Synthesis and antimicrobial activity of 2-(2-ketothiophen-yl)-3- (substituted aryl)-5-{methylene-(4-haloaryl)}-1-thiazolidin-4-ones

Article abstract of DOI:10.13005/ojc/290232

New 2-(2-ketothiophen-yl)-3-(substituted aryl)-5-{methylene-(4-haloaryl)}- 1-thiazolidin-4-ones synthesized by condensation of 2-(2-ketothiophen-yl)-3- (substituted aryl) -1-thiazolidin-4ones with p-fluoro, p-chloro- and p-bromo- benzaldehydes were characterized by their elemental analyses, molecular weight determination and 1R and ¹HNMR spectroscopy. Some of the synthesized compounds have been screened in vitro for their antimicrobial activity against B. subtilis, S. aureus, E. coli, and P. aeruginosa bacteria and C. albicans and A. niger fungi. Almost all the tested compounds displayed pronounced biological activities.

Full text of DOI:10.13005/ojc/290232

ISSN: 0970-020 X
CODEN: OJCHEG
2013, Vol. 29, No. (2):
Pg. 617-621
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Est. 1984
Synthesis and Antimicrobial Activity of
2-(2- ketothiophen-yl)-3-(substituted aryl)-
5-{methylene-(4-haloaryl)}-1- thiazolidin-4-ones
GEETA RAGHAV, SANIDHYA UPADHYAY and R. K. UPADHYAY*
Department of Chemistry, N. R. E.C.College, Khurja, India.
C. C. S. University Meerut, India
*Corresponding author E-mail: rkupadhyay@gmail.com
(Received: February 01, 2013; Accepted: March 16, 2013)
ABSTRACT
New 2-(2-ketothiophen-yl)-3-(substituted aryl)-5-{methylene-(4-haloaryl)}-1-thiazolidin-4-
ones synthesized by condensation of 2-(2-ketothiophen-yl)-3-(substituted aryl) -1-thiazolidin-
4ones with p-fluoro, p-chloro- and p-bromo- benzaldehydes were characterized by their elemental
analyses, molecular weight determination and 1R and 1HNMR spectroscopy. Some of the
synthesized compounds have been screened in vitro for their antimicrobial activity against B.
subtilis, S. aureus, E. coli, and P. aeruginosa bacteria and C. albicans and A. niger fungi. Almost all
the tested compounds displayed pronounced biological activities.
Key words: Antimicrobial Activity, Bacteria, Fungi.
INTRODUCTION
screened for diverse biological properties but
majority of reports pertain to their antimicrobial
evaluation in search of new potential antimicrobial
agents with a zeal to address the long persisting
problem of drug resistance of some bacteria and
fungi. The high biological significance in general
and antimicrobial potential of this class of
compounds in particular impelled us to synthesize
new thiazolidinone derivatives by condensation of
2-(2-ketothiophen-yl)-3-(substituted aryl) -1-
thiazolidin-4ones with 4-fluoro-, 4-chloro- and 4-
Among the wide range of small ring
heterocycles that containing nitrogen and sulphur
have been under investigation for pretty long time
because of their multifarious medicinal potential
especially as antimicrobials. A survey of literature
has revealed that 4-thiazolidinones possessing
thiazole nucleus have been shown to have
manifold biological activities such as antiviral, anti-
HIV, anticancer, anticonvulsant, analgesic, anti-
inflammatory, antihistaminic, antituberculostatic,
antibacterial, antifungal etc, properties1-12. Although
plenty of these versatile molecules with variety of
substituted groups at position 2, 3and 5 of
thiazolidinone nucleus have been synthesized and
bromo- benzaldehydes in continuation to our
13-15
previous work
and to screen some of them as
typical examples in vitro for antimicrobial activities
against some Gram-positive and Gram-negative
bacteria and fungi.

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EXPERIMENTAL
by cyclocondensation of ketoazomethiones,
obtained by condensation of 2-thiophene glyoxal
General Procedure for the Synthesis of and primary amines, with thioglycolic acid as
Compounds
reported earlier16.
Preparation of 2-(2-ketothiophen-yl)-3-
(substituted aryl) -1-thiazolidin-4-ones
All the title compounds were synthesized
Where,
X= NO2, CH3, OCH3, Cl and H
1a: o- NO2 1b: m- NO2 1c: p- NO2 1d: o- CH3 1e: m- CH3 1f: p- CH3 1g: p- OCH3 1h: p – Cl 1i: H
Preparation of 2-(2-ketothiophen-yl)-3- separated were filtered and washed with water
(substituted aryl)-5-{methylene-(4-haloaryl}-1- repeatedly and crystallized from ethanol. Crystal of
thiazolidin-4-ones
products was dried in air. Chemicals used in the
For the synthesis of these compounds synthetic work were BDH/ E.Merck laboratory
each of the precursors (1a-i) (0.05mol) was mixed reagents whereas solvents for TLC work were
with p-fluoro, p-chloro- and p-bromo- benzaldehydes analytical reagents.
(0.05mol) and sodium acetate (2.0gm) in dry
methanol and reaction mixtures were refluxed for
The purity of the synthesized compounds
about 20 h on water bath. Concentrated reaction was checked by TLC and impure samples were
mixtures were cooled to room temperature and purified either by column chromatography or by
poured into ice cold water with stirring. The solids washing with the solvent as identified by TLC
Where,
y = F (2a-i)
= Cl (3a-i)
= Br (4a-i)

RAGHAV et al., Orient. J. Chem., Vol. 29(2), 617-621 (2013)
619
Physico-chemical and antimicrobial analyses
Elemental analyses for carbon, hydrogen,
(CH2) group of thiazolidinone ring (1a-i) and
aldehyde (CHO) group of benzaldehydes leads to
the formation of a new >C = CH - C< functional
moiety between thiazolidinone ring carbon and CH
of aldehyde group of benzaldehydes with the
release of a water molecules whereas other groups
of the reactants remained intect.The infrared spectra
of the synthesized compounds displayed all the
frequencies of characteristic groups of 1a-i, and
2a-i, 3a-i and 4a-i, υC=O, υC-N, υC-S-C of
pentacycle thiazolidinone ring and its adjacent C=O
group õC=O (chain) and υC=C & υC-H of benzene
ring in 1666-1769cm-1, 1298-1367cm-1, 663-736 cm-
1, and 1605-1669 cm-1 and 1441-1603 cm-1 & 2995-
3113cm-1 regions17 respectively except bands
corresponding to CH2 of thiazolidinone ring (1a-i)
and C=O of aldehydes (2a-i, 3a-i and 4a-i). The
absence of these bands of reactants and
appearance of two new bands in 1804-1949 cm-1
and 2893-2955 cm-1 regions attributed to υC=CH-
and υC-H respectively clearly indicate
condensation of methylene group of 1a-i with
carbonyl group of aldehydes. Bands corresponding
to ortho, meta and para disubstitution in benzene
ring appeared in 733-768 cm-1, 745-761 cm-1 and
810-842 cm-1 regions respectively in the spectra of
the products. In order to confirm infrared results
regarding condensation of the mentioned reactants
1H NMR spectra of nine compounds (2c, 2f, 2g, 3c,
3f, 3g, 4c, 4f and 4g) as typical examples have been
examined. The absence of chemical shift
corresponding to methylene (CH2) group 2H of
thiazolidinone ring and appearance of a new singlet
peak in δ 1.53-2.50 ppm range attributed18 to >C =
CH - C< 1H strongly support IR inferences. Benzene
and thiophene ring protons displayed their
chemical shifts in δ 6.56-7.98 ppm region.
nitrogen and sulphur contents of the synthesized
compounds were performed on a variro El-III
elemental – R analyzer. Melting points determined
in open glass capillaries were uncorrected.
Molecular weights of the compounds were
determined by Rast’s method using camphor as
solvent. IR spectra were recorded in KBr medium
in 4000-500 cm-1 range on Thermo Nicolet Nexus
FT-IR spectrometer. 1H NMR spectra were recorded
in dimethylsulphoxide medium on Bruker-400 Mhz
spectrophotometer.
Antimicrobial activity against Bacillus
subtilis, Staphylococcus aureus, Escherichia coli,
and Pseudomonas aeruginosa bacteria and
Candida albicans and Aspergillus niger fungi was
determined by the micro broth dilutions technique.
Mueller-Hinton broth was used as the test medium.
Serial two-fold dilutions from ranging from 400µg/
ml to 25µg/ml in DMSO-water (1:4, v/v). Mueller-
Hinton broth was used as nutrient medium to grow
and dilute the drug suspension. DMSO was used
as diluents.The inoculum was prepared using a 4-
6 h broth culture for each bacteria and 24 h culture
for fungi strains adjusted to a turbidity equivalent to
a 0.5 to 0.6 optical density diluted to broth media to
give a final concentration in Elissa plate.The plates
were covered with sterilized aluminium foil to
prevent evaporation and incubated at 35-370C for
24 h for bacteria and 48 h for fungi. The minimum
inhibitory concentrations (MIC), defined as the
lowest concentration of the compound giving
complete inhibition of visible growth, were
determined. Ampicillin(standard antibiotic) and
griseofulvin ( standard antifungal drug) were as
positive controls for antimicrobial and antifungal
screening.
It is observed (Table2) that all the compounds
irrespective to the nature of substituted groups in
both benzene rings are better bactericides and
fungicides than standard reference drugs in general
except unsubstituted aniline product (3i).
Compounds 2g, 3e and 4g with high antifungal
activities could be assumed as selective drugs for
both of the test fungi. Almost same antibacterial and
antifungal activities of 2e and 3e containing fluoro
and chloro substitutents with common m-OCH3
group, and 3a and 4a containing chloro and bromo
substitutents with common o-NO2 group may be due
to small difference in electronegativities of halogen
RESULTS AND DISCUSSION
Analytical and physical data of the
synthesized compounds are noted in table1.
Theoretically proposed molecular formulae of the
products are in fair agreement with their elemental
analyses and molecular weight data.
The condensation of 1a-i with p-halogen
substituted benzeldehydes involving methylene

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RAGHAV et al., Orient. J. Chem., Vol. 29(2), 617-621 (2013)
621
Table 2: Antimicrobial activity of compounds (MIC, µg/ml)
Microorganisms
Compound
S.subtilis
S.aureus
E.coli
P.aeruginosa
C.albicans
A .niger
2e
2g
3a
3e
3i
4a
4g
50
25
50
50
50
50
100
64
¯
50
25
50
50
¯
50
50
100
¯
50
25
50
50
50
50
50
64
¯
50
50
50
50
¯
50
50
100
¯
25
25
50
25
50
25
25
¯
50
25
25
25
50
50
25
¯
Ampicillin
Griseofulvin
80
80
substitutents in each pair of compounds. However
the effect of electronegativity of halogen
substitutents is more pronounce in exhibiting
antibacterial activities as has been observed in 2g
and 4g containing fluoro and bromo substitutents
with common OCH3 group. Compound 2g having
more electronegative halogen substitutent, fluoro,
is better antibactericide than 4g of bromo
substitutent. Among all the compounds however
2g is the best in exhibiting both, antibacterial and
antifungal activities against all the microbes.
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