A General Mechanism for the Oxidative Cleavage of Amine Disulfides and Cystine in Aqueous Iodine. Isolation of Cyclic Sulfinamides

Article abstract of DOI:10.1021/jo00201a001

When disulfides are cleaved by aqueous iodine, neighboring group participation facilitates the rate of reaction and the formation of cyclized products.The series of bis-disulfides 2 was prepared, X = N(CH3)2, 1, NH2, 2, N(CH3)3⁺, 3, as well as 2, 4.The tertiary amine, 1, is oxidized by aqueous I2 at a rate which is accelerated by as much as 10⁶ over the rate of reaction of the quaternary ammonium iodide salt 3.The oxidation products of 1 are the sulfinic and sulfonic acids while 3 yields the sulfonic acid.Aqueous iodine reacts with the primary amines 2 and 4 at moderately accelerated rates to give the cyclic sulfinamides, isothiazolidine 1-oxide from 2 and tetrahydro-1,2-thiazine 1-oxide from 4.This oxidative cyclization reaction is the most direct route to these cyclic sulfinamides.At a given pH, the rate law for the oxidation of 1 and 2 is -d/dt = -k.At high pH, compound 4 has the same rate law.The kinetic data for 4 at low pH and for 3 resemble those reported in a classical study of the aqueous iodine oxidative cleavage of cystine.The kinetics and mechanisms of these reactions will be discussed.