Polyfluoroheterocyclic compounds. Part XV. Formation and nucleophilic substitution of polyfluoropyridazinium cations

Abstract

Under strongly acidic conditions, nucleophilic attack on tetrafluoropyridazine and on 3,5,6-trifluoro-4-methoxypyridazine by water or methanol leads to substitution of the fluorine atoms at C-3 and C-6 in preference to those at C-4 and C-5 which have previously been shown to be more reactive towards nucleophilic reagents under basic conditions. Treatment of tetrafluoropyridazine with water in sulphuric acid solution gives 3,4,5-trifluoro-1H-pyridazin-6-one, and similar treatment with methanol gives 3,4,5-trifluoro-6-methoxypyridazine (at 0°) or 4,5-difluoro-3,6-dimethoxypyridazine (at 20°). All four fluorine atoms of tetrafluoropyridazine are replaced by chlorine when it is treated with ethereal hydrogen chloride at 18°. Spectroscopic evidence suggests that the acid-catalysed reactions involve nucleophilic attack on protonated polyfluoropyridazinium cations, and two N-alkyl-tetrafluoro-pyridazinium tetrafluoroborates have been prepared and shown to give exclusively 1-alkyl-3,4,5-trifluoropyridazin-6-ones on treatment with water. Factors affecting the orientation of the products of nucleophilic attack on poly-fluoropyridazinium cations are discussed. Structures have been assigned to the two isomeric difluoromethoxy-pyridazinones resulting from the acid-catalysed hydroxylation of 3,5,6-trifluoro-4-methoxypyridazine, by relating them to 3,4-difluoro-5,6-dimethoxypyridazine and 3,5-difluoro-4,6-dimethoxypyridazine.