Title | Paracetamol LAB Report |
---|---|
Course | Healthy system from Atom to Gene |
Institution | University of Sunderland |
Pages | 17 |
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PARACETAMOL LAB REPORT: SYNTHESIS AND ANALYSISINTRODUCTIONParacetamol, also known as acetaminophen, is an analgesic and antipyretic drug which is commonly used to treat mild to moderate pain and to reduce fevers caused by illnesses such as the flu (NHS, 2016). It is commonly administered through eit...
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PARACETAMOL LAB REPORT: SYNTHESIS AND ANALYSIS INTRODUCTION Paracetamol, also known as acetaminophen, is an analgesic and antipyretic drug which is commonly used to treat mild to moderate pain and to reduce fevers caused by illnesses such as the flu (NHS, 2016). It is commonly administered through either the mouth or rectally but can also be given intravenously in emergency situations. Paracetamol is one of the most frequently prescribed drug in the UK (Toft, 2010) and can also be bought as an over-the-counter (OTC) medicine in retail pharmacies and supermarkets. Paracetamol was first discovered in 1877 and synthesised in 1878 by reducing pnitrophenol with tin in glacial acetic acid which produced p-aminophenol that was then acetylated in situ by acetic acid. This process was simplified throughout the years to acetylating p-aminophenol with acetic anhydride
[Appendix 1]
.
SAFETY and COSHH
Acetone
Carcinogenic
Irritant
Corrosive
Harmful
4-aminophenol 14M acetic anhydride
Toxic
Flammable
Chemical Name
Oxidising
Paracetamol Preparation:
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Special Requirements/Other: Wear appropriate equipment including lab coat, safety glasses and gloves should be worn at all times. Rinse any equipment used with acetone. Experiment must be conducted in the fume cupboard. Skin must be washed immediately if it comes into contact with the acetic anhydride. Disposal: Wipe up any spillages immediately; sodium carbonate should be used on acid spillages before cleaning. Dispose water from recrystallization and any washings into the aqueous acidic waste container. Dispose acidic waste in non-halo waste bin. Dispose filter paper in the organic solid waste bin.
4-aminophenol
Paracetamol
Dimethylaminobenzaldehyd
Carcinogenic
Irritant
Corrosive
Harmful
Chemical Name
Toxic
Oxidising
Flammable
Paracetamol Analysis:
e
Methanol
Sodium hydroxide (0.1M)
Special Requirements/Other: Wear appropriate equipment including lab coat, safety glasses and gloves in order to handle concentrated solutions. Disposal: Wipe up any spillages immediately and, in case of chemicals coming into contact
with
skin,
wash
with
soap
and
water.
Dispose
4-aminophenol
2
and
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dimethylaminobenzaldehyde in the halo waste bin in the fume cupboard.
SYNTHESIS OF PARACETAMOL In this experiment, paracetamol was synthesised via reacting 4-aminophenol with acetic anhydride. The mechanism for this reaction is a nucleophilic acyl substitution, with water as the solvent [Appendix 2]. The lone pair of electrons on the amine of the 4aminophenol attacks the C=O bond of the acetic anhydride, causing it to break and resulting in a positive charge on the nitrogen. The negative charge on the oxygen reforms the C=O bond, causing the other C-O bond to break. The positive nitrogen loses a proton when the negative oxygen attacks, forming ethanoic acid and leaving paracetamol molecule. To produce 4-nitrophenol, phenol can be reacted with dilute nitric acid at room temperature [Appendix 3]. A disadvantage of this reaction if that a mixture of 2- and 4nitrophenol is formed (Clark, 2004). Another method can be to react phenol with sodium nitrate (an oxidising agent) and sulphuric acid (a dehydrating agent); the yield of 4-nitrophenol is greater for this reaction so it is preferred (Khazaei, 2010).
METHOD: Synthesis of Paracetamol Firstly, 5.448g of 4-aminophenol was weighed by difference and added to a wide mouthed, 100mL conical flask
[Figure 1]
. Using a measuring cylinder, 15.00mL of
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distilled water and 6.00mL of acetic anhydride were both measured and added to the conical flask containing the 4-aminophenol. The magnetic stirrer was placed in the flask and the flask itself was then placed on the hot plate stirrer and heated to 150 oC for approximately 10 minutes, whilst continuously being stirred, until the solution was deemed homogenous and clear. At this point, the flask was taken off the plate and placed inside an ice water bath so as to allow the reaction mixture to cool and for a precipitate. The precipitated product was then collected via filtration with a Buchner funnel. The product was washed with approximately 20.00mL of cold water and then pulled dry on the filter paper for a few minutes before transferring into a pre weighed 100mL conical flask. The mass of the crude product was found to be 6.885g. For every one gram of crude product, 6.00mL of hot water was to be added for hot recrystallization; therefore approximately 41.00mL of hot water was placed into the conical flask containing the crude product. The conical flask was then placed on the hot plate and heated to 150160oC until all the powder had become soluble and dissolved. Once this occurred, the conical flask was put inside an ice water bath until fine, glossy crystals formed. The resulting precipitate was then filtered under vacuum using a Buchner flask and funnel; the product left on the filter paper was left to dry before transferring into a pre weighed sample bag using a spatula
[Figure 2]
.
RESULTS – Synthesis of Paracetamol Figure 1: Results Table – Weight of 4-Aminophenol
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Reactant: 4-
Weight of Weighing Boat (g)
aminophenol 0.925
Weight of Sample + Weighing Boat (g)
6.382
Weight of Weighing Boat after Transfer (g)
0.934
Weight of Sample (g)
5.448
Figure 2: Results Table – Weight of Paracetamol Product: Paracetamol Weight of Conical Flask (g)
73.430
Weight of Sample + Conical Flask (g)
80.315
Weight of Sample (g)
6.885
Figure 3: Percentage Yield of Paracetamol Moles of 4-aminophenol, C6H7NO = mass/ Mr Moles of 4-aminophenol, C6H7NO = 5.448/ 109 Moles of 4-aminophenol, C6H7NO = 0.04998 The ratio of 4-aminophenol to paracetamol is 1:1 therefore – Moles of paracetamol, C8H9NO2 = 0.04998 Theoretical mass of paracetamol, C8H9NO2 = moles x Mr Theoretical mass of paracetamol, C8H9NO2 = 0.04998 x 151
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Theoretical mass of salicylic acid = 7.547 g Percentage Yield = Actual Yield/Theoretical Yield x 100 Percentage Yield = 6.885/7.547 x 100 Percentage Yield = 91.23 %
METHOD: Analysis of Paracetamol Determination of Melting Point: A sample of paracetamol was taken and placed into a capillary tube, sealed and then inserted into the melting point apparatus. The tube was observed and the temperature of when the product began to melt and had fully melted was recorded [Figure 4]
.
Loss on Drying: A 0.9827g sample of paracetamol was weighed by difference on to a watch glass and placed in the oven at 105oC. The sample was then reweighed after approximately two hours and the percentage loss was calculated
[Figure 5, Figure 6]
.
Infrared Spectrum: Another sample of paracetamol was taken so as to acquire an infrared spectrum [Appendix 4]
.
Limit Test – Content of 4-aminophenol:
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A 1.0383g sample of paracetamol was weighed by difference and added to a test tube containing 10.00mL of methanol [Figure 7]. A 1.00mL of 5mg/mL sample of 4aminophenol standard solution was added to a second test tube along with 9.00mL of methanol. Ten drops of the dimethylaminobenzaldehyde reagent was placed into each tube and left to stand for 10 minutes. The colour and intensity of each test tube was observed and compared against each other
[Figure 8].
UV Assay – Content of Paracetamol: Firstly, a stock solution of the sample was prepared by weighing 0.1120g of the paracetamol by difference into a 100mL volumetric flask
[Figure 9]
. The flask was then
filled up to the mark with 0.1M of NaOH and inverted twenty times to ensure the product had fully dissolved and had an even distribution. To prepare the sample solution, 1.00mL of the stock solution was taken and placed into a separate 100mL volumetric flask and made up to the mark with 0.1M of NaOH and inverted another twenty times to achieve homogeneity of the solution. To measure absorbance, the wavelength was set at 257nm on a spectrophotometer and zeroed using a 1cm cuvette filled with 0.1M NaOH. The cuvette was then rinsed and filled with the sample solution of paracetamol and the absorbance was read and recorded from the instrument [Figure 10].
RESULTS – Analysis of Paracetamol 7
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Figure 4: Melting Point of Paracetamol Sample and Literature Value Sample Melting Point (oC)
168-170
Literature Melting Point (oC)
168-172
Figure 5: Results Table – Weight of Paracetamol Before and After Drying Wet Sample
Dry Sample
Weight of Watch Glass (g)
26.9201
26.9201
Weight of Watch Glass and
27.9028
27.7736
Sample (g) Weight of Sample (g)
0.9827
0.8535
Figure 6: Percentage Loss on Drying Percentage Loss = Change in Mass/Original Mass x 100 Percentage Yield = 0.9827 – 0.8535/0.9827 x 100 Percentage Yield = 13.15 %
Figure 7: Results Table – Weight of Paracetamol for Limit Test
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Paracetamol Weight of Weighing Boat (g)
0.9275
Weight of Sample + Weighing Boat (g)
1.9703
Weight of Weighing Boat after Transfer (g)
0.9325
Weight of Sample (g)
1.0383
Figure 8: Limit Test Colour Observed Control: 4-aminophenol Standard
Intense, bright yellow solution
Solution Sample: Paracetamol
Pale yellow, less intense solution (in comparison to control)
Figure 9: Results Table – Weight of Paracetamol for UV Assay Paracetamo
Weight of Weighing Boat (g)
l 0.9508
Weight of Sample + Weighing boat (g)
1.0639
Weight of Weighing Boat after Transfer (g)
0.9519
Weight of Sample (g)
0.1120
Figure 10: Absorbance Results
Absorbance
Reading 1
Reading 2
0.573
0.573
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Figure 11: Calculation of Concentration using Beer-Lambert Law A
= A (1%, 1cm) x c x l
0.573 = 715 x c x 1 c
= 0.573 / 715 x 1
c
= 8.0139 x 10-4 g/L
Figure 12: Calculation of Percentage Purity Concentration of sample = 0.112 / 100 = 1.12 x 10 -3 Percentage Purity = Concentration of pure product/Concentration of sample x 100 Percentage Purity = (8.0139 x 10-3/1.12 x 10-4) x 100 Percentage Purity = 71.55%
DISCUSSION The percentage yield for the paracetamol sample was 91.23% which not significantly lower than 100%, suggesting that human error in conducting the experiment was mostly likely the reason for the loss e.g. not all of the sample will have been transferred from the filter paper into the conical flask, the weighing of the reactant may have been inaccurate due to surrounding or there may have been a parallax error when measuring the acetic anhydride. The yield could have been improved by repeating the experiment and taking averages.
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The melting point for the sample of paracetamol was found to be 168-170 oC which is within the range of the literature value (Department of Health, 1998). The slightly lower value of the sample is possibly due to impurities in the sample. The percentage loss on drying was 13.5%, which is a lot higher than the BP value of 0.5% (Department of Health, 1998). This could be due to the fact that the sample was not oven dried before recrystallization because of time constraints. Another explanation would be that impurities in the sample were evaporated whilst heating. The presence of paracetamol was confirmed in the infrared spectra as the peaks relating to key functional groups were identified
[Appendix 5]
and compared to a control
infrared spectra of paracetamol and similarities were seen. For example, the peak at 1649.14 cm-1 and 1224.80 cm -1 shows the existence of the amide group in paracetamol. The peaks in the range of 1433.11-1504.48 cm -1 detects the benzene ring. In comparison to the spectra of 4-aminophenol, the main difference is the C=O bond is not observed. In the 4-aminophenol spectra
[Appendix 6]
, a peak at 3278.10 cm -1
shows the occurrence of the C-N bond which is not seen in the paracetamol infrared. This is most likely due to impurities in the sample and due to the surroundings. The limit test showed that there was still an amount of 4-aminophenol in the sample; although the content of 4-aminophenol that had remained in the paracetamol was less than 5% due to the intensity of yellow in the sample being significantly paler than the control test tube containing the standard solution of 4-aminophenol. Paracetamol does not undergo the same reaction with dimethylaminobenzaldehyde due to it having an amide group whereas the 4-aminophenol has a primary amine which can undergo condensation to form the azo dye
[Appendix 7]
.
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The percentage purity of paracetamol was calculated to be 71.55%, which is a considerably lower value than the BP value of 99%-101% (Department of Health, 1998). The main reason for this value would be the impurities in the sample, including the starting material of 4-aminophenol (confirmed by the limit test). It’s possible the reaction did not go to completion, as well as the fact that human errors would’ve occurred during the experiment.
CONCLUSION Both of these experiments – the preparation and the analysis of paracetamol – can be considered a success as the aim was achieve i.e. paracetamol was synthesised and was proved to be in the sample through the analytical and synthetic results. The melting point of the sample was within the range assigned by the British Pharmacopeia and the percentage yield was calculated to be relatively high. The infrared spectrum confirmed the sample to be paracetamol by identifying key functional groups thereby validating the accuracy of the experiment. The percentage purity and value was a lot lower than the literature value states it should be but this is explained by the content of 4-aminophenol which was established to be in the sample by the limit test.
PARACETAMOL POISONING
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Paracetamol toxicity is caused by the excessive consumption or overdose of the drug and is the most common causes of poisoning worldwide due to it being so easily available and the fact that most people are unaware of the dangers associated with taking it. Symptoms are not likely occur in the first 24 hours after taking a serious and/or potentially fatal dose of approximately 150mg/kg, for an adult (considerably lower for a child). However, with time, the patient develops signs of liver damage, including lowing blood sugar, low blood pH and a tendency bleed. To treat a paracetamol overdose, activated charcoal is given within the hour to decrease the amount absorbed in the gastrointestinal tract. If the timing of ingestion is unknown or if the overdose was staggered over an hour or more; all patients should be given N-acetylcystiene to replenish glutathione stores – glutathione is needed to breakdown paracetamol – although this is most effective in the first 8 hours. Patients should be referred to ICU if these is fulminant liver failure as the only remaining option would be a liver transplant (Patient Platform Limited, 2016).
REFERENCES NHS (2017) Paracetamol. [Online] http://www.nhs.uk/conditions/Painkillersparacetamol/Pages/Introduction.aspx [Accessed 28 February 2017] Toft, J. (2010) Top 10: most prescribed drugs in the UK [Online] https://medicinesideeffects.wordpress.com/2010/12/16/the-top-ten-of-prescribeddrugs-in-england/ [Accessed 1 March 2017]
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Department of Health (1998) British pharmacopeia: volume 1. London: Stationary Office Patient Platform Limited (2016) Paracetamol poisoning [Online] http://patient.info/doctor/paracetamol-poisoning [Accessed 2 March 2017] Clark, J. (2004) Ring reactions of phenol [Online] http://www.chemguide.co.uk/organicprops/phenol/ring.html [Accessed 1 March 2017] Khazaei, A. (2010) An efficient method for the nitration of phenols [Online] http://www.sid.ir/en/VEWSSID/J_pdf/95520101C12.pdf [Accessed 1 March 2017]
APPENDICES [Appendix 1]: Conversion of p-aminophenol, via acetylation with acetic anhydride, to paracetamol.
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[Appendix 2]: Mechanism for the reaction between 4-aminophenol and acetic anhydride.
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[Appendix 3]: Nitration of Phenol
[Appendix 4]: Infrared Spectra of Paracetamol 10 0 % T 5 0 400 0
360 0
320 0
Measurement
cm-1
280 0
240 0
200 0
180 0
160 0
140 0
120 0
100 0
80 0
60 0
FTIR
FTIR Measurement cm-1 09-Feb-17 3:14:13 PM
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[Appendix 5]: Interpretation of Spectra Peak (cm-1)
Bond
1649.14
N-H
1224.80
C=O
1240.23
C-O
1433.11-1504.48
Benzene Ring
[Appendix 6]: Infrared Spectra of 4-aminophenol (Starting Material) cm-1
[Appendix 7]: Reaction of 4-aminophenol with N,N- dimethylaminobenzaldehyde
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