Synthesis and antimicrobial evaluation of some 4-thiazolidinone derivatives containing polynuclear hydrocarbon

Article abstract of DOI:10.14233/ajchem.2016.20066

Some 4-thiazolidinone derivatives have also been known to be associated with several biological activities thus can be utilized as promising scaffold for developing analogues. Aryl aldehydes were treated with naphthylamine to yield corresponding Schiff's

Full text of DOI:10.14233/ajchem.2016.20066

Asian Journal of Chemistry; Vol. 28, No. 11 (2016), 2521-2523
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.20066
Synthesis and Antimicrobial Evaluation of Some 4-Thiazolidinone
Derivatives Containing Polynuclear Hydrocarbon
*
NEELAM VERMA , RAJ BHUSHAN SINGH and KULDEEP SINGH
Faculty of Pharmacy, Shambhunath Institute of Pharmacy, Jhalwa, Allahabad-211 012, India
*Corresponding author: E-mail: pharmaneelam10@gmail.com
Received: 5 May 2016;
Accepted: 13 July 2016;
Published online: 10 August 2016;
AJC-18031
Some 4-thiazolidinone derivatives have also been known to be associated with several biological activities thus can be utilized as promising
scaffold for developing analogues. Aryl aldehydes were treated with naphthylamine to yield corresponding Schiff’s bases. The Schiff’s
bases were treated with thioacetic acid in the presence of anhydrous ZnCl2 to afford 4-thiazolidinone derivatives then all the compounds
were characterized and evaluated for antibacterial and antifungal activity. Compounds having methoxy group at meta- and para-position,
dimethylamino and hydroxyl group at para-position was found to be biologically active.
Keywords: 4-Thiazolidinone, Schiff’s bases, Antimicrobial, Polynuclear hydrocarbon.
an amine, a carbonyl compound and a mercaptoacetic acid
yield 4-thiazolidinone. The water formed during cyclization
is removed by using anhydrous zinc or sodium sulphate as a
dessicant (Fig. 1).
INTRODUCTION
Chemical transformation of known active molecule
involves the use of already known principle on reported active
molecule for the search of new molecules, which could have
an increased potency, a better activity profile and improved
safety [1]. Imines have been reported to possess biological
activity [2]. Some 4-thiazolidinone derivatives have also been
known to be associated with several biological activities such
as antibacterial, antifungal anticonvulsant, antiviral, sedative,
hypnotic, antitubercular, anthelmentic, anticonvulsant, anti-
histaminic, anticancer and antiinflamatory activity thus can
be utilized as promising scaffold for developing analogues
[3]. It has been reported that groups like hydroxyl, methoxy,
ethoxy, chloro in the phenyl ring increases the activity of parent
compound [4,5]. So far no systematic attempt has been made
to study the effect of polynuclear hydrocarbon on the anti-
microbial activity. So keeping in view the present work involves
the synthesis, characterization and evaluation of antibacterial
activity of some novel 4-thiazolidinone derivatives containing
polynuclear hydrocarbons.
Synthesis of Schiff’s bases
Naphthalene-1-yl-(2-nitro-benzylidene)amine: A
mixture of α-naphthylamine (3 mmol) and benzaldehyde
derivatives (3 mmol) in methanol (30 mL) containing 3-4 drops
of glacial acetic acid was refluxed for 3 h. Thin layer chromato-
graphy was monitored to check the completion of the reaction.
Thereafter reaction mixture was cooled to room temperature.
The solid was filtered, washed with cold ethanol, dried and
recrystallized using a mixture of hexane and acetone (9:1) [6].
Synthesis of 4-thiazolidinone derivatives: A mixture of
Schiff’s bases (3 mmol) and mercaptoacetic acid (3 mmol)
in anhydrous 1:4-dioxane (30 mL) was refluxed for 8 h. The
progress of the reaction was monitored by thin layer chroma-
tography. The mixture was cooled and the residue was filtered,
dried and washed with cold water. The pure product was isolated
by column chromatography using chloroform and hexane (8:2)
as eluent and silica (100-120) as adsorbent [7].
EXPERIMENTAL
Spectral characterization of 4-thiazolidine derivatives
General synthetic procedure involves the two step
synthesis proceed via imine formation in the first step followed
by attack of sulphur nucleophile on the imine carbon followed
by attack of nitrogen on the carboxylic moiety and finally
intramolecular cyclization with elimination of water involve
2-(2-Nitrophenyl)-3-(naphthalene-1-yl)thiazolidin-4-
one (1a): m.f.: C19H14N2O3S, yield: 43 %, PMR (CDCl3, δ in
ppm): 3.6 (s, 1H, -CH-thiazolidine ring), 5.8 (m, 1H, -CH-
thiazolidine ring), 7.15 (s, 2H, -CH2-naphthalene ring), 7.23

2522 Verma et al.
Asian J. Chem.
R1
R2
O
R1
N
R2
R3
N
C
H
R3
NH2
SHCH2COOH
Anhyd. ZnCl2
CH3COOH
+
OHC
S
(III)
R1
(II)
(I)
R2
R3
IV
R1 = R24 = NO2, OCH3; R3 = R25 = OCH3, OC2H5, Cl, OH, (CH3)2-N-; R4 = OCH3
Fig. 1
(s, 1H, CH-benzene), 8.1 (s, 1H, CH-benzene). IR (KBr, νmax
,
cyclic), 668-602 (C-S-C), 1140 (CO- cyclic), M+1 Peak-
345.50.
2-(3,4-Dimethoxyphenyl)-3-(naphthalene-1-yl)thia-
zolidin-4-one (1e): m.f.: C22H23NO2S, yield: 43 %, PMR (CDCl3,
δ in ppm): 3.6 (s, 1H, -CH-thiazolidine ring), 5.8 (m, 1H, -CH-
thiazolidine ring), 7.15 (s, 2H, -CH2-naphthalene ring), 7.23 (s,
cm-1): 1724 (CO- cyclic), 2950 (CH2-S- cyclic), 1680 (CON-
cyclic), 668-602 (C-S-C), 1140 (CO- cyclic), M+1 Peak-
360.30.
2-(4-Hydroxyphenyl)-3-(naphthalene-1-yl)thiazolidin-
4-one (1b): m.f.: C19H15NO2S, yield: 43 %, PMR (CDCl3,δ in
ppm): 3.6 (s, 1H, -CH-thiazolidine ring), 5.8 (m, 1H, -CH-
thiazolidine ring), 7.15 (s, 2H, -CH2-naphthalene ring), 7.23
1H, CH-benzene), 3.71 (s, 3H-, CH3-benzene). IR (KBr, νmax
,
cm-1): 1724 (CO- cyclic), 2950 (CH2-S- cyclic), 1680 (CON-
cyclic), 668-602 (C-S-C), 1140 (CO- cyclic), M+1 Peak- 375.49.
2-(4-Chlorophenyl)-3-(naphthalene-1-yl)thiazolidin-4-
one (1f): m.f.: C19H14NOSCl, yield: 43 %, PMR (CDCl3, δ
in ppm): 3.6 (s, 1H, -CH-thiazolidine ring), 5.8 (m, 1H, -CH-
thiazolidine ring), 7.15 (s, 2H, -CH2-naphthalene ring), 7.23
(s, 1H- benzene). IR (KBr, νmax, cm-1): 1724 (CO- cyclic), 2950
(CH2-S- cyclic), 1680 (CON- cyclic), 668-602 (C-S-C), 1140
(CO- cyclic), M+1 Peak- 349.50.
(s, 1H, CH-benzene), 5.8 (s, 1H- OH-benzene). IR (KBr, νmax
,
cm-1): 1724 (CO- cyclic), 2950 (CH2-S- cyclic), 1680 (CON-
cyclic), 668-602 (C-S-C), 1140 (CO- cyclic), M+1 Peak-
331.39.
2-(4-Dimethylaminophenyl)-3-(naphthalene-1-yl)-
thiazolidin-4-one (1c): m.f.: C21H20N2OS, yield: 43 %, PMR
(CDCl3, δ in ppm): 3.6 (s, 1H, -CH-thiazolidine ring), 5.8 (m,
1H, -CH-thiazolidine ring), 7.15 (s, 2H, -CH2-naphthalene
ring), 7.23 (s, 1H, CH-benzene), 2.78 (s, 3H- CH3-benzene).
IR (KBr, νmax, cm-1): 1724 (CO- cyclic), 2950 (CH2-S- cyclic),
1680 (CON- cyclic), 668-602 (C-S-C), 1140 (CO- cyclic), M+1
Peak- 359.50.
2-(4-Methoxyphenyl)-3-(naphthalene-1-yl)thiazolidin-
4-one (1d): m.f.: C20-H17NO2S yield: 43 %, PMR (CDCl3,δ in
ppm): 3.6 (s, 1H, -CH-thiazolidine ring), 5.8 (m, 1H, -CH-
thiazolidine ring), 7.15 (s, 2H, -CH2-naphthalene ring), 7.23 (s,
Evaluation of antimicrobial activity: Antimicrobial
activity of the 4-thiazolidinone derivatives were determined by
cup plate method [8] using bacterial strains such as Staphylococcus
aureus, Escherichia coli, Pseudomonas aeurginosa and Bacillus
subtilis and antifungal activity against fungal strain of Candida
albicans [9,10]. Antibiotic ofloxacin was used as standard drug
for determination of antimicrobial activity at concentration of
100 µg/mL [11] and econazole was used as standard drug for
determination of antifungal activity at concentration of 100
µg/mL [12] (Table-1).
1H, CH-benzene), 3.68 (s, 3H- CH3-benzene). IR (KBr, νmax
,
cm-1): 1724 (CO- cyclic), 2950 (CH2-S- cyclic), 1680 (CON-
TABLE-1
ANTIMICROBIAL ACTIVITY OF 4-THIAZOLIDINONE DERIVATIVES
Diameters (mm) of zones of inhibition for microorganism
Compound
Conc. (µg/mL)
100
B. subtilis
15.7
NA
S. aureus
15.5
NA
E. coli
15.7
NA
7.5
P. aeurginosa
15.7
NA
C. albicans
Ofloxacin
Econazole
NA
16.5 0.1
100
100
8.6
7.9
8.5
–
–
–
–
–
–
–
–
–
–
–
–
1a
1b
1c
1d
1e
1f
150
100
150
100
150
100
150
100
12.8
5.2
9.6
9.6
12.8
8.6
14.5
6.7
11.5
5.8
13.3
6.5
4.9
9.2
15.9
7.9
15.7
5.7
10.2
5.7
12.7
4.7
7.9
8.5
15.8
7.5
15.5
5.4
11.4
5.2
12.7
5.3
9.7
9.7
16
8.5
15.1
5.9
15.8
5.9
4.8
150
100
150
10.5
10.2
10.5
*Zone of inhibition were measured as average of triplet; Highly active = Inhibition zone > 12 mm; Moderately active = Inhibition zone 6-12 mm;
Slightly active = Inhibition zone < 6 mm; Not active (NA) = Indicate no zone of inhibition.

Vol. 28, No. 11 (2016)
Synthesis of Some 4-Thiazolidinone Derivatives Containing Polynuclear Hydrocarbon 2523
active at concentration of 150 µg/mL. Almost all compounds
were inactive at concentration of 50 µg/mL.
RESULTS AND DISCUSSION
All the reactions were carried out in dried glassware. Pre-
coated TLC was used for monitoring the progress of reaction
and visualization was done in iodine chamber. The synthesized
compounds were purified using recrystallization/column
chromatography.After physical characterization, the compounds
were subjected to spectral analysis.1H NMR spectra recorded
on Brucker WM-300 at 300 spectrometers, chemical shifts
are reported in parts per million shift (δ-value) from TMS (δ)
as an internal standard. Coupling constant are given in hertz.
Mass spectra were recorded on a JEOL-SX-102 instrument
using direct analysis in real time (DART). FT-IR spectra were
taken on Perkin-Elmer AX-1 spectrometer and values are
expressed in cm-1. Solubility, melting points, Rf values were
determined for each compound.
The synthesized compound 1c was found to be highly active
against S. aureus and P. aerugnosa, E. coli at concentration of
150 µg/mL. Compound 1d was found to be highly active
against E. coli, S. aureus and P. aerugnosa at concentration
of 150 µg/mL and moderately active against B. subtilis at
concentration of 150 µg/mL. Compound 1e was found to be
highly active against P. aeruginosa at concentration of 150
µg/mL and moderately active against E. coli and S. aureus at
concentration of 150 µg/mL. Compound 1f was found to be
moderatly active against B. subtilis and S. aureus at concen-
tration of 150 µg/mL. Compound 1a was found to be slightly
Econazole was used as standard drug for determination
of antifungal activity, which was highly active at concentration
of 100 µg/mL. All the compounds were found to be inactive
against C. albicans. However, compounds having methoxy
group at meta- and para-position, dimethylamino and hydroxyl
group at para-position of was found to be more active against
some microbes.
REFERENCES
1. C.G. Warmath, The Practice of Medicinal Chemistry, edn 2, p. 69 (2004).
2. M.R. Manrao, R.K. Sethi, R.C. Sharma and P.S. Kalsi, J. Indian Chem.
Soc., 73, 695 (1996).
3. R. Yadav, S.D. Srivastava and S.K. Srivastava, Indian J. Chem., 44B,
1262 (2005).
4. D.P. Mehta, N.P.S. Sengar and A.K. Pathak, Oreint. J. Chem., 24, 441
(2008).
5. P.N. Patel and Y.S. Patel, Cogent Chem., 1, 1048558 (2015).
6. M.M. Hania, E-J. Chem., 6, 629 (2009).
7. H. Behbehani and H.M. Ibrahim, Molecules, 17, 6362 (2012).
8. Indian Pharmacopoeia, Ministry of Health and Family Welfare;
Published by Controller of Publications, New Delhi; A101, vol. II (1996).
9. N.S. Ncube, A.J. Afolayan and A.I. Okoh, Afr. J. Biotechnol., 7, 1797
(2008).
10. J.M. Andrews, J. Antimicrob. Chemother., 48(suppl 1), 5 (2001).
11. M. Sultana, S. Arayne and H. Furkan, Pak. J. Pharm. Sci., 18, 59 (2005).
12. M. Chutia, P.D. Bhuyan, M.G. Pathak, T.C. Sarma and P. Boruah, LWT-
Food Sci. Technol., 42, 777 (2009).