SYNTHESIS AND CHARACTERIZATION OF SOME 4-SUBSTITUTED THIAZOLIDINONE DERIVATIVES

This study is concerned with the synthesis and characterization of 4-thiazolidinone derivatives )3a-3h(. These compounds were prepared by reacting mercaptoacetic acid with the appropriate Schiff bases (imines) by heating at 50-60 °C in chloroform with moderate yields (5175 %). The structures of these 4-thiazolidinone derivatives were established on the basis of the spectral studies using IR, H-NMR, CNMR, C-NMR DEPT and MS.


INTRODUCTION
Thiazolidinones are ketone derivatives and are of the saturated form of thiazol (called thiazolidin). 1,3-thiazidolidin-4-one can be described as a heterogeneous pentagonal ring consisting of five members including one nitrogen atom and one sulfur, as shown in Figure 1.
Thiazolidinones and their derivatives presentation a large variety of activities such as antibiotic, diuretic, tuberculostatic, organoleptic, antileukaemic and antiparasitical. 1,2 As far as literature is concerned, little is known about thiazolidinones and their bioactivity. The chemistry of thiazolidin-4-one ring system is a considerable interest because it is the core structure in various synthetic pharmaceuticals, whose display a broad spectrum of biological activities. These heterocyclic compounds are having an atom of sulfur at position 1, an atom of nitrogen at position 3, and a carbonyl group at position 4. 3 The substitution can be done at positions 2, 3, and 5, the greatest difference in structure and properties is exerted by the group that will be attached with the carbon atom in position 2 Figure 2 The carbonyl group present in the moiety is highly unreactive.

EXPERIMENTAL PART
The 1H-NMR spectra were recorded using VARIAN spectrophotometer (500 MHz), the 13C-NMR spectra were recorded using a VARIAN spectrophotometer (75 MHz). The chemical shift values are expressed in δ (ppm), using tetramethylsilane (TMS) as internal standard and d6-DMSO as the solvent.

Preparation of mono-imines (2a-2c).
In general, the mono-imines (2a-2c) were prepared by the reaction of the mixture of 0.01 mol amine with 0.01 mol aldehyde in 20 ml of methanol or ethanol and 4-6 drops of glacial acetic acid. The reaction mixture was refluxed for 0.5-9 hours, and the progress of the reaction was followed by TLC using hexane:ethyl acetate 7:3 as eluent. After completion the reaction, the solvent was evaporated, and the residue was recrystallized from a suitable solvent.

Preparation of mono thiazolidinones (3a-3c)
A mixture of appropriate Schiff bases (0.01 mol) (2a-2c) and thioglycolic acid (0.01 mol, 0.20 ml) in a suitable solvent (50) ml was refluxed for 10-30 hours. Water formed during the reaction was removed azeotropically by a Dean-Stark apparatus. The progress of the reaction was monitored by TLC using hexane:ethyl acetate 6:4 as eluent. This mixture of reaction are treated with sodium bicarbonate solution to remove unreacted acid. The obtained solids were filtered, washed and purified by recrystallization from dichloromethane to give color powders.

Preparation of bis thiazolidinones (3d-3e)
A mixture of appropriate Schiff bases (0.02 mol) (2d-2e) and thioglycolic acid (0.02 mole, 0.40 mL) in a suitable solvent (50 ml) was refluxed for 10-30 h, water formed during the reaction was removed azeotropically by a Dean-Stark apparatus. The progress of the reaction was checked by TLC using hexane : ethyl acetate 6:4 as eluent . This mixture of reaction was treated with sodium bicarbonate solution to remove unreacted acid. The obtained solid was filtered, washed and purified by recrystallization from dichloromethane to give color powder.

RESULTS AND DISCUSSION
Thiazolidinones 3a-3e have been prepared by reaction of the appropriate Schiff bases (2a to 2e) with thioglycolic acid in a suitable solvent (benzene or chloroform).

Analysis of infrared spectra
The IR spectra of thiazolidinones 3a to 3e in KBr disk show six band groups correspond to the stretching vibration of the aromatic C-H, aliphatic C-H, carbonyl amide group, aromatic C=C, the C-N and bending vibration of S-C bonds, occur within the ranges 3107-2980, 2975-2887, 1691-1654, 1399- 1361, 738-654, and 925-617 cm-1 respectively. The absorption frequencies are affected by substitution of the phenyl ring, and the substitution by electron-donating groups (methyl group decreases) while substitution by electron-withdrawing groups (flouro) increase the vibrational frequencies.

Analysis of 13C-NMR spectra
The 13C NMR spectrum of 3a showed thiazolidin-4-one ring signals at δ 36 ppm for C5 carbon 5) at δ 49.94 ppm for C2 atom. A multiplet for aromatic carbons at δ 107-139 ppm, a singlet of carbonyl group at δ 177.06 ppm and a signal for C4 carbon of the ring were observed at δ 179.78 ppm.