Oxidation radical mechanisms

The introduction of additional alkyl groups mostly involves the formation of a bond between a carbanion and a carbon attached to a suitable leaving group. S,.,2-reactions prevail, although radical mechanisms are also possible, especially if organometallic compounds are involved. Since many carbanions and radicals are easily oxidized by oxygen, working under inert gas is advised, until it has been shown for each specific reaction that air has no harmful effect on yields. 

The reaction follows a free radical mechanism and gives a hydroperoxide a compound of the type ROOH Hydroperoxides tend to be unstable and shock sensitive On stand mg they form related peroxidic derivatives which are also prone to violent decomposi tion Air oxidation leads to peroxides within a few days if ethers are even briefly exposed to atmospheric oxygen For this reason one should never use old bottles of dialkyl ethers and extreme care must be exercised m their disposal... 

Metal Catalysis. Aqueous solutions of amine oxides are unstable in the presence of mild steel and thermal decomposition to secondary amines and aldehydes under acidic conditions occurs (24,25). The reaction proceeds by a free-radical mechanism (26). The decomposition is also cataly2ed by V(III) and Cu(I). 

The same products may be made from primary alkoxides by the violent reaction with elementary chlorine or bromine. A radical mechanism has been proposed to account for the oxidation of some of the alkoxy groups (54) ... 

Homogeneous Oxidation Catalysts. Cobalt(II) carboxylates, such as the oleate, acetate, and naphthenate, are used in the Hquid-phase oxidations of -xylene to terephthaUc acid, cyclohexane to adipic acid, acetaldehyde (qv) to acetic acid, and cumene (qv) to cumene hydroperoxide. These reactions each involve a free-radical mechanism that for the cyclohexane oxidation can be written as... 

Most of the free-radical mechanisms discussed thus far have involved some combination of homolytic bond dissociation, atom abstraction, and addition steps. In this section, we will discuss reactions that include discrete electron-transfer steps. Addition to or removal of one electron fi om a diamagnetic organic molecule generates a radical. Organic reactions that involve electron-transfer steps are often mediated by transition-metal ions. Many transition-metal ions have two or more relatively stable oxidation states differing by one electron. Transition-metal ions therefore firequently participate in electron-transfer processes. 

The radical mechanism is supported by a number of findings for instance, when the electrolysis is carried out in the presence of an olefin, the radicals add to the olefinic double bond styrene does polymerize under those conditions. Side products can be formed by further oxidation of the alkyl radical 2 to an intermediate carbenium ion 5, which then can react with water to yield an alcohol 6, or with an alcohol to yield an ether 7 ... 

Mn(III) is able to oxidize many organic substrates via the free radical mechanism [32], The free radical species, generated during oxidation smoothly initiate vinyl polymerization [33-35]. Mn(III) interacts also with polymeric substrates to form effective systems leading to the formation of free radicals. These radicals are able to initiate vinyl polymerization and, consequently, grafting in the presence of vinyl monomers. 

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

Titov claims that the free radical mechanism applies for nitration of aliphatic hydrocarbons, of aromatic side chains, of olefins, and of aromatic ring carbons, if irf the latter case the nitrating agent is ca 60—70% nitric acid that is free of nitrous acid, or even more dil acid if oxides of nitrogen are present... 

This statement does not mean, however, that the mechanism of diazotization was completely elucidated with that breakthrough. More recently it was possible to test the hypothesis that, in the reaction between the nitrosyl ion and an aromatic amine, a radical cation and the nitric oxide radical (NO ) are first formed by a one-electron transfer from the amine to NO+. Stability considerations imply that such a primary step is feasible, because NO is a stable radical and an aromatic amine will form a radical cation relatively easily, especially if electron-donating substituents are present. As discussed briefly in Section 2.6, Morkovnik et al. (1988) found that the radical cations of 4-dimethylamino- and 4-7V-morpholinoaniline form the corresponding diazonium ions with the nitric oxide radical (Scheme 2-39). 

A-(2-Hydroxyimino-l,2-diphenylethylidene)aniline (13) gave 2,3-diphenylqui-noxahne (12) [neat AC2O, reflux, <24 h [monitored by thin-layer chromatography (tic)] 57% via the isolable acetoxyimino intermediate by a radical mechanism] or 2,3-diphenylquinoxaline 1-oxide (14) [Pb(OAc)4, CH2CI2, 25°C, 1 h 48%] when unsymmetric aniline substrates were used, two... 

In this chapter, we discuss free-radical substitution reactions. Free-radical additions to unsaturated compounds and rearrangements are discussed in Chapters 15 and 18, respectively. In addition, many of the oxidation-reduction reactions considered in Chapter 19 involve free-radical mechanisms. Several important types of free-radical reactions do not usually lead to reasonable yields of pure products and are not generally treated in this book. Among these are polymerizations and high-temperature pyrolyses. 

Mechanisms of aldehyde oxidation are not firmly established, but there seem to be at least two main types—a free-radical mechanism and an ionic one. In the free-radical process, the aldehydic hydrogen is abstracted to leave an acyl radical, which obtains OH from the oxidizing agent. In the ionic process, the first step is addition of a species OZ to the carbonyl bond to give 16 in alkaline solution and 17 in acid or neutral solution. The aldehydic hydrogen of 16 or 17 is then lost as a proton to a base, while Z leaves with its electron pair. 

When catechol was oxidized with Mn04 under aprotic conditions, a semiquinone radical ion intermediate was involved. For autoxidations (i.e., with atmospheric oxygen) a free-radical mechanism is known to operate. 

This was also accomplished with BaRu(0)2(OH)3. The same type of conversion, with lower yields (20-30%), has been achieved with the Gif system There are several variations. One consists of pyridine-acetic acid, with H2O2 as oxidizing agent and tris(picolinato)iron(III) as catalyst. Other Gif systems use O2 as oxidizing agent and zinc as a reductant. The selectivity of the Gif systems toward alkyl carbons is CH2 > CH > CH3, which is unusual, and shows that a simple free-radical mechanism (see p. 899) is not involved. ° Another reagent that can oxidize the CH2 of an alkane is methyl(trifluoromethyl)dioxirane, but this produces CH—OH more often than C=0 (see 14-4). ... 

Although these reactions are formulated as ionic reactions via 947 and 949, because of the apparent partial formation of polymers and inhibition of the fluoride-catalyzed reaction of pyridine N-oxide 860 with aUyl 82 or benzyltrimethylsilane 83 by sulfur or galvinoxyl yet not by Tempo, a radical mechanism caimot be excluded [61, 62]. The closely related additions of allyltrimethylsilane 82 (cf. Section 7.3) to nitrones 976 are catalyzed by TMSOTf 20 to give, via 977, either o-unsatu-rated hydroxylamines 978 or isoxazoHdines 979 (cf also the additions of 965 to 962a and 969 in schemes 7.20 and 7.21). 

A subsequent detailed analysis of the permanganate oxidation of the tertiary hydrogen atom of 4-phenylvaleric acid in 2.5 M potassium hydroxide solution supports the caged radical mechanism. The reaction order is two overall, A h/ d is ca. 11.5, ring substitution has little elfect on the rate (p 0) and the oxidation proceeds with a net 30-40 % retention of optical configuration. 

Cannabinidiol (CBND, 2.18) and cannabinol (2.19) are oxidation products of CBD and A9-THC formed by aromatization of the terpenoid ring. For the dehydrogenation of THC a radical mechanism including polyhydroxylated intermediates is suggested [10,11]. CBN is not the sole oxidation product of A9-THC. Our own studies at THC-Pharm on the stability of A9-THC have shown that only about 15% of lost A9-THC is recovered as CBN. 

Sadrzadeh, S.M.H. and Eaton, J.W. (1992). Hemt obin-induced oxidant damage to the central nervous system. In Free Radical Mechanisms of Tissue Injury (eds. M.T. Moslen and C.V. Smith) pp. 24—32. CRC Press, Boca Baton. 

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