Hands-on Activity:
    Making Aspirin

    This activity allows students to re-create the work of Felix Hoffmann and Arthur Eichengrün for themselves by synthesizing aspirin from salicylic acid. A helpful resource in carrying out this activity is SourceBook (Orna, Mary Virginia; Schreck, James O., and Heikkinen, Henry editors, ChemSource, Inc., 1998). This resource contains a macroscale aspirin synthesis that can be substituted for the microscale synthesis described here. Whichever version you choose, you are urged to look through both to see the similarities and differences in questions and extensions. Choose the parts that work for you and your classes.

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      Major Concept
      Expected Student Background
      Time Required
      Safety
      Advance Preparation
      Pre-Lab Discussion
      Anticipated Student Results
      Answers to Data Analysis
      Answers to Extensions
      Relevant National Science
      Education Standards
      Relevant New Jersey State Science
      Curriculum Standards

    Major Concept

    The synthesis of aspirin is classified as an esterification reaction. This is a substitution reaction where an alcohol (the –OH group from salicylic acid) reacts with an acid [anhydride] (acetic anhydride) to form an ester, acetylsalicylic acid (ASA).

    The first “symbolic equation” is given to help those students who might have difficulty seeing the subtleties of the actual reaction. This might be thought of as a more concrete approach at representing the reaction.

    The "symbolic equation"

    The proper chemical equation

    Expected Student Background

    It is assumed that students have read the background section dealing with salicylic acid, so they will know that ASA was produced from SA.

    Time Required

    The experiment will take one 50-minute class period for the synthesis, an overnight drying step, and a second day for final observations, measurements, calculations, and the color tests and melting point determination.

    Safety

    1. You should review all the safety concerns in this experiment before students may continue.

    2. Both the acetic anhydride and the sulfuric acid are potentially dangerous materials for students to handle. Thus, the directions state that the teacher will dispense these materials—and in a fume hood, for added safety. Dispense the two liquids from small LDPE dropping bottles (not wash bottles) to minimize your exposure, too.

    3. Even so, care must be taken to ensure that students do not spill these materials as they walk back to their lab stations. The teacher needs to be ever-vigilant.

    4. One student should remain with the hot plate at all times.

    5. The small amount of ASA produced in the experiment may be dumped down the drain if in solution, or thrown in the trash if still in crystal form.

    MSDS Sheets for Reagents Used

    The following MSDS sheets are available on-line from Cornell University:

      Acetic anhydride
      Iron (III) chloride hexahydrate
      Salicylic acid
      Sulfuric acid

    Advance Preparation

      For Day 1

      Prepare the acetic anhydride and concentrated sulfuric acid dropping bottles.

      Set out the small container of salicylic acid.

      Purchase commercial aspirin tablets for the iron(III) chloride test. (Or obtain them from the school nurse.)

      If you have access to a vacuum filtration system, its use will speed up the filtration process.

      For Day 2

      Prepare the 1% iron(III) chloride solution (1 g iron(III) chloride in 100 ml of solution).

      Be aware that students may not have enough product to do a melting point determination. You might want to take a few aspirins and mix them with some SA to make a mixture, and then ask students to use this (as representative of their product sample) to determine melting point ranges.

      Set up the mineral oil baths for the melting point determinations, if you plan to do this step. See page 9 of the Chemistry in Medicine module of the SourceBook for the materials and description of the apparatus and procedure.

    Pre-Lab Discussion

    1. Briefly explain the goal (synthesis) and the type of reaction (esterification). Make sure that the students grasp the connections among the macroscopic materials they are working with, the symbols written in the chemical equation, and the unseen molecules that are being torn apart and rebuilt at the microscopic level. While this seems simple, the connections are not always apparent to the students.

    2. Stress material hazards as listed in Student Version and in teacher notes above.

    3. Remind students to measure masses precisely.

    4. Review theoretical and % yield calculations. (These could wait until day 2.)

    5. Explain the iron(III) chloride test. Many phenols (R-OH) produce colored coordination compounds with iron(III) ions. These complex anions are composed of 6 molecules of the phenol combined with 1 iron(III) ion. Since salicylic acid has a phenolic –OH group, it produces the positive (purple) test with iron(III) chloride. When SA reacts completely to produce ASA, the phenolic group is replaced with an acetate (acetyl) group, so the iron test would be negative. Of course, students will not get 100% yield, so some SA remains to make their sample purple in the iron test.

    6. Describe the method of determining the melting point range (from the temperature at which solid first begins to melt to the temperature at which the solid is completely melted, if you do this part of the experiment).

    Anticipated Student Results

    1. The SA should turn dark purple; the prepared sample should be dark purple (due to SA contamination), and the commercial aspirin sample will probably be a pale orange color (indicating no SA contamination).

    2. This microscale experiment may not provide enough product sample to test melting point. While capillary tubes don't require much sample, students don't have much sample, either. If you want to pursue this experiment, refer to the SourceBook's Chemistry in Medicine experiment's Lab Activity: Teacher Notes, p. 9, which accompanies this module, for directions. These can be photocopied for student use. Values for melting point ranges will be broad, typically between 128 and 137°C, again indicating relative impurity.

    3. See p. 10 of the Teacher Notes from SourceBook's Chemistry in Medicine for a description of the experiment using a Spectronic 20 visible wavelength spectrophotometer to determine the amount of SA in the lab product versus that in an actual aspirin tablet.

    For more information, at other Web sites...

      "How to Make Aspirin Today" — a song about making aspirin by Thomas Ott, to the tune of the Sesame Street theme.

    Relevant National Science Education Standards

      Unifying Concepts and Processes — The students will learn the workings of a system that is the chemical reaction that produces aspirin.

      Science as Inquiry — The readings familiarize the students with the steps of scientific inquiry as they investigate the results of their reactions.

      Physical Science — Understanding the structure of molecules and chemical reactions are central to the activity.

      Science and Technology — The activity demonstrates the science that has been applied to pain-relief technology.

      Science in Personal and Social Perspectives — Personal health is central to this activity of aspirin synthesis.

      History and Nature of Science — The activity connects the students with the research of Felix Hoffmann and Arthur Eichengrün.

    Relevant New Jersey State Science Curriculum Standards

      5.1 The readings familiarize the students with the steps of scientific inquiry as they investigate the results of their reactions.
      5.2 Aspirin is a major discovery whose story nicely meets this standard. Here the students re-create that discovery.
      5.4 Many scientific principles must be applied to re-create the invention of aspirin.
      5.3 Mathematical calculations are central to this activity.
      5.6 This activity involves the students directly with changes taking place at the molecular level during the synthesis of aspirin.

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