Benzylic hydrogenation, with radicals

The treatment of compounds possessing primary, secondary, and especially tertiary benzylic hydrogens with oxygen, usually under irradiation, results in a free-radical chain reaction giving hydroperoxides as the final products (equation 161). 

Free-radical Reactions.—number of further publications have appeared concerning the free-radical insertion of fluoro-olefins into C—H bonds (see Voi. 2, p. 122). Perokide-initiated reaction of toluene, and other alkyl benzenes having benzylic hydrogens, with hexafluoropropene yields mainly the adduct (89) and some of the indane (90) arising from cyclization of the initially formed radical, with subsequent dehydrogenation. The indane (90) yields the corresponding indene with ethanolic... 

The comparative ease with which a benzylic hydrogen is abstracted leads to high selectivity m free radical halogenations of alkylbenzenes Thus chlorination of toluene... 

As we saw when discussing allylic brommation m Section 10 4 N bromosuccm imide (NBS) is a convenient free radical brommatmg agent Benzylic brommations with NBS are normally performed m carbon tetrachloride as the solvent m the presence of peroxides which are added as initiators As the example illustrates free radical bromi nation is selective for substitution of benzylic hydrogens... 

The mechanism of benzylic bromination is similar to that discussed in Section 10.4 for allylic bromination of alkenes. Abstraction of a benzylic hydrogen atom generates an intermediate benzylic radical, which reacts with Br2 to yield product and a Br- radical that cycles back into the reaction to carry on the chain. The Br2 necessary for reaction with the benzylic radical is produced by a concurrent reaction of HBr with NBS. 

When the iron sandwich complex bears an arene substituent with at least one benzylic hydrogen, the acidity of the latter is enhanced by the 7t-complexation to the 12e fragment FeCp+. The pKa of the conjugate acid of superoxide radical... 

Similarly, when both the Cp and arene ligands are permethylated, the reaction of 02 with the Fe1 complex leads to C-H activation of the more acidic benzyl bond [57]. When no benzylic hydrogen is present, superoxide reacts as a nucleophile and adds onto the benzene ligand of the FeCp(arene)+ cation to give a peroxocyclohexadienyl radical which couples with a Fe Cp(arene) radical. A symmetrical bridging peroxo complex [(Fe"Cp)2(r 5-C6H60)2] is obtained. The C-H activation reactions of the 19e Fe1 radicals BH can be summarized as follows... 

The results of chain transfer studies with different polymer radicals are compared in Table XIV. Chain transfer constants with hydrocarbon solvents are consistently a little greater for methyl methacrylate radicals than for styrene radicals. The methyl methacrylate chain radical is far less effective in the removal of chlorine from chlorinated solvents, however. Vinyl acetate chains are much more susceptible to chain transfer than are either of the other two polymer radicals. As will appear later, the propagation constants kp for styrene, methyl methacrylate, and vinyl acetate are in the approximate ratio 1 2 20. It follows from the transfer constants with toluene, that the rate constants ktr,s for the removal of benzylic hydrogen by the respective chain radicals are in the ratio 1 3.5 6000. Chain transfer studies offer a convenient means for comparing radical reactivities, provided the absolute propagation constants also are known. 

Although it proved possible to conclude from the results of further experiments with the perester that succinimidyl radicals from this source could abstract benzylic hydrogen from toluene, the reaction system presented further difficulties which are still unresolved. For example, when solutions of NBS and MBN are mixed in the dark, a high concentration of [32] is immediately produced. Whilst this helped to establish the origin of the 27-line spectrum, it constitutes a fresh mechanistic puzzle. 

Fig. 7 Reactions of toluene with HO radical. HO can abstract a benzylic hydrogen atom (a) or add to the aromatic ring at the ipso (b), ortho (c), meta (d), and para (e) positions relative to the methyl group. Each resultant radical can decompose by various pathways, depending on temperature and pressure.

When chlorination or bromination of alkenes is carried out in the gas phase at high temperature, addition to the double bond becomes less significant and substitution at the allylic position becomes the dominant reaction.153-155 In chlorination studied more thoroughly a small amount of oxygen and a liquid film enhance substitution, which is a radical process in the transformation of linear alkenes. Branched alkenes such as isobutylene behave exceptionally, since they yield allyl-substituted product even at low temperature. This reaction, however, is an ionic reaction.156 Despite the possibility of significant resonance stabilization of the allylic radical, the reactivity of different hydrogens in alkenes in allylic chlorination is very similar to that of alkanes. This is in accordance with the reactivity of benzylic hydrogens in chlorination. 

This process competes favorably with benzylic hydrogen abstraction in toluene, less in ethylbenzene, and least in cumene (31). Such reactions do not seem significant in the oxidation of benzene derivatives. However, naphthalene reacts about 20 times as rapidly with phenyl radical as does benzene (16), and radical addition to the naphthalene nucleus may at least partly account for the slow oxidation rate in the methylnapthalenes. Among the minor products from both methylnaphthalene oxidations were compounds of molecular weight 296 ... 

Radical fragmentation of 2-nitrophenyl-azo-trityl resin was studied in the presence of various radical acceptor solvents to elucidate possible radical reaction pathways. When using benzene as solvent, only 2-nitro-bi-phenyl was formed as the product of radical substitution reaction (SNR) in 67% yield. Hydrogen-radical abstraction from the polymer backbone (e.g., from the benzylic units of polystyrene) was completely suppressed. When toluene was used as solvent, a mixture of the following products was obtained nitrobenzene, 4-methyl-2 -nitrobisphenyl, 2-methyl-2 -nitro-bisphenyl, and 3-methyl-2 -nitrobisphenyl (9 9 1 1). In the case of toluene, the nitro-aryl radicals undergo H-abstraction with radical substitution as a competing reaction pathway. These results indicate that H-abstraction... 

In a study dealing with the construction of a 5 -aza-naphthacene derivative, conditions of the radical reaction did not affect the SMA framework present in the starting material. This result could be explained either by the steric hindrance of the silyl group that inhibits the abstraction of the benzylic hydrogen atom to create the corresponding radical species, or this radical, if created, is too stable to react efficiently.153... 

Suitable alkylbenzene side chains are oxidized at the benzylic position under the action of mCPBA, air, and NaHC03 to generate the corresponding ketones. The oxygen-centered radical formed from mCPBA, abstracts the benzylic hydrogen atom of the benzylic substrate (68) to form a benzylic radical, and then it reacts with molecular oxygen... 

While these reactions are of limited use in the synthesis of complex molecules, they are very interesting from a mechanistic point of view. It has been firmly established that benzylic or allylic radicals and metal centered radicals are formed as intermediates through hydrogen atom transfer from the M-H bond to the C-C double bond. Interestingly, the addition of the hydrogen atom is reversible as demonstrated by isotope scrambling with deuterated olefins. If the radicals possess multiple sites for hydrogen atom abstraction, olefin isomerization can ultimately occur. HAT to unactivated olefins was not observed. 

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