The Essence of Esterification

Reading Assignment: Smith, J.G. Organic Chemistry, McGraw Hill: New York. 2nd ed: pgs. 848-850, 3rd ed:
847-848, 4th ed: 882-883. You may find this interesting:
http://www.rsc.org/chemistryworld/Issues/2009/February/TheSweetScentOfSuccess.asp
Introduction:
Esters are a large group of important compounds. A small sampling of ester containing drugs is shown below.

aspirin
analgesic,
anti-inflammatory

epothilone
macrolactone
anti-cancer

cocaine
stimulant

erythromycin
macrolide antibiotic

Triglycerides, or fats, also belong to the ester family:

Polyesters are polymers made up of repeating ester units and are important in the fabric industry (see Dacron,
below). Dacron is formed by condensation of terephthalic acid and ethylene glycol to form
polyethyleneterephthalate (PET). PET is also an important component of many plastic bottles used to contain
soft drinks and water.

Many esters occur naturally and compose a significant fraction of the fragrant oils of fruits and flowers. Some
of these the scents created by these esters include wintergreen, raspberry, grape, rum, pineapple, banana, and
many others. Esters are often used as the artificial flavors in many of the foods we eat. This lab will explore
the synthesis of some of these fragrant and flavorful esters.
One method of synthesizing esters is the acid-catalyzed condensation of an organic acid with an alcohol (figure
1). This transformation is known as the Fischer Esterification, named after the Nobel Prize winning German
Chemist Emil Fischer.
O

O
R

OH

cat. H +
R'OH

OR' +

H 2O

Figure 1. General Fischer Esterification Reaction

The Fischer Esterification is another example of a nucleophilic acyl substitution reaction (which other reaction
have you seen this semester in lab that involved a nucleophilic acyl substitution reaction?). As you work
through the mechanism pay attention to the fact that the reaction conditions are strongly acidic (what kinds of
intermediates make sense in these conditions). It is also important to notice that this reaction is a completely
reversible reaction. How could you apply Le Chteliers principle to push the equilibrium towards the desired
products? What could you do experimentally to convert the ester back into the carboxylic acid?
Because some functional groups are not stabile in the strongly acidic conditions required for the Fischer
Esterification other synthetic methods have been developed to create esters. You have most likely learned at
least two additional methods. Can you name them?
For this weeks lab you will research the scents created by a set of esters (see the pre-lab assignment) then
choose one to synthesize in lab via the Fischer Esterification. You will be given the option of combining one of
four alcoholsmethanol, ethanol, propanol, and isopropanolwith one of four carboxylic acidspentanoic
(valeric) acid, hexanoic (caproic) acid, cinnamic acid, and salicylic acid.
Experimental Procedure:
1.
2.
3.

Measure out 5 mL of your chosen alcohol and add to a 25 mL round bottom flask.
Add a stir bar to the flask.
Add concentrated sulfuric acid to the flask. Add slowly and carefully to prevent splattering.

In the Hood for the Liquid Carboxylic Acids (they smell awful)
4.
5.

Measure out the determined amount of your carboxylic acid and add to your reaction flask.
Cap with a #3 rubber stopper from the stockroom.

At Your Station:
6.
7.
8.
9.
10.

Stir the reaction mixture for one minute. Note that some solid carboxylic acids will not dissolve
completely until heated.
Remove the stopper and connect a condenser tube to the round bottom flask. Connect the chilled water
to the condenser tube and turn it on so that you have a slow flow through the tube.
Heat the reaction to the point of reflux using a sand bath. What is the difference between boiling and
reflux?
Reflux for 60 minutes. You may wish to start on your post-lab during this time.
Remove from heat.

11.

12.

13.
14.
15.

16.
17.
18.
19.

Slowly add 10% sodium carbonate solution to the reaction flask while stirring (add through the top of
the attached condenser tube to prevent bubbling over of the solution). What is the purpose of adding the
sodium carbonate?
a.
If the solutions separate when added together, stir vigorously.
b.
Add the sodium carbonate solution until the reaction flask no longer bubbles with an addition of
the solution (15+ mL) (What are the bubbles?)
c.
Check the pH of the solution. If the pH is greater than 8, the process is complete. Otherwise,
add more sodium carbonate solution, while stirring, until the pH is 8 or greater. You may need
to reheat the mixture.
Extract the solution with 5 mL dichloromethane (DCM) three times using a separatory funnel, collecting
the organic layer each time. (Is the organic layer the top or bottom layer? How can you test your
hypothesis?) Remember never to discard any layers until you are sure that you have isolated the desired
product.
Dry the organic solution with sodium sulfate (Na2SO4).
Suction filter the solution to remove the sodium sulfate.
Concentrate the solution using the rotary evaporator.
a. Transfer your solution to a clean, PREWEIGHED 25 mL round bottom flask. Use 1-2 mL
dichloromethane to rinse the filter flask to aid in the transfer.
b. Set the rotary evaporator water bath temperature to 40-60C (the boiling point of
dichloromethane is 37C). Evaporate the dichloromethane and any remaining alcohol. The
esters are all liquids at elevated temperatures with very high boiling points, so after most of the
DCM is removed, increase the vacuum to full strength to evaporate any remaining solvent. If the
solvent is coming off slowly, increase the water temperature. Continue to evaporate until there is
no apparent further decrease in the volume of your product.
c. Reweigh the 25 mL round bottom flask containing your product to determine percent yield.
Enjoy and characterize the scent of your product by carefully wafting the scent towards your nose.
Analyze your product by IR and 1H NMR.
Calculate percent yield.
Complete the post-lab worksheet.

Pre-Lab Notebook:
Objective: Include the main goal of this experiment.
Reaction: Show the reaction you will perform in lab (use structures of the alcohol and acid you have
chosen). The reaction is catalyzed by sulfuric acid.
Mechanism: Draw the mechanism of the reaction of your chosen carboxylic acid and alcohol in the
presence of catalytic sulfuric acid.
As the reaction is reversible, what are two things that can be done to increase the yield of the ester as the
product (remember Le Chateliers Principle)?
Table of reagents and products: include the information from the pre-lab activity, as well as actual
volumes and masses used.
Procedure: Reference the lab handout and provide a simple outline.

In-lab Notebook:
Observations- record EXACT amounts of reagents used (use table similar to the one in the pre-lab worksheet),
detailed observations, and any changes you have made to the written procedure.
All information above should be written directly into your lab notebook. The duplicate pages will be turned in
with the rest of your lab report. You will NOT be required to write a conclusion for this experiment. Instead
complete the post-lab worksheet and turn it in with your notebook pages.
References:
1. Linda B. Buck, The Nobel Prize in Physiology or Medicine 2004; Nobel Lecture on Unraveling the Sense of
Smell.
http://nobelprize.org/nobel_prizes/medicine/laureates/2004/buck-lecture.html (accessed Sep 2009)
2. Richard Axel, The Nobel Prize in Physiology or Medicine 2004; Nobel Lecture on Scents and Sensibility: A
Molecular Logic of Olfactory Perception. http://nobelprize.org/nobel_prizes/medicine/laureates/2004/axellecture.html (accessed Sep 2009)
3. Turin, Luca. The Secret of Scent: Adventures in Perfume and the Science of Smell; Harper Perennial: New
York, 2007. 4. The Science of Smell Part 1:Odor perception and physiological response
http://www.extension.iastate.edu/Publications/PM1963A.pdf (accessed Oct 2009).

******************************************************************************************

Essence of Esterification Pre-Lab Activity - this will not be a separate worksheet.

Instead include the requested information from below in your pre-lab notebook.
The following information has been obtained from thegoodscentscompany.com
Methanol
CH3OH

Ethanol
CH3CH2OH

Propanol
CH3CH2 CH2OH

Isopropanol
(CH3)2CHOH

Methyl Pentanoate

sweet green fruity
apple pineapple
nutty
Methyl Hexanoate

fruity pineapple
ether

Ethyl Pentanoate

sweet fruity apple
pineapple green
tropical
Ethyl Hexanoate

sweet fruity
pineapple waxy
green banana

Propyl Pentanoate

ethereal fruity
pineapple metallic
animal
Propyl Hexanoate

sweet fruity juicy
pineapple green
tropical

Isopropyl Pentanoate

fruity pineapple

Salicylic Acid

Methyl Salicylate

wintergreen mint

Ethyl Salicylate

sweet wintergreen
mint floral spicy
balsam

Propyl Salicylate

vine clover fruity
plum

Isopropyl Salicylate

vine clover orchid

Cinnamic Acid

Methyl Cinnamate

sweet balsam
strawberry cherry
cinnamon

Ethyl Cinnamate

sweet balsam
fruity spicy
powdery berry
plum

Propyl Cinnamate

musty vine amber

Isopropyl Cinnamate

balsam fruity tropical
cinnamyl berry
strawberry peach

Pentanoic (Valeric) Acid

Hexanoic (Caproic) Acid

Isopropyl Hexanoate

fruity pineapple
logenberry berry

Before the lab, determine with your partner which of the above esters you wish to synthesize and complete
the following questions in your pre-lab notebook. thegoodscentscompany.com may be helpful.
Name of Ester:

Name of Carboxylic Acid:

Name of Alcohol:

Ester Scent:

Ester Appearance:

Ester Boiling Point:

Note: the reaction requires only a catalytic amount of sulfuric acid. However, concentrated sulfuric acid, in
excess, acts as a drying agent to remove water from the reaction.
Determine your reaction conditions using the provided equivalencies. To do so, determine the amount (g and/or
mL) of carboxylic acid, alcohol, and H2SO4 you will need. The alcohol will act as your solvent and will be 5
mL in volume. Determine all masses and volumes relative to this value.
Recall that an equivalency (eq) is a mole to mole ratio (for example, for a 1 eq carboxylic acid to 5 eq alcohol
ratio, you will use five times the moles (not grams or mL) of alcohol compared to your carboxylic acid).
**Include this table in your pre-lab notebook**
Eq

Carboxylic
Acid

Moles

MW,
g/mol

Mass, g

Density,
g/mL

Volume
mL

Actual
volume
or g
measured

Actual
moles
used

1 eq

Alcohol
5 eq
Concentrated
(18M)
H2SO4

5 mL

1 eq

**Include your calculations in your pre-lab notebook.**

Sample Calculation: Alcohol: Isopropanol, Carboxylic Acid: Pentanoic Acid
Density
MW
EQ
MW
Density
5 mL Isopropanol * 0.79 g * 1 mol * 1 mol Pentanoic Acid * 102.13 g * 1 mL = 1.44 mL Pentanoic Acid
1 mL
60.1 g
5 mol Isopropanol
1 mol
0.93 g

You will use these calculated values as your volume and mass amounts of reagents when you do your lab.

MW
(g/mol)
Density
(g/mL)

Pentanoic
Acid

Hexanoic
Acid

Salicylic
Acid

Cinnamic
Acid

Methanol

Ethanol

Propanol

Isopropanol

102.13

116.16

138.12

148.17

32.04

46.07

60.1

60.1

0.93

0.92

---

----

0.79

0.79

0.80

0.79

Essence of Esterification Post-Lab Name:__________________________Section:___________

Draw the structure of the ester you hoped to synthesize:

Literature Scent:_____________________________ Actual Scent:_____________________________

Literature Appearance: :_________________________Actual Appearance:______________________
Use the above information and your IR and 1H NMR data to discuss the success of this synthesis. Did you
synthesize your chosen ester? Was the starting material completely converted to product? How pure is your
product? Be sure to state evidence to back up your claims. Be sure to staple a copy of your labeled IR and 1H
NMR spectra to this worksheet.

Draw the mechanism of the reaction with your chosen carboxylic acid and your alcohol in the presence of
catalytic sulfuric acid. Include the structure of the desired product.

Determine the percent yield of your product (show all your work):

Why did you use 5 equivalents of alcohol instead of just 1 equivalent and a full equivalent of sulfuric acid
instead of a catalytic amount? Explain the equivalencies provided according to Le Chateliers principle.

Briefly research and give a few interesting facts about your product, including what it is used for.