Ravikumar Seetharama - Mild and selective oxidation of sulfur compounds in trifluoroethanol: Diphenyl disulfide and methyl phenyl sulfoxide., Org Syn 2003; 80: 184-189.

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    1. Procedure


      Diphenyl disulfide. In a 100-mL, round-bottomed flask equipped with a   magnetic stirrer are placed   11.0 g (10.25 ml, 0.1 mol) of benzenethiol and 50 mL of trifluoroethanol(Note 1). The mixture is stirred and cooled in   an ice bath (Note 2) and 12.5 mL   (3.73 g, 0.11 mol) of 30% aqueous hydrogen peroxide (Note 3) is added dropwise over a period of 15   min through an addition funnel. After completion of the addition,   the ice bath is removed and the reaction mixture is allowed to   stir at room temperature for 24 hr. Diphenyl disulfide is sparingly soluble   in trifluoroethanol and precipitates out of   solution. The solids are collected on a Buchner funnel and dried under vacuum to   afford 10.6 g of diphenyl disulfide (97%) (Note 4). Sodium sulfite 2.52 g (0.02 mol) is   added to the mother liquor to decompose the excess peroxide and   the mixture is heated in a water   bath at 50°C for 30 min. A starch iodide test is negative.   The liquid is transferred to a 100-mL,   round-bottomed flask, fitted with a distillation unit having a Vigreux column (5   cm). The flask is heated in an oil   bath and the solvent is distilled to recover the   trifluoroethanol (Note 5).  

        Methyl phenyl sulfoxide. To a     100-mL, round-bottomed flask    equipped with a magnetic stirrer    are added 12.4 g (0.1 mol) of     thioanisole and 50 mL of trifluoroethanol (Note 1). The mixture is stirred and cooled     in an ice bath (Note 6) and 12.5 mL     (3.73 g, 0.11 mol) of 30% aqueous hydrogen peroxide is added     dropwise over 30 min using an addition funnel(Note 7). After completion of the addition,     the ice bath is removed and the reaction mixture is stirred at     room temperature for 8 hr (Note 8). Sodium sulfite (2.52 g, 0.02     mol) is added to decompose the excess hydrogen peroxide and the     mixture is heated in a water bath at 50°C for 30 min (a starch     iodide test is negative). The flask is fitted with a     distillation unit having a Vigreux column (5 cm) and heated     with an oil bath to remove the solvent by distillation (Note 5). Ether (100 mL) is added to the     residue and the mixture is dried over 28     g of magnesium sulfate. Solids are     removed by filtration and washed with ether (2 × 50 mL). The combined     filtrate and washings are concentrated under vacuum to afford     14.9 g of a slightly yellow oil     that crystallizes upon cooling in an ice bath. The crude     sulfoxide is transferred to a 25-mL     distillation flask with the aid of a small amount     ofdichloromethane. After removal     of solvent, simple short path distillation (Note 9) of the crude product affords     12.8 g (91%) of pure methyl phenyl sulfoxide (Notes     10, 11).  


      Methods of preparation. Diphenyl disulfide can be prepared by   the action of hydrogen peroxide in acidic or basic   media,2 iodine-hydrogen iodide,3 Sm/BiCl3 in water,4bFeCl3/Nal4c, and by using bromine-aqueous potassium hydrogen carbonate.4 Methyl phenyl sulfoxide has also been   prepared from thioanisole by the action of   hydrogen peroxide inmethanol,5 mCPBA,5b peroxytrifluoroacetic acid6 and sodium periodate.7

      Merits of preparation. Selective oxidative   transformation of thiols to disulfides is of interest for both   biological8 and synthetic reasons.2 Most of the existing methods involve   the use of metal catalysts or halogenated reagents, which lead to   the formation of side-products.

      Organic sulfoxides are useful intermediates for the construction   of many chemically and biologically significant   molecules.9 Most of the current methods for the   oxidation of sulfides to sulfoxides10 suffer from over-oxidation to   sulfones. Even when controlling the reaction temperature, it is   difficult to avoid over-oxidation in most of the reported   procedures.

      The present procedure is based on the use of fluoroalkyl alcohols   as solvents in oxidation reactions. The method is efficient and   versatile, and produces disulfides and sulfoxides under mild   conditions. These reactions have also been developed using   hexafluoroisopropyl alcohol (HFIP) as solvent with a large   variety of substrates (alkyl sulfides, alkyl thiols, vinyl   sulfides, fluorinated vinyl sulfides, thioglucosides) by Bégué et   al.11,12 Replacement of HFIP with trifluoroethanol, a more common and less   expensive solvent, also allows the use of mild conditions and   affords high yields of disulfides and sulfoxides without   contamination. 30% Aqueous hydrogen peroxide is inexpensive and,   since water is the sole byproduct, this method is environmentally   friendly.

      Cooling is advisable during the addition of hydrogen peroxide, but the remainder of   the reaction can be carried out at ambient temperature. This   method may be useful for large-scale reactions since trifluoroethanol can be recovered.

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