6.6 Radical Reactions

Radical Reactions

Radical reactions involve highly reactive species with unpaired electrons. Unlike polar reactions, they proceed through homolytic bond cleavage and typically follow a chain reaction mechanism. They can be kicked off by heat, light, or chemical initiators, and they show up in processes ranging from polymerization to combustion.

Characteristics of Radical Reactions

A radical (or free radical) is a species with an unpaired electron. Radicals are electrically neutral, which already makes them behave very differently from the charged intermediates you see in polar reactions.

• Radicals form through homolytic bond cleavage, where each atom takes one electron from the broken bond
  • Compare this to heterolytic cleavage in polar reactions, where one atom takes both electrons
• Radical reactions often follow a chain reaction mechanism with initiation, propagation, and termination steps
  • Polar reactions typically don't involve chain mechanisms
• Radicals are less sensitive to steric hindrance than polar intermediates
  • A radical center is smaller than the corresponding carbocation, so bulky groups around it matter less
• These reactions are often exothermic with relatively low activation energies
  • Radicals are so reactive that they don't need much energy to get over the transition state, and there's no charge buildup to stabilize
• Initiation requires an energy input: heat ($\Delta$), UV light ($h\nu$), or a chemical initiator like a peroxide (ROOR) or azo compound
  • Polar reactions rely on acids, bases, or other polar reagents instead
• Bond dissociation energy (BDE) governs how easily a particular bond undergoes homolysis. Weaker bonds break more readily to form radicals

Stages of Radical Chain Reactions

Every radical chain reaction moves through three stages. The propagation steps are where the actual chemistry happens, and they sustain themselves because each step regenerates a reactive radical.

1. Initiation: A non-radical species undergoes homolytic cleavage to generate radicals.

   • Example: $\text{Cl}_2 \xrightarrow{h\nu} 2\;\text{Cl}\cdot$
   • This step consumes energy (endothermic) and produces the first radicals that start the chain.

2. Propagation: Each radical reacts with a stable molecule to produce a new radical, keeping the chain going. There are two common types:

   • Hydrogen abstraction: $\text{R}\cdot + \text{R'–H} \rightarrow \text{R–H} + \text{R'}\cdot$
   • Addition to a multiple bond: $\text{R}\cdot + \text{C=C} \rightarrow \text{R–C–C}\cdot$
   • The sum of all propagation steps gives the overall balanced equation for the reaction.

3. Termination: Two radicals meet and destroy each other, ending the chain.

   • Combination: $\text{R}\cdot + \text{R'}\cdot \rightarrow \text{R–R'}$
   • Disproportionation: One radical transfers a hydrogen to another, producing two stable molecules. For example: $\text{R–CH}_2\text{–CH}_2\cdot + \text{R'}\cdot \rightarrow \text{R–CH=CH}_2 + \text{R'–H}$

The overall rate depends on all three stages. Under the steady-state approximation, the concentration of radicals stays roughly constant during the reaction because the rate of initiation equals the rate of termination.

Types of Radical Reactions

• Radical substitution: An atom or group is replaced by a radical. The classic example is halogenation of alkanes, where a C–H bond is replaced by a C–X bond.
• Radical addition: A radical adds across a multiple bond. Polymerization reactions work this way, with monomers adding one after another.
• Radical rearrangement: Atoms reorganize within a radical species through intramolecular shifts. These are less common than in carbocation chemistry but do occur.

Factors Affecting Radical Reactions

Radical stability is the biggest factor controlling selectivity. More substituted radicals are more stable because of hyperconjugation, the same effect that stabilizes carbocations.

• Stability order: tertiary > secondary > primary > methyl
• A more stable radical forms more easily (lower activation energy for that step), so reactions tend to favor products that go through the most stable radical intermediate.

Antioxidants are compounds that shut down radical chain reactions by scavenging free radicals. Vitamin E, for instance, donates a hydrogen atom to a radical, producing a much less reactive radical that can't continue the chain. This is why antioxidants matter in both biology and industrial chemistry.

Applications of Radical Reactions

Polymerization: Polymers like polyethylene and polystyrene are made through radical chain reactions. A peroxide or azo compound generates the initial radical, which then adds to the $\text{C=C}$ double bond of a monomer. Each addition creates a new radical at the chain end, so the polymer keeps growing until termination occurs.

Halogenation of alkanes: Chlorination and bromination of alkanes are textbook radical substitution reactions. Light or heat cleaves the $\text{X–X}$ bond homolytically. The halogen radical then abstracts a hydrogen from the alkane, and the resulting alkyl radical reacts with another $\text{X}_2$ molecule. Bromination is more selective than chlorination because the hydrogen abstraction step is more endothermic for $\text{Br}\cdot$, making it more sensitive to differences in C–H bond strength.

Combustion: Burning hydrocarbons in engines and power plants is a radical process. A spark or heat generates the first radicals from fuel molecules, and a complex web of hydrogen abstraction and addition reactions with $\text{O}_2$ follows.

Lipid peroxidation: Reactive oxygen species like the hydroxyl radical ($\text{HO}\cdot$) can abstract a hydrogen from a lipid in a cell membrane. The resulting carbon radical reacts with $\text{O}_2$ to form a peroxyl radical ($\text{ROO}\cdot$), which abstracts hydrogen from a neighboring lipid, propagating damage through the membrane.

Enzyme-catalyzed radical reactions: Some enzymes use radical intermediates. Ribonucleotide reductase, for example, converts ribonucleotides to deoxyribonucleotides by generating a thiyl radical ($\text{RS}\cdot$) from a cysteine residue. That thiyl radical abstracts a hydrogen from the substrate to initiate the reduction.