Kinetics of the Aqueous Periodate Oxidation of Aliphatic Disulfides and Thioethers

Article abstract of DOI:10.1021/jo00296a009

Water-soluble aliphatic disulfides are oxidatively cleaved by borate-buffered periodate at 23 deg C.The reaction conditions were selected because they are used for the oxidation of methionine in protein modification, and we wanted to test the reactivity of the disulfide linkage in various bifunctional molecules under these conditions.A colorimetric method was developed which uses 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) to determine the concentrations of periodate.The γ-substituted amine-disulfide 1b consumes 4 equiv of periodate at a rate which is accelerated 100-fold over that of 4,4'-dithiodibutanol (1c) and forms the cyclic sulfinamide 3 an sulfonamide 4.To account for the stoichiometry and acceleration, we have proposed intermediates in which a nucleophilic sulfur atom attacks an oxygen atom of periodate to give an anhydride or complex rather than invoking direct oxygen atom transfer.The γ- and δ-hydroxy disulfides 1a and 1c consume 5 equiv of periodate and are oxidized to the sulfonic acids.The rate of DL-methionine (2a) oxidation in water is reported, along with the oxidations of dibutyl sulfide (2c) and of 1,5-dithiacyclooctane (2d) in 50percent aqueous ethanol.The oxidation of 2d is only 2.1 times faster than the oxidation of 2c, showing that the transannular sulfur atom in 2d does not participate in the oxidation.A comparison of the rate of periodate oxidation of disulfides, thioethers, and ethylene glycol under the same conditions shows that it is possible for these processes to be competitive.