Radicals benzylic abstraction

Alkyl Side Chains of Aromatic Rings. The preferential position of attack on a side chain is usually the one a to the ring. Both for active radicals such as chlorine and phenyl and for more selective ones such as bromine such attack is faster than that at a primary carbon, but for the active radicals benzylic attack is slower than for tertiary positions, while for the selective ones it is faster. Two or three aryl groups on a carbon activate its hydrogens even more, as would be expected from the resonance involved. These statements can be illustrated by the following abstraction ratios ... 

The transfer constant for f-butylbenzene is low, since there are no benzylic C—H bonds present. Primary halides such as n-butyl chloride and bromide behave similar to aliphatics with low transfer constants, corresponding to a combination of either aliphatic C—H bond breakage or the low stability of a primary alkyl radical on abstraction of Cl or Br. The iodide,... 

Toluene-d4, -d5, and -d6 remained constant -d3 decreased, and - 2 increased. This indicates some exchange, probably by way of a benzyl radical that abstracts protium in place of the original deuterium. Toluene-a-d3, refluxed for 2 hours in acetic acid with the same concentration of cobalt acetate and cobalt bromide, was recovered unchanged. Hydrogen, of course, could be furnished by the acetic acid however, in the Ci4 hydrocarbons, the product of molecular weight 187 amounted to about 15% of that of 186. Presumably these are chiefly methyldiphenylmethane and bibenzyl, respectively. 

The EPR spectra of the NHC boryl radicals that were generated through HAT to the ferf-butoxyl radical clearly show the delocalized 7i-type nature of these intermediates postulated to be essential by calculations [10, 12]. It was also demonstrated that the decay of the EPR signals could be fitted to a second-order decay having 2kt = 9 x 106 M-1 s-1. In agreement with this kinetic analysis, the NHC boryl radicals ultimately dimerize to give bis-NHC diborane derivatives. With the aid of EPR spectroscopy it was also established that the NHC boryl radicals readily abstract bromine atoms from primary, secondary, and tertiary alkyl bromides. However, chlorine atom abstraction is much slower and useful only for benzyl chloride. 

Irradiation of NADH model compounds in the presence of benzyl bromide or p-cyanobenzyl bromide in acetonitrile brings about reduction of the benzyl halides to the corresponding toluene compounds114. Like the S l substitution reaction, this photoreduction also occurs via an electron-transfer chain mechanism. Unlike in that case, though, here an electron transfer from the excited state of the NADH compound is solely responsible for the initiation step. In the propagation, the benzyl radical produced by C—Br bond cleavage in the radical anion abstracts hydrogen from the NADH compound. This yields a radical intermediate, from which electron transfer to benzyl bromide occurs readily (equations 39-42). 

The O radical abstracts hydrogen from aliphatic compounds relatively rapidly (but about a factor of two more slowly than OH) while it adds to olefinic and aromatic compounds very slowly, if at all. E.s.r. experiments have demonstrated that the reaction of O" with toluene or crotonate leads predominantly to the radicals formed by abstraction and not by addition (Neta et al., 1972) as shown by reactions (26) and (27) above. These findings have since been used for the production of radicals by abstraction from compounds which tend normally to add. For example, a series of substituted benzyl radicals have been produced by reaction of O with substituted toluenes (Neta and Schuler, 1973). 

The mechanism of the Wohl-Ziegler bromination involves bromine radicals (and not imidoyl radicals). The radical initiator is homolytically cleaved upon irradiation with heat or light, and it reacts with Bra (which is always present in small quantities in NBS) to generate the Br- radical, which abstracts a hydrogen atom from the allylic (or benzylic) position. The key to the success of the reaction is to maintain a low concentration of Bra so that the addition across the C=C double bond is avoided. The Bra is regenerated by the ionic reaction of NBS with the HBr by-product. 

Answer The thermal homolysis of the weak oxygen-chlorine bond in r-butyl hypochlorite produces a r-butoxy radical that starts the chain. This radical will abstract a hydrogen atom from the benzylic methylene of 1-phenylpropane to give a resonance-delocalized benzylic radical, the most stable of all the possible alternatives. The propagation loop completes when the benzylic radical abstracts a chlorine atom from t-butyl hypochlorite and creates a r-butoxy radical to start the process over again. The products are 1-chloro-1-phenylpropane and r-butanol. 

The reaction is believed to proceed through a SET from the benzyl ether 36 to the DDQ to generate benzyl radical cation 39 and a DDQ radial anion 40. Abstraction of the proton of radical cation 39 by 40 results in the formation of the radical benzyl ether cation 41 and DDQ anion 42. Deprotonation of ketone 16 by anion 42 generates enolate 43, which then undergoes addition to 41 to furnish the desired oxidative alkylated ether 38. 

Valuable insight of multiple additions of free radicals came from the ESR spectroscopic investigations of benzyl radicals, C-labeled at the benzylic positions [97,98]. These radicals can be prepared in situ by photolysis of saturated solutions of Cgo in labeled toluene containing about 5% di-ferf-butyl peroxide. Thereby, the photochemically generated ferf-butoxy radicals readily abstract a benzylic hydrogen atom from the toluene. Two radical species with a different microwave power saturation behavior can be observed. One radical species can be attributed to an allylic radical 63 and the other to a cyclopentadienyl radical 65 formed by the addition to three and five adjacent [5]radialene double bonds, respectively (Scheme 11). In these experiments no evidence for the radical 61 is found, which is very likely a short-lived species. 

Figure 7.10 displays the reaction profile for the hydrogen abstraction by phenoxy and benzyl radicals on PPE and the PPE derivatives/>HO-PPE andPCH3O-PPE. The a-PPE radicals are stabilized relative to the /3-PPE radicals by delocalization of the unpaired electron into the aromatic ring [79]. The substituent effect on the a-PPE radical can be deduced from the reaction profile of the phenoxy abstraction (left side of Figure 7.10) for the benzyl abstraction (right side of Figure 7.10), the benzyl radical also carries a substituent. The stability of the /3-PPE radical is not influenced by the substituents, but the a-PPE radical is stabilized by the hydroxy and methoxy substituents. 

The substituent effect on the reaction energies of the phenoxy abstraction is remarkably large, even though we can deduce from the benzyl abstraction that the substituent effect on the PPE radical is small. Analysis of the substituent effects on phenol and phenoxy [91] shows that the phenoxy radical is stabilized and phenol is destabilized by the methoxy substituents. The phenoxy and phenol effects are additive, resulting in a large total substituent effect for the a- and /3-channels. 

The second reaction is a radical chain reaction. A radical initiator abstracts the benzylic hydrogen atom of cumene, producing a 3° benzylic radical. Then a chain reaction with oxygen, which exists as a paramagnetic diradical in the ground state, produces cumene hydroperoxide ... 

In the first step, oxygen abstracts a hydrogen atom from the benzylic carbon, setting the stage for a chain reaction that begins when the cumene hydroperoxy radical shown abstracts a benzylic hydrogen from a second molecule of cumene. 

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