Reactions of α-isobutyl-α-(methylthio)methylene Meldrum's acid with primary amines in aqueous DMSO

Abstract

The aminolysis of α-isobutyl-α-(methylthio)methylene Meldrum's acid 7 with primary amines, namely, n-butylamine, glycinamide, and methoxyethylamine in DMSO–H2O (50:50, v/v) at 20 °C is overall second-order but first-order in both 7 and amines. The reaction with aminoacetonitrile (AA) is overall third-order, first-order in substrate, and second-order in amine at low amine concentration, while at high amine concentration and high pH the dependence on amine is first-order. A general three-step mechanism has been proposed for all these reactions. For the former group of amines, the first step is a rate-limiting attack of the amine to form the tetrahedral intermediate (TA±), followed by a fast acid–base equilibrium and a fast RNH3+- or H2O-assisted leaving group expulsion. For AA, general base catalysis was confirmed from the dependence of kA on [AA]f and on [OH–]. For all four amines, a good Brønsted plot of log k1 vs. pKaAH in DMSO–H2O (50:50, v/v) with βnuc = 0.34 ± 0.02 was observed. These observations are consistent with the suggested mechanism.Key words: nucleophilic vinylic substitution reactions, primary amines, α-isobutyl-α-(methylthio)methylene Meldrum's acid, three-step mechanism.