Adapted from ChemSource Vol.2, 1994, Chemistry in Medicine (MEDI)

Developed By:
Margaret DeLacy and Fred Weinhardt
Washington-Lee High School
1300 North Quincy Street
Arlington, VA 22201
703 358-6221

Time Frame:
2 class periods

Overview: In this laboratory activity students will explore the use of botanicals as medicines throughout history. Approximately 30% of all medicines have a plant origin. This number increases to 60% if you consider medicines that at one time were derived from plants, but have more recently been synthesized in the laboratory. Students will synthesize aspirin as an example of a medicine that was originally derived from a botanical source, the bark of the white willow tree. Aspirin (acetylsalicylic acid) will be synthesized using salicylic acid and acetic anhydride with sulfuric acid as a catalyst. The procedures used are very similar to the ones used by Felix Hoffman who first synthesized aspirin in 1893 (see Background in Student Notes).

The activity will begin with a class discussion on the use of aspirin throughout history. Students will then perform a two part laboratory, first conducting a reaction of salicylic acid with acetic anhydride (in the presence of sulfuric acid) recrystallizing the product, and then determining the percentage yield.

Student Objectives:
By the end of this activity, students should be able to:

• Understand the functional drawing of a chemical compound.

• Identify basic functional groups and understand how they can replace each other in a chemical molecule.

• Realize that slight modifications in chemical structure can alter a substance's effect on an organism.

• Understand how compounds can be synthesized.

• Understand the versatility of aspirin in treatment.

• Discuss the traditional use of herbs and plants as medicines.

Preparation/Procedure

1. Prepare the hot water baths on the hot plates, the burets or measuring pipets containing acetic anhydride, and the cold water bath (ice slurry in 400 mL beaker) immediately before class.

2. To "set the stage" for the aspirin synthesis, bring willow bark, willow leaves, and spiraea branches into the classroom. Discuss with students that these plants all contain salicin, a substance with analgesic characteristics, which is the precursor to salicylic acid. Hippocrates was making potions from willow trees back in the 5th century B.C. to control fever and ease the pain of childbirth. Reverend's Stone's letter concerning the benefits of willow bark would be appropriate to read and share at this point (see "An account of the use of willow in the cure of Ague" in the Supplemental Materials for this lesson).

3. Include information in the discussion about the negative side effects of salicylic acid (it was bitter and irritating when taken orally) and the attempts by chemists to alter the acid so it could be tolerated by humans and still be effective in reducing pain and fever. Salicylic acid was first neutralized with sodium to produce sodium salicylate, which had a better taste, but irritated the stomach a lot. Next, chemists modified the salicylic acid to produce phenylsalicylate, which when broken down, released the toxic substance phenol. Finally, acetylsalicylic acid, the compound we know as "aspirin," was produced and is the same compound the students will make in this lab (see "The Design Stages of Aspirin" in Supplemental Materials of the lesson How Aspirin Works.)

4. If students have not used a buret or set up a funnel/filtration system before, it may be necessary to demonstrate. Emphasize the importance of safety precautions when using acid. Explain that the reaction synthesis is quite vigorous and certain steps (addition of sulfuric acid, acetic anhydride, and water) need to be done in a fume hood.

5. Sequencing of the steps in the synthesis and crystallization of aspirin must be carefully monitored. The aspirin product may be set aside and air-dried for one or two days.

6. Students will need to understand that the process of creating the aspirin was very fast and that there is a good possibility that some impurities are present. Washing the aspirin with water helps purify the product. This is a good place to bring up issues such as quality control and the role of the FDA in setting standards for drug and medicine distribution.

7. The importance of getting an "actual yield" as close as possible to a "theoretical yield" when making medicines should be stressed in the context of manufacturing economics and its impact on rising medical costs that are passed on to the patient.

8. Close observations of the crystal structure should be noted and the aspirin saved for future use in the lab How Aspirin Works.

The addition of acetic anhydride and water to the reaction mixture produce a vigorous reaction with some vapor. If possible, add these substances in a fume hood. If a fume hood is not available, perform the experiment in a well-ventilated area.

CAUTION: Remember to always add acid to water when diluting acid with water. Concentrated sulfuric acid is dangerous! To avoid mishaps, the teacher should administer 5 drops of the acid to the aspirin mixture under a fume hood at the appropriate time, with both students and teacher wearing goggles and lab aprons. For additional safety precautions, or to save time, the teacher may want to measure and distribute the salicylic acid and acetic anhydride for the students.

Do not wait long after measuring out the acetic anhydride, as the substance will evaporate quickly, and will effect yield.

If the students are not experienced working with acids, this activity can be done as a demonstration. The yield is substantial and one execution will produce enough aspirin for an entire class to use for the How Aspirin Works activity. Use beakers and lab equipment that are glass, not plastic. The aspirin will adhere to the plastic and much of the yield will be lost.

During wait time, students can begin to answer follow-up questions, read articles from the Supplemental Material, or work out equations for the reaction taking place.

To decrease wait time for filtration, you may want to use a vacuum filtration system. This requires a Buchner funnel, rubber disk, and filter flask with a water aspirator attachment.