SYNTHESIS OF ASPIRIN
"For cold or fever, the minor pains of arthritis, headache... or for just about whatever ails you... more doctors recommend ASPIRIN." So the TV and magazine advertisements tell us, and we must believe it because aspirin is the most widely bought and used drug in the history of modern medicine. Aspirin acts upon the central nervous system, suppressing pain and fever.
Aspirin (acetylsalicylic acid) is formed by the reaction between acetic acid and salicylic acid.
This esterification reaction is reversible, however, and the presence of water can lead to hydrolysis of the aspirin. Thus, an anhydrous (“without water”) reagent could lead to better yields of product. This reagent is acetic anhydride.
Acetic anhydride is a clear, colorless, mobile (free-flowing) liquid with a sharp odor similar to that of acetic acid. It hydrolyzes in water to yield acetic acid. In its liquid or vapor state, acetic anhydride can irritate body tissues, possibly leading to the death of such tissue. Acetic anhydride melts at –73°C, boils at 139°C, and has a density of 1.080 g/mL at 15°C. It is flammable with a flash point of 54°C. This compound is readily combustible and represents a fire hazard.
In this experiment you’ll synthesize the organic molecule we call aspirin (acetylsalicylic acid).
Procedure:
Weigh out 0.9 – 1.1 grams of salicylic acid (record exactly how much you used) and mix it with 2 mL of acetic anhydride in a 50-mL Erlenmeyer flask. CAUTION: Acetic anhydride is a reactive chemical that can cause skin burns on contact; if you get some on your hands, wash immediately with soap and water, and try not to inhale acetic anhydride vapors. Swirl, and then add two drops of concentrated sulfuric acid. Note the change in temperature of the mixing flask. Prepare the apparatus shown.
Heat the water in the 400-mL beaker to boiling. Then place the Erlenmeyer flask in the hot water for 5 minutes. Remove the flask from the beaker, add 20 mL of distilled water to the reaction flask, and stir the mixture to keep the organic material broken up. After adding the distilled water, return the flask to the boiling water bath, and continue to heat for 5 to 10 minutes.
Remove the reaction flask from the heating bath, and allow the mixture to cool slowly to room temperature. The aspirin should begin to crystallize upon cooling. After the aspirin has cooled to close to room temperature, put the Erlenmeyer flask into an ice bath for a while to complete the crystallization. Filter the product using a suction filtration apparatus, and wash twice with 15-mL portions of cold distilled water. Transfer the wet aspirin to a double layer of filter paper on a watch-glass. Carefully place the aspirin in your drawer until next week to allow it to dry. Next week, you will weigh the crystals, and record the melting point range.
Suction Filtration
Assembled Apparatus Filter Flask Büchner Funnel Neoprene Adapter
1. Clamp your filter flask to a support rod.
2. Place a neoprene adapter in the neck of the flask.
3. Place the Büchner funnel on the neoprene adapter.
4. Place a piece of 5.25 cm filter paper in the Büchner funnel, and wet it with a few mLs of water.
5. Connect the filter flask to the water aspirator with your thick tubing, and turn on the aspirator to start the vacuum.
6. Pour the aspirin solution into the funnel. You may need to press down on the funnel to initiate the vacuum. Scrape the crystals out of the beaker with your spatula. You may rinse the container with a few mLs of cold water solvent to get the last little bit out.
Melting Point Determination
Melting point (although more accurately it should be called melting range) is a fundamental physical property of a substance. A pure substance should have a melting range of one degree of less. The melting range should also be close to the reported value in the chemical literature. Impure substances usually have wide melting ranges (over several degrees), and generally melt lower than the reported value.
There are several techniques and pieces of apparatus that can be used to take a melting point. We will be using the Meltempâ apparatus. Although rather simple-looking, this apparatus costs over $300 to replace now, so handle it carefully!
The melting point of a substance is determined in the following manner.
1. Introduce a small amount (about 1-2 mm) of dry, finely powdered crystals into a capillary tube. Be sure that the crystals pack tightly. This can be accomplished by tapping the closed end of the capillary tube on the bench top.
2. Place the capillary tube (closed end down) in the slot of the Meltemp®. Be careful not to break the tube in the apparatus. Notice that the Meltemp® can hold three tubes at once.
3. Heat the sample and record the melting range. This range starts when the sample just begins to liquefy, and ends when the sample has totally liquefied. You will have to look in the eyepiece and watch the sample. When the sample just begins to liquefy, you will have to look up at the thermometer and record the temperature. You then look back down at the sample and watch it until it has totally liquefied, then look back up at the thermometer, and record this temperature.
The rate of heating is critical for obtaining a good melting point. If you heat the apparatus too fast, you may miss the end of the melting range, because the sample will have completely melted before you can look back down at it. Therefore, you should set a rate of heating of no more than about 5° per minute while your sample is melting. This is done by adjusting the voltage appropriately. For example, let’s assume you have a sample that melts at 150°. Looking at the table of heating curves, you can see that some voltage settings would not be appropriate. Voltages of less than 40 would never reach 150°. Voltages of 80 or higher would have the temperature increasing so rapidly, you would miss the melting point. A voltage in the range of 50-60 would have a reasonable rate of temperature increase, and would probably work well. Notice that at 50 volts, it would take approximately 12 minutes to reach 150°.
Precautions:
1. The heating block of the Meltemp® gets very hot (surprise!). Therefore, do not touch it with your fingers or nose (yes, your nose can get close to it) when taking a melting point.
2. Check the temperature on the thermometer before you insert your capillary. If the temperature is higher than the melting point of your sample, it will melt immediately, and you will have to prepare another sample.
3. Don’t break off the capillary tubes in the Meltemp®. If you do, or if you find broken tube pieces in a Meltemp®, please notify your instructor so it can be cleaned out. Broken tubes reduce the efficiency of the apparatus.
Formal Report Format
This needs to be typed, except for calculations, which may be written in neatly in ink. Use the headings provided.
1. Title Page
a. Descriptive title with between 15-25 words (yes, I count them!)
b. Your Name(s)
c. Date(s) the experiment was performed
d. Course and section number
Start the rest of the report on a new page
2. Purpose of the experiment: What did you do? Why is aspirin an important compound to make?
3. Procedure and observations. Write down the exact procedure you used, including the amounts of each chemical. If you did something different than the given procedure, explain what you did and why. Include any observations made while you were doing the experiment: odors, a change in temperature, a solid dissolving, a solid forming, etc.
4. Data and Calculations: Show all of your work, including units.
a. Grams of salicylic acid used.
b. Grams of aspirin produced.
c. Melting point range of aspirin.
d. Calculate the number of moles of salicylic acid.
e. Calculate the number of moles of acetic anhydride.
f. Which has the fewest number of moles?
g. How many moles of aspirin could you make? Explain.
h. Calculate the maximum number of grams of aspirin you could have made. This is the theoretical yield.
i. Calculate your percent yield. This is 100 times your grams of aspirin, divided by the theoretical yield.
5. Questions
a. How pure do you thing your aspirin is? What does the appearance indicate about the purity? What does the melting point range indicate about the purity?
b. Why did we use an excess of acetic anhydride in this experiment?
c. Find three over-the-counter medications that contain aspirin. For each, list the name of the medication, the amount of aspirin it contains, and what other active ingredients it contains, if any, and their amounts. Also list what medical problem the aspirin is supposed treat.
6. Conclusion: How successful was your experiment? Explain your reasoning. Suggest one thing we could have done to try to improve the percent yield of aspirin. Tell why you think this suggestion should improve the yield. Try to limit your suggestion to something that could realistically be done in our laboratory period.