Thiol 1,4-addition reaction, mechanism

Although the mechanism of this reaction has not been studied as thoroughly as that of the thiol addition reaction, there appears to be considerable similarity in the main features of the reaction. Thus, although the transition state may well differ in a number of details, the transition state shown earlier (Figure 10) appears to predict the correct configuration for the products of the selenophenol addition as well as of the thiophenol addition to cyclohexenones. 

In accordance with the above discussion, general base catalysis is not found in thiol addition reactions to aldehydes and ketones only specific base catalysis is prevalent (Lienhard and Jencks, 1966). This is in contrast to the general base-catalyzed hydration of ketones or aldehydes. The reactions of the carbonyl group at the carboxylic acid level of oxidation have much in common with the reactions of the carbonyl group at the aldehyde or ketone level of oxidation. In an excellent review on simple carbonyl addition reactions Jencks (1964) has discussed in detail the mechanisms of catalyzed additions to the carbonyl group of ketones and aldehydes. For general base-catalj ed additions the mechanism... 

Japanese workers (50,51) were the first to observe optical activity in the addition of thiols to electron-poor olefins (eq. [9]) The e.e. was not determined, but these observations led us to attempt using a cinchona alkaloid as the catalyst in the addition of thiophenol to cyclohexenone. The reaction lends itself admirably to a scope, limitations, and mechanism study, and the results have been published in detail (19). An important mechanistic difference between the addition of the dodecanethiol to isopropenyl methyl ketone and the addition of thiophenol to a cyclohexenone (eq. [1]) lies in the sequence of chirality-producing steps. In the former case, chirality is produced when the proton adds to the a-caibon atom of the ketone—after thiol addition has taken place. In the latter... 

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

This reaction is based on a stoichiometric reaction of multifunctional olefins (enes) with thiols. The addition reaction can be initiated thermally, pho-tochemically, and by electron beam and radical or ionic mechanism. Thiyl radicals can be generated by the reaction of an excited carbonyl compound (usually in its triplet state) with a thiol or via radicals, such as benzoyl radicals from a type I photoinitiator, reacting with the thiol. The thiyl radicals add to olefins, and this is the basis of the polymerization process. The addition of a dithiol to a diolefin yields linear polymer, higher-functionality thiols and alkenes form cross-linked systems. 

The basis for cross-linking in the elastomers in these studies is the addition of thiols to olefmic double bonds. This reaction has been studied by a number of investigators.61-65 It has been shown that the addition reaction proceeds by a radical mechanism. The rate of cross-linking of polybutadiene can be strongly promoted by relatively small amounts of polythiols.66 For example, G(X) values increased from 5 (pure polybutadiene) to 29 when 1 wt. percent of dimercaptodecane was added and to more than 49 on the further addition of o-dichlorobenzene (see Table 5.2). 

The effects of adding various metal ions and metal complexes on the rate of a model oxidation reaction have been studied in some detail The model reaction chosen—the oxidation of ethanethiol in aqueous alkaline solution in the presence of metal-containing catalysts—involves the transfer of an electron from the thiol anion to the metal The catalytic activity of additives depends upon the solubility of the particular metal complex and varies according to the nature of the ligand attached to the metal ion. In conjunction with different metals, the same ligand can act either as a catalyst or as an inhibitor. The results are discussed in the light of proposed reaction mechanisms. 

Cyclization of either of the thiols (24) with acid provided the saturated thia-PGIi analogs (26) as a 2.7 1 mixture of the exo and endo isomers.271 Although many addition reactions of thiols to alkenes are radical reactions catalyzed by light, oxygen, or other radical initiators, conversion to (26) was not effected under photolytic conditions or with AIBN. A radical chain mechanism for selenothiolactonization has also been reported recently.275... 

Besides extensive kinetic investigations, less detailed polarographic studies can provide useful information on the course of certain reactions. For example, in the reaction of 2,3-dimercaptopropanol with 1,4-ben-zoquinone (34), the anodic wave of 2,3-dimercaptopropanol vanishes with increasing concentration of quinone, when the ratio of thiol to quinone reaches 1 2 (Fig. 13). An anodic wave corresponding to oxidation of hydroquinone is also obtained. In the reaction, which is irreversible, neither cathodic disulphide waves nor anodic waves corresponding to monothiols appear. Thus an addition-reduction mechanism (14) can be postulated. 

Further evidence for the addition of H2S to carbon-carbon double bonds very early in sediments, and further insights into reaction mechanisms, have been reported by Vairavamurthy and Mopper in 1987 and 1989 (109.110). They identified 3-mercaptopropionic acid (3-MPA) as a major thiol in anoxic intertidal marine sediment and demonstrated that the thiol formation could occur by the reaction of HS with acrylic acid in sediment water and seawater at ambient temperature The formation of 3-MPA was hypothesized to occur by a Michael addition mechanism whereby the nucleophile HS adds to the activated double bond in the a,/3-unsaturated carbonyl system ... 

In the field of thiochemistry, the photocatalytic synthesis of mercaptans represents an interesting chemical route. Schoumacker et al. [60] performed the synthesis of propan-1-thiol by addition of H2S on propene in contact with illuminated Ti02 or CdS catalysts, according to a reaction mechanism implying photogenerated SH radicals. 

Concerning the stereochemical course of this reaction, Wynberg has proposed a mechanism based mainly on kinetic measurements and structures of substrates in pioneering work on the asymmetric thiol addition catalyzed by cinchona alkaloids. In our case, various sterically modified analogs of the base catalyst are readily achievable, and elucidation of the mechanism appears mainly dependent on the effects of the structure of the catalyst on the optical yields. From the experimental results, three notable points must be taken into consideration, namely,... 

Previous study [18] on oxidation of thiols by transition metal oxide(s) in the presence of olefins resulted in the formation of corresponding sulphides indicating a free radical addition reaction in which metal oxide acts as an initiator for the production of thiyl radicals(RS-). The disulphide is formed by the dimerization of thiyl radieals (RS )- Based on this, a mechanism for thiol oxidation by manganese nodule (Only oxides of Mn, Fe, Co and Cu in manganese nodule are responsible for oxidation of thiols) is delineated as follows ... 

Since thiols and thiyl radicals are known to readily undergo addition reactions at unsaturated carbon centers (199, 202, 204), a possible mechanism for this inactivation reaction is shown in Scheme 43. Addition of the active site nucleophilic or radical species followed by protonation or electron transfer, respectively, would yield the thioacrylate derivative and inactive enzyme. Of course, addition to C-2 of propargylic acid is also possible, forming a 2-substituted acrylate derivative instead. 

The facts that thiols are good H-atom donors toward alkyl radicals and that silyl radicals are among the most reactive known species for abstraction and addition reactions suggest that any class of compounds which allows the transformation of a thiyl to a silyl radical via a fast intramolecular rearrangement will potentially be a good radical-based reducing agent. The silanethiols 11 and 12 are found to have this property [84, 85]. The reductions of bromides, iodides and isocyanides by thiol 12 are demonstrated to follow the expected mechanism [85]. 

Chapter 11 deals with free radicals and their reactions. Fundamental structural concepts such as substituent effects on bond dissociation enthalpies (BDE) and radical stability are key to understanding the mechanisms of radical reactions. The patterns of stability and reactivity are illustrated by discussion of some of the absolute rate data that are available for free radical reactions. The reaction types that are discussed include halogenation and oxygenation, as well as addition reactions of hydrogen halides, carbon radicals, and thiols. Group transfer reactions, rearrangements, and fragmentations are also discussed. 

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