Hydrolytic and Associative Behavior of Aromatic Amides in Aqueous Solution

Abstract

Rate constants for alkaline hydrolysis (in 0.1N NaOH) of aromatic amides such as nicotinamide, benzamide, phenylacetamide, cinnamamide, and their corresponding N-alkyl substituted analogs were determined at 25°and 90°in order to investigate the effect of molecular structure on the stability of these amides against hydroxyl ion attack. Stability constants of these aromatic amide complexes with theophylline and 8-methoxycaffeine at 25°were also computed from phase-solubility data. The results have shown that cinnamamides are most stable against hydroxyl ion attack and formed the most stable complexes with the alkylxanthines while phenylacetamides are least stable in alkaline hydrolysis and least associative with alkylxanthines among benzene derivatives. Both hydrolytic behavior and associative tendency of these amides are discussed in relation to the extent of conjugation of the amide group with the rest of the molecule.