ABSTRACT
Rapid tautomerism, involving switching of hydrogen from one nitrogen to the other, as in imidazoles, means that substituted pyrazoles are inevitably mixtures, and a nomenclature analogous to that used for imidazoles is employed to signify this: 3(5)-methylpyrazole, for example. However, the quaternisation of a 1-substituted pyrazole generally requires more vigorous conditions, no doubt because of steric impediment to reaction due to the substituent on the adjacent nitrogen. Poor yields are obtained on bromination of isothiazole and isoxazole with bromine, again with attack at C-4, but with activating groups present, halogenation proceeds better. Isothiazoles are reductively desulfurised using Raney nickel, with loss of the ring. Catalytic hydrogenolysis of the N-O bond in isoxazoles takes place readily over the usual noble metal catalysts, and this process is central to the stratagem in which isoxazoles are employed as masked 1,3-dicarbonyl compounds. Preparative deprotonations of this same isoxazole proceed exclusively at the 5-methyl substituent, allowing subsequent reactions with electrophiles at that position.
