Aspirin: Chemical Test Analysis of a Clean Sample

Introduction

Aim

To produce a pure sample of aspirin and then analyse the product by conducting several chemical tests to therefore show whether the crude sample and the purified sample produced are pure or impure.

Hypothesis

A sample of aspirin will be produced; however, the tests carried out to determine the purity of aspirin will show impure samples were produced.

Background

Aspirin, known as acetylsalicylic acid, is an analgesic nonsteroidal anti-inflammatory drug which is used to relieve headaches, muscle pains and aches as well as reduce fever that can be caused by a common cold. Aspirin can be found in all supermarkets and pharmacies, it can be found and dispensed in many different forms, it can be sold as tablets or suppositories, which means it can be taken orally or rectally.

Aspirin is derived from willow bark, the willow bark has been used for thousands of years dating back to the Egyptian era, and during this era was used as an anaesthetic and to help relieve fever, this was then carried on to later eras. However, later on in the 1700s was when the discovery and synthesis of aspirin started to occur, when Reverend Edward Stone, who at the time thought he was suffering from malaria, had first recorded his findings after accidentally swallowing willow bark and had come to the conclusion that its antipyretic effects could be a cure for malaria or other illnesses which involve fever and shivering. This continued and many scientists contributed to the isolation and chemical synthesis. However, it was not until 1897 that Felix Hoffman, a Bayer chemist had successfully synthesised aspirin, then John Vane, a pharmacologist had updated the method and was able to synthesise aspirin that prevented the production of prostaglandin 70 years later. However, despite aspirin being a safe drug to ingest, many people today still choose to take willow bark extract as a natural herbal remedy and alternative to aspirin.

Aspirin is an aromatic molecule, containing a conjugated system meaning its structure has chemical bonds which interchange from single to double bonds. As a result of the conjugated system of benzene, this means that if the light was shown on the molecule it would be able to absorb light due to the difference in energy between the molecular orbitals. When the light is absorbed the electron becomes excited, it is then promoted to a higher molecular orbital, as the electron falls back to its ground state, it releases energy and this energy can be seen on the Ultraviolet (UV) Visible Spectroscopy. Aspirin acts as an acid due to the carboxyl group attached to the six-membered benzene ring. Aspirin also contains an ester link and a hydroxyl group. Due to aspirins' multiple functional groups, this means it is able to undergo many chemical reactions.

Synthesis of Aspirin

To produce aspirin, acetic anhydride and salicylic acid must be reacted together as well as phosphoric acid which will act as a catalyst to produce aspirin and acetic acid as a by-product. The purpose of phosphoric acid in the synthesis of aspirin is it acts as a catalyst and as it is known as a strong acid it will therefore produce hydrogen ions. As phosphoric acid is acting as a catalyst it, therefore, decreases the activation energy of acetic anhydride to make it more electrophilic, thus activating the electrophile, and allowing the acetate ion (CH3COO-) from acetic anhydride which will therefore become associated with the H+ ion from the phenolic hydroxy group that is found in salicylic acid. This will therefore bond to form acetic acid as a by-product. The chemical reaction taking place here is called an electrophilic substitution, where acetic anhydride will act as the electrophile.

Ferric Chloride Test

Ferric chloride is a solution which gives rise to highly coloured complexes with phenol. This test is used to test the purity of the crude and recrystallised aspirin produced in the laboratory. The substances being tested with ferric chloride are phenol, salicylic acid, crude aspirin and recrystallised aspirin. Phenol is being tested to show the colour change with ferric chloride and salicylic acid is being tested as it is a reactant in the synthesis of aspirin. If the crude and/or recrystallised aspirin turns a dark purple, it will indicate that the product will contain phenol and therefore contain some traces of salicylic acid which will therefore mean the aspirin will be impure.

Thin Layer Chromatography (Tlc)

Thin-layer chromatography (Tlc) is a method used to analyse a substance by separating the substance into the individual compounds that were held within the compound. This method works by placing the Tlc plate into the developing solvent and watching the dots on the Tlc plate move up the plate. The most nonpolar substance will travel the highest up the plate and if a spot has travelled a small distance up the plate, this suggests the compound is more polar. Once the Tlc has taken place and the plate has been placed under UV light and the spots have been traced by a pencil, the Rf value can then be calculated.

Procedure

The procedure carried out was in the Robert Gordon University MPharm session 2019/2020 Semester 1 Laboratory Manual PH1135 Pharmaceutical chemistry and was experiments 9 and 10 that were carried out.

Results and Discussion

Percentage Yield of Crude and Recrystallised Products

From the results shown from figure 5, it can be seen that the percentage yield of the crude sample was 110.30%, this implies that the sample was still wet after 10 minutes in the oven. If the experiment was to be carried out again, the sample would have been left in the oven for another 5 minutes maximum to prevent the sample to become burnt and to try to remove excess water to produce a sample that has little to no impurities.

However, the percentage yield of the recrystallised product was 49.74%, this percentage indicates a high mass of impurities in the sample after the sample had been recrystallised and placed in the oven.

Ferric Chloride Test

The initial colour of all the substances was colourless, when the ferric chloride was added, it changed the phenol from colourless to a transparent deep purple, and the salicylic acid went from colourless to dark indigo. The crude aspirin went from a colourless to dark indigo and the recrystallised aspirin changed from colourless to light pink. Due to the ferric chloride turning substances to deep indigo only if they contained a phenolic group, it would suggest that phenol and salicylic acid should have turned a dark purple due to their physical structure which contains a phenyl group. However, the colour change of the crude aspirin suggests that there were still traces of the salicylic acid in the crude sample which then led the recrystallised to still contain salicylic acid, due to its abnormal colour change which if there were no traces of a phenolic group, it would have remained colourless.

Melting Point

The melting point of the crude sample of aspirin recorded was 123°C and the melting point of the purified sample of aspirin was 125°C and the literature melting point of aspirin is 135°C. When the melting point of the crude product is lower than the literature melting point, it is said that the sample is not pure and contains impurities, from this, it can be said that both the crude and recrystallised products contained impurities even after recrystallizing the crude sample to try to eliminate impurities. The melting point of the salicylic acid was found to be 155°C and the literature melting point of salicylic acid is said to be 159°C.

Thin Layer Chromatography (Tlc)

The results seen in figure 9, this had shown that the salicylic acid had a higher Rf value than both the crude and pure aspirin, this shows that salicylic acid was the most nonpolar out of all of the compounds tested. Both the pure aspirin and the crude aspirin were within a 0.1cm difference between the compounds, which suggests their purity would have been close to the same, this can also be said about their Rf values.

The results, however, after the ferric chloride solution had been sprayed over the Tlc plate, showed that the salicylic acid had a blue mark, the pure aspirin had a light blue mark and the crude aspirin had a faint blue mark. The salicylic acid was expected to have a blue mark as it contains a phenolic group, and this will cause the ferric chloride solution to turn blue over the salicylic acid spot.

However, the pure aspirin and the crude aspirin suggest that they both contained a phenyl group and the only way this is possible, is if the crude aspirin had been hydrolysed, therefore converting some of the aspirin back to salicylic acid, therefore the compound would then contain a phenolic group which would cause the dots on both the pure aspirin and crude aspirin to turn blue indicating the products contained impurities. This would therefore suggest that due to both aspirin products contain a phenyl group, it would therefore decrease the purity of both aspirin products.

However, both the aspirin products had similar Rf values, the pure aspirin had a lower Rf value which indicates that it was less polar and contained a lower concentration of phenyl than the crude aspirin. This suggests that despite the pure aspirin-containing Impurities, it was purer than the crude sample and it also revealed that the recrystallisation of the crude product had removed excess water and impurities from the pure sample, therefore producing a purer sample than the crude sample which was anticipated.

BP Assay for Aspirin

The BP limit for aspirin is 99.5% for the product to be classed as pure aspirin and therefore able to be consumed. From figure 8, it can be seen that sample one had a limit of 96.56% and sample 2 had a limit of 97.04%. Due to both samples being below the BP limit, it can be said that the samples contained impurities, therefore being unsafe to consume the samples.

Infrared Spectroscopy

If infrared spectroscopy was carried out to analyse both samples of aspirin, this would be able to determine what possible impurities were in the samples as infrared (IR) spectroscopy works by providing sufficient energy so the bonds within the compound do not break, however, they bend or stretch. The wavelength from the infrared radiation allows the bond to absorb the energy when it vibrates, and this is dependent on the strength and the atoms that make up the bond. Infrared spectroscopy allows compound functional groups or bonds to be easily identified on a spectrum.

Conclusion

In conclusion, from the chemical analysis tests carried out after the aspirin was synthesised, it can be said that despite the aspirin being successfully synthesised, the crude and recrystallised samples were not pure as seen from the results of numerous chemical tests performed on both the crude aspirin and the purified aspirin.