Ammonolysis of Alkyl Halides

Ammonolysis of Alkyl Halides

An alkyl or benzyl halide contains a carbon–halogen bond that is readily cleaved by a nucleophile — this is the same substitution chemistry used elsewhere for haloalkanes. Ammonia itself can act as that nucleophile: when an alkyl or benzyl halide is treated with an ethanolic solution of ammonia, the halogen is displaced and replaced by an amino ($-\text{NH}_2$) group. This cleavage of the C–X bond by an ammonia molecule is given the specific name ammonolysis. The reaction is carried out under sealed conditions (a sealed tube) at around 373 K, since it needs elevated temperature and pressure to proceed at a useful rate.

The mechanism is a straightforward nucleophilic substitution: the lone pair on nitrogen attacks the electrophilic alkyl carbon, displacing the halide ion and forming a substituted ammonium salt, which then loses a proton to give the free primary amine.

Why the reaction does not stop at the primary amine

The primary amine formed in this first step is itself not inert — it still carries a lone pair on nitrogen and is, if anything, a better nucleophile than ammonia. So it does not simply sit in solution; it goes on to attack a further molecule of the alkyl halide, and the process repeats, escalating step by step:

The end result of ammonolysis, therefore, is not a clean single product but a mixture of primary, secondary and tertiary amines together with some quaternary ammonium salt. The free amine of interest can be liberated from its ammonium salt by treating the salt with a strong base such as NaOH:

$\text{R}-\overset{+}{\text{N}}\text{H}_3\overset{-}{\text{X}} + \text{NaOH} \longrightarrow \text{R}-\text{NH}_2 + \text{H}_2\text{O} + \overset{+}{\text{N}}\text{a}\overset{-}{\text{X}}$ …