Synthesis and Evaluation of Thiazolidinone Derivatives
Letters in Drug Design & Discovery, 2011, Vol. 8, No. 1 83
MATERIALS AND METHODS
Chemistry
dry toluene (10 mL). Then mercaptoacetic acid (0.010 mol)
was added and the mixture was refluxed for further 15 h.
Further treatments were the same as given under general
procedure. Yield: 38%; IR (KBr, in cm-1): 1685.56(C=O
Melting points of the compounds were determined using
an open-ended capillary method and are uncorrected. The
purity of the synthesized compounds was checked by TLC.
UV/VIS spectra were taken in a Schimadzu UV/VIS 1700
spectrophotometer. FT-IR was recorded on a Jasco FT-IR
1
str.), 1438.80 (ring C=C str.), 1372 (Ar-C-N str.),; HNMR
(DMSO d6, ꢀ in ppm): 4.10 (d, 1H, J = 15.7 Hz, 5-HA), 4.22
(dd, 1H, J = 15.7 and 1.6 Hz, 5-HB), 6.03 (s, 1H, H-2), 8.12-
8.36 (m, 8H, ArH); Mass: 272 (M+H)+.
1
spectrophotometer, HNMR spectra were recorded at 300
3-(4-Chloro-phenyl)-2-pyridin-2-yl-thiazolidin-4-one [3]
MHZ on a Bruker FT-NMR spectrophotometer and mass
spectra on a Varian Atlas CH-7 mass spectrophotometer at
70 ev. The elemental analysis was obtained on a Vario-EL
instrument.
Mixture of 4-chloroaniline (0.005 mol) and pyridine-2-
aldehyde (0.005 mol) was stirred under reflux for 2.5 h in
dry toluene (10 mL). Then mercaptoacetic acid (0.010 mol)
was added and the mixture was refluxed for further 25 h.
Further treatments were the same as given under general
procedure. Yield: 40%; IR (KBr, in cm-1): 1693.13(C=O
str.), 1472.70 (ring C=C str.), 1362.86 (Ar-C-N str.);
1HNMR (DMSOd6, ꢀ in ppm): 3.80 (d, 1H, J = 15.6 Hz, 5-
HA), 4.11 (dd, 1H, J = 15.6 and 1.6 Hz, 5-HB), 5.90 (s, 1H,
H-2), 6.54-6.83 (m, 6H, ArH), 7.58-7.86 (m, 2H, ArH);
Mass: 292 (M+H)+.
General Procedure for Synthesis of 1,3-Thiazolidin-4-
Ones
Derivatives of 1,3-thiazolidin-4-one was synthesized
with slight modification in the method reported by Rawal et
al. (2007) [13]. The appropriate (hetero) aromatic amine
(0.005 mol) and appropriate (hetero) aromatic aldehyde
(0.005 mol) was stirred under reflection for 0.5 - 2.5 h in dry
benzene/toluene (10 mL). Mercaptoacetic acid (0.010 mol)
was added and the mixture was refluxed for further 3 - 45 h
(Scheme 1). The reaction was monitored by TLC (Mobile
phase: Cyclohexane and ethyl acetate 8:2, spots were visual-
ized by exposing them to iodine vapor). After completion of
the reaction, the reaction mixture was concentrated to dry-
ness under reduced pressure and the residue was taken up in
ethyl acetate. The organic layer was successively washed
with 5% aqueous citric acid, water, 5% sodium hydrogen
carbonate, and then finally with brine. The organic layer was
dried over sodium sulfate, filtered and solvent was removed
under reduced pressure to get crude (solid or oily) product.
The oily residue was solidified by treatment with a mixture
of ethanol and diethyl ether. All the compounds were recrys-
tallized from ethanol. The synthesized compounds were
found highly to be soluble in DMSO, soluble in DMF,
CHCl3, ethanol and methanol, and sparingly soluble in water.
The structures of synthesized compounds were elucidated by
3-(4-Chloro-phenyl)-2-(3-nitro-phenyl)-thiazolidin-4-one
[4]
Mixture of 4-chloroaniline (0.005 mol) and 3-
nitrobenzaldehyde (0.005 mol) was stirred under reflux for 2
h in dry toluene (10 mL). Then mercaptoacetic acid (0.010
mol) was added and the mixture was refluxed for further 35
h. Further treatments were the same as given under general
procedure. Yield: 43%; IR (KBr, in cm-1): 1709 (C=O str.),
1458.89 (ring C=C str.), 1362 (Ar-C-N str.); 1HNMR
(CDCl3, ꢀ in ppm): 3.98 (d, 1H, J = 15.3 Hz, 5-HA), 4.18 (d,
1H, J = 15.3 Hz, 5-HB), 6.06 (s, 1H, H-2), 7.29-7.66 (m, 6H,
ArH), 7.93-8.02 (m, 2H, ArH); Mass: 336 (M+H)+.
2,3-Bis-(4-chloro-phenyl)-thiazolidin-4-one [5]
Mixture of 4-chloroaniline (0.005 mol) and 4-
chlorobenzaldehyde (0.005 mol) was stirred under reflux for
2 h in dry benzene (10 mL). Then mercaptoacetic acid (0.010
mol) was added and the mixture was refluxed for further 33
h. Further treatments were the same as given under general
procedure. Yield: 45%; IR (KBr, in cm-1): 1694.16 (C=O
1
means of FTIR, HNMR, FAB-MS and elemental analyses.
The results of elemental analyses for N and S were found to
be within ± 0.4% of the theoretical values.
1
str.), 1490 (ring C=C str.), 1365 (Ar-C-N str.); HNMR
(CDCl3, ꢀ in ppm):
3.96 (d, 1H, J = 15.5 Hz, 5-HA),
4.10 (d, 1H, J = 15.5 Hz, 5-HB), 6.26 (s, 1H, H-2), 6.48-6.53
2-(4-Chloro-phenyl)-3-(6-methyl-pyridin-2-yl)-thiazolidin-
4-one [1]
(m, 2H, ArH), 7.08-7.34 (m, 5H, ArH); Mass: 325 (M+H)+.
Mixture of 6-methyl-2-aminopyridine (0.005 mol) and 4-
chlorobenzaldehyde (0.005 mol) was stirred under reflux for
2 h in dry benzene (10 mL). Then mercaptoacetic acid was
(0.010 mol) was added and the mixture was refluxed for fur-
ther 30 h. Further treatments were the same as given under
general procedure. Yield: 42%; IR (KBr, in cm-1): 2964 (C-H
str. for CH3), 1683.30 (C=O str.), 1493.32 (ring C=C str.),
1355 (Ar-C-N str.), 1270 (C-O-C Str.); 1HNMR (CDCl3, ꢀ in
ppm): 2.55 (s, 3H, OCH3), 3.89 (d, 1H, J = 15.7 Hz, 5-HA),
4.15 (dd, 1H, J = 15.7 and 1.9 Hz, 5-HB), 5.94 (s, 1H, H-2),
6.92-7.98 (m, 7H, ArH); Mass: 306 (M+H)+.
3-(4-Chloro-phenyl)-2-(4-hydroxy-3-methoxy-phenyl)-
thiazolidin-4-one [6]
Mixture of 4-chloroaniline (0.005 mol) and 4-hydroxy-3-
methoxy benzaldehyde (0.005 mol) was stirred under reflux
for 2 h in dry benzene (10 mL). Then mercaptoacetic acid
(0.010 mol) was added and the mixture was refluxed for fur-
ther 24 h. Further treatments were the same as given under
general procedure. Yield: 32%; IR (KBr, in cm-1): 3480 (-
OH str.), 1695.12 (C=O str.), 1462.74 (ring C=C str.),
1
1218.65 (C-O-C str. for -C-O-CH3); HNMR (CDCl3, ꢀ in
ppm): 3.78 (s, 3H, OCH3), 3.86 (d, 1H, J = 15.7 Hz, 5-HA),
4.16 (d, 1H, J = 15.7 Hz, 5-HB), 5.12 (s, 1H, -OH), 5.94 (s,
1H, H-2), 6.82-7.06 (m, 7H, ArH); Mass: 337 (M+H)+.
3-(2 -pyridin-2-yl)-2-pyridin-2-yl-thiazolidin-4-one [2]
Mixture of 2-aminopyridine (0.005 mol) and pyridine-2-
aldehyde (0.005 mol) was stirred under reflux for 0.5 h in