Aspirin Synthesis - Introduction to Organic Chemistry - Lecture Notes, Study notes of Organic Chemistry

Download Aspirin Synthesis - Introduction to Organic Chemistry - Lecture Notes and more Study notes Organic Chemistry in PDF only on Docsity! C O OH OH CH3 C O O C CH3 O H2SO4 C O OH O C CH3 O AspirinSalicylic Acid EXPERIMENT TWO SYNTHESIS OF ASPIRIN: ESTER FORMATION Discussion Although active salicylates are found in the bark of willow trees (trees of the genus Salix, from whence salicylic acid derives its name), all aspirin sold today is synthesized from phenol, which, in turn, is obtained from petroleum. In this experiment, you will conduct only the last step of the commercial synthesis, the conversion of salicylic acid to aspirin using the Fisher ester synthesis. The reaction of salicylic acid with acetic anhydride occurs rapidly. The reactants and a sulfuric acid catalyst are mixed, then warmed in a hot water bath. Solid salicylic acid is insoluble in acetic anhydride. Aspirin is soluble in a hot mixture of acetic anhydride and acetic acid, which is formed as the reaction proceeds. Thus, the course of the reaction can be followed by the disappearance of the solid salicylic acid. The reaction is essentially complete when all the salicylic acid has dissolved. Aspirin is only slightly soluble in a cold mixture of acetic anhydride and acetic acid. Therefore, as the mixture is cooled to room temperature, the aspirin precipitates. At the end of the reaction period, the mixture contains aspirin, acetic anhydride, and acetic acid. Acetic acid is miscible with water, and acetic anhydride reacts fairly rapidly with water to yield acetic acid. By adding water to the reaction mixture and allowing the aqueous mixture to stand at room temperature for a few minutes, we can achieve a reasonable separation-the contaminants dissolve in the water, and the aspirin precipitates. Because of the presence of acetic acid and because aspirin is slightly soluble in water, about 10% of the aspirin remains in solution. Therefore, the mixture is thoroughly chilled before filtration and crystallization. An additional small amount of aspirin can be recovered from the mother liquor if it is allowed to stand overnight. Despite this fact, it is not good practice to leave the bulk of the aspirin in acidic solution for an extended period of time because it will undergo a slow hydrolysis to yield salicylic acid and acetic acid, a typical acid-catalyzed ester hydrolysis. EQUIPMENT Docsity.com 400-mL beaker (for hot water bath) dropper two 125-mL Erlenmeyer flasks 10-mL and 100-mL graduated cylinders spatula thermometer vacuum filtration assembly two watch glasses CHEMICALS acetic anhydride, 5.0 mL salicylic acid, 2.8 g conc. sulfuric acid, 3-4 drops TIME REQUIRED: 1 hour plus overnight drying and time for a melting-point determination STOPPING POINTS: after the initial vacuum filtration; while the product is crystallizing from water; while the final product is being air-dried >> SAFETY NOTE: Acetic anhydride is volatile and is a strong irritant. PROCEDURE Place 2.8 g of salicylic acid in a dry 125-mL Erlenmeyer flask, then add 5.0 mL acetic anhydride and 3-4 drops concentrated sulfuric acid. Mix the resultant white slurry thoroughly with a spatula, and place the flask in a warm water bath (45-50EC) for 5-7 min. Swirl or stir the mixture occasionally to dissolve all the solid material. Because the reaction is slightly exothermic, a small temperature rise can be detected. Allow the flask to cool. The aspirin begins to precipitate when the temperature of the solution is about 35-40EC, and the mixture becomes semisolid. When this occurs, add 50 mL water and break up any lumps with a spatula. Allow the mixture to stand for an additional 5 minutes, then chill the flask in an ice bath and remove the crystals by vacuum filtration. Crystallize the crude aspirin from 25 mL of warm water not exceeding 80EC (see Experimental Note). Allowing the mother liquor to sit overnight may produce a second crop of crystals. Air-dry the crystals and determine the percent yield and melting point. EXPERIMENTAL NOTE At temperatures exceeding 80EC, aspirin forms an oil that dissolves organic impurities from the water; in this case, it may be difficult to redissolve the aspirin in water. If the solid does not dissolve in 25 mL of water, add more water from a dropper. Let the mixture warm 2-4 minutes between additions to allow the solid to dissolve. Docsity.com