Kinetics and mechanism of reactions of substituted (methylthio)benzylidene Meldrum's acids with primary amines in aqueous DMSO

A kinetic study of the aminolysis of substituted (methylthio)benzylidene Meldrum's acids, 2‐SMe‐Z with the aliphatic primary amines, n ‐butylamine, glycinamide, methoxyethylamine, and aminoacetonitrile, in aqueous DMSO at 20 °C is reported. With all amines the reaction is strictly second‐order, that is, first‐order in 2‐SMe‐Z and first‐order in the amine. A three steps mechanism has been proposed. The first step is a rate‐limiting attachment of the amine to form the tetrahedral intermediate ( T   A ± ), and the subsequent steps are a fast acid–base equilibrium followed by a fast R‴CH 2 NH   3 +or H 2 O catalyzed expulsion of the leaving group. The Brönsted plot for k 1 for the reaction of 2‐SMe‐H with four primary amines showed a good correlation between log k 1 and p K   a AHwith β nuc  = 0.32 ± 0.02, a slightly lower value than that for the reactions of secondary amines (β nuc  = 0.41 ± 0.01). The Hammett plot for n ‐butylamine yields ρ( k 1 ) = 0.40 ± 0.05 which is smaller than that for the reaction of piperidine with the same substrates (ρ( k 1 ) = 0.72 ± 0.07) and also for the reactions of HOCH 2 CH 2 S − (ρ( k 1 ) = 1.18), CF 3 CH 2 O − (ρ( k 1 ) = 1.14) and OH − (ρ( k 1 ) = 1.11) addition to 2‐H‐H (ρ( k 1 ) = 1.11). All these observations are consistent with the suggested mechanism. Copyright © 2006 John Wiley & Sons, Ltd.