13.1: Synthesis of Aspirin Lab Procedure

Learning Objectives

• Synthesize Aspirin

 

Background

Over history, many compounds obtained from nature have been used to cure ills or to produce an effect in humans. These natural products have been obtained from plants, minerals, and animals. In addition, various transformations of these and other compounds have led to even more medically useful compounds. During this semester, you will have an opportunity to isolate some pharmacologically active natural products and to synthesize other active compounds from suitable starting materials.

Analgesics are compounds used to reduce pain, antipyretics are compounds used to reduce fever. One popular drug that does both is aspirin. The Merck Index, which is an encyclopedia of chemicals, drugs and biologicals, lists the following information under aspirin: acetylsalicylic acid; monoclinic tablets or needle-like crystals; mp 135 °C (rapid heating); is odorless, but in moist air it is gradually hydrolyzed into salicylic and acetic acids; one gram dissolves in 300 mL of water at 25 °C, in 100 mL of water at 37 °C, in 5 mL alcohol, in 17 mL chloroform.

An aspirin tablet contains a small amount of aspirin (usually 300-400 mg) in a starch “binder” and sometimes contains other ingredients like caffeine and buffers. When aspirin is ingested, it is broken down to salicylic acid by the basic conditions in the small intestine. It is then absorbed into the bloodstream.

In this experiment, the salicylic acid is the limiting reactant and the acetic anhydride is in excess. After the reaction heating period is over, the excess unreacted acetic anhydride will be hydrolyzed by the addition of water to the mixture: water reacts with acetic anhydride to form 2 molecules of acetic acid.

The solid synthesized aspirin will be collected using vacuum filtration. Any other reaction ingredients that are soluble (this includes acetic acid, phosphoric acid, and water) will pass through the filter paper.

The collected aspirin will be tested for its purity using FeCl3 (aq). Iron (III) ion reacts with phenols to form a purple complex. Salicylic acid contains a phenol group, but acetylsalicylic acid does not. Therefore, if you add FeCl3 to an aspirin sample and you see a purple color, it means that there is still some salicylic acid present and the sample is impure.

The collected aspirin will then be purified by recrystallization. In this purification method, the crude aspirin will be dissolved in a small amount of warm ethanol. Water will then be added and the solution will be cooled slowly and then chilled. The acetylsalicylic acid will recrystallize, and the solid impurities (unreacted salicylic acid) should remain dissolved in the solution. The solid aspirin will again be collected using vacuum filtration and tested for purity. This aspirin should be purer than the original aspirin.

The final product will be dried and weighed and the theoretical and percent yields will be calculated.

 

Experimental Procedure

Materials and Equipment

125-mL Erlenmeyer flask, 400-mL beaker, hot plate or Bunsen burner, ice, salicylic acid, acetic anhydride, 5- or 10-mL graduated cylinder, stirring rod, 600-mL beaker, dropper, 85% phosphoric acid (H3PO4), iron (III) chloride solution, ethanol, Buchner filtration apparatus, filter paper, spatula, watch glass, thermometer, ring stand and ring clamp, capillary tube, latex tubing/rubber band.

 

Safety

• Acetic anhydride is irritating to the nose and sinuses. Keep this compound under the hood at all times, and avoid breathing the vapors. Keep the acetic anhydride bottle capped after taking out the reagent.
• The aspirin that you make in this lab is NOT pure enough to be taken internally! Do not ingest the aspirin! Wear your safety goggles and gloves, especially when handling concentrated phosphoric acid.
• Waste Disposal:
  • All waste must be placed in the organic waste containers in the fume hood.
  • Be especially careful when handling the phosphoric acid and acetic anhydride.

 

SYNTHESIS OF ASPIRIN (acetylsalicylic acid)

1. Weigh out about 1 gram of salicylic acid on a piece of weighing paper. To do this, first weigh a piece of weighing paper. Place some salicylic acid on the weighing paper and weigh again. Add or remove solid until you have about 1 gram of it on the paper. Record the mass of the weighing paper plus the solid. Subtract to determine the mass of the salicylic acid. Place this solid into a 125-mL Erlenmeyer flask.
2. In the hood, measure out 3.0 mL of acetic anhydride in a small graduated cylinder and add it to the flask.
3. Add 3 drops of concentrated (85%) phosphoric acid. This will be the catalyst for the reaction.
4. Start heating the reaction, and stir gently with a stirring rod. Once the water bath starts boiling, start timing the reaction. When the mixture has been allowed to react at 100°C (the temperature of boiling water) for 15 minutes, you can consider the reaction to be complete. During the heating time, put 3 mL of water in each of two test tubes and chill these two test tubes in an ice bath. (These tubes of cold water will be used to rinse the solid aspirin after you collect it on the filter paper.)
5. After the reaction has gone on for 15 minutes at 100°C, add 1 mL of deionized water to the flask. This water will react with any excess acetic anhydride, converting it to acetic acid.
6. Remove the flask from the water bath. Add 9-10 mL of deionized water to the flask and swirl it around to mix it. As the flask cools, crystals of aspirin will start to form. When you see crystals, put the flask in an ice bath for 10 minutes. If acetylsalicylic acid does not begin to crystallize out, scratch the walls of the flask with a glass rod.

 Vacuum filter the product using a Buchner funnel (see figure below for setup). You can use some of the filtrate to rinse the Erlenmeyer flask if necessary. After the liquid has gone through the funnel, pour one of the 3-mL portions of chilled rinse water over the sample to rinse it. When this water has gone through the funnel, rinse the solid with the second chilled portion of water. Leave your aspirin on vacuum for several minutes – this will draw air through the sample and will help dry the aspirin.

Figure \(\PageIndex{1}\): Collecting the crude Aspirin. Apparatus for vacuum filtration Image from: Wikipedia

 

Recrystallization of Aspirin

1. Set aside a small amount of the crude aspirin you obtained– you will test its purity later. (You will need enough to test its melting point and to test its reactivity with FeCl3.)
2. Transfer the rest of the crude aspirin to a 50-mL Erlenmeyer flask. Add 4 mL of ethanol and warm the flask on a hot plate until all of the solid dissolves. Immediately remove the flask from the heat and slowly add 13 mL of cold water. Crystals should form. Chill this solution in an ice-water bath, and collect the crystals using vacuum filtration as you previously did.
3. Carefully lift the filter paper with the crystals on it and place it on a clean watch glass. Leave this aspirin in your bin to dry until the next laboratory period.
4. At the following laboratory period (when your aspirin is dry), weigh the aspirin on a piece of weighing paper or a weighing boat. (You will need to scrape it off of the filter paper.)

 

Ferric Chloride Test for Salicylic Acid

1. For the FeCl3 test, the samples do not have to be dry. To do the test, get 4 test tubes. Place 1 mL of ethanol and 2 drops of FeCl3 solution in each tube. Add a few crystals of salicylic acid to one test tube. Add a few crystals of your crude aspirin product to the second tube. In the third tube, place a few crystals of the recrystallized aspirin. Don’t add anything else to the fourth tube – it will be your “blank”. Shake each of the tubes and record your observations.

 

Melting point

1. Weigh the product, determine its melting point (lit mp 135-136 °C) and calculate the percentage yield. Dispose your sample in waste container under the fume hood.

 

Melting point instructions

1. Obtain a capillary tube from your instructor. Press the open end of the capillary tube into the powder. Then turn the tube over and tap the tube lightly against the lab bench to allow the powder to fall into the sealed end. Repeat until you have a depth of about 2-mm of solid in the tube.
2. Assemble your equipment as shown in the diagram in Figure 1.
3. Use a large 400-mL beaker half-filled with tap water for the hot water bath. Use a small piece of latex tubing like a rubber band to attach the capillary tube to your thermometer. The sealed end should be close to the bulb of the thermometer. Place a slotted stopper around the thermometer, and using a clamp, suspend it in the water bath. Slowly heat the water (about 3 degree/minute), using a hot plate. Carefully watch the solid. When the solid melts, note the temperature. Stir the bath continuously and watch your sample carefully.
4. The melting point is the temperature at which liquid first appears. Record your melting point.
5. Your aspirin sample and the capillary tube (together) should be disposed of in the labeled waste container provided when you are finished.

Figure \(\PageIndex{2}\): Melting point assembly