Nitrile sulfides Part 16. Synthesis of 1,2-benzisothiazoles via nitrile sulfide cycloaddition reactions

Abstract

The cycloaddition reactions of nitrile sulfides have been used to prepare benzisothiazole quinones and 1,2-benzisothiazole-5,6-dicarboxylates. The nitrile sulfides, generated by thermal decarboxylation of 1,3,4-oxathiazol-2-ones, reacted with 1,4-naphthoquinone to afford 3-substituted naphtho [2,3-d]isothiazole-4,9-diones (17), together with nitriles as by-products. The corresponding reactions with 1,4-benzoquinone yielded regioisomeric mixtures of 2:1 adducts. The 1,2-benzisothiazole-5,6-dicarboxylates were synthesised by a sequence involving both nitrile sulfide and Diels-Alder cycloaddition reactions. Dimethyl 3-phenylisothiazole-4,5-dicarboxylate (34), prepared from benzonitrile sulfide and dimethyl acetylenedicarboxylate (DMAD), was converted into the 4,5-bis(dibromomethyl) analogue 37 via the bis(dihydroxymethyl) compound 35. Treatment of 37 with sodium iodide in the presence of DMAD afforded dimethyl 3-phenyl-1,2-benzisothiazole-5,6-dicarboxylate (30) via the isothiazole o-quinodimethane 32.

Identification of new scaffolds with anti-tumor action toward human glioblastoma cells

“…[8][9][10] Conversely, the isothiazolequinones are an extremely rare class of compounds with only a few synthetic compounds containing this skeleton reported in the literature to date. 11,12 Therefore, they can be considered as a very attractive target for biological evaluation.…”