Aspirin Is One of the Most Widely Used Compounds - Coursework Example

Aspirin is one of the most widely used compounds in the world. It is used for a number of reasons in the medical community, including as ananalgesic and for its blood thinning properties. Due to its popularity, there are several different brands of aspirin on the market, all of which will have different amounts of salicylic acid as their active ingredient. Using the determination of this purity as a base, the experiment will compare the effectiveness of different purification methods, as well as exploring several important chemical ideas, such as concentration and theoretical yields. The whole experiment has been risk assessed to ensure complete safety in the laboratory during the process of this experiment. The first experiment in this investigation involves synthesizing aspirin from salicylic acid. This is important because it shows the content of the commercially available aspirin brands and also acts as another testable example of acetylsalicylic acid for the investigation. There are then three different methods of testing the purity of aspirin. The first is known as a back titration and relies on the principles of pH. This experiment uses different types of acid to react with a known concentration of NaOH to investigate how much acetylsalicylic acid is present in each compound. The result of this can be seen using an indicator, phenolphthalein. The second method is another type of titration called forward titration. This relies on the principles behind the general chemical reaction acid + base = salt + water, because aspirin neutralises a cold solution of sodium hydroxide. This again can be measured using the indicator phenolphthalein. The final method is known as colourimetry, and relies on the principle that the colour we see is an object reflecting certain wavelengths of light. In this case, differing concentrations of a chemical compound will cause different amounts of a certain wavelength of light to be reflected. By measuring the light reflected using a colourimeter, we can see how much of the acetylsalicylic acid is present in each compound. Aims 1) (AS) Which brand of commercially available aspirin is the purest? To determine the purity of aspirin, we can use one of several different methods. In this case, a back titration, a standard titration and a colourimetry experiment will be undertaken to determine the amount of acetylsalicylic acid in each of three commercially available aspirin brands (as well as acetylsalicylic acid created in the laboratory – see below). Back titration involves using phenolphthalein as an indicator, as well as the principles of the pH scale to determine how much of the acid is present by using known quantities of a basic solution (in this case NaOH). Colorimetry involves the use of iron (III) chloride, a strongly coloured compound, to determine how much of the acetylsalicylic acid is available by using a previously calibrated scale of light reflection and colour density. 2) (AS) Which purification method is the most appropriate and accurate? To answer this aim, we need to compare the three methods outlined above, colourimetry, standard titration and back titration. We can do this by seeing which produces the most consistent results by adding the results to a chart and measuring the standard deviation of the results given. 3) (AS) Which type of titration (back or forward) is the most appropriate in this situation? There are two types of titration that can be used in this experiment. Back titration relies on the use of an excess of alkali and reacting this excess with acid to determine the concentration. Forward titration relies on the acid + base = salt + water principle. We can see which one works faster and gives standardised results. 4) (AS) Which type of acid (monoprotic or diprotic or triprotic) is the most effective in the purification process? A monoprotic acid is one that can donate one proton per molecule during the dissociation process; a diprotic can donate two and a triprotic can donate three. Hydrogen chloride (HCl) is an example of a monoprotic acid, sulphuric acid (H2SO4) an example of a diprotic and Phosporic Acid (H3PO4) an example of a triprotic acid. In the back titration process, an acid needs to be used. By using each of these three acids in the experiment, we can see which is the most effective (fastest and most accurate). 5) (A2) How is aspirin synthesized? To answer this, it is necessary to complete the synthesis of aspirin in the laboratory. This has the added benefit of being available for use in the purity testing. Acetylsalicylic acid is synthesized in a acetylation reaction between salicylic acid and an acetyl group donor, in this case ethanoic anhydride. 6) (A2) How pure is laboratory synthesized aspirin compared to commercially available tablet brands? To answer this, we can take three different brands of commercially available aspirin and the same amount of our laboratory synthesized compound. Then, using the methods (colourimetry and back titration) mentioned above, we can find out how much acetylsalicylic acid is found in the compounds available. 7) (A2) How does the hydrolysis of aspirin in an ethanol solution with sodium hydroxide help assess the quantity of acetylsalicylic acid in aspirin tablets? This method can help us to determine how much acetylsalicylic acid is present in aspirin tablets because it is assessed using a known quantity of a basic solution. To achieve neutral (as indicated by the phenolphthalein solution) we need to have exactly the same amount of acid. From the known quantity of base, then, the exact amount of acetylsalicylic can be calculated because it will be the same as the amount of basic solution needed to change the colour of the indicator to one that indicates neutral. Chemical Ideas Aspirin, or acetylsalicylic acid, is one of the most widely used analgesics in the world. Aspirin can be bought anywhere with no prescription and is used for the treatment of minor aches and pains, as well as fever reduction. Aspirin can also be recommended as a blood thinner to be taken daily where needed1. As evidenced by the chemical name acetylsalicylic acid, aspirin is an acetyl purification of salicylic acid. The name of salicylic acid itself comes from the Latin Salix, meaning willow tree, and this is precisely where salicylic acid can be found in nature2. The structure of salicylic acid involves 2-hydroxybenzoic acid (a monobenzoic acid) and a beta hydroxy acid, and is shown below. We can use the above salicylic acid to create the active ingredient in aspirin tablets, acetylsalicylic acid. This works using an anhydride (see below) for an acetylation reaction, such as that seen below. An acetylation reaction involves the transfer of an acetyl group from one compound to another, in this case from the acetic anhydride to the salicylic acid to create acetylsalicylic acid3. The chemical formula for this reaction is as follows: Salicylic Acid + Acetic Anhydride ? Acetylsalicylic Acid + Acetic Acid C7H6O3 (aq) + C4H6O3 (l) ? C9H8O3 (aq) + C2H4O2 (aq) This will give a solid which can be tested for purity, as discussed below. Carrying out this reaction will ensure that aim 5 (how is aspirin synthesized?) and aim 6 (How pure is laboratory synthesized aspirin compared to commercially available tablet brands?) can be answered appropriately. Acetic anhydride is the simplest acid anhydride, but there are many others which can also be used. It exists under standard conditions as a liquid, and it has a strong smell4. Acetic acid, the product of this reaction, is another organic compound which exists in a colourless, liquid state under standard conditions. Like acetic anhydride, it has a strong smell. Like many other acids, it can act as a corrosive agent and thus needs careful control in the laboratory5. In commercially sold drugs, there are often several additions to the main active ingredient. These are usually to make the drug more palatable (glucose additions, for example) or to help the active ingredient. The aim of this practical, then, is to deduce how much of the active ingredient (i.e. acetylsalicylic acid) is present in commercially available aspirin tablets6. Another one of the aims mentioned above is aim one, “to test the purity of aspirin and compare different brands to see which one is the purest”. One of the best ways of doing this is through a method known as titration7. The titration method applicable here is based on the chemical principle of pH, as shown below: Adding a base of a pH of 10 to an acid of a pH of 4 would give a neutral (pH 7) solution. This principle can be used to determine how much of an alkaline solution (such as NaOH) is present by adding known concentrations of an acid solution (such as HCl)8. Because aspirin itself is a weak acid, the type of titration involved here is known as a back titration, which involves adding an excess amount of the base and using a HCl titration to find out the amount of unreacted base. This principle is illustrated below: The reaction of acetyl salicylic acid with the sodium hydroxide is given below. This is the reaction we are actually measuring, but using a HCl titration9. C6H4(COOH)(OCOCH3) (aq) + 2NaOH (l) ? C6H4(COOH)ONa (aq) + Na(OCOHH3) (l) + H2O (l) Completing this will give a value, which will answer aim eight: How does the hydrolysis of aspirin in an ethanol solution with sodium hydroxide help assess the quantity of acetylsalicylic acid in aspirin tablets? Adding a catalyst is known to speed up the rate of reaction. Using different acids, we can use the same experiment as before to speed up the reaction and see the results, which will in turn help us to achieve aim four, or “which type of acid (monoprotic, diprotic or triprotic) is the most effective catalyst?”. The forward titration method is more simple and relies on the formula: CH3COO.C6H4.COOH + NaOH ? CH3COO.C6H4.COONa + H2O This formula is an acid + base = salt + water for salicylic acid and sodium hydroxide. Again, we can use phenolphthalein to work as an indicator 10. Salicylic acid is an intense purple colour when combined with iron (III) chloride, which makes it an ideal compound for use in colourimetry. Colourimetry relies on the principle that a coloured liquid will reflect light of certain wavelengths (which is why it appears a certain colour to the human eye). The amount of a compound present will cause a different amount of light to be reflected (see aim 8 about the chemistry of colour), which allows us to work out how much of the chemical is present and thus how pure the aspirin sample is 11. Justification of Choice of Methods There are certain chemically proven ways to show the purity of aspirin, or the % yield of salicylic acid in these tablets. The first aim here suggests that it is important to test the effectiveness of several different methods, and this means completing at least two different types of test on the commercially available aspirin. One of the most widely used ways of testing the purity of aspirin is known as back titration. This involves destroying the aspirin using a known concentration of an alkali. This leaves a certain quantity of the alkali remaining, and back titration then involves using a known quantity and concentration of an acid to help determine the amount of alkali remaining. In this case, the amount of acid needed to turn the solution neutral will be equal to the amount of alkali, and subtracting this from the starting concentration of alkali will give the amount of alkali used in the reaction. This is a very accurate method, and as previously mentioned, very widely used, which is why this was chosen. All of the elements needed to carry out this practical are also available in the laboratory. The risk assessment for these items is carried out below. Colorimetry is a widely used way of testing chemicals based on the principal of light reflection. In this case, the equipment is available in the laboratory. We need to use more than one different method to answer aim two. Chemically, it is always important to do a number of tests. In this case, part of the method suggests that each type of aspirin be tested three times; this will help give us a mean that is a more accurate result than the use of simply one test which could be false. Another important thing in chemistry is comparison, and this is why the methods here suggest using at least three different brands of commercially available aspirin to show how much salicylic acid is found in these tablets. Repeating the experiment will also give a more accurate rate of reaction, which will help to answer some of the aims above. Risk Assessment Chemical Quantities Used Hazard Actual/Perceived Risk Precautions Salicylic Acid12 Synonyms: 2-hydroxybenzoic acid, o-hydroxybenzoic acid, retarder W, SA, SAX, Verrugon Molecular formula: C7H6O3 CAS No: 69-72-7 EC No: 200-712-3 Produced in volumes under 10cm3 Harmful by inhalation, ingestion and through skin absorption. Irritant. Chronic effects: laboratory experiments have shown mutagenic effects. May cause harm to the unborn child. May act as a sensitizer. Low. Only small quantities are being used. Do not inhale. Wear safety goggles to prevent eye irritation. Acetylsalicylic acid13 Synonyms: aspirin, 2-(acetyloxy)benzoic acid, acetyl salicylic acid, O-acetylsalicylic acid, acetol, acetophen, A.S.A., ASA, acenterine, acetosal, 2-acetoxybenzoic acid, entrophen, rodine, numerous further trade names Use: analgesic, antipyretic Molecular formula: C9H8O4 CAS No: 50-78-2 EC No: Less than 1g of commercially available and laboratory synthesized tablets. Concentration unknown but low. Harmful if swallowed in quantity. Skin, eye and respiratory irritant. May act as an allergen in susceptible people. Low. Quantities used are not enough to cause harm if swallowed. Ensure safety goggles are warn to prevent eye irritation. Wash off of skin immediately if spilled. Sulphuric Acid14 Synonyms: oil of vitriol, mattling acid, vitriol, battery acid, dipping acid, electrolyte acid, vitriol brown oil Molecular formula: H2SO4 CAS No: 7664-93-9 EC No: 231-639-5 EC index No: 016-020-00-8 ~0.1M - dilute Corrosive, the more concentrated solutions can cause serious burns to the mouth, eyes and skin. Harmful by ingestion and through skin contact. Low concentration being used, and thus will not be corrosive. May act as an irritant. Wear goggles to prevent eye irritation and immediately clean up spills. Wash off skin if any contact occurs. Ethanoic anhydride15 Synonyms: acetic acid anhydride, acetic oxide, ethanoic anhydride, acetic oxide, acetyl ether, acetyl oxide, ethanoic anhydrate Molecular formula: (CH3CO)2O CAS No: 108-24-7 EC No: 203-564-8 Annex I Index No: 607-008-00-9 Small quantities of very dilute ethanoic anhydride Posion. Corrosive. Causes severe burns. Harmful if swallowed or inhaled. Causes severe respiratory irritation. Eye contact may cause serious irritation or burns. Typical TLV/TWA 5 ppm. Typical PEL 5 ppm. Will not be corrosive in this situation due to very low strength and quantities used. It will merely be an irritant. Some danger is present. Wear goggles to prevent eye irritation and immediately clean up spills. Wash off skin if any contact occurs. Hydrochloric acid16 Synonyms: muriatic acid, chlorohydric acid, dilute hydrochloric acid, diulte HCL Molecular formula: HCl CAS No: 7647-01-0 EC No: 231-595-7 250ml of ~0.1M dilution Corrosive. Inhalation of vapour is harmful. Ingestion may be fatal. Liquid can cause severe damage to skin and eyes. TLV 5 ppm. Will not be corrosive in this low concentration: information given is for 1M HCl. May act as an irritant on skin. Wear safety goggles to protect eyes from irritation. Do not inhale vapour or ingest. Clean spills immediately. Ethanol17 Synonyms: ethanol, grain alcohol, fermentation alcohol, alcohol, methylcarbinol, absolute alcohol, absolute ethanol, anhydrous alcohol, alcohol dehydrated, algrain, anhydrol, Cologne spirit, duplicating fluid 100C, ethyl hydrate, ethyl hydroxide, jaysol, jaysol s, molasses alcohol, potato alcohol, sekundasprit, spirits of wine, spirit, synasol, tecsol Molecular C2H5OH CAS No: 64-17-5 EC No: 200-578-6 Annex I Index No: 603-002-00-5 60ml of pure ethanol Causes skin and eye irritation. Ingestion can cause nausea, vomitting and inebriation; chronic use can cause serious liver damage. Note that "absolute" alcohol, which is close to 100% ethanol, may nevertheless contain traces of 2-propanol, together with methanol or benzene. The latter two are very toxic, while "denatured" alcohol has substances added to it which make it unpleasant and possibly hazardous to consume. Typical OEL 1000 mg/m3. Very small quantities being used so ingestion may not cause nausea or inebriation. May cause skin or eye irritation. Wear safety goggles during the practical and wash off skin immediately to prevent any irritation. Phenolphthalein18 Synonyms: 2-(bis-(4-hydroxyphenyl)methyl)benzoic acid, 3,3-bis(p-hydroxyphenyl)phthalide, 3,3-bis(4-hydroxyphenyl)-1(3H)-isobenzofuranone, NCI-C55798, feen-a-mint gum Use: Indicator, veterinary cathartic, laxative Molecular formula: C20H14O4 CAS No: 77-09-8 EC No: Droplets of pure phenolphthalein May act as a skin, eye or respiratory irritant. Animal experiments indicate a theoretical risk that this material may be carcinogenic in humans if ingested at high levels over a long period. Very small quantities used. No probable risk. Wear safety goggles and clean up spills immediately. Sodium Hydroxide19 Synonyms: caustic soda, soda lye, lye, white caustic, aetznatron, ascarite, Collo-Grillrein, Collo-Tapetta, sodium hydrate, fotofoil etchant, NAOH, STCC 4935235, sodium hydroxide pellets, Lewis red devil lye, stamperprep, tosoh pearl Molecular formula: NaOH CAS No: 1310-73-2 EC No: 215-185-5 Annex I Index No: 011-002-00-6 250ml of ~0.1M Very corrosive. Causes severe burns. May cause serious permanent eye damage. Very harmful by ingestion. Harmful by skin contact or by inhalation of dust. Typical STEL 2 mg m-1. Information given is for 1M sodium hydroxide and the risks presented are less severe for the concentration being used in this experiment. Actual risks are much lower. As before, wear safety goggles during the experiment to avoid irritation and make sure all spills are cleaned up immediately. Rinse off skin in case of contact. Phosphoric Acid20 Low concentrations Will act as an irritant but not a corrosive in the small amounts being used here. Wear goggles to prevent eye irritation and immediately clean up spills. Wash off skin if any contact occurs. Iron (III) Chloride21 Synonyms: ferric chloride, iron (3+) chloride, flores martis, iron chloride, iron trichloride Molecular formula: FeCl3 CAS No: 7705-08-0 EC No: 231-729-4 Low concentrations Corrosive - causes burns. Harmful by inhalation, ingestion and in contact with skin. Will act as an irritant but not a corrosive in the small amounts being used here. Wear safety goggles throughout the experiment and clean up spills immediately. Methods Synthesis of Aspirin Equipment 2-hydroxybenzoic acid Ethanoic anhydride Phosphoric acid Cold water Conical flask Pipette Condenser Fume cupboard Hot water bath Iced water bath Glass rod Buchner funnel Suction apparatus Watch glass Scales Instructions 1. Weigh out 1g of 2-hydroxybenzoic acid accurately and add to a clean, dry conical flask. 2. Add 2cm3 of ethanoic anhydride and 10 drops of phosphoric acid to this conical flask. 3. Put the condenser on the conical flask and transfer to the hot water bath inside the fume cupboard. 4. Swirl the mixture for around a minute or until all the solid has dissolved, then leave to warm for 5 minutes inside the fume cupboard. 5. Add 5cm3 of cold water to the conical flask, and stand in the iced water bath until precipitation is completed (stir with glass rod if necessary). 6. Filter the product using the Buchner funnel and suction apparatus. 7. Transfer the filtered product to a watch glass, and leave for 24 hours. Back Titration Equipment Aspirin samples Hydrochloric acid, conc., 37%wt % Sulphuric acid Phosphoric acid Ethanol Phenolphthalein (indicator solution) Standardized solution of sodium hydroxide Burettes x 4 Pestle & Mortar Weighing bottle Water bath Scales Method 1. Prepare 250ml of ~0.1M HCl. To make this, take 2.08mL of 37% HCl and add it to 247.92mL of water. This is because 37% HCl is 12N. C1V1 = C2V2 12N x V1 = 0.1N x 250ml V1 = (0.1 x 250)/12 V1 = 2.08mL 2. Compare this to the standardized NaOH. To do this, fill a burette with the ~0.1M HCl solution. Then fill three flasks with 50mL of distilled water and 3 drops of the phenolphthalein indicator to each flask. Add HCl from the burette: 35ml, 40ml and 45ml to flask 1 2 and 3 respectively. Swirl to mix. Add NaOH solution to the second burette and titrate to the phenolphthalein endpoint (pink) to find the precise molar dilution of HCl. 3. Prepare the samples of aspirin. Weigh three of each type of tablet to determine how much each commercially available tablet weighs precisely. Use the pestle and mortar to create a thin powder, and remove 1g of each sample. Add 60mL of ethanol from a graduated cylinder to a flask, and then add 9 drops of phenolphthalein indicator. Swirl until dissolved. 4. Take one third (20mL) of the previously prepared liquid and titrate is NaOH until the first permanent pink colour. Double this, and then add some excess NaOH using the burette. Record the total volume of NaOH added to each flask. Do this three times to create three samples. 5. Add each of the three flasks to a warm water bath to speed up the hydrolysis reaction. Leave for 20 minutes, then remove and leave to cool for a further 5 minutes. 6. Using the burette containing ~).1M HCl solution, titrate the excess base in each of the three previously prepared flasks with the HCl until the pink colour is replaced by a cloudy white. 7. Measure the amount of titrated HCl and record. Repeat for all aspirin samples. 8. Repeat all experiments with phosphoric and sulphuric acid. Colourimetry of Aspirin Equipment Method Titration Equipment Method Bibliography 1. Cogill, Ms Adelene et al. Salters Advanced Chemistry: A2 Chemical Storylines, 3rd edition. 3rd ed. London: Heinemann, 2009. Print. (p15) 2. Cogill, Ms Adelene et al. Salters Advanced Chemistry: A2 Chemical Storylines, 3rd edition. 3rd ed. London: Heinemann, 2009. Print. (p16) 3. Otter, Chris. Chemical ideas. 3rd ed. London: Heinemann, 2009. Print. (p140) 4. Otter, Chris. Chemical ideas. 3rd ed. London: Heinemann, 2009). Print. (p231) 5. http://www.chemistry-react.org/go/Tutorial/Tutorial_21681.html. Re:Act Chemistry. 6th September, 2011 6. http://www.chemistry-react.org/go/Topic/Default_4.html. Re:Act Chemistry. 6th September, 2011 7. http://www.4college.co.uk/a/index.php Salter’s Chemistry. 7th September, 2011 8. http://www.4college.co.uk/a/index.php Salter’s Chemistry. 5th September, 2011 9. http://www.rsc.org/images/Aspirin_tcm18-189278.pdf Aspirin. 6th September, 2011 10. http://www.rsc.org/images/Aspirin_tcm18-189278.pdf Aspirin. 6th September, 2011 11. http://scidiv.bellevuecollege.edu/Chemistry/Chem161/Chem161labs/Apirin%20titration.pdf Aspirin Titration. 5th September, 2011 12. http://msds.chem.ox.ac.uk/SA/salicylic_acid.html Salicylic Acid Hazard Card. 6th September, 2011 13. http://msds.chem.ox.ac.uk/AC/acetylsalicylic_acid.html Acetyl Salicylic Acid Hazard Card. 6th September, 2011 14. http://msds.chem.ox.ac.uk/SU/sulphuric_acid.html Sulphuric Acid Hazard Car. 6th September, 2011 15. http://msds.chem.ox.ac.uk/ET/ethanoic_anhydride.html Ethanoic Anhydride Hazard Card. 6th September, 2011 16. http://msds.chem.ox.ac.uk/HY/hydrochloric_acid.html Hydrochloric Acid Hazard Card. 6th September, 2011 17. http://msds.chem.ox.ac.uk/ET/ethanol.html Ethanol Hazard Card. 6th September, 2011 18. http://msds.chem.ox.ac.uk/PH/phenolphthaline.html Phenolphthaline Hazard Card. 6th September, 2011 19. http://msds.chem.ox.ac.uk/SO/sodium_hydroxide.html Sodium Hydroxide Hazard Card. 6th September, 2011 20. http://msds.chem.ox.ac.uk/PH/phosporic_acid.html Phosphoric Acid Hazard Card. 6th September, 2011 21. http://msds.chem.ox.ac.uk/IR/iron_III_chloride.html Iron (III) Chloride Hazard Card. 6th September, 2011 Read More