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Kirdahy 1

Synthesis of Acetaminophen

Ryan Kirdahy SCH 121 02 May 2nd, 2016

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Title: Synthesis of Acetaminophen Introduction: Acetaminophen is a very common fever reducer and pain reliever. It is routinely used as an

ingredient in many prescription and nonprescription medicines to reduce symptoms of pain, cough, flu, colds, and treat allergies (Acetaminophen Information). Fever reducers are known as antipyretics, and analgesics can be defined as pain relievers. Acetaminophen has both of these properties. It is an antipyretic because it targets the center in the brain that regulates temperature. Acetaminophen sends signals to lower the reduce the temperature of the body and in turn, reduces a fever. Also, it reduces the pain felt by the user by decreasing the body’s sensitivity to pain. This means a greater amount of pain must be present to overcome the effects of acetaminophen. However, acetaminophen cannot reduce the inflammation that may be causing the pain being experienced, it just masks the pain (List of NSAIDs). Examples where acetaminophen is an active ingredient are Dayquil (Over-the-Counter) and Oxycodone, which is a prescription (Common Medicines). The chemical formula is C8H9NO2. Acetaminophen can be synthesized using p-aminophenol (Figure 1) and anhydride (Figure 2) and an acid catalyst (H3O). The product of this reaction is acetaminophen and acetic acid. Acetate would originally form, but would protonate to form acetic acid. The objective was to perform and record the process of synthesizing acetaminophen.

Figure 1: General structure of p-aminophenol

Figure 2: General Structure of Acetic Anhydride

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Figure 3: General structure of Acetic Acid

Figure 4: General balanced synthesis reaction of acetaminophen

III.

Results: P-aminophenol was a white powder that was added to an Erlenmeyer flask in the amount of

1.53 g. Twenty-five milliliters of distilled water was also added to the solution. This was followed by 20 drops of 85% phosphoric acid. The p-aminophenol did not fully dissolve in the solution immediately, so it the liquid was clear with white particles in it. Two milliliters of acetic anhydride were added to Erlenmeyer flask. The Erlenmeyer flask was added to an ice bath on a hot plate and the solution dissolved and it became uniform. After 30 minutes the solution became a milky, white precipitate. The solution was filtered and the white precipitate was the left. Twenty milliliters of distilled water were added to the white precipitate, and the solution was added to an ice bath for recrystallization to occur. White/off-white crystals formed. After filtering the crystals, they were weighed. The acetaminophen crystals had a total mass of 0.37 g. One week later the crystals were reweighed at a mass of 0.32 g. The loss of mass was water being evaporated off. The melting point of acetaminophen is 169 C. The acetaminophen crystals

Kirdahy 4 were added to a Mel-Temp instrument to determine the melting point. The melting point was found to be between 171-172 C which is close to the expected melting point, so it was a fairly pure compound. The chemical equation in Figure 4 is a balanced reaction because all of the atoms on the the reactant side can be accounted for on the product side of the reaction. The acid catalyst is not accounted for in the reaction because it is not changed throughout the reaction. The starting mass of p-aminophenol (Figure 1) was 1.53 g. From that 1.53 g of paminophenol, 0.37 g of acetaminophen was obtained. After one week the product had a decrease in mass as the water evaporated, so the actual yield of the experiment was 0.32 g. To calculate the theoretical yield for the experiment, a limiting reagent must be determined. It is necessary to convert them both to moles of acetaminophen to compare the results. The starting mass of paminophenol (1.53 g) must be converted to moles of acetaminophen by using the conversion of 1 mole p-aminophenol/109.13 g (molar mass of p-aminophenol) to get from grams of paminophenol to moles of p-aminophenol. From there, another conversion must be made by using 1 mole acetaminophen/1 mole p-aminophenol. This step makes the reaction go from moles of paminophenol to moles of acetaminophen. The result of this calculation is 0.0140 moles acetaminophen. To compare this to the other reactant another conversion must be made. This conversion starts with 2.0 mL of acetic anhydride. The first step in the equation is to use the density of acetic anhydride (1.08 g acetic anhydride/1 mL) to convert it to grams. The next step is to convert from grams of acetic anhydride to moles of acetic anhydride, so the conversion 1 mole acetic anhydride/102.09 g (molar mass of acetic anhydride) is used. The final step is to convert to moles of acetaminophen so it can be compared to the first conversion. This is done by using 1 mole acetaminophen/1 mole acetic anhydride. The result of this equation is 0.0212 moles

Kirdahy 5 acetaminophen. Between these two, p-aminophenol is the limiting reagent. By using the limiting reagent, the theoretical yield can then be determined. The limiting reagent (0.0140 moles acetaminophen) must be converted to grams of acetaminophen so the conversion factor 151.163 g acetaminophen (molar mass of acetaminophen)/1 mole. The theoretical yield is 2.116 g of acetaminophen. The actual yield of pure acetaminophen (0.32 g acetaminophen) can then be divided by the theoretical yield of pure acetaminophen (2.116 g acetaminophen) and multiplied by 100 to get the percent yield. The percent yield of pure acetaminophen was 15.123%. Refer to attached sheet for calculations.

IV.

Discussions: During recrystallization, heat causes the solvent to dissolve because solubility increases with

an increase in temperature. This forms a supersaturated solution, which is a solution with excess solvent. A supersaturated solution will form crystals during recrystallization, so when the solvent is cooled the end product will be pure crystals. The crystals are pure because the impurities should be either completely soluble or insoluble at all temperatures. This excludes the impurities from the final crystal structure. There are many reasons as to why the product in most reactions are not pure, especially with amateur organic chemistry students. The first possibility as to why the product may not be pure is cross-contamination. This could be a very common issue in a lab setting where several groups are using the same equipment. If the equipment is not cleaned properly, there could be left over residue from whatever was used previously. It is important to clean the glass wear and any other tools thoroughly with distilled water before the experiment. It is key that it is distilled water because normal water can cause there to be more impurities (Sources of Impurity).

Kirdahy 6 Another issue with having inexperienced students in a lab setting could be human error in packaging. Some compounds may be very similar in color, texture, or other characteristics. These similarities could lead to mislabeling or misuse of different compounds. This would cause impurities for the obvious reason of either mixing the wrong compounds or creating a mixture of the wrong compounds because they have similar external characteristics (Sources of Impurity). The melting point can effectively be used to determine the purity of a product when the melting point is known. Once the melting point is known, it is possible to observe the temperature at which the compound melts. If the compounds melted at a temperature close to the expected melting point, it can be assumed that the compound is mostly pure. A very pure compound will have a uniform melting point with a range of less than one degree Celsius because it is a very uniform compound. The more impurities will cause an increase in the melting point range or completely change the melting point (Melting Point Determination). Phenacetin can be synthesized from the reactants acetaminophen and ethyl iodide. These reactants need hydrogen iodide and potassium carbonate as acid catalysts to help increase the rate at which the reaction occurs.

Figure 5: General synthesis of phenacetin

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V.

Conclusion:

Acetaminophen is a very popular in many prescription and nonprescription drugs because of its antipyretic and analgesics properties. It is capable of reducing fevers and also reducing pain. It is obtained by synthesizing p-aminophenol and acetic anhydride with the presence of an acid catalyst. This reaction yields acetaminophen and acetate, but in the presence of a base the acetate is protonated and becomes acetic acid. In the reaction, 1.53 g of p-aminophenol was used along with distilled water and 85% phosphoric acid. After performing the reaction and carrying out a filtration, 0.37 g of acetaminophen product was obtain. This was left to sit for one week to dry out any excess water. After one week, the final mass was 0.32 g of acetaminophen. After calculating the actual yield of pure acetaminophen (0.32 g) and the theoretical yield of pure acetaminophen (2.116 g) it was possible to calculate the percent yield of pure acetaminophen. The percent yield of pure acetaminophen for this reaction was 15.123%. To help determine purity it was compared to the actual melting point of acetaminophen (169 C). It was discovered that the melting point range for the acetaminophen obtained was 171-172 C.

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Works Cited Administrator. "Sources of Impurity." Orpharch-1 (n.d.): n. pag. SOURCES OF IMPURITY. Web. 3 May 2016. . "Common Medicines with Acetaminophen." KnowYourDose.org. N.p., 2015. Web. 03 May 2016. . "Melting Point Determiantion." Melting Point Determiantion. N.p., n.d. Web. 04 May 2016. . "NSAID List: NSAIDs." NSAID List: NSAIDs. N.p., Dec. 2008. Web. 04 May 2016. . "U.S. Food and Drug Administration." Acetaminophen Information. FDA, 13 Apr. 2016. Web. 30 Apr. 2016. .