Oxidative couplings of thiols to disulfides

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... 

Tetrabutylammonium chlorochromate, (C4H9)4XCr03CI, is formed by adding a solution of chromium trioxide in concentrated hydrochloric acid to a solution of tetrabutylammonium hydrogen sulfate in 5 N hydrochloric acid at 0 °C. The dry compound is used in chloroform for the oxidation of alcohols to carbonyl compounds and the oxidative coupling of thiols to disulfides [619],... 

The oxidative coupling of thiols catalyzed by Fem-exchanged montmorillonite in phosphate buffer (pH 7.2) has also been demonstrated (Scheme 3.48) [151]. This system gives the corresponding disulfide as the sole product, which is in contrast to a previous report [152], where oxidation of thiols catalyzed by ion-exchanged clay gave the sulfide as the major product. 

Oxidations by oxygen and catalysts are used for the conversion of alkanes into alcohols, ketones, or acids [54]-, for the epoxidation of alkenes [43, for the formation of alkenyl hydroperoxides [22] for the conversion of terminal alkenes into methyl ketones [60, 65] for the coupling of terminal acetylenes [2, 59, 66] for the oxidation of aromatic compounds to quinones [3] or carboxylic acids [65] for the dehydrogenation of alcohols to aldehydes [4, 55, 56] or ketones [56, 57, 62, 70] for the conversion of alcohols [56, 69], aldehydes [5, 6, 63], and ketones [52, 67] into carboxylic acids and for the oxidation of primary amines to nitriles [64], of thiols to disulfides [9] or sulfonic acids [53], of sulfoxides to sulfones [70], and of alkyl dichloroboranes to alkyl hydroperoxides [57]. 

Synthetic strategy Oxidation of thiols to disulfides (oxidative coupling)... 

The selective aerobic (O2) oxidative coupling of thiols in several imidazolium-based ionic liquids is studied in the absence of any base/metal catalysts. Disulfides are obtained from the corresponding thiols in good to excellent yields in l-hexyl-3-methylimidazolium bromide ([hmim]Br). Furthermore, a H NMR-based mechanistic study of the S-S bond formation demonstrated the cooperative role of halide anion and imidazolium cation of [hmimJBr. ... 

Another very important factor in protein architecture is the disulfide —S—S— link. Remote parts of the polypeptide chain can be held close together through the oxidative coupling of two cysteine thiol groups to form a disulfide bridge ... 

An attractive reaction has been reported for BY, which is able in ethanol to catalyze the oxidative coupling of various thiols to disulfides (eq 16). ... 

Air, the cheapest oxidant, is used only rarely without irradiation and without catalysts. Examples of oxidations by air alone are the conversion of aldehydes into carboxylic acids (autoxidation) and the oxidation of acyl-oins to a-diketones. Usually, exposure to light, irradiation with ultraviolet light, or catalysts are needed. Under such circumstances, dehydrogenative coupling in benzylic positions takes place at very mild conditions [7]. In the presence of catalysts, terminal acetylenes are coupled to give diacetylenes [2], and anthracene is oxidized to anthraquinone [3]. Alcohols are converted into aldehydes or ketones with limited amounts of air [4, 5, 6, 7], Air oxidizes esters to keto esters [3], thiols to disulfides [9], and sulfoxides to sulfones [10. In the presence of mercuric bromide and under irradiation, methylene groups in allylic and benzylic positions are oxidized to carbonyls [11]. 

The thiol form (12) is susceptible to oxidation (see Fig. 2). Iodine treatment regenerates thiamine in good yield. Heating an aqueous solution at pH 8 in air gives rise to thiamine disulfide [67-16-3] (21), thiochrome (14), and other products (22). The disulfide is readily reduced to thiamine in vivo and is as biologically active. Other mixed disulfides, of interest as fat-soluble forms, are formed from thiamine, possibly via oxidative coupling to the thiol form (12). 

Disulfides. Thiols are oxidized to disulfides by dimethyl sulfoxide. This oxidative coupling is particularly useful for coupling of aryl thiols (equation I). 

The question then becomes—how does Pb(lV) become associated to I for the required electron transfer to occur Two anchoring places in I are conceivable, sulfur and nitrogen atoms, with precedent in the literature. While thiols are oxidized readily to disulfides and sulfides are converted to sulfoxides, aromatic amines are transformed to amides by LTA. However, the nitrogen atom of I is not part of an aromatic amine but an imine instead, and little if anything is known about the coupling of this unsaturated function with LTA. Besides, products II-IV exhibit this imine function unchanged. Consequently, compound I, as it stands, is likely to become linked with lead at the sulfur atom. 

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