Synthesis of Aspirin

Synthesis of Aspirin

Aspirin is a medicine commonly used nowadays to relieve the effects of many mild illnesses spanning from total relief from pain and aches; headaches, tooth, arthritis, and muscles; to keep blood clotting and lower stroke risk and heart attack; to decrease fever and potentially avoid some cancers.

Aspirin does have a rich history of development that could have started in 3000BC during the discovery of willow tree medicines as the best for curing many ailments, although its use for inflammation and pain relief was noted in the Elbers Papyrus after another 1500 years. The willow tree bark was used in quite the same manner for the next few thousand years, even though it wouldn't be until 1828, 4800 years after the discovery of its usefulness, that the active component of willow bark was separated from the Latin Salix crystals by the German chemist Joseph Buchner. The crystals were deemed relatively pure at the time, but a year later Henri Leroux of France succeeded in obtaining them in purer forms. In the following years, various pharmacists/chemists made findings, which we all know housed salicylic acid. The Italian Chemist Raffaele Piriam was the person that managed to formulate a technique which he called Salicylic Acid (SA) containing a more refined form of salicin from the willow extract.

After these findings, the use of Salicylates, salts of salicylic acid and esters, became more common for the cure of fever, inflammation, and pain among doctors but with varying degrees of success due to unforeseen complications like gastric discomfort of the stomach and mouth lining. It wasn't until about 1897 when Bayer Pharmaceuticals' Felix Hoffmann developed a method of synthesizing acetylsalicylic acid after having been charged with seeking a substitute for salicylic acid that didn't induce gastric irritation four years earlier.

Synthesis of Aspirin

Aspirin is the generic term for the acetylsalicylic acid drug, commonly utilized as a pain killer or for fever reduction. Salicylic acid, a name derived from Salix, the willow family of plants, was produced through willow bark extracts. Willow bark teas have been used as remedies for headaches and other tonics in folk medicine. These days, salicylic acid is administrated in the form of aspirin which is fewer upsets the stomach less than salicylic acid. Salicylic acid responds with surplus acetic anhydride in the preparation of aspirin. As a driving force, a small quantity of a solid acid is used to accelerate the reaction. Phosphoric acid will be used as a catalyst in this experiment. The surplus acetic acid with the inclusion of water will be consumed. The aspirin formula is not very water-soluble, so when there is an addition of water, the aspirin product can catalyze. Aspirin's synthesis process is shown below:

Since acetic acid is very water-soluble, it is easily isolated from the product of aspirin. The "crude product" is the aspirin extracted in this stage. It is possible to obtain a "purified product" by recrystallizing the crude product in hot ethanol. The crude product will be the ideal product in this experiment. For this reaction, the percentage yield of the crude product is known. The product's purity will also be analyzed. Three various methods will be used to analyze the product: titration, melting point, and spectroscopic assay.

The range of pure aspirin melting point is 138-140°C, and the range of melting point of the starting material for salicylic acid is 158-161°C. If your crude sample includes impurities, the product's number of melting points will be smaller than the range of pure aspirin. Your range of melting point may also exceed 2 degrees.

The moles of the acetylsalicylic acid present can get its estimate from the titration of your sample, provided that your crude sample does not contain a large amount of acid impurity.

Aspirin's spectroscopic analysis may require iron (III) complexing to the deprotonated shape of salicylic acid (salicylate ion) to provide a purple solution. Only salicylate ion is the single acid that complexes to iron(III). Your aspirin product will be compared with a standard 0.15% ferricsalicylate solution as well as a commercial aspirin tablet. Aspirin can decompose (hydrolysis) into acetic acid and salicylic acid in the existence of moisture. This reaction is the inverse of the synthesis reaction. In an aspirin sample, the optimum allowable quantity of free salicylic acid is 0.15%.

Reaction Mechanism

The phenol group's oxygen atom instigates a nucleophilic attack on carbon in the acetic anhydride's carbonyl bond. As a result, the phenol group's oxygen charges positively and the electrons in the acetic anhydride forming the carbonyl bond are driven on to the bond's oxygen and therefore become negative. In the phenol group, the relationship between oxygen and hydrogen cuts, where the oxygen carries both electrons and stabilizes. The proton expels from the formation, and then the carbonyl bond reforms as the oxygen delocalize the electrons it acquired and becomes stable.

Purification Process

The purification process is relatively simple and is carried out through the cold and hot filtering process.

The impure acetylsalicylic acid crystals should be added with distilled water. Using acetylsalicylic acid properties and being soluble in hot water and insoluble in cold, insoluble impurities can be eliminated by heating the combination of acetylsalicylic acid crystals to the stage where the acetylsalicylic acid crystals dissolve in the solution. It is then necessary to filter this hot solution into a clean beaker. The filter paper trapped any insoluble impurities, but the soluble acetylsalicylic acid passes. It is then required to put the hot filtered mixture inside ice water to recrystallize it. When cold, the mixture can be filtered again with a Hirsch funnel, a sidearm flash, a vacuum pump, and a filter paper. As the acetylsalicylic acid is crystalline, the filter paper should stop it and eliminate any soluble impurities. It is easy to wash and dry what is left in the filter paper with distilled water. The dried crystals should be a pure form of acetylsalicylic acid or aspirin, given that the synthesizing process has been completed.