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Experiment 6- Aspirin
Introduction Aspirin is probably the most recognizable analgesic (pain reliever) in use today. It was first synthesized in 1893 at the Bayer Chemical Company in Germany from salicylic acid. Salicylic acid was first marketed for pain relief in 1763 though it has a sour taste and irritates the mouth and stomach lining. Aspirin (acetylsalicylic acid) did not have as severe side effects. Many other derivatives of salicylic acid have been tried, but none work as well as aspirin. In addition to analgesic properties, aspirin is also an antipyretic (fever reducer) and an antirheumatic (used in treating arthritis). Side effects of aspirin, besides stomach irritation, include thinning of the blood and possible allergic reactions. Many commercial suppliers of aspirin use additives such as sodium bicarbonate, sodium citrate, aluminum hydroxide and others to counteract the acidity of aspirin. In general, all brands of aspirin work about equally well. In recent years other analgesics, acetaminophen and ibuprofen, have gained widespread over the counter use. The chemical structures of these, as well as aspirin are shown below.
UeWr 6 c o la r t s od .0 r te o

v w a ino hp tu . ie Mc t s ic re

Acetaminophen, found in Tylenol and Datril, has both analgesic and antipyretic activity. Acetaminophen does not reduce swelling but is the only analgesic of these three which is recognized as safe for use during pregnancy. Ibuprofen, the active ingredient in Motrin, Advil and Nuprin, is not only a pain reliever, but is also an excellent antiinflammatory agent and is comparable to aspirin in

30 the treatment of arthritis. The antiinflammatory activity is attributed to the fact that these agents inhibit prostaglandin synthesis in the body. Several products, such as B.C. powders and Goody's headache powder, are available which contain a combination of more than one type of analgesic. In today's experiment, you will synthesize aspirin from salicylic acid and acetic anhydride as shown in the figure above. This synthesis involves making an ester from an alcohol and an anhydride. There are also other good methods used to make esters. Laboratory Activities A. B. Make aspirin from salicylic acid and acetic anhydride. Purify your aspirin by recrystallization from toluene (at the discretion of the instructor)

Precautions Both acetic anhydride and sulfuric acid are corrosive. Exposure to excessive amounts of toluene should be avoided. Do not eat the aspirin that you make.

31 Aspirin Synthesis Place about 2 g (record exact mass) of salicylic acid in a 125 mL Erlenmeyer flask. Using a pipette, add: 5 mL of acetic anhydride (caution: corrosive) 5 drops of conc. sulfuric acid (caution: corrosive) 1 boiling bead or boileezer Place the mixture on the large hotplate in the hood which is set on the lowest heat setting. Swirl the flask frequently as it is gently heated for 20 minutes. The solution should be tan to light amber in color upon completion of the reaction. An excessively dark color, formed when overheated, could indicate decomposition.

Crystallization of product Remove flask from hot plate and allow it to cool for 5 minutes. After the cooling, slowly add about 1 mL of water, swirling the whole time. Place flask in an ice-water bath and allow it to cool thoroughly. Once cool, slowly (especially at first) add an additional 50 mL of water using a pipette, constantly swirling. Once crystals have begun to form, the water can be added more rapidly. During this procedure, crystallization may be induced by gently scratching the inside of flask with a glass stirring rod (ask your instructor about the proper technique here). Cooling too rapidly or adding the water too fast may result in the product oiling out instead of crystallizing (and this may happen even when one is patient and careful). If the product oils out, crystals may still be obtainable. As soon as the oil droplets are noticed, reheat the mixture until it is homogenous, remove from the hotplate and allow to slowly cool to room temperature, and finally cool in an ice-water bath before resuming with water addition. Once again scratching the sides may help. A seed crystal may help in very stubborn cases.

32 Isolation of Crystals Collect the aspirin crystals by vacuum filtration through a bchner funnel. Make sure you wet the filter paper with cold water before pouring your crystals in. Rinse with three 5-mL portions of ice-cold water to help remove impurities. Leave crystals in the funnel with the aspirator on, drawing air through the crystals until dry. Transfer the impure crystals to dry, preweighed paper and determine the mass of the product.

33 Recrystallization At the discretion of the instructor, you may purify the aspirin by recrystallization from toluene. Place the sample of impure aspirin in a small Erlenmeyer flask and add 5 mL of toluene and a boiling stone. Heat the mixture almost to the boiling point in the hood. If all of the aspirin is not dissolved at this point, add 1 mL of toluene and continue heating. Repeat this process until it is completely dissolved (it is important to have it dissolved completely, otherwise you will not obtain pure aspirin). If there is any water present, then you will see a layer of water on the bottom of the flask. If this happens, pour the top layer (aspirin/toluene) into another flask while leaving the water behind. Once the sample has dissolved completely at the boiling point, remove from the hot plate and allow to cool slowly. Once cooled to room temperature, immerse the flask in an icewater bath to maximize crystal formation and then collect the crystals using suction filtration. If necessary, rinse crystals out of flask using ice-cold toluene.

Melting Point Analysis of Product At the discretion of the instructor, the identity and purity of the aspirin can be confirmed by measuring the melting point. Place a small quantity of thoroughly dry (ideally, let aspirin dry for a few days) product in a capillary tube such that the sample is 1-2 mm high when packed. Your instructor will demonstrate the proper method of packing the tube and operating the melting point apparatus. A melting point that is close to the standard value is one indication of the identity of your product. Likewise, a significantly different melting point may indicate that a different product has formed. Generally an impure product will melt over a range of greater than 2C and will be lower than the melting point of the pure product. Pure aspirin melts from 138-140C.

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Experiment 6 Laboratory Record

Data and calculations: mass of salicylic acid used: formula weight of salicylic acid: moles of salicylic acid used: volume of acetic anhydride: density of acetic anhydride:

Name:_______________________

__________ grams 138.12 g/mole __________ moles __________ mL 1.082 g/mL

formula weight of acetic anhydride: 102.09 g/mole moles of acetic anhydride: __________ moles

Use structures and write the balanced equation for the formation of aspirin in this experiment (salicylic acid + acetic anhydride gives aspirin + acetic acid)

limiting reagent: formula weight of aspirin: theoretical yield:

________________ 180.16 g/mole __________ grams

Record observations during reaction (while heating on the hot plate)

Record observations from crystallization (adding water, cooling, filtering)

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mass of impure aspirin crystals: percent yield

__________ grams __________ %

If you purified the aspirin by recrystallization, answer the following: amount of toluene required __________ observations during recrystallization:

mass of purified aspirin: _____________ percent yield of purified aspirin: ________% observed melting point range of purified aspirin _____ - _____ C

Answer each of the following questions: 1. At the end of the synthesis part of the procedure, it was suggested that you rinse your crystals with cold water. a) What were you trying to remove? (list several likely compounds)

b)

What would happen if you used warm water instead?

2. You used acetic anhydride as a reagent to make aspirin. Write 2 different complete reaction equations showing other reagents (which are not acid anhydrides) which could also react with salicylic acid to make aspirin.