67 failures at extracting acetaminophen from Excedrin(R) I have adapted the lab experiment described in this J. Chem. Ed. article for the organic chemistry lab course I teach. In the past year, the first year of implementation, I have had 67 failures (100% failure rate) on the extraction part of this experiment.

The experiment involves the isolation/separation of the active components in Excedrin(R): acetylsalicylic acid, acetaminophen, and caffeine. 



The experiment is in two parts. Part 1 involves analysis by TLC and separation by column chromatography. This part works beautifully. Part 2 involves separation by successive extractions with increasingly strong bases. Acetylsalicylic acid was extracted with 10% aqueous Na2CO3. Then, acetaminophen was extracted with 3 M NaOH. Finally, caffeine was recovered by evaporation of the remaining organic layer. 

In Part 2 We recovered lots of acetylsalicylic acid and caffeine, but no-one recovered any acetaminophen. Below is a list of things I tried in order to improve the results. None of them worked. I know from TLC analysis of the initial organic solution that acetaminophen was present. What happened to it?

Things I have tried:


Changing the concentration of both bases (up and down).
Using a weaker base for the first extraction (like NaHCO3 or Na3PO4). 
Increasing the HCl concentration used to work up the second extraction. 
No acetaminophen was extracted with the weak base, nor was any left
behind after the second extraction.


Where has my acetaminophen gone?
Did you notice any change of colour (e.g. to brown) and/or the formation of gunk upon adding the 3M NaOH?

I'd assume one would have to boil it, but is the following scenario conceivable under your conditions:


alkaline hydrolysis of the acetaminophen (paracetamol) to p-aminophenol
aerial oxidation to the corresponding quinone imine
partial polymerisation of the latter


You have confirmed that acetaminophen was initially there. A a change in the constitution of Excedrine since the publication of the article can thus be excluded. Isn't a reaction (hydrolysis or whatever) under your extraction not the most likely explanation for the vanished acetaminophen?