Aminolysis of oxalate esters in toluene: A model for a carboxylate buried in a hydrophobic environment at an active site

We have examined the aminolysis of the mono-o-nitrophenyl ester of oxalic acid by piperidine in toluene with the purpose of determining how a carboxylate “buried” at an active site might affect an enzyme-catalyzed reaction. The oxalate ester and piperidine form an ion pair (R₂NH₂⁺⁻O₂CCO₂Ar) even in extremely dilute toluene solutions. This conclusion is supported by the kinetic effects of acidic and basic additives and by a “concentration inversion” experiment. The oxalate ester was found to react more than three orders of magnitude faster than o-nitrophenyl acetate. The neighboring carboxylate in the ion pair apparently accelerates the decomposition of a tetrahedral intermediate by accepting a proton from the amine nitrogen. The implications of this anchimeric assistance to enzymatic systems is discussed briefly.