Organic Chemistry - Synthesis of Aspirin

VI. Results and Discussions In this experiment the synthesis of acetylsalicylic acid became possible through the induction of an acetyl functional group into a chemical compound or simply acetylation. In this particular synthesis, the acetylation used acetic anhydride as the acetylating agent which readily reacts with the free hydroxyl group. The mechanism in the acetylation of salicylic acid begin when hydroxyl group attached in the salicylic acid protonates the α-carbon in the carbonyl group of the acetic anhydride(also known as ethanoic anhydride) which will eventually yield the acetylated product due to the displacement of acetate and loss of proton during the reaction.

Figure 11.1 Mechanism for the reaction involved in the synthesis of acetylsalicylic acid from

salicylic acid. (Image retrieved from:

http://alevelchem.com/img/aspirin_preparation.gif) The first part of the synthesis was the preparation of the acetylsalicylic acid, in which 1 g of the starting material which is the salicylic acid was dissolved in a 3 mL acetic anhydride and 5 drops of 85% phosphoric acid. The used of acetic anhydride instead of acetic acid as an acetylating agent in this synthesis was one of the relevant point in this experiment because the speed of reaction between salicylic acid and acetic anhydride is faster compared to the reaction between acetic acid and salicylic acid also the used of acetic anhydride in the synthesis gives a higher yield compared with the used of acetic acid. Addition of 5 drops 85%

phosphoric acid in during the experiment was also relevant because it hastens the dissolving of salicylic acid also it makes acetic anhydride more electrophilic. If in the case an acetyl chloride was used as an electrophile during the synthesis addition of phosphoric acid in the reaction will definitely not be needed because acetyl chloride is electrophilic enough. After the mixing/dissolving the salicylic acid with acetic anhydride and 85%phosphoric acid, the mixture then was subjected into heat for about 15 minutes. Heating the mixture turned the heterogeneous white colored mixture into a homogeneous colorless liquid solution. This observed change in the color of mixture upon heating indicates that the salicylic acid becomes more soluble or it completely was dissolved due to the increased in temperature. Upon heating the mixture, addition of 2 mL distilled water followed, in this step a heterogeneous thickened mixture was observed with presence of slightly formed white precipitate. Thus adding of water in the mixture upon heating slight formed the desired product which is the aspirin. The visibility of aspirin upon adding water is due to the fact that aspirin does not readily dissolve in water. Also, adding water upon heating the mixture decomposes the excess acetic anhydride used to react with the salicylic acid. Next upon adding 2 mL distilled water, addition of 20 mL ice-cold water in the mixture and placing it in an ice-bath further made the desired product aspirin more visibly formed. Upon cooling the mixture, suction filtration comes next, in which white powdered substance was obtained during isolation. After suction filtration the precipitate in the filter paper was allowed to dry using a steam bath and after drying some traces of small bits of sugar like crystalline solids became visible. Next part of the experiment was the purification of the crude product/aspirin obtained during the preparation of acetylsalicylic acid from salicylic acid or simply the recrystallization of the aspirin. To start with the recrystallization process, 0.85 g of crude aspirin from a total of 0.89 g of crude product obtained during the preparation of acetylsalicylic acid was allowed to dissolve in a 95% ethanol dropwise until all the crude aspirin completely dissolves. After completely dissolving the crude aspirin, addition of cold distilled water dropwise follows and then the mixture was allowed to cool in an ice bath both this step gave an observable reappearance of sugar like crystals which was first observed during the preparation of acetylsalicylic acid. After the observed reappearance of the desired recrystallized/purified aspirin suction filtration follows

and in this step more visible crystals left in the filter paper was observed. Upon suction filtration the filter paper together with the more visible crystals was again allowed to dry under the steam bath and after drying much more visible fine crystals was observed. Aspirin was recrystallized in this experiment using 95% ethanol and not with hot water because knowing that aspirin undergoes reactions as of esters once hot water was used during the recrystallization there would be a great tendency that the aspirin will be hydrolysed and may yield back into carboxylic acid. After the preparation of acetylsalicylic acid, recrystallizing/purifying the crude aspirin the last part of the synthesis was the characterization of aspirin or simply distinguishing the differences between a pure salicylic acid, commercialized acetylsalicylic acid & the laboratory synthesized acetylsalicylic acid using various characterization tests. Three various tests namely, FeCl 3 test which tests the presence of impurities specifically the presence of unreacted salicylic acid in the synthesized aspirin, KMnO4 test which detects the presence of 1º alcohols, 2º alcohols and phenols in the compounds and lastly the Starch test which utilized an I2/KI solution or simply iodine solution to detect the presence of starch in between the commercial and synthesized aspirin. In the FeCl 3 test only the synthesized aspirin yields a positive result in which the mixture turned into a bright purple solution which indicated that the synthesized aspirin still contains unreacted salicylic acid in this case, we must consider using more amount of excess acetic anhydride to completely utilized the limiting reagent which is the salicylic acid. Next test was the KMnO4 test, in this particular test only the salicylic acid again yields into a positive result because in its structure it contains a benzene ring with attached OH group or simply the sturucture of phenol. Last characterization test conducted was the Starch test in which the commercial aspirin yield a positive result because it contains starch in its composition. As for the quantitative analysis in this experiment the percent yield of the crude aspirin was 68.3% in which the acetylated 1.0 g of salicylic acid only yields to 0.89 g of crude aspirin somehow far from the theoretical yield which was 1.304 g of crude aspirin supposedly. This discrepancy in the percent yield may be attributed to the incomplete acetylation of salicylic acid by acetic anhydride thus much more excess reagent must be used to completely consume the limiting reagent which is the salicylic acid to have a higher yield of the desired product. And for the percent

recovery of the crude aspirin it yielded 58.8% pure aspirin meaning that the synthesized aspirin was almost pure but not perfectly pure this may because of the experimental error occur during weighing, filtration (improper washing of crystals, using warm/hot solvent in washing/ rapid crystallization which may trapped some impurities), transfer, drying and other unknown factor that greatly affects the purity of the aspirin And lastly for the melting point determination of the crude and recrystallized aspirin, the crude aspirin got a MP range (102ºC-104ºC) and for the synthesized aspirin it got a MP range (112ºC-139ºC). Compared with the literature value of the MP of a pure aspirin which is 136ºC, the MP range of the crude aspirin seems very far this may be due to presence of some impurities during the first part of the experiment specifically the presence of unreacted salicylic acid and for the synthesized aspirin though it has the literature value of the MP of pure aspirin it is still not enough to conclude that the synthesized aspirin is pure enough because the MP range of synthesized aspirin is quite wide meaning it might have loose, uneven packing of crystals resulting in the wide MP range. VII. Summary and Conclusion As for the summary, the synthesis was of acetylsalicylic acid from a commercially available compound which is salicylic acid was indeed a useful process in organic chemistry. Through simple preparation of acetylsalicylic acid by acetylation of salicylic acid, and recrystallization a much more safer and useful organic compound was obtained from a highly strong compound which is salicylic acid. In this experiment, a successfully synthesized aspirin was obtained yet it may not be useful enough because of some impurities that is present in the compound. VIII. References Moore, William. Laboratory Manual for Organic Chemistry: A Microscale Approach. New York: McGraw-Hill, c1996. Print. Jones [et al.]. Laboratory Manual to accompany World of Chemistry: Extended Version.

Orlando, Florida: Sanders College Publishing, c1991. Print.

Szafran, Zsi. Microscale general chemistry laboratory : with selected macroscale experiments.

New York: Wiley & Sons, Inc.,c1993. Print.

Division of Organic Chemistry and Natural Products. Laboratory Manual for a course in Basic

Organic Chemistry (Chem 40.1). Institute of Chemistry, College of Arts

and Sciences,

University of the Philippines Los Baños, College, Laguna: Ninth

Printing, c2013. Print. Henrickson [et al.]. A Laboratory for general, organic, and biochemistry. 5th ed. New York, USA: McGraw-Hill,c2007. Print

IX. Remarks and Recommendations A much more useful and safe aspirin might be synthesized during this experiment if the Institute of Chemistry may have provide a much more clean laboratory materials, much precise and accurate laboratory equipments and such materials needed in a full synthesis of aspirin.