19.12:
Preparation of Amines: Alkylation of Ammonia and Amines
Ammonia and alkyl halides react through alkylation of nitrogen via an SN2 mechanism to give monoalkylammonium salts, which on subsequent deprotonation give primary alkylamines.
Alkylation makes the nitrogen center more nucleophilic, and successive alkylations repeat until all N–H protons are substituted with alkyl groups. This generates a complex mixture of amines with varying degrees of alkylation.
For example, consider methylamine formed from the nucleophilic attack of ammonia on methyl halide, followed by deprotonation of nitrogen from the generated monomethylammonium salt.
Methylamine attacks another molecule of methyl iodide to give dimethylammonium salt, and deprotonation of the salt produces dimethylamine.
Further alkylation produces trimethylamine, and finally, the quaternary ammonium salt, and the process stops. The overall reaction—going from ammonia to the quaternary ammonium salt—is called exhaustive alkylation.
The direct alkylation method is less efficient as it produces polyalkylated products.
Nevertheless, good yields of quaternary ammonium salts can be obtained through exhaustive alkylation, while primary amines can be successfully synthesized using a large excess of ammonia.
19.12:
Preparation of Amines: Alkylation of Ammonia and Amines
Alkylation is one of the methods used to prepare amines. Direct alkylation of ammonia or a primary amine with an alkyl halide gives polyalkylated amines along with a quaternary ammonium salt through successive SN2 reactions. This process of making the quaternary salt through the direct alkylation method is called exhaustive alkylation.
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering this, specific reaction conditions, such as excess ammonia, must be used to exclusively make primary amines.
Since tertiary halides are more hindered, they are not the substrates of choice for alkylation reactions. Although secondary alkyl halides are far less hindered and can be alkylated, they are also not preferred as substrates due to their tendency to undergo elimination reactions.
Since ammonia is cheaply available, alkylations using ammonia as the substrate are the most common.