Thiol reaction with epoxide

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). 

Episulfides, which can be generated in situ in various ways, react similarly to give P-amino thiols, and aziridines give 1,2-diamines. Triphenylphosphine similarly reacts with epoxides to give an intermediate that undergoes elimination to give alkenes (see the Wittig reaction, 16-47). 

The cleavage of epoxides by water is a classical reaction. Such epoxide cleavage can be catalyzed by both acids and bases in aqueous media. In the presence of other nucleophiles, the corresponding nucleophilic ringopening products are obtained with the nucleophiles being incorporated into the products.68 Examples include azides, iodides, and thiols in the presence or absence of metal salts in aqueous media. The pH of the reaction medium controls the reactivity and regioselectivity of the... 

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... 

Attention may now be directed to the reactions of aromatic thiols with epoxides. Mu tz,IH for example, haa investigated the course of addition of thiophenol to propylene oxide, both in alkaline and in acidic solutions. Significantly lower yields obtained in acid tended to confirm the premise that thiophenoxide ion rather than undissociated thiophenol is the attacking nucleophile. Likewise predictable was the isolation of two isomeric phenylthioprcpanois under add conditions, hut of only one in base (Eq. 663). 

For example, polymers having hydroxyl end groups can be prepared by reaction of polymer lithium with epoxides, aldehydes, and ketones III-113). Carboxylated polymers result when living polymers are treated with carbon dioxide (///) or anhydrides (114). When sulfur (115, 116), cyclic sulfides (117), or disulfides (118) are added to lithium macromolecules, thiol-substituted polymers are produced. Chlorine-terminus polymers have reportedly been prepared from polymer lithium and chlorine (1/9). Although lithium polymers react with primary and secondary amines to produce unsubstituted polymers (120), tertiary amines can be introduced by use of p-(dimethylamino)benzaldehyde (121). 

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. 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

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. 

There are four major pathways of metabolism for acrylonitrile formation of glucuronides, direct reaction with glutathione to form cyanoethyl mercapturic acid, direct reaction with the thiol groups of proteins, and epoxidation to 2-cyanoethylene oxide. N-AcetyT S-(2-cyanoethyl)-L-cysteine is a major urinary metabolite in human volunteers exposed to 5-10 mg. 

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