SBC214: Organic Chemistry Patel Practical : 3 800403469 Due date: 08.09.

2010

Student: Jandree Student ID: Demonstrator: Josh

SYNTHESIS OF ASPIRIN INTRODUCTION

Salicylic acid occurs naturally in the bark of willow trees (Pfeffer 2010). Prior to the 1800s, willow bark was often brewed into a tea, or chewed to relieve pain. While the salicylic acid is effective at reducing pain it was found to irritate the lining of the stomach. In 1899 a German chemical company began converting salicylic acid into the ester acetylsalicylic acid (Tarbell & Price 1957). This is the chemical known commonly as aspirin. Esterifying the salicylic acid to give aspirin reduces the irritation of the stomach lining. The German chemical company is still in existence today and still produces Bayer Aspirin. Aspirin (acetylsalicylic acid) is a versatile drug that is consumed in huge quantities worldwide. It is a non-steroidal anti-inflammatory drug (NSAID) with a wide range of physiological effects. At very low doses, aspirin is used to treat and prevent heart attacks and blood clots. At higher doses it is used as an analgesic to reduce pain and as an antipyretic to reduce fever. The reaction for this experiment shown below is a nucleophilic acyl substitution.

The advantage of using acetic anhydride is that you do not produce water which can be used for hydrolysis of the newly formed ester. Concentrated phosphoric acid will be used to keep everything in the acidified, protonated state. In the reaction it is the OH group that is reacted with acetic anhydride and the carboxylic acid remains unchanged (Tae, 2007).

AIM
The aim of this experiment is to produce Acetylsalicylic acid. Characterisation will be determined by IR spectrometry and NMR spectrometry, these will be compared to literature values. A melting point will be determined to access its purity and a percentage yield will also be calculated.

EXPERIMENTAL
As per the SBC214 practical manual pages 35- 38. Changes, additions/improvements and/or precautions: The IR spectrum was obtained using the BIO RAD Excalibur Series spectrometer. The Thermoline Australia steam bath was used and set to 85 degrees celcius. The NMR was collected on 270 MHz JEOL NMR Spectrometer

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SBC214: Organic Chemistry Patel Practical : 3 800403469 Due date: 08.09.2010

Student: Jandree Student ID: Demonstrator: Josh

RESULTS
Aspirin: Mass of Vial = 14.805g Mass of flask w/ aspirin = 14.983g (Mass of flask w/ crude product) (Mass of flask) = Mass of crude product 14.983g 14.805g = 0.178g Mass = 0.178g Molar mass = 180.16g/mol Moles = mass / molar mass = 0.178g /180.16g/mol = 9.88x10-4mol salicylic acid: Mass = 0.288g Molar mass = 138.12g/mol Moles = mass / molar mass = 0.288g /183.12g/mol = .00157mol % yield = (moles of product / moles of starting material) x 100 = 9.88x10-4mol / .00157mol x 100 = 62.9% Observed m.p (C) 139 - 142 Literature m.p (C) 135

Compound Acetylsalicylic acid

DISCUSSION
Reaction: To avoid forming an equilibrium mixture acetic acid will not be used in this experiment, instead acetic anhydride will be used. This reaction produces acetic acid as a second product instead of water. Because no water is formed in the reaction the aspirin cant hydrolyze to reform salicylic acid.(Tae,2007). During the reaction process the initial reaction that takes place is that of the 85% phosphoric acid reacting with the acetic anhydride and the reaction is outlined below.

Aromatic rings are acetylated in the presence of acid. The mechanism for the reaction of the OH group and acetic anhydride is shown below.

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SBC214: Organic Chemistry Patel Practical : 3 800403469 Due date: 08.09.2010

Student: Jandree Student ID: Demonstrator: Josh

In this reaction one of the lone pairs on the OH on the salicylic acid attacks the slightly positive carbon atom. This carbon is slightly positive due to the resonance effects of the oxygen that it is bonded to ( Weizmann et al. 1984). Due the acidic conditions, the oxygen molecule of the acetic anhydride gets protonated, this is what causes the resonance effect to take place. The following process is the production of a water molecule and acetic acid as outlined by the mechanism below: The hydrogen is removed from the oxygen by reaction with the dihydrogen phosphate ion which was formed earlier in the reaction steps, and the product is formed (Xula).

The key features of the reaction workup were the addition of 0.5ml of water to the reaction, this addition of water decomposes excess acetic anhydride. Using the Hirsch funnel to filtrate the product must be done properly otherwise product may be lost if excess D.I. water is used to recover more product. During the purification process hot distilled water is added to the crystals and this improves the quality and purity of the product as it is then recrystalized slowly. Percentage Yield and Purity: According to the equation that represents the formation of acetylsalicylic acid from salicylic acid, 1 mole of salicylic acid produces 1 mole of acetylsalicylic acid. However, only 62.9% of the expected amount of acetylsalicylic acid was yielded. Possible reasons for the loss of product include: As there is no easy way to agitate the mixture whilst the reaction occurs, less product is likely to form Movement of desired product from vial to Hirsch funnel and then from Hirsch funnel to the Craig tube and then to the tile and then into the vial to be weighed, many transferences cause a loss if product. Some product eluted to the bottom of the Hirsch funnel.

A melting point ranging from 139 - 142C indicates that the product was impure as the literature melting point is 135C. The main impurity in the crystallized aspirin will be salicylic acid, which will co-precipitate with the aspirin if the procedure is done too quickly ( Tarbell & Price 1957). Also as the product was unable to be agitated during the reaction it is possible that not all the salicylic acid would have been synthesised in the reaction process. Characterisation IR and NMR Spectra:

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SBC214: Organic Chemistry Patel Practical : 3 800403469 Due date: 08.09.2010

Observed IR (cm-1) 1616 1650 1754 3130 1301 Expected IR (cm-1) (McMurray, 2008) 1600 - 1400 1725 - 1700 1750 - 1730 3300 - 2500 1300 - 1000

Student: Jandree Student ID: Demonstrator: Josh

Functional Groups Aromatic Ring C=C (aromatic), Carboxylic Acid C=O (carboxylic acid), Ester C=O (ester), O-H (carboxylic acids), C-O (ester/carboxylic acid),

The first portion of the useful region of aspirin IR. As expected, there is a peak at 1605 cm-1 corresponding with the benzene ring. Also, there are peaks present at 1680 and 1750 cm-1, which correspond to the 2 carbonyls present in the molecule, even though they are slightly shifted from the expected 1730-1740 cm-1 range. The peak at 1680 cm-1 is shifted to a lower wave number than the expected range due to conjugation with C=C in the attached benzene ring.The second portion of the useful region of aspirin IR. This broadness is expected, between 2500 and 3500 ppm, due to the presence of the carboxylic acid in the aspirin molecule.

Functional Group CO2H CH3 4 aromatic CH

Observed NMR (ppm) Not shown 2.3552 7.12-8.14

Literature NMR (ppm) ( Mayo 2010) 11.2 2.35 7.14-8.13

The 1H NMR spectrum of aspirin shows 6 signals, due to six different hydrogen environments. The signals in the 7-8 ppm range are typical for hydrogens attached to an aromatic (benzene) ring. The hydrogen of the carboxylic acid (COOH) produces a broad signal at 11.2 ppm and the CH3 group is at 2.2 ppm. (VISC).

CONCLUSION
The reaction of salycilic acid with acetic anhydride in the presence of the acid produced the desired product, the IR and MS obtained were used to identify the structure of the product to confirm it has been formed. The % yield was low therefore the overall reaction procces may not hav been fully completed.

QUESTIONS
Please see attached.

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SBC214: Organic Chemistry Patel Practical : 3 800403469 Due date: 08.09.2010

Student: Jandree Student ID: Demonstrator: Josh

REFERENCES Mayo DW, Pike RM & Forbes DC, Microscale Organic Laboratory: With Multistep and Multiscale Syntheses, 2010, 236-237 McMurray S,2008, Organic Chemistry, 7th Edn, p 425, Thomson Education, USA. Pfeffer, F, 2010, SBC 214 Organic Chemistry Laboratory Manual, Deakin University, Australia Tae,O,2007, Synthesis Of Asprin, California State University, retrieved 3 September 2010, <http://www.csun.edu/chemistry/documents/Aspirin.pdf>. Tarbell, DS & Price, JA, 1957, Use of Mixed Carboxylic-Carbonic Anhydrides for Acylations on Carbon and Oxygen, Journal of Organic Chemistry, vol. 22, pp. 245- 250, retrieved 3 September 2010, <http://pubs.acs.org/doi/pdf/10.1021/jo01354a005>. Victorian Institute For chemical Sciences [VISC], retrieved 3 September 2010, <http://www.vicsco.com.au/downloads/NMR.pdf>. Weizmann, CH, Bergmann ED & Sulzbacher, M, 1984, Derivates of Salcylic acid, Journal of Organic Chemistry, Vol. 13, pp. 796-799, retrieved 3 September 2010, <http://pubs.acs.org/doi/pdf/10.1021/jo01164a002>. (Xula) Synthesis Of Asprin, Xavier University Of Louisiana,retrieved 3 September 2010, <http://www.xula.edu/chemistry/documents/orgleclab/24Aspirin.pdf>.

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SBC214: Organic Chemistry Patel Practical : 3 800403469 Due date: 08.09.2010

Student: Jandree Student ID: Demonstrator: Josh

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