Covalent hydrates as transient species in heterocyclic rearrangements. Part I. The ring fission of some s-triazolopyrazines

Abstract

Hydrolysis of the s-triazolo[4,3-a]pyrazines (1) and (3) gives rise to pH profiles whose ‘apparent pKa’ values differ markedly from those measured. A steady-state treatment is derived for transient intermediates with a lifetime sufficient for them to exist as an equilibrium mixture of the possible ionic forms. In the general case, these ‘apparent pKa’ values represent no one actual pKa value but, instead, various combinations of rate and protonation constants. The reaction mechanism is discussed and reasons are given for believing these transient intermediates to be covalent hydrates. In particular, this postulate leads to reasonable predictions concerning relative rate and equilibrium constants and the approximate pKa values of the covalently hydrated species themselves. Qualitative evidence suggests that the acid-catalysed rearrangement of compound (1) to the imidazo[2,1-c]-s-triazole (5) is a general reaction of s-triazolo[4,3-a]pyrazines.