Nucleophilic Acyl Substitution: The Synthesis of Esters Anjelika Mae L.

Marquez Department of Mining, Metallurgical and Materials Engineering, University of the Philippines, Diliman, Quezon City February 7, 2014 February 21, 2014 Abstract This experiment synthesized ethyl butyrate, a pineapple scent, by reacting ethanol with butyric acid via nucleophilic acyl substitution specifically known as a Fisher esterification. Concentrated H2SO4 was added as a catalyst and the solution was made to reflux. The resulting solution was made to stratify and the collected organic layer was purified. 7.85g of ethyl butyrate was obtained and the theoretical yield is 10.49g. A percent yield of 74.84% was obtained. I. Introduction Esters are compounds with a general formula of II. Methodology RCOOR where R may be a hydrogen, alkyl group, or an aryl group. R is the same with R except it cannot be In a 25-mL round bottom flask, 5.28 mL of ethanol hydrogen. and 8.28 mL of butyric acid was mixed and boiling stones were added. Boiling stones made of calcium Esters are naturally occurring compounds. Esters carbonate should not be added. 2-3 drops of with low and intermediate molar mass from acids and concentrated H2SO4 were added to the mixture to alcohols containing up to 10 carbons are liquids with hasten reaction. The mixture was then attached to a distinct fragrant odors. The distinctive flavors and odors reflux condenser and was allowed to reflux for 45 to 60 of fruit are from one or a combination of these esters. minutes. After refluxing, the mixture was cooled to Esters are used as flavors and scents. Esters with low room temperature and was poured into a 30-mL molar masses are volatile and can be used in paints, separatory funnel. The flask where the reaction varnishes and lacquers. Esters with high molar mass occurred was washed with cold water and the washings from acids and alcohols with 16 or more carbons are were added to the separatory funnel. This step was waxes. They are used to prepare furniture and repeated until the aqueous layer was twice the volume automobile waxes. of the organic layer. The mixture was shaken and was Esters can be synthesized by reaction of carboxylic allowed to stratify. To hasten the separation, saturated acid and alcohol, acyl chloride and alcohol or phenols, NaCl solution was added. Solid NaHCO3 was added until the acid was completely removed. The crude ester or acid anhydrides and alcohol or phenol. should be clear; if it is not clear then there is water in In this experiment, the butyric acid was made to the organic layer. The clear organic layer was then react with ethanol in the presence of an acid catalyst collected and dried by adding 1.00g of anhydrous H2SO4 in a reflux set-up producing an ester, ethyl Na2SO4. The resulting product was then transferred to a butyrate, and water. This process is called Fischer pre-weighed vial. esterification. The presence of acid increases the rate at which equilibrium is achieved but it does not affect the III. Results and Discussion direction of the reaction. Water can be removed or an The experiment synthesized ethyl butyrate, a excess of alcohol must be added to aid in the pineapple scent, by the process of esterification. Fischer completion of the reaction and shift the equilibrium to esterification involves the use of an alcohol and a the right. If this is not done, hydrolysis reaction may carboxylic acid with an acid catalyst that will produce an occur since esterification is a reversible reaction. ester and water. In the experiment ethanol was the alcohol used, butyric acid was the carboxylic acid and concentrated H2SO4 was the acid catalyst. Figure 1: General Reaction of Fischer Esterification

Figure 2: Reaction of butyric acid with ethanol forming ethyl butyrate and water

The reaction follows Le Chateliers principle which states that If a dynamic equilibrium is disturbed by changing the conditions, the position of equilibrium moves to counteract the change. In the experiment, excess amount of alcohol was added to shift the equilibrium to the right. Also, water was removed so that the equilibrium will not shift to the left. The acid catalyst doesnt affect the shifting of equilibrium but it increases the rate at which the reaction occurs. In the first step of the reaction, the carbonyl was protonated to make it more electrophilic. The resulting oxonium is capable of resonance. H2SO4 is added to strengthen the electrophile in the carbonyl group leading to a faster reaction. Because of the acid catalyst, calcium carbonate boiling stones cannot be added since it will dissolve.

Figure 5: Formation of ethyl butyrate Heat and continuous stirring also help to make the reaction go faster. The heat and continuous stirring is provided by the reflux set-up. With the reflux set-up, the compounds will not evaporate since it will be condensed and stay in the mixture. After the reflux set-up, the mixture is cooled first to room temperature. The reaction flask was washed with cold water and the washings were mixed again with the mixture to maximize the crude ester obtained. Cold water was used to prevent further reactions from taking place. NaCl is then added to hasten the separation of layers. Solid NaHCO3 was added and effervescence can be observed because of the reaction of its reaction with H2SO4. 2NaHCO3 + H2SO4Na2SO4+2H2CO3H2O+CO2(gas)
OH

Figure 3: Protonation of the carbonyl The oxygen in the alcohol is the nucleophile that will attack the electrophilic C in the C=O bond. The electrons will move toward the oxonium ion thus the hydrogen is deprotonated

OH OH

NaOH was not used because the use of NaOH, a strong base, will produce more water and may lead to a reversal of the reaction, a hydrolysis reaction. Figure 4: Attack of the nucleophile on the carbonyl carbon and deprotonation of hydrogen The OH is to be protonated to make a good leaving group, H2O. The electrons of the adjacent oxygen will help remove the leaving group. The oxonium ion will be deprotonated again leaving the ester product, ethyl butyrate. 2NaOH(aq) + H2SO4Na2SO4+ 2H2O Na2SO4 is added to dry the mixture and remove excess alcohol from crude ester. The solution is dry if a clear solution is obtained. The experiment produced a good product yield of 74.84%. The theoretical yield is 10.49g and the amount of ester synthesized in the experiment is 7.85g. Possible sources of errors may be the lack of reflux time. 60 minutes may not have been enough for the reactants to completely form the ester. Some of the alcohol or water may not have been completely

removed from the mixture resulting in an acid-catalyzed hydration of alcohol. Also distillation, which we did not do, might have given a better result. Weight of vial Weight of ester Percent yield Boiling point 82.94 7.85 74.84% -

based on le chateliers principle. The limiting reagent is the butyric acid and the excess is ethanol. Another method is removing the other product, water, so that it will not have a reverse reaction. 2 Give the equation to explain the relevance of using NaHCO3 over NaOH in neutralizing H2SO4?

2NaHCO3 + H2SO4Na2SO4+2H2CO3H2O+CO2(gas) 2NaOH(aq) + H2SO4Na2SO4+ 2H2O 3 How was excess alcohol removed from the crude ester after the reaction was completed? By addition of Na2SO4 to dry the mixture. 4 Write a mechanism for the acid-catalyzed esterification of the carboxylic acid and alcohol used

Table 1: Experimental Results IV. Conclusion The butyric acid which had a pungent smell turned into that of a sweet-smelling scent. This means that an ester was indeed synthesized. A good percent yield of 74.84% was obtained so the experiment is a success. The experiment can be improved by distilling the product. It would have yielded a product with fewer impurities. The percent yield will be more significant if the product obtained is pure. V. References Brown T., LeMay, H, E, & et al. Chemistry: The Central Science 11th Edition. Pearson education south asia PTE, LTD., 2009. Dietmar Kennepohl, David Law, Rob Carmichael, Lois Browne,. Organic chemistry II Lab Manual. Athabasca University, 2002. Hein, Best, Pattison, Arena. Introduction to General, organic, and biochemistry 8th ed. John wiley & sons, Inc, 2005. J, McMurry. Organic Chemistry(1984). United states of america: wadsworth, n.d. Organic Chemistry Laboratory Manual . University of the Philippines Quezon city, 2008. VI. Appendices 1 How did you use Le Chatelier's principle to ensure a reasonable yield of the ester? Which starting material is used as the limiting reagent? Which reagent was used in excess? Suggest another method that will favor the formation of esters In the experiment, excess amount of alcohol was added to shift the equilibrium to the right. This action was

5 If you were preparing an ester with ethanol, why is it necessary to use absolute ethanol? So that there is no risk of adding water into the mixture