Initial plan-Aspirin Background Aspirin is a commercial drug that most people use some time in their lives.

In 400BC, Hippocrates, known as the father of modern medicine, used a brew of willow leaves to ease the pain of childbirth. In 1763 Rev. Edward Stone used willow bark brew to reduce fevers due to malaria. It was in the 1840s, when organic chemists working with willow bark isolated and identified the active ingredient salicin (salix means willow in Latin ). In 1870, Professor von Nenki of Basle demonstrated that salicin was converted into salicylic acid in the body. Salicylic acid then was used on patients with fevers. Symptoms were relieved but the compound appeared to cause irritation of the lining of the mouth, gullet and stomach. In the 1890s, Felix Hoffmann of the Bayer Company in Germany made aspirin which had the medicinal properties without a horrid taste and irritation to membrane. He did this by making slight modifications to the structure of salicylic acid. Because aspirin is not very soluble in water, Bayer decided to sell the medicine in the form of tablets. Aims Using pure salicylic acid produce aspirin using varying methods: Using microwaves, c. Phosphoric acid and c. Sulphuric acid. Then purify the samples by recrystallisation. With the three samples of aspirin obtained and a sample of pure aspirin analyse their purity using varying methods: by comparing melting points, using the technique of tlc, forward and backward titration and colometric techniques.This will show which method of producing aspirin provides the purest form. I will also be able to calculate the yield from the results.

Equipment and chemicals required for the preparation of aspirin using C. Phosphoric acid fume cupboard 25cm^3 pear shaped flask Hot water bath 10cm^3 measuring cylinder Bath of iced water Glass stirring rod Buchner funnel and suction apparatus Watch glass 2g 2-hydroxybenzoic acid 4cm^3 of ethanoic anhydride 16 drops of C. phosphoric acid Preparation of aspirin using c. phosphoric acid 1. Take 2g of salicylic sample and weigh it accurately. Put this into a dry pear shaped flask and add 4cm^3 of ethanoic anhydride followed by 16 drops of phosphoric acid. Put a condenser on the flask. 2. In a fume cupboard warm the mixture in a hot water bath, with swirling, until all the solid has dissolved and then warm for another (5) minutes. 3. Carefully add 10cm^3 of cold water to the solution.

4. Stand the flask in a bath of iced water until precipitation appears to be complete. 5. It may be necessary to stir vigorously with a glass rod to start the precipitation process. 6. Filter off the product using a Buchner funnel and suction apparatus. 7. Wash the product with a little cold water, transfer to a weighed watch glass and leave to dry overnight. 8. Weigh the final product

Equipment and chemicals required for the preparation of aspirin using c. Sulphuric acid Access to a fume cupboard 100cm^3 conical flask 10 cm^3 measuring cylinders x2 100cm^3 beaker glass rod apparatus for vacuum filtration Hirsch funnel 4g salicylic acid 8cm^3 ethanoic anhydride c. Sulphuric (VI) acid 10 drops 8cm^3 glacial ethanoic acid water bath containing crushed ice Preparation using c. Sulphuric acid 1. Working in a fume cupboard, shake 4g of salicylic acid with 8cm^3 of ethanoic anhydride in a 100cm^3 conical flask. 2. Add 10 drops of sulphuric acid and continue agitating the flaks for about (10) minutes. Crystals of aspirin will appear and soon the whole will form a crystalline mush. 3. Dilute by stirring in 8cm^3 of cold galacial ethanoic acid and cool by placing in water bath containing crushed ice. 4. Filter off the crystals using a Hirsch funnel washing once with ice cold water. 5. Dry purified sample on filter paper and weigh it. Equipment and chemicals required for the preparation of aspirin using Microwave oven fume cupboard microwave oven thermometer (0-110c) 10cm^3 measuring cylinders 250cm^3 beaker x2 glass rod glass petri dish apparatus for vacuum filtration Hirsch funnel salicylic acid 5g ethanoic anhydride 5cm^3 ice cubes water bath containing crushed ice

Preparation of aspirin using microwave oven 1. weigh 5g of salicylic acid into a 250cm^3 beaker 2. Working in a fume cupboard, add 5cm^3 ethanoic anhydride, using a small measuring cylinder, so as to wet the acid uniformly. 3. cover the beaker with a glass petri dish 4. Place the beaker and petri dish in a microwave oven. Also put a beaker containing 200cm^3 of water into the oven. 5. Irradiate the sample at full power for one minute. Stop the oven and gently swirl the beaker. 6. Irradiate to achieve a temperature of 120-130C.. 7. Carefully remove the hot beaker containing the reaction mixture from the oven. allowing the beaker to cool and then add about 50cm^3 of water that contains a few ice cubes. Stir mixture. 8. Now cool beaker by placing it in a water bath containing crushed ice. Coninue to stir the mixture to prevent clumps of solid forming. 9. When the mixture is cold, filter off the crystals using a Hirsch funnel, washing once with ice- cold water. 10. Dry purified sample on filter paper and weigh it. Equipment and chemicals required for Recrystallisation weighing boats scales samples of aspirin 100cm^3 beaker Distilled water 10cm^3 measuring cylinder heatproof mat tripod gauze Bunsen burner 25cm^3 measuring cylinder funnel 250cm^3 conical flask 500cm^3 beaker x2 Buschner funnel and suction apparatus filter paper stirring rod Ice watch glass spatulas Recrystallisation 1. Weigh the impure aspirin that you are going to recrystallize. 2. Transfer the sample to a 100cm^3 beaker. Add 10cm^3 of distilled water to the beaker and place that into a 500cm^3 beaker half filled with water. Warm the mixture until the crystals have dissolved using Bunsen burner flame. 3. If the crystals do not dissolve and 5cm^3 more of the distilled water and continue to warm the mixture.

4. Once the crystals have dissolved add 20cm^3 of warm water allow time to let the crystals form. 5. Use fluted filter paper to filter the warm solution into a 250cm^3 conical flask. Throw away residue as the product and any insoluble impurities remains in solution in the filtrate. (or sepearte sheet involving sodium bicarbonate solution)- Need to do risk assess for this Equipment 1. 2. 3. 4. 5. 6. weighing boats scales samples of aspirin 150cm^3 beaker Distilled water 25cm^3 measuring cylinder funnel Buschner funnel and suction apparatus filter paper stirring rod Ice watch glass spatulas 6M HCl Sodium bicarbonate solution Weigh the impure aspirin that you are going to recrystallize. Place the crude aspirin in a 150 ml beaker Add 20ml of saturated sodium bicarbonate solution Stir until no more CO2 is given off Remove the polymeric solid by vacuum filtration Place the filtrate (the solution) in a 150ml beaker and slowly add 6M HCl stirring as you do so 7. Cool the mixture in an ice bath until crystals form and collect the product by vacuum filtration 8. Wash the crystals with a little ice water. Equipment required for the melting point melting point tubes watch glass Bunsen burner and heat proof mat Melting point apparatus: small beaker containing oil or glycerol in which is supported a 0-360c thermometer with small rubber bands for attaching the melting pointing tubes, or a commercial apparatus. Melting point 1. Heat the end of a capillary tube in a Bunsen burner flame until the glass softens and the end is sealed. 2. Do not heat the tube so strongly that it bends. Leave it on a heatproof mat to cool.

3. Make sure that your samples of solid are dry, by leaving them in a desiccator or an oven at 50 C overnight. Fill the melting point tube to a depth of 0.5 cm with dry impure aspirin 4. Seal a second tube and fill it to a depth of 0.5 cm with dry crystals of purified aspirin. 5. Place each tube in the melting point apparatus, slowly increase the temperature and note the temperature range over which the substances melt. A simple but effective apparatus consists of a beaker of oil or glycerol in which is supported a 0360 C thermometer. 6. The two melting point tubes are attached to the thermometer close to the bulb using a rubber band. This apparatus makes it easy to compare the behaviour of the two solids.

Equipment required for the tlc technique tlc plate and pencil watch glass four test tubes and stand capillary tubes chromatography chamber (small beaker with a petri dish for a lid) Fume cupboard and short wavelength UV lamp Ethanol (3 or4 )iodine crystals the samples of aspirin sample of pure aspirin sample of pure salicylic acid chromatography solvent (cyclohexane, ethyl ethanoate, ethanoic acid (200: 100: 1) 1cm^3 0.1moldom^-3 neutral iron (III) chloride solution aluminium foil

Tlc 1. Make sure that you do not touch the surface of the tlc plate with your fingers during this activity. Handle the plate only by the edges and use tweezers if possible. 2. Take a tlc plate and using a pencil (not a biro or felt tip pen) lightly draw a line across the plate about 1 cm from the bottom. Mark five equally spaced points on this line. 3. Place small amounts (about 1/3 of a spatula measure) of the aspirin samples, pure salicylic acid and the pure sample of aspirin in three separate test-tubes. Label the test-tubes so that you know which is which. Add 2cm^3 of distilled water to each. 4. To each test tube add two drops of neutral iron (III) chloride solution and agitate to mix. Noting down observations. 5. Make up 5 cm3 of solvent by mixing equal volumes of ethanol and dichloromethane in a test-tube. Add 1 cm3 of the solvent to each of the samples on a watch glass. If possible do this in a fume cupboard. 6. Use capillary tubes to spot each of your samples onto the tlc plate. Allow

the spots to dry and then repeat three more times. The spots should be about 12 mm in diameter. 7. After all the spots are dry, place the tlc plate in the developing tank making sure that the original pencil line is above the level of the developing solvent ethyl ethanoate. Put a lid on the tank and allow to stand in a fume cupboard until the solvent front has risen to within a few millimetres of the top of the plate. 8. Remove the plate from the tank and quickly mark the position of the solvent front. Allow the plate to dry. 9. Observe the plate under a short wavelength UV lamp and lightly mark with a pencil any spots observed. 10. Place the plate in a jar or beaker containing a few iodine crystals. Put a cover on the jar and warm gently on a steam bath until spots begin to appear. Do this in a fume cupboard if possible.

Equipment for colorimetric techniques colorimeter volumetric flask distilled water ethanol aspirin of varying concentration 1cm^3 5% aqueous iron(III) ammonium sulphate solution pH buffers Colometric techniques 1. 2. 3. 4. 5. Dissolve 0.2g of aspirin in a 50/50 water ethanol mixture in a volumetric flask add 1cm^3 of 5% aq iron(III) ammonium sulphate solution adjust the volume to 100cm^3 Set the colorimeter at 530nm - It is necessary to prepare a calibration curve before using the aspirin with the colorimeter. To create a calibration curve, a range of 2-hydroxybenzoic acid concentrations must be used. - Measure out 2cm3 of each concentration and add 2 drops of iron (III) chloride to each using a pipette. - Pour each solution into separate cuvettes and place in the colorimeter (under a yellow-green filter). Record each reading and draw a graph or use a data logger - Next, dissolve 0.2g of the aspirin sample in a 50:50 water:ethanol mixture in a 100cm3 volumetric flask and add 1cm3 of a 5% aqueous iron (III) chloride solution before adjusting the volume to 100cm3 with more of the water/ethanol mixture - Take a sample of this mixture and put it in a cuvette. Take a reading with the colorimeter.

Or 1. To prepare a calibration curve, prepare a purple Fe3+ complex from salicylic acid and neutral FeCl3.

2. To prepare neutral iron (III) chloride solution, pour 1cm3 of Iron (III) chloride solution. Add sodium carbonate solution, drop by drop, until a trace of brown ppt just remains after shaking. 3. Add a few drops of this neutral iron (III) chlorides solution to the phenol solution May need to let asprin hydrolyse a bit in a damp area. Equipment required for forward titration scale weighing boats burette white tile 100cm^3 conical flask 10cm^3 measuring cylinder aspirin samples Pure aspirin 30cm^3 95% ethanol 60cm^3 0.1 moldm^-3 NaOH solution Phenolphthalein indicator Forward Titration 1. 2. 3. 4. 5. Accurately weigh 0.1g of aspirin sample into a 100cm^3 conical flask Add 15ml of 95% ethanol and a dropper full of phenolphthalein indicator. Reweigh the used weighing boat and record the mass Swirl the flask carefully until all the aspirin powder has dissolved Slowly titrate the aspirin with the NaOH solution from the burette. Record the volume needed to produce the first tinge of pale pink colour in the indicator. This measures the end point of the titreation 6. Record initial and final burette readings 7. Repeat titrations twice more Equipment required for back titration scales weighing boats 250cm^3 conical flask x2 Pipette filler 25cm^3 pipette Bunsen burner Gauze Tripod 250cm^3 beaker funnel 50cm^3 burette white tile burette stand 25cm^3 beaker spatulas phenolphthalein indicator 150 cm^3 0.1moldm^-3 HCl solution Distilled water

30cm^3 1moldm^-3 NaOH solution

Back titration 1. Weigh the sample of aspirin accurately to 1.5g 2. Transfer into a 250cm^3 conical flask. 3. Add 25cm^3 of NaOH solution into the flask and the same volume of distilled water and heat in a water bath for 10 minutes, swirling the flask occasionally, avoid boiling. 4. Remove samples from the water bath and cool for 5 minutes 5. Transfer with washings to a 250cm^3 standard flask and make up to mark with distilled water. 6. Pipette 25cm^3 of hydrolysed solution into a conical flask. 7. Titrate slowly using the HCl solution, titrate the excess base until the pink colour disappears Risk assessment for the preparation of aspirin (all methods) Substance/ Harzardous nature Handling apparatus Use the lowest c. Phosphoric acid Corrosive concentration possible.
Use the smallest volume possible. Wear eye protection, including when making or disposing of solutions. Wear protective gloves if concentrated acid is handled on anything larger than a test-tube scale. Add the concentrated acid slowly to cold water when diluting, never the reverse; stir frequently to ensure good mixing.

Disposal

Glass ware

It causes burns. It reacts violently, becoming very hot, when mixed with water. It decomposes if heated strongly, forming toxic oxides of phosphorus. Can cause cuts if broken and not handled with care

Hot water Pure Salicylic acid

May burn

Handle with care and take care with sudden temperature changes of glassware. Before heating check if it is Pyrex. No running while handling glassware Handle with care Wear goggles, apron and gloves

Clean up carefully. If glass is broke, pick up large pieces of glass then sweep smaller pieces. Then place all the pieces in the glass only bin in the lab.

Inhalation can cause coughing, sore

throat. Can cause redness and pain on contact with skin Ethanoic anhydride Wear goggles, gloves and an apron. Use in fume cupboard. Inhalation causes sore throats, shortness of breath. Contact causes blisters and skin burns non-ionising radiation

Microwave oven

C. Sulphuric acid

Microwave ovens should be operated and maintained according to instructions, so that microwaves cannot leak out. Wear gloves, aprons and goggles.

Corrosive It causes severe burns. It reacts violently, becoming very hot, when mixed with water. For a 15-minute exposure, the vapour concentration in the atmosphere should not exceed 3.0 mg m-3. Risk assessment for melting point Substance/ Harzardous nature apparatus Bunsen burner Fire hazard

Handling Ensure long hair is tied back. Flame is on safety flame when not in direct use Handle with care and take care with sudden temperature

Disposal

Glass ware

Can cause cuts if broken and not handled with care

Clean up carefully. If glass is broke, pick up large pieces of

changes of glassware. Before heating check if it is Pyrex. No running while handling glassware Risk assessment for Tlc Substance/ Harzardous nature apparatus UV lights UV radiation is harmful to the eyes. Glass ware Can cause cuts if broken and not handled with care

glass then sweep smaller pieces. Then place all the pieces in the glass only bin in the lab.

Handling Do not look directly at the lamp Handle with care and take care with sudden temperature changes of glassware. Before heating check if it is Pyrex. No running while handling glassware Keep away from fire and heat

Disposal

Clean up carefully. If glass is broke, pick up large pieces of glass then sweep smaller pieces. Then place all the pieces in the glass only bin in the lab.

ethanol

Dichloromethane

Highly flammable. If Bunsen burners are being used nearby for other food tests, there is a serious fire risk. Breathing high concentrations causes headaches. It degreases the skin. There is limited evidence of a carcinogenic effect.

Use in fume cupboard, wear gloves and goggles

Pure salicylic acid

Wear goggles, apron and gloves. Avoid directly inhaling

Inhalation can cause coughing, sore throat. Can cause redness and pain on contact with skin

Iodine crystals

Wear goggles, apron Must be carefully and gloves. Work in disposed of. fume cupboard if possible. Keep away from any heat source and phosphorus and ammonia.

Harmful-can cause severe burns if it comes in contact with the skin. The gas emitted can be harmful and cause respiratory difficulties or even death. These crystals can produce gas even if they are merely warmed by direct sunlight. Chemicals such as phosphorus and ammonia should never be kept in the same vicinity as iodine crystals. Dangerous for environment Neutral iron (III) chloride solution 0.1 moldm^-3 Wear gloves and goggles

Toxic, highly corrosive and acidic

Cyclohexane

Keep away from heat sources.

Dispose of carefully.

Highly flammable, harmful and dangerous for the environment Ethyl ethanoate Keep away from heat sources wear gloves and goggles.

Highly flammable and Irritant Ethanoic acid Wear eye protection wear gloves

Corrosive

Risk assessment for colometric techniques Substance/ Harzardous nature apparatus Electrical appliances Can cause electrical shocks if not approached with care

Handling Make sure hands are dry when approaching plug and do not approach with metal objects in hands.

Disposal

Glass ware

Can cause cuts if broken and not handled with care

ethanol

Handle with care and take care with sudden temperature changes of glassware. Before heating check if it is Pyrex. No running while handling glassware Keep away from fire and heat

Clean up carefully. If glass is broke, pick up large pieces of glass then sweep smaller pieces. Then place all the pieces in the glass only bin in the lab.

Highly flammable. If Bunsen burners are being used nearby for other food tests, there is a serious fire risk. 5% aqueous Iron (III) ammonium sulphate solution Handle with caution Wear goggles and gloves

Irritant pH buffers Wear goggles and gloves

Irritant Risk assessment for forward and backward titration Substance/ Harzardous nature Handling apparatus 95% ethanol Keep away from fire and heat

Disposal

Glass ware

Highly flammable. If Bunsen burners are being used nearby for other food tests, there is a serious fire risk. Can cause cuts if broken and not handled with care

Handle with care and take care with sudden temperature

Clean up carefully. If glass is broke, pick up large pieces of

0.1 moldm^-3 NaOH solution

changes of glassware. Before heating check if it is Pyrex. No running while handling glassware Wear goggles and gloves

glass then sweep smaller pieces. Then place all the pieces in the glass only bin in the lab.

Phenolphthalein indicator Hot water 0.1moldm^-3 HCl solution

Irritant to eyes and skin Low risk of being flammable Can burn

Keep away from heat source Handle with care Wear gloves and goggles

Low hazard- may irritate cuts and cause harm to eyes 1moldm^-3 NaOH solution Handle with care, wear goggles and gloves

Corrosive-It causes severe burns; it is particularly dangerous to the eyes.

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