Part 9: Core Practical 16: preparing and purifying aspirin

Explain the chemistry and purpose of each preparation step, calculate limiting yield and uncertainty, and use melting range as evidence about a dry purified product.

Acylate the phenolic OH while retaining COOH

Aspirin is 2-ethanoyloxybenzoic acid, also called acetylsalicylic acid. It is prepared from 2-hydroxybenzoic acid and ethanoic anhydride with an acid catalyst. The phenolic OH becomes –O–C(=O)CH₃; the ring’s COOH group remains. The product therefore contains both an ester and a carboxylic acid.

Ethanoic anhydride supplies an ethanoyl group and forms ethanoic acid as coproduct. This is acylation of an oxygen-containing group. Do not put the new CH₃CO group on the acid oxygen and leave the phenolic OH unchanged: that would have the wrong connectivity.

The acid catalyst increases reaction rate by activating the acylating reagent. The Pearson procedure uses concentrated sulfuric acid; some authorised teaching variants use phosphoric acid. Use the actual centre method and state the catalyst used rather than merging different quantities from different procedures.

Measure the starting quantity and retain volatile material

The preparation uses a balance, suitable reaction flask, condenser, clamp/support and controlled water-bath heating. Measure the 2-hydroxybenzoic acid and the required excess ethanoic anhydride, add the specified small amount of catalyst and warm for the prescribed time. A condenser limits loss of volatile material while heating proceeds.

The water jacket is filled from the lower inlet, vapour condenses back to the flask, and the apparatus must remain appropriately vented. Use anti-bumping measures appropriate to the procedure and handle hot glass cautiously. Ethanoic anhydride and concentrated acid are corrosive; the reaction and quench need the specified containment and eye/skin protection.

Measure by difference where appropriate so the recorded mass reflects material transferred. Keep a preparation record with actual masses, heating conditions and observations. A theoretical yield must be based on the material that actually entered the reaction, not on a nominal label mass.

Water destroys excess anhydride and helps crystallisation

After the reaction, introduce water/ice as directed by the approved procedure to hydrolyse remaining ethanoic anhydride to ethanoic acid. This process releases heat; addition and cooling must control the temperature and splashing. It is not simply dilution of an unchanged reagent.

Cooling the mixture decreases aspirin’s solubility and promotes crystal formation. Collect the crude solid using a Büchner funnel and suction flask, then wash with a small quantity of ice-cold suitable solvent, commonly water at this stage. The wash removes soluble acid and other impurities while limiting loss of aspirin.

The solid is crude even if it is white. Unreacted 2-hydroxybenzoic acid and trapped mother liquor may remain. Recrystallisation and drying are separate operations needed before a useful final mass and melting range are obtained.

Purify by solubility, then dry before measuring

Dissolve crude aspirin in the minimum suitable hot ethanol–water mixture specified by the centre method. Hot-filter if insoluble material is present, using warmed apparatus to prevent premature crystallisation. Cool the clear solution, allow crystals to develop, then use an ice bath if appropriate to improve recovery.

Collect by suction filtration, wash sparingly with cold suitable solvent and dry under conditions that do not decompose the product. Soluble impurities stay mainly in the mother liquor, while insoluble impurities are removed at hot filtration. Too much solvent or excessive washing sacrifices recovery; too little washing can leave contamination.

Ethanol is flammable, so the purification stage needs appropriate heating without exposed flames nearby. The isolated laboratory sample is for analysis and must not be consumed. A low mass can reflect work-up losses even if the chemical conversion was good; a high mass may reflect water or impurities rather than excellent synthesis.

Original worked example: limiting quantity to dry yield

Suppose 2.30 g of 2-hydroxybenzoic acid reacts with excess ethanoic anhydride. Using Mᵣ values 138.0 for the acid and 180.0 for aspirin, n(acid) = 2.30/138.0 = 0.0166667 mol. The 1:1 reaction gives the same theoretical amount of aspirin.

Theoretical aspirin mass = 0.0166667 × 180.0 = 3.00 g. If 2.25 g dry purified aspirin is isolated, percentage yield = 2.25/3.00 × 100 = 75.0%. Retain guard digits in intermediate amounts; round the final result according to the measured data.

If a wet sample instead weighs 3.12 g, its apparent yield is 104%. That cannot be a pure dry yield for the stated limiting reactant and equation. Residual solvent, impurities or an incorrect starting quantity must be investigated. Incomplete reaction and product loss both lower yield but need different improvements.

For an illustrative balance with uncertainty ±0.01 g per reading, a mass found by subtracting two independent readings has a maximum absolute uncertainty of ±0.02 g. On 2.25 g product, this is 0.02/2.25 × 100 = 0.89%. This estimates the measurement contribution only; it does not quantify purity or chemical losses.

Use a melting range and identify the cause of an error

Fill a capillary with a small amount of dry powdered sample and heat slowly near the expected range. Record onset and complete melting. Pearson’s teaching sheet uses 136°C as a reference for aspirin; use the reference and conditions supplied in a question. Impurities commonly depress and broaden a melting range.

An original sample melting over 128–133°C provides weaker purity evidence than a narrow range close to the reference. Recrystallisation/drying may improve it. Rapid heating or calibration error can also distort the measured range, so distinguish a composition problem from a measurement problem. A melting match is supporting evidence, not proof of pharmaceutical-grade purity.

Unreacted 2-hydroxybenzoic acid is a plausible impurity. A chromatographic comparison with starting material and a suitable aspirin reference can supplement melting data. IR evidence can also support phenolic-OH acylation, but the product still has an acid OH, so “all OH absorption disappears” would be wrong.

Explain the trade-off in a proposed improvement: a smaller cold wash reduces dissolved-product loss, but insufficient washing leaves soluble impurities; another recrystallisation can improve purity but further reduce isolated mass. Record actual observations and reasons. Knowing the explanation does not replace the supervised apparatus and technique competence assessed in the practical endorsement.

Quick checks

Original Finesse questions. Reveal the indicative worked solutions after attempting each question; these are not official Edexcel mark allocations.

Sources