Tetrabutylammonium bromide and K 2CO 3: An eco-benign catalyst for the synthesis of 5-Arylidene-1,3-Thiazolidine-2,4-diones via Knoevenagel condensation

Article abstract of DOI:10.1080/17415993.2014.970555

Phase-Transfer catalyzed, energy-efficient and facile synthesis of 5-Arylidene-1,3-Thiazolidine-2,4-diones was developed. Three independent variables (temperature, bases and phase-Transfer catalyst (PTC)) were screened through one-factor-At-A time (OFAT) study. The optimum reaction conditions suggested by the OFAT analysis were the use of tetrabutylammonium bromide (8mol%) and potassium carbonate (1mmol) for the reaction at 100°C. The nitrogen of PTC stabilizes carbonyl groups of thiazolidine-2,4-dione (TZD). The active methylene hydrogen of TZD forms potassium salt with potassium carbonate and generates 5-Arylidene-1,3-Thiazolidine-2,4-diones (1-16) through nucleophilic attack on the carbonyl carbon of arylaldehydes. The prominent advantages of this new process are economic viability, shorter reaction time (15min), simple product isolation (non-chromatographic method), good to excellent yields (78-96%) and solvent-free conditions.

Full text of DOI:10.1080/17415993.2014.970555

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Tetrabutylammonium bromide and
K CO : an eco-benign catalyst for
2
3
the synthesis of 5-arylidene-1,3-
thiazolidine- 2,4-diones via
Knoevenagel condensation
ab
a
a
T. Durai Ananda Kumar , N. Swathi , J. Navatha , C.V.S.
ac
d
Subrahmanyam & K. Satyanarayana
a
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju
College of Pharmacy, Hyderabad 500 090, Telangana State, India
b
Centre for Pharmaceutical Sciences, JNT University, Hyderabad
5
00 085, Telangana State, India
c
Faculty of Pharmacy, Osmania University, Hyderabad 500 007,
Telangana State, India
d
Natco Pharma Ltd, Natco Research Center, B-13, Industrial
Estate, Sanath Nagar, Hyderabad 500 018, Telangana State, India
Published online: 04 Nov 2014.
To cite this article: T. Durai Ananda Kumar, N. Swathi, J. Navatha, C.V.S. Subrahmanyam & K.
Satyanarayana (2015) Tetrabutylammonium bromide and K CO : an eco-benign catalyst for the
2
3
synthesis of 5-arylidene-1,3-thiazolidine- 2,4-diones via Knoevenagel condensation, Journal of
Sulfur Chemistry, 36:1, 105-115, DOI: 10.1080/17415993.2014.970555
To link to this article: http://dx.doi.org/10.1080/17415993.2014.970555
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Journal of Sulfur Chemistry, 2015
Vol. 36, No. 1, 105–115, http://dx.doi.org/10.1080/17415993.2014.970555
Tetrabutylammonium bromide and K CO : an eco-benign
2
3
catalyst for the synthesis of 5-arylidene-1,3-thiazolidine-
,4-diones via Knoevenagel condensation
2
a,b∗
a
a
a,c
T. Durai Ananda Kumar , N. Swathi , J. Navatha , C.V.S. Subrahmanyam
K. Satyanarayana
and
d
a
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Hyderabad 500
b
0
90, Telangana State, India; Centre for Pharmaceutical Sciences, JNT University, Hyderabad 500 085,
c
Telangana State, India; Faculty of Pharmacy, Osmania University, Hyderabad 500 007, Telangana State,
India; Natco Pharma Ltd, Natco Research Center, B-13, Industrial Estate, Sanath Nagar, Hyderabad 500
d
018, Telangana State, India
(Received 19 June 2014; accepted 25 September 2014)
Phase-transfer catalyzed, energy-efficient and facile synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones
was developed. Three independent variables (temperature, bases and phase-transfer catalyst (PTC)) were
screened through one-factor-at-a time (OFAT) study. The optimum reaction conditions suggested by the
OFAT analysis were the use of tetrabutylammonium bromide (8 mol%) and potassium carbonate (1 mmol)
for the reaction at 100°C. The nitrogen of PTC stabilizes carbonyl groups of thiazolidine-2,4-dione (TZD).
The active methylene hydrogen of TZD forms potassium salt with potassium carbonate and generates
5
-arylidene-1,3-thiazolidine-2,4-diones (1–16) through nucleophilic attack on the carbonyl carbon of ary-
laldehydes. The prominent advantages of this new process are economic viability, shorter reaction time
15 min), simple product isolation (non-chromatographic method), good to excellent yields (78–96%) and
(
solvent-free conditions.
Keywords: phase-transfer catalyst; Knoevenagel condensation; 5-arylidene-1,3-thiazolidine-2,4-dione;
OFAT study; green synthesis
*
Corresponding author. Email: anandurai78@gmail.com
This article makes reference to supplementary material available on the publisher’s website at http://dx.doi.org/
0.1080/17415993.2014.970555.
1
ꢀ
c 2014 Taylor & Francis

1
06 T. Durai Ananda Kumar et al.
1. Introduction
Design of benign organic transformations to reduce, eliminate and replace hazardous resources
energy and solvents) is a major concern of green chemistry.[1] Knoevenagel condensation
(
generates carbon–carbon (C–C) bonds and plays a pivotal role in synthetic transformations of
medicinal chemistry research.[2] Knoevenagel condensation is useful in the construction of
clinical candidates [3] such as pioglitazone, rosiglitazone and englitazone (PPARγ agonists),
epalrestat (aldose reductase inhibitor), nifedipine (calcium channel blocker), atorvastatin (HMG-
CoA reductase inhibitor), entacapone (COMT inhibitor), sulindac (anti-inflammatory agent) and
lumefantrin (antimalarial agent).
The Knoevenagel condensation of the active methylene group of thiazolidinone (1,3-
thiazolidine-2,4-dione/rhodanine) and aryl aldehydes generates 5-arylidene-thiazolidinones.
These scaffolds exhibited antidiabetic,[4] antimicrobial [5] and anti-cancer [6] properties. The lit-
erature demonstrates the aldose reductase,[7] β-lactamase,[8] hepatitis C virus protease,[9] JNK
stimulatory phosphatise 1 (JSP 1), [10] tyrosine phosphatase,[11] protein mannosyl transferase
1
(PMT1) [12] and enoyl-acyl carrier protein (enoyl-ACP) reductase [13] inhibitory potentials
of 5-arylidene-thiazolidinones. The representative analogues are under clinical development for
their inhibitory potential against phospholipase A2, cyclooxygenase-2 and 5-lipoxygenase.[14]
The agonistic activity of these molecules on peroxisome proliferator-activated receptor gamma
(PPARγ ) and free fatty acid receptors (FFAR1 and FFAR2) is well appreciated.[15,16]
These prominent properties prompted medicinal chemists to develop a facile and efficient
process for the generation of 5-arylidene-1,3-thiazolidine-2,4-diones. Several bases such as
piperidine,[17] piperidinium acetate,[18] sodium acetate [19] and ammonium acetate [20]
were utilized to accelerate the Knoevenagel condensation. The catalytic function of urea and
thiourea,[16] benzoic acid,[21] polyethylene glycol-300,[22] potash alum,[23] L-proline,[23]
boric acid,[23] oxalic acid,[23] ionic liquids,[24] Bakers yeast,[25] Mg-doped Ce–Zr [26] and
morpholine [27] were utilized in the improved syntheses.
Microwave,[28] ultrasonication [29] and grinding-assisted methods [30] were also utilized to
improve the yield of 5-arylidene-1,3-thiazolidine-2,4-diones. However, these methods are asso-
ciated with limitations, such as low yield, prolonged heating, toxic residues, carcinogenic amines,
expensive catalysts and are of important environmental concern. Hence, an efficient and versa-
tile procedure (mild reaction conditions) to construct 5-arylidene-1,3-thiazolidine-2,4-diones is
in great demand. Phase-transfer catalysts (PTCs) are one of the most powerful greener tools in
fine chemical synthesis.[31]
In light of the above-mentioned facts, the effect of eight PTCs in the synthesis of 5-arylidene-
1,3-thiazolidine-2,4-diones was investigated and were found to be effective promoters.
2. Results and discussion
In continuation of our research interest on PTCs,[32,33] herein we report that the PTC promoted
efficient synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones (Scheme 1) through Knoevenagel
condensation. The condensation of anisaldehyde and 2,4-thiazolidinedione generated 5-(4-
methoxybenzylidene)-1,3-thiazolidine-2,4-dione (compound 1) and was selected as our model
reaction. The effects of temperature, bases and catalysts (PTCs) in the model reaction were
examined. The reaction at room temperature with tetrabutylammonium bromide (TBAB) and
piperidine gave trace yields (detected in TLC) and the reaction at 60°C produced 38% yield
(requires purification). However, the reaction at 100°C gave higher yield (52%) of compound 1.

Journal of Sulfur Chemistry 107
Scheme 1. TBAB catalyzed synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones (1–16).
Table 1. TBAB
catalyzed
condensation
of
4-methoxybenzadehyde
and
thiazolidine-2,4-dione using different bases.
Entry
Bases
Piperidine
Potassium carbonate
Potassium carbonate
Potassium carbonate
Potassium carbonate
Tyrosine
Ammonium acetate
Potassium hydroxide
Potassium phosphate
Triethyl amine
Concentration (mmol)
Yield (%)
1
2
3
4
5
6
7
8
9
7
2
2
1.5
1
0.5
2
2
2
2
2
52
69
81
91
43
Trace*
47
58
Trace*
26
Note: Reaction conditions: 4-methoxybenzadehyde (5 mmol), thiazolidine-2,4-dione (5 mmol), TBAB (10
mol%), heated with stirring at 100°C for 15 min; * = detected in TLC.
At higher temperatures, collision of molecules is appreciable due to their substantial kinetic
energy and enhances the reaction yield.
The effect of seven different bases, namely piperidine, potassium carbonate, tyrosine, ammo-
nium acetate, potassium hydroxide, potassium phosphate and triethyl amine at 2 mmol concen-
tration was studied. In the presence of potassium carbonate, the reaction gave a good yield (69%,
Table 1, entry 2) of compound 1. The reaction with potassium hydroxide, piperidine and ammo-
nium acetate produced fairly good yields (58%, 52% and 47%, respectively), while triethyl amine
produced a very poor yield (26%). However, tyrosine and potassium phosphate gave only trace
yields. Potassium carbonate was chosen as the suitable base from this analysis for further investi-
gation and it was examined at four different concentrations (0.5, 1, 1.5 and 2 mmol). The reaction
with 1 mmol concentration of potassium carbonate gave excellent yield (91%, Table 1, entry 4).
The catalytic potential of eight PTCs, namely TBAB, benzyltriethylammonium chlo-
ride (BTEAC), benzyltrimethylammonium chloride (BTMAC), tetrapropylammonium bromide

1
08 T. Durai Ananda Kumar et al.
Table 2. Condensation of 4-methoxybenzadehyde and thiazo-
lidine-2,4-dione using different PTCs.
Entry
Catalysts
Concentration (mol%)
Yield (%)
1
2
3
4
5
6
7
8
9
TBAB
TBAB
TBAB
TBAB
BTEAC
BTMAC
TPAB
CTAB
TBAI
TPEAC
TEAB
10
12
8
91
72
96
69
51
45
49
21
53
48
37
6
10
10
10
10
10
10
10
10
11
Note: Reaction conditions: 4-methoxybenzadehyde (5 mmol), thiazolidine-2,4-
dione (5 mmol), potassium carbonate (10 mol%), heated with stirring at 100°C
for 15 min.
(TPAB), cetyltrimethylammonium bromide (CTAB), tetrabutylammonium iodide (TBAI), triph-
enylethylammonium chloride (TPEAC) and tetraethylammonium bromide (TEAB) at 10 mol%
was investigated next. The reaction with potassium carbonate (1 mmol) and TBAB (10 mol%)
exhibited the highest catalytic potential (91%, Table 2, entry 1). This analysis permitted the
ranking of catalysts as TBAB > TBAI > BTEAC > TPAB > TPEAC> TEAB > BTMAC>
CTAB. Higher catalytic potential of TBAB, TBAI and BTEAC reactions can be correlated with
their substrate extraction potential (TBAB > TBAI > BTEAC). The reason for the lower cat-
alytic function of CTAB is the high aliphatic load.[34,35] The catalytic potential of TBAB at four
different concentrations (6, 8, 10 and 12 mol%) was explored further. TBAB at 8 mol% in the
presence of potassium carbonate (1 mmol) produced a very high yield (96%, Table 2, entry 3).
Scheme 2. Phase transfer catalysis mechanism involved between the two phases in the Knoevenagel condensation
[14, 26].

Journal of Sulfur Chemistry 109
Further increase in the catalyst concentration did not produce a significant effect on the yield
enhancement.
The synthesis of 5-(4-hydroxybenzylidene)-1,3-thiazolidine-2,4-dione (2) under the hetero-
geneous system (n-butanol and water, 1:1) was performed in order to investigate the substrate
extraction potential of PTC. PTC shuttles between two phases and activates the carbonyl groups
of TZD and aryl aldehydes (Scheme 2). It combines with the active methylene group of TZD
present in the aqueous phase and transfers it into the organic phase (seat of reaction). The
migrated PTC-TZD undergoes nucleophilic attack with aryl aldehydes and produce 5-arylidene-
1,3-thiazolidine-2,4-dione.[14,26] This investigation produced a similar trend to that of the
homogenous reaction (Table 3).
The available literature describes only small-scale synthesis. Hence, the condensation of mul-
tifold concentrations (1, 2, 5 and 10 folds) of 4-hydroxybenzaldehyde and thiazolidine-2,4-dione
under the optimized conditions was carried out to test the utility of the reaction for process
development programs. The trends indicated linearity between 2-fold and 10-fold concentration
2
increases (Table 4). The yields are appreciable and high ( > 69%). The R values of curvelinear
trend (0.9177) and log scale (0.9991) are indicative of the significance of prediction. Therefore,
the present work demonstrates that the optimized conditions can be applied to multifold reaction.
Sixteen 5-arylidene-1,3-thiazolidine-2,4-dione analogues were prepared using the optimized
conditions. The yields of 5-arylidene-1,3-thiazolidine-2,4-diones were found to be in the range
of 78–96% (Table 5). The synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones was compared
with methods reported in the literature (Table 6). All catalysts gave very good yields ( > 82);
however, a few have distinct disadvantages. The major limiting factors are large reaction time and
laborious workup. The toxicological studies revealed the genotoxic nature of urea and thiourea,
which also produce dermatitis.[36,37] Ionic liquids and PEG300 are carcinogenic, while cerrium
Table 3. Condensation of 4-methoxybenzade-
hyde and thiazolidine- 2,4-dione under the hetero-
geneous system using different PTCs.
Entry
Catalysts (8 mol%)
Yield (%)
1
2
3
4
5
6
7
8
TBAB
BTEAC
BTMAC
TPAB
CTAB
TBAI
92
78
71
74
29
85
73
70
TPEAC
TEAB
Note: Reaction conditions: 4-methoxybenzadehyde (5
mmol), thiazolidine-2,4-dione (5 mmol), potassium car-
bonate (10 mol%), refluxed with stirring for 60 min.
Table 4. Multifold synthesis of 5-(4-hydroxybenzylidene)- 1,3-thi-
azolidine-2,4-dione (compound 2) under the optimized conditions.
Entry
Number of folds
Yield (%)
1
2
3
4
1
2
5
91
84
76
69
10
Note: Reaction conditions: 4-hydroxybenzadehyde (5 mmol), thiazolidine-2,4-
dione (5 mmol), TBAB (8 mol%), potassium carbonate (1 mmol), heated with
stirring at 100°C for 15 min

1
10 T. Durai Ananda Kumar et al.
Table 5. TBAB catalyzed synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones (1-16).
Melting range (°C)
Compound code
Ar
Rf
Yield (%)
Observed
Reported (Reference)
1
2
3
4
5
6
7
8
9
4-OCH3C6H4
4-OHC6H4
C6H5
4-Cl–C6H4
0.70
0.68
0.60
0.47
0.64
0.66
0.73
0.64
0.71
0.49
0.72
0.65
0.76
0.70
0.70
0.81
96
91
93
94
90
92
81
95
83
78
87
86
89
84
86
92
214–216
280–281
239–240
222–224
216–217
274–276
219–220
276–277
194–195
234–236
239
281–283
246–248
234–236
228–230
210–212
216–218 (17)
283–285 (26)
240–242 (30)
267–268 (23)
220–221 (17)
282–283 (23)
215–216 (23)
276 (23)
194 (23)
222 (30)
222 (30)
-
4-F–C6H4
4-N,N–CH3–C6H4
2,4-Cl–C6H3
2-OHC6H4
4-OH, 3-OCH3–C6H3
2-Furyl
2-Thienyl
4-NO2–C6H4
3-OHC6H4
3,4-OCH3–C6H3
5-CH3–Furfuryl
2,5-OCH3–C6H3
1
0
1
1
12
13
14
15
16
-
-
-
New
Table 6. Comparison of proposed and literature methods for the synthesis of 5-(4-methoxybenzylidene- 1,3-thiazo-
lidine-2,4-dione (compound 1).
TBAB (8
mol%) +
K2CO3
Urea/
thiourea
(10 mol%)
Mg-doped
Ce–Zr
yeast (2 g) (200 mg)
Catalyst
concentration)
PEG300 (5
mL)
Alum (10
mol%)
Bnmim[Cl]
(0.5 mol)
Bakers
(
Solvent
Solvent free Solvent free Solvent free Water (10 mL) Solvent free Ethanol
Ethanol +
(
30 mL)
water
(
20 mL)
Time (min)
Yield (%)
Reference
Comments
15
96
Present
10
93
Ref. [16]
180
82
Ref. [22]
90
12
94
Ref. [24]
2400
50
90
92
88
Ref. [23]
–
Ref. [25] Ref. [26]
Practicality, Dermatitis, Carcinogenic
Carcinogenic Laborious Expensive
viable
explosive,
genotoxic
work up
and eco
pollutant
and zirconium are expensive.[38,39] In the present method, purification of the compounds is
done through simple washing (non-chromatographic method) with cold toluene–ethanol mixture
(1:1, 1 mL), and this is a major advantage of our method.
3. Conclusion
The utility of PTC in the straight forward synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones by
Knoevenagel condensation was established for the first time. This solvent-free (benign) method-
ology is applicable to a wide range of substrates (aryl aldehydes and heteroaryl aldehydes). This
energy-efficient procedure is consistent with high atom economy (economic viability) of a green
chemistry strategy. The multifold reactions substantiated the utility of this protocol in pharma-
ceutical process chemistry. The attractive features of this new protocol are shorter reaction time,
simple product isolation (non-chromatographic method) and good to excellent yields.

Journal of Sulfur Chemistry 111
4. Experimental section
Melting points were determined in the DBK program melting point apparatus and expressed
in °C and were uncorrected. Aluminum-backed plates coated with silica 60 F254 (Merck) were
used for reactions monitoring by thin layer chromatography. The chromatograms were visualized
under UV light (254 and 366 nm) and by staining with iodine. The structures of the synthesized
1
13
compounds were established using IR, NMR ( H and C) and mass spectra. The IR spectra
were recorded on an IR affinity-1 spectrophotometer (Schimadzu, Japan) using DRS 8000 and
−
1
1
13
are expressed in cm . H NMR and C NMR spectra were recorded on an Avance 300 NMR
spectrophotometer (Bruker, Switzerland). The chemical shifts were reported as parts per million
(δ ppm), using tetramethylsilane as an internal standard. Mass spectrum was recorded on GC-
AccuTOF (Jeol, USA, Inc).
4.1. General method for one-factor-at-a-time investigations
A mixture of anisaldehyde (5 mmol), thiazolidine-2,4-dione (5 mmol), base and PTC loaded
in the 25 ml flat bottom flask was heated with stirring. The reaction mixture was cooled to
room temperature, poured into a beaker containing crushed ice (5 g). The isolated precipitate
was washed with cold toluene–ethanol mixture (1:1, 1 mL) and air dried.
4.2. Phase-transfer catalysis in heterogeneous (liquid–liquid) system
4-Hydroxy benzaldehyde (5 mmol) and thiazolidine-2,4-dione (5 mmol) were dissolved in
n-butanol–water mixture (10 mL, 1:1) loaded in the flask. PTC (8 mol%) and potassium car-
bonate (1 mmol) were added to the flask and refluxed with stirring for 60 min. The organic layer
was washed with water (several times), isolated product was washed with cold toluene–ethanol
mixture (1:1, mL) and air dried.
4.3. Synthesis of 5-arylidene-1,3-thiazolidine-2,4-diones (1–17)
Thiazolidine-2,4-dione was prepared by condensing equimolar quantities of urea and
chloroacetic acid. A mixture of aryl/heteroaryl aldehyde (5 mmol), thiazolidine-2,4-dione (5
mmol) and potassium carbonate (1 mmol) was heated with stirring at 100°C in the presence
of TBAB (8 mol%) for 15 min. The reaction mixture was cooled to room temperature, poured
into a beaker containing crushed ice (5 g). The precipitate was separated by filtration under vac-
uum. The isolated product was washed with cold toluene–ethanol mixture (1:1, 1 mL) and air
dried.
(
5Z)-5-(4-Methoxybenzylidene)-1,3-thiazolidine-2,4-dione (1): FT-IR (KBr, cm−1): 3226
(
NH symmetric stretching), 3050 (ArCH stretching), 1728 (C=O stretching), 1696 (C=O
stretching), 1510 (C=C stretching), 1340 (C−O−C stretching), 1317 (C−N stretching), 701
1
(
7
(
C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 11.72 (s, 1H, NH), 7.43 (s, 1H, =CH),
.08 (d, 2H, J = 6.0 Hz, Ar-H), 6.62 (d, 2H, J = 6.0 Hz, Ar-H), 2.70 (s, 3H, OCH3). MS m/z
+
%): 235.07 (M ,3), 164 (34), 149 (44), 121 (48), 93 (23), 77 (73), 69 (4).
(
5Z)-5-(4-Hydroxybenzylidene)-1,3-thiazolidine-2,4-dione (2): FT-IR (KBr, cm−1): 3428
(
OH stretching), 3162 (NH symmetric stretching), 3033 (ArCH stretching), 1739 (C=O stretch-
ing), 1681 (C=O stretching), 1365 (C−N stretching), 1281 (C−O−C stretching), 676 (C−S−C
1
stretching). H NMR (300 MHz, DMSO-d6): δ 9.70 (brs, 2H, OH phenolic, TZD-NH), 7.58 (s,
1
3
1
H, =CH), 7.40 (d, 2H, J = 8.49 Hz, Ar-H), 6.87 (d, 2H, J = 8.49 Hz, Ar-H). C NMR (300
MHz, DMSO-d6): δ 116.34 (1C, =CH), 119.02 (1C, C5, TZD ring), 123.95 (C4, Ar), 132.38

112 T. Durai Ananda Kumar et al.
(
−
2C, C2, C5, Ar), 159.90 (2C, C5, C6, Ar), 167.54 (1C, −C=O, C2 of TZD ring), 168.09 (1C,
+
C=O, C of TZD ring); MS m/z (%): 221 (M , 24), 150 (100), 121 (20), 77 (9), 69 (15),
4
55 (17).
(
5Z)-5-Benzylidene-1,3-thiazolidine-2,4-dione (3): FT-IR (KBr, cm−1): 3223 (NH symmet-
ric stretching), 3034 (ArCH stretching), 1698 (C=O stretching), 1632 (C=O stretching), 1431
1
(
1
C−N−C stretching), 638 (C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 12.63 (s,
H, NH), 7.80 (s, 1H, =CH), 7.59–7.61 (d, 2H, J = 8.49 Hz , Ar-H), 7.48–7.56 (m, 3H, Ar-H);
+
MS m/z (%): 205 (M , 4), 134 (72), 108 (9), 89 (37), 63 (46).
(
5Z)-5-(4-Chlorobenzylidene)-1,3-thiazolidine-2,4-dione (4): FT-IR (KBr, cm 1): 3189 (NH
−
symmetric stretching), 3021 (ArCH stretching), 1712 (C=O stretching), 1688 (C=O stretching),
1
1
(
465 (C−N stretching), 634 (C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 12.50
s, 1H, NH), 7.73 (s, 1H, =CH), 7.52 (d, 2H, J = 8.82 Hz, Ar-H), 7.06 (d, 2H, J = 7.11 Hz,
Ar-H.
(
5Z)-5-(4-Fluorobenzylidene)-1,3-thiazolidine-2,4-dione (5): FT-IR (KBr, cm−1): 3128 (NH
symmetric stretching), 3043 (ArCH stretching), 1753 (C=O stretching), 1698 (C=O stretching),
1
1
443 (C−N stretching), 1146 (C−F stretching), 639 (C−S−C stretching). H NMR (300 MHz,
DMSO-d6): δ 12.61 (s, 1H, NH), 7.79 (s, 1H, =CH), 7.34–7.68 (m, 4H, Ar-H). MS m/z (%):
+
2
23.12 (M , 12), 222.08 (100).
(
5Z)-5-[4-(Dimethylamino)benzylidene]-1,3-thiazolidine-2,4-dione (6): FT-IR (KBr, cm−1):
3
109 (NH symmetric stretching), 3007 (ArCH stretching), 1725 (C=O stretching), 1680 (C=O
1
stretching), 1517 (C=C stretching), 1340 (C−N stretching), 647 (C−S−C stretching). H NMR
(
6
1
300 MHz, DMSO-d6): δ 12.30 (s, 1H, NH), 7.65 (s, 1H, =CH), 7.39 (d, 2H, J = 9 Hz, Ar-H),
+
.78 (d, 2H, J = 8.73 Hz, Ar-H), 3.00 (s, 6H, N,N−CH3). MS m/z (%): 248 (M , 35), 177 (100),
61 (15), 134 (12), 89 (24), 63 (10).
(
5Z)-5-(2,4-Dichlorobenzylidene)-1,3-thiazolidine-2,4-dione (7): FT-IR (KBr, cm−1): 3447
1
(
NH), 3038 (=CH), 1675 (C=O), 1616 (C=O), 1431 (C−N), 645 (C−S). H NMR (300 MHz,
DMSO-d6): δ 12.79 (s, 1H, NH), 7.83 (s, 1H, =CH), 7.54 (m, 3H, Ar-H). MS m/z (%): 275. 99
+
(
M , 15), 274.05 (63), 272.04 (100).
(
5Z)-5-(2-Hydroxybenzylidene)-1,3-thiazolidine-2,4-dione (8): FT-IR (KBr, cm 1): 3421
−
(
NH symmetric stretching), 3030 (ArCH stretching), 1776 (C=O stretching), 1678 (C=O
stretching), 1454 (C=C stretching), 1334 (C−O−C stretching), 1247 (C−N stretching), 748
1
(
8
1
C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 12.47 (s, 1H, NH), 10.51 (s, 1H, OH),
+
.01 (s, 1H, =CH), 7.31 (t, 2H, Ar-H), 6.97 (q, 2H, Ar-H). MS m/z (%): 221 (M , 11), 196 (8),
78 (12), 150 (24), 121 (55), 107 (77), 91 (100), 78 (75), 65 (30).
(
5Z)-5-(4-Hydroxy-3-methoxybenzylidene)-1,3-thiazolidine-2,4-dione (9); FT-IR (KBr,
−
1
cm ): 3480 (OH stretching), 3192 (NH symmetric stretching), 3034 (ArCH stretching), 1737
1
(
C=O), 1678 (C=O), 1516 (C=C), 1290 (C−O−C stretching). H NMR (300 MHz, DMSO-
d6): δ 9.77 (br, s, 2H, OH, NH), 7.57 (s, 1H, =CH), 7.15 (d, 1H, J = 1.6 Hz, Ar-H), 7.02 (dd,
+
J = 1.6, 1.6 Hz, 1H, Ar-H), 6.87 (d, 2H, J = 8.00 Hz, Ar-H); MS m/z (%): 251.1 (M , 12),
2
50.1 (100).
(
5Z)-5-(Furan-2-ylmethylidene)-1,3-thiazolidine-2,4-dione (10); FT-IR (KBr, cm−1): 3123
(
NH symmetric stretching), 3032 (ArCH stretching), 1728 (C=O stretching), 1681 (C=O
1
stretching), 1475 (C−N stretching), 1284 (C−O−C stretching), 685 (C−S−C stretching). H
NMR (300 MHz, DMSO-d6): δ 12.44 (s, 1H, NH), 8.03 (s, 1H, =CH), 7.06-7.59 (m, 3H, Ar-H).
+
MS m/z (%): 195 (M , 8), 124 (100), 96 (57), 69 (52).
(
5Z)-5-(Thiophen-2-ylmethylidene)-1,3-thiazolidine-2,4-dione (11): FT-IR (KBr, cm 1):
−
3
124 (NH symmetric stretching), 3045 (ArCH stretching), 1732 (C=O stretching), 1681 (C=O
1
stretching), 1595 (C=C stretching), 1415 (C−N stretching), 634 (C−S−C stretching). H NMR
(
300 MHz, DMSO-d6): δ 12.55 (s, 1H, NH), 8.04 (s, 1H, =CH), 7.98 (d, 1H, J = 4.98 Hz, Ar-
+
H), 7.65 (d, 1H, J = 3.48 Hz, Ar-H), 7.25 (q, 1H, Ar-H). MS m/z (%): 211 (M , 2), 140 (26), 96
(
17), 82 (30), 69 (48).

Journal of Sulfur Chemistry 113
(
5Z)-5-(4-Nitrobenzylidene)-1,3-thiazolidine-2,4-dione (12): FT-IR (KBr, cm−1): 3268 (NH
symmetric stretching), 3034 (ArCH stretching), 1678 (C=O stretching), 1610 (C=O stretching),
1
1
1
411 (C−N stretching), 631 (C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 12.75 (s,
H, NH), δ 8.32 (d, 2H, J = 8.8 Hz, Ar-H), 7.91 (s, 1H, =CH), 7.83 (d, 2H, J = 8.40 Hz, Ar-H).
−
1
(
5Z)-5-(3-Hydroxybenzylidene)-1,3-thiazolidine-2,4-dione (13): FT-IR (KBr, cm ): 3302
(
NH symmetric stretching), 3070 (ArCH stretching), 1753 (C=O stretching), 1691 (C=O
stretching), 1591 (C=C stretching), 1448 (C−O−C stretching), 1236 (C−N stretching), 790
1
(
7
C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 9.89 (s, 1H, NH), 7.65 (s, 1H, =CH),
.30 (s, 1H, OH), 7.02 (d, 2H, J = 9 Hz, Ar-H), 6.87 (s, 1H, Ar-H).
(
5Z)-5-(3,4-Dimethoxybenzylidene)-1,3-thiazolidine-2,4-dione (14): FT-IR (KBr, cm−1):
3
216 (NH symmetric stretching), 3044 (ArCH stretching), 1731 (C=O stretching), 1693 (C=O
stretching), 1501 (C=C stretching), 1332 (C−O−C stretching), 1315 (C−N stretching), 714
1
(
7
C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 12.52 (s, 1H, NH), 7.75 (s, 1H, =CH),
.17 (d, 2H, J = 6.8 Hz, Ar-H), 7.11 (d, 2H, J = 12.0 Hz, Ar-H), 3.81 (s, 6H, 3,4-OCH3). MS
+
m/z (%): 265.2 (M , 23), 264.1 (100).
(
5Z)-5-[(5-Methylfuran-2-yl)methylidene]-1,3-thiazolidine-2,4-dione (15): FT-IR (KBr,
−
1
cm ): 3185 (NH symmetric stretching), 3037 (ArCH stretching), 1681 (C=O stretching), 1616
(
C=O stretching), 1411 (C−N stretching), 1284 (C−O−C stretching), 686 (C−S−C stretch-
1
ing). H NMR (300 MHz, DMSO-d6): δ 12.41 (s, 1H, NH), δ 8.03 (s, 1H, =CH), δ 7.13 (d, 2H,
+
J = 8.70 Hz, Ar-H), δ 2.71 (s, 3 H, CH3). MS m/z (%): 209 (M , 30), 138 (100), 109 (10), 95
(
15), 81 (13), 69 (7), 51 (9).
(
5Z)-5-(2,5-Dimethoxybenzylidene)-1,3-thiazolidine-2,4-dione (16): FT-IR (KBr, cm−1):
3
444 (NH symmetric stretching), 3028 (ArCH stretching), 1732 (C=O stretching), 1680 (C=O
stretching), 1591 (C=C stretching), 1344 (C−O−C stretching), 1220 (C−N stretching), 680
1
(
7
2
C−S−C stretching). H NMR (300 MHz, DMSO-d6): δ 12.85 (s, 1H, NH), 7.89 (s, 1H, =CH),
.06 (s, 2H, Ar-H), 6.89 (s, 1H, Ar-H), 3.81 (s, 3H, OCH3), 3.73 (s, 3H, OCH3); MS m/z (%):
+
65 (M , 100), 179 (100), 151 (23), 136 (23), 108 (12), 97 (17), 82 (13), 69 (5).
Acknowledgements
The authors are thankful to the President, Gokaraju Rangaraju Educational Society, Hyderabad and the Chairman, Natco
Pharma Ltd, Hyderabad, for providing the necessary facilities.
Supplemental data
Supplemental data for this article can be accessed at 10.1080/17415993.2014.970555.
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