Synthesis of Asa

CHEMISTRY 101.1
Intermediate Chemistry Laboratory I Institute of Chemistry University of the Philippines, Diliman

I.

Synthesis of Salicylic Acid Purpose: Part I of the experiment illustrates the base hydrolysis of an ester, methyl salicylate, to form salicylic acid through nucleophilic acyl substitution. Procedure: Dissolve 12 g NaOH in 70 mL water in a 150 mL round bottom flask. Add 5.0 mL methyl salicylate and reflux the reaction mixture at its boiling point for 15 minutes using a stirrer hotplate and stirring bar. Cool the mixture to room temperature. Carefully add 3 M H2SO4 in 1 mL increments until a white precipitate forms and remains when the mixture is stirred. Add 0.5 mL more acid to ensure complete precipitation of salicylic acid. Cool the mixture in an ice water bath (≤ 5°C). Rinse the precipitate well with ice-cold water. Recrystallize the products from water in 50-mL Erlenmeyer flask. Obtain the weight of the dried product and compute for the %yield. Measure its melting point and compare it to literature value. Give the chemical equations involved in the synthesis of salicylic acid. Waste Disposal: Neutralize any acid in the filtrate using aqueous sodium carbonate and flush it down the sink with copious amounts of water. References: [1] Mohrig, J. R.; Hammond, C. N.; Morrill, T. C.; Neckers, D. C. 1998 Experimental Organic Chemistry, New York: Freeman, pp. 32-36. [2] www.chemblink.com

II.

Potentiometric Determination of the Purity and Acid Dissociation Constant of Salicylic Acid Purpose: Part II of the experiment utilizes the concept of potentiometric titration in the determination of the pKa, a measure of the relative acidity of an acid, of the salicylic acid product in Part I. Potentiometric titration will also be used to determine the purity of salicylic acid.

Procedure: Prepare the following solutions: 250 mL of 0.50 M stock NaOH solution and 250 mL of 0.050 M standard NaOH solution from 0.50 M NaOH. Standardize 0.050 M NaOH by

References: [1] Analytical Chemistry Academic Group. Analytical Chemistry Laboratory Manual 2007 ed., Institute of Chemistry, University of the Philippines, Diliman, Quezon City. [2] Potentiometric Titration of an Unknown Weak Monoprotic Acid. East Stroudsburg University. 2008. Available in the internet: http://www.asdlib.org/onlineArticles/Gross_Potentiometry/UnkAcidLab.pdf Retrieved September 24, 2008. [3] Potentiometric Titration of Weak Acid: A Weak Acid/Strong Base Titration. Clark College. 2005. Available in the internet: http://www.web.clark.edu/nfattaleh/classes/135/Sp05/Labs/PotTitrSp05.pdf Retrieved September 24, 2008. [4] Skoog, D. A.; West, D. M.; Holler, F. J.; Crouch, S. Fundamentals of Analytical Chemistry 8th ed., Singapore: Brooks Cole, 2004. [5] Potentiometric Titration. Towson University. 2008. Available in the internet: http://www.towson.edu/~topping/Experiment5Chem210.doc Retrieved March 12, 2009. III. Synthesis of Acetylsalicylic Acid Purpose: This experiment uses the synthesized salicylic acid in Part I to prepare acetylsalicylic acid (ASA). Salicylic acid itself in unsuitable as a drug because it does not taste good and it causes gastric irritation. To eliminate these unfavorable characteristics, salicylic acid is esterified to acetylsalicylic acid. ASA passes through the stomach unchanged before being hydrolyzed by the basic medium of the intestine to form the active compound. Procedure: The following procedure should be done in a fume hood. Dissolve salicylic acid (3.0 g) in acetic anhydride (5.0 mL) in a dry 100 mL round-bottom flask. Swirl the flask and carefully add 3 drops of concentrated sulfuric acid. Cover the flask with a small watch glass to prevent condensation of water inside the flask during heating on the steam bath. Heat the flask on a steam bath for 15 minutes. Remove the flask from the steam bath and while the contents are still hot, cautiously add water (5 mL) dropwise. After the reaction subsides, add ice-water (35 mL) all at once, and swirl the flask for a few seconds. Remove the flask from the fume hood and chill it in an ice-bath. If the crystallization id slow, it may be helpful to scratch the inside of the flask with a stirring rod. After crystallization is complete, decant the liquid from the flask into a funnel, minimizing transfer of crystals. Beak up any lumps of solid in the flask using a stirring rod and add ice-water (10 mL). Swirl the flask, chill briefly and empty all the contents of the flask into the funnel. Use an additional 10 mL of chilled water to transfer any solid which may be left in the flask. Determine the mass of the dried product and compute for the %yield. Compare its melting point with literature value. Reference: [1] Williamson, K. L. 1994 Macroscale and Microscale Organic Experiments, Lexington, MA: DC Heath and Company, pp. 379-384.