Park, Gloria Hye Oh
Excedrin Lab
Purpose: The purpose of this lab was to isolate and purify the components of an extra strength Excedrin tablet using a combination of solubility differences and a chemically active extraction. Abstract: The Rf values of the components of the Extra Strength Excedrin tablet were found to be: acetaminophen (0.37), aspirin (0.68), and caffeine (0.21). The melting points for the three components were found to be: 162C for acetaminophen, 148C for aspirin, and unknown for caffeine. . Introduction: Extra Strength Excedrin is an over the counter pain reliever that contains a binder and three ingredients: acetaminophen (4-acetamidophenol), aspirin (acetylsalicylic acid) and caffeine. The separation and isolation of all three active components requires various steps. Chemically active extraction is a liquid-liquid extraction that separates components based on their solubility. In a chemically active extraction of a compound is chemically altered to change its solubility in a solvent. This is done by acid-base reactions. Thus, this extraction method is commonly referred to as an acid base extraction. Crystallization is a technique used to further purify compounds. When a solution is heated and then allowed to cool slowly, crystallization of the pure substance results. The formation of crystals in solution separates out a pure compound while impurities usually remain in solution. If the solution is cooled too quickly, the crystals will be smaller and trap impurities. Thin Layer Chromatography (TLC) is a process that can be used to test the purity of the separated compounds. This is done by spotting a sample at the bottom of a TLC plate and then placing the plate in a shallow amount of developing solution. The spots on the plate are then visualized by using UV light. During the mobile phase the solvent moves up the TLCs plate (stationary phase) by capillary action carrying the compounds with it. The distance traveled by the compounds depends on its structure. The plate is then measured using Rf values. Rf (ratio to front) is the ratio of the distance traveled by the substance to the total distance traveled by the developing agents (See diagram Appendix I). This value reflects the affinity of the compounds for the stationary versus the mobile phases. Experimental: The procedure was followed directly as laid out in the lab manual with a few exceptions. A 500 mg sample of Excedrin was used for the initial separation. Calibration of the melting point apparatus was not needed. Results: Acetaminophen, caffeine, and aspirin were isolated from a 500 mg sample of Excedrin. The percent recovery for all three components were: 0.002% of acetaminophen (0.01g), 0.01% of aspirin (0.05g), and 0% of caffeine because it did not crystallized. Under experimental conditions, the Rf values of the 1
components of the Excedrin were determined to be: acetaminophen (0.37), aspirin (0.68), and caffeine (0.21). Also the melting points for the three components were 162C for acetaminophen and 148C for aspirin. There are no results for caffeine because there was no crystallization. See Appendix I and II for charts and calculations. Discussion: The three active ingredients in Excedrin, Acetaminophen, caffeine, and aspirin were isolated and purified. Separation was accomplished by first separating the components using methylene chloride. The binder and acetaminophen are insoluble in methylene chloride. Thus, separation can be achieved by dissolving aspirin and caffeine in methylene chloride and using filtration to remove the binder and acetaminophen. Treatment of binder the and acetaminophen mixture with hot ethanol results in the acetaminophen being dissolved. The binder is then filtered off. The solvent, ethanol, can then be evaporated leaving behind crude acetaminophen. The other two components, aspirin and caffeine, can be separated from the methylene chloride layer by chemically active extraction. Aspirin, which is acidic, is removed by addition of NaOH, an aqueous base, as a water soluble salt. Caffeine, which is basic, remains in the methylene chloride layer. The methylene chloride layer is evaporated leaving behind crude caffeine. Treatment of the aqueous layer with HCl, an aqueous acid, regenerates aspirin from its salt. See appendix III for an outline of this separation. This separation scheme was based on the solubility of the components of Excedrin to methylene chloride. As shown in appendix V, aspirin contains a carboxylic acid group making it acidic, while the caffeine contains an amine groups making it basic. Thus, these two components dissolve in an organic solvent (methylene chloride). Acetaminophen is acidic and contains a phenol and an amide group; however, it is not soluble in methylene chloride. The insolubility of acetaminophen in methylene chloride allows for the easy separation of Excedrin components. However, if all the components in Excedrin were soluble in methylene chloride, another solvent would have to be used to initially separate the components. See appendix IV for a modified separation scheme. Both acetaminophen and aspirin were successfully crystallized while there was no crystallization with caffeine. Caffeine could not be crystallized because we did add not enough anhydrous sodium sulfate to the methylene chloride layer and drying process might not have been completed. Another possible source of error could be the rapid cooling of the caffeine mixture. Slower cooling could have yielded some crystals. Both cases may be the cause of these results. The purity of the crystallized components was assessed using thin-layer chromatography (TLC) analysis. As seen by the TLC results in Appendix II, acetaminophen, aspirin, and caffeine should show one spot with different Rf values. The Excedrin track should show three different spots, each with a Rf value similar to one of the three components. However in this experiment caffeine could not be analyzed due to the lack of purified caffeine. The distance traveled by the compounds depends on its interaction with the adsorbent. Aspirin and acetaminophen interact strongly with the absorbent. Also because the structure of
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acetaminophen more closely resembles aspirin than the structure of caffeine, the acetaminophen and the aspirin are closer together (see Appendix V for structures of Excedrin components). Caffeine has a high affinity for the stationary phase and thus did not move as far as the other two components. When aspirin is exposed to moisture, like when a bottle is opened, the compound breaks down into salicylic acid and acetic acid. Acetic acid is the main constituent of vinegar. Thus, the breakdown of aspirin in an old bottle of aspirin produces a vinegar-like smell due to the production of acetic acid. Tablets with high concentrations of aspirin also have a noticeable vinegar-like odor. A specific temperature range was recommended for each water bath because the temperatures specified were high enough to evaporate the solvent but still below the boiling point of the solute. This range also took into account the temperature at which unwanted reactions could take place such as the hydrolysis of aspirin to give salicylic acid.
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