Topic 20 · page 15 of 15

Core Practical 16: preparing aspirin

Warm 2-hydroxybenzoic acid with ethanoic anhydride and a little acid catalyst, crystallise the crude aspirin, recrystallise it, then check its purity by melting temperature and calculate the percentage yield.

15 min read20.420.5(iv)20.5(viii)

Read first: Recrystallisation, melting and boiling temperatures, Choosing a procedure and controlling risk

Aim and reaction 20.4

To prepare a sample of aspirin (2-ethanoyloxybenzoic acid) from 2-hydroxybenzoic acid, to purify it by recrystallisation, to check its purity from its melting temperature, and to calculate the percentage yield.

The –OH group on the benzene ring of 2-hydroxybenzoic acid is a phenol group. It reacts with ethanoic anhydride to form an ester, with ethanoic acid as the other product.

CX7HX6OX3+(CHX3CO)X2O→CX9HX8OX4+CHX3COOH \ce{C7H6O3 + (CH3CO)2O -> C9H8O4 + CH3COOH}
The reaction for the preparation of aspirin drawn with skeletal formulae. 2-Hydroxybenzoic acid, with a carboxylic acid group and an OH group on neighbouring ring carbons, reacts with ethanoic anhydride with a phosphoric acid catalyst to give aspirin, with a carboxylic acid group and an ethanoate ester group on neighbouring ring carbons, and ethanoic acid.
The phenol OH becomes an ethanoate ester. The COOH group is unchanged.

Method 20.4

PracticalPreparing crude aspirin

  1. Weigh about 2 g of 2-hydroxybenzoic acid into a dry pear-shaped flask. Record the mass.
  2. In a fume cupboard, add about 4 cm³ of ethanoic anhydride and a few drops of concentrated phosphoric acid.
  3. Warm in a hot water bath at about 80 °C for about 20 minutes, swirling from time to time.
  4. Add cold water carefully to destroy the excess ethanoic anhydride. Cool the flask in ice until crystals form, scratching the inside if necessary.
  5. Filter under reduced pressure, wash with a little ice-cold water, and press the crystals dry.

Quantities and the temperature are typical. If your teacher's method differs, follow it. The reasons for each step stay the same.

Step Reason
dry flask ethanoic anhydride reacts with water
ethanoic anhydride in excess the reaction goes to completion; the anhydride is cheap
fume cupboard the vapour of ethanoic anhydride is harmful and irritating
water bath, not a flame the anhydride is flammable
cold water added at the end it reacts with the excess anhydride and makes the aspirin crystallise
cool in ice aspirin is only slightly soluble in cold water, so more crystals form
wash with ice-cold water removes the soluble impurities without dissolving much aspirin
(CHX3CO)X2O+HX2O→2 CHX3COOH \ce{(CH3CO)2O + H2O -> 2CH3COOH}

The excess ethanoic anhydride is turned into ethanoic acid, which dissolves in the water and is filtered off.

What you see

Observation Explanation
the solid dissolves on warming it dissolves in, and reacts with, the hot anhydride
a smell like vinegar ethanoic acid is formed as a by-product
white crystals form on cooling in ice aspirin is only slightly soluble in cold water
the crude product melts low and over a range it is impure

Purifying and checking 20.420.5(iv)20.5(viii)

The crude aspirin contains traces of 2-hydroxybenzoic acid and other impurities. Recrystallise it, as on page 13.

PracticalRecrystallising aspirin

  1. Dissolve the crude aspirin in the minimum volume of hot solvent, such as hot water, or hot ethanol with water added.
  2. Cool slowly, then in an ice bath, so crystals form.
  3. Filter under reduced pressure and wash with a little ice-cold solvent.
  4. Dry the crystals between filter papers or in a desiccator.
  5. Measure the melting temperature with a capillary tube.

Pure aspirin melts sharply at about 136 °C. The crude product melts lower and over a wider range, so the recrystallised product, with a narrow range close to 136 °C, shows that the aspirin is purer.

Calculating the yield 20.4

Worked examplePercentage yield of aspirin

Illustrative data. 2.00 g of 2-hydroxybenzoic acid (MrM_\text{r} = 138.0) gives 1.80 g of pure aspirin (MrM_\text{r} = 180.0).

  1. n(2-hydroxybenzoic acid) = 2.00 ÷ 138.0 = 0.01449 mol.
  2. The equation is 1 : 1, so the theoretical n(aspirin) = 0.01449 mol.
  3. Theoretical mass = 0.01449 × 180.0 = 2.609 g.
  4. Percentage yield = 1.80 ÷ 2.609 × 100 = 69.0%.

Worked exampleChecking that the anhydride is in excess

Illustrative data. 4.0 cm³ of ethanoic anhydride (density 1.08 g cm⁻³, MrM_\text{r} = 102.0) is used with 2.00 g of 2-hydroxybenzoic acid.

  1. Mass of anhydride = 4.0 × 1.08 = 4.32 g, so n = 4.32 ÷ 102.0 = 0.0424 mol.
  2. n(2-hydroxybenzoic acid) = 0.01449 mol, from the worked example above.
  3. The ratio is 0.0424 ÷ 0.01449 = 2.9, so the anhydride is in about threefold excess and the acid is the limiting reactant.
  4. The yield is therefore worked out from the 2-hydroxybenzoic acid, never from the anhydride.

Why the yield is below 100% 20.4

Source of loss or error Effect
some product stays dissolved in the cold water or the recrystallisation solvent lowers the yield
product left on the glassware and filter paper lowers the yield
the reaction does not go to completion lowers the yield
some aspirin hydrolyses in hot water during recrystallisation lowers the yield
crystals not dried properly the mass is too high, so the yield appears too high

Check yourself

  1. Explain why ethanoic anhydride is used instead of ethanoic acid, and state the role of phosphoric acid.
  2. Why is cold water added at the end of the reaction, and why must the water used to wash the crystals be ice-cold?
  3. 3.00 g of 2-hydroxybenzoic acid gives 2.70 g of aspirin. Calculate the percentage yield.
  4. Calculate the mass of 2-hydroxybenzoic acid needed to make 2.50 g of aspirin if the percentage yield is 69.0%.
  5. Crude aspirin melts at 128–133 °C. After recrystallisation it melts at 135–136 °C. Explain what this shows.
  6. A student reports a percentage yield of 104%. Suggest what has gone wrong and how to find out.

Answers cover these until you have tried the questions

  1. A phenol reacts slowly with a carboxylic acid and the reaction is reversible, so the yield is low. The anhydride is more reactive, so the reaction is faster and it goes to completion. Phosphoric acid is a catalyst: it speeds up the reaction and is not used up.
  2. Cold water reacts with the excess ethanoic anhydride, forming ethanoic acid that dissolves, and it makes the aspirin crystallise. Ice-cold water is used for washing because aspirin is only slightly soluble in cold water; warm water would dissolve some of the product and lower the yield.
  3. n(2-hydroxybenzoic acid) = 3.00 ÷ 138.0 = 0.02174 mol. Theoretical mass of aspirin = 0.02174 × 180.0 = 3.913 g. Percentage yield = 2.70 ÷ 3.913 × 100 = 69.0%.
  4. n(aspirin) needed = 2.50 ÷ 180.0 = 0.013889 mol. At 69.0% yield the amount of acid needed is 0.013889 ÷ 0.690 = 0.02013 mol. Mass = 0.02013 × 138.0 = 2.78 g.
  5. The crude sample melted below the pure value of about 136 °C and over a 5 °C range, so it was impure. After recrystallisation the melting range is narrow (1 °C) and close to the data-book value, so the aspirin is much purer.
  6. A yield over 100% is impossible for a pure product, so the crystals must be wet (they contain solvent or water) or impure (for example they contain 2-hydroxybenzoic acid). To find out, dry the crystals thoroughly and weigh them again, and measure the melting temperature: a low or wide range shows impurity.