Experiment 8: Aldol Condensation Using an Unknown Aldehyde and an Unknown Ketone

Adapted from "Experimental Organic Chemistry," Mohrig, J. R.; Morrill, T. C.; Hammond, C.
N.; Neckers, D. C. W. H Freeman and Company, New York, pp 408-418.
Scenario
The Aldol Dye Co. manufactures dyes using the double aldol condensation of a ketone with two
equivalents of an aldehyde. The resulting conjugated dienones have yellow to orange colors
depending on the structure of the starting materials. They have recently received a shipment of
ketones and aldehydes, but due to a mishap during the shipping the labels on the bottles are
unreadable. You have been called in to help identify the materials so that they can be used. To
do this you will obtain IR spectra of the starting materials in order to distinguish between the
aldehydes and ketones. You will also perform aldol reactions with the various ketones and
aldehydes and characterize the products by 1H NMR in order to determine the structure of each
component. The possible aldehydes are benzaldehyde, 4-methylbenzaldehyde (p-tolualdehyde),
4-methoxybenzaldehyde (p-anisaldehyde), and E-3-phenyl-2-propenal (cinnamaldehyde). The
possible ketones are acetone, cyclopentanone, cyclohexanone, and 4-methylcyclopentanone.
CHO

CHO

CHO

CHO
Benzaldehyde

CH3

OCH3

4-Methylbenzaldehyde

4-Methoxybenzaldehyde

Cinnamaldehyde

CH3
Acetone

Cyclopentanone

O
R

O
H

R'

Cyclohexanone
O

Base
R'

4-Methylcyclohexanone

R
R'

R'

Yellow to orange dye

Scientific Method
The problem you face is to identify the starting materials and products in an aldol reaction,
where you don't know the structures of the components. You will be give two unknowns, one of
which will be an aldehyde and one a ketone. You will use IR to determine which starting
materials is the aldehyde and which is the ketone. After making the aldol product, you will
determine its structure, and thus the structure of your starting materials.

The Aldol Condensation:

The formation of carbon-carbon bonds is of fundamental importance in organic synthesis. In
most cases it is necessary to build large molecules from smaller ones. Often, this requires the
formation of new carbon-carbon bonds. The aldol condensation is a classic reaction that allows
two carbonyl compounds to be condensed together to give a new carbon-carbon bond, in this
case a double bond. In a typical aldol reaction, a small amount of enolate is formed by
deprotonation of an aldehyde or ketone. The enolate can then attack the electrophilic carbon of
an aldehyde, resulting formation of a new carbon-carbon bond. Protonation of the product gives
a hydroxy aldehyde (or ketone) known as the aldol product. This product can react further with
base to lose water and give a ,-unsaturated aldehyde (or ketone).
O
H3C

H2C

H2C

OH
H3C

+ H2O

O
H

H3C

C
H2
OH

O
H

O
H3C

O
H3C

-OH

+ -OH

H3C

C
H

H2O

O
H

+ H2O

In the scenario of this experiment, all of the aldehydes lack -hydrogens, so they cannot form
enolates. The ketones can all form enolates, but generally cannot act as the electrophile in an
aldol reaction. Thus we would expect the ketone enolate to attack the aldehyde. Since all of the
ketones are symmetrical, they can actually react on both sides of the ketone to give a doubly
conjugated ketone product.
Understanding the Experiment:
IR analysis of the starting materials: IR spectroscopy is a powerful method to determine which
functional groups are present in a molecule. Carbon compounds are particularly easy to identify
in an IR spectrum by their strong absorbance around 1700 cm-1. Using IR, it is possible to
distinguish between difference classes of carbonyl compounds. Aldehydes typically are found
around 1725 cm-1, while ketones are typically a little lower (1715 cm-1). Another important
distinction between aldehydes and ketones is the aldehyde C-H bond. It's stretching frequency is
found around 2700-2800 cm-1). Few other things come in this region.
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The exact structure of the compound will affect the stretching frequency of the C=O bond. In the
case of cyclic ketones, the size of the ring will affect the stretching frequency. Smaller rings
give higher stretching frequencies. For example, cyclopentanone will appear around 1740 cm-1,
while cyclohexanone has a stretching frequency very similar to that of a non-cyclic ketone (1715
cm-1). Conjugated aldehydes and ketones appear at lower stretching frequencies. A conjugated
alkene or aromatic group provides additional resonance structures with C-O single bonds, thus
weakening the C=O bond. A weaker bond will give a lower frequency stretch. Thus
benzaldehyde has a stretching frequency of 1700 cm-1, which is about 15 cm-1 lower than a
typical aldehyde.
O

O
R

R
O

O
R

O
R

NMR analysis of the products: The products can be analyzed using the techniques that we've
discussed already. The key to distinguishing among the various possible products is to consider
how the structures would differ in the NMR spectrum. For example, there are three starting
materials that have methyl groups. In two cases, 4-methylbenzaldehyde and 4methylcyclohexanone, the methyl group is attached to carbon groups. In the case of 4methoxybenzaldehyde, the methyl group is attached to oxygen. Very different chemical shifts
would be expected for these two products. Using similar logic, it will be possible to distinguish
among all of the possible products.
Directions:
You will be assigned two vials containing your unknowns. One will be labeled with a code
number and 2 mL. The other will be labeled with a code number and 0.5 mL. Note the code
numbers in your lab book. The volumes indicate how much of each liquid should be used in the
reaction.
Using your 10 mL graduated cylinder, place 2 mL of one unknown (the one labeled 2 mL) and
0.5 mL of the other unknown into a small Erlenmeyer flask containing a magnetic stirring bar.
Add 10 mL of ethanol and 7.5 mL of 2 M sodium hydroxide solution to the flask. Stir the
solution with a magnetic stirrer for 15 minutes, or longer if precipitate appears to still be
forming. A large amount of yellow or orange precipitate should form. If it does not, heat your
reaction on a hot plate at low setting for 10-15 minutes and then allow to cool. Usually heating
is not necessary, unless you do not receive precipitate after stirring at room temperature.
When the precipitation is complete, cool the flask in ice-water for 10 minutes. While the flask is
cooling, obtain 20 mL of 95% ethanol and place it in a test tube. Do the same with 8 mL of 4%
acetic acid in 95% ethanol. Chill the test tubes in ice water.

Collect the product by vacuum filtration using a Bchner funnel. Disconnect the vacuum tube
from the filter flask and rinse the product with approximately 8 mL of ice-cold ethanol.
Reconnect the vacuum and draw the liquid through your product. Repeat this washing with 8
mL of the ice-cold acetic acid/ethanol solution, and finally with an additional 8 mL of ice-cold
ethanol.
You will purify your product by recrystallization. Before doing so, you must identify the
appropriate solvent for your product. To do this place a small amount (20-30 mg) of your crude
product in 2 test tubes. In one test tube add 10 drops of 95% ethanol. Swirl the mixture to see if
the compound dissolves. If it immediately dissolves, then ethanol is too good of a solvent. If it
does not immediately dissolve, heat the test tube in a hot water bath. If the product will not
dissolve, add a few more drops of ethanol and heat again. If it still will not dissolve, then ethanol
is not a good enough solvent for recrystallization. If the product does dissolve upon heating,
then place the test tube in an ice bath to see if crystals form. If they do, then ethanol is a suitable
recrystallization solvent. Repeat this procedure with toluene. In the case of toluene it may be
necessary to add a few drops of hexane to induce recrystallization. If neither ethanol or toluene
appear satisfactory, try a 9:1 mixture of ethanol and acetone. The correct solvent for your
product will be the one that dissolves your compound upon heating and gives nice crystals upon
cooling.
Once you have chosen your recrystallization solvent, carry out the recrystallization with your
remaining crude product. Once crystals have formed, vacuum filter them. You may use a small
amount of ice-cold solvent (the one you chose for your recrystallization) to wash your crystals.
Place the crystals in your drawer to dry until the next week. Clean your NMR tube with acetone
during the first week of the experiment, so that it will be ready for the product analysis next
week.
Analysis:
Obtain the melting point of your recrystallized product. The expected melting points are listed
below.

Acetone

ketones
Cyclopentanone Cyclohexanone

113 C
175 C
129-130 C
144 C

189 C
235-236 C
212 C
225 C

Aldehydes

Benzaldehyde
p-tolualdehyde
p-anisaldehyde
Cinnamaldehyde

118 C
170 C
159 C
180 C

4-methyl
cyclohexanone
98-99 C
113-113.5 C
141-142 C
163-164 C

IR analysis: To prepare your sample, place a couple drops of your unknown on the salt plate.
Cover with the second salt plate and obtain the spectrum as instructed by your TA.
NMR analysis: Place 20-30 mg of your product in a clean, dry test tube. Add 1 mL of CDCl3.
Add 0.8 mL of this solution to your NMR tube. Use the guides in the lab to determine if you
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have the right amount of solution in your sample. Obtain the NMR spectrum as directed by your
TA. You will receive the raw FID file by email. You will process this data using MestRec as
described in additional handouts.
Turn in your remaining recrystallized product to your TA in a labeled vial.