Journal of the Iranian Chemical Society, Vol. 3, No. 3, September 2006, pp. 233-241.
JOURNAL OF THE
Neat Reaction Technology for the Synthesis of 4-Oxo-thiazolidines Derived from
2-SH-Benzothiazole and Antimicrobial Screening of Some Synthesized
K.G. Desai a,*, J.P. Ravalb and K.R. Desaic
aDepartment of Chemistry, Faculty of Science, Synthetic Organic Chemistry Research Laboratory,
Veer Narmad South Gujarat University, Surat, Gujarat State, India
bIndustrial Chemistry Division, Department of Chemistry, V.N.S.G. University, Surat, Gujarat State, India
cChemistry Department, Organic Chemistry Division, Faculty of Science, V. N.S.G. University, Surat,
Gujarat State, India
†This paper is dedicated to Prof. K.R. Desai in recognition of his outstanding contributions to “Green Chemistry”
(Received 8 April 2006, Accepted 2 May 2006)
The synthesis of 4-thiazolidinones 4a-j in a good yields from the heterocyclization reaction of 2-(benzothiazol-2-ylthio)-
N'-benzylideneacetohydrazide 3a-j with SHCH2COOH in DMF in the presence of a catalytic amount of anhydrous ZnCl2
under microwave irradiation is described and compared with conventional synthesis methods. All structures of the newly
synthesized compounds were elucidated by elemental analysis and spectral data. Some of the new compounds were tested
against bacteria (Gram– ve and Gram+ ve) and fungi.
Keywords: 4-Thiazolidinones, Heterocyclization, Microwave effect, Antimicrobial activity
proving the synthetic utility of MORE chemistry in routine
organic synthesis [10,11]. It can be termed “e-chemistry”
because it is easy, effective, economical and eco-friendly
and is believed to be a step toward green chemistry.
following earlier reported applications of MORE [15-18]
chemistry, we now report a novel, environmentally benign
approach using a facile, ZnCl2-mediated microwave
synthesis of 4-thiazolidinones.
Regents, Instrumentation and Measurements
catalyst were of analytical grade and used directly. All the
melting points were determined using a PMP-DM scientific
melting point apparatus and are uncorrected. The purity of
compounds was checked routinely by thin layer
2-Mercaptobenzothiazole derivatives are known to
possess various biological activities . 4-Thiazolidinones
are also well known for versatile pharmacological activities
such as hypnotic , anaesthetic , antifungal ,
anthelmintic , and antiviral  agents, as well as CNS 
stimulants. The incorporation of the 4-oxothiazolidine
moiety into a 2-mercaptobenzothiazole scaffold enhances its
activity . The synthetic route of the abovementioned
compounds is shown in Scheme 1.
In the last few years, microwave-induced organic
reaction enhancement (MORE) chemistry has gained
popularity as a non-conventional technique for rapid
synthesis  and many researchers have described
accelerated organic reactions, with a large number of papers
*Corresponding author. E-mail: email@example.com
Under the framework of green chemistry [12-14], and
All reagents, 2-mercaptobenzothiazole, solvents and
Desai et al.
chromatography (TLC) using silica gel-G coated Al-plates
(0.5 mm thickness, Merck) and spots were visualized by
exposing the dry plates to iodine vapor. IR spectra (υmax in
cm-1) were recorded on a Shimadzu FT-IR 8300
spectrophotometer using KBr or the Nujol technique; 1H
NMR spectra were acquired on a Bruker WM 400FT 400
MHz NMR spectrometer using CDCl3 or DMSO-d6 as the
solvent and TMS as the internal reference (chemical shifts in
ppm); 13C NMR was performed on a Varian AMX 400 (100
MHz) spectrometer using solutions in CDCl3 and mass
spectra were acquired on a Jeol JMS D-300 spectrometer
operating at 75 eV. The elemental analysis (C, H, N) of
compounds was performed on Carlo Erba-1108 elemental
analyzer. Their results were found to be in good agreement
with the calculated values. The microwave assisted reactions
were carried out using a QPro-M Microwave Sample
Preparation System (Questron Technologies Corporation,
Mississauga, Ontario, Canada), wherein microwaves are
generated by magnetron at a frequency of 2450 MHz having
an output energy range of 100 to 500 watts and an infrared
sensor for temperature control with an attached reflux
condenser with constant stirring (to avoid the risk of high
pressure development). The QPro-M apparatus used, as
shown in Fig. 1, was especially well-suited for stringent
reaction conditions, including anhydrous atmosphere.
(benzothiazolylthio)acetate (1). Mercaptobenzothiazole
of ethyl 2-
(0.01 mol, 1.67 g) and ethylchloroacetate (0.01 mol, 1.22
ml) in dry acetone (4 ml) in the presence of anhydrous
K2CO3 (1 g) were placed in a round bottom flask and
microwave irradiated (300 W, 61-62 oC) for 4.0 min [21,22].
Upon completion of the reaction (monitored by TLC), the
reaction mixture was allowed to cool to room temperature
and the treated with cold water. The separated solid was
filtered, washed with water and recrystallized from
chloroform to furnish compound 1, yield 76%, as a white
crystal. m.p.: 58-59 oC. Anal.: Calcd. for C11H11NO2S2: C,
52.18; H, 4.22; N, 5.40. Found: C, 52.16; H, 4.23; N, 5.38%;
IR: ν (cm-1) 3023 (aromatic ring), 1070 (aliphatic ether), 638
(C-S), 1723 (>C=O of ester), 1614 (-C=N-), 1223 and 1041
(C-O-C), 721 (C-S-C) and 2915, 2871, 1423, 713 (-CH2 and
-COOCH2CH3), 4.13 (q, 2H, J = 7 Hz, -COOCH2CH3), 4.46
(s, 2H, S-CH2-), 6.73-7.87 (m, 4H, Ar-H).
(benzothiazolylthio)acetate (1). An equimolar solution of
2-mercaptobenzothiazole (0.01 mol, 1.67 g) and ethyl
chloroacetate (0.01 mol, 1.22 ml) in dry acetone (4 ml) in
the presence of anhydrous K2CO3 (1 g) was refluxed on a
water bath for 16 h. The solvent was removed by vacuum
distillation and the residue was recrystallized from
chloroform to furnish compound 1, yield 66%, as a white
solid. m.p.: 58-59 oC.
Microwave-mediated synthesis of 2-(benzothiazol-2-
1H NMR: δ (ppm) 1.23 (t, 3H, J = 7 Hz,
of ethyl 2-
a) ClCH2COOC2H5, anhydrous K2CO3, dry acetone; b) NH2NH2, ethanol; c) substituted aromatic aldehyde,
2-3 drops of gl. AcOH, ethanol; d) SHCH2COOH, anhydrous ZnCl2, DMF.
Neat Reaction Technology for the Synthesis of 4-Oxo-thiazolidines
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