Thiols to sulfonic acids

Cysteic acid is obtained in nearly quantitative yield from cysteine with aqueous hydrogen peroxide in the presence of iron(II) ions.397 Molybdates and tungstates have also been used as effective catalysts for similar transformations.398 An excellent route for the oxidation of 2-thioethanol to isothionic acid has been developed.399 Heteropolyoxometallates supported on alumina400 can also be used to oxidize a range of organo-sulfur compounds. For example, alkyl monosulfides to sulfoxides and sulfones, and thiols to sulfonic acids are a few possibilities (Figure 3.98). 

Figure 5.10 Oxidation of thiols to sulfonic acid salts using metal activated hydrogen peroxide.

Oxidation of Thiols and Other Sulfur Compounds to Sulfonic Acids Thiol-sulfonic acid oxidation... 

Thiols, sulfoxides, sulfones, disulfides,407 and other sulfur compounds can be oxidized to sulfonic acids with many oxidizing agents, though for synthetic purposes the reaction is most important for thiols.408 Among oxidizing agents used are boiling nitric acid and barium... 

For a general review of Ihe oxidation of thiols, see Capozzi Modena, in Patai The Chemistry of the Thiol Group. pt. 2 Wiley New York, 1974, pp. 785-839. For a review specifically on the oxidation to sulfonic acids, sec Gilbert Sulfonation and Related Reactions Wiley New York. 1965, pp. 217-239. 

Alkyl and aryl sulfides (i.e. thioethers) are readily oxygenated to sulfoxides and sulfones (equation 4), whereas thiol groups can be converted to either disulfides or to sulfonic acids (equation 5). 

Just as mild oxidation converts thiols to disulfides, vigorous oxidation converts them to sulfonic acids. KMn04 or nitric acid (HN03), or even bleach (NaOCl), can be used as the oxidant for this reaction. Any Lewis structure of a sulfonic acid requires either separation of formal charges or more than 8 electrons around sulfur. Sulfur can have an expanded octet, as it does in SF4 (10 electrons) and SF6 (12 electrons). The three resonance forms shown here are most commonly used. Organic chemists tend to use the form with an expanded octet, and inorganic chemists tend to use the forms with charge separation. 

More energetic oxidation of thiols leads to sulfonic acids, Thiophenol dissolved in a solution of potassium hydroxide in dimethylformamide is oxidized by oxygen at 23.5 °C over a 22-h period to benzenesulfonic acid in 91% yield [53], Lauryl mercaptan gives dodecanesulfonic acid in 100% isolated yield upon treatment with potassium peroxymonosulfate, 2KHS05 KHS04 K2S04, at room temperature for 30 min [205]. 

Wallace and Schriesheim dried the solvent by distillation under nitrogen over Linde I3X molecular sieve (calcined under N at 350° for 4 hrs.) and stored it in a dry box equipped with a moisture conductivity cell. They found it superior to DMF or tetramethylurea as solvent for base-catalyzed (KOH or NaOH) autoxidation of thiols and disulfides to sulfonic acids. It is superior also for base-catalyzed autoxidation of alkylthiophenes and toluene, and of 5-0,2 cyclic ketones to the corresponding dibasic acids."... 

A limited number of drugs contain a sulfur atom. Thus, thiol compounds (Figure 32.6d) can be oxidized to sulfenic acids, sulfinic acids, and finally to sulfonic acids. Depending on the substrate, the pathway is mediated... 

Thiols can be oxidized to sulfonic acids by stronger oxidizing agents. This method is generally applicable and has often been used for preparation of specific sulfonic acids. Nitric acid583,584 or potassium permanganate585... 

Disulfides can be oxidized to sulfonic acids in the same way as thiols 589-593... 

In the recent drive to prepare mesoporous solid acid catalysts for liquid phase processes, a popular approach has been to tether sulfonic acid groups to mesoporous silica supports. The preferred method for functionalising has been to incorporate 3-mercaptopropylsilane in the synthesis gel for the mesoporous silica, and then, after precipitation and isolation, to oxidise the thiol group to sulfonic acid. These materials have exhibited relatively high catalytic activity and the approach is emerging as one of the most successful for preparing acid forms of porous silica. 

Thiol compounds can be oxidized to disulfides, or to sulfenic, sulfinic and finally to sulfonic acids. Similarly sulfides are easily converted by monpoxygenases to sulfoxides and then to sulfones. Thiocarbonyl derivatives are also substrates of monooxygenases, forming 5-monoxides (sulfines) and then 5-dioxides (sulfenes). The latter are highly reactive metabolites, specially towards nucleophilic sites in biological macromolecules, and are beUeved... 

A number of substances in this group contain a thiol group, which is predicted to be metabolized by methylation followed by oxidation, conjugation with GSH, S-glucuronidation and/or oxidation to sulfonic acids. These would be the major routes... 

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