A theoretical interpretation of protonation and hydration reactions for the quinazolines

Abstract

Theoretical calculations have been carried out on a series of quinazolines including monomethyl and monomethoxy-substituted compounds. The electron densities, bond orders, electrophilic and nucleophilic superdelocalisabilities, and energy changes were obtained for several structures. These structures were considered as steps in the protonation and hydration of the quinazolines which normally occur under acidic conditions. Comparison of the calculated terms and pK values gave reasonable correlations for each step in this process. The best relationships were the electrophilic superdelocalisability at the nitrogen in position 1 of the neutral compound with the pK for monoprotonation, and the nucleophilic superdelocalisability at position 4 of the diprotonated compound with log K for the hydration process. These data as well as the overall equilibrium pK values can most readily be interpreted in terms of a stepwise process involving two subsequent protonations of the quinazoline structure followed by hydroxylation of the 4 position.