Kinetic Study on Michael-type Reactions of 1-Phenyl-2-propyn-1-one with Alicyclic Secondary Amines: Effect of Medium on Reactivity and Mechanism

Abstract

Second-order rate constants (kN) have been measured for Michael-type addition reactions of a series of alicyclic secondary amines to 1-phenyl-2-propyn-1-one (2) in MeCN at 25.0 <TEX>${\pm}$</TEX> 0.1 <TEX>${^{\circ}C}$</TEX>. All the amines studied are less reactive in MeCN than in <TEX>$H_2O$</TEX> although they are more basic in the aprotic solvent by 7-9 p<TEX>$K_a$</TEX> units. The Bronsted-type plot is linear with <TEX>$\beta_{nuc}$</TEX> = 0.40, which is slightly larger than that reported previously for the corresponding reactions in <TEX>$H_2O$</TEX> (<TEX>$\beta_{nuc}$</TEX> = 0.27). Product analysis has shown that only E-isomer is produced. Kinetic isotope effect is absent for the reactions of 2 with morpholine and deuterated morpholine (i.e., <TEX>$k^H/k^D$</TEX> = 1.0). Thus, the reaction has been concluded to proceed through a stepwise mechanism, in which proton transfer occurs after the rate-determining step. The reaction has been suggested to proceed through a tighter transition state in MeCN than in H2O on the basis of the larger <TEX>$\beta_{nuc}$</TEX> in the aprotic solvent. The nature of the transition state has been proposed to be responsible for the decreased reactivity in the aprotic solvent.