Thioethers from disulfides

Sodium sulfide and sodium sulfide -f- sulfur Sym. thioethers and disulfides from halides... 

Earland and Raven [65] have examined the reaction of A-(mercap-tomethyl) polyhexamethyleneadipamide disulfide (XV) with alkali. Under alkaline conditions that produce lanthionyl residues in wool, no thioether is formed from this polymeric disulfide however, cyanide readily produces thioether from either (XV) or wool fiber. Therefore, the mechanism for thioether formation must be different in these two reactions. Because this polymeric disulfide (XV) contains no beta-hydrogen atoms (beta to the disulfide group), a likely mechanism for formation of lanthionyl residues in keratins, under alkaline conditions, is the beta-elimination scheme [64] (the reaction depicted by Equation F). Other mechanisms that have been suggested for this reaction have been summarized by Danehy and Kreuz [66]. 

Salts of hydrogen cyanide have also been found to be capable of nucleophilic cleavage of the disulfide bond in keratin fibers [72]. In addition, nearly quantitative conversion of cystinyl residues to lanthionyl residues can be achieved in this reaction [73]. The most plausible mechanism is given in Equations G and H [65]. This mechanism consists of two nucleophilic displacement reactions the first by cyanide on sulfur and the second by mercaptide ion on carbon. The following mechanism is consistent with the observed formation of thioether from the reaction of N-(mercaptomethyl)polyhexamethyleneadipamide disulfide (XV) with cyanide, but not with alkali [65]. 

Electrochemical reduction of disulfides Reaction with electrophiles Thioethers from halides... 

P. which contain only amino acid residues are called homomeric P., whereas P. with non-amino acid constituents are known as heteromeric P. Each of these classes is further subdivided into homodetic P., which contain only peptide bonds, and heterodetic P, which contain other bonds, e.g. ester, thioether or disulfide. Heterodetic P. possessing one or more ester bonds as hetero link are called Depsipeptides (see). The classification of depsipeptides does not accord entirely with the homomeric/heteromeric system it has arisen from the fact that the synthesis of these peptides presents rather special problems. There are two types of homomeric depsipeptides O-peptides contain ester-linked hydroxyamino acids, and they may be linear or cyclic (i. e. lactones) in S-peptides or thiodepsipep-tides, the mercapto group of a cysteine residue is acy-lated with an amino acid. Heteromeric depsipeptides contain hydroxy acids as the hetero component, and they are also known as peptolides. P. with non-amino... 

Without additional reagents Sulfenyldilorides from thioethers or disulfides Protection of phenol groups as tert- miy ethers... 

Due to the stability and availability of carboxylic acids, they remain some of the most attractive starting points for the synthesis of complex organic compounds. Using these compounds as substrates, the decarboxylative thiolation of carboxylic acids has been achieved using silver nitrate as a promoter (Scheme 5.15) [16]. Disulfides served as the sulfur source for this chemistry, and moderate to good yields of the thioethers from a host of aUcyl carboxylic acids. 

Pyrrolethiols, readily obtained from the corresponding thiocyanates by reduction or treatment with alkali, rapidly oxidize to the corresponding disulfides. They are converted into thioethers by reaction with alkyl halides in the presence of base. Both furan- and thiophene-thiols exist predominantly as such rather than in tautomeric thione forms. 

Experiments with cyclic thioethers (80JCS(P1)1693), thiourea, thiocyanate and ethyl xan-thate always led to destruction of oxaziridines (73AJC2159). Products of complicated consecutive reactions could be isolated but only with some difficulty, e.g. (92) from a reaction with carbon disulfide (74JOC957), and (93), obtained by trapping with butadiene a product of a reaction between an oxaziridine and a thiirane (80JOC1691). 

Thioethers are neutral stable compounds that can be freed from acidic and basic impurities as described for disulfides. They can be recrystallised from organic solvents and distilled without decomposition. They have sulfurous odours. 

However, since SMCC forms nonreversible thioether linkages with sulfhydryl groups, it only can be used in the preparation of immunotoxins if intact A-B toxins are employed in the conjugate. In such conjugates, the A chain still have the potential for reductive release from the B-chain subunit after cellular docking and internalization. Immunotoxins prepared with A-chain or single-subunit toxins will not display cytotoxicity if crosslinked with SMCC, since the crosslinker does not create cleavable disulfide bonds upon conjugation. 

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