Transition state radical abstraction

By the Hammond postulate, the transition state for abstraction of a hydrogen by a chlorine atom resembles the reactants and has only a small amount of radical character. Therefore, the transition state leading to a tertiary radical is only slightly more stable than the transition state leading to a primary radical. 

The alkyl radical-forming step is exothermic for chlorination, endothermic for bromination. Applying Hammond s postulate to these elementary steps, we conclude that alkyl radical character is more highly developed in the transition state for abstraction of hydrogen by a bromine atom than by a chlorine atom. Thus, bromination is more sensitive to the stability of the free-radical intermediate than chlorination and more selective. 

FIGURE 11.50 (a) Because the transition state for abstraction by chlorine lies roughly half way between starting material and product there can be little selectivity, (b) The product-like transition state for abstraction by bromine means that the radical on carbon will be well developed and the substitution pattern of the carbon atom (tertiary, secondary, primary, or methyl) will be relatively important in determining the ultimate major product. 

The transition states for abstraction of hydrogen from an alkane by chlorine and bromine radicals are very different from each other. In the transition states for abstractions by bromine, the radical on carbon is far more developed than it is in the abstractions by chlorine, which means that differences in the stabilities of different radicals will be far more important in determining the major product of the bromine abstractions than in the chlorine abstractions (Fig. 11.50). 

Diethylaminosulphur trifluroide converts cyclo-octanol into a mixture of cyclooctyl fluoride (70%) and ds-cyclo-octene (30%). Kinetic data suggests that there is considerable C—Br bond breaking in the transition state for abstraction of bromine from cycloalkyl bromides by phenyl radicals, and that anchimeric assistance by an adjacent bromine atom to bromine abstraction depends upon the accessibility of a trans-periplanar alignment of leaving and neighbouring groups. ... 

Abstractions of H adjacent to ethers and amines are important examples, the heteroatom adj acent to the site of reaction providing a favorable polar contribution to the transition state for abstraction by the electrophilic oxy radical, and providing stabilization for the product radical. Examples of the use of DTBP in this way include the study of anomeric radicals by Ingold and co-workers (eq 1), and a synthesis of substituted tetrahydrofurans (eq 2). ... 

This behavior stems from the greater stability of secondary compared with primary free radicals The transition state for the step m which a chlorine atom abstracts a hydro gen from carbon has free radical character at carbon... 

This proposal, however, has been criticized on the basis of transition state theory (74). Hydroperoxy radicals produced in reaction 23 or 24 readily participate in chain-terminating reactions (eq. 17) and are only weak hydrogen abstractors. When they succeed in abstracting hydrogen, they generate hydrogen peroxide ... 

Nevertheless, many free-radical processes respond to introduction of polar substituents, just as do heterolytic processes that involve polar or ionic intermediates. The substituent effects on toluene bromination, for example, are correlated by the Hammett equation, which gives a p value of — 1.4, indicating that the benzene ring acts as an electron donor in the transition state. Other radicals, for example the t-butyl radical, show a positive p for hydrogen abstraction reactions involving toluene. ... 

Important differences are seen when the reactions of the other halogens are compared to bromination. In the case of chlorination, although the same chain mechanism is operative as for bromination, there is a key difference in the greatly diminished selectivity of the chlorination. For example, the pri sec selectivity in 2,3-dimethylbutane for chlorination is 1 3.6 in typical solvents. Because of the greater reactivity of the chlorine atom, abstractions of primary, secondary, and tertiary hydrogens are all exothermic. As a result of this exothermicity, the stability of the product radical has less influence on the activation energy. In terms of Hammond s postulate (Section 4.4.2), the transition state would be expected to be more reactant-like. As an example of the low selectivity, ethylbenzene is chlorinated at both the methyl and the methylene positions, despite the much greater stability of the benzyl radical ... 

The selectivity observed in most intramolecular functionalizations depends on the preference for a six-membered transition state in the hydrogen-atom abstraction step. Appropriate molecules can be constmcted in which steric or conformational effects dictate a preference for selective abstraction of a hydrogen that is more remote from the reactive radical. 

It has been proposed that oxygen adds to the excited keto group [- (112)]. The rearrangement of the resulting hydroxyhydroperoxy diradical (112) could then proceed by intramolecular hydrogen abstraction involving a six-membered cyclic transition state, followed by fission of the former C —CO bond to form the unsaturated peracid (113) as the precursor of the final product. Such a reaction sequence demands a hydrogen atom in the J -position sterically accessible to the intermediate hydroperoxy radical. 

Upon the irradiation the nitrous acid ester 1 decomposes to give nitrous oxide (NO) and an alkoxy radical species 3. The latter further reacts by an intramolecular hydrogen abstraction via a cyclic, six-membered transition state 4 to give an intermediate carbon radical species 5, which then reacts with the nitrous oxide to yield the 3-nitroso alcohol 2 ... 

The enhanced selectivity of alkane bromination over chlorination can be explained by turning once again to the Hammond postulate. In comparing the abstractions of an alkane hydrogen by Cl- and Br- radicals, reaction with Br- is less exergonic. As a result, the transition state for bromination resembles the alkyl radical more closely than does the transition state for chlorination, and the stability of that radical is therefore more important for bromination than for chlorination. 

However, the situation is not as clear-cut as it might at first seem since a variety of other factors may also contribute to the above-mentioned trend. Abuin et a/.141 pointed out that the transition state for addition is sterically more demanding than that for hydrogen-atom abstraction. Within a given series (alkyl or alkoxy), the more nucleophilic radicals are generally the more bulky (i.e. steric factors favor the same trends). It can also be seen from Tabic 1.6 that, for alkyl radicals, the values of D decrease in the series primary>secondary>tertiary (i.e. relative bond strengths favor the same trend). 

The secret of the cyclisation is that salt (4) decomposes to radical (5) (and Cl ) which abstracts a hydrogen atom from the fourth carbon atom along the chain (5, arrows) via transition state (6) to give radical (7). This recaptures Cl (from Cl ) to give (8) which cyclises to (3) very easily. 

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