7.5.3 Nucleophilic Substitution

• The lone pair on the nitrogen atom in amines makes them good nucleophiles, just like ammonia
• When ammonia reacts with a haloalkane a nucleophilic substitution reaction takes place forming a primary amine
• For example chloromethane reacts with ammonia in two steps to make methylamine and ammonium chloride

CH₃Cl + NH₃ → [CH₃NH₃]⁺Cl ^-

[CH₃NH₃]⁺Cl ^- + NH₃ → CH₃NH₂ + NH₄+Cl ^-

• The methylamine is also a good nucleophile so can undergo further substitution with chloromethane to make dimethylamine

CH₃Cl   + CH₃NH₂ → [(CH₃)₂NH₂]⁺Cl ^-  

[(CH₃)₂NH₂]⁺Cl ^- + NH₃ → (CH₃)₂NH + NH₄+Cl ^-

• The dimethylamine can further substitute giving a tertiary amine, trimethylamine

CH₃Cl + (CH₃)₂NH → [(CH₃)₃NH]⁺Cl ^-  

[(CH₃)₃NH]⁺Cl ^- + NH₃ → (CH₃)₃N + NH₄+Cl ^-

• The final substitution occurs when the tertiary amine reacts with the chloromethane to make a quaternary ammonium salt

CH₃Cl + (CH₃)₃N → [(CH₃)₄N]⁺Cl ^-  

• Since all these multiple substitutions occur it is not a very efficient way to synthesise amines
• If you want to just produce the primary amine then a large excess of ammonia is used to ensure it is the dominant nucleophile in the reaction vessel

Mechanism of nucleophilic substitution

The mechanism of nucleophilic substitution between ammonia and a halogenoalkane

• In the first step the ammonia acts as a nucleophile and in the second step it acts as a base