Oxidation of thiols

Thiols may be oxidised to disulphides by the intermediate formation of covalent 4a flavin-sulphur adducts subsequent nucleophilic attack by another thiol anion displaces dihydroflavin as a good leaving group (XXXXIV). 

The above reactions have been described in terms of substrate oxidation which is the predominant metabolic pathway. However, as enzymes are catalysts the reaction in the reverse direction - reduction of substrate by dihydroflavin - will occur by the microscopically reversed mechanisms. 

General method for oxidation of thiols to disulfides 576 The thiol (0.1 mole) is dissolved in dimethyl sulfoxide (50 ml) and stirred at 80-90° for 8 h. Then charcoal is added and the mixture is cooled, filtered, and stirred into 10 parts of ice-water. After 3 h the disulfide is isolated by filtration or extraction with ether, yields being 80-100%. 

Bis-(4-cyanobenzyl) disulfide 578 / -(Mercaptomethyl)benzonitrile (5 g) is dissolved in 95% ethanol (100 ml), treated with concentrated ammonia solution (25 ml), and exposed to the air for 4 days. The pale yellow needles that separate are recrystallized from 95% ethanol the yield is 70.4% (3.5 g), and the m.p. 148°. 

Bis-(o- and /Mnethoxy- and -ethoxy-phenyl) disulfide 461 The alkoxythiophenol is dissolved in somewhat more than the calculated amount of 10% sodium hydroxide solution, and the theoretical amount of finely powdered iodine is added, whereupon the disulfide separates in crystalline form. After addition of a little sulfur dioxide solution the product is collected and recrystallized from ethanol. 

Bis(benzothiazol-2-yl) disulfide 579,580 A solution of benzothiazole-2-thiol in the calculated amount of dilute sodium hydroxide solution is treated with the calculated amount of aqueous potassium hexacyanoferrate(m) solution. The precipitated disulfide is collected, washed with water, and recrystallized from benzene, the m.p. then being 186°. 

Cyclic disulfides are obtained from dithiols of suitable structure. Luttring-haus and Hagele581 used iron(m) chloride as oxidant for the preparation of 2,3-dihydro-1,2-benzodithiol and l,2,3,4-tetrahydro-2,3-benzodithiin. cis- and /raflj -l -Cyclohexanedimethanethiol can be oxidized in the same way, yielding, respectively, cis- and /ra/w-perhydro-2,3-benzodithiin (2,3-dithiadecalin), both of which exist in the preferred chair conformation  

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A major difference between alcohols and thiols concerns their oxidation We have seen earlier m this chapter that oxidation of alcohols gives compounds having carbonyl groups Analogous oxidation of thiols to compounds with C=S functions does not occur Only sulfur is oxidized not carbon and compounds containing sulfur m various oxida tion states are possible These include a series of acids classified as sulfemc sulfimc and sulfonic according to the number of oxygens attached to sulfur... 

Of these the most important are the sulfonic acids In general however sulfonic acids are not prepared by oxidation of thiols Arenesulfomc acids (ArS03H) for example are prepared by sulfonation of arenes (Section 12 4)... 

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. 

Gas-phase oxidation of thiols has been discussed in some depth (33). This review mainly emphasi2es atmospheric processes, but a section on nitrogen oxides and thiols appears to be broadly appHcable. The atmospheric oxidation chemistry of thiols is quite different from that of alcohols. 

Alkyl sulfonic acids are prepared by the oxidation of thiols (36,37). This reaction is not quite as simple as would initially appear, because the reaction does not readily go to completion. The use of strong oxidants can result in the complete oxidation of the thiol to carbon dioxide, water, and sulfur dioxide. 

Gentle oxidation of thiols leads generally to disulfides When tetrafluoro-1,4-benzeneditliiol is added to dimethyl sulfoxide, a macrocyclic tetradisulfide is formed [102] (equation 94)... 

Oxidation of thiol 287 with air in glyme gave disulfide 288, which on intramolecular oxidative coupling with A,)V-dibromoisocyanurate formed macrocycle 289 in 42% yield (Scheme 188) (99MI3). 

Oxidation of sulfides to sulfoxides and oxidation of thiols to disulfides... 

Although the oxidation of thiols with chlorine or bromine in the presence of water gives sulfonyl halides or sulfonic acids, the reaction of thiols with a stoichiometric amount of BTMA Br3 and sodium hydroxide in dichloromethane-water at room temperature gives disulfides in good yields (Fig. 29) (ref. 37). 

The catalyst effectiveness decreased upon increasing the concentration of the intercalated complexes via aggregation of the closely associated complexes.164 Sulfides were also oxidized by heterogeneous Co(II) complexes.163 Catalytic oxidation of thiols was mediated by Mo complex intercalated in a layered double hydroxide.166... 

A particular interest for clinical applications was a possibility for detection of dopamine by its oxidation on nickel [19], cobalt [65], and osmium [66] hexacyanofer-ates. Except for oxidation of dopamine, cobalt and osmium hexacyanoferrates were active in oxidation of epinephrine and norepinephrine. For clinical analysis it is also important to carry out the detection of morphine on cobalt [67] and ferric [68] hexacyanoferrates, as well as the detection of oxidizable amino acids (cystein, methionine) by manganous [69] and ruthenium [70] hexacyanoferrate-modified electrodes. In general, oxidation of thiols was first shown for Prussian blue [71] and nickel hexacyanoferrate [72], This approach has been used for the detection of thiols in rat striatum microdialysate [73], Alternatively, the detection of thiocholine with Prussian blue was employed for pesticide determination in acetylcholine-esterase test [74],... 

Dimethyl-7-methylthio-6,8,9-triazaisoalloxazine (6,8,9-triazaflavin) 495 was prepared [86JCR(S)382] by cyclocondensation of 479 with N-methylalloxan 494. Compounds 495 was more active than 3,10-dimethyli-soalloxazine in the oxidation of thiols. 

These findings may or may not be applied to DHLA. The chain mechanism of reaction of thiols with superoxide suggests that the first step of this reaction is the oxidation of thiols ... 

Regeneration of superoxide during the oxidation of thiols hints at the possible prooxidant effect of these antioxidants. This suggestion was recently confirmed by Mottley and Mason [212] who have showed that superoxide was formed in the oxidation of DHLA by horseradish peroxidase in the presence of phenol. However, DHLA is dithiolic compound and the other mechanisms such as the concerted mechanism, which has been proposed earlier for flavonoids may be realized (Figure 29.6). 

The conversion (19) of thiols to disulphides coupled with reduction of flavin (vitamin B2 family) is a topic of import in connection with coenzyme reactivity in flavoenzymes. Since flavin oxidation of thiols involves nucleophilic attack of thiolate ion in the rate-determining step (Loechler and Hollocher, 1975 Yokoe and Bruice, 1975), this biologically important reaction would be markedly affected by hydrophobic environments. 

Oxidation of thiols and related compounds with organoselenium(IV) and organotellurium(rV) compounds 102 Other oxidations with selenoxides and telluroxides 106 Thiolperoxidase and haloperoxidase-like activity of organoselenides and organotellurides 108... 

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