Synthesis of Acetaminophen using different Techniques in Lab, Lab Reports of Organic Chemistry

Download Synthesis of Acetaminophen using different Techniques in Lab and more Lab Reports Organic Chemistry in PDF only on Docsity! Oganesyan, Chem-105 Synthesis of Acetaminophen1 Target Molecule: Acetaminophen Introduction Acetanilide, phenacetin, and acetaminophen are mild analgesics (relieve pain) and antipyretics (relieve fever). Preparation of acetaminophen involves treating an amine with an acid anhydride to form an amide. In this case, p-aminophenol, the amine, is treated with acetic anhydride to form an amide, acetaminophen. Experimental SAFETY PRECAUTIONS • Wear safety glasses or goggles at all times in the laboratory. • Acetic anhydride is corrosive and its vapor is irritating to the respiratory system. Avoid skin contact and inhalation of the vapors. In the event of skin contact, rinse well with cold water. If the vapors are inhaled, move to an area where fresh air is available. • P-aminophenol is harmful by inhalation and by contact with the skin. In the event of skin contact, rinse well with cold water. If the vapors are inhaled, move to an area where fresh air is available. Techniques: please read the techniques from PLK and the notes at the end of the handout. • Vacuum filtration • Recrystallization • Melting point determination • Thin Layer Chromatography (TLC) A. Synthesis of acetaminophen 1. Weigh ~ 1.5 g of purified p-aminophenol (MW = 109.1 g/mol) and place this in a 50 mL Erlenmeyer flask. Using a graduated cylinder, add 1.7 mL of acetic anhydride (MW = 102.1 g/mol, d = 1.08 g/mL) and 4.5 mL of water. 2. Place a magnetic stir bar in the flask and heat the reaction mixture on a hot place. Monitor the temperature of the reaction (keep it at ~100oC). 3. After the solid has dissolved (it may dissolve, precipitate and re-dissolve), heat the mixture for an additional 10 minutes to complete the reaction. 4. Remove the flask from the hot plate, and allow it to cool to room temperature slowly. If crystallization 1 Adapted from Pavia’s Organic Laboratory Techniques, Saunders College Publishing, Philadelphia (1990). does not occur, scratch the inside walls of the flask and immerse in an ice bath for 10-15 minutes. 5. Collect the crystals by suction filtration on a Buchner funnel. Rinse the flask with two portions of 1 mL of ice-cold water and transfer this to the Buchner funnel. Dry the crystals for 10 minutes by allowing air to be drawn through them while they remain on the Buchner funnel. Transfer the crystals to a watch glass and record the weight of the crude product (MW = 51.2 g/mol). Calculate the crude percent yield. 6. Obtain a couple of crystals of the crude product, dissolve them in acetone (bulk acetone is acceptable) and spot a TLC plate on the base line with the product. Spot the starting material and the authentic acetaminophen product (reference solutions are available on the cart). Check the spots under UV light, place the plate into the eluting chamber with 50:50 mixture of ethyl acetate/hexanes, and proceed with elution. 7. Remove the plate from the chamber, let it dry, and trace the spots under UV light. Calculate the Rf values. 8. Proceed with the purification step. B. Decoloraization of Crude Acetaminophen (performed only if the crude product is contaminated with colored impurities). 1. Add your crude acetaminophen product to a 50 mL Erlenmyer flask containing 15 mL of sodium dithionite solution (prepare the solution by dissolving 2.0 g of sodium dithionite in 15 mL deionized water). 2. Heat the mixture at ~100oC for 15 min, stirring it occasionally with a spatula. 3. Let the solution to cool down to room temperature, and then precipitate the product on an ice bath (induce crystallization by scratching the inside wall of the flask with a glass rod). 4. Vacuum-filter the solution on a Buchner funnel and wash the precipitate with small (~2 mL portions) of ice-cold water. 5. Dry the crystals for 5-10 min, record the changes in appearance of the product, and reweight it again. Compare the weight with that of obtained for the crude product. 6. Save the decolorized product in your locker until the next class period. C. Purification of Acetaminophen 7. Place all of the acetaminophen in a 50 mL Erlenmeyer flask. 8. In another flask, place ~ 7 mL of a solvent mixture composed of 50% water and 50% methanol by volume, with a boiling stone. Place this flask on a hot plate. When the solvent begins to boil, add small portions of hot solvent until the solid dissolves. Use minimum amount of the hot solvent to dissolve the CP SM AP CP = crude product SM = starting material (4-aminophenol) AP = authentic acetaminophen Fig. 1. Recrystallization procedure. VACUUM FILTRATION Vacuum filtration is used to quickly collect the solid product from the solution. Reduced pressure allows for easy and quick removal of solvent, and the solid precipitate is collected on a Buchner funnel. Clamp a side arm flask securely to a ring stand. Place the rubber adaptor in the side arm flask. Place the Buchner funnel on the adaptor. Get a piece of filter paper and put it in the Buchner funnel. Connect the side arm flask to a vacuum source - always use thick-walled since Tygon tubing will collapse under reduced pressure. Wet the paper with a small amount of the solvent to be used in the filtration. Turn on the water aspirator. Wet the paper - this causes the paper to adhere to the plate and keeps materials from passing under the paper during filtration. Make sure that the paper is secured on the filter, that air is being drawn through the paper, and that all of your apparatus is securely clamped. If you are using a Neoprene filter adaptor, you might need to press on the funnel to engage the seal and thus the vacuum. Now you are ready to begin filtration. Filter the solution. Pour the mixture to be filtered onto the filter paper. The vacuum should rapidly pull the liquid through the funnel. Watch that particulates do not creep under the edges of the paper. If this happens, start over and carefully pour portions of the solution onto the very center of the paper. Watch that particulates do not creep under the edges of the paper. If this happens, start over and carefully pour portions of the solution onto the very center of the paper. Notice that the vacuum has pulled the solvent through the filter and into the filter flask. Rinse the solids. Rinse the cake with a small amount of fresh, cold solvent to help remove impurities that were dissolved in the filtrate. Disconnect the rubber tubing before turning off the water aspirator. Remove the filter paper and the collected solid that is on it. Usually you will set it on a watch glass and let it air dry for a while; p). Rinse the flask with a little fresh solvent and pour it into the filter funnel. Disconnect the vacuum AT THE FLASK and before turning off the water aspirator. This prevents water from being sucked into the vacuum flask. Carefully remove the filter paper and solid from the Buchner funnel. Set the filter cake onto a watch glass to air dry. Fig. 2. Vacuum filtration procedure Fig. 3. Preparation of filter paper for gravity filtration Guidelines for writing report on ‘Acetaminophen’ experiment (15 pt) The report should be not longer than three pages, double-spaced (font size 12). Please follow the instructions given below: 1. Abstract: The abstract should state the purpose of the experiment, the method used, and brief summary of experimental results. Be very specific: you know what and how much you’ve made, and how you’ve made it. 2. Reactions: synthesis of acetaminophen (arrow-pushing mechanism). 3. Results/Discussion: Tabulate your experimental results as in the table below. If the results are not successful, explain why (go back to your procedure and observations and try to connect the outcomes with the steps performed: did you loose your compound there, did you heat the reaction too long, etc?) Even if your experiment was a complete failure, try to come up with an intelligent explanation. Report on the TLC analysis: comparison of the starting material, crude, and purified product and the authentic acetominophen sample. Remember, this section of your experiment counts for the largest portion of points. compound Number of spots Rf values Purity Acetaminophenol Crude product Purified product Authentic acetaminophen Compound Amount, g % Yield mp, oC Color Texture Crude (wet) Crude (dried) Purified 4. References: follow the instructions in the manual and the handout provided. You will be graded on the yields (crude and purified), mp range for the pure compound, the color and texture of your product, and the TLC plate. You do not include this section in your report, this is just for your reference in regards to the points earned.