Protonation equilibria of cardiotonic polyaza heterocycles

Abstract

The pK_a values of fifteen sulmazole analogues have been measured spectrophotometrically. The major protonation sites for most of these heterocycles were determined by ¹H and ¹³C n.m.r. methods. Sulmazole (1), isomazole (7), 1H-imidazo[4,5-d] pyridazine (14), 1H-pyrrolo[2,3-c]pyridine (17), and 1H-pyrrolo[3,2-c]pyridine (18) underwent protonation at the pyridyl nitrogen. The purine (11) and 7H-imidazo[4,5-e]-1,2,4-triazine (16) were protonated mainly at N-1, and 1H-imidazo[4,5-c]pyridazine (13) at N-2. The benzimidazole (4) and 1H-imidazo[4,5-b]pyrazine (15) were protonated at the imidazole nitrogens. In some cases the various 1H- and 3H-tautomers were identified; their relative proportions were found to vary with the ring system.