Multi-step Synthetic Routes

A large number of organic products are made from a few starting compounds using appropriate reagents and conditions
Knowing how organic functional groups are related to each other is key to the synthesis of a given molecule
The main functional groups you need to know are
- Alkanes
- Alkenes
- Haloalkanes
- Nitriles
- Amines
- Alcohols
- Carbonyls (aldehydes & ketones)
- Hydroxynitriles
- Carboxylic acids
- Esters
- Acyl chlorides
- Primary and secondary amides

Exam Tip

You also need to be able to identify the functional groups of these chemicals in structures that are given to you

Aliphatic Reaction Pathways

The key interconversions between functional groups are summarised here:

Aliphatic Reactions Table

Reactant	Product	Reagents	Reaction
Alkene	Hydrogen halide	Electrophilic addition	-
Alkene	Alcohol	Hydration	Steam + H₂SO₄/ heat
Alkene	Alkane	Hydrogen + Ni catalyst / 150 °C	Electrophilic addition / hydrogenation
Alcohol	Alkene	Al₂O₃ or conc. acid / heat	Elimination / dehydration
Alcohol	Haloalkane	NaX + H₂SO₄/ heat under reflux	Nucleophilic substitution
Haloalkane	Alcohol	NaOH (aq) / heat under reflux	Nucleophilic substitution
Alkane	Haloalkane	Halogen / UV light	Free radical substitution
Primary alcohol	Aldehyde	Oxidation	K₂Cr₂O₇ / H₂SO₄/ Distillation
Secondary alcohol	Ketone	Oxidation	Heat
Primary alcohol	Carboxylic acid	Oxidation	Heat under reflux
Aldehyde	Primary alcohol	NaBH₄ / H₂O	Reduction
Ketone	Secondary alcohol	NaBH₄ / H₂O, NaCN	Reduction
Haloalkane	Nitrile	Nucleophilic substitution
Haloalkane	Amine	NH₃ / ethanol	Nucleophilic substitution
Nitrile	Carboxylic acid	H₂O / HCl	Hydrolysis
Aldehyde	Hydroxynitrile	NaCN / H⁺	Nucleophilic addition
Alcohol	Ester	Esterification	Carboxylic acid / H₂SO₄
Carboxylic acid	Ester	Alcohol / H₂SO₄	Esterification
Ester	NaOH(aq)	Alkaline hydrolysis	Carboxylate salt and alcohol
Ester	Carboxylic acid	Dilute acid	Acid hydrolysis
Carboxylic acid	Acyl chloride	SOCl₂	Chlorination
Acyl chloride	Carboxylic acid	H₂O	Hydrolysis
Acyl chloride	Primary amide	NH₃	Nucleophilic addition elimination
Acyl chloride	Secondary amide	Primary amine	Nucleophilic addition elimination

Aromatic Reaction Pathways

The key aromatic reactions are summarised here:

Aromatic Reactions Table

Reactant	Product	Reagents	Reaction
Benzene	Methylbenzene	CH₃Cl / AlCl₃	Alkylation / Electrophilic substitution
Benzene	Bromobenzene	Br₂ / FeBr₃	Bromination / Electrophilic substitution
Benzene	Chlorobenzene	Cl₂ / AlCl₃	Chlorination / Electrophilic substitution
Benzene	Nitrobenzene	HNO₃ / H₂SO₄	Nitration / Electrophilic substitution
Nitrobenzene	Aminobenzene / phenylamine / aniline	Sn / HCl	Reduction
Aminobenzene	2,4,6-tribromoaminobenzene / 2,4,6-tribromoaniline	Bromine	Electrophilic substitution
Benzene	Phenylethanone	CH₃COCl / AlCl₃	Acylation / Electrophilic substitution
Phenylethanone	1-Phenylethanol	NaBH₄	Reduction

Designing a Reaction Pathway

The given molecule is usually called the target molecule and chemists try to design a synthesis as efficiently as possible
Designing a reaction pathway starts by drawing the structures of the target molecule and the starting molecule
Determine if they have the same number of carbon atoms
- If you need to lengthen the carbon chain you will need to put on a nitrile group by nucleophilic substitution
Work out all the compounds that can be made from the starting molecule and all the molecules that can be made into the target molecule
- Match the groups they have in common and work out the reagents and conditions needed

Worked example

Suggest how the following synthesis could be carried out:

Ethene to 1-aminopropane

Answer

Organic synthesis WE Answer 2, downloadable AS & A Level Chemistry revision notes

Exam Tip

Sound knowledge of all of the different reactions is beneficial as the A-level course simply states that you should be able to design a multistage synthesis

Past papers generally go to four steps in a multistep reaction although there is no clear limit stated

Multi-step Synthetic Routes (CIE A Level Chemistry)

Revision Note