Synthesis and Characterization of Aspirin

SYNTHESIS AND CHARACTERIZATION OF ASPIRIN AND % COMPOSITION OF AN ASPIRIN TABLET Reference: Londa L. Borer & Edward Barry, Journal of Chemical Education, Vol 77, No 3 March 2000 Theory Aspirin is a common pharmaceutical product used to relieve aches and pains, to reduce inflammation and to lower fevers. The chemical name is acetylsalicylic acid (ASA). Aspirin is a weak acid with Ka = 3.27 × 10-4. O

C

OH O

C

O

CH3 acetylsalicylic acid (aspirin)

In most medications, the active ingredient is only a part of the entire capsule. Aspirin is a relatively old drug; however it is still in use. Some of the current research includes gastrointestinal effects and its possible use in preventing heart attacks. In this series of experiments, you will synthesize aspirin and characterize it using TLC and m.p. Fillers are used to counteract the side effects of the drug. In this lab, the filler is removed and is tested for the presence or absence of starch.

Procedure Synthesis and Purification of Aspirin Aspirin can be prepared by the reaction of acetic anhydride and salicylic acid in the presence of an inorganic acid as a catalyst. The reaction takes place at the phenol functional group.

O

C

OH

O

OH +

Salicylic Acid

H3C

O

O

C

C O

H+ CH3

Acetic anhydride

C

OH O

C

O

O

CH3 Acetylsalicylic acid (aspirin)

+

H3C

C

OH

Acetic acid

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Weigh ~ 0.42 g of salicylic acid (MW = 138.1) in a small test tube. Add a boiling chip. Add 3 drops of phosphoric acid followed by 30 drops of acetic anhydride (MW = 102.1, d = 1.08 g/mL). Make sure to recap the bottle of acetic anhydride. Mix the reactants in a vortex mixer. Cork the test tube loosely. Clamp the test tube in a water bath (use a 400 mL beaker half filled with water as the water bath) maintained between 90 ° and 100 °C. The mixture is heated for about 10 minutes. If all the salicylic acid is not dissolved, add 10 more drops of acetic anhydride. Continue heating for 5 more minutes. Add 2 mL of water dropwise to the mixture and mix well. Cool the test tube to room temperature. If aspirin crystals do not form, scratch the inside walls of the test tube and then place the test tube in an ice bath. Filter the crystals using suction filtration. Dry the crystals in an oven at 100 °C for 20 minutes. Determine the yield of aspirin and its melting point. The reported melting points of pure aspirin are 135 -136 °C and that of salicylic acid is 159 °C.

Purity of Prepared Aspirin Thin layer chromatography can be used as an indication of purity. Prepare separate samples of salicylic acid, prepared aspirin and commercial aspirin samples in methanol. You have to grind the commercial aspirin sample before dissolving in methanol. All of the commercial aspirin sample may not dissolve in methanol. Spot a TLC plate with all samples. Develop a TLC plate in a jar which contains a developing solution of ethyl acetate - ethanol – acetic acid (25:1:1). The spots can be detected under a UV lamp. Determine Rf values and compare the prepared aspirin to commercial aspirin.

Ferric Chloride Test You can perform this test on a sample of your product that is not completely dry. To determine if there is any starting material (salicylic acid) present in the product, carry out the following procedure. Obtain 3 small test tubes. Add 0.5 mL of water to each of the 3 test tubes. Dissolve a small amount of salicylic acid to first test tube, add a similar amount of your prepared aspirin to the second test tube and us ethe 3rd test tube as a control. Add 1 drop of 1% ferric chloride solution to each test tube, shake and observe the color. The presence of salicylic acid is usually indicated by a color ranging from red to violet.

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THE PERCENT COMPOSITION OF AN ASPIRIN TABLET A. Analysis Of The Theoretical Percent ASA In An Aspirin Tablet Record the mass of three aspirin tablets separately. Using the stated amount of acetyl salicylic acid/tablet, calculate the theoretical percent of acetylsalicylic acid in each tablet. Average the results. What percent of the total weight of the tablet is active ingredient?

B. Analysis Of The Filler in the Commercial Tablet To a commercial aspirin solid tablet, add 2-3 drops of iodine solution. For comparison, place a few drops of iodine solution on a slice of potato.

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SYNTHESIS AND CHARACTERIZATION OF ASPIRIN AND % COMPOSITION OF AN ASPIRIN TABLET YOUR NAME ______________________________ Results and Conclusion

SYNTHESIS AND PURIFICATION OF ASPIRIN

Mass of salicylic acid (g)

_____________

Mass of aspirin (g)

_____________

Melting point of aspirin (lit) °C

_____________

Melting point of aspirin (prepared) °C

_____________

Theoretical yield of aspirin (g)

_____________

Percent yield of aspirin (g)

_____________

Show work.

Sketch the TLC plate used in this experiment. Label the spots. Comment on the purity of the prepared aspirin.

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List the Rf values. Salicylic acid

_____________

Aspirin (commercial)

_____________

Aspirin (prepared)

_____________

Explain your observations of the ferric chloride test.

THE PERCENT COMPOSITION OF AN ASPIRIN TABLET Analysis Of The Theoretical Percent ASA In An Aspirin Tablet

Aspirin tablet 1

Aspirin tablet 2

Aspirin tablet 3

Mass in g

ASA/tablet in g

Theoretical % ASA/tablet

Average theoretical % ASA/tablet =

Analysis Of The Filler in the Commercial Tablet Comment on the composition of the filler based on your observations.

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