Cleavage reactions of 4-thiazolidinone-2-thiones: reactions with 5-arylhydrazono-4thiazolidinone-2-thiones

In continuation to our interest in the chemistry of thiazolidinone ring systems, owing to their considerable biological activities, we re-Port here on the behaviour of 5-arylhydrazono-4-thiazolodinone-2-thiones [6] la and b toward the action of a variety of nucleophilic reagents. Thus, subjecting la and b to the action of aliphetic amines affected elimination of the arylhydrazono group with concomitant ring cleavage to afford the thiooxalic acid amides 2a-c. This is in analogy with arylhydrazono group elimination in 4-arylhydrazono5-imino-3-pyrazolinones by amines

Heterodyne synthesis: synthesis of fused thiopyrano [2,3-d] thiazole, [1] benzopyrano ['3,'4: 4,5] thiopyrano [2,3-d] thiazole and thiazolo [3,4-c] -triazine derivatives

The biological and medicinal activities of substituted thiazolidines have been well reviewed, besides, the use of thiopyrano derivatives as anti-malarial drugs has prompted us to synthesize compounds having both thiazolidine and thiopyrano moieties of expected biological activities. The reactions of the highly coloured 5- salicylidenethiazolidine -2, 4-dithione and acrylonitrile at room temperature, in acetic acid, afforded a colourless 1:1 adduct, as inferred from its analytical data, which may have any of the structures 2-5. structures 3-5 were ruled out based on the 1H NMR data of the adduct which can be readily interpreted in terms of 6- cyano-7-o-hydroxyphenyll-5, 6-dihydrothiopyrano [2,3-d] thiazolidine-2 thione. The region-chemical assignment was based on proton chemical shift, which is in agreement with the favourable interaction between the sulphur atom of the heterodyne component, >C=C-C=S, and the Beta carbon atom of the dienophile. On the other hand, when 1 was reached with either acrylonitrile and/or ethyl acrylate in refluxing acetic acid, one and the same product was obtained; a fused benzopyrano- ['3, '4: 4,5] thiopyrano [2,3-d] thiazole- 2-thioxo 6[H]- one [6] as inferred from its analytical and spectral data. The formation of 6 is assumed to proceed through cycloaddition followed by concomitant loss of ethanol. The reaction of 1 with N-phenylmaleimide, maleic anhydride and dimethyl acetylenedicarboxylate in acetic acid, afford the colourless 1:1 adducts 7, 8 and 9, respectively. The gross structures of compounds 7-9 were assigned on the vasis of their analytical and spectral data; the sterochemical assignment of 7 and 8 was a consequence of proton coupling constants. Subjecting the anhydride 8 to the action of aniline in benzene afforded the amide 10, which is readily dehydrated by the action of acetic acid containing anhydrous sodium acetate to afford 7. The behaviour of 1 toward the action of malononitrile has also been investigated. Thus, treatment of 1 with malononitrile, at room temperature, in absolute ethanol, and in the presence of triethylamine afforded the colourless adduct 11. The structure of 11 was based on its analytical and spectral data, besides its unambiguous synthesis, by the reaction between thiazolidine 2, 4- dithione and salicylidenemalononitrile. On the other hand, when the reaction of 1 with malononitrile was carried out in refluxing ethanol, a fused benzopyraro ['3, '4: 4,5] thiopyrano [2,3-d] thiazole - 2 thione derivative 12 was based on its analytical and spectral data; furthermore, compound 12 was found to be identical with the product obtained by refluxing 11 in absolute ethanol in the presence of thriethlamine. Attempts to S-alkylate the potassium salt of 1 by the action of methyl iodide, ethyl bromoacetate and/or phenacyl bromide were unsuccessful, and instead, one and the same product was isolated. Structure 13 was assigned for the product based on its analytical and IR data; besides, its alkaline hydrolysis afforded 3-meracaptocoumarin, proved to be identical via its S-benzyl derivative with an authentic sample [8]. The reaction of 1 phenylhdrazine at room temperature, effected saliclidene group cleavage, with the formation of 4- phenylhydrazono-2-thiazolidinethione[9] [14]. The raction of 14 with acetyl chloride afforded 4-N1- acetylphenylhydrazono-2-thiazolidinethione [15]. Subjecting 14 to the action of ethyl bromoacetate and phenacyl bromide, in refluxing ethanol, and in the presence of few drops of triethylamine, afforded the fused thiazole [3,4-c]- triazine derivatives 16 and 17, respectively. The structures of 15-17 were based on their analytical and spectral data; besides, the acid hydrolysis of 15 and 16 yielded 4-thiazolidinone-2-thione[10]. This is in analogy with the reported behaviour of 2-phenylhydrazono-4-thiazolidinone derivatives toward the action of the same reagents[11]