Amines

Amines are derivatives of ammonia (NH₃) where one, two, or three hydrogen atoms are replaced by organic groups. The nitrogen atom has three bonds and one lone pair of electrons — it is this lone pair that gives amines their basic character and nucleophilic reactivity. Think of nitrogen as always carrying a small negative charge cloud (the lone pair) that it is ready to share with anything positive or electrophilic.

Classification depends on how many carbon groups are attached to nitrogen. A primary (1°) amine has one carbon group and two N–H bonds (RNH₂). A secondary (2°) amine has two carbon groups and one N–H (R₂NH). A tertiary (3°) amine has three carbon groups and no N–H (R₃N). A quaternary ammonium salt (R₄N⁺) has four carbon groups and a positive charge — it has no lone pair and is not basic in the usual sense. This classification refers to the nitrogen, not the carbon attached to it (unlike alcohols).

For primary amines, replace the terminal “-e” of the alkane with -amine, or add “amino-” as a prefix when the amine is a substituent. For secondary and tertiary amines, name the largest group as the parent and use N-alkyl prefixes for the smaller groups attached to nitrogen (N- indicates the substituent is on N, not C).

Amines are basic because the nitrogen lone pair can accept a proton. The strength of this basicity — measured as pKb or, more usefully, as the pKa of the conjugate acid (the ammonium ion R-NH₃⁺) — varies enormously between amine types. Understanding these differences is clinically important because the degree of ionisation at physiological pH determines how well an amine drug crosses membranes.

Aliphatic amines (alkyl groups on N) are more basic than ammonia because alkyl groups are electron-donating — they push electron density toward nitrogen, making the lone pair more available to accept a proton. Aromatic amines (like aniline) are far less basic because the nitrogen lone pair is partially delocalised into the π system of the benzene ring, making it less available for protonation. The nitrogen in aniline is essentially "distracted" by the ring, so it is a much weaker base.

Primary and secondary amines can form hydrogen bonds through their N–H bonds, but nitrogen is less electronegative than oxygen. So amines have higher boiling points than alkanes of similar mass, but lower than comparable alcohols. Lower-molecular-weight amines (methylamine, ethylamine) are gases at room temperature and have a distinctly unpleasant fishy smell. Trimethylamine is the compound responsible for the smell of rotting fish. Many amines are water-soluble due to hydrogen bonding with water. Tertiary amines cannot donate H-bonds but can accept them.

Because the nitrogen lone pair is nucleophilic, amines react with electrophiles. Alkylation occurs when an amine attacks an alkyl halide (RX). The nitrogen attacks the electrophilic carbon, displacing the halide — an SN2 reaction. The problem is that the initial product (a secondary amine salt) is itself nucleophilic and reacts further with more alkyl halide, giving a mixture of primary, secondary, tertiary amines and quaternary salt. This over-alkylation makes simple N-alkylation a poor synthetic route to a specific product.

Acylation is far more selective. Reacting an amine with an acid chloride (or anhydride) gives an amide. The amide product is no longer basic (the lone pair is delocalised into the C=O), so it does not react further. This is the basis of the Schotten-Baumann reaction (amine + acid chloride with aqueous NaOH as base to neutralise HCl). Acylation is used to protect amines in synthesis and forms the basis of peptide bond formation.

When a primary aromatic amine (ArNH₂, like aniline) reacts with nitrous acid (HNO₂, generated in situ from NaNO₂ + HCl) at 0–5°C, a diazonium salt (ArN₂⁺Cl⁻) forms. This is diazotisation. The diazonium group (–N≡N⁺) is an excellent leaving group and is the key to converting anilines into a vast range of other benzene derivatives.

Temperature is critical. Diazonium salts are unstable above 5°C — they decompose rapidly. The reaction must be performed in an ice bath, and the diazonium salt must be used immediately (it is never isolated as a dry solid — it can explode). Primary aliphatic amines also react with HNO₂, but give unstable diazonium ions that decompose immediately to carbocations — useful for creating carbocations, but not for the controlled chemistry of aromatic diazonium salts.

Diazonium salts are extraordinarily versatile — they allow us to introduce almost any substituent onto a benzene ring that would be impossible by direct electrophilic substitution. The N₂⁺ group leaves as N₂ gas (an excellent, irreversible driving force), and the carbon that was bonded to it is left as an aryl carbocation (or radical) that reacts with a variety of nucleophiles or coupling partners.