Kinetic studies on the reactions of 3-isothiazolones with 2-methyl-2-propanethiol

Abstract

The kinetics of the ring-opening reactions of the 3-isothiazolones (1a-d) with aqueous 2-methyl-2-propanethiol has been explored at pH 4. The results strongly suggest that the reaction is second order in thiol and third order overall. Extrapolation of the kinetic data gives third-order rate constants that lie in the order (1a) > (1b) > (1c) > (1d) in line with the known biological activity of these derivatives. The mechanism of the reaction is thought to involve attack by one thiol at the sulfur atom of the isothiazolone with the concomitant hydrogen bonding of a second thiol to the amide nitrogen. Calculations of the structure and electronic properties of the isothiazolones at the RHF 6-3IG** level are supportive. © 2007 Wiley Periodicals, Inc.