synthesis of aspirin lab report, Schemes and Mind Maps of Chemistry

Download synthesis of aspirin lab report and more Schemes and Mind Maps Chemistry in PDF only on Docsity! Esterification reaction: the synthesis and purification of 2- Acetoxybenzoic acid and subsequent analysis of the pure product (acetylsalicylic acid ) via Thin-Layer Chromatography. Andra C. Postu Department of Chemistry, American University, Washington, D.C. 20016 Date of Publication: February 25, 2014 ABSTRACT: An esterification reaction was performed in order to convert salicylic acid to acetylsalicylic acid, the prodrug and active ingredient in Aspirin. Salicylic acid is made less acidic by converting its alcohol functional group into an ester so that it is less damaging to the digestive system in the human body. The purpose of the experiment is to synthesize, isolate, and purify 2-acetoxybenzoic acid and analyze salicylic acid, crude product, and acetylsalicylic acid via Thin-Layer Chromatography to determine if pure aspirin was synthesized. The amount of crude aspirin synthesized was 3.029 grams and the amount of pure aspirin synthesized was 2.169. The theoretical yield was 2.520 grams. Thus, there was a percent error of 13.93 % and percent yield of 86.07%. TLC analysis showed that acetylsalicylic had a higher Rf value than salicylic acid (.800 vs. .315 Rf value, respectively). The salicylic acid was more polar because of its extra polar functional group and did not travel as far. Thus, pure aspirin was synthesized. INTRODUCTION 2-Acetoxybenzoic acid, more commonly known as Aspirin, is a white, crystalline substance most commonly known for its pain-relieving qualities1,2. Acetylsalicylic acid (active ingredient of Aspirin) is an acetyl derivative of salicylic acid and the prodrug of the active metabolite, salicylic acid.2 Aspirin is a salicylate drug because it is an ester of salicylic acid. It is commonly known for its pain relieving properties. However, it does not only serve as an analgesic but also as an antipyretic, anti-inflammatory, and antiplatelet medication2. The main metabolite of acetylsalicylic acid, salicylic acid, is an essential part of the human metabolism3. Salicylic acid is an integral part of pain management and was often used by ancient cultures, such as the Native Americans, who extracted the chemical from willow tree bark3. This fundamental compound can cause stomach irritation and is bitter tasting, so a milder prodrug called acetylsalicylic acid was synthesized in 1893 by the German chemist Felix Hoffmann who worked for Bayer2,3,4. Acetylsalicylic acid is a type of drug that is formulated deliberately so that it will deteriorate in the body into the active drug5. This prodrug was developed because it is much less abrasive when delivered to the body and is much more easily absorbed6. The active drug, salicylic acid, is the active metabolite because it is the form of the drug after the body has processed it. Edward Stone of Oxford University discovered salicylic acid in 1763 from the bark of willow tree4,5,6. Aspirin works by suppressing the synthesis of prostaglandins and thromboxanes in the human body3,4,5. Prostaglandins function as local hormones produced in the body that aid in the transmission of pain signals, regulate the hypothalamic thermostat, and inflammation2. Thromboxanes are involved in the aggregation of platelets that form blood clots. It does this by the irreversible inactivation of prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase 2, an enzyme that is needed in the synthesis of prostaglandin and thromboxane.5 Aspirin serves as the acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the prostaglandin-endoperoxide synthase enzyme. The ability of aspirin to diminish inflammation is due to its inhibition of the synthesis of prostaglandins. Aspirin alters the oxygenase activity of prostaglandin synthetase by moving the acetyl group to a terminal amine group4. Though aspirin has numerous benefits, there are several adverse affects as well. It is particularly damaging to the stomach lining and there is an increased risk of gastrointestinal bleeding3,5. The risk of stomach bleeding increases with use of drugs such as warfarin and alcohol6. Large doses can cause a ringing in the ears, or tinnitus. Some people may have allergy- like symptoms including hives and swelling because of a possible salicylate intolerance1. Aspirin can cause swelling of skin tissues (angioedema), increase risk of Reye’s syndrome and can cause hyperkalemia1,2,3. Although most commonly known for its anti-inflammatory properties and pain-reducing qualities, acetylsalicylic acid is also an effective fever-reducer and has been to shown to prevent the progression of existing cardiovascular issues such as heart attacks or strokes in low does on a long term basis. Aspirin’s antiplatelet effects come from its ability to inhibit the synthesis of thromboxane, which otherwise bind platelets together in areas where vessel damage has occurred 4 . These platelets can clot together and become harmful otherwise. It also controls fevers through a similar mechanism (prostaglandin system) and the inhibition of PTGS that is not reversible5. Thin Layer Chromatography (TLC) is a chromatography technique that is used to separate mixtures that are non-volatile such as salicylic acid, acetylsalicylic acid, and the crude RESULTS Figure 1: Structure of Salicylic Acid, Acetic anhydride, and Acetyl salicylic acid The structures of salicylic acid, acetic anhydride, and acetylsalicylic acid are pictured above with their functional groups clearly visible in red. Mass= Density x Volume (Eq.1) Mass (g) acetic anhydride used= (1.08 g/mL) x (5.00 mL) Mass (g) acetic anhydride= 5.40 g Mass of aspirin synthesized (g)= (Mass of aspirin and filter paper) – (Mass of filter paper) (Eq.2) Mass of aspirin synthesized (g)= (3.159 g)-(.1300 g) Mass of aspirin synthesized (g)= 3.029 Mass of purified aspirin product (g)= (Mass of purified aspirin and filter paper)- (mass of filter paper) (Eq.3) Mass of purified aspirin product (g)= (2.299 g)- (.1300 g) Mass of purified aspirin product (g)=2.169 Table 1: Synthesis of Aspirin Data Salicylic Acid Acetic anhydride Acetylsalicylic acid " http://www.chemspider.com/Chemical-Structure. 2157.html " http://www.chemspider.com/Chemical-Structure. 331.html " http://www.chemspider.com/Chemical-Structure. 7630.html Mass of salicylic acid used (g) 2.009 Volume of acetic anhydride used (mL) 5.000 Mass of acetic anhydride used (1.08 g/mL) used (g) 5.400 Mass of aspirin and filter paper (g) 3.159 The table above depicts the various masses and volumes of calculated and raw data in the synthesis of aspirin. 2.009 grams of salicylic acid was used with 5.000 mL of acetic anhydride. The calculated mass of acetic anhydride was calculated using it’s known density for a mass of 5.400 grams. The mass of aspirin and filter paper was 3.159 grams. The mass of the filter paper was .1300 grams. Thus, the calculated value of crude synthesized aspirin was 3.029 grams. Following purification, the calculated mass of the final aspirin product was 2.169 grams. Theoretical Yield (Eq.4) 2.0 g salicylic acid (1 mole/138.0 g) = 0.014 moles 5 mL acetic anhydride (1.08 g/mL) = 5.4 g 5.4 g (1 mole/102 g) = 0.05 moles There is a smaller molar amount of salicylic acid so it is the limiting reagent. Therefore, the theoretical yield of acetylsalicylic acid is 0.014 moles. 0.014 moles acetylsalicylic acid (180 g/mole) = 2.52 g Percent Error =(experimental mass - theoretical mass) / theoretical value x 100% (Eq.5) Percent Error=(2.169-2.520)/2.520 x 100 Percent Error=13.92 % Percent Yield = (experimental mass/theoretical mass) x 100% (Eq. 6) Percent Yield=(2.169/2.520) x 100 Percent Yield= 86.07 % Table 2: Theoretical Yield, Percent Error, and Percent Yield The calculated theoretical yield was 2.520 grams. Thus, the percent error was 13.93 % and the percent yield was 86.07%. Figure 2: TLC Plate with Salicylic Acid, Crude Product, and Final Product under UV Light Mass of filter paper (g) .1300 Mass of crude aspirin synthesized (g) 3.029 Mass of purified aspirin product (g) 2.169 Theoretical Yield (g) 2.520 Percent Error 13.93 % Percent Yield 86.07% " Pictured above is the TLC plate with salicylic acid, crude product, and final purified produce under UV light, respectively. The final product (acetylsalicylic acid) traveled the furthest up the TLC plate. The salicylic acid travelled the smallest distance. Rf Value= (distance from start to center of substance/distance from start to solvent front) (Eq. 7) Rf Value= (2.0 cm/6.35 cm) Rf Value=.315 Table 3: Rf Values of Salicylic Acid, Crude Product, and Final Product from TLC Analysis The salicylic acid travelled the smallest distance with and Rf value of .315. Crude acetylsalicylic acid had an Rf value of .480. The purified acetylsalicylic acid product traveled the furthest up the TLC plate with an Rf value of .800. DISCUSSION The esterification reaction is a term for a general reaction in which two reactants, an alcohol and an acid, form an ester in the final product2. This reaction can be used to synthesize aspirin from salicylic acid. These types of reactions are typically reversible, so most esterification reactions are equilibrium reactions. Le Chatelier’s principle is a pillar of modern chemistry that states that any change imposed on a system that is in equilibrium will cause the system to adjust to a new equilibrium in order to counteract the change2. The reaction is slow in pure acetic anhydride, therefore phosphoric acid was used as a catalyst for the reaction because it is a strong acid2. According to Le Chatelier’s principle, an excess amount of acetic anhydride Salicylic Acid Rf value .315 Crude Acetylsalicylic Acid Rf value .480 Pure Acetylsalicylic Acid Rf value .800 CONCLUSION A total of 2.169 grams of pure aspirin was synthesize out of a possible yield of 2.52 grams. Thus, there was a 13.93 % error and 86.07% product yield. TLC analysis further confirmed these results due to the observation that aspirin had a higher Rf value that salicylic acid (.800 vs. .315, respectively), thus demonstrating that the one of polar functional groups had been converted to an ester. This makes aspirin less acidic and therefore less damaging to the digestive system of the human body. In the future, special care should be given to the washing of the crystals with cold distilled water to maximize yield. Also, a stronger acid catalyst such sulfuric acid could be used to further increase the rate of reaction. Mechanism 1: Reaction between salicylic acid, phosphoric acid, and acetic anhydride Mechanism 2: Reaction of Water and byproducts REFERENCES (1) Pehlic, E.; Nuhanovic, M.; Sapcanin, A.; Banjanin…, B. Characterization of acetylsalicylic acid with thin-layer chromatography and hot--stage microscopy depending to solvent system. 2012. (2) Klein, D. Organic Chemistry: 2nd ed.;Wiley:Hoboken, 2013. (3) Williamson, K and Katherine Masters. Macroscale and Microscale Organic Experiments, 6th ed.; Brooks/Cole, 2011. (4)Rainsford, K. History and development of the salicylates. Aspirin and Related Drugs 2004, 1– 23. (5)Olmsted, J. A. Synthesis of Aspirin: A General Chemistry Experiment. Journal of Chemical Education 1998, 75. (6)Truelove, J.; Hussain, A.; Kostenbauder, H. Synthesis of 1-O-(2’-acetoxy)benzoyl-alpha-D-2- deoxyglucopyranose, a novel aspirin prodrug.Journal of pharmaceutical sciences 1980, 69, 231– 2. Andra Postu Organic Chemistry Lab II Lab Partner: Michael Bible February 19, 2014