O acetylation

The phenolic oxygen of salicylic acid receives an acetyl group from ethanoic anhydride. Acyl substitution forms an ester while retaining the separate carboxyl group; proton transfer gives ethanoic acid as the co-product.

Reagents
Ethanoic anhydride; acid catalyst
Conditions
Controlled acid-catalysed acetylation
Reaction class
O-acetylation
Equation
C7H6O3 + C4H6O3 -> C9H8O4 + CH3COOH

Overview

The phenolic oxygen of salicylic acid receives an acetyl group from ethanoic anhydride. Acyl substitution forms an ester while retaining the separate carboxyl group; proton transfer gives ethanoic acid as the co-product.

Transformation

Salicylic acid → Aspirin

Equation
C7H6O3 + C4H6O3 -> C9H8O4 + CH3COOH
Reactants
Salicylic acid + Acetic anhydride
Products
Aspirin + Ethanoic acid
Reagents
Ethanoic anhydride; acid catalyst
Environment
Controlled acid-catalysed acetylation
Reaction class
O-acetylation
Mechanism
nucleophilic acyl substitution
Evidence level
source-backed molecular example

Reference procedure

Aspirin crystallisation and purity assessment

Salicylic acid + ethanoic anhydride → acetylsalicylic acid + ethanoic acid

Materials and quantities

  • Salicylic acid
  • Ethanoic anhydride with the reference phosphoric-acid catalyst
  • Water for the prescribed quench and washing

Apparatus

  • Dry reaction flask and condenser
  • Water bath and cooling bath
  • Suction-filtration apparatus

Procedure

  1. Warm the acetylation mixture in a water bath as directed by the reference.
  2. Follow the source’s controlled water addition, then cool to promote crystallisation.

Work-up and isolation

  1. Collect and cold-wash the crystals by suction filtration; dry before weighing.
  2. Compare the melting range with a reference and assess free salicylate using a separate analytical aliquot.

Critical controls

  • Excess anhydride must be treated through the specified work-up before isolation.
  • Dry crystals before measuring yield.
  • Purple iron(III) colour reports free salicylate rather than aspirin itself.

Practical techniques

Controlled heating

Apply the stated temperature deliberately, using a heat source and vessel suited to the solvent, scale and required temperature rather than treating ‘heat’ as a complete procedure.

Setup

  1. Select the bath from the cited temperature: a water bath is limited to temperatures near 100 °C, while higher temperatures require an appropriate oil or sand bath or another specified heater.
  2. Clamp the vessel securely and position the temperature probe so it measures the reaction or bath consistently without touching the heater.
  3. Use a vented arrangement unless the cited method explicitly specifies pressure-rated equipment; ordinary glassware must not be improvised as a sealed reactor.
  4. Bring the mixture to the stated temperature gradually and start timing only after the working temperature is reached.

Operating checks

  • Use electric heating rather than a naked flame for flammable organic solvents.
  • Add anti-bumping granules before heating, not to a hot liquid.
  • Do not infer a temperature, duration or scale when the source gives only the word ‘heat’; obtain the substrate-specific procedure first.

Filtration under reduced pressure

Collect an insoluble solid while drawing the liquid through a filter using reduced pressure.

Setup

  1. Clamp the flask and seat the paper with the specified solvent before collecting a cooled crystal suspension.
  2. Retain the filtrate until the desired solid has been recovered.

Operating checks

  • Use vacuum-rated glassware and the laboratory-approved vacuum setup.
  • Release the vacuum safely before shutting down the suction source. Filtration removes bulk liquid; further drying may be needed.

Melting range and solid purity

Record the interval from first melting to complete melting to compare a dry solid with reference data.

Setup

  1. Load a small, compact sample and heat slowly near its expected melting temperature.
  2. Record the start and end temperatures for crude, purified and reference samples under comparable conditions.

Operating checks

  • Impurities often lower and broaden the range; residual solvent can do the same.
  • A matching range alone cannot uniquely identify a compound. Decomposition is not ordinary melting.

Scope and limitations

Scope
The phenolic OH of salicylic acid becomes an acetate ester.
Limitations
The carboxyl group remains; identity and purity require separate analytical checks.

Related reactions

References

  1. A-level Chemistry 7405: Organic chemistryAQA · AQA specification

    Checked 2026-09-16. Supports A-level topic coverage, including acid anhydrides, acylation and aspirin, amines, amino acids, polymers, synthesis and analysis. Coverage varies by examination board.

  2. The preparation of aspirinRoyal Society of Chemistry · RSC Education

    Salicylic-acid acetylation with ethanoic anhydride, phosphoric-acid catalysis, crystallisation and suction filtration.

  3. The melting point of aspirinRoyal Society of Chemistry · RSC Education

    Dry samples and observed melting ranges as evidence of purity rather than a stand-alone identity claim.

  4. Analysis of aspirin tablets on a microscaleRoyal Society of Chemistry · RSC Education

    Supports iron(III) complex colour as a check for free salicylate in aspirin samples.

  5. Pearson Edexcel International Advanced Level Chemistry Student Practical GuidePearson Education Limited · Pearson qualifications · 2018

    Supports the practical distinctions between reflux, distillation, liquid-liquid separation, washing and drying in organic preparations.

  6. Evaporation, filtration and crystallisation: teaching practical scienceRoyal Society of Chemistry · RSC Education

    Distinguishes filtration, crystallisation and post-16 reduced-pressure isolation.