Oxidation in Fluoro Alcohols: Mild and Efficient Preparation of Disulfides from Thiols

Abstract

Quantitative oxidative conversion of thiols to disulfides was effected by aqueous 30% H 2 O 2 in trifluoroethanol at ambient temperature under neutral conditions. Selective oxidative conversion of thiols to disulfides is of interest from both a biological 1 and a synthetic point of view. 2 It was found that under biological conditions this reaction occurs in the presence of oxidants such as flavins, cytochromes and dehydroascorbic acid. 3 Thiols are among functional groups which can be easily over oxidized and therefore extensive studies have been carried out for their controlled oxidation. 4 Although hydrogen peroxide is known to oxidize some thiols to disulfides, 2a this requires very long reaction times and proceeds only in strong acidic or basic conditions. Reagents like iodine/hydrogen iodide, 5 bromine-aqueous potassium-hydrogencarbonate, 4c molecular bromine, 6 Sm/BiCl 3 in aqueous medium, 7 FeCl 3 /NaI 2b and KMnO 4 −CuSO 4 2c were reported in the literature to effect oxidative coupling of thiols to disulfides. Enzymatic 8 and electrochemical 9 methods are also known to perform this oxidative transformation. Most of the existing methods involve the use of metal catalysts or reagents like halogens and always suffer with effluents due to these reagents. So there is a need to develop a clean, mild and efficient methodology to synthesize aliphatic, aromatic and heteroaromatic disulfides.

Fluorinated Alcohols: A New Medium for Selective and Clean Reaction

“…17 It can be anticipated that due to their efficiency, fluorinated alcohols will be increasingly used as solvents and that their many advantages over other solvents can be exploited in other reactions for improving processes and cleaner chemistry. We are still actively involved in this objective.…”

A Straightforward and Mild Method of Tethering Monosaccharides to Thieno[2,3-d]pyrimidinones via the Copper(I)-catalyzed Azide-Alkyne ‘Click Chemistry’

“…In addition to the signals of the thienopyrimidinone, the biomolecules, and the linker moieties, diagnostic signals for the 1,2,3-triazole ring were found in the NMR spectra [δ = 7.7 -7.8 ( 1 H NMR), δ = 120 -122 and 142 -146 ppm ( 13 C NMR)]. Although homodisulfides are generally synthesized via oxidative coupling of their corresponding thiols [23], many procedures are offered for this conversion including using halogen-containing reagents [24], metal ions [25] and hydrogen peroxide [26]. Sucholeiki [27] reported that thioethers can readily be used for the attachment of organic molecules to solid supports and can undergo light-induced heterogeneous C-S bond cleavage upon irradiation with 350 nm light.…”

Quinolinium tribromide; a mild and very efficient oxidant in organic synthesis

“…In recent years, much effort has been invested in the preparation of disulfides in solvent-free conditions, but most of them have employed some volatile organic solvents such as dichloromethane in the work-up step. 22 The green chemistry with ether as a work-up solvent is an advantage of our work. In addition, in comparison with two structurally analogous tribromides, PHP (pyridinium hydrobromide perbromide) and BPHP (bipyridinium hydrobromide perbromide), this reagent is more reactive and oxidize thiols in shorter reaction time.…”