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 ± 0.1°C. All the amines studied are less reactive in MeCN than in H2O although they are more basic in the aprotic solvent by 7-9 pKa units. The Brønsted-type plot is linear with βnuc = 0.40, which is slightly larger than that reported previously for the corresponding reactions in H2O (βnuc = 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., kH/kD = 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 βnuc in the aprotic solvent. The nature of the transition state has been proposed to be responsible for the decreased reactivity in the aprotic solvent.