Phenyl methyl thioether

Irradiation of 5-phenyl thiolacetate (203) in benzene gives diphenyl disulfide (206) as major product (52%). However, minor amounts of ortho-rearranged (204) and para-rearranged (205) products are also formed, along with thiophenol (17%) and methyl phenyl thioether (208) (19%) (Scheme 54) [155],... 

Methyl phenyl thioether with hexadecane in an aqueous culture medium of diammonium hydrogen phosphate, magnesium sulphate, traces of ferrous sulphate containing yeast extract after inoculation with Corynebacterium equi, FO 3730 and incubation during 3 days at 30°C, afforded (R)-methyl phenyl sulphoxide in quantitative yield (enantiomeric excess 75%) (ref. 181). 

Deall lation. Chloroformates such as vinyl chloroformates (40) are used to dealkylate tertiary amines. Chloroformates are superior to the typical Von Braun reagent, cyanogen bromide, because of increased selectivity producing cleaner products. Other chloroformates such as aHyl, methyl, phenyl, and trichloroethyl have also been used in dealkylation reactions. Although the dealkylation reaction using chloroformates is mostiy carried out on tertiary amines, dealkylation of oxygen or sulfur centers, ie, ethers or thioethers, can also be achieved. a-Chloroethyl chloroformate [50893-53-3] (ACE-Cl) (41,42) is superior to all previously used chloroformates for the dealkylation reaction. ACE-Cl has the advantage that the conditions requked for ACE... 

Coulometric measurements demonstrated the formation of the thioether with an electricity consumption of one Faraday per mole. However, the thioether yield was only of the order of 50% and, in addition, the presence of sulphinate ion in the electrolysis solutions was shown by methylation with CH3I, when methyl phenyl sulphone was formed and determined. 

As the final example in this section, a Li-mediated carboaddition/carbocycliza-tion process will be described. Thus, Cohen and coworkers observed a 5-e%o-trig-cy-clization by reaction of the lithium compound 2-349 and a-methyl styrene 2-350 to give 2-352 via 2-351 (Scheme 2.82). Quenching of 2-352 with methanol then led to the final product 2-353 [189]. In this process, 2-349 is obtained by a reductive lithia-tion of the corresponding phenyl thioether 2-348 with the radical anion lithium 1-(dimethylamino)naphthalenide (LDMAN) (2-354). Instead of the homoallylic substance 2-348, bishomoallylthioesters can also be used to provide substituted six-membered ring compounds. 

Homofamesyl iodide 7 was prepared by the reaction sequence shown in the margin. Of interest here is the two-step transformation of an alkyl halide into a Crextended alkyl halide.9 Compound 30 is first subjected to a nucleophilic substitution by an urganolithium species with formation of a homoallylic phenyl thioether This is then methylated in a second step to an intermediate sulfonium salt. The final SN2 reaction with an iodide ion releases thioanisol as a stable leaving group to give compound 7. 

Another class of peroxidases which can perform asymmetric sulfoxidations, and which have the advantage of inherently higher stabilities because of their non-heme nature, are the vanadium peroxidases. It was shown that vanadium bromoperoxidase from Ascophyllum nodosum mediates the production of (R)-methyl phenyl sulfoxide with a high 91% enantiomeric excess from the corresponding sulfide with H202 [38]. The turnover frequency of the reaction was found to be around 1 min-1. In addition this enzyme was found to catalyse the sulfoxidation of racemic, non-aromatic cyclic thioethers with high kinetic resolution [309]. 

The oxidation is conveniently carried out by addition of the thioether to a slight excess of aq. 0.5 M Na-metaperiodate at ice bath temp. The reaction is complete in 3-12 hrs. and affords pure sulfoxide, usually in better than 90% yield. It appears expedient to use a mixed solvent system, e. g. methanol-water, in those cases where water-solubility of thioether is slight.— E Methyl phenyl sulfide methyl phenyl sulfoxide. Y 99%. F. e. s. N. J. Leonard and C. R. Johnson, J. Org. Chem. 27, 282 (1962) Am. Soc. 84, 3701 (1962). 

As described previously for trifluoromethyl ethers, Umemoto [23c] reported on the trifluoromethylation of thiols with -(trifluoromethyl) dibenzothiophenium triflate affording the corresponding trifluoromethyl thioethers in medium to good yield. Otherwise, trifluoromethyl phenyl thioethers and ring-substituted analogs are readily made from iodo- or bromoarenes, methyl difluoro(fluorosulfonyl)acetate and elemental sulphur in the presence of cuprous iodide in hexamethylphosphoric triamide (HMPA) or A-methylpyrrohdone (NMP) (Scheme 10). 

The oxidative cleavage of ethers to give carbonyl compounds has been demonstrated using UFe (readily available deficient in U) as oxidant. The reaction is regiospecific with methyl ethers (89 90). Phenyl thioethers have also been shown to undergo oxidative cleavage via a-chlorination (Scheme 41) giving, as shown, a route from alkenes or alkyl halides to aldehydes. 

Hydrogen peroxide is frequently used as an oxidizing agent in organic chemistry. One application is for the oxidation of thioethers to sulfoxides. For example, methyl phenyl sulfide was oxidized to methyl phenyl sulfoxide in 99% yield in methanol in 18 hours (or 20 minutes using a TiCls catalyst) ... 

A hexadentate N202S2 ligand (116) has been synthesized as a dithiaalkyl-substituted triazene-1-oxide and forms an unusual hexacoordinated zinc complex with thioether donors. Both the phenyl and the methyl derivatives form structurally characterized octahedral complexes.896... 

The readily available benzotriazolyl derivative of dimethyl sulfide, compound 821, can be alkylated on a-carbon in a stepwise manner to provide (a,a-disubstituted)alkyl thioethers 823 (Scheme 131). Hydrolysis of these thioethers under mild conditions (5% H2S04 at room temperature) furnishes ketones 824 in high yields. The anion derived from mono substituted (benzotriazol-l-yl)methyl thioether 822 adds to butyl acrylate to give intermediate 826 that can be hydrolyzed to y-ketoester 825. In another example of reactivity of a-(benzotriazol-l-yl)alkyl thioethers, treatment of thioether 822 with BunLi followed by phenyl isocyanate converts it into a-ketoanilide 828, via intermediate adduct 827 <1998JOC2110>. 

For the addition of ethylene, EtOAc as solvent was particularly advantageous and gave 418 in 60% yield (Scheme 6.86). The monosubstituted ethylenes 1-hexene, vinylcyclohexane, allyltrimethylsilane, allyl alcohol, ethyl vinyl ether, vinyl acetate and N-vinyl-2-pyrrolidone furnished [2 + 2]-cycloadducts of the type 419 in yields of 54—100%. Mixtures of [2 + 2]-cycloadducts of the types 419 and 420 were formed with vinylcyclopropane, styrene and derivatives substituted at the phenyl group, acrylonitrile, methyl acrylate and phenyl vinyl thioether (yields of 56-76%), in which the diastereomers 419 predominated up to a ratio of 2.5 1 except in the case of the styrenes, where this ratio was 1 1. The Hammett p value for the addition of the styrenes to 417 turned out to be -0.54, suggesting that there is little charge separation in the transition state [155]. In the case of 6, the p value was determined as +0.79 (see Section 6.3.1) and indicates a slight polarization in the opposite direction. This astounding variety of substrates for 417 is contrasted by only a few monosubstituted ethylenes whose addition products with 417 could not be observed or were formed in only small amounts phenyl vinyl ether, vinyl bromide, (perfluorobutyl)-ethylene, phenyl vinyl sulfoxide and sulfone, methyl vinyl ketone and the vinylpyri-dines. 

Carbon-13 shift values of parent heterocycloalkanes [408] collected in Table 4.61 are essentally determined by the heteroatom electronegativity, in analogy to the behavior of open-chain ethers, acetals, thioethers, thioacetals, secondary and tertiary amines. Similarly to cyclopropanes, three-membered heterocycloalkanes (oxirane, thiirane, and azirane derivatives) display outstandingly small carbon-13 shift values due to their particular bonding state. Empirical increment systems based on eq. (4.1) permit shift predictions of alkyl- and phenyl-substituted oxiranes [409] and of methyl-substituted tetrahydropyrans, tetrahydrothiapyrans, piperidines, 1,3-dithianes, and 1,3-oxathianes [408], respectively. Methyl increments of these heterocycloalkanes are closely related to those derived for cyclohexane (Table 4.7) due to common structural features of six-membered rings. 

Substitution of alkyl or aryl hydrocarbon groups, such as phenyl and methyl for H on hydrogen sulfide, H2S, leads to a number of different organosulfur thiols (mercaptans, R-SH) and sulfides, also called thioethers (R-S-R). Structural formulas of examples of these compounds are shown in Figure 1.19. 

Enantiomer separation of various compounds such as barbituric acids, benzoin, MTH-proline, glutethimide, a-methyl-oc-phenyl-succinimide, y-phenyl-y-butyrolac-tone, methyl-mandelate, l-(2-naphthyl)ethanol, mecoprop methyl, diclofop methyl and fenoxaprop methyl by pressure supported CEC on a permethyl-P-cyclodextrin modified stationary phase was described by Wistuba and Schurig [42-44]. Three different separation beds were used (i) permethyl-P-cyclodextrin was covalently attached via a thioether to silica (Chira-Dex-silica) [42], permethyl-P-cyclodextrin was linked to a dimethylpolysiloxane and thermally immobilized (ii) on silica (Chirasil-Dex-silica) [43] or (iii) on a silica monolith (Chirasil-Dex-monolith) [44], respectively. 

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 asymmetric ene reaction with catalyst 98 is restricted to activated aldehydes as is indicated by the data in Table 16. The rates of the reaction are such that it is not applicable to internal olefins. A variety of 1,1-disubstituted alkenes can be used to give good asymmetric induction with the fastest rates observed with phenyl vinyl thioethers. Turnover can be realized with the more reactive aldehydes and/or alkenes but only in the presence of molecular sieves. The reaction of chloral with a-methyl-styrene shows that higher induction can be achieved with lower temperatures although the reaction is slower. The nature of the solvent affects the rate of the reaction. The reaction is much slower in toluene than in dichloromethane. 

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