In projected SAR studies on the novel diheteroarylamide-based anti-HIV agent (1C8), one objective was to evaluate the influence of incorporating the central amide motif into a 5-membered pyrazolone ring (1). It was envisaged that the key 3-hydrazino-5-nitrobenzisothiazole intermediate (3) for the synthesis of pyrazolone 1 could be prepared through the reaction of 3-methoxy / 3-chloro-5-nitrobenzisothiazole (2a and 2b) with hydrazine. Surprisingly, the compounds isolated in these reactions corresponded to the ring-opened hydrazonate 5 and the sulfur-bridged-2,1-benzisothiazole dimer 6. In a further study where 2b was reacted with phenylhydrazine, a different rearranged product 7 was isolated. Meisenheimer complex (4) formation, favored by the presence of the 5-nitro substituent on the benzisothiazole ring, was postulated to be a key feature in the formation of these deep-seated rearranged products. Mechanisms leading to the formation of the rearranged products, supported by Density Function Theory calculations, will be presented.

Reaction of 3-Cl/OMe substituted 5-nitrobenzisothiazoles with hydrazine: Novel rearrangement pathways via intramolecular formation of pivotal Meisenheimer complexes

ACS Spring Meeting 2021

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