Amides and Amino Acids

This guide covers subtopics 34.3, Amides, and 34.4, Amino acids, from Topic 34, Nitrogen compounds, of Cambridge International AS & A Level Chemistry 9701, 2025–2027 series. This is A Level content, completing Topic 34 alongside Amines: Aliphatic and Aromatic, Basicity and Azo Dyes.

Before studying this

This resource assumes acyl chloride reactions and the addition-elimination mechanism from Carboxylic Acids and Acyl Chlorides, amine basicity from Amines: Aliphatic and Aromatic, Basicity and Azo Dyes, and the Brønsted-Lowry theory from Acids and Bases: The Brønsted-Lowry Theory.

Syllabus coverage

CAMBRIDGE INTERNATIONAL AS & A LEVEL CHEMISTRY 9701 — A Level, Topic 34

34.3 Amides — recalling amide production from ammonia or a primary amine with an acyl chloride, both at room temperature; describing amide hydrolysis (aqueous alkali or aqueous acid) and reduction of the C=O group with LiAlH₄ to form an amine; explaining why amides are much weaker bases than amines.

34.4 Amino acids — describing the acid/base properties of amino acids and zwitterion formation, including the isoelectric point; describing peptide (amide) bond formation between amino acids to give di- and tripeptides; interpreting and predicting electrophoresis results for amino acid/dipeptide mixtures at varying pH (assembling the apparatus is not tested).

Producing and reacting amides

Production. An amide forms from ammonia or a primary amine reacting with an acyl chloride at room temperature — already met as one of acyl chlorides’ characteristic reactions in Carboxylic Acids and Acyl Chlorides:

CH₃COCl + NH₃ → CH₃CONH₂ (ethanamide) + HCl

CH₃COCl + CH₃NH₂ → CH₃CONHCH₃ (N-methylethanamide) + HCl

Hydrolysis. An amide hydrolyses under either acidic or alkaline conditions, breaking the C–N bond:

• Aqueous alkali: CH₃CONH₂ + NaOH → CH₃COONa + NH₃ (gives the carboxylate salt and ammonia/amine)
• Aqueous acid: CH₃CONH₂ + H₂O + HCl → CH₃COOH + NH₄Cl (gives the carboxylic acid and the ammonium/aminium salt)

Reduction. LiAlH₄ reduces the C=O of an amide specifically (not the whole molecule) to give an amine:

CH₃CONH₂ —[LiAlH₄]→ CH₃CH₂NH₂

This is, in fact, one of the four amine-production routes already listed in Amines: Aliphatic and Aromatic, Basicity and Azo Dyes.

Why amides are much weaker bases than amines

Amides are essentially non-basic in aqueous solution, in sharp contrast to amines. The reason is structural: an amide’s nitrogen lone pair delocalises into the adjacent C=O group (overlapping with the carbonyl’s π system, giving the C–N bond partial double-bond character), rather than remaining localised on nitrogen the way an amine’s lone pair does.

This delocalisation does two things at once: it makes the lone pair far less available to bond to an incoming H⁺ (directly reducing basicity, the same delocalisation-reduces-availability logic already met for phenylamine), and it’s also stabilising for the neutral amide itself, so there’s an extra energetic cost to protonating nitrogen and disrupting that stabilisation. Both effects point the same way: amides are dramatically less basic than the amines they’re structurally related to.

Amino acids: acid-base properties and zwitterions

An amino acid contains both a basic amine group (–NH₂) and an acidic carboxyl group (–COOH) in the same molecule — and in practice, the more acidic –COOH proton transfers internally to the more basic –NH₂ group, giving a zwitterion: a single species carrying both a positive and a negative charge simultaneously, with no net charge overall.

H₂NCH(R)COOH ⇌ ⁺H₃NCH(R)COO⁻ (the zwitterion form)

How an amino acid’s overall charge changes with pH:

• In acidic solution (low pH, excess H⁺ available): the carboxylate end of the zwitterion picks up an extra H⁺, giving an overall positively charged cation, ⁺H₃NCH(R)COOH.
• In alkaline solution (high pH, excess OH⁻ available): the ammonium end of the zwitterion loses H⁺, giving an overall negatively charged anion, H₂NCH(R)COO⁻.
• At the isoelectric point, a specific pH characteristic of that amino acid, the molecule exists predominantly as the neutral zwitterion, with no net charge — the pH at which the amino acid would not migrate in an electric field at all.

Peptide bonds

Two amino acids can react together, with the –COOH of one and the –NH₂ of the other condensing (losing H₂O) to form an amide (peptide) bond, giving a dipeptide:

H₂NCH(R¹)COOH + H₂NCH(R²)COOH → H₂NCH(R¹)CONHCH(R²)COOH + H₂O

A third amino acid can react at either free end of the dipeptide (its free –COOH or free –NH₂) to extend it into a tripeptide, and so on — the same peptide-bond-forming reaction repeated, building up a longer chain one amino acid at a time.

Electrophoresis

Because an amino acid’s net charge depends on the pH of its surroundings (as above), a mixture of different amino acids or dipeptides can be separated by electrophoresis: a sample is placed on damp paper/gel soaked in a buffer of chosen pH, an electric field is applied across it, and each species migrates towards the electrode of opposite charge to its own — at a rate that depends on the size of its net charge at that particular pH.

Interpreting and predicting results. At a given pH:

• A species with its isoelectric point below that pH carries a net negative charge at that pH, and migrates towards the positive electrode (anode).
• A species with its isoelectric point above that pH carries a net positive charge, and migrates towards the negative electrode (cathode).
• A species at exactly its isoelectric point carries no net charge and does not migrate at all.

This means a mixture of amino acids with different isoelectric points can be separated at a single, well-chosen buffer pH, since each will carry a different net charge (and so travel a different distance, in a different direction, or not at all) even though they might look chemically very similar otherwise. (Only interpreting/predicting the outcome is required — not how to set up the apparatus.)

Common mistakes

Trying to hydrolyse an amide under the same mild conditions as an acyl chloride. Unlike acyl chlorides, amides are relatively resistant to hydrolysis and generally need heating with fairly concentrated aqueous acid or alkali, not just room-temperature water — the C–N bond in an amide is considerably less reactive than the C–Cl bond in an acyl chloride.

Assuming amides are basic because amines are. The delocalisation of the nitrogen lone pair into the carbonyl group is the entire point of this subtopic — amides are essentially neutral/non-basic in water, a genuinely different behaviour from amines, not just a “weaker version” of the same basicity.

Drawing an amino acid’s structure without the zwitterion, at neutral pH. At physiological or neutral pH, the correctly drawn structure is the charge-separated zwitterion (⁺H₃N–CHR–COO⁻), not the uncharged H₂N–CHR–COOH form, even though the molecular formula is the same either way.

Predicting migration direction from charge without checking which electrode is which. A species with a net negative charge moves towards the positive electrode (opposite charges attract) — it’s easy to state the direction backwards under exam pressure.

Quick revision checklist

• Amide: acyl chloride + NH₃/primary amine, room temperature
• Amide hydrolysis: alkali → carboxylate salt + amine; acid → carboxylic acid + ammonium/aminium salt
• LiAlH₄ reduces an amide’s C=O to give an amine
• Amides are much weaker bases than amines: lone pair delocalises into C=O
• Amino acid: zwitterion at neutral pH; cation in acid; anion in alkali; no net charge at the isoelectric point
• Peptide (amide) bond: –COOH of one amino acid + –NH₂ of another, loses H₂O
• Electrophoresis: migration direction and extent depend on net charge at the chosen pH, relative to each species’ isoelectric point

Related resources

• Carboxylic Acids and Acyl Chlorides — the acyl-chloride reaction that produces amides
• Amines: Aliphatic and Aromatic, Basicity and Azo Dyes — the basicity comparison amides contrast with
• Acids and Bases: The Brønsted-Lowry Theory — the proton-transfer ideas behind zwitterion formation
• Condensation Polymerisation and Polymer Degradability — peptide bonds as the repeat linkage in a polyamide (protein) chain
• Cambridge AS & A Level Chemistry hub

Written against Cambridge International AS & A Level Chemistry 9701, 2025–2027 series. Always check the current syllabus for your examination year.