Rapid amidic hydrolysis: a competitive reaction pathway under basic conditions for N-(hydroxymethyl)benzamide derivatives bearing electron-donating groups

Studies of N-(hydroxymethyl)benzamide derivatives have concluded that the hydroxide-dependent reaction occurs via a specific-base catalyzed deprotonation of the hydroxyl group followed by rate-determining loss of the benzamidate and generation of the aldehyde. The 3-methyl, 4-methyl, and 4-methoxy-N-(hydroxymethyl)benzamide reaction mechanism deviates at higher [HO−] with amidic hydrolysis becoming competitive and having reaction half-lives of ∼17 s, in 1 M KOH, I = 1.0 M (KCl), 25 °C. An intramolecular general-base catalyzed mechanism has been suggested for the amidic hydrolysis reaction.