H-Rate profile for release of salicylic acid from benzaldehyde disalicyl acetal

A mixed acetal of benzaldehyde in which one of the salicyclic acid moieties is replaced by methoxy has also been studied. It, too, shows a strong rate enhancement attributable to intramolecular general acid catalysis. 

The case of intramolecular participation in ester hydrolysis has been extensively studied using acetylsalicylic acid (aspirin) and its derivatives. The kinetic data show 

Mechanism III cannot be immediately distinguished from the first two because of the kinetic equivalence of the reagents involved, which are in rapid equilibrium  

Mechanism I has been ruled out by an isotopic labeling experiment. The mixed anhydride of salicylic acid and acetic add is an intermediate if nucleophilic catalysis occurs. This molecule is known to hydrolyze in water with about 25% incorporation 

The extent to which intramolecular nucleophilic catalysis of the type depicted in mechanism I is important is a function of the leaving ability of the alkoxy group, as is demonstrated by a study of a series of phthalate monoesters  

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