Intermediate thiyl

The -elimination of a thiyl radical (RS ) terminated a remarkably productive tandem radical bicyclization in Parker s formal total syntheses of ( )-codeine and ( )-morphine (see Scheme 14).29 Subjection of aryl bromide 72 to the conditions indicated generates transient aryl radical 73, an intermediate which engages the substi-... 

The degradation of tetrachloromethane by a strain of Pseudomonas sp. presents a number of exceptional features. Although was a major product from the metabolism of CCI4, a substantial part of the label was retained in nonvolatile water-soluble residues (Lewis and Crawford 1995). The nature of these was revealed by the isolation of adducts with cysteine and A,A -dimethylethylenediamine, when the intermediates that are formally equivalent to COClj and CSClj were trapped—presumably formed by reaction of the substrate with water and a thiol, respectively. Further examination of this strain classified as Pseudomonas stutzeri strain KC has illuminated novel details of the mechanism. The metabolite pyridine-2,6-dithiocarboxylic acid (Lee et al. 1999) plays a key role in the degradation. Its copper complex produces trichloromethyl and thiyl radicals, and thence the formation of CO2, CS2, and COS (Figure 7.64) (Lewis et al. 2001). 

It has been demonstrated that the MCR enzyme is active only if the metal center of coenzyme F430 is in the Ni1 form.1857 The natural substrate Me-CoM or simple methyl thioethers, however, do not react with Ni1 F430, which has lead to the proposal of a catalytic mechanism in which the addition of a thiyl radical to the S atom of the thioether giving a sulfuranyl radical intermediate is... 

The radicals (14) formed may be trapped with, for example, (10) above. Simple alkyl thiyl radicals such as MeS have been detected as reaction intermediates they are highly reactive. Relatively stable oxygen-containing radicals are also known. Thus the phenoxy radical (15),... 

The half-order of the rate with respect to [02] and the two-term rate law were taken as evidence for a chain mechanism which involves one-electron transfer steps and proceeds via two different reaction paths. The formation of the dimer f(RS)2Cu(p-O2)Cu(RS)2] complex in the initiation phase is the core of the model, as asymmetric dissociation of this species produces two chain carriers. Earlier literature results were contested by rejecting the feasibility of a free-radical mechanism which would imply a redox shuttle between Cu(II) and Cu(I). It was assumed that the substrate remains bonded to the metal center throughout the whole process and the free thiyl radical, RS, does not form during the reaction. It was argued that if free RS radicals formed they would certainly be involved in an almost diffusion-controlled reaction with dioxygen, and the intermediate peroxo species would open alternative reaction paths to generate products other than cystine. This would clearly contradict the noted high selectivity of the autoxidation reaction. 

The product cystine is presumably formed in the recombination of two thiyl radicals. This free-radical model is suitable for formal treatment of the kinetic data however, it does not account for all possible reactions of the RS radical (68). The rate constants for the reactions of this species with RS-, 02 and Cu L, (n = 2, 3) are comparable, and on the order of 109-10loM-1s-1 (70-72). Because all of these reaction partners are present in relatively high and competitive concentrations, the recombination of the thiyl radical must be a relatively minor reaction compared to the other reaction paths even though it has a diffusion controlled rate constant. It follows that the RS radical is most likely involved in a series of side reactions producing various intermediates. In order to comply with the noted chemoselectivity, at some point these transient species should produce a common intermediate leading to the formation of cystine. 

The attack by the thiolate anion on the N-oxide oxygen of 62 produces the intermediate sulfenic acid derivative 65, which, in the presence of thiols, further reacts with the thiolate anion, to give the oxime 66, which has been isolated among the reaction products. By contrast, spontaneous loss of the halide anion from 65 affords the ni-troso intermediate 67 that, by losing NO and the thiyl radical directly, or through 68, produces the a-nitrosoolefm 69. By a Michael type reaction with water this last product immediately yields the final oxime 70, which has been isolated among the reaction products. 

Reaction 7.74) [84], That is, (TMS)3Si radical added to the double bond of allyl sulfides, giving rise to a radical intermediate that undergoes (3-scission with the ejection of the thiyl radical. Hydrogen abstraction from the silane completes the cycle of these chain reactions. 2-Functionalized allyl tris(trimethylsilyl)si-lanes (71) have been employed in the radical-based allylation reactions. 

Only compounds of type I and II, which contain both metal and sulfur, were found to act as inhibitors. Compounds III and IV, for example, were ineffective. The inhibition of indene oxidation by zinc dithio-phosphates was considered to be a key result in this work since it rules out the intermediate formation of free thiyl radicals. There is adequate evidence (2, 9, 16, 17, 22) that thiyl radicals, including (RO)2PS2, add rapidly to olefins and that in the presence of oxygen the following sequence of reactions would occur. 

Although there is little doubt that the electron transfer reaction (Reaction 2) is involved in the over-all reaction (21), the suggestion that quantitative yields of disulfide (13) arise from the dimerization of thiyl radicals is inconsistent with the observed behavior of other free radicals (24). It seems preferable to suggest that some kind of coordination occurs as a prerequisite to the transfer of electrons (12,15). In this case, metal-thiol complexes should be formed as intermediates in the oxidation, in which the metal acts not only as an electron acceptor but also to locate the resultant thiyl entities in close proximity, thereby favoring dimerization reactions and producing disulfide. The electrons gained by the metal may then be passed on to an oxygen molecule. The over-all reaction may be represented as... 

Schmittel M, Ghorai MK (2001) Reactivity patterns of radical ions - a unifying picture of radical-anion and radical-cation transformations. In Balzani V (ed) Electron transfer in chemistry, vol 2. Organic molecules. Wiley-VCH, Weinheim, pp 5-54 Schoneich C, Bonifacic M, Dillinger U, Asmus K-D (1990) Hydrogen abstraction by thiyl radicals from activated C-H-bond of alcohols, ethers and polyunsaturated fatty acids. In Chatgilialoglu C, Asmus K-D (eds) Sulfur-centered reactive intermediates in chemistry and biology. Plenum, New York, pp 367-376... 

When the amino group is fully deprotonated, the rate of the H-transfer is 1.5 x 10s s4, but also around pH 7 the reaction is still fast, at the ms timescale (for a quantum mechanical study see Rauk et al. 2001). Upon the decay of the amnioal-kyl radicals formed in reaction (35) ammonia as formed in a yield that points to disproportionation as the major process (Zhao et al. 1997). The fact that the ami-noalkyl radical is the thermodynamically favored species does not mean that the repair of DNA radicals by GSH (Chap. 12.11) is not due to its action as a thiol. As with many other examples described in this book, the much faster kinetics that lead to a metastable intermediate (here the formation of the thiyl radical) rather than the thermodynamics as determined by the most stable species (here the aminoalkyl radical) determine the pathway the the reaction. In fact, the C-H BDE of the peptide linkage is lower than the S-H BDE and repair of DNA radicals by peptides, e.g., proteins would be thermodynamically favored over a repair by thiols but this reaction is retarded kinetically (Reid et al. 2003a,b). 

Sulfur free-radical chemistry is largely governed by the ability of sulfur to form three-electron bonded intermediates. A case in point is the complexation of a thiyl radical with a thiolate ion (for an analogy with the halide and other pseudohalide systems, see Chap. 5.2). These disulfide radical anions are characterized by strong absorptions in the UV-Vis (Adams et al. 1967). Complexation can occur both intermolecularly as well as intramolecularly. For GSH, for example, the stability constant of the disulfide radical anion is 2900 dm3 mol1 (Mezyk 1996a). The protonated disulfide radical anion is not stable, but such intermediates are known in the cases of the intramolecular complexes [reactions (39) and (40) Akhlaq and von Sonntag 1987]. 

Similar three-electron-bonded intermediates must also be formed in the well-known thiyl radical-induced scrambling of disulfides (Owen and Ellis 1973). Mechanistic details have been studied using the pulse radiolysis technique which allowed the identification the three-bonded intermediate and the determination of some equilibrium constants, but also gave evidence that this system may be more complex than described by reactions (42) and (43) (Boni-facic and Asmus 1984). 

In the initially proposed mechanism, the intermediate 2-nitro-2-propyl radicals, Me2(N02)C, undergo two reactions with the more basic (nucleophilic) thiolates addition of thiolates leading to SRN1 products (Equation 10.20 in Scheme 10.32), and SET to yield the nitro anion and thiyl radicals (RS ), Equation 10.21, which combine to give disulfide. 

In order to be complete in our discussion of methods for generation of fluori-nated radicals, it must be mentioned that perfluoroalkyl radical intermediates are also formed in every reaction in which radical species such as halogen atoms, thiyl radicals, or other carbon radicals add to fluoroolefins. As will be seen in Sect. 6.3.2, such processes are especially important in the telomerization or polymerization of fluorinated olefins... 

A mechanism was proposed in which the perferryl iron-oxeme, resulting from heterolytic cleavage of the 0-0 bond of the iron-peroxy intermediate, abstracts an electron from the 0=0 double bond of the carbonyl group of the aldehyde. The reduced perferryl attacks the 1-carbon of the aldehyde to form a thiyl-iron-hemiacetal diradical. The latter intermediate can fragment to form an alkyl radical and thiyl-iron-formyl radical. The alkyl radical then abstracts the formyl hydrogen to produce the hydrocarbon and C02 (Reed et al 1995). 

Aiyar J, Borges K, Floyd RA, et al. 1989. Role of chromium(V), glutathione thiyl radical and hydroxyl radical intermediates in chromium(VI)-induced DNA damage. Toxicol Environ Chem 22 135-148. 

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