Thioether oxidation

The a- and y-pyridinethiones can be oxidized to the corresponding sulfonic acids, e.g. (134), by reagents such as alkaline permanganate, nitric acid and peracids (67FES1069). Thioether oxidation gives the corresponding sulfone, e.g. (135 Scheme 125). 

Oxidation Carbon-Sulfur Systems. The most common metabolic process that affects a C-S system is S-oxidation. The S atom is oxidized to a sulfoxide. In the case of thioketones, the C=S double bond is converted to a C=0 bond. For thioethers, oxidative S-dealkylation is a possibility. 

The racemic API, modafinil, can be synthesized via several approaches. For example, treatment of a-phenyl benzenemethanethiol 8 with methyl chloroacetate 9 at 100 °C for 4 h gave the methyl ester of benzhydrylsulfanylacetic acid, 10. Treatment of 10 with ammonia produced amide 11. The subsequent thioether oxidation was easily carried out using H202 to deliver modafinil, 1 (Scheme l).26... 

The mechanism of thioether oxidation is described as involving electrophilic attack of 02 on the sulfur atom (or conversely nucleophilic attack of thioether S on 02) leading to the formation of sulfoxides and... 

Very recently, Fedin, Kim and colleagues synthesized a homochiral metalorganic polymeric material, [Zn2(bdc)(L-lac)(dmf)] (DMF) (36), by using a one-pot solvothermal reaction of Zn(NO3)2, L-lactic acid (L-H2lac) and 1,4-benzenedicarbox-ylic acid (H2bdc) in DMF [53]. This 3-D homochiral microporous framework exhibited permanent porosity and enantioselective host-guest sorption properties towards several substituted thioether oxides. Although 36 could catalyze the oxidation of thioethers to sulfoxides with size and chemoselectivity, no asymmetric induction was observed. 

The asymmetric oxidation of sulfides represents a straightforward access to chiral sulfoxides that are useful compounds for asymmetric synthesis as chiral auxiliaries and also for the synthesis of biologically active molecules. Among the different methods to perform these reactions, titanium-mediated thioether oxidation is one of the most attractive. Indeed, Kagan ° and Modena independently showed that the use of chiral titanium complexes derived from Sharpless reagent allows the asymmetric oxidation of prochiral sulfides (Scheme 7.6). 

To get a greener process, Jackson and coworkers reported a study dedicated to the use of immobilised Schiff base ligands for asymmetric thioether oxidation (Scheme 7.9). The salen ligand derivative 13, linked to a Wang resin, formed an extremely robust titanium complex, which allows the system to be reused several times without erosion of conversion and enantioselectivity. No leaching of titanium was detected in the reaction solvent. 

According to detailed kinetic studies [10], cis-RuCl CMe SO) is much less active [5,6] in thioether oxidation than trans-RuBr (Me SO). ... 

Thioether oxidation is catalyzed by Ce(IV), whose function is to effect the first step in the above scheme and to oxidize a hydrated form of the cation radical to the sulfoxide. Reoxidation of the... 

The synthetic sequence involving formation of a thioether, oxidation to the corresponding sulfone and the RBR need not be performed consecutively, although it almost invariably is when applied to the synthesis of complex targets. An example in which divorcing the sulfone preparation from the RBR was actually beneficial to the synthetic strategy is seen in the total synthesis of the resorcylic acid macrolactone (RAL) aigialomycin D by Harvey and coworkers. ... 

The critical role of the nitrosonium complex in thioether oxidations with NO was probed by its selective activation at -78 °C in dichloromethane solution [22] ... 

NO used for thioether oxidation to sulphoxides is unique in that it can be employed as a reagent in stoichiometric amounts or as a catalyst for autoxidation. Oxygen alone cannot oxidise thioethers at ambient temperatures and atmospheric pressures, so NO must be the active agent in the catalytic oxidation. There is strong correlation between the oxidative conversion of thioethers to sulphoxides and the concentration of [R S, NO ] complexes. The enhanced reactivity of an alkyl thioether such as dibutyl sulphide relative to diphenyl sulphide directly parallels the difference in the steady-state concentrations of the corresponding nitrosonium donor-acceptor complexes [22] [Bu S, NO ], [Ph S, NO ]. The same trend in the structure/reactivity relationship is more clearly shown in the oxidative conversion of the homologous thioethers in... 

Anchimerically assisted redox reactions. Vn. A conparison of the effects of neighboring primary, secondary, and tertiary amine groups on the kinetics and mechanism of thioether oxidation by aqueous iodine, J. Org. Chem. 48 (14), 2371-2374 (1983). 

In acetonitrile, catalytic thioether oxidation may exhibit a short induction phase which is followed by the main reaction (Figure 1). This induction period depends on the concentrations of CEES, Au, and O2. At higher concentrations the induction period is shorter (Table 1 shows the [O2] dependence of the induction period). During the induction period the system remains colorless, neither CEES nor O2 are consumed, and no CEESO is formed. At the end of the induction period, the solution rapidly becomes yellow. The electronic absorption spectmm of this yellow species is fully... 

In general, other stoichiometries for OVatr thioether oxidations are also possible including the more common "oxidative dehydrogenation" process (eq 4 for substrate = SubH2). These reactions are more favourable for... 

This mechanism has been proposed for some thioether oxidations by and the conversion of 2 to Q-Au -CEES and CEESO can te assisted by H20 eq 24. However, this mechanism is also very unlikely in our catalytic system analysis of the reaction kinetics unambiguously rules it out. If eqs 22 and 23 were rate limiting, then the overall rate would be eq 25. 

In principal, a radical-chain thioether oxidation initiated by Au(III) complexes may also take place. Such a mechanism has been proposed by Riley et al. for aerobic thioether oxidation catalyzed by Ce salts. This sulfoxidation reaction proceeds in CH3CN at elevated temperatures (> 70 °C). The proposed mechanism includes the reduction of Ce(IV) by thioether to form the radical cation RaS", which is efficiently trapped by Oa to give RaS OO. The latter radical, being a strong oxidant, reoxidizes Ce(III) to... 

The simplest procedure for sulfoxide synthesis is thioether oxidation by H2O2, and acids are efficient catalysts for this reaction. In the presence of protons H202is a potential intermediate in Au(I) reoxidation by 02,eq 28 ... 

An interesting feature of our Au-based catalysts is the high substrate selectivity during competitive thioether oxidation (Figure 10). When equal amounts of two thioethers (0.36 M total thioether concentration), THT and CEES, are added simultaneously to the Au(ni)/NOj7(Cr)2 system, the initial rates of oxidation of the two substrates are 9 x 10 and 5 x 10 M s . 

Cimpeanu, V., Parvulescu, V., Parvulescu, VJ., Thompson, J.M., and Hardacre, C. (2006) Thioethers oxidation on dispersed Ta-silica mesoporous catalysts in ionic liquids. Catal Today, 117 (1-3), 126-132. 

A homogeneous catalyst for selective Oj oxidation at ambient temperature. Diversity-based discovery and mechanistic investigation of thioether oxidation by the Au(III)Cl2N03(thioether)/02 system, E. Boring, Y. V. Geltii, and C. L. Hill, J. Am. Chem. Soc., 2001,123, 1625. 

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