Alkylation of thiols

Bolton, J. L. Turnipseed, S. B. Thompson, J. A. Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins studies utilizing amino acid and peptide models. Chem.-Biol. Interact. 1997, 107, 185-200. 

S-Alkylation of thiols by carbene complexes can be a useful approach to a-(alkylthio)- or a-(arylthio)ketones, although few examples of intramolecular [975,1193] or intermolecular [497,1043,1230-1233] S-H bond insertion reactions of electrophilic carbene complexes have been reported. Yields are sometimes low, probably because of the poisoning of the catalyst by the thiol. Examples are given in Table 4.15. 

Table 4.15. Preparation of thioethers by S-alkylation of thiols with electrophilic carbene complexes.

The Pd-catalyzed enantioselective allylic alkylation of thiols in the presence of BPA is limited to aryl and heteroaryl thiols [10]. However, allylic thioesters should... 

Alkylation of thiols.2 Dimethylfonnamide dimethyl acetal reacts with heterocyclic mercapto derivatives in boiling benzene or acetonitrile to give the corresponding alkyl-thio derivatives in excellent yields ... 

Thioethers. Alkylation of thiols with alcohols under the Mitsunobu reaction conditions is catalyzed by imidazole. 

Sulfides. Et4NHC03 or (Et4N)2C03 can serve as base in the alkylation of thiols. 

Selenium/Sulfur Acids. A strong base such as sodium hydride is not normally needed to facilitate alkylation of thiols. However, it was necessary to use sodium hydride for the alkylation of 5-bromo-i>-pentano-1,4-lactones (eq 45). The base typically employed for this transformation (NaOMe) is not compatihle with the lactone functionality. 

J. Nishiyama and T. Kuninori, Assay of thiols and disufides based on the reversibility of N-ethylmaleimide alkylation of thiols combined with electrolysis, Anal. Biochem., 1992, 200, 230-234. 

Other cases of alkylation of thiols were studied. Dithiols can be alkylated by halocarboxylic acids in high yields imder ultrasonic PTC conditions, but details are not readily available. ... 

If the substrate is an alcohol, some dialkyl ethers can be synthesized in a two-phase version of the Williamson synthesis, and thioethers or dithioacetals result from alkylation of thiols, with alkyl halides or CH2CI2 respectively, under similar conditions. The related reaction of equation (2) has been used to make an evaluation of several catalysts, and it has been found that the larger, more symmetrical, quaternary ions are the most efficient. 

Sulfides are prepared in an analogons way by alkylation of thiols in the presence of base, such as hydroxide. The base generates the alkanethiolate, which reacts with the halo-alkane by an Sn2 process. Becanse of the strong nucleophilicity of thiolates, there is no competition from hydroxide in this displacement. 

Salvatore RN, Smith RA, Nischwitz AK, Gavin T. A mild and highly convenient chemoselective alkylation of thiols using CS2CO3-TBAI. Tetrahedron Lett. 2005 46 8931 8935. 

Firouzabadi H, Iranpoor N, Jafarpour M. ZrCLj dispersed on dry silica gel provided a useful reagent for 5-alkylation of thiols with alcohols under solvent-free conditions. Tetrahedron Lett. 2006 47 93-97. 

Alkylation of thiols is represented by their reaction with O-alkyl NN-di-cyclohexylureas at 100—110 and -keto sulphide synthesis using CF3-... 

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