Aminolysis of Benzyl 4-Pyridyl Carbonate in Acetonitrile: Effect of Modification of Leaving Group from 2-Pyridyloxide to 4-Pyridyloxide on Reactivity and Reaction Mechanism

Abstract

A kinetic study is reported for nucleophilic substitution reactions of benzyl 4-pyridyl carbonate 6 with a series of alicyclic secondary amines in MeCN. The plot of pseudo-first-order rate constant (k obsd ) vs.[amine] curves upward, which is typical for reactions reported previously to proceed through a stepwise mechanism with two intermediates (i.e., a zwitterionic tetrahedral intermediate T ± and its deprotonated form T -). Dissection of k obsd into the second-and third-order rate constants (i.e., Kk 2 and Kk 3 , respectively) reveals that Kk 3 is significantly larger than Kk 2 , indicating that the reactions proceed mainly through the deprotonation pathway (i.e., the k 3 process) in a high [amine] region. This contrasts to the recent report that the corresponding aminolysis of benzyl 2-pyridyl carbonate 5 proceeds through a forced concerted mechanism. An intramolecular H-bonding interaction was suggested to force the reactions of 5 to proceed through a concerted mechanism, since it could accelerate the rate of leaving-group expulsion (i.e., an increase in k 2 ). However, such H-bonding interaction, which could increase k 2 , is structurally impossible for the reactions of 6. Thus, presence or absence of an intramolecular H-bonding interaction has been suggested to be responsible for the contrasting reaction mechanisms (i.e., a forced concerted mechanism for the reaction of 5 vs. a stepwise mechanism with T ± and T -as intermediates for that of 6).