Amines are organic derivatives of ammonia. Primary amines () and secondary amines () can be synthesized through various chemical reactions depending on the desired structure and available starting materials. This section outlines the primary methods for their preparation.
This method involves the reaction of an alkyl halide with ammonia.
When an ethanolic solution of ammonia () is heated with an alkyl halide (e.g., bromoethane) in a sealed tube at , the nitrogen atom in ammonia, being nucleophilic, attacks the electrophilic carbon of the alkyl halide. This initially forms an alkylammonium salt. This salt then reacts with excess ammonia to produce the free primary amine.
ethylamine
A significant challenge with this method is that the reaction does not stop at the primary amine stage. The newly formed primary amine is also nucleophilic and can react further with the alkyl halide, leading to a mixture of secondary, tertiary amines, and eventually quaternary ammonium salts. This process is known as over-alkylation.
(diethylamine)
(triethylamine)
(tetraethylammonium bromide)
At the end of the reaction, the addition of a strong alkali, such as , liberates the free primary, secondary, and tertiary amines from their respective salts. However, the quaternary ammonium salt is unaffected by the alkali. The mixture of primary, secondary, and tertiary amines can then be separated by fractional distillation due to their different boiling points.
To favor the production of the primary amine and minimize over-alkylation, a large excess of ammonia is typically used. However, even with excess ammonia, the yield of the primary amine is often low.
Compounds containing nitrogen, such as nitriles, nitro compounds, and amides, can be reduced to amino groups using various reducing agents. These methods generally offer better control over the degree of alkylation compared to ammonolysis.
The reduction of alkyl or aryl nitriles () yields primary amines. This reduction can be achieved using strong reducing agents like Lithium Aluminum Hydride () or by sodium in ethanol ().
Nitriles can also be reduced catalytically by reacting with hydrogen gas () in the presence of a metal catalyst, typically nickel (), to form primary amines.
When an amide () is treated with a strong reducing agent like Lithium Aluminum Hydride (), the carbonyl group () of the amide is reduced to a methylene group (), forming a primary amine. This is an important method for chain lengthening as it retains all carbon atoms.
This reaction is used to convert an amide into a primary amine with one less carbon atom than the starting amide. The amide is treated with bromine () in an aqueous or ethanolic solution of sodium hydroxide ().
Nitro compounds (especially nitrobenzene) are reduced to primary amines using metals in acidic media (like or ) or by catalytic hydrogenation.
Aniline can be prepared by the reduction of benzene diazonium chloride or via the hydrolysis of diazonium salts in specific conditions, though it is more commonly used as a starting material for other derivatives.