Synthesis and Purification of Acetylsalicylic Acid Essays

Synthesis and Purification of Acetylsalicylic Acid (ASA or Aspirin) Introduction Salicylic acid is a phenol as well as a carboxylic acid. It can therefore undergo two different types of esterification reactions, creating an ester either with the hydroxyl or with the acid. In the presence of acetic anhydride, acetylsalicylic acid (aspirin or ASA) is formed. Correspondingly, an excess of methanol will form methyl salicylate, which is also an analgesic. In this experiment, we will use the first reaction in order to prepare aspirin. Salicylic acid will not react significantly with acetic acid to produce aspirin. Acetic acid anhydride, however, is more reactive than acetic acid because its acetate group (CH3CO2-1) is a much better leaving group than the HO-1 from the acetic acid. The reaction has one complication, however, in that an esterification can occur between the phenol and acid portion of adjacent salicylic acid molecules. Further, more molecules can bind to the remaining free substituents on these molecules to create a macromolecule, or polymer. The polymer is formed as a by-product. Acetylsalicylic acid will react with sodium bicarbonate to form a water- soluble sodium salt, whereas the polymer remains insoluble. This difference will be used to purify the aspirin product. The most likely impurity in the final product is salicylic acid, which can be either unconsumed reactant, or the result of hydrolysis of the aspirin product. Salicylic acid is removed during the purification steps as well. Salicylic acid, like most phenols, forms a highly colored complex with ferric chloride, and is easily detected. Aspirin does not form the colored complex because the hydroxyl has been acetylated. [pic] Background Reading McMurry, J., Organic Chemistry, 8th Ed., pp 830 and 835 (7th Ed, pp 802 & 806-7). J. Beran, Lab Manual for Principles of General Chemistry, 9th and 8th Ed., Experiment 19, pg 231. Key Words phenol, carboxylic acid, ester, acid anhydride, macromolecule Compound, Reaction, and Yield Data Provide systematic names for the reactant and product in the substance section. Provide tabulated and experimental melting ranges for product. Report mass and moles for the reactant and product, and calculate yield % on a molar basis. Mechanism The mechanism is called nucleophilic acyl substitution. It is similar, but not identical, to the hydrolysis on pg 830 in McMurry 8e. The electrophile is an acid anhydride, not an acid chloride. The entering nucleophile is salicylic acid (its phenol O), not water. On the resulting tetrahedral intermediate, the H from salicylic acid moves to the middle O on the anhydride. Finally, the leaving group is acetic acid, rather than chloride. No base is involved. Provide structures of all intermediates in your lab report. Substances 2.0 g salicylic acid 5.0 mL acetic anhydride 5 drops concentrated H2SO4 25 ml saturated NaHCO3(aq) 3.5 mL concentrated HCl Apparatus one 125-mL Erlenmeyer flask 70-mm filter paper and Buchner funnel 250-mL or 500-ml vacuum flask Procedure Part A: Synthesis 1. Weigh 2.0 g of salicylic acid crystals. Place in a 125-ml Erlenmeyer flask. 2. In a hood, slowly add 5.0 ml of acetic anhydride and 5 drops of concentrated sulfuric acid to the flask Caution - Concentrated H2SO4 solutions are corrosive and cause acid burns. Carboxylic acid anhydrides are corrosive and extremely hygroscopic. They will cause burns, and they have a strong vinegar-like odor. Use gloves and avoid all contact with skin, eyes, and nose. Perform entire step in fume hood. 3. Swirl the flask gently until the salicylic acid has completely dissolved. If mixture solidifies completely, proceed to step 4. 4. Heat the flask in a boiling water bath (100 oC) for a minimum of 10 minutes. Clamp the flask to a stand so that it does not fall over into the water bath. 5. Allow the flask to cool slightly, and then place in an ice bath to crystallize the acetylsalicylic acid. If necessary, gently scratch the bottom of the flask with a glass rod (to initiate crystal formation on microscopic glass particles). 6. After crystals have formed, add 50 ml of DI water, and cool the mixture in an ice bath. Do not add water until crystallization is complete. Also, place a beaker of DI water in the ice bath and cool to use in later steps. 7. Collect the product by vacuum filtration using a 70-mm filter paper and Buchner funnel. The filtrate can be used to rinse the Erlenmeyer flask repeatedly until all of the crystals have been collected. 8. Rinse the crystals collected in the funnel with 5 - 10 ml of 5 oC DI water. Then, apply vacuum to the crystals for 30 seconds to remove all of the