nitrogen nucleophiles

Meaning: A nitrogen nucleophile uses the lone pair on nitrogen to attack an electrophilic atom. Examples are ammonia, amines, hydrazine, hydroxylamine, azide (N₃⁻) and the phthalimide anion. Nitrogen is less electronegative than oxygen, so its lone pair is held less tightly, and a neutral amine is usually a better nucleophile than an alcohol or water of similar size.

On the MCAT: Amines attack acyl chlorides, anhydrides and esters to give amides (nucleophilic acyl substitution), aldehydes and ketones to give imines (primary amines) or enamines (secondary amines), and alkyl halides by SN2. Excess ammonia is used in alkylation because the product amine is also nucleophilic and keeps reacting. Azide followed by reduction, or the Gabriel synthesis, makes primary amines without that overalkylation. Peptide bond formation uses the α-amino group as the nucleophile.

Common confusion: Not every nitrogen is nucleophilic. An amide nitrogen is poorly nucleophilic because its lone pair is delocalized into the carbonyl by resonance, and an ammonium ion (RNH₃⁺) has no free lone pair. Check whether the lone pair is available: at low pH amines are protonated and react poorly.