Substituent effects on the pKa values and rates of hydrolysis of arylmethylene-erythromycylamines

Abstract

The pK_a values and rates of hydrolysis of a series of N-benzylidene derivatives of the macrolide antibiotic, erythromycylamine (I) have been measured. Anomalies in the correlations of the pK_a values with the Hammett equation and of the mechanism of hydrolysis with that of an analogous series of N-benzylidene-1,1-dimethylethylamines have been explained in terms of steric and electronic interactions involving the macrolide ring and the unusual effect of ortho-methoxy-substituents.