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Module 1: Practical chemistry for exams›PAG 6.1 - Synthesis of aspirin

PAG 6.1 - Synthesis of aspirin

An overview of PAG 6.1 - Synthesis of aspirin

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In OCR Chemistry Required Practical 6 (PAG 6.1), aspirin is prepared via a two-stage synthesis.

Stage 1: The alkaline hydrolysis of the ester methyl 2-hydroxybenzoate, and its acidification forming 2-hydroxybenzoic acid.

Stage 2: The synthesis of aspirin, from the hydrolysis product, and an acylating agent.

The resulting product is purified and analysed.

In OCR PAG 6.1: Synthesis of aspirin, there are several important safety requirements to be aware of (beyond normal lab practice such as wearing goggles).

Ethanoic anhydride and concentrated ethanoic acid vapour should not be inhaled – always dispense in a fume cupboard.
Several chemicals are harmful if inhaled – complete the practical in a well-ventilated area.
Immediately clean up any spills of acid or alkali.

Experimental method for OCR Chemistry Required Practical 6 (PAG 6.1)

Part 1 – Preparation of 2-hydroxybenzoic acid.

EXPERIMENTAL METHOD OCR PAG 6.1 - PART 1. 1. Prepare the starting material – methyl 2-hydroxybenzoate. Add about 2.5 cm³ of methyl 2-hydroxybenzoate (known as oil of wintergreen) to a 10 cm³ measuring cylinder and record the mass. Pour the oil of wintergreen into a pear-shaped flask. Reweigh the measuring cylinder to find the exact mass of oil of wintergreen used. 2. Add the alkali. Using a 50 cm³ measuring cylinder, measure out about 25 cm³ of 2.0 mol dm⁻³ sodium hydroxide solution. Add the alkali to the pear-shaped flask. Add a few anti-bumping granules. 3. Heat under reflux. Heat the reaction mixture under reflux using a boiling water bath, or electric heater, for about 30 minutes. Leave the reaction mixture to cool, then pour it into a 100 cm³ beaker. Place this beaker into a larger beaker with iced water. 4. Neutralise with acid. Add drops of 2.0 mol dm⁻³ hydrochloric acid to the product beaker. A white precipitate will form. Continue adding acid, and stir with a glass rod until no more white solid is precipitated. 5. Recover the product by vacuum filtration. Arrange a Buchner funnel and filter flask and attach to a pump. Vacuum filter, and wash the product with a little cold water. Collect the dried product as a white solid, and determine the mass for the yield calculation by weighing.

Experimental method for OCR Chemistry Required Practical 6 (PAG 6.1)

Part 2 – Acylation of 2-hydroxybenzoic acid.

EXPERIMENTAL METHOD OCR PAG 6.1 - PART 2. 1. Weigh a sample of 2-hydroxybenzoic acid. Measure out about 2.0 g of 2-hydroxybenzoic acid (salicylic acid) into a sample tube. Weigh the sample and record the mass. Tip the solid into a 100 cm³ conical flask, and reweigh the sample tube to determine the exact mass of solid transferred. 2. Add ethanoic anhydride and sulfuric acid. Measure out 4 cm³ of ethanoic anhydride, and pour it into the flask. Add five drops of concentrated sulfuric acid catalyst. 3. Agitate the reaction mixture. Shake the flask gently from side to side for about 10 minutes. A crystalline ‘mush’ will form suddenly. This is the crude aspirin product. 4. Dilute the product with ethanoic acid. Using a small measuring cylinder, measure out 4 cm³ of glacial ethanoic acid. Pour the ethanoic acid into the reaction flask and swirl to mix. This will dilute the reaction mixture, making it mobile and easier to filter. 5. Filter the product. Filter off the product under reduced pressure using a Buchner funnel and filter flask. Wash the product on the funnel with a little cold water and allow it to dry on a watch glass. Collect the dried solid sample in a weighed sample tube, and reweigh to find the mass of dried product aspirin. This is used in yield calculations.

Experimental method for OCR Chemistry Required Practical 6 (PAG 6.1)

Part 3 – Purification of the product and melting point determination.

EXPERIMENTAL METHOD OCR PAG 6.1 - PART 3. 1. Dissolve the crude product in a minimal amount of warm ethanol. Warm 30 cm³ of ethanol in a small conical flask on an electric hotplate (not a naked flame). Add a little ethanol at a time to the solid in a small beaker and stir with a glass rod. Keep the product on the hot plate and continue to stir until it is completely dissolved. 2. Cool the mixture and allow the product to recrystallise. When the solid has dissolved completely, remove it from the heat and allow it to cool slowly. Needle-like crystals of pure aspirin will slowly form. 3. Filter the recrystallised product. When completely cold, collect the crystals by filtration under reduced pressure. Wash with cold ethanol, and allow to dry. Collect the crystals in a weighed sample tube, and determine the mass of pure dry aspirin. 4. Load the materials in a melting point tube. Seal a capillary melting point tube in a Bunsen flame. Crush a little of the pure aspirin product on a watch glass with a stirring rod. Carefully stab the open end into the powdered sample. 5. Measure the melting point. Insert the loaded melting point tube into the melting point apparatus and place a 0–250 °C thermometer alongside the sample. Heat the tube and observe the temperature at which the sample begins to melt, and when a clear liquid forms. Compare the range of values to the stated melting point for aspirin. © Medify

Experimental method for OCR Chemistry Required Practical 6 (PAG 6.1)

Part 4 – TLC analysis.

EXPERIMENTAL METHOD OCR PAG 6.1 - PART 4. 1. Prepare a chromatography plate. Rule a pencil margin 1 cm from the short side of a TLC plate. Mark four equally spaced crosses for the samples: Pure aspirin, Impure aspirin from part 2, Recrystallised aspirin from part 3, 2-hydroxybenzoic acid from the start. Pour 0.5 cm depth of the chromatography solvent provided into a beaker and place a lid or watch glass on the beaker. 2. Apply samples to the plate. Using a dimple plate, add a few crystals of the four different samples to separate dimples. Add a drop of ethanol to each sample to dissolve the solid. Dip a capillary tube into the sample solution. Touch the capillary tube onto a sample cross on the TLC plate, allow the sample to dry and reapply another spot. 3. Run the chromatogram. Remove the lid from the solvent beaker and place the TLC plate carefully into the solvent, which must not be higher than the sample spots. Rest the plate on the side of the beaker, and replace the lid. Allow the solvent to rise three-quarters of the way up the plate. 4. Mark the solvent front and locate sample spots. Remove the TLC plate, and immediately mark the solvent front in pencil. Allow the plate to dry. Examine the plate under a UV lamp, or place the plate in a beaker with a crystal of iodine and cover the beaker. When the sample spots are visible mark the centre of each spot in pencil. 5. Measure distances and calculate Rf values. Measure the distance travelled by each spot from the origin line to the centre of the spot, and also the solvent front. Use the measurements to calculate Rf values.

The precision of the balance used is critical for ensuring the accuracy of mass measurements and subsequent calculations.

A digital laboratory scale with a circular weighing platform and a blue control panel displaying a reading of 0.00.

Do

Measure solids and liquids precisely. Ensures accurate mole calculations and enthalpy values. A balance with a resolution of at least two decimal places should be used.

A digital weighing scale with a round platform and a red control panel displaying '0.0' on a green screen.

Don't

Use a balance with a resolution of 1 decimal place or lower.

Temperature control in the preparation of aspirin is essential.

A laboratory setup featuring a beaker filled with blue liquid, a thermometer inserted into the beaker, and a Bunsen burner underneath the beaker, all resting on a wire mesh support.

Do

Monitor the temperature carefully, using a water bath and ensuring it does not exceed 65 °C to avoid decomposing

A laboratory setup showing a conical flask containing blue liquid, placed on a wire mesh over a Bunsen burner. The burner is lit, producing a flame underneath the flask, and there are red wavy lines indicating heat.

Don't

Allow the temperature to rise above 65 °C – overheating may degrade the aspirin product.

Take care when filtering the aspirin product under reduced pressure.

A diagram illustrating a Bucher funnel setup. The image includes a Bucher funnel at the top, with filter paper inside it. Below, a flask is connected to a water pump, and a drop of liquid is shown falling from the funnel into the flask.

Do

Filter the aspirin gently under reduced pressure to collect the solid efficiently. Dampening the filter paper and starting the suction before adding the reaction mixture creates a good seal.

A diagram illustrating a Bucher funnel setup, with labeled components including a Bucher funnel, filter paper, and a water pump connected to a flask.

Don't

Apply excessive force during filtration – this could cause the filter paper to tear and the solid to be sucked through to the collection vessel.

When purifying ethyl ethanoate, a suitable drying agent should be used.

A laboratory flask with a narrow neck and a wide base, containing a blue liquid at the bottom.

Do

Use anhydrous sodium sulfate to remove any water from the ethyl ethanoate before distillation.

A laboratory flask with a narrow neck and a wide base, containing a blue liquid.

Don't

Allow any water to remain in the ethyl ethanoate – this can interfere with the purity of the final product and therefore lead to inaccurate yield calculations.

Best practice when preparing a TLC plate.

A glass filled with water, with a pencil poised above it. Below the water line, there are five labeled points marked A, B, C, D, and E, connected by a dashed line.

Do

Use a pencil to draw a faint baseline 1 cm from the bottom and apply small, equally spaced spots using a capillary tube.

A diagram showing a container filled with light blue water. At the bottom, there are five dark circles labeled A, B, C, D, and E, with a dashed line above them. A pen is positioned at the top right, poised to touch the water.

Don't

Use a pen to draw the baseline – the ink may be soluble in the solvent, affecting the results.
Place spots close together – these can run up the plate together and be hard to distinguish.

The level of the solvent in the developing chamber is important in thin layer chromatography.

A diagram showing a TLC plate positioned above a solvent in a beaker. The TLC plate is labeled at the top, and the solvent is labeled at the bottom. There are five points marked A, B, C, D, and E along the bottom of the TLC plate, with an upward arrow indicating the movement of the solvent.

Do

Ensure the solvent level is below the pencil line when placing the plate in the chamber.

A diagram showing a TLC plate submerged in a solvent within a beaker. The TLC plate is positioned vertically with an upward arrow indicating movement. Below the plate, there are labels A, B, C, D, and E marked along a dashed line.

Don't

Let the solvent cover the spots – they will dissolve into the solvent and move from their original start-point.

The timing of plate removal in thin layer chromatography is critical for robust analysis.

An illustration showing a solvent front at the top. Below it, there are five labeled points marked A, B, C, D, and E, arranged in a horizontal line.

Do

Remove the plate when the solvent front is ~1 cm from the top and dry it in a fume cupboard before viewing under UV.

Two diagrams showing a solvent front. The first diagram shows a light blue background with a dashed line and labels A, B, C, D, and E at the bottom. The second diagram also has a light blue background with a solvent front indicated, and the same labels A, B, C, D, and E at the bottom.

Don't

Leave the plate too long – if the solvent front goes to the top of the plate the distance moved by the solvent cannot be quantified.
Remove the plate too soon – if the solvent front has not moved far the separation will be less and the R_f calculations will lack resolution.

Identify the center of each component spot when analysing thin layer chromatography.

A diagram showing a container with water and three bubbles labeled A, B, and C. The text '5.39 / 7.85 = 0.69' is positioned above two bubbles, and '1.3 / 7.85 = 0.17' is below the bubbles. A ruler is displayed on the right side, marked with measurements from 0 to 11.

Do

Use a ruler to measure from the baseline to the centre of each spot and to the solvent front.

$An illustration showing a container with three blue circles labeled A, B, and C at the bottom. Above the circles, there are two fractions: 5/7.85 = 0.64 and 0.9/7.85 = 0.11. To the right, there is a ruler marked with measurements from 0 to 11, with fractional divisions of 1/4 and 1/2.$

Don't

Measure to the base of the spots – the R_f is based on the mean movement of the sample.

Calculate theoretical and percentage yields for the preparation of 2-hydroxybenzoic acid and then aspirin using the 1:1 stoichiometric ratio, and

Compare the chromatogram of the product with pure aspirin and 2-hydroxybenzoic acid. Calculate the values using:

The melting point can be compared to known values, a narrow melting range close to 138–140 °C supports a pure aspirin product.