Oxidation of a thioether

There is huge potential in the combination of biocatalysis and electrochemistry through reaction engineering as the linker. An example is a continuous electrochemical enzyme membrane reactor that showed a total turnover number of 260 000 for the enantioselective peroxidase catalyzed oxidation of a thioether into its sulfone by in situ cathodic generated hydrogen peroxide - much higher than achieved by conventional methods [52],... 

Several replacement reactions at C-4 in sydnones may be carried out but aqueous bases must be avoided. Butyllithium can be used to displace bromine from a 3-phenylsydnone the resulting organolithium salt can be carbonylated, will add to ketones, and forms a silyl derivative (80CB1830). A sydnone Grignard derivative can also be made and will add ketones in the normal way (80JCS(Pl)20). Sodium borohydride will reduce a sydnone sulfone, formed by oxidation of a thioether (Table 5) with hydrogen peroxide, back to the unsubstituted sydnone (74T409). 

The purpose of this paper is to present a perspective of the Green Chemistry Issues typically pertinent to the manufacture of Fine Chemicals. This is exemplified by describing the process development of the oxidation of a thioether to a sulphone. By Fine Chemicals I am referring to products generally described as consumer products, pharmaceuticals, agrochemicals, electronic chemicals and similar speciality effect chemicals. The scale of manufacture of a product in this class can vary from tens of kilograms to thousands of tonnes per annum. That class is distinct from bulk chemicals manufactured in excess of hundreds of thousands of tonnes per annum. 

No or little ring closure can be expected in chains containing less than six amino acid residues. For better control it appears to be preferable to apply esters which are fairly inactive but can be activated when cyclization is desired. For instance, oxidation of a thioether to the electron-withdrawing sulfone... 

For the unusual microbial oxidation of a thioether catalyzed by a dioxygenase see [1182]. 

The most widely applied method to prepare sulfones is the oxidation of thioethers. In the course of these oxidations sulfoxides must occur as intermediates. However, since oxidation mechanisms for thioethers and sulfoxides are partly different, these oxidations will be discussed separately. A recently published method337,338 allows oxidation of a... 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Chiral sulfoxides have emerged as versatile building blocks and chiral auxiliaries in the asymmetric synthesis of pharmaceutical products. The asymmetric oxidation of prochiral sulfides with chiral metal complexes has become one of the most effective routes to obtain these chiral sulfoxides.We have recently developed a new heterogeneous catalytic system (WO3-30% H2O2) which efficiently catalyzes both the asymmetric oxidation of a variety of thioethers (1) and the kinetic resolution of racemic sulfoxides (3), when used in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR], Optically active sulfoxides (2) are produced in high yields and with good enantioselectivities (Figure 9.3). ... 

The API fluphenazine enanthate undergoes oxidation of a secondary aryl thioether to the resulting sulfoxide (Fig. 74) (112). 

The Orsay system. A good example of serendipity is the discovery by Kagan and co-workers46 at Orsay that 1 mol of water was necessary to produce the active catalyst able to oxidize prochiral sulfides to sulfoxides with high ee. Optimization of the stoichiometry of the titanium complex permitted the determination of the combination Ti(0-i-Pr)4/(/ ,/ )-DET/H20 (1/ 2/ 1) at -20 °C in CH2C12 as the optimal conditions to achieve high enantioselectivity. Table 6 shows some representative results obtained for the oxidation of several thioethers with tert-butyl hydroperoxide (TBHP) under these conditions.50,51... 

Although it is frequently more convenient to make imidazole and benzimidazole sulfones (and sometimes sulfoxides) by direct oxidation of the thioethers, 4-tosyl groups can also be introduced quite conveniently by a ring synthesis based on the reagent TOSMIC (see Section 4.2 and Scheme 4.2.1). 

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