Organic Synthesis

Section 1 of 9Preparing an organic solid

Skills covered

• Using appropriate apparatus to record a range of measurements.
• Heating with a water bath, electric heater or sand bath.
• Using laboratory apparatus for a variety of techniques.
• Purifying a solid by recrystallisation.
• Using melting point apparatus.
• Handling solids and liquids safely.

Common preparations

• Common preparations aspirin, benzoic acid, and nitration of methyl benzoate

Section 2 of 9Recrystallisation

• Principle
  • a hot solvent dissolves both the solid and the impurities, and as the solution cools the solid crystallises and the impurities stay in solution
  • Use the minimum amount of hot solvent to avoid losing product.

1

Dissolve the impure solid in the minimum volume of hot solvent.

2

If solid impurities remain, filter the hot solution.

3

Let the solution cool to room temperature so crystals form.

4

Filter off the crystals, faster using Buchner apparatus under reduced pressure.

5

Wash the crystals with fresh cold solvent.

6

Dry them on filter paper.

• Notes
  • Repeating recrystallisation increases purity but lowers the yield each time.
  • Slow cooling gives larger, well-defined crystals that are easier to filter and dry.

Section 3 of 9Melting point determination

Information

• Information the melting point shows the purity and identity of a solid
• It can be matched to a known substance to identify or confirm a product.
• Closeness to the data-book value shows purity.

Impurities

• Impurities they lower the melting point and broaden the range
• Pure substances have sharp, well-defined melting points.
• Impure substances melt over a wide range.

Key skills

• Prepare the melting point tubes correctly.
• Use a totally dry, finely powdered sample, crushed on filter paper or a white tile.
• Heat the tubes very slowly.
• Repeat, normally three times.

Method

• Method use the first tube for an approximate range, then repeat with much slower heating
• Apparatus can be an oil bath, a Thiele tube or a melt station.

Quoting

• Quoting give a melting point as a range, and reference a data-book value if available

Section 4 of 9Functional groups for synthesis

Functional groups for synthesis

Principle

• Principle many products are made from a few starting compounds with suitable reagents and conditions
• Knowing how functional groups are related is key.

Groups to know

• Groups to know alkanes, alkenes, haloalkanes, nitriles, amines, alcohols, carbonyls, hydroxynitriles, carboxylic acids, esters, acyl chlorides,
  • and primary and secondary amides
  • (aldehydes and ketones)
• You must also identify these groups in structures given.

Section 5 of 9Aliphatic reaction pathways

Change	Reagents and conditions
Alkane to haloalkane	Halogen, UV light (radical substitution)
Alkene to alkane	H2, nickel catalyst
Alkene to haloalkane	Hydrogen halide, room temperature
Alkene to alcohol	Steam, H3PO4 or H2SO4 catalyst
Haloalkane to alcohol	Aqueous NaOH, heat
Haloalkane to nitrile	Ethanolic KCN, reflux
Haloalkane to amine	Excess ethanolic ammonia, heat under pressure
Alcohol to haloalkane	NaBr with H2SO4 (HX in situ)
Alcohol to alkene	Concentrated H2SO4 or Al2O3, heat
Alcohol to aldehyde / carboxylic acid / ketone	Acidified K2Cr2O7: distil, reflux, or heat
Carbonyl to alcohol	NaBH4
Carbonyl to hydroxynitrile	HCN (KCN with acid)
Nitrile to amine	LiAlH4 in dry ether, or H2 with Ni
Nitrile to carboxylic acid	Dilute acid or alkali then acid, heat
Carboxylic acid to ester	Alcohol, concentrated H2SO4, reflux
Carboxylic acid to acyl chloride	SOCl2
Acyl chloride to amide / ester	Ammonia or amine / alcohol

Section 6 of 9Aromatic reaction pathways

Change	Reagents and conditions
Benzene to nitrobenzene	Concentrated HNO3 and H2SO4, 25–60 °C
Nitrobenzene to phenylamine	Sn with concentrated HCl, reflux, then excess NaOH
Benzene to halobenzene	Halogen with AlCl3 or FeBr3 carrier
Benzene to alkylbenzene	Chloroalkane with AlCl3
Benzene to acylbenzene (ketone)	Acyl chloride with AlCl3
Phenol to bromophenol	Bromine water, room temperature

Section 7 of 9Designing a reaction pathway

1

Draw the structures of the target molecule and the starting molecule.

2

Check whether they have the same number of carbons; to lengthen the chain, add a nitrile group by nucleophilic substitution.

3

List all compounds that can be made from the starting molecule and all that can be converted into the target.

4

Match the groups they have in common and work out the reagents and conditions.

Example

• Example ethene to 1-aminopropane
• Ethene + HBr gives bromoethane.
• Bromoethane with ethanolic KCN gives propanenitrile, adding one carbon.
• Reduction with LiAlH₄ or H₂/Ni gives 1-aminopropane.

Level

• A Level requires multistage synthesis; past papers generally go to four steps

Section 8 of 9Key terms

Term	Meaning
Recrystallisation	Purifying a solid by dissolving in hot solvent and allowing crystals to form on cooling
Buchner filtration	Faster filtration under reduced pressure
Melting point range	The temperatures from first to complete melting, narrow for a pure substance
Target molecule	The molecule a synthesis is designed to produce
Hot filtration	Filtering a hot solution to remove insoluble impurities

Section 9 of 9Exam technique

1

Using too much solvent in recrystallisation — this reduces the yield

2

Quoting a melting point as one value — give a range

3

Saying impurities raise the melting point — they lower it and widen the range

4

Forgetting the in-between step that lengthens the chain by a nitrile in a synthesis