I. SynopsisThe synthesis of aspirin is known in organic chemistry as an esterification reaction. In this experiment, preparation of aspirin were conducted and followed by recrystallisation to have it purified. Aspirin was prepared from salicylic acid and acetic anhydride. Concentrated sulphuric acid was added to speed up the reaction. It was then heated in water bath, removed, let it cooled and product was collected by suction filtration. As product collected was impure, purification was carried out by recrystallization. Then melting point of the product was determined in order to check the purity of aspirin.
Theoretical yield of aspirin expected from 2. 4g of salicylic acid was calculated to be 3. 15g. With the actual yield that was measured to be 0. 99g, percentage yield could be calculated, which was 31. 43% yield. Temperature range for the melting point was 138. 6oC – 149. 3oC. The product obtained was in powdery form aspirin. II. Introduction1. Objective1. 1This experiment was conducted so that students could familiarize with the preparation of some simple organic compound1. 2Students know how to purify the compound by recrystallisation2.
History of aspirinThe effects of aspirin-like substances were found since the ancient Greeks which was the use of the willow bark as a fever fighter. The leaves and bark of the willow tree contain a substance called salicin, a naturally occurring compound similar to acetylsalicylic acid, the chemical name for aspirin. During the 1800s, various scientists extracted salicylic acid from willow bark and produced the compound synthetically. Then, in 1853, French chemist Charles F. Gerhardt synthesized a primitive form of aspirin, a derivative of salicylic acid.
In 1897 Felix Hoffmann, a German chemist working at theBayer division of I. G. Farber, discovered a better method for synthesizing the drug. The manufacture of aspirin has paralleled advancements in pharmaceutical manufacturing as a whole, with significant mechanization occurring during the early twentieth century. Now, the manufacture of aspirin is highly automated and, in certain pharmaceutical companies, completely computerized. While the aspirin production process varies between pharmaceutical companies, dosage forms and amounts, the process is not as complex as the process for many other drugs.
In particular, the production of hard aspirin tablets requires only four ingredients: the active ingredient (acetylsalicylic acid), corn starch, water and lubricant. III. TheoryAspirin (or acetyl salicylic acid) is kind of ester, a group of organic compounds. Esters can be obtained by reacting carboxylic acid and alcohol together in a process reaction known as esterification. There are few methods of aspirin production. We can either react salicylic acid with acetic acid, or react salicylic acid with acetyl chloride and even react salicylic acid with acetic anhydride.
Acetate anhydride is used in this experiment. It acts as acid to react with alcohol to yield aspirin. The overall reaction is between salicylic acid (-OH groups) and acetic anhydride (carboxyl group) and with catalyst such as sulphuric acid (H2SO4) to speed up reaction. Acetic anhydride C4H6O3 is preferably used due to the advantage being cheap and less corrosive. It also can be formed by removing a water molecule from two acetic acid molecules. The excess of acetic anhydride will react with water produced by this reaction.
Thus, by shifting the reaction to the right will improve the yield of the acetylsalicylic acid. Alternative catalysts that can be used are sulphuric acid or phosphoric acid. IV. Procedures1. Preparation of Aspirin1. 12. 4 grams of salicylic acid were weighed in a dry 100ml conical flask1. 2The conical flask was placed in the fumehood and 6ml of acetic anhydride were added1. 33-4 drops of concentrated sulphuric acid were then added and the solution were swirled to mix1. 4In order to complete the reaction, the mixture was heated in a water bath for 10-15 minutes1.
5Flask was removed from the water bath. While it was still hot, 1ml of distilled water was added using a dropper to decompose the excess acetic anhydride1. 6An additional 40ml of cold water was added, and then the mixture was stirred and rubbed with a stirring rod to induce crystallization. 1. 7The product was collected by suction filtration and was washed with a little of cold water2. Recrystallisation of Aspirin1. 1The crude product was dissolved in 5ml of ethanol in a 100ml conical flask and warmed on a hot plate1. 230ml of hot water was added to the solution1. 3The solution was then cooled1.
4A watch glass with a piece of filter paper was weighed and then recorded1. 5The crystals were filtered and dried in the oven at 100oC for 20 minutes1. 6The recrystallised product was cooled in the desiccator for 10 minutes and then the crystal was weighed together with the watch glass and filter paper1. 7Yield of aspirin and percentage yield of recrystallised aspirin were calculated1. 8Melting point of aspirin were then determined1. 9Lastly, some crystal aspirin sample were kept for further reference and the rest of aspirin waste were discarded into container specialized for aspirin wasteV.
Results and CalculationWeight of salicylic acid2. 40 gWeight of dry recrystallised aspirin 0. 99 gPercent yieldMoles of salicylic acid used 0. 0175 molTheoretical number of moles of aspirin0. 0175 molTheoretical weight of aspirin 3. 15 gPercent yield === 31. 43% yieldMelting PointTemperature range 138. 6oC – 149. 3oCAppearancePowdery crystalVI. DiscussionAs the salicylic acid was prepared, there was a need that we used a dry conical flask, this was because water would break down the acetic anhydride C4H6O3 so it might affect the product that we wanted.
While 6ml of acetic anhydride was added, the flask was placed in fumehood so as to reduce the irritating and smelly odor came from the acetic anhydride. 4 drops of concentrated sulphuric acid were added as it would speed up the reaction because it acts as a catalyst. After the mixture was heated and removed from the fumehood, 1ml of distilled water was added in order to stop the reaction, it was as well as to decompose the excess acetic anhydride. An additional of 40ml cold water was added, stirred and rubbed with a stirring rod so we could induce crystallization and get the crystal of aspirin.
While doing the suction filtration to collect the product, filtrate paper was washed with a little of cold water, this would minimize the paper from breaking. The crude product aspirin prepared was quite impure, so there was a need to purify it. It could be accomplished by the process of recrystallisation. The purpose of recrystallisation was to purify insoluble aspirin because pure substances were not usually obtained in organic reaction due to incomplete reaction of some starting materials that was found with the product. Hence, purification could remove any unreacted salicylic acid and acetic anhydride.
The impure aspirin was dissolved in warm ethanol. The solution was then cooled slowly and the aspirin crystallizes out of solution leaving the salicylic acid and other impurities behind. The determination of melting point was to identify and estimate the purity of product aspirin. Most pure organic compounds have sharp melting point. Generally, an impure compound would exhibit a melting point lower than that of the pure compound. A good solvent does not dissolve the compound at low temperature (at room or 4oC) but dissolves at higher temperature (the compound is soluble).
Precautions include using just enough water to dissolve sample at high temperature, doing the filtration when the solution is hot, and cooling slowly to obtain nice crystals, and then cooling on ice to improve yield. High yield can also be obtained by further Re-crystallization. Some safety considerations were that to avoid contact skin with acetic anhydride and concentrated sulphuric acid or breathe in the vapour as it was highly corrosive and could cause irritation to the skin.
An excess of these could be disposed of in the sink, if it was spoiled, wiped it up with a wet paper towel and threw it in the trash. The acetic anhydride could cause bad burns, so it was used in the hood. To remove the conical flask from the water bath, safety glassed and gloves were used as flask was hot. Concentrated sulphuric acid was poured to solution, instead of the solution to concentrated sulphuric acid because the heat of solution would cause it to boil and the acid to spatter. The aspirin waste was discarded into aspirin waste container after the experiment had been done. VII. ConclusionAspirin is prepared from chemical synthesis by acetylating salicylic acid with acetic anhydride.
After the experiment, students were able to conduct synthesis of aspirin, acquire the skills of recrystallisation using normal filtration and reinforce the technique of melting point determination. VIII.
ReferencesGraedon and Ferguson, 1993. The Aspirin Handbook: A User’s Guide to the Breakthrough Drug of the Nineties. Australia: Bookman. Kolias. & Co. , 2002. How to make aspirin [online]. Available from: http://www. kolias. com/science/meltingpoint. htm [Accessed 26 Oct 2007]Synthesis of Protein. [online]. Available from:http://intro. chem. okstate. edu/ChemSource/medicine/lab1.htm [Accessed 26 Oct 2007]Bayer, 2006.
The History of Aspirin. [online]. Available from:http://www. bayeraspirin. com/pain/asp_history. htm [Accessed 26 Oct 2007]IX. AppendixQuestions and Answers1. What could be the reasons for a sample with(i) lower melting point than expected? If aspirin melts at a temperature below the expected melting point, two possibilities exist: either the product is impure or it is not aspirin. In this case, it is because the presence of impurities in the product, as it might have contaminated with salicylic acid. (ii) higher melting point than expected?
The achieved product is in a saturated condition, in other word, it is too concentrated. It might be caused by the solution were mixed with some other solution. 2. What need to be considered for crystallization of any organic solid? During crystallization, all impurities will be removed. For soluble impurities, extra care must be taken when the impurities pass through the filter paper together with solvent upon suction filtration as crystallized product might be lost in this step. Besides, the solvent used must have high solubility and obey the rule “like dissolves like”.