Stepwise proton transfer in the acid-catalysed hydrolysis of 3,1-benzoxazin-4-ones: electrostatic or hydrogen-bond stabilisation of the conjugate acid

Abstract

The hydrolysis of 3,1-benzoxazin-4-ones is catalysed by buffer acids and by intramolecular carboxylic acid groups suitably placed on the heterocyclic nucleus. Small or inverse deuterium oxide solvent isotope effects on the acid catalytic terms are consistent with both inter- and intra-molecular acid catalyses proceeding through a pre-equilibrium protonation mechanism. Proton transfer to the N-1 position concerted with attack at C-2 is not expected because the N-1 protonated 3,1-benzoxazin-4-one is a relatively stable species. The function of the 8-carboxy-anion in the catalysed ring hydrolysis of 8-carboxy-3,1-benzoxazin-4-one is to stabilise the protonated nitrogen (N-1) by electrostatic or hydrogen-bonding interaction.