Aspirin and Analgesics - Synthesis and Analysis - Lab #21 | CH 106, Lab Reports of Chemistry

Download Aspirin and Analgesics - Synthesis and Analysis - Lab #21 | CH 106 and more Lab Reports Chemistry in PDF only on Docsity! CH106 Lab 21: Aspirin & Analgesics 279 LAB 21: ASPIRIN AND ANALGESICS: SYNTHESIS & ANALYSIS PURPOSE: To synthesize aspirin from wintergreen or from salicylic acid. To test the purity of aspirin by testing for the presence of phenols. To use thin-layer chromatography to identify substances in analgesics. SAFETY CONCERNS: Always wear safety goggles. Acetic Anhydride and Acetic Acid are irritating to skin, eyes, and mucus membranes. If contacted, wash with soap and copious amounts of water. ASPIRIN: History: The bark of the willow tree was used by ancient Native Americans to counter fever and pain. Europeans learned of willow bark’s medicinal properties in 1763 when clergyman Edward Stone presented his findings to the Royal Society of London. Willow bark extract was found to be a powerful drug with analgesic (pain reliever), antipyretic (fever reducer), and anti- inflammatory (reduces swelling) properties. In 1838 organic chemists isolated the active ingredient and identified it as salicylic acid, named from salix, Latin for the willow tree. Although an effective remedy, the use of salicylic acid was limited because it damaged mucous membranes of the mouth and esophagus, and caused hemorrhaging of the stomach lining. It was determined that the acidic phenol group could be responsible for the damaging effects so in 1893 German chemist Felix Hoffman, working for the firm of Bayer, synthesized an ester of salicylic acid, acetylsalicylic acid. Acetylsalicylic acid was marketed by Bayer under the trade name of aspirin. During World War I the U.S. Government seized Bayer’s assets and sold them and the Bayer name to Sterling Products which became Sterling Winthrop Inc. Biological Effect: Aspirin works to relieve fever and pain by inhibiting the formation of prostaglandins, a class of 20-carbon acids that form at the site of an injury and are responsible for causing the inflammation and pain. Aspirin works as a blood thinner by also inhibiting the formation of thromboxins which aid in the production of blood clots. Aspirin should not be given to children who have influenza or chicken pox because of the risk of the rare but often fatal Reye’s Syndrome. Children suffering from these diseases should be given a nonaspirin pain reliever such as acetaminophen. Unless directed by a physician, aspirin should not be taken during the last 3 months of pregnancy. CH106 Lab 21: Aspirin & Analgesics 280 Preparation and Reactivity: Aspirin is easily prepared in the laboratory by esterification of salicylic acid with acetic acid. + Acetic Acid + Salicylic acid Acetylsalicylic acid (Aspirin) Water C O OH OH C O O C O OH CH3 H O HC O HO CH3 Esterification Hydrolysis H+ Preparation of aspirin by treatment of salicylic acid with acetic anhydride, however, is much faster than traditional esterification so is more practical for us to do in a limited laboratory time. + Acetic Acid + Salicylic acid (138 g/mol) Acetylsalicylic acid= Aspirn (180 g/mol) Acetic Anhydride C O OH OH C O O C O OH CH3 CH3 C O C CH3 O O CH3 C OH O Like salicylic acid, aspirin is an analgesic, antipyretic, and anti-inflammatory; but it is much less irritating to the stomach. Aspirin does cause slight gastrointestinal bleeding that can, over time, cause iron deficiency or gastric ulcers. These complications can be avoided with enteric-coated aspirin, which does not dissolve until reaching the small intestine. The basic conditions in the small intestine hydrolyze the acetylsalicylic acid to salicylic acid, which is absorbed into the bloodstream. In commercial aspirin tablets about 325 mg (5 grains) of aspirin is bound together with inert materials called binders, whose function is to hold the tablet together. Some manufactures apply a micro-coating of hydroxypropyl methylcellulose to prevent the tablet from dissolving in the mouth but permit it to dissolve in the stomach. Sometimes buffers are added to combat stomach irritation. Aspirin may be reconverted into salicylic acid in either of two ways; hydrolysis in an acidic solution which is the reversing of the equilibrium esterification to make it, or by hydrolysis with base (called saponification). If aspirin is stored over a long period of time, especially under moist conditions, the hydrolysis reaction takes place, and the characteristic odor of vinegar (acetic acid) is easily detected. Generally, "old" aspirin tablets contain traces of acetic acid and salicylic acid. CH106 Lab 21: Aspirin & Analgesics 283 PROCEDURES: ACTIONS: I. SYNTHESIS OF ASPIRIN: A. PREPARATION: 1. In the fume hood prepare a boiling water bath by heating about 150 mLs of water in a 400 mL beaker over a hot plate. 2. Carefully mass 2.00g1 of salicylic acid and put it into a 125 mL Erlenmeyer flask. 3. Under the fume hood2 carefully add 5 mL of acetic anhydride3 to the flask of salicylic acid and swirl or stir to mix. 4. Slowly add 10 drops of 85% phosphoric acid, (H3PO4) to the salicylic acid and acetic anhydride and mix well. 5. Place the flask and its contents in the boiling water bath under the hood and stir until all the solid dissolves. 6. Let react over steam bath for about 10 minutes. Then remove the flask from the hot water and let it cool to room temperature. 7. Cautiously4 add 20 drops of deionized water to the cool mixture.5 8. When the reaction is complete and the flask is room temperature, add another 50 mL of ice water directly to the reaction flask and then cool the mixture by placing the flask in an ice bath for about 10 minutes. Crystals of aspirin should form. 6 B. COLLECTION OF ASPIRIN CRYSTALS 9. Set up a Buchner or Hirsh funnel apparatus and moisten the filter paper. 10. Turn on the water aspirator and pour the aspirin product onto the filter paper in the funnel. 7 11. Use a spatula to transfer any aspirin crystals left in the flask to the funnel and rinse the inside of the flask into the funnel with a 10 mL portion of ice cold water. 8 12. Spread the aspirin crystals out on the filter paper in the Buchner funnel and continue to draw air through the funnel to help dry the crystals. 9 13. Turn off the water aspirator and use a spatula to lift and transfer the filter paper with the aspirin residue on it to a watch glass. Allow the crystals to air dry. 10 NOTES: 1The measurement does not need to be exactly 2.00g, however, you do need to know exactly how much you do have. Report whatever mass you obtain to the accuracy of your balance so that you can most correctly determine the percent yield of your product when you are done. 2Acetic anhydride is irritating to the nose and sinus. Handle carefully. 3Acetic anhydride is used in excess so the salicylic acid is the limiting reagent. 4Keep your face away from the top of the flask: The acetic acid vapors that are produced are irritating. 5The water is stopping the reaction by hydrolyzing any unused acetic anhydride into acetic acid. 6If no crystals appear, gently scratch the insides of the flask with a stirring rod. 7The aspirin product will be the residue that remains on the filter paper. 8The 10 mLs of ice water can be used a little at a time to make several small rinses. Several small rinses will be more effective at transferring product that one large rinse. 9This helps to partially dry the crystals. 10You may need to let your crystals dry in your drawer until the next lab period to get an accurate weight for yield calculations and an accurate melting point in Part IIE. CH106 Lab 21: Aspirin & Analgesics 284 14. Weigh your dry sample to the accuracy of your balance. Determine the mass of your aspirin product to the accuracy of your balance and report this actual yield on your report sheet. C. CALCULATIONS: 15. From your calculations in your Prelab assignment, record the maximum possible (theoretical) yield of aspirin that could be made from the 2.00 grams of salicylic acid with which you began on your report sheet. 16. Calculate the percent yield of aspirin you obtained. 11 II. ANALYSIS: A. CHROMATOGRAPHY: 1. Obtain a silica TLC plate12 with fluorescent indicator cut to a size of 6 x 10 cm. 2. Draw a light line with pencil13 about 1 cm above14 the bottom of the short end of the plate. Mark 6 spots on the line equally spaced but away from the edges. Label the spots from A to F. 3. Using clean capillary pipettes, one for each substance, make tiny spots of each of the following substances on the appropriately labeled marks until there is sufficient sample spotted on the plate. 15 A: salicylic acid dissolved in ethanol B. acetylsalicylic acid dissolved in ethanol C. your prepared aspirin dissolved in ethanol16 D. caffeine dissolved in ethanol E. acetaminophen dissolved in ethanol F: Extra Strength Excedrin dissolved in ethanol 4. Obtain a chromatography developing chamber, or make one from a 400 mL beaker, a piece of Saran wrap that covers, and a rubber band. 5. Carefully pour about 50 mLs of chromatography solvent (50% ethyl acetate and hexane) into the chamber to a level of 0.5-0.6 cm14 and cover the chamber with a lid or saran wrap.17 6. Carefully set the TLC plate in the solvent in the chromatography developing chamber.18 Cover and allow the beaker to remain undisturbed as the solvent moves up the plate. 7. When the solvent has risen almost to the top of the plate, remove the plate and draw a pencil line along the solvent front quickly before it dries. 11Percent yield = (actual yield/theoretical yield) X 100. 12Be sure you handle the plates at the edge only to avoid transferring substances from your fingers and to avoid rubbing the silica from the plate. 13Any markings or labels must be drawn with pencil rather than pen to avoid separation of any ink pigments. Pencil markings and labels must also be made very lightly to avoid scraping the silica from the plate. 14It is important that the solvent level is below the spots you place on the TLC plate so that the solvent does not simply wash the samples away. 15When the spot dries you can apply again. The spot must be kept small and not allowed to flow into larger spots. Dark spots under UV light indicate the presence of a sample containing an aromatic ring. 16Take a small crystal of your sample and dissolve it in a few drops of ethanol. 17The developing chamber must be covered to avoid evaporation of the solvent from the plate and from the chamber itself. 18The sides of the TLC plates should not touch the sides of the chamber. The solvent must rise up the plate from the bottom only and not from the sides of the plate. CH106 Lab 21: Aspirin & Analgesics 285 8. When the solvent has evaporated from the TLC plate, observe it under UV light.19 Circle each spot and draw a picture of the spots on your report sheet. 9. Measure the distance from the origin to the solvent front and measure the distance from the origin to the center of each spot. Calculate the Rf value for each spot and record them next to each spot on your report sheet. 10. Determine and label the identity of each spot19 on the report sheet and formulate conclusions as to the purity of your prepared aspirin and as to the make up of extra strength Excedrin. 11. Place used chromatography solvent in the organic waste solvent container. B. PH: 12. Obtain 5 test tubes (any size) and label them A, B, C, D, & E. 13. Into tube A place 3 mL of 0.15% Salicylic acid solution. Into tubes B, C, D, and E, place about 3 mL of deionized water.20 14. Into tubes B, C, D, and E, add a few crystals (the amount on the tip of a spatula) of the indicated solids: Tubes B; add Commercial Aspirin (crushed). Tube C; add Buffered Aspirin (crushed). Tube D; add Aspirin product you prepared in Part I. Tube E; add Acetylsalicylic acid. Mix each well21 15. Stir each mixture A through E and touch the wet stirring rod to a piece of pH indicator paper. Compare the color of the wet paper to the chart on the container and record the pH. 17. From your results make some conclusions as to potential throat, esophagus or stomach irritation. 18. Use the same samples A through E for the test for phenols. C. TEST FOR PHENOLS: 16. To each of the sample tubes A through E add 5 drops of 0.1 M ferric chloride (FeCl3) solution. Mix well. Record your observations.221 19. From your data make some conclusions as to the composition of your prepared aspirin as well as the other samples. 20. Conclude whether the Aspirin you made in Part I would be considered pure by USP standards. 23 19Compounds containing an aromatic ring will appear dark under the UV light. Those without an aromatic ring will not appear at all. Salicylic Acid show fluorescent blue under UV light. 20The measurement does not need to be exact. You can determine 3 mls for the first tube with a graduated cylinder and then eyeball the height of water in each of the other tubes to match. 21Mixing can be done by tapping the sides of the test tubes, by stirring with a glass rod, or by stoppering and shaking. 22Any free salicylic acid either unreacted during synthesis or resulting from hydrolysis of aspirin, reacts with the Fe+3 ion to give a purple color. More salicylic acid in the sample results in a deeper color. A purple color resulting from addition of Fe+3 to aspirin or acetylsalicylic acid indicates that the product is either impure or that decomposition has taken place. 23The maximum salicylic acid allowed in commercially prepared aspirin products is 0.15%. If the sample test has a lighter color than a 0.15% standard, the sample would be considered pure by United States Pharmacopeia (USP) standards. If the sample is darker, it is impure and not considered safe for ingestion. However, no matter what the results of the test, your laboratory- prepared aspirin must not be ingested! CH106 Lab 21: Aspirin & Analgesics 288 CH106 Lab 21: Aspirin & Analgesics 289 LAB 21: ASPIRIN & ANALGESICS: NAME___________________ REPORT: PARTNER_________DATE___ I. SYNTHESIS OF ASPIRIN: STARTING REAGENT Salicylic Acid PRODUCT Acetylsalicylic Acid Molar Mass Grams (Actual grams used) (Theoretical yield: grams expected: Show calculations) Moles (Actual Moles used: Show calculations) (Theoretical moles expected:) Yield, grams (Actual experimental yield) Percent Yield (% yield: Show calculations) Error Analysis: Are your experimental results as expected or are there discrepancies? Explain II. ANALYSIS: A. Chromatography: Draw and label each spot. Summary & Conclusions: Identity of Excedrin Components from Product Label: Identity of Excedrin Components from TLC: Error Analysis: (how does this compare to expected?) Purity of prepared Aspirin from TLC Error Analysis: (how does this compare to expected?) A B C D E F CH106 Lab 21: Aspirin & Analgesics 290 Tests for Quality: A. 0.15 % Salicylic acid B. Commercial Aspirin C. Buffered Aspirin D. Prepared Aspirin E. Acetylsalicylic Acid B. pH Conclusions? (Has decomposition occurred? Does a buffer affect pH?) C. Test for Phenols (Color after rxn w/ FeCl3) Conclusions? (+ or -) Would it be USP approved? (Yes or No) Error Analysis: Are your experimental results as expected or are there discrepancies? Explain D. Identity of Binder in Commercial Aspirin Results: (Describe Color after addition of I2) Conclusions? (Identity? Explain how you know) E. Melting point Salicylic Acid (Known) Acetylsalicylic Acid (Known) Your Aspirin (By experiment) Melting point Conclusions? (How pure is your aspirin? Explain how you know) Error Analysis: Are your experimental results as expected or are there discrepancies? Explain