Organic synthesis routesAQA A-Level Chemistry: Revision notes
Section 1
Planning a multi-step synthesis
Many organic compounds cannot be made in one step. A synthesis is a sequence of reactions, each converting one functional group into another. In the exam you will plan routes of up to four steps using only the reactions in your specification.
Work backwards from the target: ask which functional group it contains, then which compound would give that group in one reaction. Repeat until you reach the starting material. For each step state the reagent, the conditions (heat, reflux, catalyst, solvent) and the organic product.
Write the target at the right, the starting material at the left, and fill in the middle compounds from both ends.
Section 2
The reaction toolkit
Aliphatic routes
- alkene to haloalkane: HBr (addition)
- haloalkane to alcohol: NaOH(aq), heat under reflux (nucleophilic substitution)
- haloalkane to alkene: ethanolic NaOH or KOH, heat (elimination)
- haloalkane to nitrile: KCN in aqueous ethanol, heat (adds one carbon)
- haloalkane to amine: excess ethanolic NH₃, heat in a sealed tube
- nitrile to amine: H₂ with Ni catalyst, or LiAlH₄ in dry ether
- primary alcohol to aldehyde: acidified K₂Cr₂O₇, distil; to carboxylic acid: heat under reflux
- secondary alcohol to ketone: acidified K₂Cr₂O₇, heat
- carboxylic acid and alcohol to ester: warm with concentrated H₂SO₄ catalyst
Aromatic routes
- benzene to nitrobenzene: concentrated HNO₃ and concentrated H₂SO₄ at about 50 °C
- nitrobenzene to phenylamine: Sn and concentrated HCl, reflux, then NaOH
- phenylamine to an amide: acyl chloride
Use the right conditions for each step: NaOH(aq) gives an alcohol but ethanolic NaOH gives an alkene.
Section 3
Worked example: propene to propanone
Step 1: propene + HBr gives 2-bromopropane (major product via the more stable secondary carbocation).
Step 2: 2-bromopropane heated under reflux with NaOH(aq) gives propan-2-ol.
Step 3: propan-2-ol heated with acidified potassium dichromate(VI) gives propanone.
Three steps, each a reaction from the specification. If the route started with the primary carbocation product, 1-bromopropane, you would end up with propanal instead, so check the position of the functional group at every stage.
Always state which functional group changes at each step.
Section 4
Atom economy and yield
Percentage atom economy = (M(r) of desired product ÷ sum of M(r) of all reactants) × 100.
Example: C₂H₅Br + NaOH → C₂H₅OH + NaBr. M(r) of reactants = 108.9 + 40.0 = 148.9; M(r) of ethanol = 46.0; atom economy = 30.9%.
Addition reactions that give one product have 100% atom economy. Substitution and elimination reactions make by-products, so their atom economy is lower.
The overall yield of a synthesis is the product of the yields of each step, so it falls quickly as steps are added: four steps each at 80% give 0.80⁴ = 41%.
Use all the reactants in the denominator, including those that become by-products.
Section 5
Why chemists design greener processes
Chemists aim to design processes that:
- use no solvent, so there is less waste, no solvent to separate and recycle, less energy needed, and no flammable or toxic vapours
- use non-hazardous starting materials, so there is less risk to workers and the environment, and fewer safety precautions
- have fewer steps, so less energy, time and cost, a higher overall yield, and less waste
- have a high atom economy, so more of the reactant atoms end up in the product, less waste, and raw materials are used more efficiently
These aims make a process more sustainable and usually cheaper.
Link each feature to a consequence: fewer steps, so a higher overall yield; high atom economy, so less waste.
Must Know
- A synthesis is a sequence of reactions; plan backwards from the target, up to four steps
- For every step give reagent, conditions and the organic product
- Atom economy = M(r) desired product ÷ total M(r) of reactants × 100
- Overall yield is the product of the step yields
- Greener design: no solvent, non-hazardous starting materials, fewer steps, high atom economy
That's the notes covered.
Carry on to the next subtopic.
Exam questions on Organic synthesis routes
- A pharmaceutical company is redesigning the production of a drug intermediate. The existing process has five steps, is carried out in a chlorinated organic solvent and starts from a toxic compound. The company wants a greener process.Explain why chemists aim to design processes that use no solvent and that start from non-hazardous materials.2 marks
- Ethanol can be made by two routes. Route A: hydration of ethene with steam, C₂H₄ + H₂O → C₂H₅OH. Route B: hydrolysis of bromoethane with aqueous sodium hydroxide, C₂H₅Br + NaOH → C₂H₅OH + NaBr. Relative atomic masses: H = 1.0, C = 12.0, O = 16.0, Na = 23.0, Br = 79.9.Use the atom economies to justify why a chemist would prefer Route A to Route B.2 marks
- A research chemist plans to make organic compounds from simple starting materials. Only reactions from the A Level specification are to be used, and each synthesis may have up to four steps.Devise a two-step synthesis of propan-1-amine, CH₃CH₂CH₂NH₂, from bromoethane. For each step, give the reagents and conditions and the name or formula of the organic product.3 marks
Written by the Exaim team, led by Shaun Daswani (Head of Upper Secondary, Improve ME Institute; MSc Financial Mathematics, Imperial College London; BSc, UCL) and Jason Daswani (operational lead, Improve ME Institute; LSE).