Reactivity of benzohydrazide derivatives towards acetylation reaction. Experimental and theoretical studies

We herein report an experimental and theoretical study on the acetylation reaction of benzohydrazide derivatives towards p-nitrophenyl acetate (NPA). The kinetic data are consistent with a stepwise mechanism with the nucleophilic attack as the rate determining step. From the theoretical analysis it is found that benzohydrazide derivatives establish intramolecular proton rearrangement. The enol form appears as the active species for nucleophilic attack. A reaction mechanism incorporating keto-enol pre-equilibria is proposed. The study is completed with a local reactivity analysis describing the most reactive centers for nucleophilic attack together with a site activation analysis describing inductive substituent effects.