Thiols oxidation to disulfides

The 3-methyl- and 3-phenyl-l,2,3-oxadiazolinium salts 96 and 97 are capable of oxidizing thiols to disulfides <1995MI817>. New dihydro-1,2,3-benzoxadiazoles, prepared by the reaction of 1,2-benzoquinones with diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) in the presence of triphenylphosphine (Section 5.03.9.4), have been shown to undergo catalytic hydrogenolysis to give phenols (Equation 12) <20050L5139>. 

The dihalides are susceptible to decomposition by hydrolysis. The dibromides oxidize thiols to disulfides, selenols to diselenides, and diphenyl tellurium to diphenyl tellurium oxide. Hydrazine reduces the dihalides to the parent compounds1. 

Little has so far been reported on the chemistry of teUurones. The preparation of several dialkyl tellurones by H2O2 or air oxidation of the corresponding tellurides or telluroxides has been claimed, but it is doubtful whether those compounds were isolated in a pure tellurone form. In 1982 the first definitely characterized tellurone, bis(4-methoxyphenyl) tellurone (60), was prepared by periodate oxidation of the corresponding telluroxide (59 equation 50). Both (59) and (60) woric as mild useful oxidants which show some chemoselectivities and readily oxidize thiols to disulfides. The preparation of dodecyl 4-methoxyphenyl tellurone by a similar method has also been claimed. ... 

Oxidations. The reagent oxidizes benzylic tilcohob to the corresponding aldehydes and secondary alcohols to the ketones in satisfactory yield. Ot more significance it oxidizes thiols to disulfides in CH CI. in high yield Oximes... 

It should be stressed that in order to use the delayed nitroprusside reaction for the detection of acetyl CoA it was necessary first to remove the large amounts of the free mercaptans, mostly glutathione, from the yeast Kochsaft which otherwise would have strongly interfered with the color reaction. We achieved this by titration of the Kochsaft with iodine, thereby oxidizing thiols to disulfides which do not any longer react with nitroprusside at alkaline pH. The identity of the sulfhydryl component of our active preparations with coenzyme A was finally proved in various ways which should not be discussed here in detail. 

In Summary The naming of thiols and sulfides is related to the system used for alcohols and ethers. Thiols are more volatile, more acidic, and more nucleophilic than alcohols. Thiols and sulfides can be oxidized, thiols to disulfides or sulfonic acids and sulfides to sulfoxides and sulfones. 

The most important oxidation from a biochemical perspective is the conversion of thiols to disulfides... 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

Selenoxides and telluroxides also function as mild oxidants for the conversion of thiols to disulfides as shown in equations (16) and (17) for the reaction of thiophenol with diphenylselenoxide (47) and diphenyltelluroxide (48). Mechanistically, the oxidation of thiols to disulfides with selenoxides and telluroxides is a multi-step process, which takes advantage of the ease with which tellurium(IV) and selenium(IV) species form trigonal bipryamidal... 

Fig. 21 General mechanism for the oxidation of thiols to disulfides with selenoxides or telluroxides.

A reasonable mechanism for the iodine oxidation of 5-Trt cysteine peptides is given in Scheme 6. 45 Reaction of iodine with the divalent sulfur atom leads to the iodosulfonium ion 5 which is then transformed to the sulfenyl iodide 6 and the trityl cation. Sulfenyl iodides are also postulated as intermediates in the iodine oxidation of thiols to disulfides. The disulfide bond is then formed by disproportionation of two sulfenyl iodides or by reaction between the electrophilic sulfur atom of R -S-I and the nucleophilic S-atom of a second R -S-Trt molecule. The proposed mechanism suggests that any sulfur substitution (i.e., thiol protecting group) capable of forming a stabilized species on cleavage, such as the trityl cation, can be oxidatively cleaved by iodine. 

There is also an expectation that thiols can be directly oxidized through to disulfides (RSSR in Fig. 4.4B) (Mestres et ah, 2000 Rauhut et ah, 1996), a mechanism also suggested for the case of 3MH (Murat et ah, 2003) where a protective effect from anthocyanins present in the wine was noted. In one study, the concentrations of both ethanethiol and the related oxidized form of diethyl disulfide in a red wine were found to decrease over a 60-day period, and at a greater rate under aeration (Majcenovic et ah, 2002). However, in a survey of wines over five vintages, the older wines were shovm to contain higher concentrations of diethyl disulfide, and lower concentrations of ethanethiol (Fedrizzi et ah, 2007). 

Although the oxidation of thiols to disulfides in the presence of a catalyst is a reaction of commercial interest, it is only comparatively recently that the marked effects of impurities on the system has been realized. Wallace and co-workers (13, 14) have studied the metal-catalyzed oxidation of some thiols in the presence of a few metal ions and complexes under comparable conditions, and they have suggested a general mechanism for the reaction, based on Reactions 1, 4, 5, 6, and 7. The rate of reaction was found to depend on the chemical nature and the physical state of the catalyst. The reaction was suggested to involve metal complexes in the solid state (13). 

In summary, the oxidation of thiols to disulfides is quantitative in aqueous alkaline solution and may best be effected at high oxygen pressures in the presence of a catalyst. The catalyst should dissolve in the alkaline solutions, and of the simple metal salts, the addition of copper, cobalt, and nickel results in the most effective catalysis. 

Catalysts of this type are also extraordinarily reactive for the oxidative coupling of thiols to disulfides, and the reaction is quantitative in a wide variety of organic solvents. In this case, the analogous first step would be... 

Kinetic Studies Provide Only Limited Mechanistic Information. While such studies are invaluable and frequently indicate the nature of pre-rate-determining steps, they provide almost no information concerning such vital fast steps as electron transfers and rearrangements. For example, despite extensive studies of the kinetics of acetaldehyde and vinyl acetate syntheses, it is clear only that olefin, nucleophile, and palladium combine in a complex. The nature of the rate-determining step as well as the details of post-rate determining product forming steps remains uncertain (7,94). In some cases—e.g., the metal-catalyzed autoxi-dation of thiols to disulfides—re-oxidation of metal to its catalytically... 

In 1966, it was found that stoichiometric amounts of Fe203 were capable of oxidizing acyclic thiols to disulfides in hydrocarbon media at 55 °C (Scheme 3.47) [149]. 

Oxidations of hydrocarbons (cycloalkanes, cycloalkenes, aromatics) photo-catalyzed by metallotetrapyrroles lead to the formation of epoxides, aldehydes, ketones, alcohols, and carboxylic acids both in solutions and polymer matrices. These processes frequently occur as selective (one-product formation) reactions. Irradiation with visible light has a pronounced accelerating effect on such important industrial processes as the oxidation of thiols to disulfides (Merox process [265]) in a treatment of petroleum distillates or waste water cleaning. 

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