Synthesis of Tylenol and Aspirin

Synthesis of Aspirin and Tylenol
Kyla Wykoff

Abstract Aspirin and Tylenol were synthesized by means of crystallization, recrystallization, and melting point determination. Synthesis produced significantly high percent yields for aspirin, however, produced extremely low and impure percent yields for Tylenol. A second group was also used to compare results and errors, in which they too were also producing extremely low percent yields of Tylenol. Therefore, error was based on the specific protocol used.
Introduction
Aspirin, acetylsalicylic acid, was first synthesized by a German chemist, Gerhardt, in 1853, but his reports went largely ignored. However, forty years later, in 1893, Felix Hofmann, also German, reinvestigated Gerhardt's work and proved it to be true. Acetylsalicylic acid was found to be medically effective for both reducing fevers and relieving pain (Synthesis). Today aspirin has many uses, which include; reducing fevers, reducing headache pain, relieve swelling and joint pain often associated with arthritis, enhances the elimination of uric acid. Acetylsalicylic acid, aspirin, is prepared by reacting salicylic acid with acetic anhydride:


Figure 1. Chemical Equation for Aspirin Synthesis (Aspirin)

Tylenol, acetaminophen, is also used both as a fever reducer and pain reliever. Acetaminophen is prepared by reacting ammonia with acetic acid:

Figure 2. Chemical Equation for Tylenol Synthesis (Acetaminophen)

The purity of an aspirin or Tylenol sample can be obtained by determining the melting point. The presence of impurities always lowers the melting point of any substance; the higher the concentration of impurities, the lower the melting point will be (Preparation).
Experimental
Synthesis of Aspirin To synthesize aspirin, the following materials are needed: Salicylic acid, acetic anhydride, concentrated sulfuric acid, ethanol, dropper, 125mL Erlenmeyer flask, beakers (400mL, 100mL, 20mL), graduated cylinders (10mL, 25mL), hot plate, watch glass, stirring rod, vial to hold sample, ring stand, clamp, Buchner funnel, filter paper, vacuum filtration flask, ice, thermometer, melting point capillary tube, and melting point apparatus. In a 125mL Erlenmeyer flask place 2.00 g of salicylic acid. Add 5mL of acetic anhydride, then swirl flask to wet the crystals. Add 5 drops of concentrated sulfuric acid, then heat flask in boiling water for about 10 minutes. Remove flask from water bath and add 10mL of distilled ice water. Chill the mixture in ice bath until crystals no longer form, stirring occasionally. If solid does not appear, reheat flask in hot water bath and cool again. Set up vacuum filtration apparatus. Insert filter paper into funnel and turn on water aspirator. Decant the liquid onto the filter paper, being very careful to keep the transfer of any solid to a minimum. Add 15mL of cold water to flask, swirl, and chill again. Pour liquid and crystals onto filter paper. Repeat process until transfer of the crystals is complete. Wash crystals with 10mL of water, and utilize the vacuum to dry the crystals as best as possible. Determine and record the mass of the crude aspirin.
Recrystallization
Place crystals into 100mL beaker. Add 8mL of ethanol, and 25mL of water to beaker. Warm mixture in hot water bath until the aspirin has dissolved. Cover beaker with watch glass, remove from heat, and allow to cool slowly. Set beaker in ice bath, needle-like crystals will begin to form. Collect crystals by vacuum filtration. Wash crystals with two 10mL volumes of ice water, and utilize vacuum to dry crystals as best as possible. You may want to leave your crystals sit out overnight on a watch glass, in order for them to completely air dry. After drying, transfer crystals to a pre-weighed vial. Determine and record the mass of the aspirin crystals.
Melting Point Determination Fill melting point capillary tube to a depth of 0.2cm with aspirin crystals. Place tube in melting point apparatus. Pure aspirin melts at 135 degrees Celsius. Determine the melting point of crystals, then calculate percent yield (Preparation).
Synthesis of Tylenol To synthesize Tylenol, the following materials are needed: Acetic anhydride, p-aminophenol, concentrated phosphoric acid, ethanol, dropper, 125mL Erlenmeyer flask, beakers (400mL, 100mL, 20mL), graduated cylinders (10mL, 25mL), hot plate, watch glass, stirring rod, vial to hold sample, ring stand, clamp, Buchner funnel, filter paper, vacuum filtration flask, ice, thermometer, melting point capillary tube, and melting point apparatus. Fill 400mL beaker half full with water. Place beaker on hot plate and bring water to a boil. In a 125mL Erlenmeyer flask place 1.5 g of p-aminophenol. To flask, add 25mL of water and 20 drops of concentrated phosphoric acid, and swirl until amine has completely dissolved. Turn off hot plate and place flask into hot water. Add 2mL of acetic anhydride to flask and leave in warm water for 10 minutes. Remove flask and place in ice water bath. Stir to crystallize mixture. Keep flask in ice water bath for 30 minutes. Collect crystals in funnel using vacuum filtration. Wash crystals with 10mL of water and allow to dry. Determine and record mass of crude Tylenol, acetaminophen.
Recrystallization
place crystals in 100mL beaker. Add 20mL of water and heat on hot plate until crystals dissolve. Remove beaker and allow mixture to cool. When crystals begin to appear, place beaker in ice bath for 20 minutes. Collect the crystals by vacuum filtration. Wash with 10mL of water. Transfer filter paper and crystals to watch glass and allow to dry overnight. Determine and record the mass of the acetaminophen.
Melting Point Determination Fill melting point capillary tube to depth of 0.2cm with acetaminophen crystals. Place tube in melting point apparatus. The melting point of pure acetaminophen is 169-171 degrees Celsius, and p-aminophenol melts at 189-190 degrees Celsius. Determine the melting point of crystals, then calculate the percent yield (Preparation).
Results
Data of Our Group Melting Point Percent Yield
Aspirin,
acetylsalicylic acid 134-136 C 98.80%
Tylenol, acetaminophen 151-155 C 14.81%

Data of Comparing Group Melting Point Percent Yield
Aspirin,
acetylsalicylic acid 133-136 C 88.70%
Tylenol, acetaminophen 145-148 C 32.55%

Discussion and Conclusion Although this experiment did not produce the most desired results, it went very smooth and was very interesting. It was really fascinating to be able to synthesize and produce two compounds that are used daily, and to be able to understand how they are made. The production of aspirin turned out fairly well, with a relatively substantial percent yield. However, the production of the Tylenol didn't go as smoothly, with a very low and insignificant percent yield. The melting points of our samples efficiently showed how accurate our samples were, and the relative amounts of impurities that they contained. Both groups used the same protocols for both the synthesis of aspirin and the synthesis of Tylenol. Considering the fact that both groups produced a significant amount of pure aspirin, and yet both did not do so well synthesizing the Tylenol, it may be safe to say that this margin of error could be due to the specific protocol used. Experimental error can be ruled out because of the fact that both groups produced such low percent yields for the Tylenol, while producing high percent yields for the aspirin. This experiment could be taken further by re-synthesizing Tylenol, yet, with a different protocol from the one used in this experiment.