Reactivity and selectivity of the reaction of O,O-diethyl 2,4-dinitrophenyl phosphate and thionophosphate with thiols of low molecular weight

Abstract

A reactivity and selectivity study of O,O-diethyl 2,4-dinitrophenyl phosphate (1) and O,O-diethyl 2,4-dinitrophenyl thionophosphate (2) with a series of thiols of low molecular weight: N-acetyl cysteine (NAC), L-cysteine (Cys), homocysteine (Hcys), glutathione (GSH), and D-penicillamine (Pen) was conducted. Results show that (i) these nucleophiles only attack at the aromatic moiety of both triester derivatives, (ii) a kinetic control product by sulfhydryl attack of thiols was observed in the reactions of both triesters with Cys and Hcys, followed by an intramolecular amine attack leading to a thermodynamic control product. The kinetic study leads to the proposal of Meisenheimer complex formation and then proton transfer to the reaction media as the mechanism of these reactions.