When you are asked to plan a multi-step synthesis, a systematic approach helps.1. Compare the functional groups in the starting material and the target.
2. Compare the number of carbon atoms. If the chain must get longer, you need a carbon-carbon bond forming step: KCN with a halogenoalkane, HCN with an aldehyde or ketone, or a Grignard reagent.
3. Work backwards from the target. Ask: what could this be made from in one step? Repeat until you reach something you can make from the starting material.
4. Give full reagents and conditions for every step, and name each intermediate.
5. Check the route: fewer steps give a higher overall yield; avoid very hazardous reagents where possible; consider whether a product will be a racemic mixture.Worked example: convert ethene into propanoic acid.
The target has three carbons, ethene has two, so one carbon must be added. Propanoic acid can be made by hydrolysing propanenitrile, which can be made from bromoethane, which can be made from ethene.
Step 1: ethene + HBr at room temperature → bromoethane.
Step 2: bromoethane + KCN in ethanol, heat under reflux → propanenitrile.
Step 3: propanenitrile + dilute acid, heat under reflux → propanoic acid.An alternative for steps 2 and 3 is a Grignard route: bromoethane + Mg in dry ether → ethylmagnesium bromide, then CO2 followed by dilute acid → propanoic acid.Second example: ethanal to 2-hydroxypropanoic acid. Add HCN (with KCN) to give 2-hydroxypropanenitrile, then heat under reflux with dilute acid to hydrolyse the nitrile group. Because the cyanide ion can attack the planar C=O from either side, the product is a racemic mixture.
2. Compare the number of carbon atoms. If the chain must get longer, you need a carbon-carbon bond forming step: KCN with a halogenoalkane, HCN with an aldehyde or ketone, or a Grignard reagent.
3. Work backwards from the target. Ask: what could this be made from in one step? Repeat until you reach something you can make from the starting material.
4. Give full reagents and conditions for every step, and name each intermediate.
5. Check the route: fewer steps give a higher overall yield; avoid very hazardous reagents where possible; consider whether a product will be a racemic mixture.Worked example: convert ethene into propanoic acid.
The target has three carbons, ethene has two, so one carbon must be added. Propanoic acid can be made by hydrolysing propanenitrile, which can be made from bromoethane, which can be made from ethene.
Step 1: ethene + HBr at room temperature → bromoethane.
Step 2: bromoethane + KCN in ethanol, heat under reflux → propanenitrile.
Step 3: propanenitrile + dilute acid, heat under reflux → propanoic acid.An alternative for steps 2 and 3 is a Grignard route: bromoethane + Mg in dry ether → ethylmagnesium bromide, then CO2 followed by dilute acid → propanoic acid.Second example: ethanal to 2-hydroxypropanoic acid. Add HCN (with KCN) to give 2-hydroxypropanenitrile, then heat under reflux with dilute acid to hydrolyse the nitrile group. Because the cyanide ion can attack the planar C=O from either side, the product is a racemic mixture.