What you'll learn

• How to plan a synthetic route by working backwards from a target molecule.
• The key functional group interconversions you need for Edexcel A-Level organic chemistry.
• How to lengthen a carbon chain using cyanide ions and carbonyl chemistry.
• How to judge a route using reagents, conditions, yield, purity and safety.

The big idea: making a target molecule

In this topic, you are not learning lots of brand-new reactions from scratch. You are learning how to combine reactions you already know into a route.

A target molecule is the compound you are trying to make. A synthetic route is the sequence of reactions used to get there.

For example, converting propan-1-ol into propanal is a functional group interconversion: an alcohol group becomes an aldehyde group.

Your synthesis toolbox

Before planning routes, you need a reliable mental map of common conversions. The diagram below summarises many of the most useful aliphatic reactions for A-Level synthesis.

Oxidation and reduction

A primary alcohol can be oxidised to an aldehyde or further to a carboxylic acid.

• Primary alcohol → aldehyde: acidified potassium dichromate(VI), distil.
• Primary alcohol → carboxylic acid: acidified potassium dichromate(VI), reflux.
• Secondary alcohol → ketone: acidified potassium dichromate(VI), reflux.
• Aldehyde → carboxylic acid: acidified potassium dichromate(VI), reflux.
• Aldehyde or ketone → alcohol: sodium tetrahydridoborate(III), NaBH₄.

Planning backwards: retrosynthesis

A useful question is: What immediate precursor could make this target in one known reaction?

For example, if the target is a carboxylic acid, possible precursors include:

• a primary alcohol, using oxidation under reflux;
• an aldehyde, using oxidation;
• a nitrile, using acidic hydrolysis.

Lengthening the carbon chain

Many reactions change functional groups but keep the same number of carbon atoms. In synthesis, you often need to add carbon atoms.

Two especially important A-Level methods are:

1. Halogenoalkane to nitrile

A halogenoalkane reacts with cyanide ions, CN⁻, by nucleophilic substitution:

R–X → R–CN

Reagents and conditions:

• potassium cyanide, KCN;
• ethanol as solvent;
• heat under reflux.

The carbon in the CN group becomes part of the main carbon chain, so this adds one carbon atom.

For example:

CH₃CH₂Br → CH₃CH₂CN

Bromoethane has two carbon atoms; propanenitrile has three.

2. Carbonyl compound to hydroxynitrile

An aldehyde or ketone reacts with HCN in the presence of KCN catalyst to form a hydroxynitrile.

This is a nucleophilic addition reaction. The carbonyl group, C=O, is attacked by CN⁻, and the product contains one extra carbon atom.

Acids, acyl chlorides, esters and amides

Carboxylic acids are useful synthesis “hubs” because they can be converted into several derivatives.

A carboxylic acid derivative is a compound related to a carboxylic acid where the –OH part has been replaced by another group.

Useful conversions:

• Carboxylic acid + alcohol ⇌ ester + water, using concentrated H₂SO₄ or HCl catalyst and reflux.
• Carboxylic acid → acyl chloride, using SOCl₂.
• Acyl chloride + alcohol → ester.
• Acyl chloride + NH₃ → amide.

Acyl chlorides are much more reactive than carboxylic acids, so they are often used when a faster or higher-yielding route to an ester or amide is needed.

Aromatic synthesis routes

For benzene-based compounds, remember the common aromatic sequence:

Benzene → nitrobenzene → phenylamine → diazonium salt → azo dye

Key reagents and conditions:

• Benzene to nitrobenzene: concentrated HNO₃ and concentrated H₂SO₄, about 50 °C.
• Nitrobenzene to phenylamine: Sn and concentrated HCl, then NaOH.
• Phenylamine to diazonium salt: NaNO₂ and HCl below 10 °C.
• Diazonium salt to azo dye: phenol or aromatic amine in alkaline conditions.

This matters because exam routes often ask you to make an aromatic amine, dye, amide or substituted benzene from benzene.

Evaluating a synthesis

A good route is not just chemically possible. It should also be practical.

Consider:

• Number of steps: fewer steps usually give a better overall yield.
• Yield: each step loses some product.
• Purity: products may need distillation, recrystallisation or drying.
• Safety: reagents such as HCN, SOCl₂ and acyl chlorides need care.
• Selectivity: if a molecule has several functional groups, a reagent may react with more than one.

$$percentage\; yield=\frac{actual\; yield}{theoretical\; yield}\times 100$$

Checking the product

In practical synthesis, you often need evidence that you made the intended compound.

Common checks include:

• IR spectroscopy: useful for identifying bonds such as O–H, C=O, N–H and C≡N.
• Mass spectrometry: gives molecular mass and fragmentation evidence.
• NMR spectroscopy: helps confirm carbon and hydrogen environments.
• Melting temperature or boiling temperature: a sharp value close to the data-book value suggests good purity.