Concurrent nucleophilic and general acid catalysis of the hydrolysis of a phosphate triester

Abstract

The hydrolysis of diethyl 8-dimethylaminonaphthyl-1-phosphate is catalysed by the neighbouring dimethylammonium group, with a rate acceleration, compared with diethyl naphthyl-1-phosphate, of almost 10⁶. The effective pK_a of the naphtholate leaving group is reduced from 9.4 to 3.4 by partial protonation in the transition state. The reaction is catalysed by oxyanion nucleophiles, and it is shown that a common nucleophilic mechanism, enhanced by general acid catalysis by the neighbouring dimethylammonium group, accounts for all the observed reactions. The efficiency of general acid catalysis depends on the extent of negative charge development on the leaving group oxygen in the transition state for P–O cleavage, and the strength of the intramolecular hydrogen bond in reactant and transition state.