Free energy relationships and intramolecular general acid catalysis

Variations in reactivity of substituted salicylic acid derivatives are appraised in the light of the work of Jencks on transition-state structures, variations in transition-state structure and variations in reaction mechanism. The transition states for the intramolecular general acid-catalysed hydrolyses of a variety of compounds derived from salicylic acid are shown to be closely related to those for the corresponding spontaneous hydrolysis reactions of compounds derived from substituted phenols. Free energy relationships are used to estimate the potential benefits of improving intramolecular hydrogen bond geometry in an aqueous environment. Copyright (C) 2004 John Wiley Sons, Ltd.