A Level Chemistry: Amides and Amino Acids — Revision Notes

Condensed for the final weeks. For the full explanation, use the Amides and Amino Acids study guide.

Amides

Formed from an acyl chloride plus ammonia or an amine.

RCOCl + NH3      ->  RCONH2  (primary amide)
RCOCl + R'NH2    ->  RCONHR' (N-substituted amide)

Amides are neutral, not basic, even though they contain nitrogen. The lone pair on the nitrogen is delocalised into the adjacent C=O group, so it is not available to accept a proton. That is the standard “why is an amide not basic like an amine” question, and delocalisation is the answer. This delocalisation does two things at once: it makes the lone pair far less available to bond to an incoming H⁺, and it is also stabilising for the neutral amide itself, so there is an extra energetic cost to protonating the nitrogen and disrupting that stabilisation.

Hydrolysis:

• Acid hydrolysis → carboxylic acid + ammonium salt.
• Alkaline hydrolysis → carboxylate salt + ammonia.

Worked equations: CH₃CONH₂ + NaOH → CH₃COONa + NH₃ (alkaline hydrolysis); CH₃CONH₂ + H₂O + HCl → CH₃COOH + NH₄Cl (acid hydrolysis).

Reduction: LiAlH₄ reduces the C=O of an amide specifically to give an amine — CH₃CONH₂ →[LiAlH₄] CH₃CH₂NH₂. This is one of the standard amine-production routes.

Amino acids

General formula H₂NCHRCOOH — an amine group and a carboxylic acid group on the same carbon.

Zwitterions: the acid group donates a proton to the basic amine group within the same molecule, giving H₃N⁺CHRCOO⁻. The molecule carries both charges but is overall neutral.

This explains their unusual physical properties, which is what questions test:

• High melting points — the ionic attractions between zwitterions are far stronger than the intermolecular forces in comparable molecules.
• Soluble in water, insoluble in non-polar solvents — the charges interact strongly with polar water.

Behaviour with pH:

Condition	Form
Low pH (acidic)	H₃N⁺CHRCOOH — cation, moves to the cathode
Isoelectric point	Zwitterion — no net charge, does not move
High pH (alkaline)	H₂NCHRCOO⁻ — anion, moves to the anode

The isoelectric point is the pH at which the amino acid exists as the zwitterion with no net charge. Because it differs between amino acids, it is the basis of separation by electrophoresis — apply a voltage at a chosen pH and each amino acid migrates differently.

Predicting the direction of migration at a given pH: a species whose isoelectric point is below that pH carries a net negative charge and migrates to the anode; a species whose isoelectric point is above that pH carries a net positive charge and migrates to the cathode; a species at exactly its isoelectric point carries no net charge and does not migrate.

Amino acids are chiral (except glycine, whose R group is H, so it has no four different groups). Naturally occurring amino acids are almost exclusively the L-form.

Dipeptides and tripeptides

The peptide bond –CONH– forms by condensation between the amine group of one amino acid and the carboxyl group of another, releasing water. Joining two amino acids gives a dipeptide; joining three gives a tripeptide — this is as far as 9701 takes peptide chemistry.

Hydrolysis with aqueous acid (e.g. dilute or concentrated HCl), heated under reflux, breaks a dipeptide or tripeptide back down into its constituent amino acids, reversing each peptide bond in the chain.

Beyond the syllabus (not assessed at this level): the folding of many amino acids into a full protein — primary, secondary (α-helix, β-pleated sheet) and tertiary structure, disulfide bridges between cysteine residues — is background context only. 9701 stops at di- and tripeptides and does not require any of this terminology.

Exam traps

• Saying amides are basic like amines.
• Explaining zwitterion properties without linking to the ionic attractions.
• Forgetting that glycine is achiral.
• Confusing which electrode an amino acid moves to at a given pH.
• Forgetting that a peptide bond forms by condensation, releasing water.
• Trying to recall protein secondary/tertiary structure (α-helix, β-pleated sheet, disulfide bridges) for this syllabus — it’s background only; 9701 stops at di- and tripeptides.

Self-test

1. Why is an amide not basic?
2. What is a zwitterion, and why does it give amino acids high melting points?
3. Define the isoelectric point and give its practical use.
4. Which amino acid is achiral, and why?
5. Give the reagent and conditions for hydrolysing a tripeptide back to its three constituent amino acids.
6. Write the equation for the alkaline hydrolysis of ethanamide, and name the products.
7. An amino acid has an isoelectric point of 6.0. Predict its direction of migration in electrophoresis at pH 9.0.

Answers: 1. The nitrogen lone pair is delocalised into the adjacent carbonyl group, so it is not available to accept a proton. 2. A species with both a positive and a negative charge but no overall charge, formed by internal proton transfer; the strong ionic attractions between zwitterions require much more energy to overcome than ordinary intermolecular forces. 3. The pH at which an amino acid exists as a zwitterion with no net charge; since it varies between amino acids, it allows separation by electrophoresis. 4. Glycine — its R group is a hydrogen atom, so the central carbon does not carry four different groups. 5. Aqueous acid (e.g. dilute or concentrated hydrochloric acid), heated under reflux, which hydrolyses each peptide bond in turn to release the free amino acids. 6. CH₃CONH₂ + NaOH → CH₃COONa + NH₃; the products are sodium ethanoate and ammonia. 7. Its isoelectric point (6.0) is below the buffer pH (9.0), so it carries a net negative charge and migrates towards the anode.