Michael-type Reactions of 1-(X-substituted phenyl)-2-propyn-1-ones with Alicyclic Secondary Amines in MeCN and H2O: Effect of Medium on Reactivity and Transition-State Structure

Abstract

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for Michael-type reactions of 1-(X-substituted phenyl)-2-propyn-1-ones (2a-f) with a series of alicyclic secondary amines in MeCN at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The <TEX>$k_N$</TEX> value increases as the incoming amine becomes more basic and the substituent X changes form an electron-donating group (EDG) to an electron-withdrawing group (EWG). The Br<TEX>${\o}$</TEX>nsted-type plots are linear with <TEX>${\beta}_{nuc}$</TEX> = 0.48 - 0.51. The Hammett plots for the reactions of 2a-f exhibit poor correlations but the corresponding Yukawa-Tsuno plots result in much better linear correlations with <TEX>${\rho}$</TEX> = 1.57 and r = 0.46 for the reactions with piperidine while <TEX>${\rho}$</TEX> = 1.72 and r = 0.39 for those with morpholine. The amines employed in this study are less reactive in MeCN than in water for reactions with substrates possessing an EDG, although they are ca. 8 pKa units more basic in the aprotic solvent. This indicates that the transition state (TS) is significantly more destabilized than the ground state (GS) in the aprotic solvent. It has been concluded that the reactions proceed through a stepwise mechanism with a partially charged TS, since such TS would be destabilized in the aprotic solvent due to the electronic repulsion between the negative-dipole end of MeCN and the negative charge of the TS. The fact that primary deuterium kinetic effect is absent supports a stepwise mechanism in which proton transfer occurs after the rate-determining step.