Micro scale Synthesis of Acetyl Salicylic Acid
Salicylic acid was a key component of medical treatment throughout history, dating back to the Greeks and their use of willow tree bark. Felix Hoffman, working for Friedrich Baeyer and Company in 1893, acetylated salicylic acid. This new drug reduced the irritating side effects of salicylic acid and became one of history's most popular drugs commonly referred to as aspirin. Effects of aspirin are still not fully understood and under investigation. Because of the lower pKa of benzoic acid group, aspirin exists as a water soluble salt in the intestinal tract and allows for absorption into the bloodstream. This same acidity, when released from a slowly dissolving tablet does cause local irritation to the stomach lining. Therefore, many times aspirin is administered in powder form or as a buffered tablet. Aspirin can be made by the acid catalyzed Esterification of salicylic acid, a benzene ring substituted with both a carboxylic acid and an alcohol group. We will acetylate salicylic acid using acetic anhydride, an acid anhydride. After synthesizing aspirin, we will analyze our product using different techniques.
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Reaction Mechanism: See Attached
Typically Organic reactions occur in Mechanism Steps. This illustration indicates the steps that will take place in our reaction.
Materials C Small reaction vial C Heating Setup C Beral-type pipet (2) C Small 50 ml Beaker C Test tube tongs C Small graduated cylinder C Buchner funnel vacuum setup C Salicylic acid C Acetic anhydride C Phosphoric acid, concentrated C Ice water Experimental Procedure 1. Place 1.0 g of salicylic acid and 2.5 mL of acetic anhydride in a reaction vial. Weigh the salicylic acid as it is being added to the vial. Add 5 drops of concentrated Phosphoric Acid to the vial. 2. Seal the vial with a Teflon-coated cap. Make sure the cap is on tight. Shake the reaction mixture. 5. Using tongs, place the sealed vial in the Heating Well located in front of the room. Note the time and return to pick up the vial in exactly 10 minutes. 5. Place 10 mL of ice and distilled water in a 50 ml Beaker. 6. After 10 minutes, use tongs to remove the vial from the heating device and place on the counter for a minute to cool. All the solids should be dissolved before removing the vial from the heating device. If solids still remain return the vial to the heating device.
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Isolation of Product 7. Carefully pour the contents of the reaction vial into the beaker which contains the ice water . White crystals should form shortly after the reaction mixture is added to the ice water. Rinse the reaction vial with 1-2 mL of distilled water and add it to the beaker. Swirl the beaker with the solution. 8. Add some more ice to the mixture and let stand for about 5-10 minutes. 9. Filter the acetylsalicylic acid while it is still cold using a Buchner funnel. Wash with 2-3 mL of cold water. Synthesis of Aspirin Data Table
Mass of Salicylic Acid Molecular Formula of Salicylic Acid Moles of Salicylic Used Molar Mass of Salicylic Acid Density of Acetic Anhydride Volume of Acetic Anhydride Used Mass of Acetic Acid Used Molecular Formula of Acetic Anhydride Moles of Acetic Anhydride Used Limiting Reagent Mass of Aspirin Synthesized Molecular Formula of Aspirin Molar Mass of Aspirin Moles of Aspirin Synthesized Theoretical Yield of Aspirin Synthesized Experimental Yield of Aspirin % Yield based on Quantity
Grams C7H6O3 mol g/mol 1.080 g/ml 2.50 ml g C4H6O3 mol grams C9H8O4 g/mol mol g g
Calculations:
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1. Thin-layer Chromatography - In thin-layer chromatography, there is a stationary phase (silica gel fixed on a plate backing) and a mobile phase (solvent). Depending on the functional groups possessed by a molecule, it interacts with these phases uniquely and differently than other molecules. So, if a mixture of molecules is applied to the TLC plate and the solvent is allow to flow through the silica gel, those molecules that interact better with the mobile phase than the stationary phase move quicker to the end of the TLC plate and separate from the other molecules. If the identity of the molecules to be separated is known, the composition of the mobile phase can be customized to maximize the difference in interaction of the molecules with the mobile phase and thereby increase the separation of the molecules on the TLC plate. Because salicylic acid and acetylsalicylic acid have different functional groups, we will use thin-layer chromatography to separate them in each of our time point samples. Preparing your TLC plate for developing Using your spot plate, place several crystals of samples: 100% salicylic acid, 100% acetylsalicylic acid, and your product into separate "spots." Take a TLC plate and lightly draw a line with a pencil,1 cm parallel to one edge. Lightly mark 3 evenly spaced marks on the parallel line. Added a couple drops of methanol to one of your spot plate samples and solublize your sample. Using your uL syringe, apply a small drop of the methanolic sample on its respective mark on the TLC plate. After the spot dries, reapply another drop of the methanolic sample. Rinse your syringe in methanol, and repeat the solubilization/loading for each of the samples. After all the samples have been loaded and the spots are completely dry, you are ready to "develop" your TLC plate o Developing your TLC plate Add a small amount of 57:40 :3 (cyclohexane: dichloromethane: glacial acetic) developing solvent into a 1 L TLC Chamber. Soak a folded paper towel in the developing solvent and place it in the bottom and against the wall of the beaker. Place the dried TLC plate in the beaker so that the solvent is touching the plate but below the spotted samples . Place a large watchglass over the beaker and allow the solvent to rise. After the solvent front has stop rising or approaches the top of the TLC plate, remove the plate, mark the solvent front with a pencil, and allow the plate to dry in the hood. o After your TLC plate is dry, use a UV lamp to circle all compounds in each sample. Then, determine each compound's Rf value. Also, note the size of the salicylic acid and acetylsalicylic spots. Are their relative sizes o
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reversing as the reaction proceeds? Why do the "spots" of salicylic acid and acetylsalicylic acid have different colors under the UV light? synthesized aspirin
commercial aspirin
salicylic acid
distance spot traveled (cm) distance eluting solution traveled (cm) Rate of Flow- Rf Value
Placing Samples on TLC Plate Developing TLC Plate
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