3-Aryl-2-sulfanylpropenoic acids as precursors for some novel ( Z )-5-substituted-2-alkoxy-2-trichloromethyl-4-thiazolidinones

3-Aryl-2-sulfanylpropenoic acids 1a-d react with trichloroacetonitrile under various reaction conditions to give different products. Thus, reaction of 1a-d with trichloroacetonitrile in absolute ethanol and in the presence of few drops of triethylamine at room temperature affords 1,3-oxathiolan-5-one derivatives 4a-d . Whereas, compounds 1a-d react with trichloroacetonitrile in primary alcohols under reflux to afford the corresponding 2-alkoxy-2-trichloromethylthiazolidin-4-one derivatives 7a-l . Reaction of compounds 1a-d with trichloroacetonitrile or other nitriles 11a-c in refluxing glacial acetic acid gave 5-arylmethylene-2,4-thiazolidinediones 8a-d . The structures of all the newly synthesized products were confirmed based on elemental and spectral data, and a plausible mechanism is postulated to account for their formation. X-ray crystallography was carried out for the products 4a and 7b .


Introduction
2][3][4][5] Additionally, 3-aryl-2-sulfanylpropenoic acids have been found to be useful antidotes for heavy metal poisoning.For example, 3-furyl-2sulfanylpropenoic acid in particular has been shown to protect against cadmium intoxication in rats. 6An earlier investigation indicated that post-cadmium exposure treatment with certain 3aryl-2-sulfanylpropenoic acids is effective in decreasing liver and kidney cadmium burden in rats. 73-Aryl-2-sulfanylpropenoic acids can inhibit neuraminidases. 84][15] The biological significance of this class of compounds impelled us to continue working on synthesis of new oxathiolane and thiazolidinone derivatives.We report here the reaction of 3-aryl-2-sulfanylpropenoic acids with trichloroacetonitrile and other nitriles under various reaction conditions to give new 1,3-oxathiolanes, which were transformed into the corresponding thiazolidin-4-one derivatives.

Results and Discussion
The reaction of 3-aryl-2-sulfanylpropenoic acids 1a-d with trichloroacetonitrile in absolute ethanol and in the presence of a few drops of triethylamine as basic catalyst at room temperature afforded the products 4a-d.The structures of the products were confirmed by elemental analyses and spectral data (IR, 1 H NMR, 13 C NMR, MS and X-ray).For example, the IR spectrum of the isolated product 4a taken as a typical example of the series showed two absorption bands at ν 3388 and 3309 cm -1 corresponding to the amino group and one absorption band at 1751 cm -1 corresponding to lactone carbonyl group.The 1 H NMR spectrum of the same product revealed a broad singlet signal (2H, D2O exchangeable) at δ = 4.51 ppm attributable to NH2, and a singlet signal at δ = 7.81 ppm due to a vinylic proton and the aromatic proton signals.The 13 C NMR spectrum of 4a exhibited the following signals: 113.0 ppm for C-1, 115.5 ppm for C-2, 175.5 ppm for C-3, 133.0 ppm for C-4 and 138.7 ppm for C-5, beside the aromatic carbons.Its mass spectrum showed molecular ion peaks at m/z 360 (M+1) + and 361 (M+2) + consistent with the assigned structure.
Based on these spectral data the oxathiolane structures 4a-d were assigned to the above reaction products and alternative structure 3 could be dismissed (Scheme 1).X-ray analysis of compound 4a (Figure 1, Table 1) gives conclusive evidence for the assigned structure 4. The formation of 4 is assumed to proceed first via addition of the thiol moiety in sulfanylpropenoic acid derivative 1a to the cyano carbon in trichloroacetonitrile, affording the non-isolable acyclic imine 2. This, in turn cyclizes to the final isolated product 4 via addition of the oxygen nucleophile to the activated azomethine group.
On the other hand, it was found that compounds 1a-d react with trichloroacetonitrile in absolute ethanol in the presence of few drops of triethylamine at refluxing temperature to afford pale yellow crystalline products.It was expected that this reaction would afford thiazole derivatives 3. The IR spectrum of 7b taken as a typical example of the reaction products showed an absorption band at ν 1680 cm -1 attributable to a lactam carbonyl group.The 1 H NMR spectrum of the same product revealed a triplet signal at δ = 1.22 ppm and a quartet signal at δ = 3.70 attributable to ethoxy protons.A singlet signal (1H, D2O exchangeable) appeared at δ = 10.46 ppm, attributable to an NH, a singlet signal at δ = 7.47 ppm due to vinylic proton and a singlet signal at δ = 6.10 due to methylene (O-CH2-O) protons, besides the aromatic protons.The  2) confirmed the structure deduced from NMR studies.Compounds 7a-d can also be obtained by refluxing 4a-d in absolute ethanol in the presence of triethylamine.Similarly, refluxing of 4a-d in other alcohols like methanol or n-propanol in the presence of few drops of triethylamine afforded 2-alkoxy-2trichloromethyl-4-thiazolidinone derivatives 7e-l.Transformation of 4a-d into 7a-l is assumed to proceed via ring opening of lactone ring by alcohol to afford the non-isolable acyclic intermediates, then cyclization with elimination of water to afford the final isolated products 7.It was of interest to extend this study to reactions conducted in acetic acid and we found that heating 1a-d with trichloroacetonitrile in acetic acid at reflux afforded coloured solid products.The structure of the isolated products was confirmed by elemental analysis and spectral data (IR, 1 H NMR and MS).The IR spectra of the isolated products showed in each case absorption at max 3176-3216 due to NH group and absorption at max.1753-1679 cm -1 due to carbonyl groups.
The 1 H NMR spectra of these products revealed in each case a broad singlet signal (1H, D2O exchangeable) at δ ~ 11.25-12.90attributable to NH, besides a vinylic CH proton at δ ~ 7.56-7.71ppm.The mass spectra together with elemental analyses confirmed the structures 8a-d.These structures were chemically confirmed by an alternative method via condensation of 2,4thiazolidinedione (9) with aromatic aldehydes 10a-d in glacial acetic acid in the presence of anhydrous sodium acetate to give products corresponding in all respects (mp, mixed mp and IR) with products 16,17 8a-d.
The formation of structure 8 is assumed to proceed via addition of the thiol moiety in the sulfanylpropenoic acid to the cyano carbon in trichloroacetonitrile, then cyclization with elimination of water to give non-isolable product 2. Acid hydrolysis then affords the 5-arylidene-2,4-thiazolidinediones 8.
Compounds 8a-d are assumed to be formed via elimination of chloroform, followed by cyclization with elimination of water, then acid hydrolysis with elimination of active nitrile molecule to afford 8 (Scheme 3).

Experimental Section
General.Melting points were determined on an Electrothermal 9100 apparatus.The IR spectra were recorded as KBr pellets on a Perkin-Elmer 1430 spectrophotometer.The 1 H NMR spectra were taken on a Varian Gemini 300-MHz spectrometer in DMSO-d6 using TMS as internal standard.Mass spectra were measured on a Shimadzu GCMS-GB 1000 PX (70 ev).Elemental analyses were obtained using an Elementar CHNS analyzer Vario EL III (Germany), at the Microanalyses Center of Cairo University, Giza, Egypt.The X-ray crystal analysis was carried out at Dokki National Centre (NRC) at Dokki, Giza, Egypt.3-Aryl-2-sulfanylpropenoic acids were synthesized according to literature procedures. 18

13 C
Scheme 1An X-ray crystallographic study of a single crystal of 7b (Figure2, Table2) confirmed the structure deduced from NMR studies.Compounds 7a-d can also be obtained by refluxing 4a-d in absolute ethanol in the presence of triethylamine.Similarly, refluxing of 4a-d in other alcohols like methanol or n-propanol in the presence of few drops of triethylamine afforded 2-alkoxy-2trichloromethyl-4-thiazolidinone derivatives 7e-l.Transformation of 4a-d into 7a-l is assumed to proceed via ring opening of lactone ring by alcohol to afford the non-isolable acyclic intermediates, then cyclization with elimination of water to afford the final isolated products 7.