Aspirin Lab Manual

FOUNDATION IN SCIENCE
INTRODUCTION TO PRACTICAL ORGANIC CHEMISTRY – MAKING AND PURIFYING ORGANIC COMPOUNDS
Stage 1 – Deciding how much reagent to use Most organic reactions do not go to completion; most reach an equilibrium position with significant quantities of reactants still remaining. In addition, separating the desired product from the rest of the reaction mixture, and then purifying it, will result in the loss of more of the product. The amount of product obtained expressed as a percentage of the theoretical maximum amount possible and is known as the percentage yield. Percentage yield = Actual mass of product × 100 Predicted mass of product

When deciding on quantities of reactants to use, you must consider: how much product you require the likely percentage yield

Stage 2 – Apparatus and getting started Reactions which need to be heated strongly over a period of time require either reflux apparatus or distillation apparatus (Fig. 1).

Figure 1: Distillation apparatus

Reflux is required if the reactants, catalyst or solvent is volatile and likely to escape. Distillation is preferred if the product is volatile, or if there is a danger of further reaction. Many reactions are very vigorous at the beginning and can react violently. Often it is necessary to keep the mixture cool as the reactants are being mixed (using a cold water bath or even ice bath). A sensible precaution is to use a dropping funnel (Fig. 2) to add one of the reagents. After the reactants have been mixed, it is then necessary to heat the mixture to whichever temperature results in the best yield.

Stage 3 – Separating the product from the reaction mixture

Figure 2: Dropping funnel Solids can be separated from the reaction mixture by filtration. This is usually best achieved using a Buchner apparatus (funnel and flask) connected to a vacuum pump (Fig. 3).

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Liquids can be separated from the reaction mixture using a separating funnel (if the product is immiscible with the reaction mixture) or by distillation (if the product is miscible with the reaction mixture. Figure 4: Separating Funnel

Figure 3: Buchner apparatus connected to a vacuum pump Stage 4 – Purification of the product Solids are purified by a process called recrystallization (Fig. 5):  The solid is dissolved in the minimum possible quantity of hot solvent, specifically chosen so that the solid is soluble in the solvent when hot but not when cold.  A few impurities (such as grit) will not dissolve in the hot solvent. These can then be removed, if necessary, by filtering the mixture through a pre-heated funnel.  The solution is then cooled to below room temperature using an ice-bath. The pure solid should crystallise out of the cold solution.  The solid can be separated by filtration under reduced pressure using a Buchner apparatus. A small amount of cold solvent can be added to wash the crystals.  The crystals must then be dried between filter paper, and then placed in an oven to dry completely.

Figure 5: Recrystallisation Stage 5 – Testing the Purity of the Product A simple method for testing the purity of the product is to carry out a melting point determination. Pure substances melt at a fixed temperature. Impurities cause the product to melt at a lower temperature and over a broader range of temperatures. Melting point determinations are carried out in the following way:  Break off around 5 cm of a capillary tube and seal one end in a Bunsen burner. Page 2

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Pack 1 cm of the solid as densely as possible into the sealed end of the capillary tube. Place the capillary tube in the melting point apparatus (Fig. 6). Ensure that the apparatus heats up very slowly as the expected melting point of the substance approaches. Record the temperature when the liquid starts to melt and when it finishes melting. Compare the melting point range to the known melting point of the pure solid. A pure sample will melt sharply at a temperature close to the known melting point.

Figure 6: Melting point determination Important hazards and safety precautions Organic compounds and reactions are often hazardous. The following table shows some of the typical hazards, and the precaution that needs to be taken as a result: Hazard Reagent is harmful, toxic, or corrosive Precaution Wear safety spectacles Wear gloves Flood affected areas if there is a spillage Reagent is flammable Harmful gas or vapours are produced Avoid naked flames Use a fume cupboard

Health and Safety Notes    It is the responsibility of the student to carry out and be responsible for their own safety risk assessment before carrying out this experiment. Wear lab coat, gloves and safety glasses at all times. Assume that all of the reagents and liquids are toxic, corrosive and flammable.

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Practical 1: Carry Out Some Organic Tests
Aim: To carry out tests for the presence of organic functional groups and to make accurate observations. Requirements • Ethanol • 2-methylpropan-2-ol • Butan-1-ol • Butan-2-ol • Acidified potassium dichromate. • ethanal or propanal • Brady’s reagent • cyclohexene • 1-bromobutane • dilute ethanoic acid (2 mol dm-3) • bromine water • sodium hydrogen carbonate solid • sodium hydroxide solution • silver nitrate solution • dilute nitric acid • 250 cm3 beaker • anti-bumping granules • test tubes and a test tube holder • thermometer (-10 oC to 110 oC) The concentrations of the aqueous solutions in these experiments need to be sufficient to ensure that obvious reactions take place. In practice, this is likely to mean 2 mol dm-3 for most solutions. To make up the the acidified dichromate(VI) solution: dissolve 2 g of potassium dichromate(VI) in 80 cm3 of deionised or distilled water and slowly add 10 cm3 of concentrated sulfuric acid to the solution, with cooling. Label the solution TOXIC and CORROSIVE. Experiment This experiment is divided into five parts. In every case, you should present all of your observations in a neat Table. The presentation of a clearly organised record of your observations is an important skill which you will be expected to demonstrate as part of this assessment. Part 1 – A test for an alcohol oxidation using acidified dichromate In this experiment you will investigate the alcohols ethanol and three isomeric alcohols- butan-1-ol, butan-2-ol and 2-methylpropan-2-ol with formula C4H9OH, for their reactivity with acidified dichromate. 1. Prepare a hot water bath by heating 100 mL of tap water in a 250 mL beaker to 80 oC. Turn the Bunsen off. 2. Into four separate labelled test tubes place 2 mL of ethanol, butan-1-ol, butan-2-ol and 2methylpropan-2-ol respectively. 3. Pour 1 mL of acidified K2Cr2O7 into each of the test tubes containing the alcohols and heat them in a hot water bath for 5 minutes. If the aqueous and alcoholic phases do not mix, shake the mixture occasionally. 4. Observe carefully for any evidence of reaction and note the relative rate of the reaction of each alcohol. Where a reaction has taken place carefully smell the contents of the tube. Write your observations in a suitable table. F60CH3 Page 4

Part 2 – A test for an aldehyde using Brady’s reagent 1. Using a beaker of hot water (50 oC to 60 oC), gently warm approximately 5 cm3 of Brady’s reagent in a test tube. 2. Add a few drops of ethanal to the warmed test reagent in the test tube. Wait a few minutes and record your observations. Part 3 – A test for an alkene (a test for unsaturation) 1. To approximately 1 cm3 of cyclohexene in a test tube, add an equal volume of bromine water and shake the contents of the tube vigorously from side to side. 2. Record your observations. Part 4 – A test for a carboxylic acid 1. Place one small spatula measure of solid sodium hydrogen carbonate in a test tube and add to it approximately 2 cm3 of dilute ethanoic acid. 2. Record your observations. Part 5 – A test for a haloalkane. 1. Using a teat pipette, add approximately 5 drops of 1-bromobutane to 1 cm3 of sodium hydroxide solution in a test tube. Warm the contents of the test tube for a few minutes, by placing it into a beaker filled with hot water at approximately 60 oC. 2. Acidify the contents of the test tube by adding 2 cm3 of dilute nitric acid and then add 1 cm3 of silver nitrate solution. 3. Record your observations. Questions 1. Which alcohols are oxidised by acidified Cr2O72-? 2. Write balanced half equations and then total chemical equations for the reaction of acidified Cr2O72- with alcohols used. 3. There is a fourth isomeric alcohol with formula C4H9OH. Draw a structural formula for this isomer and write its systematic (IUPAC) name. Predict how you would expect this isomer to react with acidified Cr2O72-. 4. Write an equation showing the reaction of a) ethanal (or propanal) with Brady’s reagent b) cyclohexene with bromine water c) ethanoic acid with sodium hydrogen carbonate d) 1-bromobutane in the silver nitrate test. 5. The structural formula of ascorbic acid is given below. Identify the functional groups and describe the tests you would do to identify those functional groups.

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Practical 2: Prepare a Solid Organic Compound
Introduction Aspirin is prepared by the acylation of salicylic acid (2-hydroxybenzenecarboxylic acid) using ethanoic anhydride as the acylating agent. The reaction can be represented as follows. HOOCC6H4OH + (CH3CO)2O → HOOCC6H4OCOCH3 + CH3COOH salicylic acid ethanoic anhydride aspirin ethanoic acid Aspirin (2-acetyloxybenzoic acid) is an antipyretic drug (reduces fever by lowering body temperature) and an analgesic (relieves pain). Aspirin does not react in the acidic conditions in the stomach, but is hydrolysed in the alkaline conditions found in the intestines to produce ethanoate ions and salicylate (2-hydroxybenzoate) ions. Salicylates lower the body temperature of feverish patients and have a mild analgesic effect relieving headaches and other pain. The toxic dose is relatively high, but symptoms of poisoning can occur with quite small quantities. Requirements  salicylic acid  100 cm3 conical flask  10 cm3 measuring cylinder  ethanoic anhydride  concentrated sulfuric acid in a dropping bottle  400 cm3 beaker  Tripod, gauze and Bunsen burner  anti-bumping granules  250 cm3 beaker  Reduced pressure filtration apparatus (Buchner apparatus connected to a vacuum pump)  Filter paper  Glass stirring rod  Deionised or distilled water in a wash bottle  Spatula  25 cm3 measuring cylinder  Boiling tube  ethanol  Thermometer (-10 oC to 110 oC)  Capillary tube  Melting point apparatus

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Experiment Stage 1: Preparation of Crude Product 1. Weigh out approximately 6.00 g of salicylic acid directly into a 100 cm3 conical flask. 2. Record the mass of salicylic acid used. 3. Using a 10 cm3 measuring cylinder, add 10 cm3 of ethanoic anhydride to the flask and swirl the contents. 4. Add 5 drops of concentrated sulfuric acid to the flask and swirl the mixture in the flask for a few minutes to ensure thorough mixing. 5. Warm the flask for twenty minutes in a 400 cm3 beaker of hot water at approximately 60 oC. The temperature in the flask should not be allowed to rise above 65 oC. 6. Allow the flask to cool and pour its contents into 75 cm3 of water in a beaker, stirring well to precipitate the solid. 7. Filter off the aspirin under reduced pressure, avoiding skin contact. 8. Collect the crude aspirin on a double thickness of filter paper and allow it to dry. Stage 2: Separation of the product from the reaction mixture 9. Using a 25 cm3 measuring cylinder, measure out 15 cm3 of ethanol into a boiling tube. 10. Prepare a beaker half-filled with hot water at a temperature of approximately 75 oC. The safest way to do this is to use a kettle of boiling water and add water from the kettle to cold water in the beaker until the temperature is at approximately 75 oC N.B. The boiling point of ethanol is 78 oC and the temperature of the water in the beaker should not be allowed to go above this. Stage 3: Purification of the crude product 11. Use a spatula to add the crude aspirin to the boiling tube and place the tube in the beaker of hot water. 12. Stir the contents of the boiling tube until all of the aspirin dissolves into the ethanol. 13. Pour the hot solution containing dissolved aspirin into approximately 40 cm3 of water in a 100 cm3 conical flask. If a solid separates at this stage, gently warm the contents of the flask in the water bath until solution is complete. You should avoid prolonged heating, since this will decompose the aspirin. 14. Allow the conical flask to cool slowly and white needles of aspirin should separate. 15. If no crystals have formed after the solution has cooled to room temperature, you may need to use an ice bath and to scratch the insides of the flask with a glass stirring rod to obtain crystals. 16. Filter off the purified solid under reduced pressure and allow it to dry on filter paper. Stage 4: Confirmation of yield and purity 17. Record the mass of the dry purified solid. 18. Determine the melting point of the sample. Analysis The structure of salicyclic acid is: a) Using structural formulae, write an equation for the reaction between salicyclic acid and ethanoic anhydride and describe the reaction mechanism involved. Calculate the theoretical yield of aspirin which should be formed from 6.00 g of salicylic acid. Calculate the percentage yield of aspirin from your experiment and comment on the reasons for the losses that have occurred during the preparation and the purification of the solid. The melting point of pure aspirin is 134-136 oC. How pure is your sample? Explain the main safety precautions you took during this experiment and why you took them. Calculate the atom economy for the preparation of aspirin by this method. Page 7

b) c) d) e) f)

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Consider the reasons why the alternative preparative method which uses ethanoyl chloride rather than ethanoic anhydride, is not favoured by industry even though this alternative method has a higher atom economy. Health and Safety Notes  Salicylic acid is an irritant.  Phosphoric acid is corrosive.  Ehanoic anhydride is flammable.    It is the responsibility of the student to carry out and be responsible for their own safety risk assessment before carrying out this experiment. Wear lab coat, gloves and safety glasses at all times. Assume that all of the reagents and liquids are toxic, corrosive and flammable.

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Practical 3: Distil a Product from a Reaction
Preparation of ethanal Ethanol can be oxidised by the dichromate (VI) ion in acidic solution. The first product of the oxidation is ethanal, which can be further oxidised to form ethanoic acid. By carefully changing the reaction method, one or other product can be obtained. The ethanal preparation should be performed in a fume cupboard. Requirements  simple distillation apparatus OR Quickfit apparatus  acidified potassium/sodium dichromate(VI)  protective gloves  stand and clamp  10 cm3 measuring cylinder  25 cm3 measuring cylinder  anti-bumping granules  test tube/conical flsk  thermometer (-10 oC to 110 oC)  Two 250 cm3 beakers  ethanol  teat pipette/dropping funnel  2,4-Dinitrophenylhydrazine (2,4-DNPH, Brady's reagent)  test tube  Deionised or distilled water in a wash bottle The student sheet assumes that simple distillation apparatus will be used and this can be made by using a boiling tube fitted with a bung with a right-angled glass delivery tube. The delivery tube needs to be long enough to go into a test tube which is immersed in cold water in a beaker. The alternative is for the Centre to provide Quickfit apparatus and guidance to students in its assembly. This apparatus will lead to a more ethanal being collected because it is condensed more efficiently using a water-cooled Liebig condenser. To make up the the acidified dichromate(VI) solution: dissolve 2 g of potassium dichromate(VI) in 80 cm3 of deionised or distilled water and slowly add 10 cm3 of concentrated sulfuric acid to the solution, with cooling. Label the solution TOXIC and CORROSIVE. Precautions • • • Wear eye protection and laboratory coat. Work in the fume cupboard when preparing ethanal. Wear gloves when taking samples of concentrated sulphuric acid

Method 1. Using a 25 cm3 measuring cylinder, carefully measure out 12 cm3 of the solution of acidified potassium dichromate(VI) which has been provided for this experiment. Pour this oxidising agent into a round-bottomed flask. You should wear protective gloves when handling the corrosive oxidising agent. F60CH3 Page 9

2. Cool round-bottomed flask in cold water in a beaker. 3. Using a 10 cm3 measuring cylinder, carefully measure out 2 cm3 of ethanol. 4. Using a teat pipette/dropping funnel, slowly add the 2 cm3 of ethanol dropwise, to the oxidising agent in the cooled round-bottomed flask (immersed in cold water in a beaker), shaking the round-bottomed flask gently to mix the contents. 5. After the addition of ethanol, add some anti-bumping granules to the flask and set up the apparatus shown below:

Ethanol

Round –bottomed flask Acidified dichromate

N.B. There should be rapid flow of water round the condenser. Ask your lecturer to adjust the flow if you do not feel confident – it is easy to create too much pressure in the rubber tubes. 6. Clamp the round-bottomed flask in a beaker of water. Heat this beaker of water gently and slowly distil off approximately 5 cm3 of liquid distillate into a test tube/conical flask which is immersed in cold water in a beaker. Keep the test tube/conical flask cool to avoid loss of the volatile ethanal. Cautiously note its characteristic smell. Stopper the test tube/conical flask and keep it in iced water. Carry out the test described below on the distillate to confirm that ethanol has been formed in this reaction. If you have time, take samples and test using the Brady’s test. Test on the distillate to confirm the formation of ethanol 3. Using a beaker of hot water (50 oC to 60 oC), gently warm approximately 5 cm3 of Brady’s reagent in a test tube. 4. Add 10 drops of the distillate containing ethanal to the warmed test reagent in the test tube. Wait a few minutes and note what happens. You should have produced a yellow/orange/red precipitate.

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