NUCLEOPHILIC ACYL SUBSTITUTION: SYNTHESIS OF ESTHERS

Lawrence Dhaniel L. De Jesus

Department of Chemistry, University of Southern Mindanao, Kabacan, North Cotabato
Date Performed: December 6, 2017
Date Submitted: December 6, 2017

I. Introduction

Esters are carboxylic acid derivatives through which an acyl carbon bears an alkoxy substituent (-OR) rather than
the hydroxyl substituent (-OH) of the acid. They are one of the most vastly produced naturally occurring organic
compounds, and unlike their predecessors (the low-molecular-weight acids) esters are pleasant-smelling liquids, which
are commonly responsible for the fragrance of fruits and flowers.
The chemical industry produces Esters for a variety of purposes. For example, ethyl acetate is a commonly used
organic solvent and polyesters are a main component of plastics. The most common use of esters in the fashion industry
is their being a constituent in the production of perfumes, essential oils and food flavouring.
Esters can be naturally acquired, but they can also be synthesized in the laboratory. The most common method of
synthesizing esters is through the Fischer Esterification reaction, which makes use of the nucleophilic acyl substitution
mechanism. The key to this mechanism is the addition of a nucleophile to the carbonyl carbon which forms a tetrahedral
intermediate. An electron pair from the oxygen displaces the leaving group, Y, which then results in generating a new
carbonyl compound.

Fig 1. Nucleophilic acyl substitution mechanism (McMurry, 2011, p.335)

In the Fischer esterification reaction, there is a direct conversation of a carboxylic acid (-COOH) and an alcohol (-
OH) into an ester, usually catalysed by a mineral acid such as a concentrated sulphuric acid (H2SO4). The catalyst enhances
the addition of the weak nucleophilic alcohol to the carbon-oxygen double bond by protonating the carbonyl oxygen,
thereby giving the carboxylic acid a positive charge and rendering it much more reactive. Subsequent loss of water from
the tetrahedral intermediate yields the ester product.1

II. Materials & Reagents

Materials

Hot plate
3 Test tubes w/ Rack
Pasteur Pipettes
Stirring Rods
Water Bath
Test tube holder
Reagents

Anthranilic Acid
Salicylic Acid
Sulfuric Acid
Methyl Alcohol

III. Methodology

A. Banana-Scented Ester (Isoamyl Acetate)

Prepare Isoamyl Acetate by putting 6 drops of Isoamyl alcohol in 10cm Test tube. Add 2 drops of glacial acetic acid to
the solution and stir. Proceed to add a drop of concentrated sulphuric acid and then place on a boiling water bath with
a test-tube holder, keep about it for 3 minutes. After wards, remove the test-tube and place on a rack, add 20 drops
of distilled H2O and then record the odour.

B. Grape-Scented Ester (Methyl Anthranilate)

Pour 0.2 grams of anthranilic acid into a test tube and add 6 drops of methyl alcohol, mix. Add a drop of distilled
sulphuric acid and then mix. Place in a water bath of boiling water and then let stay for 3 minutes. Afterwards, remove
the test tube and place on a rack. Add 15 drops of distilled H2O and then record the odour.

C. Wintergreen-Scented Ester (Methyl Salicylate)

Pour 0.2 grams of salicylic acid to a test tube and add 6 drops of methyl alcohol, mix. Add a drop of concentrated
sulphuric acid and mix the solution. Place in a water bath of boiling water and let stay for 3 minutes. Remove the test
tube and place in a rack. Add 15 drops of distilled H2O and then record the odour.

IV. Results and Discussion

The synthesis of the esters started with the reaction of the acids with the alcohols which involves the protonation
of the carbonyl carbon of each acid respective by H2SO4, making it positively charged. What then followed was the
nucleophilic attack of the electron-rich oxygen alcohol, giving a tetrahedral intermediate. Proton transfers took place after
and the loss of water happened giving the desired product, the esters: Isoamyl Acetate, Methyl Anthranilate, and Methyl
Salicylate. The whole process is a reversible reaction so significant measures were done to ensure the formation of the
desired ester. One is the addition of water, showing the acids as the limiting reagent, for the reaction to drive forward.
Removal of the aqueous layer was also necessary to prevent hydrolysis that will favour the reaction towards the reactants
and to increase the esters yield and purity. These two follows Le Chateliers principle which implies that when equilibrium
of a system is disturbed by changing its conditions, the position of equilibrium moves to counteract the change.

V. Conclusion
Based on the results, it is safe to conclude that the esters were successfully synthesized from the reaction of the
alcohols (Isoamyl Alcohol, Methyl Alcohol) and their respective acids with H2SO4 as a catalyst, which is the main objective
of the experiment. The reaction was called a Fischer esterification which follows a nucleophilic acyl substitution
mechanism.

VI. References
1. Gilbert, J., & Martin, S. (2011). Experimental Organic Chemistry: A Miniscale and Microscale Approach. (5th ed.).
Cengage Learning.