Free radical halogenation

Halogenation of saturated hydrocarbons is a substitution reaction. The reaction typically involves free radical pathways. The regiochemistry of the halogenation of alkanes is largely determined by the relative weakness of the C–H bonds. This trend is reflected by the faster reaction at tertiary and secondary positions.

Free radical chlorination is used for the industrial production of some solvents:^[2]

CH₄ + Cl₂ → CH₃Cl + HCl

Naturally occurring organobromine compounds are usually produced by free radical pathway catalyzed by the enzyme bromoperoxidase. The reaction requires bromide in combination with oxygen as an oxidant. The oceans are estimated to release 1–2 million tons of bromoform and 56,000 tons^[which?] of bromomethane annually.^[3]

The iodoform reaction, which involves degradation of methyl ketones, proceeds by the free radical iodination.

Fluorination

Because of its extreme reactivity, fluorine (F₂) represents a special category with respect to halogenation. Most organic compounds, saturated or otherwise, burn upon contact with F₂, ultimately yielding carbon tetrafluoride. By contrast, the heavier halogens are far less reactive toward saturated hydrocarbons.

Highly specialised conditions and apparatus are required for fluorinations with elemental fluorine. Commonly, fluorination reagents are employed instead of F₂. Such reagents include cobalt trifluoride, chlorine trifluoride, and iodine pentafluoride.^[4]

The method electrochemical fluorination is used commercially for the production of perfluorinated compounds. It generates small amounts of elemental fluorine in situ from hydrogen fluoride. The method avoids the hazards of handling fluorine gas. Many commercially important organic compounds are fluorinated using this technology.

Addition of halogens to alkenes and alkynes

Unsaturated compounds, especially alkenes and alkynes, add halogens:

R−CH=CH−R' + X₂ → R−CHX−CHX−R'

In oxychlorination, the combination of hydrogen chloride and oxygen serves as the equivalent of chlorine, as illustrated by this route to 1,2-dichloroethane:

4 HCl + 2 CH₂=CH₂ + O₂ → 2 Cl−CH₂−CH₂−Cl + 2 H₂O

The addition of halogens to alkenes proceeds via intermediate halonium ions. In special cases, such intermediates have been isolated.^[5]

Bromination is more selective than chlorination because the reaction is less exothermic. Illustrative of the bromination of an alkene is the route to the anesthetic halothane from trichloroethylene:^[6]

Iodination and bromination can be effected by the addition of iodine and bromine to alkenes. The reaction, which conveniently proceeds with the discharge of the color of I₂ and Br₂, is the basis of the analytical method. The iodine number and bromine number are measures of the degree of unsaturation for fats and other organic compounds.

Halogenation of aromatic compounds

Aromatic compounds are subject to electrophilic halogenation:

R−C₆H₅ + X₂ → HX + R−C₆H₄−X

This kind of reaction typically works well for chlorine and bromine with electron-rich aromatic substrates. Often a Lewis acidic catalyst is used, such as ferric chloride.^[7] Many detailed procedures are available.^[8][9] When the aromatic substrate contains electron-withdrawing groups, halogenation does not proceed with the halogens. Potassium bromate in the presence of acid can, however, be used to brominate otherwise recalcitrant aromatic substrates, such as nitrobenzene.^[10]

Because fluorine is so reactive, other methods, such as the Balz–Schiemann reaction, are used to prepare fluorinated aromatic compounds.

Other halogenation methods

In the Hunsdiecker reaction, carboxylic acids are converted to organic halide, whose carbon chain is shortened by one carbon atom with respect to the carbon chain of the particular carboxylic acid. The carboxylic acid is first converted to its silver salt, which is then oxidized with halogen:

R−COO⁻Ag⁺ + Br₂ → R−Br + CO₂ + Ag⁺Br⁻

CH₃−COO⁻Ag⁺ + Br₂ → CH₃−Br + CO₂ + Ag⁺Br⁻

Many organometallic compounds react with halogens to give the organic halide:

RM + X₂ → RX + MX

CH₃CH₂CH₂CH₂Li + Cl₂ → CH₃CH₂CH₂CH₂Cl + LiCl