Experimental Procedure

The reaction mixture will be heated in a water bath at ~85ºC (this will already be set up for you when you arrive to the lab).

Partner 1:

Obtain 4.0 mL of acetic anhydride (pre-measured) from the reagent fumehood at the front of the laboratory and measure the 10 mL of DI water at your fumehood.

Partner 2:

Weigh out 3.0 g of 4-aminophenol using the weigh paper at one of the balances at the front of the laboratory.

Synthesis of Crude Tylenol ®

Reaction assembly, round bottom flask clamped into a water bath over a stir plate

  1. Add the 4-aminophenol (solid) to the 100 mL round bottom flask containing a stir bar. The flask is in the water bath already!
  2. Measure out 10 mL of DI water (wash bottle) using a 25 mL graduated cylinder and add it to the 100 mL round bottom flask.
  3. Heat the mixture in the water bath for 2 minutes with stirring (turn on stirring by pressing the ↺ button on the hotplate).
  4. Add the acetic anhydride (quickly) from the vial directly into the round bottom flask.
  5. Continue heating and stirring the reaction mixture for 5 more minutes. Most, if not all, of the 4-aminophenol should dissolve at this time. If it doesn't fully dissolve, that is okay! 
    (The only way the reaction won't work is if acetic anhydride is added before 4-aminophenol.)
  6. When 5 minutes have passed, remove the round bottom flask from the water bath by lifting the clamp up the support stand.
  7. Remove the larger beaker from the hotplate to cool and dump the water into the sink (it will be used for the ice water bath).
  8. Allow the round bottom flask to continue stirring at room temperature for 2-3 minutes so it is cool to touch. You should start your calculations at this point.
  9. Prepare your ice water bath by filling the large beaker with ice from the ice box at the back of the lab and water.
  10. If your round bottom flask has cooled enough to be safely touched, transfer the flask to an ice-water bath for 5 minutes. You can do this by moving the support stand with the flask away from the hotplate, and lowering the clamp with the flask so that the flask sits in the large beaker. You can keep the stir bar in the flask. The product should precipitate out of the solution at this time. If your product does not precipitate, ask for assistance.
  11. Vacuum filtration assembly, Buchner funnel on a filter flask connected to the vacuumYou will collect the crude Tylenol® by suction filtration. Check the equipment set-up at the front if unsure. While waiting for your product to precipitate, prepare the vacuum filtration by adding a filter paper to the funnel and spraying a small amount of DI water to wet the paper.
  12. Once ready to filter, turn the vacuum on by turning the yellow knob on the outside edge of your fume hood counterclockwise until you feel resistance. Don’t turn the vacuum on too much, to avoid tearing the filter paper. When the vacuum is turned on you should see water drip into from the Buchner funnel into the vacuum flask.
  13. Use a small amount of cold deionized water to assist in the transfer of the solid to the suction filtration apparatus. You can put your DI water bottle in the ice bath to cool the water down. Ask a volunteer how to remove the stir bar from the Buchner funnel.
  14. While your product is being filtered, take a clean, dry 100 mL beaker to a balance and measure its mass. Record the mass in your Results section. 
  15. Transfer your crystals of crude Tylenol ® to the 100 mL beaker. Determine the mass of your beaker and product. Do not use water for this step.
  16. Describe the appearance of your crude product in the Results section.
  17. Calculate the mass of crude Tylenol ® you have prepared in the Results section. 
  18. Dispose of the liquid filtrate in the filter flask in the black aqueous waste container before continuing to the recrystallization.

Video of the synthesis of acetaminophen:

Expand/Collapse Transcript

When you arrive to the lab, your workstation in the fume hood will be set up for you with all equipment needed. Can you name all the equipment you see on the screen?

The flask will already be placed in a water bath preheated to 85° C. Take your scoopula and bring it with you to the balance area where you will weigh the 4-aminophenol.

Before weighing the solid, take one of the weighing papers and fold it in half diagonally. Place it on one of the top loading balances and zero its mass by pressing the tare button. Weigh approximately 3 grams of the 4-aminophenol by scooping it out of the jar. It is okay if you go a bit above 3 grams, you can record the exact mass to take it into account when you calculate your yield this is what chemists do!

Once done at the balance, take the weighing paper by the corners and carry your solid and scoopula back to your workstation. Use the folded weighing paper as a funnel to add the 4-aminophenol in the flask. Measure 10 mL of deionized water in the graduated cylinder and add it to the flask as well.

Press the circular arrow on the hot plate to start the stirring. Your flask was set up with a magnetic stir bar inside which will spin once the stir function of the hot plate is on.

Wait 2 minutes before adding the acetic anhydride. We portioned 4 mL of the reagent in vials for you, so you can bring it to your fume hood and pour directly into the round bottom flask.

After about 5 minutes since the addition of acetic anhydride, remove your round bottom flask from the water bath. You will need to loosen the fastener on the clamp that holds it to the rod in the fume hood. Ask for help if you need. Lift the flask first to remove the water bath, then lower the flask closer to the hot plate so the stirring can continue.

Empty the water bath into one of the sinks then use the large beaker as a scoop to take some ice and add some tap water to make the ice bath. Lower the flask into the ice bath to cool its content and maximize the precipitation of the acetaminophen product.

Prepare for vacuum filtration by adding a filter paper to the Buchner funnel and wetting it with some deionized water. On the outside of the fume hood, you will find a yellow dial that controls the vacuum. Turn this dial counterclockwise until you feel resistance. You should see water dropping down into the vacuum flask rapidly or add more water to the Buchner funnel if you want to ensure the suction is strong enough.

Transfer the reaction mixture to the Buchner funnel. You can loosen the acetaminophen solid with a glass rod first and rinse the round bottom flask with small portions of deionized water to ensure all the solid is transferred. Use a magnetic stir bar retriever to remove the stir bar from the Buchner funnel and rinse the stir bar with a bit of water directly into the rest of the solid.

Keep the vacuum on until the solid feels like sand when touching it in the Buchner funnel.

While waiting for the filtration to complete, weigh the empty 100 mL beaker. Zero the balance first then place the beaker and note its mass on your data sheet Back at the fume hood, turn the vacuum off by turning the yellow dial clockwise. 

Take the Buchner funnel off the assembly and transfer the solid inside the Buchner funnel to the beaker The beaker containing the crude acetaminophen is now weighed again. By subtracting the mass of the empty beaker from the mass of the beaker containing the crude acetaminophen, you can obtain the mass of crude acetaminophen product you made in the lab.

In the next video, we will show you how to perform recrystallization to obtain a acetaminophen hopefully pure enough to make Tylenol pills!

 

Recrystallization

  1. The crude product will now be purified by recrystallization using DI water as the solvent.

  2. Add 10 mL of DI water per 1 g of crude product to the beaker.
  3. Heat this mixture on a heating plate until all the product dissolves, stir the mixture occasionally using the glass rod. Set the temperature to 190 °C by using the dial on the hot plate. The magnetic stir bar is not used in recrystallization because the crystals would form on it and be of lesser quality.
  4. Once the solid has dissolved, remove it from the heat and let the solution cool, undistributed, to room temperature (~5 minutes).
  5. Move your solution to an ice-water bath for 5-10 minutes, do not disturb the beaker while it cools. 
  6. Collect the pure Tylenol ® by suction filtration using a small amount of cold DI water to assist in the transfer.
  7. Keep the solid under suction for 5 minutes. Clean and dry your 100 mL beaker.
  8. The solid crystals are acetaminophen (Tylenol ®). Collect the crystals in your 100 mL beaker and determine the final mass as well as the final percent yield. Do not use water in this transfer!
  9. The liquid filtrate after the recrystallization from the filter flask can be rinsed with tap water and can go down the drain. 
  10. Ensure all glassware has been properly properly cleaned by rinsing with lots of tap water.
  11. If time permits, consult the laboratory instructor about conducting a melting point purity test and fill in the "optional results section".

 

Video of the recrystallization of acetaminophen:

Expand/Collapse Transcript

Use the mass of crude acetaminophen you weighed to determine how much water to add for your recrystallization. Use about 10 mL of water for each gram of product and add it to the 100 mL beaker containing your acetaminophen.

Place the beaker on the hot plate and set it to 190 degrees. The goal is to heat the solution to help dissolve the acetaminophen. Recrystallization works by the assumption that impurities will be soluble in water no matter its temperature, while the acetaminophen will only dissolve in hot water. So when we cool the solution, crystals of high quality will slowly form.

Stir the solution with a glass rod while it is heating. If you notice solids on the side of the beaker when the solution is all homogeneous, you can rinse with a bit of water but not too much! The more water is added, the less acetaminophen you will recover at the end and your yield will be low.

Once all the solid is dissolved, remove your 100 mL beaker from the hot plate and let it cool to room temperature while you go prepare a new ice bath. Then cool the solution by transferring it to the ice.

As the solution cools, you will hopefully see large flaky solids forming in the beaker. To isolate the purified acetaminophen, perform vacuum filtrations just as before. Use small amounts of cold deionized water to transfer to solid and you will hopefully get some nice shiny crystals!

Transfer the solid into the 100 mL beaker and take the mass of the purified acetaminophen. You can use the previous mass of the beaker and subtract it from the mass of the beaker with the acetaminophen for this calculation.

If you have time, you can prepare a melting point sample to assess the purity of the acetaminophen. Just dip the open end of a capillary tube in the solid and tap to pack the solid in the closed end.

The next video, we will show you what taking a melting point looks like.


Waste Information

Disposing of waste properly is important for the environment and improper waste disposal can be a potential hazard. In the laboratory, we will have a waste guide to indicate where to dispose of waste and show you where each container is. Please look at the waste guide sheet provided at your benches on where things need to go. If you are ever unsure, please ask for help! :-)