Synthesis and structures of some new thiazolidin-4-ones and thiazolin-4-ones of anticipated biological activity

The condensation of ω-(4-formylphenoxy)acetophenone (3a) and its 4-bromo derivative (3b) with 2-thioxo-1,3-thiazolidin-4-one (4a) and 1,3-thiazolidin-2,4-dione (4b) in refluxing acetic acid in the presence of sodium acetate gave new E-5-arylmethylene-2-thioxo-1,3-thiazolidin-4one (5a and 5b) and E-1,3-thiazolidin-2,4-dione (5c and 5d) derivatives in good yields, respectively. However, treatment of E-(5a and 5b) with piperidine (or morpholine) in refluxing ethanol afforded new E-5-arylmethylene-2-piperidinyl (or morpholinyl)-1,3-thiazolin-4-one derivatives (6a-d). The structures of all new compounds were established from microanalytical and spectral data.


Results and Discussion
The aldehydes 3a and 3b were prepared by etherfication of ω-bromoacetophenone (1a) and its 4bromo derivative (1b) with 4-hydroxybenzaldehyde (2) in refluxing dry acetone in the presence of anhydrous K 2 CO 3 .

+ CHO O H
(1) a, R = H b, R = Br The aldehydes 3a and 3b were allowed to condense with 2-thioxo-1,3-thiazolidin-4-one (4a) and 1,3-thiazolidin-2,4-dione (4b) in refluxing glacial acetic acid in the presence of sodium acetate for 6 h to afford E-5-arylmethylene-2-thioxo-1,3-thiazolidin-4-one (5a and 5b) and E-5arylmethylene-1,3-thiazolidin-2,4-dione (5c and 5d) derivatives, respectively, in good yields.The structures of compounds E-(5a-d) were substantiated from microanalytical and spectral data.Thus, the infrared spectra showed absorptions characteristic for NH, C=O and C=S groups in addition to other absorptions correlated to the assigned structures.Further, the 1 H NMR spectra showed signals corresponding to methylene, olefinic, aromatic and NH protons.Also, the EI-MS showed correct molecular ion peaks beside some of the abundant fragments.In addition, evidence to support the structural assignment was gained from the 13 C NMR spectrum of compound 5a.
The structures of compounds E-(6a-d) were elucidated from micro-analytical and spectral data.Thus, the infrared and 1 H NMR spectra showed absorptions correlated with the assigned structures.Moreover, the EI-MS showed correct molecular ion peaks in addition to some of the abundant peaks.
The formation of compounds E-(6a-d) can be explained on the basis of a nucleophilic attack of piperidine or morpholine upon the C=S group followed by elimination of hydrogen sulfide.
The E-configuration was assigned to structures 5 and 6 on the basis that a previous study [8] from this laboratory had identified the E-and Z-isomers of analogous 5-arylmethylene compounds.It was shown that, the olefinic proton of the Z-configured isomers were more deshielded by the 4-oxo group of the thiazole moiety as compared with the E-counterparts and appeared at lower field (δ ≈ 8.00-8.20 ppm) relative to the E-isomer (δ ≈ 7.50-7.80ppm).

Experimental Section
General Procedures.Melting points are uncorrected.IR spectra were measured on a Unicam SP 1200 spectrometer as KBr discs.Unless otherwise stated, the 1 H and 13 C NMR spectra were measured in DMSO-d 6 on a Varian Gemini instrument at 200 and 50 MHz, respectively; in both cases, chemical shifts are given in ppm down-field from internal TMS.Mass spectra were recorded on a Shimadzu GC-MS Qp 1000 EX instrument operating at 70 eV.