Thiols reaction with epoxides

Reaction with thiol-moieties (alkylation) (Non)-protein -SH DNA SH-enzymes activity Folpet, epoxides... 

Epoxide ring opening reaction with thiol is known in the literature especially for the synthesis of the p-hydroxy sulfide moiety.Its regioselectivity can be modulated with pH conditions, in basic medium... 

The ring-opening reaction of epoxides with silylazide catalyzed by (salen)Cr(III)X (X = Cl, N3) complexes was studied from the mechanistic aspect, and it was applied to kinetic resolution of terminal epoxides to produce 1,2-aminoalcohols (Scheme 16.57) [73-75]. The Cr catalyst also acts as the ring-opening reaction with thiols and carboxylic acids [76, 77]. 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, aHenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphoms oxychloride [10025-87-3] POCl (H)- Because sulfonic acids are generally not converted directiy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphoms pentachlotide [10026-13-8] and phosphoms pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl haUdes (12,13). The conversion may also be accompHshed by continuous electrolysis of thiols or disulfides in the presence of aqueous HCl [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfutic acid [7789-21-17, or by reaction of the sulfonic acid or sulfonate with fluorosulfutic acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl haUde, can be achieved under oxidative halogenation conditions (15). 

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... 

Conceptually new multifunctional asymmetric two-center catalysts, such as the Ln-BINOL derivative, LnMB, AMB, and GaMB have been developed. These catalysts function both as Brpnsted bases and as Lewis acids, making possible various catalytic, asymmetric reactions in a manner analogous to enzyme catalysis. Several such catalytic asymmetric reactions are now being investigated for potential industrial applications. Recently, the catalytic enantioselective opening of meso epoxides with thiols in the presence of a heterobimetallic complex has... 

The other side of the coin is specific base catalysis (SBC) which usually involves the removal of a proton from the substrate in a fast pre-equilibrium step followed by a rate-determining reaction of the anion. Most of the base-catalysed reactions you are familiar with work by SBC. Examples include opening of epoxides with thiols. 

Reactions with Nucleophiles. The epoxide is, by far, the more reactive site and a wide variety of nucleophiles have been used (eq 2) to open the ring at C-3 such as HCl (96%), HOAc (>50%), H2S (65% as cyclized product 3-thietanol), HCN (66%), ethanol (90%), t-butanol (86%), phenyl or benzyl thiol (99% or 93%, respectively), and phenyl selenide (generated in situ from the diselenide and sodium hydroxymethyl sulfite) (>55%). If desired, the epoxide is easily formed from the chlorohydrin by treatment with excess KOH or Et3N. 

Brill and co-workers used levoglucosane as a rigid scaffold to synthesise libraries both in solution [74] and solid phase [75]. The opening of epoxide 125 by different hydroxycarboxylic acid methyl esters catalysed by Lewis acid, followed by simultaneous new epoxide formation and ester hydrolysis gave the resulting free acid ready for attachment to the solid support. Epoxide opening reactions with alkoxides, amines and thiols were carried out on solid phase... 

We introduced these guanidinium salts in a 1985 patent (Ref. 6) on the conversion of carboxylic acids to acid chlorides with phosgene. In this process, only 0.02 mol. % of HBGCI was required, two orders of magnitude less than the quantities of other catalysts typically used. Many new other applications including phosgene reactions with phenols, thiols, aldehydes, epoxides or O-demethyla-tion methods have been developed later and are discussed in this book. 

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