Rearrangement and Fragmentation Reactions of Free Radicals

Rearrangement and Fragmentation Reactions of Free Radicals 12.6.1. Rearrangement 

In a free radical, there is a third electron in the system. It cannot occupy the same orbital as the other two electrons. It is instead associated with an antibonding level, and therefore leads to a less favorable transition state for migration. The relatively more facile migration of unsaturated groups is associated with the ability of such groups to form bridged intermediates by an addition process. The unpaired electron can then be located in a more stable orbital  

The extent of radical rearrangement increases when there is considerable steric crowding at the carbon atom from which migration occurs. This trend is illustrated by 

Even in the most favorable cases, such as rearrangement of the primary radical A to the tertiary B by phenyl migration, there is a modest activation energy required  

ESR studies have shown that below -60 C, the rearrangement does not occur, 

SECTION 12.7. REARRANGEMENT AND FRAGMENTATION REACTIONS OF FREE RADICALS 

In the case of carbon tetrachloride, the radical intermediate undergoes two competing reactions intramolecular hydrogen abstraction is competitive with abstraction of a chlorine atom from carbon tetrachloride  

No product derived from the transannular hydrogen abstraction is observed in the addition of bromotrichloromethane because bromine-atom abstraction is sufficiently rapid to prevent effective competition by the intramolecular hydrogen abstraction. 

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. 

Intramolecular addition reactions are quite common when radicals are generated in molecules with unsaturation in a sterically favorable position. Cyclization reactions based on intramolecular addition of radical intermediates have become synthetically useful, and several specific cases will be considered in Section 10.3.4 of Part B. 

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This chapter discusses free-radical substitution reactions. Free-radical additions to unsaturated compounds and rearrangements are discussed in Chapters 15 and 18, respectively. Fragmentation reactions are covered, in part, in Chapter 17. 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. 

Chapter 11 deals with free radicals and their reactions. Fundamental structural concepts such as substituent effects on bond dissociation enthalpies (BDE) and radical stability are key to understanding the mechanisms of radical reactions. The patterns of stability and reactivity are illustrated by discussion of some of the absolute rate data that are available for free radical reactions. The reaction types that are discussed include halogenation and oxygenation, as well as addition reactions of hydrogen halides, carbon radicals, and thiols. Group transfer reactions, rearrangements, and fragmentations are also discussed. 

Sources of Radical Intermediates Introduction of Functionality by Radical Reactions Addition Reactions of Radicals with Substituted Alkenes Cyclization of Free-Radical Intermediates Fragmentation and Rearrangement Reactions... 

The thermal and photochemical activations of EDA complexes by electron transfer are both enhanced when the radical ions D+- or A--(either paired or free) undergo a facile first-order (unimolecular) transformation such as fragmentation, rearrangement, bond-formation, etc., which pulls the redox equilibrium and thus renders the competition from the energy-wasting back electron transfer less effective (compare Scheme 5). Critical to the quantitative evaluation of the reaction dynamics is the understanding that the typical [D+% A--] intermediates, as described in... 

In the presence of various metal ions, 2-(fluoroenone)benzothiazoline has been found to rearrange to A-2-mercaptophenylenimine, while a free radical mechanism involving the homolysis of C-S and C-N bonds has been invoked to explain the formation of 3-phenyl-1,2,4-triazole derivatives from the thermal fragmentation and rearrangement of 2-(arylidenehydrazino)-4-(5//)-thiazolone derivatives. The cycloadducts (36) formed from the reaction of 3-diethylamino-4-(4-methoxyphenyl)-5-vinyl-isothiazole 1,1-dioxide (34) with nitric oxides or miinchnones (35) have been found to undergo pyrolytic transformation into a, jS-unsaturated nitriles (38) by way of pyrrole-isothiazoline 1,1-dioxide intermediates (37). 

Secondary rearrangements apparent isomerizations through radical recombination reactions. In the rearrangement reactions considered so far, the isomerization step is the primary photochemical process, except when a biradical is formed as an intermediate for in that case the primary photochemical process is really a dissociation, even though the fragments cannot separate. There are however cases of overall isomerizations which result from the recombinations of separated free radicals formed through a process of photodissociation. The photo-Fries reaction is an important example of this mechanism, and is illustrated in Figure 4.43. 

Thus we propose the existence of a new pathway to browning in the Maillard reaction, involving sugar fragmentation and free radical formation prior to the Amadori rearrangement. 

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