Pre-Lab on Acetaminophen Synthesis

The active ingredient in the pain-killer Tylenol® has the non-IUPAC name "acetaminophen." The structure is shown at right. (You do not know how to name the compound by IUPAC rules at this point, so don't worry.)

The purpose of this experiment is to show you how acetaminophen is made and to practice using the stoichiometry calculations you have studied in class.

The reaction equation is:

The first step is to determine if the equation is balanced. This means we need to check if the number and kind of atoms are the same on both sides of the reaction arrow. On the left there are: 10 C, 13 H, 1 N, and 4 O atoms; on the right side of the arrow there are 10 C, 13 H, 1 N and 4 O atoms.
The equation is indeed balanced. This reflects the law of conservation of mass. In any reaction, bonds are broken and new ones formed to "reorganize" the same atoms into new substances.

The balanced equation now tells us that for each mole of p-aminophenol reacted, one mole acetic anhydride is needed to make one mole of acetaminophen. The other product (which we do not want to keep) is one mole of acetic acid.

The second step is to determine the number of moles of reactants. While we measure out materials in grams, what controls the chemical process is the number of moles of reactants present. The factor that connects grams and moles is the formula weight (FW). The FW tells how many grams there are in one mole of the substance, and can be calculated from the formula and the atomic weights of the atoms in the compound. How would you calculate the FW of p-aminophenol?

The other reactant in the experiment is a liquid, acetic anhydride. Liquids can certainly be weighed out, but in this procedure we are deliberately adding an excess number of moles of acetic anhydride. There are two reasons for this: (1) we want to reduce the amount of irritating vapors in the air, and (2) we want to make sure to use up all the p-aminophenol. Suppose that 10 drops acetic anhydride actually weighs 0.50 grams. How many moles of acetic anhydride are used? Are the number of moles acetic anhydride greater than (in excess of) the moles p-aminophenol?

In this experiment a solution of water and acetic acid is used as the solvent. We do not need to calculate the moles of solvents because they do not appear in the balanced equation on the reactant side.

If you were working at a drug company making acetaminophen, the company would want to know how much acetaminophen you should be able to get from the p-aminophenol you started with; chemists call this the theoretical yield. Once again, the balanced equation and the number of moles of reactants tell us what we want to know.

The balanced equation says we get one mole acetaminophen by reacting one mole p-aminophenol and one mole acetic anhydride. In this experiment, we are adding more acetic anhydride than is needed — an excess. So, what controls or limits the amount of product we can obtain is the number of moles p-aminophenol started with. The limiting reagent is the reactant which determines the amount of product that can be obtained. In any reaction, the limiting reagent is the reactant that is present in the least relative amount according to the proportions in the balanced equation. In this reaction, the limiting reagent is p-aminophenol.

Because the balanced equation says that one mole acetaminophen is formed from one mole of p-aminophenol that reacts, the theoretical yield of acetaminophen in this case is the same as the number of moles p-aminophenol actually used.

The expected yield of acetaminophen is the maximum that possibly could be formed if the reaction occurred perfectly and you were able to recover all the product. Lab work is not perfect, so you are not going to recover the theoretical yield. We can get a sense of how well the lab work (the reaction and recovery of the product) occurred by comparing the actual yield to the theoretical yield. The percentage yield is simply the ratio (actual yield of product)/(theoretical yield of product) x 100%. The actual and theoretical yields can be in units of grams (both of them) or moles (both of them).

Of course there is the pesky problem of getting the product out of the mixture in which it was formed. In this experiment, the acetaminophen ends up being not very soluble in the water and acetic acid, so that when the mixture is cooled at the end, it precipitates. The acetaminophen is recovered by filtration. The extra acetic anhydride you used decomposed in the solution to make acetic acid which is completely soluble in water. When the solid is filtered, all the other chemicals are removed by rinsing the solid with a little clean water. When the solid dries, it can be weighed and the actual and percentage yield calculated.

One last thing: the acetaminophen is not being made under pharmaceutically pure conditions, so it is not safe to ingest it. Please be sure to dispose of the product as directed by the lab instructors.