Nucleophilic Acyl Substitution: The Synthesis of Esters

Maria Angelica T. Manaloto . Department of Chemical Engineering, College of Engineering, University of the Philippines, Diliman, Quezon City 1101 Philippines . Date Performed: August 16, 2013 Date Submitted: August 28, 2013 .

An ester can be synthesized through the reaction of a selected acid and alcohol. In this experiment, synthetic banana essence was selected and was produced through the mixture of butyric acid and ethanol and the performed procedures. The synthesized ester was called ethyl butanoate. The process that was involved was a nucleophilic acyl substitution mechanism called esterification that has undergone reversible acid-catalyzed reaction of a carboxylic acid with an alcohol. The objective of synthesizing ester was successful in terms of its production; it was a clear solution with a strong pineapple odour/essence. In terms of yield, it only had a minimal percent yield compared to its theoretical, with 3.2mL of the ester and a 26.85% yield. It was taken note that the product obtained was only crude and not distilled. It was concluded that many of the compounds that contribute to the flavours and aromas of fruits and flowers are esters. In which these flavours and aromas only resulted from complex mixtures of many compound that involve esters as a large component. Introduction The experiment involves the synthesis of esters which utilizes a specific mechanism under nucleophilic acyl substitution. This mechanism is called esterification, a reversible acid-catalyzed reaction of a carboxylic acid with an alcohol with the aid of a strong-acid catalyst such as sulphuric acid. The objective of the experiment was to produce a pineapple ester from butyric acid and ethanol. Esters are derivatives of carboxylic acids that are found in a variety of natural sources. Simple esters generally have pleasant odours, and are the main components of many of the odours of fruits and flowers. Most odours and flavours are the result of a complex mixture, with one ester predomination. Because esters are easy to synthesize, flavour chemists often use esters, either one or several to reproduce or enhance natural flavours. . The chemical structure of the alcohol, the acid, and the acid catalyst used in the esterification reaction all effect its rate. Simple alcohols such as methanol and ethanol react very fast because they are relatively small and contain no carbon atom side chains that would hinder their reaction. These differing rates of reaction were first reported by Nikolay Menschutkin (1842-1907) in 1879-83. He also noted that simple acids such as acetic acid or vinegar (CH3CO2H) form esters very easily. The most common acid catalysts are hydrochloric acid, HCl, and sulphuric acid, H2SO4, because they are very strong acids. At the end of the esterification reaction, the acid catalyst has to be neutralized in order to isolate the product. German chemists, during World War II, developed solid acid catalysts or ion exchange resins for use in the manufacture of esters. These solid catalysts work well with acid sensitive esters because they can be separated from the product by filtration and therefore, the catalyst does not spend very much time in contact with the acid 1

unstable product. . The esterification process has a broad spectrum of uses from the preparation of highly specialized esters in the chemical laboratory to the production of millions of tons of commercial ester products. These commercial compounds are manufactured by either a batch or a continuous synthetic process. The batch procedure involves a single pot reactor that is filled with the acid and alcohol reactants. The acid catalyst is added and the water removed as the reaction proceeds. This method is most often used by chemists in the laboratory, but in a few cases, it is used by industry to make large quantities of esters. This batch process usually requires reactors that hold extremely large volumes of reactants. Butyl acetate is commonly prepared from butanol and acetic acid by this method. The continuous process for making esters was first patented in 1921 and has been used extensively in the manufacture of large quantities of esters. This procedure involves the mixing of streams of the reactants into a reaction chamber while the product is removed at the same time. Continuous esterification has the advantage that larger quantities of products can be prepared in shorter periods of time. This procedure can be run for days or weeks without interruption, but requires special equipment and special chemical engineering considerations. The continuous esterification process is used industrially to make methyl acetate from acetic acid and methanol and ethyl acetate from acetic acid and ethanol. The alternative process of making esters from the reaction of an alcohol with an anhydride is important in the manufacture of drugs. This reaction gives an acid as a byproduct. Acetic anhydride, a derivative of acetic acid, the acid in vinegar, is the most commonly used anhydride reactant. Phenyl

acetate, one ester prepared industrially by this method, is an important intermediate in the synthesis of acetaminophen. Aspirin, or acetylsalicylic acid, is also prepared in large scale by the esterification reaction of an alcohol with acetic anhydride. This anhydride is important in the production of cellulose acetate by the esterification of cellulose or cotton. Cellulose acetate was first prepared in 1865 and was used extensively during World War I to coat airplane wings. Today, cellulose acetate finds its largest application as the fibrous material used in cigarette filters. It is also used in various yarns and textiles and to make the tips of felt-tip pens. Phthalic anhydride, an anhydride derivative of a benzene or phenyl ring, yields dimethyl phthalate when reacted with methanol in a reaction to that described for acetic anhydride. Dimethyl phthalate is used as a mosquito repellent and in the manufacture of certain polyesters. It is also a component in hair sprays and is added to plastics to soften them. Although esters are often used as flavourings, they are rarely used as scents to be applied on the body. This is because esters are not highly stable, and can be hydrolyzed back to carboxylic acids and alcohols when exposed to perspiration. Since esterification is a reversible reaction, the addition of acid, water and heat (perspiration) favours hydrolysis. In context, unfortunately, many carboxylic acids have a very unpleasant odour. For example, the acid used in the experiment, butyric acid (butanoic acid) is the main component responsible for the odour of rancid butter. Butyric acid is formed from hydrolysis of ethyl and methyl butyrate (butanoate), esters that smell like pineapple and apple. Some esters are also bioactive. Isoamyl acetate, which smells like bananas, is also an alarm pheromone released by honey bees when they sting an intruder. The pheromone attracts other 2

bees and incites them to attack the intruder. For these reasons, fragrances are more often made from essential oils such as phenols, aldehydes, alkenes, etc. The more specific type of the mechanism that is observed in the experiment is called FischerSpeier esterification. It is esterification by refluxing a carboxylic acid and an alcohol in the presence of an acid catalyst.The reaction was first described by Emil Fischer and Arthur Speier in 1895. . Experimental Details . Given fixed measurements of the reagents, the procedure was started by mixing 5.55mL of 0.09 mol Ethanol and 8.28mL of 0.09 mol Butyric acid in a 25-mL round bottom flask. Bits of broken glass as boiling chips were added to induce calm boiling. Glass was used instead of calcium carbonate (marble) boiling stones to avoid dissolution in the acidic medium. After preparation of mixture, 2-3 drops of concentrated H2SO4 were carefully added while gently swirling the flask. *The flask was made sure it was covered while swirling since the mixture was volatile.

allowed to cool to room temperature, and then poured into a 30-mL separatory funnel. The reaction flask was rinsed with cold water and the washings were added to the separatory funnel. The rinsing was done little by little to make sure only the remaining mixture was to be added and to avoid excess water. This procedure was minimally done since the aqueous layer was not that far from having twice the volume of the organic layer. The aqueous layer was distinguished by observing which layer would increase when the washings were added. The funnel was gently shaken afterwards, and then the mixture was allowed to stand for a few minutes until the layers were stratified. The addition of NaCl was not needed since the layers were distinctly separated. After the separation of the aqueous layer, solid NaHCO3 was added to the organic layer until the acid was removed. *The acid cannot actually be completely removed, but only minimized by observing the decrease of effervescence each time NaHCO3 was added. After decreasing the acid, anhydrous Na2SO4 was added to dry. Clumps in the mixture were observed. Followed by the drying, it was decanted into a graduated cylinder; the clearness of the solution was checked, and then the volume of the obtained product was measured. Results & Discussion Data of obtained experimental results; Ester Ethyl Butanoate .

Figure 1. Reflux Set-Up

A reflux set-up was set, and the mixture was allowed to reflux for 60 minutes. After refluxing, the mixture was 3

volume molecular wt density(spec ific gravity) Theoretical yield % yield

3.2 mL 116.6 g/mol 0.879g/mL 11.92 mL 26.85%

Table 1. Experimental Data . In the experiment, the production of ethyl butanoate was obtained through esterification of ethanol and butyric acid with sulphuric acid as catalyst. The mechanism involves a reversible acid-catalyzed reaction of the carboxylic acid with the alcohol.

of the excess is unreacted, requiring extra steps to remove it, and is wasteful. A second method to drive the equilibrium towards product is to remove one of the products as it is formed. This is also an application of Le Chateliers principle. Note that one product of the esterification process is water. A simple experimental set-up can be used to remove water from the reaction mixture as the ester and water form. AS water is removed, the equilibrium is upset and corrects itself by moving towards the products. Eventually, when the final amount of water is removed and all the starting materials have reacted, the reaction has gone to completion and a 100% yield can be attained.

Figure 2. Esterification

It is important to note that this is a reversible reaction, so the acid and the alcohol reactants and ester products are in equilibrium. Once the reaction reaches equilibrium, there could be a large amount of starting material remaining, resulting in a poor yield of the ester. For esters in which the alcohol and carboxylic acid are structurally unhindered, a 1:1 mixture of alcohol and carboxylic acid will yield an equilibrium mixture that is about 70% ester. This means that if ester were to be isolated from this mixture, at best a 70% yield would be obtained. A 70% yield is not usually considered to be acceptable for a synthesis reaction. Recall Le Chateliers principle; if a ration of 3:1 or 1:3 of alcohol:carboxylic acid were used, the equilibrium would be driven towards the ester product and for unhindered systems would result in a 90% yield. In practice, often a 10:1 or 1:10 ratio is used, which results in even higher yields of ester. The drawback in this method is that the most

Figure 3. Alternative set-up,extraction of H2O The set-up used to remove water is shown above. Reactants and sulphuric acid catalyst are placed into the round-bottomed flask, which is heated. Ester and water begin to form and distill up into the air-cooled condenser along with the reactants. The vapours, upon contacting the cool tube, condense back to liquid and flow back down towards the reaction flask, The side-arm between the condenser and flask collects the descending liquid. Because water is immiscible with the organic phase and also denser than the organic phase, it will collect as a separate lower phase in the side-arm. Once the side-arm is full of liquid the organic phase overflows back into the reaction flask, leaving the lower water phase trapped at the bottom of the side-arm. Thus the water that is produced 4

in the reaction is being removed from the reaction mixture, allowing the reaction equilibrium to be driven towards the products. Eventually when all of the reactants are converted to ester and water, the reaction can be stopped. Neutralizing it with NaHCO3 will remove sulphuric acid and final distillation purifies the ester product. Sulphuric acid, H2SO4 is used as a catalyst for the reaction in order to accelerate at which the product is formed. Since a catalyst is not consumed during the course of the reaction, only a small amount of H2SO4 is needed in order for it to be effective. Heating also increased the reaction rate during the reflux process. At the end of the reaction, the obtained ester will need to be purified since it is considered contaminated with unreacted, excess acid. The technique used for purification is the extraction using the separatory funnel. The use of sodium bicarbonate, NaHCO3 allowed the removal of the carboxylic acid impurity. NaHCO3 instead of NaOH is used to neutralize H2SO4. The objective of Fischer esterification is to make an ester, which has the single bonded oxygen and a double bonded oxygen on a carbon. H2SO4 is just a catalyst. NaHCO3 already has the double bonded oxygen to the carbon, whereas the NaOH does not. When the reaction takes place, the OH of the NaHCO3 and the H of the alcohol form the side product water. NaOH is a strong base, and if it is used, it will react with the ester to form a soap. Given the reaction: RCOOR' + NaOH = RCOONa + R'OH. This will then defeat the purpose of forming an ester. To purify further, excess alcohol from the obtained crude ester can be removed by extraction, or simply by distillation processes. In this experiment, this procedure was no longer performed. . In addition to preparation of the ester

for maximum yield, absolute ethanol must be used. Since ester linkages can be easily hydrolyzed, impure ethanol could decrease yield of expected ester. Otherwise, if ethanol/water mixture is used, the ester will be broken down as soon as it is formed.

Figure 4. Fischer Esterification Reaction Mechanism The figure above illustrates the mechanism for the acid-catalyzed esterification of the carboxylic acid and alcohol used. To summarize the mechanism; In a Fischer esterification, proton 5

transfer from acid catalyst to carbonyl oxygen increases electrophilicity of carbonyl carbon. The activated carbonyl carbon is then attacked by the nucleophilic oxygen atom of the alcohol, yielding a tetrahedral intermediate. A proton transfer from the oxonium ion to a second molecule of the alcohol gives an activated complex. Protonation of one of the hydroxyl groups of the activated complex gives a new oxonium ion. Water is lost from this oxonium ion and the hydroxyl group is deprotonated resulting in the ester. Ethyl butanoate, the ester obtained in the experiment was synthesized accordingly to the explained mechanism. Synthesized from the given carboxylic acid and alcohol; butyric acid and ethanol, respectively. Considering that the production of the ester was an indication of the success of the experiment having obtained 3.2mL of crude ester, computed percent yield was 26.85%. This implied that there could have been errors during the procedure of the experiment such as; inaccurate volume measurement of reagents used, excess catalyst that may have reacted with the solution, extracted organic layer was not purely organic, and/or the reflux set-up was not properly isolated. Most carboxylic acids are suitable for the reaction, but the alcohol should generally be a primary or secondary alkyl. Tertiary alcohols are prone to elimination, and phenols are usually too unreactive to give useful yields. Strong acids like HCl and H2SO4 are common acid catalysts for a Fischer esterification. Weaker acids can be used but the reaction rate will be significantly reduced. The primary advantage to using Fischer esterification as compared to other forms of esterification is its simplicity. Since the reagents used are direct there are less waste products and environmental impacts. The disadvantages of

Fischer esterification are the slow reaction rate and reversibility of the reaction. A Fischer esterification can be easily reversed with a hydrolysis reaction. Conclusion From the experiment, the synthesized ester was measured 3.2mL with a 26.85% yield, ethyl butanoate. It is an ester with the essence of a much like of a pineapple. The recorded ester was crude without having undergone distillation process. It was successfully observed that an ester with various essences can be synthesized from selected combinations of a carboxylic acid and an alcohol. The application of this process in the industry is better understood, together with extended appreciation of how chemists are able to reproduce or enhance natural flavours through the experiment. Through research of other esters, it was noticed that the lower molecular weighted esters are generally sweet smelling but the carboxylic acids from which they are synthesized often have a disagreeable odours; having the pineapple scent from butyric acid as an example. It was also noted that although a specific aroma is recognized in a single ester, the odour resembles only a cheap imitation. References (1) Solomons, T.W.G.; Fryhle, C.B. Organic Chemistry, 10th ed.; John Wiley & Sons, Inc: 2011. (2) McMurry, J. Organic Chemistry. United States of America: Wadsworth. (3) Patai, S., ed. Synthesis of Carboxylic Acids, Esters and Their Derivatives. New York: Wiley, 1991.