Free Radical Autoxidation

The term free-radical autoxidation describes a reaction pathway in which dioxygen reacts with an organic substrate to give an oxygenated product in a freeradical chain process that requires an initiator in order to get the chain reaction started. 21 (A free-radical initiator is a compound that yields free radicals readily upon thermal or photochemical decomposition.) The mechanism of free radical autoxidation is as shown in Reactions (5.16) to (5.21).

(plus other oxidized products, such as ROOH, ROH, RC(O)R, RC(O)H). This reaction pathway results in oxygenation of a variety of organic substrates, and is not impeded by the spin restriction, because triplet ground-state dioxygen can react with the free radical R· to give a free-radical product ROO, in a spinallowed process (Reaction 5.18). It is a chain reaction, since R· is regenerated in Reaction (5.19), and it frequently occurs with long chain lengths prior to the termination steps, resulting in a very efficient pathway for oxygenation of some organic substrates, such as, for example, the oxidation of cumene to give phenol and acetone (Reaction 5.22).22

When free-radical autoxidation is used for synthetic purposes, initiators are intentionally added. Common initiators are peroxides and other compounds capable of fragmenting readily into free radicals. Free-radical autoxidation reactions are also frequently observed when no initiator has been intentionally added, because organic substrates frequently contain peroxidic impurities that may act as initiators. Investigators have sometimes been deceived into assuming that a metal-complex catalyzed reaction of dioxygen with an organic substrate occurred by a nonradical mechanism. In such instances, the reactions later proved, upon further study, to be free-radical autoxidations, the role of the metal complex having been to generate the initiating free radicals.
 

Although often useful for synthesis of oxygenated derivatives of relatively simple hydrocarbons, free-radical autoxidation lacks selectivity and therefore, with more complex substrates, tends to give multiple products. In considering possible mechanisms for biological oxidation reactions used in vivo for biosynthesis or energy production, free-radical autoxidation is not an attractive possibility, because such a mechanism requires diffusion of highly reactive free radicals.
 

Such radicals, produced in the cell, will react indiscriminately with vulnerable sites on enzymes, substrates, and other cell components, causing serious damage. 6 In fact, free-radical autoxidation is believed to cause certain deleterious reactions of dioxygen in biological systems, for example the oxidation of lipids in membranes. It is also the process that causes fats and oils to become rancid (Reaction 5.23).23,24