Aminolysis of benzyl 4-pyridyl carbonate in acetonitrile: effect of modification of leaving group from 2-pyridyl oxide to 4-pyridyl oxide on reactivity and reaction mechanism

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 (kobsd) νs. [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 kobsd into the second- and third-order rate constants (i.e., Kk2 and Kk3, respectively) reveals that Kk3 is significantly larger than Kk2, indicating that the reactions proceed mainly through the deprotonation pathway (i.e., the k3 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 k2). However, such H-bonding interaction, which could increase k2, 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 νs. a stepwise mechanism with T± and T-. as intermediates for that of 6)