Predominant oxygen-18 exchange accompanying the base hydrolysis of a tertiary toluamide: N-ethyl-N-(trifluoroethyl)toluamide. Assessment of the factors that influence partitioning of anionic tetrahedral intermediates

Abstract

The respective solvent kinetic isotope effects (SKIE) refer essentially to isolatd kinetic processs k 1 (the attack of OH − to form T 0 − ) and k 2 (the breakdown of the anionic intermediate to product). The small observed SKIE on exchange and hydrolysis is analyzed in terms of the fractionation factors for species involved in the transition states leading to the anionic tetrahedral intermediate T 0 − and away from it, respectively. The mechanism consistent for the SKIE on k hyd is suggested to involve rate-limiting breakdown of one or both of two anionic forms having a protonated N, an anionic zwitterion T ZW − or a neutral zwitterion with an encounter complex associated OH − . On the basis of SKIE, 18 O exchange, and hydrolysis data for a series of tertiary toluamides having an amine portion varying in basicity by ∼14 pK units, a unified mechanism for base-promoted hydrolysis is presented