Regio- and stereoselective synthesis of 5-halogeno(tetrachlorotelluro)methylidene-1-ethoxycarbonyl-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazinium salts

This work presents the results of a study on the electrophilic intramolecular cyclization of ethyl 1-pentynylpyrazole-5-carboxylate with halogens and tellurium tetrachloride. Alkylation of ethyl pyrazole-3(5)-carboxylate with pentynyl mesylate in the presence of cesium carbonate in a dimethylformamide medium leads to a mixture of regioisomers, which were separated chromatographically. It was found that halogenation of the obtained regioisomeric mixture of ethyl 1-pentynylpyrazole-5-carboxylate and ethyl 1-pentynylpyrazole-3-carboxylate with iodine and bromine results in halocyclization exclusively of ethyl 1-pentynylpyrazole-5-carboxylate, leading to the stereoselective formation of halomethylidene-substituted pyrazolo[1,2-a]pyridazinium salts, as confirmed by homo- and heteronuclear correlation spectral studies. The iodination and bromination of individual pentynyl esters of pyrazole further confirm that cyclization occurs only for one regioisomer. Halocyclization of ethyl 1-pentynylpyrazole-5-carboxylate with iodine halides in acetic acid yields iododibromide and 5-iodomethylidene-1-ethoxycarbonyl-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazinium chloride. The reaction of tellurium(IV) oxide in hydrochloric acid with 1-pentynylpyrazole-5-carboxylate induces tellurium-mediated cyclization, resulting in a tellurium-functionalized tetrahydropyrazolo[1,2-a]pyridazinium compound in the form of an intramolecular salt. The spectral characteristics (1H and 13C NMR) of the iododibromide, iodomethylidene-1-ethoxycarbonyltetrahydropyrazolo[1,2-a]pyridazinium chloride, and the tellurium-containing zwitterion further confirm the stereoselectivity of the heterocyclization process. As a result of this study, potentially biologically active pyrazolopyridazinium salts were obtained.