Epoxides with thioethers

The reaction of the epoxide with a thiol group yields a thioether linkage, whereas reaction with a hydroxyl gives an ether and reaction with an amine results in a secondary amine bond. The relative reactivity of an epoxy group is thiol > amine > hydroxyl, and this is reflected by... 

Cleavage of epoxides with alkylthiotriaikylsilanes. In the presence of Znl, these thiosilanes (R SSiR3) convert epoxides into /J-trimethylsilyloxy thioethers, which can be hydrolyzed to fi-hydroxy thioethers. The regioselectivity can be reversed by use of n-butyllithium as the catalyst. 

The reactivity of epoxides can be modified by various proximal functionality. For example, 2,3-epoxy sulfides 118 are converted to the corresponding TMS-thiiranium species 119 upon treatment with TMS triflate. This intermediate reacts with O-silyl amides regiospecifically to form l-substituted-3-hydroxy-2-thioethers (e.g., 120). Simple primary amines undergo polyalkylation, but imines can be used as an indirect amine equivalent <96TET3609>. 

Porath, 1974). B/s-oxirane compounds also can be used to introduce epoxide groups into soluble dextran polymers in much the same manner (Boldicke et al., 1988 Bocher et al., 1992). The epoxide group reacts with nucleophiles in a ring-opening process to form a stable covalent linkage. The reaction can take place with primary amines, sulfhydryls, or hydroxyl groups to create secondary amine, thioether, or ether bonds, respectively (Chapter 2, Section 1.7). 

A novel approach to the synthesis of desoxy sugars was made by Jeanloz, Prins and Reichstein69 in 1945. In general terms, a 1,2-epoxide was cleaved with sodium thiomethoxide to give a /3-hydroxy thioether which, in turn, was hydrogenolyzed with Raney nickel. It is apparent... 

Many different pathways, mechanisms, and enzymes are associated with activation. These include dehalogenation, AT-nitrosation of secondary amines, epoxidation, conversion of phosphothionates to phosphate, metabolism of phen-oxyalkanoic acids, oxidation of thioethers, hydrolysis of esters and peroxides. The following is a summary. 

Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

Sulfur ylides behave similarly to phosphorus ylides, but the final products are different. Figure 10-31 shows the mechanism for the prepciration of a sulfur ylide and the reaction of the sulfur ylide with a carbonyl group. Notice that the mechanism for the formation of the sulfur ylide is similar to the formation of a phosphorus ylide. However, the last step in the sulfur ylide mechanism is an internal S, 2 reaction, which eliminates the original thioether (dimethyl sulfide). The reaction of a sulfur ylide with a ketone yields epoxides, whereas the product of a phosphorus ylide with a ketone is an alkene. 

Phenolic derivatives were prepared and then converted into thioether analogs using ethanedithol followed by oxidation of this intermediate to the disulfide. Phenolic resins were prepared by electrophilic substitution of allyl phenol derivatives with formaldehyde and then flee radically copolymerizing with ethanedithol. Epoxidation was performed using epichlarohydrine. 

Conjugation with sulfhydryl groups appears to be an important detoxification process for mctin l acrylate m the guinea-pig. The thioethers were identified as A -acct l-S -(2-carboxyethyl)-L-cysteine and the corresponding monomethyl ester, with a ratio between the two metabolites of 20 1. In male rats exposed to metliyl acrylate by inhalation, depletion of nonprotein sulfhydryl compounds was most pronounced in the lung, compared to liver, kidney and blood. After administration of methyl acrylate to Wistar rats, no hydroxymercapturic acid that might be derived from the epoxide of methyl acrylate was detected. It seems unlikely, therefore, that epoxidation of the acrylic esters occurs in vivo (lARC, 1986). 

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