Chemistry · Ch 12 — Organic Compounds Containing Nitrogen

Ammonolysis of Alkyl Halides

12.5.2

Heating a haloalkane with an excess of ethanolic ammonia in a sealed tube at

elevated temperature and pressure (ammonolysis) substitutes the halogen by an amino

group:

\text{R}-\text{X} + \text{NH}_3 \longrightarrow \text{R}-\text{NH}_2 + \text{HX}

On paper this looks like a clean, one-step synthesis of a primary amine. In practice it

rarely is, because the primary amine product is ITSELF a nucleophile, often a stronger

one than ammonia (alkyl groups donate electron density onto nitrogen, making the amine's

lone pair more available), so as soon as some $\text{R}-\text{NH}_2$ has formed it

competes with the remaining ammonia for the unreacted haloalkane:

\text{R}-\text{NH}_2 + \text{R}-\text{X} \longrightarrow \text{R}_2\text{NH} + \text{HX} \longrightarrow \text{R}_3\text{N} \longrightarrow \text{R}_4\text{N}^+ X^-

The result is a statistical mixture of primary, secondary and tertiary amine plus some

quaternary ammonium salt, separable by fractional distillation but never obtained as a

single pure product directly from the reaction. A very large excess of ammonia relative

to the haloalkane biases the mixture toward the primary amine (by keeping the

concentration of competing $\text{R}-\text{NH}_2$ low relative to $\text{NH}_3$ ), but it …