S Y N T H E S I S OF A S P I R I N

1. S Y N T H E S I S OF A S P I R I N a clil lesson for the fifth class liceo st G.Cragnolini I.T.I. Malignani - Udine

2. this lesson is thought to be delivered to a fifth class of the liceo st ; the aim is to improve both cognitive and psychomotor skills ( the latter in laboratory investigation); in a fifth class students are generally supposed to master well enough general chemistry and basic information on organic chemistry; to make the presentation more effective and students willing to pay attention, problem solving approach seems to be far the most effective, concept maps are also used; G.Cragnolini I.T.I. Malignani - Udine

3. COMPETENCE LEVELS • this topic will be worked out on competence levels of increasing difficulty : • knowledge : a simple presentation that mostly implies recall information; • 2) application : laboratory investigation ; this activity implies solving problems, using methods, applying knowledge in new situations …. ; • 3) analysis : experimental data are collected, arranged, compared and analyzed; • 4) synthesis : conclusions are drawn, single facts are generalized, diagrams are produced; G.Cragnolini I.T.I. Malignani - Udine

4. INTRODUCTION a short background : aspirin is one of the oldest drugs, patented in Germany by Bayer in 1893 ; it was invented in the late 1890s by a chemist F. Hoffmann who was seeking to ease his father's arthritis pain; biological activity : aspirin is painkiller ( analgesic ) , antipyretic ( fever reducer ) and anti- inflammatory side effects : aspirin may produce gastric irritation, bleeding at present : aspirin is a source for new analgesics G.Cragnolini I.T.I. Malignani - Udine

5. how aspirin works : Injuries to human tissue trigger the release of prostaglandins, hormone like molecules that cause fever and inflammation. Prostaglandins are produced by an enzyme, the prostaglandin H2 synthase, or PGHS. This enzyme contains two protein subunits, each with a long interior channel. Molecules of arachidonic acid enter these channels and undergo a chemical transformation converting to molecules of prostaglandin H2. Aspirin prevents this change by sealing the channels: the aspirin molecule's acetyl group binds to a site inside the channel, blocking the path of the arachidonic acid. G.Cragnolini I.T.I. Malignani - Udine

6. LEARNING OBJECTIVES: • by the end of this experiment, the students should be able to demonstrate the • following proficiencies: • Select the appropriate carboxylic acid and alcohol from which to synthesize an ester. • 2. Purify an impure solid by recrystallization. • 3. Predict the solubility of a compound in a particular solvent. • 4. Test the solubility of a compound in a variety of solvents. • 5. Determine percent yield for a reaction. G.Cragnolini I.T.I. Malignani - Udine

7. LESSON PLANNING G.Cragnolini I.T.I. Malignani - Udine

8. CONCEPT MAP FOR SYNTHESISThe production of aspirin from raw materials involves the following reactions : G.Cragnolini I.T.I. Malignani - Udine

9. practically : for our laboratory experience the aim is to prepare aspirin beginning with salicylic acid and acetic anhydride; never forget to focus what the molecules are doing while mixing materials together and carrying out the reaction : as you can see we're removing the hydrogen atom from the salicylic acid turning the hydroxy group into an acetyl group; by the way, salicilic acid also can react with acetic acid to form aspirin, according to the following equation: but this reaction gives a much lower yield than does the reaction we used in the experiment; G.Cragnolini I.T.I. Malignani - Udine

10. ANALYSIS • examine the crystals under a magnifying glass and • record your observations ; • find the mass of the dry crystals and record this amount in your lab notes. • 3) test few crystals of your prepared acetylsalicylic acid with iron(III) chloride ; • test the relative purity of a sample by determining its melting point ; • 5) the composition of your product could also be tested using a spectrophotometer. G.Cragnolini I.T.I. Malignani - Udine

11. ASSESSMENT FOR OBJECTIVES -- knowing that all the acids involved in these reactions are weak organic acids, explain why the reaction involving acetic anhydride produces a much greater yield than does the one involving acetic acid; -- Why did you add hot water to the crystals, and then cool the mixture? -- Explain why the crystals formed mostly when the test tube was in the ice bath, and not before. -- Use the mass of acetylsalicylic acid you actually produced to calculate your % yield ; PROBLEM SOLVING -- from the mass of salicylic acid you used in your experiment, calculate the maximum amount of acetylsalicylic acid you could have produced ; -- form a hypothesis to explain why your % yield was so low ; G.Cragnolini I.T.I. Malignani - Udine

12. HINTS FOR BRAINSTORMING -- consider the typical role of concentrated sulphuric acid in chemical reactions, and that weak acids usually are involved in equilibrium systems; -- as you look over the equations describing the synthesis you will notice that the sulphuric acid does not appear in any of them. What role does sulphuric acid play in this synthesis reaction? -- would the reaction happen without the acid ? -- can some substance other than sulphuric acid be substituted in the reaction? Explain ; -- were the new crystals the same substance as the old ones? -- what else could be in the test tube to make your product impure? -- was the iron(III) chloride test a good one to test the purity of an aspirin sample? explain; -- was the melting point test a good one to test the purity of an aspirin sample? Explain; G.Cragnolini I.T.I. Malignani - Udine

13. FILLING THE GAPS One common impurity in this synthesis is unreacted . One way to test for the presence of unreacted salicylic acid is by treating a solution of the aspirin product with Iron(III) chloride reacts with groups attached to aromatic rings, such as in salicylic acid, to form a colored complex. Esters, such as aspirin, do not react with . The solubility of a molecular solid is influenced by three factors: (1) the between solute molecules, (2) the strength of the interactions between molecules and (3) the strength of the interactions between solute molecules and molecules. Both salicylic acid and aspirin are polar organic compounds and, in their pure forms, the intermolecular forces present are , attractions and dispersion forces. One difference between these two compounds is in the atoms involved in hydrogen bonding. Aspirin forms intermolecular hydrogen bonds and salicylic acid forms intramolecular bonds,. When the solution is at room temperature and the aspirin has crystallized, filter with and wash the solid with a small amount of . Draw air through the funnel for a few minutes to help dry the crystals. G.Cragnolini I.T.I. Malignani - Udine

14. QUESTIONS 1) calculate the theoretical yield (in grams) of aspirin for this reaction (assume that salicylic acid is the limiting reagent) Theoretical Yield = ____________ 2. calculate the percent yield of aspirin obtained in this experiment. % Yield = ___________________ 3. rank the solubility of aspirin in the various solvents, from most soluble to least soluble. _______________ > _______________ > _______________ > _______________ > _______________ most soluble 4. explain this ranking, based on intermolecular forces and the generalization “like dissolves like.” 5. what impurities remain in the aqueous phase after the aspirin is recrystallized? 6. does your solid contain unreacted salicylic acid? How do you know this? 7. if the test was positive for unreacted salicylic acid, explain why your recrystallization did not remove all of the salicylic acid. G.Cragnolini I.T.I. Malignani - Udine

15. SAFETY CONSIDERATONS this experiment uses salicylic acid, acetic anhydride and phosphoric acid; the salicylic acid may cause irritation to your skin or eyes, but are basically not hazardous; an excess of these can be disposed of in the sink; if you spill some, wipe it up with a wet paper towel and throw the towel in the trash; the acetic anhydride and phosphoric acid can cause bad burns, use them in the hood; be sure to wear gloves and safety goggles when using these chemicals; excess chemicals must be disposed of in the plastic tub of water; this will convert the acetic anhydride to vinegar and dilute the phosphoric acid; If you spill a lot of either of these, notify your instructor. G.Cragnolini I.T.I. Malignani - Udine