Kinetic evidence for the occurrence of a stepwise mechanism in the aminolysis of N-ethoxycarbonylphthalimide

Abstract

The nucleophilic second-order rate constants for the reactions of N-ethoxycarbonylphthalimide (ECPH) with morpholine, piperazine, 1,4-diazabicyclo[2.2.2]octane, and ethylenediamine exhibit a Brønsted plot of slope (β_nuc) 1.2 ± 0.3. The significantly high value of β_nuc reveals that the expulsion of the leaving group from a zwitterionic tetrahedral addition intermediate is the rate-determining step. The reactivity of hydroxylamine is nearly 10⁵-fold larger than that expected from the Brønsted plot of slope (β_nuc) 1.2. The hydroxylaminolysis of ECPH reveals general base catalysis. The results obtained on the hydroxylaminolysis of ECPH in the presence of external general base, acetate, reveal that the rate-determining step changes as the buffer concentration is increased and, consequently, it provides evidence for the existence of an intermediate on the reaction co-ordinate. The rate constants for the reactions of monoprotonated 1,4-diazabicyclo[2.2.2]octane and piperazine show positive deviations from the Brønsted plot.