Designing a Synthetic Route

• It is part of the job of an organic chemist to design a synthesis route for a known compound.
• In order to plan a synthesis route, the chemist must first look at the required compound (the target compound).
• By looking at the functional groups on the target compound, the chemist can work backwards, through a logical sequence of reactions until the suitable starting materials can be found.
• Several steps may be necessary to synthesise the target compound from a suitable starting compound.
• Along the synthesis steps there may be many intermediate compounds that have to be separated and purified from the other compounds.
• In more complex molecules, there may be more than one possible route to the target molecule.
• The preferred route is often the one with the fewest steps; however, other aspects have to be taken into consideration, such as the price of the starting materials.
• In order to design a synthesis route, it is necessary to know the reactions of the functional groups; the organic toolbox is a useful summary of the more common organic reactions.

Example of a Synthetic Route

• Paracetamol is a widely used painkiller that is often used to reduce fever.
• It is more expensive than aspirin; however it is thought to have fewer side-affects and so is a popular choice for many ailments.
• Paracetamol can be synthesised from phenol; using the organic toolkit, it is possible to plan the possible synthesis route.

Planning the Route

• The structure of paracetamol is as follows:
  1. Looking at the molecule of phenol, the phenolic hydroxyl group which is present on paracetamol is already present and so does not need to be added. To start the synthesis, a nitrogen group needs to be added to the ring. From the aromatic reactions, an NO₂ group can be added to the benzene ring in an electrophilic substitution reaction:
  2. The NO₂ group on the benzene ring needs to be converted to an amide group. This cannot be done in one step; it is first necessary to convert it to a primary amine group:
  3. The –NH₂ group is now prone to an acylation reaction in order to form the secondary amide:
• As is evident in the above synthesis, by looking at the target compound, it is possible to define a synthesis route.

Getting the correct isomer

• The yield of the main product can be lower when there are several isomers of a product molecule formed, and only one is needed.
• For example, electrophilic substitution reactions involving the benzene ring can give a number of isomeric products.
• In the nitration of methyl benzene, there are three possible products:
• The products are all solids, and so the solids must be separated using fractional crystallisation or chromatography.
• Sometimes separating the products can be difficult and time consuming; this all adds to the cost of synthesising the compound.
  

  Useful books for revision

  Revise A2 Chemistry for Salters (OCR A Level Chemistry B)
  Salters (OCR) Revise A2 Chemistry Home