Making aspirin

I made aspirin with three friends, accompanied with unremarkable school equipment, an unnerving sense of competition, and no expectations that it would go well. I think it went alright.

What is aspirin?

Aspirin has been known to humanity for millenia, however no one quite knew what it was. Chewing on willow bark happened to be a great painkiller, indeed it is due to the presence of acetylsalicylic acid in the willow tree. Bayer were the first company to synthesise it on a mass scale, and gave it the moniker aspirin which is how most people refer to it as. 

Aspirin's skeletal formula

Part 1 - making salicylic acid

Oil of wintergreen is a substance which is mainly composed of methyl salicylate, a chemical compound which can react with sodium hydroxide to produce sodium-2-hydroxybenzoate, which can later be neutralised with hydrochloric acid to produce salicylic acid. 

Salicylic acid

 

This reaction occurs under reflux, which is where you evenly heat any reactants so as to not have something explode. I've already discussed reflux reactions on my blog when working with potassium dichromate - notably, in this reaction you don't need to use any catalysts, which is nice as the perceived risk of the process failing declined by a bit.

    

I started out with 3.18g of oil of wintergreen, hopeful that the reaction wouldn't completely fail. After about forty minutes of watching our methyl salicylate bubbling nervously to the point it briefly came to a halt, it was only a matter of painstakingly adding the HCl before filtering it with a Büchner flask and vacuum pump, the latter sucking out any joy I had when completing the practical.

Come the end of the process, I had a percentage yield of about 28%, which isn't terrible considering the school equipment, poor ventilation, and not having all substances involve react. I was down to 0.75g of salicylic acid, coming into the most interesting step.

Part 2: making the aspirin

This was probably the most anxious step for many reasons:

• We used ethanoic anhydride, which is a derivative of acetic acid, the main component of vinegar. On top of the unpleasant smell, which can also be harmful, all the steps involving the anhydride had to occur in the fume cupboard. This included me swirling a test tube full of it for ten minutes.
• For a brief moment we thought all our salicylic acid was gone when it accidentally fell into an ice bath. Luckily this didn't affect our results, but we did end up with very damp aspirin.
• We used the vacuum pump again.

In the end, though, we got the aspirin we needed, all 0.44g of it. Someone in my group shaped it into a heart, and we left it in a fume cupboard to dry. Over a week later, we came back to the aspirin and it was still somewhat moist.

   

I suppose a good question might be if we could take it and cure ourselves of all our pain. Whilst a nice thought, this wouldn't work for a few reasons:

• 440mg exceeds the recommended aspirin dose for various ailments. Cardiovascular disease is worth 75mg once daily, for instance, though these doses may depend on the patient in question.
• Taking aspirin when not necessary isn't always the best idea. This Harvard article states that whilst taking aspirin every day even without an illness can reduce the risk of heart attack or stroke, you could get major gastrointestinal or brain bleeding in response. And that's without mentioning side effects such as indigestion and stomach ulcers, as well as a potential allergic response.
• My school would be legally responsible for any damages caused.
• It hadn't been purified. After all, there may have been some methyl salicylate still in the aspirin.

Step 3: Making the aspirin pure

The vacuum pump was back, unleashing its whining industrial noise yet again. This time, though, others were also swarming about and wanting me to hand it over. I relented, even though people should know what patience means. But eventually we managed to recrystallise the aspirin, which merely involved dissolving the aspirin in hot ethanol and filtering out the results to find pure crystals. We got 0.08g worth, which isn't the worst result ever, I suppose. 

Steps 4 and 5: Playing with the aspirin

I was in charge of preparing my group's thin-layer chromatography. Armed with samples of methyl salicylate, the recrystallised and impure aspirin, and some mass-manufactured aspirin powder, I had to dissolve them and delicately dot a pencil line on a piece of card-coated silica (which reminds me of microscope slides, now that I think about it). I failed twice, but on the third go got something palatable. After dipping the plate into the ominous "aspirin chromatography solvent", which could prove fatal if inhaled, we got no useful data, which was unfortunate. 

Someone else got the job of testing our pure aspirin's melting point using a melting point apparatus. They got about 130℃, which is only a few degrees shy of aspirin's actual melting point, of 138-140℃.

Epilogue

Unfortunately the aspirin ended up in a school bin, and has probably gone to landfill since. Over the course of several lessons, I managed to accomplish something I'd always wanted to do - synthesise a drug - and in the process learnt valuable lessons on teamwork, handling with care, and got more proof of how frustrating vacuums truly are. 

The aspirin in tatters