Oxidation to sulfoxide

Alkyl- and aryl-thiopyridazines are oxidized to sulfoxides, sulfones or sulfonic acids, depending on the reaction conditions. N- Oxidation can take place simultaneously. 

Both 2- and 7-methylthiopyrido[2,3- f]pyrimidines have been oxidized to sulfoxides and sulfones with hydrogen peroxide or MCPBA, as have 2-arylthio derivatives in the... 

In contrast to thiazoles, certain isothiazoles and benzisothiazoles have been directly oxidized to sulfoxides and sulfones. 4,5-Diphenyl-l,2,3-thiadiazole is converted by peracid into the trioxide (146). Although 1,2,5-thiadiazole 1,1-dioxides are known, they cannot be prepared in good yield by direct oxidation, which usually gives sulfate ion analogous to the results obtained with 1,2,4- and 1,3,4-thiadiazoles (68AHC 9)107). 

Alkylthio groups are oxidized to sulfoxides by H2O2 and readily by various oxidizing reagents to sulfones, e.g. in the imidazole series. The SR group is replaced by hydrogen with Raney nickel, and dealkylation is possible, e.g. of 3-alkylthio-l,2-dithiolyliums to give... 

Hydroxy and mercapto substituents at the 3- and 5-positions can also exist in tautomeric forms (see Section 4.01.5.2) and can be alkylated at either the substituent or the ring nitrogen atom. 3-Methoxy groups are not replaced by nucleophiles, but both 3- and 5-alkylthio groups react readily, as does 3-methoxy-l,2-benzisothiazole. Alkylthio compounds can be oxidized to sulfoxides and sulfones, and the latter readily undergo nucleophilic replacement. All the hydroxy compounds react with phosphorus pentachloride to give the chloro derivatives. 

Thiols, the sulfur analogs of alcohols, are usually prepared by Sjv 2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide gives back the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an Sk2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are much more nucleophilic than ethers and can be oxidized to sulfoxides and to sulfones. Sulfides can also be alkylated by reaction with a primary alkyl halide to yield sulfonium ions. 

Juliette LY, MR Hayman, DJ Arp (1993) Inhibition of ammonia oxidation in Nitrosomonas europeae by sulfur compounds thioethers are oxidized to sulfoxides by ammonia monooxygenase. Appl Environ Microbiol 59 3718-3727. 

Mercapto-l,2,4-thiadiazoles exist as an equilibrium of tautomers with the equilibrium favoring the thione tautomer. They are acidic with a pA a of around 5. A variety of methylating agents (e.g., diazomethane, dimethyl sulfate and methyl iodide) give S-methylated products and no N-methylation has been observed. They are readily oxidized to sulfoxides and sulfones with either z-chloroperbenzoic acid or hydrogen peroxide in acetic acid <1996CHEC-II(4)307>. There have been no new publications on S-linked substituents since the publication of CHEC-II(1996). 

The same combination of reagents, now with a 3 1 ratio of hydroperoxide to sulfide, gives a quantitative yield of RS(0)2R/. The reactions proceed to completion in about 2h at 323 K in chloroform. Only 0.3-0.5 mol% of 1 relative to RSR was needed. It was shown that oxidation to sulfoxide precedes sulfone formation. Again, the reaction is tolerant of many functional groups (42). 

Similar to nitrogen compounds, electron-rich sulfur compounds, such as the sulfides, with the lone pair of electrons on the sulfur atom, are oxidized to sulfoxides and, further, to sulfones by the H202/titanosilicate sytem (218,232, 233). Table XXXI (232) illustrates typical conversions and product selectivities for various sulfides for the reactions catalyzed by TS-1. Bulky sulfides such as alkyl, phenyl sulfides are relatively unreactive because of their steric exclusion from the pores of TS-1. Diphenyl sulfide could not be oxidized at all. As the diffusivity and, hence, the conversion of the sulfide decreases, the further oxidation of the primary product (sulfoxide) becomes more competitive, leading to increased formation of the corresponding sulfone (Table XXXI) ... 

The kinetic resolution of /3-hydroxy sulfides mediated by CHMO provides an excellent result in the case of sulfide ( )-2 and moderate results with ( )-l and ( )-3. Indeed, the enzyme-catalysed oxidation to sulfoxide 2a showed remarkable enantio- and diastereo-selectivity with an enantiomeric ratio E of 299 and with an ee > 98 % (C = 47 %). 

S-Oxidation to sulfoxide and sulfone aromatic methyl group hydroxylation... 

The development of sulfone linkers, the exploration of sulfone based chemical transformations and cleavage strategies are an important objective in soHd-phase organic synthesis. This kind of Hnker (Tab. 3.7) has been used with thioethers [108], sulfoxides [109], sulfones [110], sulfonic acids and their corresponding derivatives [111]. Because carbon-sulfur bonds can be cleaved under very mild conditions, some Hnkers have been based on this effect. They can be cleaved under reductive conditions ]112, 113], photolytic conditions [114, 115] or with strong bases [116]. Various safety catch Hnkers have been developed based on the fact that thiols can be oxidized to sulfoxides and sulfones [112, 113]. 

Oxidation to sulfoxide occurs with fuming nitric acid, whereas the sulfone is formed in sulfochromic acid ... 

The relatively rare 1,2-thiazetidine 1-oxides can be oxidized to sulfoxides with MCPBA (Scheme 25) (81TL583). 

The synthesis of sulfoxides from sulfides has been widely explored, and numerous oxidants have been investigated to achieve an efficient and selective sulfoxidation [38]. However, most of the reagents require carefully controlled conditions, including the quantity of oxidants, to avoid the formation of sulfone side products. Control to avoid formation of sulfones is particularly difficult since the first oxidation to sulfoxides requires relatively high energy [38]. m-Chloroperbenzoic acid (mCPBA) has been intensively used in the synthesis of prazole derivatives [39]. 

Sulfoxides.1 Sulfides are oxidized to sulfoxides only by TiCl3 and 30% H,0, in aqueous methanol at room temperature within about 5 minutes. Yields are >90%. 

Thiabenzenes should be considered as sulfonium betaines. They react readily with acids to give mixtures of 2H- and 4/f-thiinium salts, behave as dienes with dienophiles (Equation 9), and can be oxidized to sulfoxides. The sulfimide (450) is an aza analogue of a thiabenzene and it is oxidized by KMn04 to the corresponding sulfoximide. 

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