The Synthesis and Characterization of Aspirin (Part 1)

Purpose: To synthesize acetylsalicylic acid (aspirin), purify it, and determine the percent yield. The purity of the product will be confirmed by measuring its melting point range and later (Part 2) by spectrophotometric analysis using ultraviolet and visible spectroscopy (UV-Vis).  In the final part of this experiment (Part 3), the molecular structure of the product will be determined by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy.

The reaction that is used for the synthesis is shown below.  In this reaction, an excess of acetic anhydride (C₄H₆O₃) is added to a carefully measured amount of salicylic acid (C₇H₆O₃) in the presence of a catalyst, phosphoric acid (H₃PO₄).  The mixture is heated to form the acetylsalicylic acid (C₉H₈O₄) and acetic acid (C₂H₄O₂).  After the reaction takes place, water is added to destroy the excess acetic anhydride and cause the product to crystallize.  The aspirin is then collected, purified by recrystallization, and its melting temperature measured.  Be sure to save your product for use in Parts 2 and 3.

Safety Considerations: Wear goggles throughout this experiment.  This experiment uses salicylic acid, acetic anhydride and phosphoric acid. The salicylic acid and aspirin may cause irritation to your skin or eyes, but are basically not hazardous. An excess of these can be disposed of in the sink or, if packaged, in the trash. If you spill some, wipe it up with a wet paper towel and throw the towel in the trash. The acetic anhydride and phosphoric acid can cause bad burns. Use them only in the hood and be sure the hood fan is on!  Wear gloves when using these chemicals. Excess chemicals must be disposed of in the plastic tub of water. This will convert the acetic anhydride to vinegar and dilute the phosphoric acid. If you spill a lot of either of these, notify your instructor.

Procedure:

1. Weigh out 3.0 g of salicylic acid and place in a 250 ml Erlenmeyer flask.

2. Measure out 5.0 ml of acetic anhydride and add this to your flask. Be sure to do this in the hood and wearing your goggles.   Don't let the acetic anhydride contact your skin and don't get the vapors in your eyes.

3. Still in the hood. carefully add 5 to 10 drops of  85% phosphoric acid, a catalyst, to the flask and swirl to mix everything thoroughly.
   
4. Still in the hood, heat the mixture for about 15 minutes in a beaker of boiling water.

5. After heating, cautiously add 20 drops of distilled water to decompose the excess acetic anhydride.
   
6. Next add 20 ml of distilled water and cool in an ice bath. You can do this at your bench. If crystals do not appear, you can scratch the walls of the flask with a stirring rod to induce crystallization.
   
7. Collect the solid aspirin using a Buchner funnel and filter paper. Wash the crystals with 2-3 ml of ice cold water to remove acetic acid from the surface of the crystals. The filtrate is mostly water and can be washed down the drain. Allow the air to be drawn through the solid and filter paper for about 15 minutes to partially dry the aspirin.

8. Transfer as much of the solid as possible to a 100 mL beaker.   Add 10 mL of 95% ethanol to the beaker and warm (do not boil!) the mixture in a water bath to dissolve the crystals.  If the crystals do not all dissolve add 5 mL more of the ethanol and continue to warm the mixture to dissolve the crystals.  When the crystals are all dissolved, add 20 mL of warm water, cover the beaker with a watch glass, and let the solution cool slowly.  Crystals should form.  Complete the crystallization by cooling in an ice bath.

9. Pre-weigh a filter paper.  Collect the purified aspirin by filtration as before on the preweighed paper.  Dry the crystals by pulling air through them for about 15 minutes.  Put the product with the preweighed filter paper into a small beaker, cover with a tissue, and set aside to dry further until next week.

10.  Put the dry aspirin and the filter paper into a pre-weighed plastic bag and weigh again.

11.  Measure the melting point range with the Meltemp Apparatus (your instructor will demonstrate) and compare to the value for pure aspirin of 138-140 ^oC.   Record the melting temperature in your notebook.  Seal the bag.

12.  Calculate the weight of your product by subtracting the weight of the paper and bag from the total. Calculate the theoretical (maximum) yield.  What percent of this did you get? This is your percent yield. Record the percent yield in your notebook. Save the aspirin you prepared in a closed, labeled vial for Parts 2 and 3.

13.  Based on your percent yield and the measured melting point range, draw a conclusion about the success of your synthesis.