Oxidation of sulfoxides

The oxidation of sulfoxides to sulfones is accomplished with air in the presence of noble metal salts [10 or with sodium permanganate [837] (equations 578 and 579). 

Sodium permanganate and, especially, osmium tetroxide oxidize sulfoxides to sulfones but do not oxidize sulfides [837]. When a mixture of equimolar amounts of diphenyl sulfide, diphenyl sulfoxide, and osmium tetroxide is refluxed in ether for 48 h, the sulfoxide is oxidized in 96% yield to the sulfone, whereas the sulfide is completely recovered [837], Certain unsaturated sulfoxides treated with a catalytic amount of osmium tetroxide and trimethylamine oxide as a reoxidant are not only oxidized to sulfones but also hydroxylated at the double bond. The sulfoxide group exerts a steric influence in the hydroxylation two stereoisomers of a sulfoxide yield, by syn hydroxylation, two different stereoisomeric diols (equation 580) [1102]. 

Nitrogen analogues of sulfoxides, sulfilimines, when protected by a tosyl group at the nitrogen, are converted into nitrogen analogues of sulfones, sulfoximines, by tetrabutylammonium hypochlorite, which is pre- 

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The oxidation of sulfides to sulfoxides are occasionally found to be unsatisfactory, since the resulting sulfoxides are easily oxidized to sulfones. In order to avoid the further oxidation of sulfoxides into sulfones, several oxidizing agents have been selected. Recently, we found that BTMA Bt3 is the most effective and satisfactory oxidizing agent for this purpose. That is, the reaction of sulfides with a calculated amount of BTMA Br3 and aq. sodium hydroxide in dichloromethane at room temperature, or in 1,2-dichloroethane under reflux, gave sulfoxides in good yields (Fig. 28) (ref. 36). 

Sulfoxides are readily reduced to sulfides however, analogous to the oxidation aldehydes, the oxidation of sulfoxides to sulfones is irreversible as illustrated by the drug sulindac in Figure 5.13. 

The first example of stereospecific oxidation of sulfoxides was described by Stirling (77), who was able to synthesize (-)-( S )-benzyl... 

A rare case of asymmetric induction caused by isotopic substitution was observed (326) when optically active (+)-() )-a,a-dideuteriodi-benzyl sulfoxide 331 was chlorinated with dichloroiodobenzene in pyridine, a,a-Dideuteriobenzyl a -chlorobenzyl sulfoxide 332 was obtained as a major regioisomer with at least 78% isotopic purity. The high stereospecificity of the reaction is indicated by formation of essentially only one of the possible diastereomers. Oxidation of sulfoxide 332 affords the sulfone 334, which has high optical rotation. 

The oxidation of sulfoxides by aliphatic peroxy acids is first order in both reactants the solvent effects have also been investigated. Thiosulfinates are oxidized by peroxy acids to thiosulfonates and not disulfoxides. It had previously been proposed that the disulfoxides are formed first but homolytically cleave and recombine to give thiosulfonates. A series of ab initio calculations were performed (at the 3-210 and 6-3IG levels) which indicate little difference in the rate of oxidation of S over S(0) in the gas phase but faster S(0) oxidation in a reaction cluster. ... 

Oxidation of a snlfide to sulfoxide is known to be an electrophilic reaction, in contrast with nncleophUic oxidation of sulfoxide to sulfone. Since 2-nitrobenzenesulfinyl chloride/KOi oxidizes sulfides to sulfoxides selectively, intermediate 48 must be the actual active intermediate. Moreover, in the presence of l,4-diazabicyclo[2.2.2.]octane (DABCO), which is a radical capturing reagent, the oxidation of methyl phenyl sulfide to the sulfoxide was inhibited. In order to further detect the intermediate 48, pure 5,5-dimethyl-l-pyrroUne-l-oxide (DMPO) was used as a trapping reagent and spin adduct was obtained. The ESR spectrum of the DMPO spin adduct was obtained by the reaction of 02 with 2-nitrobenzenesulfinyl chloride (hyperfine coupling constants, aH = 10.0 G and aN = 12.8 G). 

Diphenylphosphinic chloride reacts with the superoxide anion radical (Oi ) in CH3CN under mild conditions to form the diphenylphosphinic peroxy radical intermediate 77, which shows strong oxidizing abilities in the epoxidation of alkenes, oxidation of sulfoxides to sulfones, desulfurization of thioamides to amides and oxidation of triphenylphos-phines to triphenylphosphine oxide in good to excellent yields (equation 105). ... 

Scheme 9 Mechanism of Peroxide Oxidation of Sulfoxides to Sulfones1611...

With peroxides and peroxycarboxylic acids the oxidation of sulfides to sulfoxides proceeds much more rapidly than that of sulfoxides to sulfones. The oxidation occurs by electrophilic attack of the peroxide on sulfur and, as the nucleophilicity of the sulfur atom is reduced in the sulfoxide compared to that of the sulfide, the sulfoxides are normally easily isolable (generally 1 mol of oxidant is used). Over-oxidation of sulfoxides can also be avoided with specific reagents sodium metaperiodate has been usually used. Sulfoxides are also obtained exclusively by oxidation of sulfides with the couple Mn02/Me3SiCl in methanol [76]. 

Oxidation of sulfoxides with oxo(salen)Mn(V) complexes follows second-order kinetics. Sodium hypochlorite is used as a terminal oxidant. The oxidation of substituted sulfoxides yielded a reaction constant p = -2.57. The reduction of substituted Mn(V) complexes showed a reaction constant of 0.50. A valid reactivity-selectivity principle is operative in this system. An SN2- type mechanism has been proposed.44... 

For the reaction of phenylsulfinyl propanone with Rhodococcus equi, both oxidation of sulfoxide and reduction of carbonyl group proceeded.278 The carbonyl group of (R)-sulfoxide was reduced to the corresponding (Rs,, S c)-alcohols without the reaction of sulfoxide group, while (5)-sulfoxide was oxidized first to the corresponding sulfone and then the carbonyl group was reduced to the corresponding ( -alcohol. 

Figure 3.95 Selective oxidation of sulfoxide over sulfide in the presence of peroxy acid anion.

Organic hydroperoxides are generally used for the preparation of sulfoxides from sulfides, - while sulfones can be obtained in neutral organic solvents in the presence of metal catalysts such as V, Mo and Ti oxides at 50-70 C. Two polymer-supported reagents which involve peroxy acid groups and bound hypervalent vanadium(V) and molybdenum(VI) compounds have been developed for facile oxidation of sulfoxides to sulfones. 

In shaip contrast to peroxy acid oxidation the oxidation of sulfoxides to sulfones with various transi tion metal salts proceeds much faster than that of sulfides to sulfoxides and consequently sulfoxides may be selectively oxidized to sulfones in the presence of sulfides. 

Sodium permanganate monohydrate, NaMn04 H20, which is commercially available, is used for the oxidation of alkenes to carboxylic acids [834] and of alcohols to carbonyl compounds [SJ5], the conversion of sul-finic acids into sulfonic acids [836], and the selective oxidation of sulfoxides to sulfones (sulfides are not oxidized with sodium permanganate in dioxane solutions) 837. ... 

Davis, F. A., Billmers, J. M., Gosciniak, D. J., Towson, J. C., Bach, R. D. Chemistry of oxaziridines. 7. Kinetics and mechanism of the oxidation of sulfoxides and alkenes by 2-sulfonyloxaziridines. Relationship to the oxygen-transfer reactions of metal peroxides. J. Org. 

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