Amines, Amides, Amino Acids and Proteins

Specification Reference Topic 18, points 8–17

Quick Notes

Amines are derivatives of ammonia (NH₃) and act as weak bases.
- Classified as 1°, 2°, or 3° depending on how many carbon atoms are bonded to nitrogen.
Amides contain a CONH₂ group (e.g., R–CONH₂) and are made from acyl chlorides and ammonia or amines.
Reactions of Amines
- With acids → form salts.
- With acyl chlorides → form amides.
- With halogenoalkanes → form secondary/tertiary amines.
- With copper(II) ions → form deep blue complex ions.
Basicity of Amines
- Aliphatic amines: stronger bases than ammonia (due to electron-donating alkyl groups).
- Aromatic amines: weaker bases than ammonia (lone pair on N delocalised into benzene ring).
Preparation of Amines
- From halogenoalkanes: Excess NH₃ + halogenoalkane (further substitution may occur)
- From nitriles: Reduction with LiAlH₄ in dry ether, or H₂/Ni
- From nitroarenes: Sn + HCl under reflux, then NaOH
Amides and Polyamides
- Amides made from acyl chlorides + NH₃ or amines.
- Polyamides formed by condensation of dicarboxylic acids and diamines.
Amino Acids
- Contain both –COOH and –NH₂
- Exist as zwitterions in neutral conditions (H₃N⁺–CHR–COO⁻).
  - Low pH: NH₂ gains H⁺ forms positive ion.
  - High pH: COOH loses H⁺ forms negative ion.
- Optically active (except glycine) due to chiral carbon.
Proteins and Peptides
- Proteins = polyamides formed by peptide bonds (–CONH–) between amino acids.
- Peptide bonds formed via condensation; broken by hydrolysis.
  - Acid hydrolysis: HCl under reflux, NH₃⁺ groups form.
  - Alkali hydrolysis: NaOH, COO⁻ groups form.
Separation of Amino Acids
- Use Thin-Layer Chromatography (TLC) after hydrolysis.
- Amino acids visualised using ninhydrin or UV light.
- Rf value = Distance moved by compound ÷ Distance moved by solvent.

Full Notes

Edexcel A-Level Chemistry diagram comparing amines based on NH3 and amides with a carbonyl directly bonded to nitrogen.

Amines are nitrogen-containing organic compounds based on ammonia (NH₃) and amides contain a carbonyl group (C=O) directly bonded to a nitrogen.

Amines are classified by how many carbon atoms are bonded to the nitrogen:

Edexcel A-Level Chemistry examples of primary, secondary and tertiary amines with classification by carbon groups on nitrogen.

Amines can act as weak bases because the lone pair on nitrogen can accept a proton (H⁺).

Edexcel A-Level Chemistry schematic showing amine lone pair accepting H+ to form an alkylammonium ion.

Reactions of Amines

Amines undergo nucleophilic substitution and acid–base reactions.

You need to know the following reactions, using butylamine as an example.

With water

Amines react with water to form an alkaline solution

Edexcel A-Level Chemistry reaction of butylamine with water to give an alkaline solution of alkylammonium and hydroxide ions.

With acyl chlorides

Amines react with acyl chlorides to form amides

Edexcel A-Level Chemistry formation of an amide from butylamine and ethanoyl chloride with HCl by-product.

With halogenoalkanes

Amines react with halogenoalkanes to form secondary and tertiary amines

Edexcel A-Level Chemistry nucleophilic substitution between butylamine and chloroethane to form a secondary amine and chloride ion.

With copper (II) ions

Amines react with copper(II) ions, form deep blue complex ions with excess amine ligands

Edexcel A-Level Chemistry formation of deep blue tetraamminecopper(II) complex in excess amine.

Basicity of Amines

The strength of a base depends on how readily the lone pair on nitrogen can accept a proton:

The more available the lone pair is to accept a H⁺ ion, the stronger the base
The less available the lone pair is to accept a H⁺ ion, the weaker the base

Different types of amine have different strengths.

Edexcel A-Level Chemistry comparison of base strength for aliphatic amines, ammonia and aromatic amines.

Aliphatic amines are stronger bases than ammonia, due to the electron-donating alkyl groups increasing electron density on nitrogen (positive inductive effect).

Aromatic amines (e.g., phenylamine, C₆H₅NH₂) are weaker bases than ammonia because the benzene ring withdraws electron density from nitrogen (negative inductive effect) through partial delocalisation if the nitrogen’s lone pair of electrons into the ring, reducing its availability to bond with H⁺.

Preparation of Amines

There are several methods of amine preparation you need to know.

From halogenoalkanes:

Reagents: Excess ammonia (NH₃) and haloalkane (R–X)

Edexcel A-Level Chemistry synthesis of primary amine from haloalkane with excess ammonia producing ammonium salt by-product.

R–Br + 2NH₃ → R–NH₂ + NH₄Br

Conditions: Ethanol as a solvent, sealed tube (to prevent escape of NH₃).
Limitations: If NH₃ isn’t in excess then further substitution may occur, leading to secondary and tertiary amines. This is because the primary amine formed at the start can act as a nucleophile and react with any left over halogenoalkane.

Reduction of nitriles:

Reagents: LiAlH₄ or H₂ gas + Nickel catalyst

Edexcel A-Level Chemistry reduction of nitrile to primary amine using LiAlH4 in dry ether or H2/Ni.

R–C≡N + 4[H] → R–CH₂NH₂ (using LiAlH₄ or H₂/Ni)

Conditions: Dry ether (no water present) if LiAlH₄ used, high pressure and temperature if H₂ gas used.
Advantage: Produces only primary amines (unlike halogenoalkane method).

Reduction of aromatic nitro compounds (e.g., nitrobenzene):

Reagents: Tin (Sn) + Concentrated HCl

Edexcel A-Level Chemistry reduction of nitrobenzene to phenylamine using Sn and HCl followed by NaOH work-up.

C₆H₅NO₂ + 6[H] → C₆H₅NH₂ + 2H₂O

Conditions: Heat under reflux
Final Step: NaOH is added to neutralise excess HCl and obtain free amine (turns NH₃⁺ into NH₂ group).

Preparation of Amides

Amides can be made from acyl chlorides using ammonia (forms primary amides) and amines (forms secondary and tertiary amides).

Edexcel A-Level Chemistry formation of a primary amide from an acyl chloride and ammonia with HCl.

Edexcel A-Level Chemistry formation of a substituted amide from an acyl chloride and a primary amine with HCl formed and neutralised by excess amine.

Polymerisation of Amides

Polyamides are formed by the reaction of a dicarboxylic acid with a diamine.

Edexcel A-Level Chemistry condensation polymerisation between a dicarboxylic acid and a diamine to form a polyamide with loss of water.

Amino Acids

Amino acids have both –COOH (acidic) and –NH₂ (basic) functional groups.

Edexcel A-Level Chemistry general structure of a 2-amino acid showing amine and carboxylic acid groups on the alpha carbon.

Most naturally occurring amino acids are 2-amino acids (α-amino acids) with a general structure of H₂N–CHR–COOH

2-Amino acids are optically active (except glycine) and can rotate plane-polarised light due to the chiral carbon atom.

They are also amphoteric (react with both acids and bases) and can exist as zwitterions:

Edexcel A-Level Chemistry formation of a zwitterion H3N+–CHR–COO− from an amino acid in neutral solution.

A zwitterion contains both a positive and a negative charge, e.g., H₃N⁺–CHR–COO⁻. They form when the amine group accepts a H⁺ ion and the carboxylate group has lost a H⁺ ion.

In neutral solution, the zwitterion is the dominant species.

In acidic conditions (low pH):

Edexcel A-Level Chemistry protonation of amino acid in acidic conditions to give overall positive ion with NH3+ and COOH.

The amine group (−NH₂) is protonated to (−NH₃⁺).
The molecule carries a positive charge.

In alkaline conditions (high pH):

Edexcel A-Level Chemistry deprotonation of amino acid in alkaline conditions to give overall negative ion with COO− and NH2.

The carboxyl group (−COOH) is deprotonated to (−COO⁻).
The molecule carries a negative charge.

Matt’s Exam Tip

Remember that the weak carboxylic acid group can lose a H⁺ ion at a specific pH, which might be below 7. The exact pH at which this happens depends on the strength of the acid – stronger acids lose H⁺ ions at lower pH values, forming a COO⁻ group. This explains why different amino acids exist as zwitterions at different pH levels. The same logic applies to the basic amine group gaining a H⁺ ion – the pH at which this occurs depends on the base strength. Different amino acids exist as zwitterions at slightly different pHs for this reason.

Edexcel A-Level Chemistry comparison image showing different amino acids existing as zwitterions at slightly different pH values.

Proteins and Peptides

Proteins are naturally occurring polymers of amino acids linked by peptide bonds (−CONH−).

Edexcel A-Level Chemistry schematic of a protein macromolecule composed of amino acid residues linked by peptide bonds.

Peptide bonds form by condensation reactions between amino acids, releasing water:

Edexcel A-Level Chemistry formation of a dipeptide by condensation of two amino acids with loss of water.

The process can keep happening between more amino acids, forming a polypeptide chain (polymer).

Edexcel A-Level Chemistry growth of a polypeptide chain as multiple amino acids condense forming peptide links.

Peptide bonds can be broken apart in hydrolysis reactions. The hydrolysis of proteins (with acid or alkali) releases the amino acids that made up the protein.

Edexcel A-Level Chemistry hydrolysis mechanism breaking a peptide bond to yield amino acids.

Matt’s exam tip

The conditions used for hydrolysis determine the form of the amino acids released. If acidic conditions are used, then the amino acids may exist as positively charged ions with the NH₂ group accepting a H⁺ ion to form NH₃⁺. Equally, if alkaline conditions are used, then the carboxylic acid groups may be forced to lose H⁺ ions and exist as carboxylate ions (COO⁻).

Proteins are examples of condensation polymers and can be broken apart into amino acids by hydrolysis.

Edexcel A-Level Chemistry overall scheme for acid and alkali hydrolysis of proteins to amino acids.

Acid hydrolysis: Heat with HCl under reflux.
Alkaline hydrolysis: Heat with NaOH.

Separation and Identification of Amino Acids by Thin-Layer Chromatography (TLC)

After a protein is hydrolysed and broken apart into its amino acids, the amino acids can be separated and identified using Thin-Layer Chromatography (TLC).

Edexcel A-Level Chemistry TLC separation of amino acids with visualisation by ninhydrin and calculation of Rf values.

Amino acids are separated based on their solubility in the solvent.
Chromatogram is developed using ninhydrin (colours amino acids) or UV light.
Rf values (Retention Factor) are calculated: Rf = Distance moved by compound / Distance moved by solvent
Each amino acid has a unique Rf value, allowing identification.

Summary

Amines act as weak bases and show clear reaction patterns with acids, acyl chlorides and halogenoalkanes
Aliphatic amines are stronger bases than ammonia while aromatic amines are weaker
Primary amines can be prepared from halogenoalkanes nitriles and nitroarenes
Amides form from acyl chlorides with ammonia or amines and polyamides form by condensation
Amino acids are amphoteric and form zwitterions depending on pH
Proteins are polyamides formed by condensation and are hydrolysed to amino acids
Amino acids can be separated and identified by TLC using Rf values