72694-03-2Relevant academic research and scientific papers
Thienoisothiazoles. III. The Synthesis and Reactions of 3-Phenyl-5-alkylthioisothiazole-4-carbonitriles and 3-Phenylthienoisothiazoles
Krebs, Hans-Dieter
, p. 1291 - 1306 (2007/10/02)
Oxidation of the alkyl 3-amino-4-cyano-3-phenylpropenedithioates (1), obtained by alkylation of the condensation product of 3-amino-3-phenylpropenenitrile and carbon disulfide, produced 3-phenyl-5-alkylthioisothiazole-4-carbonitrile (2a-d).The ease of nucleophilic displacement of the S-alkyl group in the isothiazole (2a) was utilized to synthesize the isothiazoles (2f-j). 3-Phenylthioisothiazole (3e) was prepared by deamination, hydrolysis and decarboxylation of the intermediate ethyl 4-amino-3-phenylthienoisothiazole-5-carboxylate (3a), which was obtained was obtained by ring-closure of ethyl 2-(4-cyano-3-phenylisothiazol-5-ylthio)acetate (2d). 3-Phenylthienoisothiazole was unreactive towards weaker electrophiles, but undergoes bromination and nitration in the α-position of the thiophen ring.The position of substituents in 5-bromo- (3w) and 5-nitro-3-phenylthienoisothiaole (4a) was verified by alternative synthesis. the attempted deamination of 4-amino-5-bromo-3-phenylthienoisothiazole (3o) and 4-amino-5-nitro-3-phenyltheienoisothiazole (3r) yielded 3-phenyl-5-nitrothienoisothiazol-4-ol (3s) only, but the isomeric 4-bromo-3-phenylthienoisothiazole (3v) was obtained bt decarboxylation of 4-bromo-3-phenylthienoisothiazole-5-carboxylic acid (3u).An alternative synthesis of the 5-nitro derivative was achieved by decarboxylation of 5-nitro-3-phenylthienoisothiazole-4-carboxylic acid (3z).Mild reduction of 3-phenylthienoisothiazole derivatives, (3a,b) and (4c), with hydrogen sulfide or hypophosphorous acid afforded the substituted 3-(α-aminobenzylidene)-2,3-dihydrothiophen-2-thiones (5a-c), and the 3-benzoyl-2-alkylthiothiophen derivatives (6a,b), were obtained by a one-step synthesis, which avoided the isolation of the air-sensitive intemediates.
