A number of molecular quantities were tested as reactivity indexes for the alkaline hydrolysis reaction of a series of 15 N-phenylacetamides para substituted in the aromatic ring. The Hammett sigma constants and the shifts of carbonyl stretching mode frequencies correlate satisfactorily with the predicted Hartree-Frock (HF)/6-31+G(d) and density functional theory B3LYP/6-31+G(d,p) energy changes for the rate-determining stage of the reaction, namely, the addition of a hydroxide ion and formation of a tetrahedral intermediate. Natural bond orbital atomic charges at the carbonyl carbon atom, the site of the nucleophilic attack, also offer a satisfactory basis for discussing the reactivity of the carbonyl compounds studied. The electrophilicity index omega describes well the overall tendency of the changing reactivity of the studied compounds. A quantitative description of the reactivity of the studied amides in the reaction considered is provided by the theoretically estimated electrostatic potential at the carbonyl carbon atom. The linear regression correlation coefficients for the connection between the energy changes for the rate-determining stage of the amide hydrolysis and the electrostatic potential at the carbonyl carbon atom are over 0.99 with both levels of theory employed. The electrostatic potential at the nuclei is recommended as an accurate local reactivity index.