Detection and kinetic characterization of SNV intermediates.: Reactions of thiomethoxybenzylidene Meldrum's acid with thiolate ions, alkoxide ions, OH-, and water in aqueous DMSO

The reaction of thiomethoxybenzylidene Meldrum's acid (5-SMe) with thiolate and alkoxide ion nucleophiles is shown to proceed by the two-step addition-elimination SNV mechanism in which the tetrahedral intermediate accumulates to detectable levels. For the reactions with thiolate ions, rate constants for nucleophilic addition (k(1)(RX)), its reverse (k(-1)(RX)), and for conversion of the intermediate to products (k(2)(RX)) were determined. For the reactions with alkoxide ions, only k(1)(RX) and k(-1)(RX) could be obtained; the intermediate in these reactions did not yield the expected substitution products, and hence no k(2)(RX) values could be determined. The reaction with OH- and water are believed to follow the same mechanism, but the respective intermediates remain at steady-state levels, and only k(1)(OH) and k(1)(H2O) for nucleophilic attack on 5-SMe were measurable. New insights regarding structure-reactivity behavior in SNV reactions are gained from comparisons of rate and equilibrium constants in the reactions of 5-SMe with the corresponding parameters in the reactions of methoxybenzylidene Meldrum's acid (5-OMe) and benzylidene Meldrum's acid (5-H). In particular, the relative importance of steric and pi-donor effects of the MeS vs. MeO group in 5-SMe and 5-OMe, respectively, and their role in affecting the intrinsic rate constants for nucleophilic addition, has been clarified by these comparisons. Our results also add support to a previous suggestion that soft-soft type interactions tend to increase intrinsic rate constants for thiolate ion addition to vinylic substrates, especially 5-SMe with the soft MeS group.