Condensed isothiazoles. Part 5. Thieno[2,3-d]isothiazoles and thieno[3,2-d]isothiazoles

Abstract

2,3-Disubstituted thiophens containing a sulphur function (SH, SMe, or SCN) and a carbonyl group (CHO or Ac) have been prepared and converted into thieno[2,3-d or 3,2-d]isothiazoles. Methods used to prepare 1,2-benzisothiazoles are often inapplicable in the thiophen series. For example, an (E)-methyl (2-methylthio-3-thienyl)O-p-nitrobenzoylketoxime (6) in hot diethylene glycol or acetic acid gave the corresponding 3-acetamido-2-methylthiothiophen (15); in concentrated sulphuric acid at –5 °C, it gave the Beckmann rearranged product (15) and a thieno[3,2-d]thiazole (19). Similarly, (E)-methyl (3-methylthio-2-thienyl)O-p-nitrobenzoylketoxime (42) gave 2-methylthieno[2,3-d]thiazole with concentrated sulphuric acid, but with acetic acid it gave the thieno[2,3-d]isothiazole (43) and 2-acetamido-3-methylthiothiophen. Heating the (E)-2-mercaptothiophen-3-carbaldoxime (27) in an inert solvent gave the corresponding thieno[3,2-d]isothiazole (14); the (E)-3-mercaptothiophen-2-carbaldoxime (47) cyclised in hot AcOH–Ac₂O, to give the thieno[2,3-d]isothiazole (44). Thieno[3,2-d]isothiazoles were also prepared by treating a methyl (2-mercapto-3-thienyl) ketone (21) with chloramine and by heating a 2-iminothieno[3,2-d]-3,1,4-oxathiazepine (29) in an inert solvent. The products obtained by selective S-alkylation of 3,5-bis(sodiomercapto)isothiazole-4-carbonitrile with ethyl bromoacetate and iodomethane were cyclised, to give 4-aminothieno[3,2-d or 2,3-c]isothiazole derivatives (34) and (36).