19.13:
Preparation of 1° Amines: Azide Synthesis
In preparing primary amines, direct alkylation of ammonia proves inefficient due to the formation of polyalkylated products. To successfully make primary amines, the azide synthesis method can be employed.
The reaction involves converting alkyl halides to alkyl azides, followed by reduction to give primary amines.
The reduction can occur in two ways: through catalytic hydrogenation or by using lithium aluminum hydride.
The reaction begins with the azide anion's nucleophilic nitrogen attacking the alkyl halide in an SN2 fashion to give an alkyl azide.
The alkyl azide formed no longer functions as a nucleophile, which inhibits the formation of polyalkylated products.
A hydride transfer to the alkylated nitrogen, followed by the loss of a nitrogen molecule forms the amide ion, which on protonation gives the primary amine.
Azides can also react with other electrophiles; for instance, a ring-opening reaction of an epoxide gives an amino alcohol.
The reaction is stereoselective as the attack of the azide ion and the departure of the ring oxygen occur in an anti manner to give a racemic product.
19.13:
Preparation of 1° Amines: Azide Synthesis
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum hydride, or by catalytic hydrogenation to primary amines. The driving force for such reactions is the elimination of nitrogen gas.
Azide synthesis also works with other electrophiles like epoxides to produce amino alcohols through stereoselective ring-opening reactions. Alkyl azides have an explosive nature and must be carefully handled.