Lab 5: Synthesis of Aspirin Objectives: - To synthesize aspirin and better understand carbonyl chemistry. - To analyze the aspirin for impurities.
Introduction: Aspirin (acetylsalicylic acid) can be prepared by the reaction between salicylic acid and acetic anhydride:
O OH O OH
OH O O O H+ O + + O O HO
In this reaction, the hydroxyl group (-OH) on the benzene ring in salicylic acid reacts with acetic anhydride to form an ester functional group. Thus the formation of acetylsalicylic acid is referred to as an esterification reaction. This reaction requires the presence of an acid catalyst, indicated by the H+ above the equilibrium arrows.
When the reaction is complete, some unreacted salicylic acid and acetic anhydride will be present, along with acetylsalicylic acid, acetic acid and the catalyst. Crystallization will be used to purify the acetylsalicylic acid. The purification process is facilitated by the addition of water after the crystals have formed. The water decreases the solubility of acetylsalicylic acid and dissolves some of the impurities.
The most likely impurity in the final product is salicylic acid itself, which can arise from incomplete reaction of the starting materials or from hydrolysis (reaction with water) of the product during the isolation steps. The hydrolysis reaction of acetylsalicylic acid produces salicylic acid. Salicylic acid and other compounds that contain a hydroxyl group on the benzene ring are referred to as phenols. Phenols form a highly colored complex with ferric chloride (Fe3+ ion). Aspirin is not a phenol because it does not possess a hydroxyl group has been converted to an ester. Because aspirin will not give the color reaction with ferric chloride, the presence of salicylic acid in the final product is easily detected. The purity of your product will also be determined by obtaining the melting point.
Pre Lab Questions: (To be submitted at the beginning of the lab period; 5 pts) 1. Summary of the procedure in your own words. 5-6 sentences is sufficient. 2. What temperature is the reaction run at and why is it heated? 3. Why is the mass of product determined on a different day than the reaction is run? 4. What type of melting point would you expect from an impure product?
Edited by M. Boeckl 2/10/11 1 Procedure: 1. Prepare a hot water bath using a 100-mL beaker and a hot plate. Use about 80 mL of water and adjust the temperature of the hot plate to 80-100°C. The temperature of the water should be about 50°C to run the reaction.
2. While the bath is coming up to temperature, weigh approximately 1.10 g salicylic acid (MW = 138.1 g/mol) and place this in a 10-mL Erlenmeyer flask. Record the actual weight.
3. Using the preset pump, dispense 2.5 mL of acetic anhydride (MW = 102.1, density = 1.08 g/mL) directly to your reaction flask. To use the pump, raise the top part straight up and then slowly lower it to dispense the liquid. Then add 4 drops of concentrated phosphoric acid. Use caution with both the acetic anhydride and the phosphoric acid. Also add a magnetic stir bar to the flask.
4. Once the bath has come up to temperature, clamp the flask so that the flask is partially submerged in the hot water bath. Stir the mixture with the magnetic stir bar until the salicylic acid dissolves. Heat the mixture for another 10-12 minutes after the solid dissolves to complete the reaction.
5. Remove the flask from the water bath. Remove the stir bar with a forceps or by using a larger magnet on the outside of the flask. The stir bar can also be recovered after filtration.
6. Allow the flask to cool to room temperature during which time the acetylsalicylic acid should begin to crystallize from the reaction mixture. If it does not crystallize, scratch the bottom of the flask with a glass rod. If necessary place in ice-water and scratch again after 5 minutes if no crystals form.
7. After crystal formation has started cool the flask for another 5 minutes on an ice-water bath until crystal formation is complete (usually when the product appears as a solid mass). At this point add 5 mL of cold water and stir with a glass rod.
8. Collect the product by vacuum filtration on a Buchner funnel. Make sure you have filter paper in your Buchner funnel and moisten it with water before you start filtering. When you have removed as much product as possible for the flask, add 5 mL of cold water to the flask, swirl the flask, and transfer the remaining crystals and the water to the Buchner funnel.
9. When all the crystals have been collected in the funnel, rinse them with several 2-mL portions of cold water.
10. Continue drawing air through the crystals on the Buchner funnel by suction until the crystals are nearly dry (approximately 5 minutes). Remove the crystals from the funnel and put them into a small pre-weighed beaker. A small portion will be removed to run the ferric chloride test and the rest will be allowed to dry until the next class period.
Edited by M. Boeckl 2/10/11 2 11. When you return to lab another day, weigh the dry product and calculate the percentage yield of acetylsalicylic acid (MW = 180.2). Determine the melting point of the product. The literature melting point is 135-136 °C.
Ferric chloride test for purity
Use the ferric chloride test to determine if there is any salicylic acid remaining in your product by carrying out the following procedure. Obtain three small test tubes. Add 0.5 mL of water to each test tube. Dissolve a small amount (about 0.05g) of salicylic acid in the first tube. Add a similar amount of your product to the second tube. You might need to put the test tubes in some hot water to dissolve the salicylic acid and your product. The third test tube, which containing only solvent, will serve as the control. Add one drop of 1% ferric chloride solution to each tube and note the color after shaking. Formation of an iron-phenol complex with Fe(III) gives a definite color ranging from red to violet, depending on the particular phenol present.
All liquid waste should go into the organic waste; the solid waste should go into the solid waste
Lab Report Guide: 1. Results (5 pts) o Calculate the percentage yield (show work, including calculating the limiting reagent). o Clearly state the result of the melting point and ferric chloride tests. Compare your melting point to the literature value.
2. Post Lab Questions (5 pts) Please type answers (State the answer to the question followed by a brief description of the evidence supporting that answer.)
1. Give three reasons why the % yield was less than 100%. Each reason should be specific to our procedure. For example, product left on glassware is not specific enough because it applies to almost procedure. Give reasons specific to this technique. 2. Describe the color, shape and size of the crystals formed. 3. Why do impure materials tend to melt at lower temperatures than pure ones? 4. If you were to repeat this experiment, what would you do differently? 5. Salicylic acid contains two acidic groups: a carboxylic acid and a phenol. Why might it be desirable to do away with one of these groups by converting salicylic acid into aspirin?
Edited by M. Boeckl 2/10/11 3