Structural Biochemistry/Organic Chemistry/Method of Fischer Esterification

Overview

In a Fischer esterification reaction, a carboxylic acid is exposed to an alcohol and an acid catalyst which results in the production of an ester and water as products. Because the reaction is reversible, the equilibrium can be determined by thermodynamics and there are procedures that can be taken to maximize the yield of the ester. The over reaction is given below:

Esterification

Fischer esterification mechanism

Procedures to maximize the ester include either the removal of water or the excess addition of the reactants. Both of these procedures take advantage of an idea known as Le Chatelier’s Principle and drive the reaction to favor the formation of the ester. When done in a laboratory setting, dry glassware should be used along with excess carboxylic acid. If the glassware is not dry, it may cause the reaction to drive towards the carboxylic acid and away from the ester. The mechanism of the reaction is given to the right:

Methods of Isolation

Reflux through a Condenser

Reflux apparatus numbered

Isolation and purification of the ester is achieved by bringing the reaction to a state of reflux. Because most organic reactions do not readily occur at room temperature, the reaction requires a period of heating and this is why refluxing is needed. Heating the reaction in an open container can result in loss of solvent while heating the reaction in a closed container is dangerous because the closed container can explode. Refluxing is a process that allows for extended heating periods without the loss of any reagents. This is achieved by a continual condensation of the vapor back to a liquid.

When connecting the condenser to the water outlet, it should be made sure that water is coming in from the bottom inlet and leaving the condenser from the top outlet or else the condenser will not be effective. When using magnetic stirring plates, a magnetic spin vane should be added to the vial/container to mix the solution. A state of reflux can be identified if there is condensation building up on the vial or container being heated. Sometimes refluxing can be done under anhydrous conditions where the reflux condenser can be equipped with a drying tube of, for example, calcium chloride. In an esterification reaction, it is essential to use a drying tube because one of the byproducts is water. According to Le'Chatellier's principles, if water is added to the ester after during the reaction, it will drive the reaction in the backwards direction towards the reagents. An anhydrous packed drying tube is used to keep the atmospheric moisture out of the reaction vessel in order to ensure maximum yield.

After a sufficient period of reflux, the ester can be prepared for purification. In order to purify/isolate the ester and obtain a maximum yield, the organic layer containing the ester product must be washed with a base such aqueous 10% sodium carbonate, MTBE (methyl tert-butyl ether) as well as methylene chloride and the MTBE-methylene chloride solvent mixture is to be completely evaporated out. Since the organic layer was produced from an acidic solution, washing it with basic sodium carbonate forms salts and alkaline materials that can be washed out with the aqueous phase. Also, the sodium carbonate will prevent the organic layer from dissolving into the aqueous layer and allow for better separation of the layers.

Column chromatography

Further purification can be achieved through the use of a chromatography column. The column can be made with a dry filter Pasteur pipette filled with a cotton plug, an adsorbent (silica gel), and a mixture compounds such as sea sand. Following elution of the ester product from the chromatography column with methylene chloride, the MTBE-methylene chloride solvent needs to be completely evaporated from the ester. If it is not entirely evaporated, it will negatively affect the purification of the ester. The percent yield of the reaction is only accurate when there is 100% conversion of the starting reactants to the products. If the evaporation is not complete, there will be more product than expected because there will still be some excess methylene chloride and the percent yield will be higher than it should be. Also, because the product will still have traces of the MTBE-methylene chloride solvent, the ester will not be pure and this will result in a impure product. This can affect, for example, the boiling-point of the ester if its physical properties were to be measured. The presence of impurities in the pure liquid decreases the vapor pressure and results in a boiling point higher than that of a pure compound. This can cause confusion in trying to identify the ester. Also, characterization by, for example, IR spectroscopy might show inaccurate functional groups because the ester is not completely pure.

Methods of Characterization and Identification

Ultramicro Boiling-point Determination

Ultramicro boiling-point is a method to determine the boiling point of a liquid and is similar to that of melting point determination. This method utilizes a melting-point capillary tube filled with the liquid that is to be observed and an inverted glass bell. The tube is heated in a Mel-Temp instrument and the boiling-point is determined by observing escaping vapor bubbles until the vapor pressure of the sample is equal to the atmospheric pressure. Smaller TLC capillary tubes can be used to get the liquid into the melting-point capillary tubes. The liquid that is to be observed must be at the bottom of the tube. In order to observe the boiling point, "glass bells" are inserted into the tube with the open end facing downwards. The bells can be made by heating TLC capillary tubes in half with, for example, a Bunsen burner and making sure that one end is open and the other closed. Air should be trapped inside the bell and the temperature can be increased until there is a steady stream of bubble exiting the bell. Eventually, all of the air that was initially inside the bell will be replaced by the vapors of the ester being observed and the bubbles will begin exiting much faster. When they exit at rate that is impossible to count, the heat should be turned off and when the last bubble exits the glass bell, the boiling point has been reached.

At this point, the vapor pressure of the sample is equal to the atmospheric pressure. Samples can be heated more than once to confirm boiling points but they are usually not as accurate as the first one.

Infrared Spectroscopy

PMMI-IR

An IR spectrum of the product can be obtained through a capillary film technique. A liquid sample is placed between two salt plates and run through a spectrometer to obtain a spectrum. The spectrum can reveal certain functional groups with varying intensity peaks and can be used to identify unknown products. The IR results can also be an indication of the reactions progress. If the IR of the product ester still contains an alcohol group stretch in the product, it can mean that the reaction has not gone to completion yet or that the ester was not properly purified.The plates can be made of NaCl or KBr and should not come into contact with water because that can dissolve the plates and destroy them. The plates are made of NaCl or KBr because they are held together by ionic interactions and won't interfere with the IR that only measures the covalent interactions. Capillary tubes can be used to drop small amounts of the liquid that is to be analyzed on one of the plates. The other plate is placed on top and should be used to try and spread the liquid to cover the entire plate. The plates are put into Infrared Spectrometers and a spectrum can be obtained by running the sample. Plates should always be cleaned with Kimwipe and washed with methylene chloride after each use. The IR spectrum to the right is an example of one corresponding to a carboxylate ester.

Nuclear Magnetic Resonance (NMR)

Although IR spectroscopy is a great way to help unravel the structure of a molecule, another technique called NMR (nuclear magnetic resonance) has further progressed the simplicity of deciphering the structure of a studied molecule. NMR, in similar ways to infrared spectroscopy, is also a characterization technique however instead of the use of infrared light, the sample is instead immersed in a magnetic field and hit with radio waves. These radio waves then encourage the nuclei of the molecule to resonate. This resonation is interpreted by a Fourier Transform algorithm which then determines the molecules surroundings, such as the structure. It should be noted that NMR works in the fashion of determining the orientation of how molecules are put together by flip motions caused by varying frequencies. The positively charged nucleus found in each element is a moving charge that creates a magnetic moment. When there is no magnetic field present or being administered to the atom, the microscopic magnets that orient the spin of the nucleus are aligned randomly. However when places in a homogeneous magnetic field, as one would do during NMR, the magnetic moments line up with the administered magnetic field. The motion caused by this alignment, the thermal motion for specifics, creates a torque which makes the magnetic moment "wobble". It is this wobble motion, or resonance, at different frequencies that can help one understand how the molecule is put together.

References

Mohrig, Jerry R., Christina Noring Hammond, and Paul F. Schatz. Techniques in Organic Chemistry. New York: W. H. Freeman and Company, 2010. Print.

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