Synthesis of Acetaminophens

Introduction:
Acetaminophen is a commonly used analgesic, which is essentially just a medicine that relieves pain (Prescott, 2000). Acetaminophen is created by synthesizing p-Aminophenol with Acetic anhydride. This reaction occurs when the amine group of the p-aminophenol is acetylated by the acetic anhydride. The resultant is an amide functional group (Ellis, 2002). However, the product that is obtained from this product is a crude solid which cannot be used as an analgesic and therefore the crude solid must be purified. This purified product is what is later put into the analgesic. In this experiment, the procedures that are important are vacuum filtration and recrystallization which are both used to obtain the Acetaminophen product. When collecting products, it is important to know how much product is left and what is lost through the experiment. To do this, the balanced equation will be looked at and then the theoretical yield will be calculated. In order to calculate the theoretical yield, two equations will be used:

Will be used for both reactants to determine which reactant is the limiting reagent. After the limiting reagent is used, then the theoretical yield will be calculated using:

This will give the mass of the Acetaminophen. The actual yield will be available in the experimental data, and using this knowledge, this equation will be used to calculate the percentage yield:

Once the percentage yield is calculated then the quality of the apparatus and procedure can be determined to obtain better results and more product in the future. The purpose of this experiment, is essentially to determine the purity of the product that is collected and filtered and recrystallized. Experimental Procedure:

The experimental procedure used for this experiment was outlined in the CHEM 123L lab manual, Experiment #1. All steps were followed without deviation. Experimental Observations:
Table 1: Experimental Data Values obtained in the Experiment Observation
Value of Observation
Mass of P-Aminophenol
3.09g
Mass of Empty Erlenmeyer Flask
95.04g
Mass of Erlenmeyer Flask after collecting precipitate
98.62g
Mass of Crude Precipitate
3.58g
Volume of Water Used
35.80mL
Mass of empty Erlenmeyer flask after second filtration
72.96g
Mass of Erlenmeyer Flask after collecting second precipitate 75.44g
Mass of Purified Product
2.48g
Melting Point from Meltemp
161.5°C
Expected Acetominophen Melting Point (Aldrich Catalogue)
168°C-172°C

Table 2: Qualitative Observations obtained in the Experiment

First 5 Minutes
The liquid was a peach colour, the powder partially dissolved within it. After Adding Acetic Acid
The liquid was clear and was a greenish-yellow colour. The product dissolved almost immediately as the acetic acid was added. After Heating; room temperature
The precipitate started to form.
In the Ice Bath
The peach colour returned, a solid precipitate started to form. After 1st Vacuum Filtration
The powder was white and was clamped together in some places due to the slight dampness, but broke apart easily. Recrystallization
Whilst heating, crude product dissolved and there was a clear liquid. In the ice bath, crystal like structures started to form. As there was not enough precipitate, the bottom was scratched and precipitate started to settle at the bottom of the flask. After 2nd Vacuum Filtration

Crystal like powder was obtained. It was white and glitter like.

Results and Calculations:

Reaction Equation for the Synthesis of Acetaminophen
C6H7NO + C4H6O3  C8H9NO2 + C2H4O2
P-aminophenol + Acetic Anhydride  Acetaminophen + Acetic Acid

Determining the Theoretical Yield of Acetaminophen
1. Determine the Limiting Reagent

Daa = 1.082g/mL (Lide, 2000)
Therefore the limiting reagent is C6H7NO.
2. Determine the Theoretical Yield

Therefore the theoretical yield is 4.28g of C8H9NO2.
Determining the Percentage Yield

Therefore the percentage yield for this reaction is 59.35%

Discussion:
In this experiment, the purpose was to collect crude Acetaminophen and then use the recrystallization process to purify the product. The data obtained from this part of the experiment later aided in finding the theoretical value and percentage yield value. When the data was tabulated and calculated it was found that the theoretical value of Acetaminophen should be 4.28g when in reality there was only 3.58g of the crude product and 2.54g of the purified product. Using the theoretical yield and the actual yield the percentage yield of the reaction was determined at 59.35%. The yield is lower than 100% due to some of the experimental errors that had occurred.

One of the reasons why the yield is below 100% is because there was a loss of product when during the transfer of product in the various steps. This loss in product changes the actual yield to a lower value which gives a yield below 100%. To ensure that there is not a loss of product a quantitative transfer cane can be done. Another reason why the yield is lower is because when the cooling and crystallized product in the Erlenmeyer flask is moved to do the vacuum filtration some of the solute is dissolved again and so will not be taken into account into the actual yield. This will decrease the amount of product. To ensure that this does not happen, this process can be done multiple times to be sure that all of the product is extracted from the solvent.

Another part of the experiment was to take the crude product and the purified product and use the MelTemp apparatus to determine the melting point. From the Aldrich Catalogue, it was seen that ideally the melting point should be between 168°C-172°C, however the actual temperature that was observed for both products was 161.5°C. This lower than expected melting point is due to the fact that the product that was collected was not 100% pure because the product that was recovered through the vacuum filtration was not completely dry. This can be avoided in the future by waiting longer to make certain that the product is completely dry. Questions:

1. A) When 5mL of water is added for every 1g of crude product, there is a faster rate of recrystallization because the solvent is more saturated with the solute and therefore able to produce more product. B) If 15mL of water is added for every 1g of crude product there would be lower rate of recrystallization and there would be less product obtained because it is more difficult for the solute to precipitate. C) A cold solvent is used for the transfer than a hot solvent because the solute will dissolve faster in the hot water and so during the filtration if the solute dissolves and gets filtered then a precipitate cannot be collected. D) The bottom of the container is scratched so that the precipitate will not get stuck in the bottom during the transfer because this will lead to the use of more solvent which makes it more difficult to recover the product.

2. In the field of Chemistry, an organic compound is any compound with carbon atoms in them. 3. Organic synthesis is a very common process and much like the synthesis done in this experiment, another common one is the Synthesis of Aspirin. This synthesis is extremely similar to the procedure done in this experiment in that instead of p-aminophenol, salicylic acid is combined with acetic anhydride to produce aspirin and acetic acid. Aspirin is made using a process called esterification where a carboxylic acid and an alcohol loses a water molecule and combines to form an ester. Aspirin is now one of the most common analgesics that are used in the world as it relieves moderate pain, reduces fevers and even alleviates arthritic conditions. (Spurlock, 2015) 4. Structures of the organic amine salicylic acid and organic amide acetylsalicylic acid respectively.

Conclusion:
In conclusion, the purpose of this experiment was to take p-Aminophenol and synthesize it into Acetaminophen using Acetic Anhydride and then determine the purity of the substance by using the melTemp apparatus. By conducting this experiment, the theoretical yield which was 4.28g of Acetaminophen and the percentage yield which was 59.35% can be obtained. The percentage yield can also aid in determining the purity because the lower the percentage yield, the lower the purity. This percentage yield was lower than the ideal due to the loss of product in the transfer.

Reference:
Ellis, Frank. (2002). Paracetamol – a curriculum resource. Royal Society of Chemistry. London. Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-5 Prescott, Laurie. (2000). Paracetamol: Past, Present, and Future. American Journal of Therapy. Lippincott Williams & Wilkins, Inc. Spurlock, Deborah. (2014). The History of Aspirin. 22 January, 2015. Web. 28 January 2015. From http://homepages.ius.edu/DSPURLOC/C122/asp.htm Stathapulos, Sue. (2015). Synthesis of Acetaminophen. CHEM 123L Laboratory Manual (pp. 12-14). Waterloo: University of Waterloo.