Preparation and Analysis of Aspirin: Procedure to Obtain a Sample of Aspirin of Acceptable Purity
Abstract
Aspirin was prepared by acetylation in this experiment, where acetic anhydride was used to add salicylic acid to the acetyl group to create acetylsalicylic acid (aspirin). This experiment was intended to prepare the aspirin and examine its purity. The purity of the sample was determined by Thin Layer Chromatography (TLC) and to reinforce the technique of melting point determination. The amount of crude aspirin synthesized was 2.4g and the amount of pure aspirin synthesized was 1.6g. the TLC analysis showed that Salicylic acid traveled a little bit further than the Aspirin and the Product that was made thus the aspirin that was synthesized was not pure enough.
Introduction
Aspirin is the painkiller that is most widely sold worldwide. Salicylic acid is the key ingredient used to synthesize aspirin; aspirin is prepared by a chemical reaction called acetylation where a hydrogen atom is replaced by an acetyl group. The substitution of the hydrogen atom of the hydroxyl group with an acetyl group requires this reaction. Salicin is present in the bark of the willow tree, and it was shown in 1870 that salicin in the human body is converted into salicylic acid. Patients were given salicylic acid to alleviate the symptoms of fever and discomfort, but it caused mouth and stomach irritation. Sodium salicylate was then made by chemists, causing less discomfort, but also causing patients to vomit. Aspirin was first developed by Felix Hofmann of the Bayer Company by adding an acetyl group to salicylic acid (acetylsalicylic acid), which had strong salicylic acid.
John Vane, a pharmacology professor, has published articles explaining the mechanism of action of aspirin. Aspirin and other anti-inflammatory medications have been shown to inhibit cyclooxygenase activity, which is responsible for producing prostaglandins that cause inflammation, pain, fever, and swelling.
An experiment was performed in which aspirin was prepared using a particular technique. Robert T. Edmunds, of the Norwich Pharmacal Company, carried out the experiment. The method used was dryness distillation that produced over 99.5 percent purity of aspirin. In this experiment, an aspirin product of high purity and yield in the form of crystals was shown to be an easier and more cost-effective way to manufacture, resulting in easy tableting. Distillation to dryness, however, is not widely used in laboratories as it is experimentally insecure.
Methodology Materials
2.4 g of sodium salicylate weighed directly into a 100 ml conical flask containing a magnetic stirrer bar. The conical flask was then taken to the assigned fume hood and added 30 mL of 2M NaOH. Stirred the mixture with the magnetic stirrer that was provided until everything was dissolved (while the heating element was switched off.). The magnetic stirrer was turned off and then crushed ice was added into the flask until the total volume was approximately 50 mL. With continuous stirring, 5.0 mL of ethanoic anhydride (commonly called acetic anhydride) was added with 3 mL plastic disposable pipettes and stirred gently for 15 minutes.
The stirrer was switched off so more crushed ice could be added until it reached 65 mL. as soon as the crushed ice was added the stirring started again. Then 16 mL of 4M HCL was added with a 3 mL plastic disposable pipette and stirred until the mixture was thoroughly mixed until heavy white precipitate started to appear.
The vacuum filtration system has been mounted in advance so that the solution can be filtered without waiting too long. To clean the conical flask, a small amount of distilled water (about 20 mL) was used to ensure that all the product was transferred to the filter paper. The object was moved to a pre-weighed watch glass to dry for approximately 30 minutes in the over. The dried product was weighed to give the estimated yield. The weight of the watch glass with the product was subtracted by the weight of the watch glass to give the weight of the product itself. The melting point apparatus was used to determine the melting point of the synthesized product.
The traditional heated block apparatus was used to calculate the melting point. Tubes that were pre-sealed from one end were provided and gently pressed the opened end into the pile of aspirin. Tapped the closed end of the capillary onto the bench top, so that the aspirin crystals work their way to the bottom. The aspirin crystals should be firmly packed and filled in the capillary tube to a depth of no more than1-2 mm. Insert the capillary tube containing the sample into the melting pointed apparatus. Record the temperature where the melting point was first observed and when it becomes a liquid completely. Two samples were obtained to determine an accurate melting point, and this was done when the sample was fully dry.
Run a thin layer chromatography (TLC) of the crude product using a commercial silica gel plate. Standard solutions of aspirin and salicylic acid in acetone were provided. to prepare a small volume (1. 0 ml max) of a solution of your own product in acetone using a small sample tube as the container. The sample does not have to be completely dry for this and the amount needed (the size of a coriander seed) will make little difference to the overall yield, so took this out from the beaker at any time you were ready. Your three solutions were made to ‘spot’ on the TLC plate.
Using a pencil three spots were marked and labeled as Asp, Sa, and P on the plate provided. Each solution was spotted two or three times on the same place and dried it thoroughly. Ensure that the eluent level (solvent A) was below the pencil line on the plate. Allowed the solvent to rise at least two-thirds of the distance up the plate. Then removed and mark the solvent distance immediately with a pencil line. Dry the plate and examine it under an ultraviolet lamp to detect spots. Marked these spots by tracing them in pencil.
Discussion
The experiment was to prepare aspirin and then analyze its purity by means of thin-layer chromatography (TLC). The melting point of the sample was also taken, varying from 137-138°C. The melting point of pure aspirin is 135°C, as compared to the sample, it shows that the melting point of the synthesized aspirin is not far from the melting point of pure aspirin. This indicates that the sample does not have a sufficient degree of purity. In the experiment, it would not be possible to produce 100% pure aspirin because some of the salicylic acids would be un-acetylated and other side reactions would influence the purity of the sample.
left-190500After Thin Layer Chromatography was performed, the result showed us that the salicylic acid (Sa) was purer than the aspirin and the product because as we can see on the picture it was more visible under UV light and it traveled a bit further down the plate than the aspirin(asp) and the product (p). The aspirin’s (Asp) first point was 0.5cm down the plate and it was a brown circular shape which was blurry and not very clear. The second point was at 1.0cm and it was half-circle blueish purple. The Salicylic acid (Sa), the first one was a brown circle shape which was 0.3cm down the plate and it was very concentrated. the second point was at 0.9cm color blue and half-circle shape. The product’s (p) first point was 0.5cm down the plate and it was a small brown color circle not very concentrated. The second point was at 0.9cm down the plate and the half-circle color was bluish purple.
Aspirin moved very far up the solvent front and because one of its acidic or polar functional groups (-OH) was converted to an ester, it is much less polar than salicylic acid. Due to its carboxylic acid group and the alcohol, it contains, Salicylic acid is even more polar. Salicylic acid was, therefore, more drawn to the polar stationary phase (silica gel) and like acetylsalicylic acid, did not travel as far up the TLC layer. Aspirin was more drawn to the mobile phase than the stationary phase.
Conclusion
In the experiment, the procedure used was used to obtain a sample of aspirin of acceptable purity. There are other strategies that may lead to higher purity aspirin preparation, such as the recrystallization process, but this would result in a lower product yield. Another technique listed in the introduction is dryness distillation, which can achieve a high degree of aspirin purity, but is considered a risk using this process. The procedure used in the experiment was safe and was still able to obtain a product with acceptable purity given that many factors would lead to the levels of impurity. Using a different process like recrystallization, however, may have resulted in a purer sample.
References
- Cammack. R, (2006), Oxford Dictionary of Biochemistry and Molecular Biology, 2nd Edition, Oxford University Press Colin Osborne, Maria Pack, 2003, Aspirin, 2nd edition, Royal Society of Chemistry
- Vane JR, Botting, RM, 2003, Pubmed.gov, the mechanism of action of aspirin, [available at https:www.ncbi.nlm.nih.govpubmed14592543] accessed: 29112017
- R.T Edmunds, 1966, Preparation of Aspirin, Norwich Pharma Co [available at https:www.google.compatentsUS3235583] accessed : 29112017
