Free-Radical Reactions

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Chapter: Organic Chemistry : Carbon-Carbon Bond Formation By Free-Radical Reactions

In such reactions one carbon serves as an electron donor (nucleophile) and a second carbon serves as an electron pair acceptor (electrophile).




In the previous chapter the formation of carbon–carbon bonds was discussed in terms of polar or two-electron processes. In such reactions one carbon serves as an electron donor (nucleophile) and a second carbon serves as an electron pair acceptor (electrophile). The result of the donor–acceptor interaction of these two species is a new carbon–carbon bond in which the electron pair is shared by the donor and acceptor.

Another way to form a bond between two carbons is for each carbon atom to supply one electron. In this case interaction between two carbons which each has a single, unshared electron would result in formation of a carbon–carbon bond. Species with unshared electrons are called free radicals, and thus formation of carbon–carbon bonds by this strategy requires carbon-centered free radicals as reactants.

Carbon-centered free radicals are carbon atoms which have three bonds and seven valence shell electrons, with the unshared electron occupying a valence orbital. They are generally thought to be planar (sp2 hybridized) and the unshared electron is in a 2p atomic orbital. They are not rigidly planar but are easily deformed to a pyramidal geometry. Because they have only seven valence level electrons, free radicals are very reactive intermediates and they rapidly undergo a variety of reactions. Because of their high reactivity, the formation of bonds by the combination of two free radicals is actually rare because the free-radical species must survive long enough to encounter another free radical with which to react. Normally free radicals undergo other reaction processes before they encounter a second free radical with which they can combine.

The reactivity of carbon-centered free radicals results from their drive to achieve an octet electronic configuration, which they do by two principal reaction processes. The first is atom transfer. This process is one in which an atom with one electron is transferred from a closed-shell molecule (fully paired, valence octets) to the free radical.

Due to the conservation of spin, a new radical species is formed. If the atom that is transferred is a hydrogen, then the process is called hydrogen abstraction and is the most common atom transfer reaction; however, other atoms can be transferred to free radicals as well. The driving force for atom transfer (abstrac-tion) reactions is usually the formation of a stronger bond and/or a more stable free radical.

A second very common free-radical reaction is addition to π systems to give a new bond and a new free radical. In this process the π bond is broken.

This process is quite common for carbon-centered free radicals because the car-bon–carbon σ bond which is formed is stronger by about 30 kcal than the π bond which is broken. Other radical species, however, are well known to undergo olefin additions as well. The addition of bromine to olefins is the key step in the anti-Markovnikov addition of HBr to olefins.

Another common feature of free-radical reactions is that they tend to be chain processes. Since any chemical reaction must exhibit conservation of spin, the reaction of a free radical with a closed-shell (fully electron paired) molecule must result in the production of a new free-radical species which can participate in subsequent free-radical reactions. The series of free-radical reactions leading to product is often a cyclic process in which the initial free radical is produced once again in the last step of the cycle so that the reaction sequence starts over again. The process is termed a chain reaction because each step of the process is linked directly to the preceding step.

Free-radical chain reactions can generally be divided into three phases:

1. Initiation is the phase of the process in which free radicals are produced that can start the chain reaction.

2. Propagation is the phase of the process in which free radicals undergo reactions which form products and produce new free radicals which can continue the chain.

3. Termination is the phase of the process in which free radicals are removed from the system by recombination or other reactions, thus interrupting the chain reaction.

A classic example is the free-radical addition of chloroform to olefins initiated by benzoyl peroxide.

Initiation normally requires molecules with weak bonds to undergo homolytic cleavage to produce free radicals. Since bond homolysis even of weak bonds is endothermic, energy in the form of heat (Δ) or light () is usually required in the initiation phase. However, some type of initiation is required to get any free-radical reaction to proceed. That is, you must first produce free radicals from closed-shell molecules in order to get free-radical reactions to occur. Benzoyl peroxide contains a weak O–O bond that undergoes thermal cleavage and decar-boxylation (probably a concerted process) to produce phenyl radicals which can initiate free-radical chain reactions.

Azobisisobutyronitrile (AIBN) is perhaps the most widely used initiator. It under-goes either thermolytic (Δ) or photolytic cleavage () to give isobutyronitrile radicals which can initiate free-radical reactions.

Hexa-n-butylditin can be photolyzed to two tri-n-butyltin radicals which are ini-tiators for tin-based free-radical reactions.

Many other free-radical initiators are available as well, and the choice of initiator is normally based on literature precedent and ease of use.

The propagation phase of a free-radical chain reaction is usually a cyclic sequence in which a molecule of product is produced and the propagating rad-ical is regenerated by the sequence. In the above example, the trichloromethyl radical adds to the double bond to give a new carbon-centered radical which abstracts a hydrogen from chloroform to produce a molecule of product and another trichloromethyl radical that continues the chain. Notice that this stage is cyclic and infinite. If a single ●CCl3 were generated, it would continue to form one molecule of product and another ●CCl3 until the olefin was converted com-pletely to product—one molecule at a time. Clearly this would be very slow, but because a single initiation event can lead to many molecules of product, one needs very little initiation. If, for example, the “chain length” of the propagation cycle is 200–300 (a common value), then one would need only a 1/200–1/300 ratio of initiator to olefin to convert the olefin completely to product. Thus initi-ation at 0.5–0.3% would suffice. If chain lengths are longer, then less initiation is required; if they are shorter, then more initiation would be required.

Termination reactions, while rare, do occur and serve to interrupt propagation cycles by removing propagating radicals from the system. Often these reactions are radical recombinations, but termination reactions also include the reaction of propagating free radicals with other species in solution (called scavengers) to give radicals incapable of participating in the propagation cycle. In the above example, a scavenger could react with either the trichloromethyl radical or the trichloromethyl addition product to give an unreactive free radical and thus inter-rupt the chain process.

The more effective a termination step is, the shorter will be the propagation cycle and the less product will be produced per initiation event. In the limiting case, if each initiation event was terminated, then no product would be produced. This is the role of “antioxidants” added to many products and most processed food. These additives scavenge free radicals produced by the reaction of oxygen with C–H bonds and prevent them from participating in oxidation propagation cycles—thus oxidative degradation is stopped or slowed markedly.

It is the reactivity of free radicals which has made them difficult to understand and control. Because of their great reactivity, they are quite unselective and tend to react with anything in solution, and hence multiple pathways and many prod-ucts are often the rule. Moreover many initiation methods fail to produce single free-radical species in a controlled and efficient fashion. As a result of these fac-tors, the use of free radicals in preparative organic chemistry has seen two distinct phases: first free-radical polymerization and then nonpolymerization reactions.

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