PAG 6.1 - Synthesis of Aspirin

Preparation of 2-hydroxybenzoic acid

• Set up reflux using a 50 cm³ pear-shaped flask, Liebig condenser & electric heater.

• Measure ~2.5 cm³ of oil of wintergreen in a 10 cm³ measuring cylinder. Record mass before & after adding to flask to get accurate mass.

• Add 25 cm³ of NaOH solution (from 50 cm³ cylinder) + anti-bumping granules to flask.

• Reflux the mixture gently for 30 min using an electric heater

• Cool the mixture, pour into a 100 cm³ beaker in an ice bath.

• Neutralise with HCl dropwise, stirring with a stirring rod until no more solid forms.

• Filter under reduced pressure, wash solid with cold distilled water.

• Dry the solid on a pre-weighed watch glass, then reweigh to find mass of dry product.

Part 2 - Preparation of Aspirin

• Weigh ~2 g of 2-hydroxybenzoic acid in a sample tube. Record mass before & after transfer to a 100 cm³ conical flask to get accurate mass.

• Measure 4 cm³ of ethanoic anhydride in a dry 10 cm³ measuring cylinder and add to flask.

• Add 5 drops of conc. H₂SO₄ and gently shake flask for 10 minutes.

• Cool flask in crushed ice to promote crystallisation.

• Add 4 cm³ of cold glacial ethanoic acid to complete the reaction.

• Filter under reduced pressure, washing solid with ice-cold distilled water.

• Transfer to a pre-weighed watchglass, dry the product, then reweigh to find mass of dry aspirin.

Part 3 - recrystallisation

• Transfer most of impure aspirin to a 100 cm³ conical flask (save a few crystals for TLC).

• Warm ~30 cm³ ethanol in a second conical flask using a hot water bath.

• Add hot ethanol in small portions until aspirin just dissolves.

• Filter hot solution quickly under reduced pressure, washing with minimal hot ethanol.

• Cool filtrate slowly, then in ice bath to form crystals.

• Filter crystals under reduced pressure, wash with ice-cold ethanol.

• Transfer to pre-weighed watchglass, dry thoroughly, then reweigh to find mass of recrystallised aspirin.

Part 4 - Thin Layer Chromatography

1. Draw a pencil line 1 cm from bottom of TLC plate; mark 4 crosses for samples.

2. Add 5 mm of chromatography solvent to a 100 cm³ beaker, cover with watchglass.

3. Dissolve 2–3 crystals of each sample in ethanol on a watchglass.

4. Use capillary tube to spot each solution on the TLC plate (repeat 3–4×, ≤5 mm wide).

5. Spot: pure aspirin, crude aspirin (Part 2), recrystallised aspirin (Part 3), and 2-hydroxybenzoic acid.

6. Place TLC plate in beaker, cover, and allow solvent to rise (15–20 min).

7. Remove when solvent is near top; mark solvent front with pencil.

8. Dry plate in fume cupboard.

9. View under UV lamp and mark spots with pencil.

Part 5 - melting point determination

1. Seal one end of a melting point tube by briefly rotating in a Bunsen flame; allow to cool.

2. Place a small amount of recrystallised aspirin on a watch glass; crush if needed.

3. Fill tube to ~5 mm depth, tap to settle aspirin at sealed end.

4. Insert into melting point apparatus and heat slowly until aspirin fully melts.

5. Record the melting point range (start and end of melting).