Synthesis of Aspirin

1. Synthesis of Aspirin Min CheNancy HuiAmy QuRosie Zhang

2. Overview • Introduction • Experiment • Chemical Used • Equipment Used • Observation • Calculation • Conclusion and Analysis • Suggested Modifications • Sources of Error

3. Introduction • Medicinal properties • pain reliever • fever reducer • swelling-reducing drug • Active ingredient - salicylic acid • Most commonly used drugs

4. Introduction • Medicinal properties of acetylsalicylic acid known for millennia • 1800’s – Salicylic Acid isolated • 1893 – Felix Hoffmann Jr. synthesized acetylsalicylic acid

5. Experiment • Prepare aspirin by chemical synthesis • Esterification reaction • ester + acid -> more complex ester • Recrystallize to purify the product • Melting point and percentage yield determine the purity of the aspirin

6. Chemical • Acetic anhydride • Salicylic acid (solid) • Sulphuric acid • Ethyl alcohol • Distilled water Acetic Anhydride Salicylic Acid

7. Equipment • Beaker • Test tubes • Balance • Graduated cylinder • Thermometer • Dropper • Hot plate • Scoopula • Melttemp apparatus • Stirring rod • Watch glass • Buchner funnel • Two pieces filter paper • Wash bottle • Dessicator with silica

8. Procedures Synthesis of Aspirin • Heat a large beaker full of water to 75-85˚C. • Weigh out 3.0 g of salicylic acid and deposit in a large test tube. • Measure 6.0 mL of acetic anhydride and deposit into the test tube as well. • Add 10 drops of 85% sulphuric acid to the test tube and stir with a stirring rod. • Place the test tube in the large beaker of water on the hot plate, stirring occasionally for about 10 minutes.

9. Procedures Crystallizing the Aspirin • Remove beaker from heat and add 20 drops of cold distilled water to the test tube. • Allow the mixture to cool to room temperature. • Cool the mixture further by placing the test tube in a large beaker full of ice water to crystallize. • Weigh the filter paper with a watch glass and fill a wash bottle with around 25 mL of chilled distilled water. • Filter the solid aspirin. • Rinse the crystals and test tube with the chilled water. • Place filter with product in a watch glass to dry. • Weigh and measure the melting point range twice.

10. Procedure • Below: The crude aspirin. This sample weighs 2.96 g. • Above: Filtering the aspirin crystals using a Buchner funnel and aspirator.

11. Procedures Recrystallizing the Crude Aspirin • Dissolve crude aspirin in 10 mL of 95% ethyl alcohol. • Warm the mixture in a hot water bath. • When all the aspirin has dissolved, pour in 10 mL of lukewarm distilled water. • Cover the beaker with a watch glass and set aside to cool slowly undisturbed overnight. • Collect crystals using vacuum filtering. • Rinse collected crystals with cold distilled water. • Allow the crystals to dry using vacuum filtering. • Weigh the sample and calculate the percentage yield out of a maximum yield of 3.9g again.

12. Procedure • Left: Dissolving the crude aspirin. • Below: Filtering the purified aspirin.

13. Procedures Finding the Melting Point Range • Place about 5 mm of aspirin crystals into a capillary tube, which is then placed into the melttemp apparatus. • Insert a mercury thermometer through the top. • Heat the apparatus until 15˚C from the expected melting point (135˚C) at which temperature the heat should be reduced. • Record the range of the melting point as the temperature at which the first drop of liquid appears up to when all the aspirin has been converted into a liquid. • Repeat the process.

14. Procedure • The melttemp apparatus (left) and a view through it (below).

15. Final Product

16. Safety • Safety Goggles • Chemical (Acid) • Fumes • Hot Plate • Don’t leave unattended

17. Observation

18. Observation Theoretical Melting Range : 134 ~ 136

19. Equations The balanced equation isC4H6O3 + C7H6O3 → C9H8O4 + C2H4O2 Word Equation Acetic Anhydride + Salicylic Acid = Aspirin + Acetic Acid

20. Calculations Moles of a molecule = (Mass of substance)/(Molar mass) • Acetic Anhydride (C4H6O3): 102.09 g/mol • 6 g / 102.09 g/mol = 0.05877 moles • Salicylic Acid (C7H6O3): 138.12 g/mol • 3 g / 138.12 g/mol = 0.02172 moles • Aspirin (C9H8O4): 180.16 g/mol • Acetic Acid (C2H4O2): 60.05 g/mol

21. Calculations • Salicylic acid is the limiting reagent • Only 0.02172 moles of aspirin will be produced. • Mass of a substance = (Moles of a substance) * (Molar mass) • 180.16 g/mol x 0.02172 mol = 3.913g aspirin

22. Calculations Crude Product Maximum yield = 3.913 gActual yield = 2.96 gPercentage yield = 75.65% Final Product Maximum yield = 3.913 gActual yield = 2.67 gPercentage yield = 68.23%

23. Melting Range Percentage Error Crude Product Average of actual melting range = 120.25°CExpected melting point = 135°CPercentage error = |135 - 120.25| / 135 = 0.1093 = 10.93% Final Product Average of actual melting range = 133.5°CExpected melting point = 135°CPercentage error = |135 - 133.5| / 135 = 0.0111 = 1.11%

24. Conclusion and Analysis • Pure aspirin obtained after filtering • Check purity its melting point. • Impurities will always lower the melting point • Aspirin= Theoretical melting range of 134-136°C. • Final product = 129.5-137.5°C. • Large rigid crystal structure • Low percentage error • Final product was 1.11%. Success in synthesizing aspirin

25. Suggested Modifications to Procedure • Temperature rise at a rate of 1-2°C per minute • Humidity kept minimum • Acetic Anhydride, Aspirin decomposes • Phosphoric acid used instead of sulfuric acid • For higher yield • Slower process

26. Sources of Experimental Error • Thermometer inaccurately measured the melting range • Sensitive digital scale • Impurities in the reactants or final product • Contaminated lab equipments • Sulfuric acid used instead of phosphoric acid • Lower yield

27. End of Presentation Any Questions?