Synthetic routes and problem solvingEdexcel International A Level Chemistry: Revision notes

Organic synthesis uses a toolkit of reactions you already know. Revise them as a map of how one functional group becomes another:

• Alkene to haloalkane (HBr), dibromoalkane (Br₂), alcohol (steam and H₃PO₄ catalyst)
• Haloalkane to alcohol (aqueous NaOH, heat), nitrile (KCN in ethanol, reflux, +1 carbon), amine (excess NH₃ in ethanol, sealed tube), alkene (ethanolic NaOH)
• Primary alcohol to aldehyde (distil with acidified K₂Cr₂O₇) or carboxylic acid (reflux); secondary alcohol to ketone
• Alcohol to haloalkane (PCl₅ or NaBr with H₂SO₄), ester (carboxylic acid and acid catalyst)
• Aldehyde or ketone to hydroxynitrile (HCN with KCN), alcohol (NaBH₄ or LiAlH₄)
• Nitrile to amine (LiAlH₄ or H₂ with Ni) or carboxylic acid (dilute acid, reflux)
• Carboxylic acid to acyl chloride (PCl₅ or SOCl₂); acyl chloride to ester, amide
• Benzene to nitrobenzene (conc HNO₃ and conc H₂SO₄, 50 °C), then to phenylamine (Sn and conc HCl, reflux, then NaOH)
• Grignard route: RMgX with CO₂ or carbonyls adds carbon

A new molecule is just familiar functional groups in a new arrangement. To predict its behaviour:

1. Circle each functional group (C=C, OH, COOH, C=O, NH₂, halogen).
2. For each, recall its reactions and tests, as the groups mostly behave independently.
3. Use bonding to predict physical properties: groups that form hydrogen bonds (OH, COOH, NH₂) raise boiling temperature and increase water solubility.

Tests: C=C decolourises bromine water; COOH gives CO₂ with sodium carbonate; a primary or secondary alcohol or an aldehyde turns acidified dichromate(VI) from orange to green; aldehydes and ketones give an orange precipitate with 2,4-DNPH; aldehydes give a silver mirror with Tollens' reagent.

Also check for stereoisomerism: E/Z isomers need a C=C with two different groups on each carbon; optical isomers need a carbon bonded to four different groups.

Work backwards from the target (retrosynthesis):

1. Compare the target and starting material: has the functional group changed? Has the carbon chain changed?
2. If the chain grows, you need a C–C bond forming step (cyanide or Grignard).
3. Choose the last step first, then ask what could make that compound, until you reach the starting material.
4. Give reagents and conditions for every step, and watch the order: some steps must come before others.

Example: ethene to propanoic acid. Ethene + HBr gives bromoethane; bromoethane + KCN in ethanol (reflux) gives propanenitrile; refluxing with dilute HCl gives propanoic acid. Three steps, with one carbon added.

Overall yield is the product of the step yields: 80% × 70% × 90% = 50.4%. Long routes lose product at every step.

Match the technique to the job:

• Reflux: heats a mixture for a long time without losing volatile liquids. Used for slow reactions and for full oxidation of a primary alcohol to an acid.
• Distillation: separates liquids with different boiling temperatures. Used to remove an aldehyde as it forms, so it is not oxidised further, and to purify the final product.
• Separating funnel: separates two immiscible liquids.
• Sealed tube or pressure vessel: for ammonia with a haloalkane, so ammonia does not escape.
• Dry conditions: for Grignard reagents, using dried glassware and ether.
• Water bath or electric heater: for flammable liquids, never a naked flame.
• Ice bath: to control exothermic reactions.

Purification methods, including washing, drying and recrystallisation, are covered under preparation and purification.

A hazard is something that can cause harm; risk is the chance of harm, depending on the hazard and how much exposure there is. Use hazard data to choose control measures:

• Flammable: no naked flames; electric heater or water bath; small quantities
• Corrosive or irritant: eye protection, gloves, dilute solutions
• Toxic or carcinogenic: gloves, avoid dust and skin contact, use a fume cupboard for volatile or toxic vapours (e.g. bromine, cyanides, aldehydes)
• Oxidising: keep away from flammable materials
• Environmental hazard: collect waste in a labelled container, never down the sink

Example: cyanide solutions must never be mixed with acid, which would release toxic hydrogen cyanide gas.