Expt #1. Synthesis of Acetaminophen

Relevant textbook readings – Nichols - Organic Chemistry Lab Techniques, Chap 1.2a-c,e; 1.3; 1.4a-c,g,h,k; 1.5a,d; 3; 6.1 (Chapter references below are from this source.)

References - (1) Experiment adapted from Synthesis of Acetaminophen, https://chem.libretexts.org/@go/page/61312 accessed 6/23/2021. (2) Dangers of Cold Water Extraction for Hydrocodone. https://welevelupnj.com/treatment/cold-water-extraction/) accessed 7/7/2023.

Overview –  In this lab you will react p-aminophenol hydrochloride with acetic anhydride to form the common pain reliever, acetaminophen as the main product. Acetic acid is also formed in this reaction as a side product. The obtained acetaminophen will be purified by recrystallization and then characterized through a melting point (mp) determination.

The goals of the lab are to (1) obtain a good yield of pure acetaminophen (2) become familiar with some of the glassware and equipment commonly used in the organic chemistry lab (3) learn how to determine the mp of a solid and how to interpret the result and (4) learn how to purify a solid through the process of recrystallization. The lab will also provide an opportunity to learn how to take good lab notes and write an effective lab report.

Procedures

Running the Reaction

1.  Clamp up a 25-mL round bottom flask (rbf).
   

2. Add 0.56 g p-aminophenol hydrochloride followed by 7 mL water and a magnetic stirbar.
   

3. Begin stirring and attach a reflux condenser and heat the mixture on a sand bath to a gentle reflux (Chap 1.4k).
   

4. While waiting for the mixture to reach reflux prepare a buffer solution of  0.5 g sodium acetate trihydrate in 1.5 mL water.
   

5. Use a Pasteur pipet to add the buffer solution to the stirring solution in the rbf. Do the addition through the top of the reflux condenser.
   

6. Immediately add 0.4 mL of acetic anhydride (also through the top of the reflux condenser).
   

7. Continue refluxing for 10 min.

Work-up

1. Cool the solution on an ice bath, stirring and scratching with a glass rod until the crude acetaminophen begins to crystallize. After crystallization begins, allow the solution to sit on the ice bath until crystal growth appears to have reached completion.
   
2. Collect the product by vacuum filtration on a Buchner funnel. (Chap 1.5d) Wash the crystals once with 1-2 mL of ice cold water and continue pulling air through them for 5-10 min so that they are reasonably dry.
   
3. Transfer the crude product to a watch glass or weighing boat and determine the yield. Calculate the percent yield and record it in your lab notes.
4. Recrystallize all but 25 mg of the crude acetaminophen from water. (Chap 3.6a).
   
5. Record the weight of the recrystallized acetaminophen.
   
6. Calculate the % recovery from the recrystallization (mass xtals/mass crude x 100) as well as the final % yield.

Characterization of Product

Obtain the melting points of both the final crystals and the crude as well as of a commercial sample of acetaminophen.(Chapter 6.1d)

Postlab Questions

    1. The solubility of acetaminophen in water at 0 °C is 7.2 g/L (ref 2).  Use this information to calculate the amount of acetaminophen lost to the filtrate in steps 2 and 4 of the procedure. Discuss the answer in terms of your % yield for the experiment.