
Preparation of 2-[4-(2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-
3-phenyl-thiazolidin-4-ones 4(a-h)—General Method
To a solution of (3a–h) (10 mmol) in DMF (30 mL) was added thiogly-
collic acid (0.7 mL, 10 mmol) and ZnCl2 (1 g) and the reaction mixture
was refluxed for 8 h, cooled and poured onto crushed ice (100 g). The
separated solid was filtered and washed with 10% NaHCO3 (10 mL).
The crude product was dried and recrystallized from DMF.
2-[4-(6-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-
3-phenyl-thiazolidin-4-one (4a)
Colorless crystals from DMF. Yield 62%, m.p. 180–182◦C; (found; C,
70.24; H, 4.69; N, 3.04. C26H21O4NS (443) requires C, 70.42; H, 4.74;
–1
N, 3.16%); IR (KBr): ν = 1722 (C O, lactone), 1699 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.45 (s, 3H, C6-CH3), 3.56 (s, 2H,
S-CH2), 4.30 (s, 1H, S-CH-N), 5.24 (s, 2H, CH2-O), 6.64 (s, 1H, C3-H),
6.98–7.93 (m, 12H, Ar-H) ppm; ms m/z 145 (Base peak, 100%).

66
K. Shivashankar et al.
2-[4-(6-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-
3-p-tolyl-thiazolidin-4-one (4b)
Colorless crystals from DMF. Yield 59%, m.p. 178–180◦C; (found; C,
70.72; H, 4.89; N, 2.91. C27H23O4NS (457) requires C, 70.89; H, 5.03;
–1
N, 3.06%); IR (KBr): ν = 1720 (C O, lactone), 1688 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.19 (s, 3H, C6-CH3), 2.36 (s, 3H,
-CH3), 3.37 (s, 2H, S-CH2), 4.21 (s, 1H, S-CH-N), 5.19 (s, 2H, CH2-O),
6.55 (s, 1H, C3-H), 6.90–8.06 (m, 11H, Ar-H) ppm.
3-(4-Chloro-phenyl)-2-[4-(6-methyl-2-oxo-2H-chromen-
4-ylmethoxy)-phenyl]-thiazolidin-4-one (4c)
Colorless crystals from DMF. Yield 35%, m.p. 188–190◦C; (found; C,
65.17; H, 4.05; N, 2.81. C26H20O4NSCl (477) requires C, 65.34; H, 4.18;
–1
N, 2.93%); IR (KBr): ν = 1720 (C O, lactone), 1690 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.50 (s, 3H, C6-CH3), 3.60 (s, 2H,
S-CH2), 4.47 (s, 1H, S-CH-N), 5.41 (s, 2H, CH2-O), 6.54 (s, 1H, C3-H),
7.14–7.95 (m, 11H, Ar-H) ppm.
3-(4-Bromo-phenyl)-2-[4-(6-methyl-2-oxo-2H-chromen-
4-ylmethoxy)-phenyl]-thiazolidin-4-one (4d)
Colorless crystals from DMF. Yield 40%, m.p. 185–187◦C; (found; C,
59.61; H, 3.71; N, 2.54. C26H20O4NSBr (521) requires C, 59.77; H, 3.83;
–1
N, 2.68%); IR (KBr): ν = 1718 (C O, lactone), 1675 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.40 (s, 3H, C6-CH3), 3.42 (s, 2H,
S-CH2), 4.39 (s, 1H, S-CH-N), 5.39 (s, 2H, CH2-O), 6.40 (s, 1H, C3-H),
7.14–7.94 (m, 11H, Ar-H) ppm.
2-[4-(7-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-
3-phenyl-thiazolidin-4-one (4e)
Colorless crystals from DMF. Yield 60%, m.p. 168–170◦C; (found; C,
70.27; H, 4.61; N, 3.04. C26H21O4NS (443) requires C, 70.42; H, 4.74;
–1
N, 3.16%); IR (KBr): ν = 1715 (C O, lactone), 1680 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.45 (s, 3H, C7-CH3), 3.49 (s, 2H,
S-CH2), 4.29 (s, 1H, S-CH-N), 5.19 (s, 2H, CH2-O), 6.53 (s, 1H, C3-H),
6.92–8.02 (m, 12H, Ar-H) ppm.
2-[4-(7-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-
3-p-tolyl-thiazolidin-4-one (4f)
Colorless crystals from DMF. Yield 52%, m.p. 204–206◦C; (found; C,
70.71; H, 4.89; N, 2.91. C27H23O4NS (457) requires C, 70.89; H, 5.03;
–1
N, 3.06%); IR (KBr): ν = 1727 (C O, lactone), 1681 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.17 (s, 3H, C7-CH3), 2.48 (s, 3H,

Aryloxymethyl Coumarinyl Thiazolidinones
67
-CH3), 3.42 (s, 2H, S-CH2), 4.22 (s, 1H, S-CH-N), 5.31 (s, 2H, CH2-O),
6.59 (s, 1H, C3-H), 7.14–7.91 (m, 11H, Ar-H) ppm.
3-(4-Chloro-phenyl)-2-[4-(7-methyl-2-oxo-2H-chromen-
4-ylmethoxy)-phenyl]-thiazolidin-4-one (4g)
Colorless crystals from DMF. Yield 38%, m.p. 120–122◦C; (found; C,
65.17; H, 4.02; N, 2.76. C26H20O4NSCl (477) requires C, 65.34; H, 4.18;
–1
N, 2.93%); IR (KBr): ν = 1721 (C O, lactone), 1686 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.47 (s, 3H, C7-CH3), 3.47 (s, 2H,
S-CH2), 4.49 (s, 1H, S-CH-N), 5.14 (s, 2H, CH2-O), 6.50 (s, 1H, C3-H),
6.84–7.90 (m, 11H, Ar-H) ppm.
3-(4-Bromo-phenyl)-2-[4-(7-methyl-2-oxo-2H-chromen-
4-ylmethoxy)-phenyl]-thiazolidin-4-one (4h)
Colorless crystals from DMF. Yield 42%, m.p. 80–82◦C; (found; C,
59.63; H, 3.65; N, 2.51. C26H20O4NSBr (521) requires C, 59.77; H, 3.83;
–1
N, 2.68%); IR (KBr): ν = 1728 (C O, lactone), 1671 (C O, amide) cm
;
1H NMR (300 MHz, DMSO-d6): δ = 2.50 (s, 3H, C7-CH3), 3.47 (s, 2H,
S-CH2), 4.36 (s, 1H, S-CH-N), 5.41(s, 2H, CH2-O), 6.54 (s, 1H, C3-H),
7.14–7.95 (m, 11H, Ar-H) ppm.
CONCLUSION
Thiazolidinone moiety has been found to enhance the anti-inflamma-
tory activity of 4-aryloxymethyl coumarins. Bromo substitution in the
arylimino moiety was found to enhance the anti-inflammatory activity.
In the antimicrobial activity chloro and bromo substitution were found
to be the most favorable for the growth inhibition of E. coli and A. niger.
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