Studies on the mechanism of the enolization reaction of Grignard reagents and ketones. Part 2. Pseudo-first-order rate and deuterium isotope effect studies

Abstract

Kinetics of enolization reactions of some alkyl mesityl ketones with alkylmagnesium bromides were studied under pseudo-first-order conditions by measuring formation of gaseous alkane. Using a large fixed excess of isopropyl mesityl ketone, the reaction was first order in ethylmagnesium bromide; with a fixed excess of ethylmagnesium bromide, the reaction was first order in ketone. At high excess variable concentrations of ketone, however, k₂ values decreased with increasing ketone concentration in a good linear relation between the two variables. When both Grignard and ketone concentrations (at 1 : 1 mole ratios) were varied, a nonlinear relationship resulted between concentrations and k₂ values. Rates did not vary significantly between highly pure and reagent grade magnesium. Reactions in tetrahydrofuran at b.p. 67 °C took place at significantly slower rates than reactions in ether at b.p. 36 °C at comparable concentrations whereas reactions in di-n-butyl ether at b.p. 141 °C occurred at a much faster rate at higher concentrations. Reactions of α-deuterio-substituted methyl, ethyl, and isopropyl mesityl ketones with ethylmagnesium bromide showed isotope effects confirming breaking of the C–H bond as the rate-determining step in accord with the proposed mechanism. Values of k_H/k_D= 2.6–3.1 indicate a moderate degree of C–H bond stretching in the transition state. A two-step mechanism is proposed.