Experiment  7

Fischer Esterification: Preparation of Isopentyl Acetate (Isoamyl Acetate)

Background

Esterification is a straightforward reaction that utilizes several key techniques in synthetic organic chemistry. One direct approach, known as the Fischer esterification reaction, involves the acid-catalyzed condensation of an alcohol and a carboxylic acid, yielding an ester and water. Esters can also be formed by the reaction of the alcohol with the acid chloride rather than the acid itself. Or, the acid anhydride may be used instead of the acid. In this experiment, we will create the ester isopentyl acetate (banana oil) via the Fischer esterification reaction.

Esters are an important group of carboxylic acid derivatives. Many esters occur naturally. They often compose a significant fraction of the fragrant oils of fruits and flowers. Fats and oils are another type of natural ester; they are actually mixtures of glycerol triesters, made of long-chain fatty acids and glycerol (glycerin: 1,2,3-propanetriol). Waxes are esters of long-chain carboxylic acids and long-chain primary alcohols. Lactones are cyclic esters that arise when a carboxyl group and an alcohol group in the same molecule condense to form an ester. Synthetic esters are also important and found in many places, including the polyesters known as Dacron, prepared from terephthalic acid and ethylene glycol, and Kodel.

Emil Fischer (1852-1919) was a German scientist who received his Ph.D. from the University of Strasbourg, studying with Adolf von Baeyer. He taught at Erlangen, Wurzburg, and Berlin Universities. Fischer's work essentially laid the foundation of modern biochemistry. Fischer was the first to synthesize phenylhydrazine, which was an important reagent in his work on elucidating the structures of most of the carbohydrates. During a three-year period beginning in 1891, Fischer established not only the basic structures, but also the configurations of all the known sugars. In the process, he developed a method to represent the three-dimensional molecular structures in two-dimensional drawings. These structures have become known as Fischer projection formulas. This work by Fischer led directly to proving the existence of the asymmetric carbon atom, a concept proposed by Van't Hoff and Lebel in 1874.

In addition to carbohydrate chemistry, Fischer did extensive work on the chemistry of purine and compounds having purine as their nucleus. Purine is one of the two nitrogen base ring systems present in DNA.

Fischer was also active in the area of protein chemistry. He demonstrated that amino acids are the basic subunits from which proteins are constructed. He also devised methods for the synthesis of many of the known amino acids. Perhaps his most ingenious contribution was the 'lock and key" hypothesis of how proteins bind with substrates of complementary shapes. This work ultimately led to our understanding of how enzymes, the catalysts of biochemical reactions, function.

Regarded as the greatest organic chemist of his time, Emil Fischer became the second chemist to receive the Nobel Prize (1902). Fischer committed suicide in 1919 following the death of his wife and the loss of two of his three sons.

The Fischer esterification is an equilibrium reaction whereas other esterification routes do not involve an equilibrium. To shift the equilibrium to favor the production of esters, it is customary to use an excess of one of the reactants, either the alcohol or the acid. In the present reaction, we will be using an excess of the acetic acid, because it is cheaper and easier to remove than the alcohol (note the similar boiling points of the alcohol and acetate). Another way to drive a reaction toward its products is to remove one of the products as it forms. In this experiment, we will remove the water formed in the reaction by adding silica beads directly to the reaction vessel and by using a drying tube with drying agent (calcium chhioride), which prevents the introduction of water.

The following figure shows the reaction for this experiment:

The mechanism for this reaction involves the nucleophilic addition of the alcohol to the carbonyl group of the protonated acid, followed by elimination of a proton. The tetrahedral intermediate is unstable under the acidic conditions of the reaction and undergoes dehydration to form the ester.

The key steps of this mechanism involve the following:

  1. Activation of the carbonyl group by protonation of the carbonyl oxygen,
  2. Nucleophilic addition to the protonated carbonyl to form a tetrahedral intermediate,
  3. Elimination of water from the tetrahedral intermediate to restore the carbonyl group.

Because esters can be hydrolyzed under acidic or basic conditions, it is not a good idea to stop this reaction before the acid catalyst has been neutralized. Hydrolysis is the breaking of the ester apart back to the acid and the alcohol. This reaction can be useful; if the hydrolysis is carried out under basic conditions, it is referred to as a saponification. Saponification is an irreversible reaction in which one mole of base is consumed per mole of ester to generate the carboxylic acid anion.

Compound MW Amount Needed mmol mp bp Density ηD
Isopentyl alcohol 88.15 20.0 mL 184 --- 130oC 0.809 1.4060
Glacial acetic acid 60.05 12.0 mL 210 16.2oC 118oC 1.049 1.3720
Sulfuric acid, 98% 98.08 1 mL --- 3oC 290oC 1.840 ---
Isopentyl acetate 130.19 --- --- --- 142oC 0.876 1.4000

EQUIPMENT AND REAGENTS: Assemble the following apparatus: A 100 ml round bottom flask, containing a small stirring bar, topped by a water condenser (with tubing) for reflux. The water condenser is topped with a calcium chloride drying tube. (The drying tube is assembled by first placing a small wad of cotton or glass wool, found at the supplies table, in the base of the tube. This cotton wad should be placed back to where the tube starts to bend, but should not be jammed tightly into the tube. Calcium chloride is then poured into the tube, and another cotton plug is used to hold the desiccant in the end.)

The apparatus is heated using a heating manifold. It is secured to the bench stands by a three prong clamp, clamped around the condenser so that the reaction vessel can be easily elevated and cooled in the air.

REAGENTS REQUIRED FOR REACTION:

REACTION CONDITIONS: The reaction flask is heated and stirred at reflux for one hour. (The reflux temperature has been reached when the isopentyl alcohol-acetate reaction mixture is smoothly boiling.)  After reflux, the resulting mixture is allowed to cool to room temperature and the stirring bar removed with forceps. (Remember to loosen the joints before the reaction is completely cooled.)

ISOLATION OF PRODUCT: The cooled reaction, containing the isopentyl acetate, is transferred to a separatory funnel and washed three times with a 20 ml portion of 5% sodium bicarbonate. This washing removes the sulfuric acid catalyst and any unreacted acetic acid that may be in the reaction flask. To do the washing, the bicarbonate solution is added to the separatory funnel, and the funnel is capped and shaken vigorously, with frequent venting.  For each washing, after the layers separate and before the next portion of bicarbonate (or water) is added, the aqueous layer is removed (this is the bottom layer since water is more dense than the isoamyl acetate). The bicarbonate and water layers are collected into another flask and eventually discarded in liquid waste.

The bicarbonate washings of the ester product are followed by a single 20 ml wash of distilled water to remove any bicarbonate solution ions that may still be mixed with product. After the water layer (bottom layer) is removed, the isoamyl acetate is transferred to an Erhlenmeyer flask. It is then dried by adding anhydrous sodium sulfate to the solution until the solid is free-flowing (no clumping). Do not add Na2SO4 to the separatory funnel since you cannot determine whether it is free-flowing.

Store your liquid product, with drying agent, until the next lab period. Prior to distillation, the anhydrous isopentyl acetate is removed from the solid sodium sulfate and put into a clean, and dry, 50-mL round bottom flask for distillation.

PURIFICATION: Purification of the crude isopentyl acetate is performed by distillation.  The entire product is added to a 50-mL round bottom flask, containing several boiling stones to prevent super-heating and bumping of the crude isoamyl acetate during distillation. A simple distillation is performed to collect the isoamyl acetate.  The flask is heated in using a heating manifold.  The isopentyl acetate will boil and condense and will be collected. This distillation will significantly purify the material, but not if there is alcohol or water present.  You should collect your material when you have a product at the appropriate boiling point of the ester.

CHARACTERIZATION: The boiling point of the liquid should be measured as the isopentyl acetate distills. The thermometer is placed in the distillation head.  A lot of heat is lost to the atmosphere when using this very small equipment, so a thermometer placed in the distillation head is a pretty good indicator of the boiling point.

An analysis of your product should include the following:

The spectra are the IR's for isopentyl alcohol (isoamyl alcohol) and isopentyl acetate (an ester).

 

 

 

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Copyright © Donald L. Robertson (Modified: 09/18/2006)