Fischer Esterification and Combinatorial Chemistry

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Introduction:
Esters are a very useful side group in chemistry. The formation and use of esters is
widely studied in organic chemistry and various other fields.
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Esters have prominent properties
that lead to a certain smell; some very pleasant.
2
Each molecule can have a different smell and
changes in connectivity or chirality can have an extreme effect on the smell of the molecule.
3
Many industries, especially the food industry, use the smell of esters to give a food or flavoring a
certain smell.
4
Given all of this it is obvious why the synthesis of esters is important. Fischer
Esterification is the process in where an alcohol reacts with a carboxylic acid in the presence of
an acid catalyst to form an ester.
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The equilibrium of the reaction can be seen in Scheme 1.










Scheme 1. Fischer Esterification Equilibrium of an alcohol and carboxylic acid.
The mechanism of the reaction shows exactly what happens during the equilibrium
reaction. The mechanism can be seen in Scheme 2.
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Scheme 2. The Mechanism of Fischer Esterification.
Scheme 2 is the mechanism of the reaction. First a carboxylic acid will be protonated by
the presence of excess protons from the acid catalyst. Then the resonance structure with the
carbocation on the carbon attached to both oxygen molecules will be attacked by a lone pair on
the oxygen of the alcohol. Then the molecule will lose a proton and lose the positive charge on
the oxygen that just attached to the carbocation. The lone pair on one of the oxygen molecules in
the alcohol groups will then be protonated by excess protons. This gives the oxygen a positive
Fischer Esterification and Combinatorial Chemistry
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charge. The bonding electrons between the positively charged oxygen and carbon will be pushed
to the oxygen and a water molecule will be lost. The lone pair on the remaining alcohol group
will be pushed to a bonding pair between the carbon and oxygen molecules. This gives the
oxygen a positive charge, which it will lose when it loses a proton. This process leaves an ester
from an alcohol and carboxylic acid.
This lab is used to show the importance of both esters and the reaction process of Fischer
Esterification. The specific product was unknown and was analyzed using NMR, IR, and GC
data. The isolated product will have a distinct odor and that can help identification. The possible
products are limited due to the limited choice of carboxylic acids and alcohols. The odor can also
be compared to known literature to help identify the product.
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Each person can perceive a
different smell, but all of the data can help to identify the structure of the isolated product.
The reaction completed in this experiment used acetic acid combined with unknown
alcohol B, to form an unknown ester. This ester smelled like bananas, and was further analyzed
using NMR, IR, and GC data. The ester is concluded to be Banana Oil, or Isoamyl acetate. This
means the starting product was Isoamyl alcohol.
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Experimental:
Banana Oil. Unknown Alcohol B (6.5mmol), acetic acid (6.0mmol), concentrated
sulfuric acid (5 drops) were added to a 5mL microscale round-bottom flask, an air condenser was
attached and the mixture was stirred and refluxed for an hour. The product was allowed to cool
to room temperature and ether (2mL) was added to round bottom. This was then washed four
times with 5% aqueous sodium bicarbonate (5mL) and once with distilled water (5mL). The
ether was evaporated using a stream of nitrogen leaving a pale yellow ester (0.672g).
1
H NMR
(60MHz, CDCl3) (ppm) 4.210, 4.095, 3.989 (t, 2H), 2.038 (s, 3H), 1.659, 1.558 (m, 2H),
Fischer Esterification and Combinatorial Chemistry
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1.507, 1.447 (m, 1H), and 0.971, 0.878 (d, 6H); IR (ATR)
max
(cm
-1
) 2958.4, 2873.1, 1739.7,
1465.1, 1366.9, and 1229.2; C (pnl mlpollon, 0C o 20C at C per min) RT
6.625min.
Results, Discussions, Conclusions:
The isolated product was identified using NMR, IR, and GC tests. Using all of the
combined data the compound structure and identity were able to be determined, as well as
identifying the starting unknown alcohol.
The NMR data is very helpful in determining the product. The starting material of acetic
acid limits the number of products to four. The NMR shows a peak at 4.210, 4.095, and 3.989
which identifies with a triplet produced from two hydrogen molecules. This indicated there are
two hydrogen molecules adjacent to two more hydrogen molecules. The peak at 2.038
corresponds to a singlet produced by three hydrogen molecules. This indicated a methyl group
attached to something without hydrogen. The peaks at 1.659 and 1.558 correspond to a multiplet
integrated for two hydrogen molecules. This indicates a CH
2
next to multiple hydrogen
molecules. The peaks at 1.507 and 1.447 ppm show a multiplet for one hydrogen molecule. This
indicated a CH group adjacent to multiple hydrogens. The final peaks at 0.971 and 0.878 ppm
indicate a doublet for six hydrogen molecules. This corresponds to two methyl groups attached
to the same CH group. Given all of this information it can be concluded that the product is
Banana Oil. The most notable peak is the doublet produced at 0.971 and 878 ppm. This indicates
the product has two methyl groups and eliminated two of the possible products. The next
significant observation is the triplet formed around the peak at 4.095 ppm. Had this been a
different molecule, it would only have produced a doublet. The final characteristic of the NMR
that distinguishes the product from the other possible products is the multiplet at the peaks
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around 1.659 and 1.558 ppm. This would not exist if the molecule was any of the other possible
products.
The IR data is used to confirm the presence of an ester within the molecule. The peaks at
2958.4 and 2873.1 show that there is a C-H stretch within the molecule. If this was not present
then the wrong molecule was isolated and it is not an organic compound. One significant peak is
at 1739.7 cm
-1
. This peak is indicative of a C=O stretch. This helps to identify one of the side
groups within the isolated product. The peak at 1465.1 cm
-1
show that there is a C-C and C-H
bond and bend of an R
2
-CH
2
group. The peak at 1366.3 cm-1 indicates another C-C and C-H
bond but is indicative of an R-CH
3
. The last notable peak is at 1229.2 cm
-1
. This peak shows that
there is an ester present in the molecule. If this peak is not present then the desired product was
no isolated.
The GC data was used to identify the purity of the isolate product. There was only one
major peak produced by the GC output. This peak was at 6.625 minutes and shows that there is a
very pure product. The peaks before 2 minutes are ignored because they are produced by the
dichloromethane solvent used.
Combining all of the spectral data, found in the supplementary data section, it can be
concluded that the isolated product is Banana Oil, also known as Isoamyl acetate. Given all of
the peaks in the NMR and IR all of the side groups and connectivity is indicative of Isoamyl
acetate. The GC data confirms that there is very little to no starting product present and the
isolated product is pure. The amount of product isolated was 0.672 g which is equivalent to
5.16mmol. Since the product is produced in a 1:1 ratio with the starting material the theoretical
yield should be 6mmol since that is the amount of limiting reagent in the starting material used.
This produced an 86% yield. This is a very high yield and can be very useful to organic chemists.
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The microscale technique produced a high yield and can be very useful to organic
chemists. The procedures from this experiment can be applied in identifying other reactions of
carboxylic acids and alcohols. The NMR, IR, and GC helped to confirm the identity of the
isolated product and can be further used in different experiments.
References:
1. Naik, S., Veerababurao, K., Gopinath, R., and Patel, B.K., Tetrabutylammonium
tribromide mediated condensation of carboxylic acids with alcohols, ARKIVOC. 2006, 1
(14), pp 119-127.
2. Rummel, S. Lab Guide for Chem 213: Introductory Organic Chemistry Laboratory.
Hayden McNeil. Plymouth, MI (2012-2013.)
3. Leitereg, T.J. et al., Chemical and seonsory data supporting the difference between the
odors of enantiomeric carvones. Journal of Agriculture and Food Chemistry, 1971, 19
(4), pp 785-787.
4. Nagao, A., and Kito, M., Liapse-Catalyzed Syntheis of Fatty Acid Esters Useful in the
Food Industry. Biocatalysis and Biotransformation, 1990, 3 (4), pp 295-305
5. Williams, R.J., Gabriel, A., and Andrews R.C., The Relation Between the Hydrolysis
Equilibrium Constant of Esters and the Strengths of the Corresponding Acids. Journal of
the American Chemical Society. 1928, 50 (5), pp 1267-1271.
6. The Good Scents Company. www.thegoodscentscompany.com 2012.
7. Advanced Chemistry Development, Inc. IUPAC Nomenclature of Organic Chemistry.
1997.


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