Free Radical Reactions

Free radicals are species with an unpaired electron; their reactions proceed by homolytic bond cleavage and self-sustaining chains rather than the electron-pair movements of ionic chemistry.

Definition

Free radical reactions are transformations that proceed through intermediates bearing one or more unpaired electrons, formed by homolytic bond cleavage and reacting by atom transfer or addition in chain processes.

Scope

This topic covers radical generation by homolysis and initiators, the initiation–propagation–termination structure of chain reactions, radical stability and bond-dissociation energies, radical halogenation and its selectivity, radical addition (including anti-Markovnikov HBr addition), and radical polymerization.

Core questions

• How are radicals generated and stabilized?
• What governs the regioselectivity of radical halogenation and addition?
• How do initiation, propagation, and termination steps combine into a chain reaction?

Key theories

Radical chain mechanism

Radical reactions consist of an initiation step that creates radicals, propagation steps that consume and regenerate them while forming product, and termination steps in which two radicals combine.

Radical stability and selectivity

Radical stability (tertiary > secondary > primary), governed by hyperconjugation and resonance and quantified by bond-dissociation energies, controls the selectivity of abstraction and addition; the reactive halogen (Cl) is less selective than the milder one (Br).

Mechanisms

Homolysis of weak bonds (peroxides, halogens under light or heat) generates radicals that abstract atoms or add to pi bonds. In radical halogenation a halogen atom abstracts a hydrogen, generating a carbon radical that reacts with another halogen molecule to continue the chain. Radical addition to alkenes follows the path giving the more stable radical, accounting for anti-Markovnikov selectivity in peroxide-initiated HBr addition.

Clinical relevance

Radical chemistry underlies oxidative damage to lipids, proteins, and DNA implicated in aging and disease, the protective action of antioxidants, and modern synthetic radical methods that form bonds under mild conditions tolerant of many functional groups.

History

Gomberg's 1900 discovery of the persistent triphenylmethyl radical proved that stable trivalent-carbon species exist; Kharasch's work in the 1930s on the peroxide effect explained anti-Markovnikov radical addition, founding modern radical chemistry.

Key figures

• Moses Gomberg
• Morris S. Kharasch
• Frank Mayo

Seminal works

• gomberg1900
• careysundberg2007a

Frequently asked questions

Why is radical bromination more selective than chlorination?

Hydrogen abstraction by bromine is endothermic and has a late, product-like transition state that strongly favors forming the most stable radical, whereas the more reactive chlorine has an early transition state and abstracts hydrogens with little discrimination.

What stops a radical chain reaction?

Termination steps, in which two radicals combine or disproportionate to give non-radical products, consume the chain carriers and halt the reaction; radical inhibitors and antioxidants work by deliberately introducing such terminations.