Kinetics and mechanism of sulfonylation of α-amino acids and dipeptides

Abstract

The kinetics of sulfonylation of several α-amino acids: Gly, dl-α-Ala, dl-Val, dl-Leu, l-Ile, dl-Thr, dl-Met, dl-Ser, and l-Pro and dipeptides: Gly—Gly, l-α-Ala—l-α-Ala, l-α-Ala—β-Ala, β-Ala—β-Ala in water—propan-2-ol and water—1,4-dioxane binary systems were studied by spectrophotometry. The rate constants for reactions involving α-amino acids and dipeptides vary in a range for 81–52900 L mol^–1 s^–1 and 1.49–75 L mol^–1 s^–1, respectively. A considerable decrease in the rate constants for sulfonylation of dipeptides compared to those of corresponding α-amino acids suggests that the basicity of amino compounds has a signifi cant eff ect on their reactivity. The activation parameters of the reactions of amino acids and dipeptides with 3-nitrobenzenesulfonyl chloride in aqueous organic media were calculated. The mechanism of sulfonylation of α-amino acids and the Gly—Gly dipeptide was simulated by constructing the potential energy surfaces of the gas-phase reactions and taking into account the specifi c solvation of nucleophiles. The processes under study were shown to proceed by the S_N2 mechanism, and the reaction pathway that corresponds to the nucleophilic attack along the near-axial direction is more favorable. It was found that the reactions of sulfonyl chlorides with solvated α-amino acids involve partial desolvation of α-amino acids occuring prior to the formation of activated complex.