Principles: Binders, for instance, starch, microcrystalline cellulose and silica gel, which are commonly found in the painkilling tablets and used to prevent the components from crumbling on storage or while being swallowed, are all insoluble in water and common organic solvents such as dichloromethane and ethanol. Solubility is one of the crucial concepts needed in order to separate the three components – acetaminophen, aspirin and caffeine in the painkilling tablet. Aspirin with a binder and caffeine are soluble in dichloromethane while acetaminophen is not.
The two main components aspirin and caffeine could be extracted when dissolving in the dichloromethane, followed by filtration. Subsequently, using the same concept, acetaminophen which dissolves in ethanol can be extracted from the binder. Solubility could be a means to separate them because conjugated base and acid which dissolve in water but not dichloromethane are formed after aspirin and caffeine react and extract with base. The aspirin in the form of a water-soluble salt can be separated by simple filtration due to the immiscibility between water and dichloromethane.
For the identification of those products obtained, melting-point determination and thin-layer chromatography is carried out. Thin-layer chromatography could act as a useful means of quickly characterizing the main active ingredients of aspirin, caffeine and acetaminophen when they do not have many other organic compounds in significant proportions. Compared with different Rf values of each other, the interrelationship among them could be found. That is a test checking whether there are any same components among the 3 commercial analgesics.
Procedures: A. Separation of acetaminophen/binder from aspirin/caffeine 1. The given tablets were grinded to very fine powder in a mortar. 2. This powder was placed in a conical flask with adding 10cm3 of dichloromethane. 3. The conical flask was put into a beaker of warm water at 30 oC. 4. The solution was filtrated. B. Separation of aspirin and caffeine 1. The filtrate obtained in Part(A) was transferred into a separating funnel. 2. 8 cm3 of 3M sodium hydroxide solution was added and the mixture was shaked thoroughly. 3.
The aqueous layer was removed and the organic solution was extracted again with 1 cm3 of water. 4. The aqueous layer was extracted and combined the layer with the previously collected aqueous extract. C. Extraction and isolation of aspirin 1. 20 drops of 3M hydrochloric acid was added drop by drop to the aqueous hydroxide extract obtained in Part(B) with testing the acidity of the extract with pH paper from time to time until the pH of the extract was nearly 3. 2. The mixture was cooled with an ice-bath if a suspension was formed.
3. The mixture was then filtered and the solid was washed with iced water. 4. The solid was then dried completely. 5. The solid obtained was weighed. D. Extraction and isolation of acetaminophen 1. The solid residue obtained in Part(A)was transferred to a conical flask. 2. 8 cm3 of ethanol was added and the mixture was boiled for 2 minutes. 3. The mixture was filtered. 4. the filtrate was transferred to a beaker and the solvent was evaporated from the filtrate completely in a hot water bath. 5. The solid obtained was weighed. E.
Extraction and isolation of caffeine 1. 0. 5g of anhydrous MgSO4 powder was added into the dichloromethane extract obtained in Part(B) until the drying agent no longer clumped together. 2. The mixture was swirled for 30 seconds to complete the drying process and the mixture was filtered. 3. The solvent was removed from the solution completely by evaporation. 4. The solid obtained was weighed. F. Melting-point determination 1. The melting points of the separated components(acetaminophen, aspirin and caffeine) were determined. G.
Thin-layer chromatography 1. The standards and the separated components in methanol were dissolved in separated test tubes. Each test tube was contained 0. 05 sample and 3 cm3 of methanol. 2. TLC was run using the given 1-butyl ethanoate/ethnaoic acid mixture as the mobile phase. 3. After the TLC plates had been developed, the mobile phase was allowed to evaporate and the TLC plates were put into an iodine chamber(TLC chamber). Result: The weight of aspirin obtained in Part(C):0. 18g The weight of acetaminophen obtained in Part(D):0. 15g.
The weight of caffeine obtained in Part(E):0. 06g Melting-point range of aspirin:158-160oC Melting-point range of acetaminophen:163-166 oC Melting-point range of caffeine:233-235 oC Thin-layer chromatography(in the end of the report) Discussion: Limitation: 1. The amount of painkilling tablets provided is not enough. Only milligrams of products are obtained. Little amount of caffeine formed(only0. 06g) may attribute to inaccurate result when carrying out thin-layer chromatography, given that 0. 05g is needed for each sample to prepare their standards.
2. Only one solvent is provided as the mobile phase. Actually, 4:1 (v/v) 1-Butyl ethanoate/ethanoic acid may not be the best solvent. Solubility of those 3 separated components could be higher in other ratios of 1-Butyl ethanoate and ethanoic acid, which gives a more significant result of distance travelled of substances tested. Sources of experimental errors: 1. In Part(E), because of the limited amount of caffeine, simple distillation could not be carried out, leading to remaining of impurity(mainly water).
A significant and accurate result could not be obtained in the thin-layer chromatography. 2. An inaccurate Rf value is obtained due to the not uniform TLC given and starting positions of the 3 substances are not the same. Major components interpreted from the Rf value may be inaccurate and result from wrong identification of the major components in these 3 substances. Improvement: 1. Different ratios of 1-Butyl ethanoate and ethanoic acid could be provided for us to test which solvents could give the most significant results 2. At least 2 tablets of painkilling drugs are given.
This could further prevent the failure of giving accurate results of thin-layer chromatography due to a lack of products formed, especially caffeine, and distillation could be carried out with a view to increasing purity of caffeine. Safety: 1. Handle all chemicals with great care. 2. Avoid direct contact of chemicals with skin. 3. Chemical waste, broken glassware and excess materials should be disposed in accordance with teacher’s instruction. Conclusion: Separation of major components (acetaminophen, aspirin and caffeine from painkilling drugs) is quite successful.
No conclusion could be drawn from the thin-layer chromatography thanks to very unclear, if not nothing, trails that acetaminophen, aspirin and caffeine are travelled. Answers to the questions: 1. How can you determine whether a sample is pure or not from melting-point determination? A1. The sample has a lower melting point than that of the literature value if it is not pure. It is because impurity in the sample leads to the disruption of original structure of that substances, resulting in weaker intermolecular forces between molecules.
2. Although acetaminophen does not contain a carboxylic acid group, it is slightly acidic. Briefly explain why. A2. After ionization of acetaminophen, followed by detaching of a proton, the carbocation formed is further stabilized by its resonance because it is a phenol.
The ease of detaching of a proton leads to the slightly acidic property. 3. Write a chemical equation to show how aspirin can be prepared from salicylic acid. A3. Salicylic acid + Acetic Anhydride ? (H3PO4, ~70oC, 10 minutes) Acetyl Salicylic Acid(Aspirin) + Acetic Acid.