Free radical pathway

Treatment of 2-methylthiirane with t-butyl hydroperoxide at 150 °C in a sealed vessel gave very low yields of allyl disulfide, 2-propenethiol and thioacetone. The allyl derivatives may be derived from abstraction of a hydrogen atom from the methyl group followed by ring opening to the allylthio radical. Percarbonate derivatives of 2-hydroxymethylthiirane decompose via a free radical pathway to tar. Acrylate esters of 2-hydroxymethylthiirane undergo free radical polymerization through the double bond. 

A chemical synthesis of prostaglandins by a free radical pathway through an endoperoxide intermediate showed a strong stereochemical preference for the formation of the endoperoxides having cis alpha and omega appendages. 

Homolytic and free radical pathways in reactions of organochromium complexes. J. H. Espenson, Prog. Inorg. Chem., 1983, 30,189-212 (85). 

N2, and bromine trifluoride at 25-35°C " are also highly regioselective for tertiary positions. These reactions probably have electrophilic, not free-radical mechanisms. In fact, the success of the F2 reactions depends on the suppression of free-radical pathways, by dilution with an inert gas, by working at low temperatures, and/or by the use of radical scavengers. 

For example, photolysis of a suspension of an arylthallium ditrifluoro-acetate in benzene results in the formation of unsymmetrical biphenyls in high yield (80-90%) and in a high state of purity 152). The results are in full agreement with a free radical pathway which, as suggested above, is initiated by a photochemically induced homolysis of the aryl carbon-thallium bond. Capture of the resulting aryl radical by benzene would lead to the observed unsymmetrical biphenyl, while spontaneous disproportionation of the initially formed Tl(II) species to thallium(I) trifluoroacetate and trifluoroacetoxy radicals, followed by reaction of the latter with aryl radicals, accounts for the very small amounts of aryl trifluoroacetates formed as by-products. This route to unsymmetrical biphenyls thus complements the well-known Wolf and Kharasch procedure involving photolysis of aromatic iodides 171). Since the most versatile route to the latter compounds involves again the intermediacy of arylthallium ditrifluoroacetates (treatment with aqueous potassium iodide) 91), these latter compounds now occupy a central role in controlled biphenyl synthesis. 

PGH synthase and the related enzyme lipoxygenase occupy a position at the interface of peroxidase chemistry and free radical chemistry and can clearly trigger metabolic activation by both mechanisms. The peroxidase pathway activates compounds such as diethylstilbestrol and aromatic amines whereas the free radical pathway activates polycyclic hydrocarbons (59). Both pathways require synthesis of hydroperoxide in order to trigger oxidation. 

There have also been several papers [61-63] on the importance of carefully establishing the reaction mechanism when attempting the copolymerization of olefins with polar monomers since many transition metal complexes can spawn active free radical species, especially in the presence of traces of moisture. The minimum controls that need to be carried out are to run the copolymerization in the presence of various radical traps (but this is not always sufficient) to attempt to exclude free radical pathways, and secondly to apply solvent extraction techniques to the polymer formed to determine if it is truly a copolymer or a blend of different polymers and copolymers. Indeed, even in the Drent paper [48], buried in the supplementary material, is described how the true transition metal-catalyzed random copolymer had to be freed of acrylate homopolymer (free radical-derived) by solvent extraction prior to analysis. 

Evidence for a free radical pathway in the foregoing cycloalkyl bromide reactions was secured by San Filippo and coworkers, who found that cis and iraws-4-r-butylcydohexyl bromide afford nearly identical product mixtures with MesSnLi, MesSnNa and MesSnK under a given set of conditions (Table 7)45. Of the various combinations examined, that of di-bromide and Me3SnLi appeared to be most favorable to S/v2 displacement. 

The product-forming steps of dehalogenations by free radical pathways were discussed earlier (see Section 18.3.1.1). In non-radical mechanisms, the dehalo-genated products (RH) will be formed mostly by reductive elimination [193, 194] however, concerted processes lead directly from RX to RH (see Sections 18.3.1.2 and 18.3.1.3). 

Espenson, James H., Homolytic and Free Radical Pathways in the Reactions of... 

Isomerization of oxepane (1) to cyclohexanol was found to occur in the presence of r-butyl hydroperoxide by a-cleavage of the oxepanyl radical intermediate (65) (76TL439). When a copper(I) chloride catalyst was present the major product was 2-(f-butyl-hydroperoxy)oxepane (77), probably also formed by a free radical pathway (Scheme 8) <80CR(291)223>. 

Thiepane (35) has been converted to 2-acetoxythiepane (137) by a homolytic mechanism using f-butyl peracetate in the presence of a copper(I) ion catalyst (67JCS(C)1130). Similarly, a-chlorination of thiepane (35) by N- chlorosuccinimide (NCS) to yield 2-chlorothiepane (132) probably occurred by a free radical pathway (Scheme 27) (69JHCU5). 

The addition of hydrogen halides to simple olefins, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule.116 When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 751).137 It must be emphasized that this is true only for HBr. Free-radical addition of HF and HI has never been observed, even in the presence of peroxides, and of HCI only rarely. In the rare cases where free-radical addition of HCI was noted, the orientation was still Markovnikov, presumably because the more stable product was formed.,3B Free-radical addition of HF, HI, and HCI is energetically unfavorable (see the discussions on pp. 683, 693). It has often been found that anti-Markovnikov addition of HBr takes place even when peroxides have not been added. This happens because the substrate alkenes absorb oxygen from the air, forming small amounts of peroxides (4-9). Markovnikov addition can be ensured by rigorous purification of the substrate, but in practice this is not easy to achieve, and it is more common to add inhibitors, e.g., phenols or quinones, which suppress the free-radical pathway. The presence of free-radical precursors such as peroxides does not inhibit the ionic mechanism, but the radical reaction, being a chain process, is much more rapid than the electrophilic reaction. In most cases it is possible to control the mechanism (and hence the orientation) by adding peroxides... 

Halogenations may also occur by a free-radical mechanism.121,218 Besides taking place in the gas phase, halogenation may follow a free-radical pathway in the liquid phase in nonpolar solvents. Radical halogenation is initiated by the alkene and favored by high alkene concentrations. It is usually retarded by oxygen and yields substitution products, mainly allylic halides. 

In studies of reaction pathways, nitrosyl radicals are frequently used as spin traps to provide evidence for free radical pathways. A caution in interpretation of these results is that the probe or products will interact with the transition metal complex in the reaction and affect the reactivity of the probe with the organic substrate or free radicals produced. A number of reactions of the stable free radicals RNO and R2NO with platinum(II) complexes have been carried out which show that such reactions must indeed be considered (equations 473-... 

The addition of thiols to C—C multiple bonds may proceed via an electrophilic pathway involving ionic processes or a free radical chain pathway. The main emphasis in the literature has been on the free radical pathway, and little work exists on electrophilic processes.534-537 The normal mode of addition of the relatively weakly acidic thiols is by the electrophilic pathway in accordance with Markovnikov s rule (equation 299). However, it is established that even the smallest traces of peroxide impurities, oxygen or the presence of light will initiate the free radical mode of addition leading to anti-Markovnikov products. Fortunately, the electrophilic addition of thiols is catalyzed by protic acids, such as sulfuric acid538 and p-toluenesulfonic acid,539 and Lewis acids, such as aluminum chloride,540 boron trifluoride,536 titanium tetrachloride,540 tin(IV) chloride,536 540 zinc chloride536 and sulfur dioxide.541... 

Depending on whether the electron pair of the broken bond is shared or not by the two new entities, the reaction sequence will involve either an ionic or a free-radical pathway, as shown in Equation (4.49) and Equation (4.50). 

This energy-rich 02 has in water (H20) only a very short lifetime (k = 2.5 x 10s s 1 in D20 it lives much longer, k = 1.6 x 104 s 1). Singlet 02 shows often only a low reactivity, but with a series of compounds, including dGuo and its derivatives, it reacts quite rapidly (for a compilation of rate constants, see Wilkinson et al. 1995). Because of its prolonged lifetime in D20, the yields of 02(1Ag)-reac-tions are much higher in this solvent than in water. In photosensitized reactions considered to occur by a free-radical pathway, these 02(1Ag)-reactions may yield... 

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