Organic nitrogen compounds

Nitrogen's lone pair is the key to this topic. It makes amines basic, lets them act as ligands and nucleophiles, and joins monomers into nylon, Kevlar and proteins. You will also meet azo dyes, the zwitterions of amino acids, and the difference between addition and condensation polymers.

Naming amines and amides

Primary amines have the –NH₂ group. CH₃CH₂CH₂NH₂ is called propylamine (the name the exam board often uses) or propan-1-amine (the IUPAC name, built like an alcohol name). With a higher-priority group present, the prefix amino- is used: CH₃CH(NH₂)COOH is 2-aminopropanoic acid.
Secondary and tertiary amines: the longest chain gives the name and other alkyl groups on nitrogen are given the locant N: CH₃CH₂CH₂NHCH₃ is N-methylpropylamine (N-methylpropan-1-amine); (CH₃)₂NCH₂CH₂CH₃ is N,N-dimethylpropylamine. If both groups are the same, (CH₃CH₂)₂NH is diethylamine.
Diamines: H₂N(CH₂)₆NH₂ is hexane-1,6-diamine.
Amides end in -amide: CH₃CONH₂ is ethanamide; CH₃CH₂CONHCH₃ is N-methylpropanamide; CH₃CH₂CON(CH₃)₂ is N,N-dimethylpropanamide.

Amines as bases

Small amines smell fishy and dissolve readily in water, because the N–H groups and the nitrogen lone pair hydrogen bond with water molecules. The lone pair on nitrogen can accept a proton, so amines are Brønsted–Lowry bases:

CH₃NH₂(aq) + H₂O(l) ⇌ CH₃NH₃⁺(aq) + OH⁻(aq)

How strong a base an amine is depends on how available its lone pair is:

Aliphatic amines are stronger bases than ammonia: alkyl groups are electron-releasing, pushing electron density onto the nitrogen and making its lone pair more available. Secondary amines, with two alkyl groups, are stronger still: diethylamine > ethylamine > ammonia.
Phenylamine is a much weaker base than ammonia: its lone pair is partly delocalised into the benzene ring, so it is less available to accept a proton. Its solutions are barely alkaline.
Amides are not basic: the nitrogen lone pair is delocalised towards the electronegative C=O group.

Salts, buffers and complexes

With acids amines form ammonium salts: CH₃NH₂ + HCl → CH₃NH₃⁺Cl⁻ (methylammonium chloride); 2CH₃NH₂ + H₂SO₄ → (CH₃NH₃⁺)₂SO₄²⁻. These ionic salts are crystalline solids that dissolve in water even when the amine does not: phenylamine is only slightly soluble, but phenylammonium chloride is soluble. Adding NaOH turns the salt back into the amine.
Basic buffers can be made from an amine and its salt, such as methylamine with methylammonium chloride, just as with ammonia and ammonium chloride.
As ligands, amines form complexes with transition metal ions, like ammonia does: [Cu(H₂O)₆]²⁺ + 4CH₃CH₂NH₂ → [Cu(CH₃CH₂NH₂)₄(H₂O)₂]²⁺ + 4H₂O, a deep blue solution.

Amines as nucleophiles

With halogenoalkanes

The lone pair also makes amines nucleophiles. A primary amine attacks a halogenoalkane in nucleophilic substitution to give a secondary amine; a second amine molecule removes a proton from the intermediate:

2CH₃CH₂NH₂ + CH₃CH₂Br → (CH₃CH₂)₂NH + CH₃CH₂NH₃⁺Br⁻

The product still has a lone pair, so it can react again, giving a tertiary amine and finally a quaternary ammonium salt, R₄N⁺X⁻, in which the nitrogen has no lone pair left. Mixtures of products are normal.

With acyl chlorides

Amines react with acyl chlorides at room temperature to give N-substituted amides (an addition–elimination reaction, see Topic 15): CH₃COCl + 2CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃⁺Cl⁻. Phenylamines react in the same way; paracetamol is made by acylating the –NH₂ group of 4-aminophenol with an ethanoyl group.

Making amines

Method	Reagents and conditions	Comment
halogenoalkane + ammonia	excess ammonia dissolved in ethanol, heated in a sealed tube: CH₃CH₂Br + 2NH₃ → CH₃CH₂NH₂ + NH₄Br	one step, but the amine formed reacts further, giving a mixture of amines. A large excess of ammonia makes the primary amine the main product.
via a nitrile	1. KCN in aqueous ethanol, heat under reflux: CH₃CH₂Br + CN⁻ → CH₃CH₂CN + Br⁻. 2. LiAlH₄ in dry ether (or H₂ with a nickel catalyst): CH₃CH₂CN + 4[H] → CH₃CH₂CH₂NH₂	gives only the primary amine, with one extra carbon; but it is two steps (lower overall yield) and KCN is highly toxic
reducing a nitroarene	tin (or iron) and concentrated hydrochloric acid, heat: C₆H₅NO₂ + 6[H] → C₆H₅NH₂ + 2H₂O	in the acid the product is the salt C₆H₅NH₃⁺Cl⁻; add NaOH to release phenylamine, then separate it by steam distillation

Azo dyes

Diazotisation: react phenylamine with nitrous acid below 10 °C. Nitrous acid is unstable, so it is made in the flask from sodium nitrite and hydrochloric acid: NaNO₂ + HCl → HNO₂ + NaCl.

C₆H₅NH₂ + HNO₂ + HCl → C₆H₅N₂⁺Cl⁻ + 2H₂O, forming benzenediazonium chloride, which contains the –N≡N⁺ group.

Keep it cold: above about 10 °C the diazonium ion reacts with water, C₆H₅N₂⁺ + H₂O → C₆H₅OH + N₂ + H⁺, releasing nitrogen gas. Much below 0 °C the reaction is too slow.

Coupling: add the diazonium salt to phenol dissolved in sodium hydroxide. The diazonium ion is a weak electrophile that attacks the activated ring: C₆H₅N₂⁺ + C₆H₅OH → C₆H₅–N=N–C₆H₄OH + H⁺.

The product, 4-hydroxyazobenzene, is a yellow-orange azo dye. The –N=N– link joins two benzene rings into one long delocalised system that absorbs visible light. Azo compounds are used as dyes, pigments and food colourings.

Polymers: addition and condensation

Addition polymers

Monomers with a C=C double bond join without losing any atoms. Draw the monomer with its other groups arranged around the double bond, then open the double bond to form the repeat unit. Propenamide, CH₂=CHCONH₂, gives poly(propenamide), –[CH₂–CH(CONH₂)]–. Poly(ethenol), –[CH₂–CH(OH)]–, has an –OH group on every other carbon, so it forms many hydrogen bonds with water and dissolves: it is used for soluble laundry bags and detergent capsules. Most poly(alkenes), with only strong non-polar C–C and C–H bonds, are unreactive and not biodegradable.

Condensation polymers: polyamides

In condensation polymerisation, two different functional groups react and a small molecule (water or HCl) is lost at each link. A polyamide forms from a dicarboxylic acid (or diacyl dichloride) and a diamine, linked by amide groups, –CONH–:

Nylon 6,6: hexanedioic acid + hexane-1,6-diamine. Repeat unit –CO(CH₂)₄CONH(CH₂)₆NH–. The "6,6" counts the six carbons in each monomer.
Kevlar: benzene-1,4-dicarboxylic acid + benzene-1,4-diamine. Repeat unit –CO–C₆H₄–CONH–C₆H₄–NH–. Its flat chains line up and hydrogen bond strongly, making it extremely strong: it is used in body armour.
One monomer with an amine group at one end and an acid group at the other can also polymerise on its own, as amino acids do to make proteins.
Asked for the type of polymer, say polyamide or polyester; asked for the type of polymerisation, say condensation.

Intermolecular forces: polyamide chains hydrogen bond to each other between the N–H of one chain and the C=O of another, as well as having dipole–dipole and London forces. Polyesters have no N–H, so only dipole–dipole and London forces act between chains; polyamides therefore have higher melting points.
Hydrolysis: the polar amide (and ester) links can be attacked, so condensation polymers are biodegradable. Acid hydrolysis of nylon 6,6 gives hexanedioic acid and the diammonium salt of the diamine (H₃N⁺(CH₂)₆NH₃⁺); alkaline hydrolysis gives the diamine and the salt of the acid (⁻OOC(CH₂)₄COO⁻).

Amino acids

An α-amino acid has an amine group and a carboxylic acid group on the same carbon, H₂NCH(R)COOH. Glycine, the simplest, has R = H: aminoethanoic acid. Others are named systematically, for example 2-amino-3-hydroxypropanoic acid (R = CH₂OH) or 2-aminobutanedioic acid (aspartic acid, with a second –COOH in the R group, an acidic amino acid). Lysine has a second –NH₂ and is a basic amino acid.

Optical activity: every amino acid except glycine has four different groups on the central carbon, so it is chiral and its enantiomers rotate plane-polarised light in opposite directions. Glycine has two hydrogens on that carbon.
Zwitterions: in the solid and in neutral solution, the acid group donates its proton to the amine group, giving a zwitterion, ⁺H₃NCH(R)COO⁻, with a positive and a negative charge but no overall charge. Strong ionic attractions between zwitterions give amino acids their high melting points, far above those of molecules held only by hydrogen bonds.
Acid–base behaviour: in acid the COO⁻ group gains a proton, giving the cation ⁺H₃NCH(R)COOH; in alkali the NH₃⁺ group loses one, giving the anion H₂NCH(R)COO⁻. With glycine: ⁺H₃NCH₂COO⁻ + HCl → ⁺H₃NCH₂COOH Cl⁻, and ⁺H₃NCH₂COO⁻ + NaOH → H₂NCH₂COO⁻Na⁺ + H₂O. Because they can take up both, amino acid solutions act as weak buffers. Extra acid or amine groups in the R group change state too.
Their functional groups also react normally: for example, heating with methanol and an acid catalyst esterifies the –COOH group.

Peptides and proteins

The –COOH of one amino acid and the –NH₂ of another condense, losing water, to form a peptide link, –CONH– (an amide group). Two amino acids give a dipeptide; because either one can provide the –COOH, two different amino acids can form two different dipeptides.
Proteins are long polypeptide chains, condensation polymers of amino acids.
The chains fold into spirals (α-helices) and sheets held in shape by hydrogen bonds between the N–H of one peptide link and the C=O of another. This three-dimensional shape is vital to a protein's job, such as an enzyme's active site.
Heating a protein with 6 mol dm⁻³ hydrochloric acid under reflux hydrolyses the peptide links, releasing the amino acids, which can then be identified by chromatography with ninhydrin (Topic 15).

Quick checks

Which is the strongest base?

Two electron-releasing ethyl groups make diethylamine's lone pair the most available. Phenylamine's lone pair is delocalised into the ring and ethanamide's towards the C=O, so both are much weaker.

Why is a large excess of ammonia used to make ethylamine from bromoethane?

Ethylamine is itself a nucleophile and can react with more bromoethane to give secondary and tertiary amines. Swamping it with ammonia makes the primary amine the main product.

Why must the diazotisation of phenylamine be kept below 10 °C?

Benzenediazonium ions are unstable when warm. The low temperature keeps them long enough to couple with phenol.

How many molecules of water are released when 50 molecules of hexanedioic acid react with 50 molecules of hexane-1,6-diamine to form one nylon 6,6 chain?

100 monomers joined in a single chain need 99 amide links, each releasing one water molecule. (For large n, 2n − 1 is usually written as 2n.)

Why do amino acids have high melting points?

In the solid, each molecule carries NH₃⁺ and COO⁻ groups, so the crystal is held together like an ionic lattice.

Which form of glycine is present at pH 1?

In strong acid both groups are protonated, giving the cation. H₂NCH₂COOH, with no charges, is never the main form in solution.

Why do polyamides usually have higher melting points than polyesters of similar chain length?

Both have C=O dipoles, but only polyamides have N–H groups able to hydrogen bond to C=O groups in neighbouring chains.

Glycine (G) and alanine (A) are joined by a single peptide link. How many different dipeptides can form from one of each?

Gly–Ala and Ala–Gly are different: either amino acid can provide the –COOH that forms the peptide link. (Allowing Gly–Gly and Ala–Ala as well would give four.)

Interactive diagrams

Pick a polymer, then raise “Monomers joined” to grow the chain. Notice which link forms, what the repeat unit is, and how many small molecules are given off.

Drag the pH slider and watch which form of glycine dominates: the cation in acid, the zwitterion near neutral, the anion in alkali.