Nitrogen compounds

📚The chemistry

34.1 Primary and secondary amines

An amine is a derivative of ammonia with one or more H atoms replaced by alkyl or aryl groups: primary RNH₂, secondary R₂NH, tertiary R₃N.

Making them

• Halogenoalkane + ammonia in ethanol, heated under pressure (sealed tube) → primary amine (topic 19).
• Halogenoalkane + primary amine in ethanol, heated in a sealed tube → secondary amine: CH₃CH₂Br + CH₃NH₂ → CH₃CH₂NHCH₃ + HBr. This is why excess ammonia is used when a primary amine is wanted.
• Reduction of an amide with LiAlH₄: the C=O becomes CH₂. CH₃CONH₂ + 4[H] → CH₃CH₂NH₂ + H₂O.
• Reduction of a nitrile with LiAlH₄ or H₂/Ni: CH₃CN + 4[H] → CH₃CH₂NH₂. A route that adds a carbon (via KCN) and ends in an amine.

Basicity

Like ammonia, amines are Brønsted–Lowry bases: the lone pair on nitrogen accepts a proton. In water they give alkaline solutions:

and they react with acids to form salts: CH₃CH₂NH₂ + HCl → CH₃CH₂NH₃⁺Cl⁻.

With acyl chlorides, ammonia and amines form amides at room temperature, by addition–elimination (topic 33), a condensation reaction that eliminates HCl.

34.2 Phenylamine and azo compounds

Making phenylamine

1. Nitrate benzene: concentrated HNO₃ and H₂SO₄, 25–60 °C → nitrobenzene.
2. Reduce with tin and concentrated HCl, heated under reflux: \[ \mathrm{C_6H_5NO_2 + 6[H] \rightarrow C_6H_5NH_2 + 2H_2O} \] In the acid, the product is present as its salt, C₆H₅NH₃⁺.
3. Add NaOH(aq) to release the free amine from its salt: C₆H₅NH₃⁺ + OH⁻ → C₆H₅NH₂ + H₂O.

Reactions of phenylamine

• Bromine water, room temperature: decolourised, with a white precipitate of 2,4,6-tribromophenylamine. Like OH in phenol, the NH₂ lone pair feeds electron density into the ring and activates the 2-, 4- and 6-positions. \[ \mathrm{C_6H_5NH_2 + 3Br_2 \rightarrow C_6H_2Br_3NH_2 + 3HBr} \]
• Nitrous acid (NaNO₂ + dilute HCl) below 10 °C → the benzenediazonium salt, C₆H₅N₂⁺Cl⁻; warming it with water gives phenol and nitrogen (topic 32).

Azo compounds

Benzenediazonium chloride couples with phenol in NaOH(aq) to form an azo compound, containing the azo group, –N=N–, linking two aromatic rings. Because delocalisation extends over both rings and the N=N, these compounds absorb visible light and are brightly coloured: they are widely used as dyes. Other azo dyes are made the same way, by coupling different diazonium salts with different phenols or aromatic amines (for example with naphthol, giving red dyes).

Relative basicity: ethylamine > ammonia > phenylamine

Basicity depends on how available the nitrogen’s lone pair is to accept a proton:

• Ethylamine: the ethyl group is electron-donating (positive inductive effect), which increases the electron density on nitrogen and makes the lone pair more available. Stronger base than ammonia.
• Ammonia: no alkyl groups; the reference point.
• Phenylamine: the lone pair on nitrogen overlaps with the delocalised π system of the ring, so it is partly delocalised into the ring and less available to accept a proton. Much weaker base than ammonia.

34.3 Amides

Amides, RCONH₂, are made from an acyl chloride with ammonia (primary amide) or a primary amine (secondary amide, RCONHR′), at room temperature.

• Hydrolysis with aqueous acid (heat): the carboxylic acid and the ammonium salt. \[ \mathrm{CH_3CONH_2 + H_2O + HCl \rightarrow CH_3COOH + NH_4Cl} \]
• Hydrolysis with aqueous alkali (heat): the carboxylate salt and ammonia gas. \[ \mathrm{CH_3CONH_2 + NaOH \rightarrow CH_3COONa + NH_3} \]
• Reduction with LiAlH₄: the C=O is reduced to CH₂, giving an amine.

Amides are much weaker bases than amines — effectively neutral. The lone pair on nitrogen is delocalised over the N–C=O group, drawn towards the very electronegative carbonyl oxygen. It is therefore not available to accept a proton.

34.4 Amino acids

An α-amino acid has an NH₂ and a COOH on the same carbon: H₂NCH(R)COOH, where R varies from one amino acid to another (H in glycine, CH₃ in alanine).

Zwitterions and the isoelectric point

The molecule contains both an acidic group and a basic group, so it can transfer a proton internally, from COOH to NH₂, forming a zwitterion: an ion with both a positive and a negative charge but no overall charge.

Solid amino acids exist as zwitterions, which is why they are crystalline solids with high melting points and are soluble in water. In solution, the form depends on the pH:

• in acid (low pH): the COO⁻ takes an H⁺, giving a cation, ⁺H₃NCH(R)COOH;
• in alkali (high pH): the NH₃⁺ loses an H⁺, giving an anion, H₂NCH(R)COO⁻;
• at the isoelectric point, the pH at which the amino acid exists mainly as the zwitterion, it has no overall charge. Each amino acid has its own isoelectric point (glycine about 6.0; those with extra acidic side chains lower, extra basic side chains higher).

Peptides

The COOH of one amino acid reacts with the NH₂ of another in a condensation reaction, eliminating water and forming an amide (peptide) bond, –CONH–. Two amino acids give a dipeptide, three a tripeptide. Two different amino acids can join in two orders, giving two different dipeptides: glycine + alanine gives Gly-Ala (H₂NCH₂CONHCH(CH₃)COOH) and Ala-Gly.

Electrophoresis

A mixture is placed in the middle of a gel soaked in a buffer of known pH, and a potential difference is applied. Each species moves according to its charge at that pH:

• if the pH is above its isoelectric point, the amino acid is negative (anion) and moves towards the positive electrode (anode);
• if the pH is below its isoelectric point, it is positive (cation) and moves towards the negative electrode (cathode);
• at its isoelectric point it has no net charge and does not move.

How far it moves depends on its charge and size: smaller and more highly charged ions move faster. So a dipeptide typically moves less far than an amino acid with the same charge. The separated spots are made visible with a developing agent (ninhydrin) and identified by comparison with standards.