Preparation of an Ester Acetylsalicylic Acid (Aspirin) BJECTIVE: To become familiar with the techniques and principle of esterification. DISCUSSIN: Aspirin is a drug widely used as an antipyretic agent (to reduce fever), as an analgesic agent (to reduce pain), and/or as an anti-inflammatory agent (to reduce redness, heat or swelling in tissues). Chemically, aspirin is an ester. Esters are the products of reaction of acids with alcohols, as shown in the following equation using type formulas: R C H + R H R C R + H 2 ACID ALCHL ESTER WATER The symbol R refers to the hydrocarbon portion (radical) of the molecules aside from the functional group. In an organic acid, R C H, the functional group is the carboxyl group (-CH) or C-H. The type of formula for an alcohol is R-H, where the functional group is the hydroxyl group (-H). The symbol R indicates that the two R-groups in the ester formula need not be the same. It has been shown by radioactive tracer methods that in the mechanism of the esterification reaction, the H group is split from the acid and the H from the alcohol. Aspirin can be made as follows: C H C H CH 3 C H + H CH 3 C + H 2 Acetic acid Salicylic acid Aspirin (containing an (acetylsalicylic acid, -H group) an ester) The use of acetic anhydride instead of acetic acid, however, is a better preparative method, because the anhydride with the water to form acetic acid tends to drive the reaction to the right as shown below. An acid catalyst also is used to speed up the reaction. CH 3 C C CH 3 C H C H + H CH 3 C + CH 3 C H Acetic anhydride Salicylic acid Aspirin Acetic acid (138.12 g/mol) (180.15 g/mol)
The theoretical yield of aspirin in grams is the mass calculated from the above equation, with salicylic acid being the limiting reagent. The actual yield of aspirin is obtained by carrying out the synthesis: item (3) in the Report form. The percentage yield is found by the following relationship: percentage yield actual yield theoretical yield x100% In this exercise, you will prepare a sample of aspirin, determine your theoretical, actual, and percentage yields, and estimate the purity of your product based on its melting point. DANGER: A C E T I C A N H Y D R I D E Vapor of liquid causes severe burns. Harmful if inhaled. Combustible. Do not get liquid or vapor in eyes, skin or clothing. Do not breathe vapor. If contacted, remove contaminated clothing at once. Immediately flush skin or eyes with plenty of water. For eyes get medical attention. Wash clothing before re-use. PRCEDURE: Day ne Day Two Day Three btain a clean, dry 50-mL Erlenmeyer flask. Add 2.0 g of salicylic acid, 5.0 ml of acetic anhydride (Caution: Avoid contact with skin), and 5 10 drops of concentrated sulfuric acid to the Erlenmeyer flask. Mix the contents by swirling gently until the reactants are in solution. Then heat the flask and contents by clamping it in a water bath maintained at 80 o C for 15 minutes. Now remove the flask from the water bath and immediately, but cautiously, add 2 ml of distilled water to decompose any remaining excess acetic anhydride. Allow the flask to cool for a few minutes and then add 20 ml of water. Place the flask in an ice-water bath; crystals should begin to appear. Sometimes it may be necessary to scratch the inside of the flask with a glass rod to initiate crystallization. While waiting for the crystallization assemble a filtration setup (see Figure 2), and familiarize yourself, if necessary, with the procedure. When crystallization seems complete, collect the aspirin on filter paper by filtering the mixture. Use the vacuum filtration with Büchner funnel. Wash the aspirin with five separate 10-mL portions of icecold distilled water. Allow the filter paper to drain. When drained, remove the filter paper and its contents from the funnel and place the opened filter paper on a paper towel to absorb moisture. In the meantime, weigh a dry sheet of filter paper to the nearest 0.1 g (1). Now, using a clean, dry stirring rod, carefully transfer the product to the weighed filter paper and allow it to air dry. When dry, weigh the product plus filter paper to the nearest 0.1 g (2). The difference is the mass of your product, or actual yield (3). Determine the melting point of your product. Heat the oil bath slowly and report the melting point as the temperature at which the last crystals disappear (4). Look up the melting point of aspirin in a handbook, and record it (5). Compare these two melting points, and comment on the purity of your product (6). Calculate the theoretical yield (7) and your percentage yield (8).
ASPIRIN
Esters Pre-Lab Discussion Esters are organic compounds formed by the reaction of an alcohol with an organic acid. This process, called esterification, can be represented by the general equation: R 1 H + R 2 CH R 2 CR 1 + H 2 alcohol acid ester water where R 1 and R 2 represent hydrocarbon radicals that may be the same or different. The name of the ester is formed from the names of the alcohol and acid that react. For example, the ester formed from ethyl alcohol (ethanol) and acetic acid is called ethyl acetate. The first part of the name comes from the alcohol and the second part from the acid. The names of all esters end in the suffix ate. The molecular equation for this reaction is: C 2 H 5 H + CH 3 CH CH 3 CC 2 H 5 + H 2 alcohol acid ester water Notice that in the formula for the ester, the acid portion is written first. The structural arrangement of the atoms in ethyl acetate is: H H H H C C C C H H H H from the acid from the alcohol Esters are liquids that have characteristic odors that resemble those of fruits or flowers. For this reason, they are used extensively in the manufacture of deodorizers, perfumes, and other products that have a fragrance. This experiment will demonstrate the preparation of esters. Three esters will be prepared and their odors noted. PURPSE Prepare several esters. EQUIPMENT Graduated cylinder, 10-mL test tubes, 25 x 200 mm (3) burner beaker, 250 ml rubber stopper, 1-hole (for test tube) safety glasses iron ring dropper pipet microspatula utility clamps (2) lab apron ring stand 10 mm glass tubing (50 cm)
SAFETY MATERIALS ethanol methanol *amyl alcohol acetic acid, glacial salicylic acid 18 M sulfuric acid *(also named n-pentyl alcohol ) Figure 1 PRCEDURE Part A: ETHYL ACETATE Place 5 ml of each of ethanol and glacial acetic acid in a 25 x 200 mm test tube. Add eight drops of 18 M H 2 S 4. CAUTIN: Handle this acid very carefully. Insert a 50 cm length of 10 mm glass tubing into a 1-hole rubber stopper. The end of the tubing should extend very slightly below the bottom of the stopper. Fill a 250 ml beaker about 200 ml of tap water. Set up the apparatus as shown in Figure 1. Gently heat the water to boiling. nce the water boils, reduce the heat and allow the water to simmer gently. D NT HEAT THE TEST TBE DIRECTLY. Heat for about 15 minutes. Turn off the flame and remove the test tube from the water bath. Allow the liquid in the tube to cool and then note and record its odor. Part B: AMYL ACETATE Repeat the procedure followed in Part A using 5 ml of amyl (n-pentyl) alcohol, 5 ml of glacial acetic acid, and eight drops of 18 M H 2 S 4. Note and record the odor of the ester. Part C: METHYL SALICYLATE Repeat the procedure again, this time using a spatula full of salicylic acid, 5 ml of methanol, and eight drops of 18 M H 2 S 4. Note and record the odor of the ester.
Report Sheet D A T A T A B L E Name B S E R V A T I N S ESTER Structure DR Ethyl acetate Amyl acetate Methyl salicylate CNCLUSINS AND QUESTINS 1. Write the equation for the three esterification reactions. Part A Part B Part C 2. What is the role of the sulfuric acid (H 2 S 4 ) in these reactions? 3. How is the H radical of an alcohol different from that of an inorganic compound (a base)? 4. In what types of products are esters used?
DATA TABLE: Preparation of an Ester Acetysalicylic Acid (Aspirin) Weight of salicylic acid used... g Weight of acetic anyhdride used... g (density = 1.08 g/ml) (1) Weight of filter paper... g (2) Weight of filter paper + aspirin... g (3) Actual yield of aspirin (2) - (1)... g (4) Melting point of the aspirin product... o C (5) Melting point of aspirin from handbook... o C (6) Comment on purity of product, based on a comparison of (4) and (5) : (7) Theoretical yield of aspirin (show calculation): (8) Percentage yield of aspirin (show calculation): Suggest modifications to this lab protocol to make it easier for co-workers to follow.