Synthesis of Aspirin: From Salicylic Acid to Acetylsalicylic Acid, Lecture notes of History

Download Synthesis of Aspirin: From Salicylic Acid to Acetylsalicylic Acid and more Lecture notes History in PDF only on Docsity! SYNTHESIS OF ASPIRIN I. OBJECTIVES AND BACKGROUND You will:  synthesize acetylsalicylic acid (aspirin) by carrying out a simple organic reaction,  separate your product from the reaction mixture by vacuum filtration,  purify your product by recrystallization,  perform a chemical test to identify the change in functional group from reactant to product, and  determine the success of your synthesis by calculating the percentage yield of your product. INTRODUCTION Aspirin is one of the most widely used medications in the world. It is employed as an analgesic (pain relief), an anti-pyretic (fever control) and an anti-inflammatory. More recently, studies have indicated that daily intake of small doses of aspirin can lower the risk of heart attack and stroke in high-risk patients. The history of aspirin and its precursor dates back to ancient times. Documents attributed to Hippocrates, the father of modern medicine, from the 4th century B.C. refer to the alleviation of pain by chewing on the bark of a willow tree or ingesting a powder made from the bark and leaves of the willow. This remedy was passed on from generation to generation. Fast forward now to the 19th century, where the field of organic chemistry began to experience tremendous growth. By 1838, chemists had managed to isolate, purify and identify the component of willow bark that provided the analgesic benefit. The compound was named salicylic acid, which was based on the genus name of the willow. Efforts to market salicylic acid met with failure, due to an unfortunate side effect-- prolonged ingestion of salicylic acid led to stomach pain, and in some cases, ulcers. Inspection of the structure of salicylic acid molecule (see figure below) sheds some light on the cause of this problem. Salicylic acid contains two functional groups, a carboxylic acid (-COOH) and an alcohol (-OH). The carboxylic acid group, as the name implies, has a tendency to generate H3O+ in aqueous solution. In addition, since the alcohol group is bound to a benzene ring, it belongs to a special class of alcohols known as phenols. Phenols have many unique properties, one of which being that they are substantially more acidic than other types of alcohols. As a result, the two acidic functional groups serve to lower the pH of the stomach, leading to the gastric distress described above.  Figure 29-1. Structures of aspirin and salicylic acid Chemists sought to modify the salicylic acid molecule, reasoning that modification of one of the functional groups could lower the acidity of the compound without affecting the medical benefits. This was achieved by taking advantage of some fundamental organic chemistry. When an alcohol is allowed to react with a carboxylic acid in the presence of an acid catalyst, the functional groups combine in a condensation reaction to form an ester and water: 2 C2H6 + 7 O2 4 CO2 + 6 H2O How many grams of carbon dioxide will form if 4.150 grams of ethane are oxidized? The balanced equation must be inspected to find the mole ratio of carbon dioxide to ethane: four moles of carbon dioxide are produced by two moles of ethane. The conversions are as follows: 2 2 2 2 2 2 1 mole ethane moles of ethane 4.150 g ethane 0.1380 mole ethane 30.08 g ethane 4 moles CO moles of CO 0.1380 mole ethane 0.2760 mole CO 2 moles ethane 44.01 g CO mass of CO 0.2760 mole CO 1 mole C         2 2 12.15 g CO O  The three steps needed to solve this problem were: 1) convert grams of ethane to moles of ethane, 2) convert moles of ethane to moles of carbon dioxide using the balanced equation, 3) convert moles of carbon dioxide to grams of carbon dioxide. You will perform a calculation similar to this one; you will use the mole relationship in the balanced equation for the synthesis of aspirin to predict the mass of purified aspirin you should theoretically have obtained based on the mass of salicylic acid that you used as starting material. Percentage Yield of Product The amount of product obtained in a chemical reaction (experimental mass) is almost always less than what was expected (theoretical mass). This difference occurs because of incomplete reaction of the reactants, side reactions (in which different products are formed), and/or loss of product from careless experimental technique. The smaller the difference is between the experimental and theoretical masses, the more successful is the synthesis. The success is measured in terms of percentage yield, which is calculated using the formula: experimental mass percent yield 100% theoretical mass        II. PROCEDURE A. Equipment Set-Up: Ice Bath 1. Partially fill a 600 mL beaker with ice. Add about 50 mL of distilled water to an Erlenmeyer flask and place it into the ice bath to cool. B. Aspirin Synthesis 1. Measure out ~3 g of salicylic acid on an analytical balance, recording its mass to the nearest 0.001 g. Transfer the salicylic acid into a second 125-mL Erlenmeyer flask (not the one with the water in it), and record the mass of the salicylic acid on your report sheet. 2. Add about 6 mL of acetic anhydride and ~1/4 mL of concentrated (18 M) sulfuric acid (using the mark on the barrel of the disposable plastic pipet) to the flask. Caution: acetic anhydride and sulfuric acid are corrosive materials. Swirl the flask until the salicylic acid has dissolved. Allow the mixture to sit at room temperature for 15 minutes with occasional swirling. During this time, assemble the vacuum filtration apparatus. C. Separation of Product from the Reaction Mixture 1. Cool the reaction flask by placing it in the ice bath. Stir constantly; the mixture should thicken to a solid or semi-solid sludge. 2. Add slowly, with stirring, 35 mL of the cooled water. Continue stirring until the mixture is a watery sludge. (Place the remaining cooled water back into the ice bath. It will be used during the vacuum filtration.) Allow the mixture to continue cooling in the ice bath for 10 to 15 minutes. During this time, determine and record the mass of your watchglass. Also, warm ~50 mL of distilled water to 50-70 ºC on a hot plate. 3. Vacuum filter the mixture. Use small portions of the cooled water to assist in rinsing the last of the crystals from the flask. 4. When filtration is complete, disconnect the vacuum tubing from the flask, then shut off the aspirator. Discard the solution in the filter flask. If all of the cooled water has been used, place another 20 mL of distilled water into the flask and return the flask to the ice bath. This water will be needed for the second vacuum filtration.