An amine's nitrogen lone pair is what gives it both of its two defining chemical properties: basicity (covered in the previous lesson — reacting with a proton) and nucleophilicity (this lesson — reacting with an electrophilic carbon). These properties are closely related but not identical, exactly as the upcoming Amine Nucleophilicity vs Basicity lesson will make explicit — for now, this lesson focuses specifically on the range of electrophiles an amine's lone pair can attack.

As a nucleophile, an amine's nitrogen readily attacks the electrophilic carbonyl carbon of carboxylic acid derivatives (following the exact same nucleophilic acyl substitution mechanism from the Carboxylic Acids unit), and can also attack the electrophilic carbon of an alkyl halide directly (a straightforward SN2 substitution).

The alkyl-halide reaction deserves special attention, because it has a structural quirk the acyl-substitution reactions don't share: when a primary amine attacks an alkyl halide via SN2, the IMMEDIATE product is a secondary amine — which is itself still a perfectly good nucleophile, with its own lone pair still available to attack a second equivalent of alkyl halide. That secondary amine can go on to react again, forming a tertiary amine, which can react yet again, forming a quaternary ammonium salt.

This means direct alkylation of an amine with an alkyl halide is notoriously prone to over-alkylation — producing a statistical mixture of primary, secondary, tertiary, and quaternary products rather than cleanly stopping at whichever single product was actually wanted. This exact problem is precisely why the next lesson in this sub-subject, Gabriel synthesis, exists as a deliberate workaround specifically for making CLEAN primary amines — and why reductive amination (also covered shortly) is often preferred over direct alkylation whenever a single, specific amine product is the actual goal.