Amine alkylation

Traditionally, aryl amination is difficult reaction which usually requires "activated" aryl halides, such as those with strong electron-withdrawing groups such as nitro groups ortho or para to the halogen atom. For the arylation of amines with unactivated aryl halides, the Buchwald-Hartwig reaction is useful. In this process, palladium complexes serve as catalysts. : ==Alkylation using alcohols==

Industrially, most alkylations are typically conducted using alcohols, not alkyl halides. Alcohols are less expensive than alkyl halides and their alkylation does not produce salts, the disposal of which can be problematic. Key to the alkylation of alcohols is the use of catalysts that render the hydroxyl group a good leaving group. The largest scale N-alkylation is the production of the methylamines from ammonia and methanol, resulting in approximately 500,000 tons/y of methylamine, dimethylamine, and trimethylamine. The reaction is poorly selective, requiring separation of the three products. Many other industrially significant alkyl amines are produced, again on a large scale, from the alcohols. Epoxides are another class of halide-free N-alkylating agents, useful in the production of ethanolamines. ==Alternative alkylation methods==

For laboratory use, the N-alkylation reaction is often unselective. A variety of alternative methods have been developed, such as the Delépine reaction, which uses hexamine. The Gabriel synthesis, involving the use of an equivalent to NH2−, only applies to primary alkyl halides. ==References==