Kinetic evidence for the occurrence of 1,3-proton transfer through a proton-switch mechanism in the aminolysis of salicylate esters

Abstract

The nucleophilic reactions of primary amines (pK_a range 5.97–10.85) with ionized methyl salicylate (MS^–) show significant solvent isotope (D₂O) effects. Ionized phenyl salicylate (PS^–) reveals high reactivity towards primary amines (pK_a >8.15) and secondary amines (pK_a range 6.24–11.32) with essentially no solvent isotope effects. However, the nucleophilic reactions of primary amines of pK_a⩽8.15 with PS^– do exhibit solvent isotope effects. These observations, coupled with the absence of nucleophilic reactivity of secondary amines towards MS^–, are attributed to the occurrence of 1,3-proton transfer in these reactions.