Peptides and Amides

Amides are a class of carbonyl compounds in which the C=O carbon is bonded to nitrogen instead of oxygen (ester) or chlorine (acyl chloride). They are the single most important functional group in biology — every protein in every living thing is held together by peptide bonds, which are simply amide linkages between amino acid residues. The same chemistry also gives us nylon, Kevlar, and paracetamol.

This lesson covers the OCR A-Level Chemistry A (H432) specification point 6.2.4 (b): formation and hydrolysis of peptide bonds in amides and proteins.

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1. Amides — Structure and Nomenclature

1.1 Structure

An amide has the general formula R–CONR'R'', where R, R' and R'' can be H or a carbon chain. The carbonyl carbon is bonded to:

• An oxygen (=O)
• A nitrogen (–NR'R'')
• A carbon (R) or hydrogen

       O
       ||
  R  - C - N(R')(R'')

Classification of amides:

Type	Nitrogen substitution	Example
Primary (unsubstituted)	–NH₂	CH₃CONH₂ ethanamide
Secondary (N-substituted)	–NHR'	CH₃CONHCH₃ N-methylethanamide
Tertiary (N,N-disubstituted)	–NR'R''	CH₃CON(CH₃)₂ N,N-dimethylethanamide

Note that "primary/secondary/tertiary" for amides counts carbons on the nitrogen of the amide — the same convention as amines (and different from alcohols).

1.2 Nomenclature

• Take the parent carboxylic acid name, drop -oic acid, and add -amide.
• For N-substituted amides, prefix the name with N-methyl-, N-ethyl- etc. showing substituents on the nitrogen.

Formula	Name
HCONH₂	Methanamide
CH₃CONH₂	Ethanamide
CH₃CH₂CONH₂	Propanamide
CH₃CONHCH₃	N-methylethanamide
CH₃CON(CH₃)₂	N,N-dimethylethanamide

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2. How Amides Form

Amides are made by reacting an amine (or ammonia) with a carbonyl compound that has a good leaving group. At A-Level you meet two routes:

2.1 Acyl chloride + amine (preferred)

As seen in Lesson 5:

$CH_3COCl + 2CH_3NH_2 \longrightarrow CH_3CONHCH_3 + CH_3NH_3^+Cl^-$CH3​COCl+2CH3​NH2​⟶CH3​CONHCH3​+CH3​NH3+​Cl−

• Fast, at room temperature.
• Mechanism: nucleophilic addition-elimination.
• Needs two equivalents of the amine: one to react, one to mop up HCl.

2.2 Carboxylic acid + amine (difficult)

$R-COOH + R'-NH_2 \longrightarrow R-CONHR' + H_2O$R−COOH+R′−NH2​⟶R−CONHR′+H2​O

• In principle the same "condensation" you saw with esters, but it does not work at room temperature.
• The amine is basic, the acid is acidic → they just form a salt (R-COO⁻ R'-NH₃⁺) rather than an amide.
• Industrially, high temperatures (200 °C+) or activating reagents are needed.
• Not tested directly by OCR, but a reminder that amides are best made from acyl chlorides.

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3. The Peptide Bond

3.1 What is a peptide bond?

When two amino acids link together, the –COOH of one reacts with the –NH₂ of another, eliminating water and forming an amide bond between them. This amide is called a peptide bond.

$H_2N-CHR_1-COOH + H_2N-CHR_2-COOH \longrightarrow H_2N-CHR_1-CO-NH-CHR_2-COOH + H_2O$H2​N−CHR1​−COOH+H2​N−CHR2​−COOH⟶H2​N−CHR1​−CO−NH−CHR2​−COOH+H2​O

The product is a dipeptide. Repeating this process builds up a chain:

• Dipeptide: 2 amino acids, 1 peptide bond.
• Tripeptide: 3 amino acids, 2 peptide bonds.
• Oligopeptide: a few amino acids.
• Polypeptide or protein: many (often 50+) amino acids.

graph LR
  A[Amino acid 1 -COOH] --> C[Peptide bond -CO-NH-]
  B[Amino acid 2 H2N-] --> C
  C --> D[Dipeptide + H2O]

3.2 Drawing peptide bonds

You need to be able to spot and draw a peptide bond in a structural formula. The bond itself is the –CO–NH– linkage between two amino acid residues. Around it you will see the α-carbons of the two residues with their side chains R₁ and R₂.

Example — glycylalanine (a dipeptide from glycine + alanine):

    H               H
    |               |
H2N-C-CO-NH-C-COOH
    |               |
    H              CH3
    (glycine)      (alanine)

The peptide bond is the CO–NH between them.

3.3 Proteins as polyamides

A protein is a polypeptide with (usually) dozens to thousands of amino acid residues strung together by peptide bonds. Because every bond in the backbone is a –CO–NH–, the entire protein backbone is a giant polyamide. The three-dimensional folding — α-helices, β-sheets, and the final "tertiary structure" — is held in place by hydrogen bonds, disulfide bridges, hydrophobic interactions and ionic bonds between side chains.

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4. Hydrolysis of Peptides and Amides