General-base catalysed hydrolysis and nucleophilic substitution of activated amides in aqueous solutions

The reactivity of 1-benzoyl-3-phenyl-1,2,4-triazole (1a) was studied in the presence of a range of weak bases in aqueous solution. A change in mechanism is observed from general-base catalysed hydrolysis to nucleophilic substitution and general-base catalysed nucleophilic substitution. A slight tendency is also observed for the more hydrophobic general bases to show higher reactivity towards 1a. Aspartame is an effective nucleophile, possibly because nucleophilic substitution is subject to intramolecular general-base catalysis. A general conclusion derived from the present results is that unexpected rate effects can only be rationalised provided that the detailed reaction mechanisms are well understood. Copyright (C) 2003 John Wiley Sons, Ltd.