Thioethers from thiol esters

Enol phosphates derived from thiol esters couple with organoaluminium reagents, catalysed by tetrakis(triphenylphosphine) palladium, to form enol thioethers, and hence ketones by hydrolysis [equation (22)]. This alkylative... 

Figure 4.8. The sulfur cycle where S° is elemental sulfur, H2S is hydrogen sulfide, S2032" is thiosulfate, SO32" is sulfite, SO/- is sulfate, R-OSO3H represents a sulfate ester, R-SO3H a sulfonic acid, R-S-R a thioether, and R-SH a thiol. (Adapted from Coyne MS. Soil Microbiology An Experimental Approach. Boston Delmar Publishers 1999.)...

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

Numerous researchers have employed thiols as weak bases in the thioalkylation reaction to ligate unprotected peptides with a haloacetyl group to form thioethers at pH 7 8.5[90 91 131-133 or thioesters at acidic to basic conditions. 108"110 Of these two reactions, thioether formation is often the choice because thioesters suffer from instability in aqueous basic conditions. Haloacetyl derivatives, either as carboxylic acids or active esters, can be attached to either the N-terminal or side-chain amines during the stepwise solid-phase synthesis of either the peptide or the core and are stable to either HF or TFA cleavage conditions. Capping an amino group with a chloroacetyl group is compatible with Fmoc chemistry when used at a terminal step. 

Therefore, it is possible to convert a variety of primary and secondary alkyl halides to alcohol, ethers, thiols, thioethers, esters, amines, and azides (Following fig.). Alkyl iodides and alkyl chlorides can also be synthesised from other alkyl halides. 

Classification and Organization of Reactions Forming Difunctional Compounds. This chapter considers all possible difunctional compounds formed from the groups acetylene, carboxylic acid, alcohol, thiol, aldehyde, amide, amine, ester, ether, epoxide, thioether, halide, ketone, nitrile, and olefin. Reactions that form difunctional compounds are classified into sections on the basis of the two functional groups of the product. The relative positions... 

Sodium sulfhydride (NaSH) is a much better reagent for the formation of thiols (mercaptans) from alkyl halides than H2S and is used much more often. It is easily prepared by bubbling H2S into an alkaline solution, but hydrosulfide on a supported polymer resin has also been used. " The reaction is most useful for primary halides. Secondary substrates give much lower yields, and the reaction fails completely for tertiary halides because elimination predominates. Sulfuric and sulfonic esters can be used instead of halides. Thioethers (RSR) are often side products. The conversion can also be accomplished under neutral conditions by treatment of a primary halide with F and a tin sulfide, such as PhsSnSSnPhs. An indirect method for the preparation of a thiol is the reaction of an alkyl halide with thiourea to give an isothiuronium salt (119), and subsequent treatment with alkali or a... 

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