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The Aldol Condensation Puzzle

Revised January 2002

The Aldol Condensation is an extremely useful carbon-carbon bond forming reaction in organic
chemistry. In this experiment, a mixed Aldol Condensation will be performed. This means that
two different carbonyl compounds will be used, but only one, the ketone, will have -hydrogens:
the aldehyde will not have -hydrogens. The overall reaction is shown below.
H

O
O

2
G

Aldehyde

H
H

C
C

Ketone

NaOH, H2O

H ethanol

Aldol Condensation Product

Some of these aldol products show cytotoxic and anti-tumor activities (see Dimmock, J. R., et al,
J. Pharm. Sci. 1994, 83(6), 852-858).
If the aldehyde has acidic -hydrogens, then it could react with itself. By choosing aldehydes
without -hydrogens, the aldehyde will react with the ketone. Although the ketone could do an
Aldol Condensation with itself as well, it usually reacts much faster with the aldehyde (why?).
The carbon-carbon double bonds that are formed are usually in the configuration shown, the socalled "trans, trans" form. Trace amounts of the "cis, trans" and "cis, cis" probably also form, but
these isomers are less likely to be solids, so they do not crystallize out of solution.
To make this lab a little more challenging, you will not know the identity of the aldehyde or
ketone you are using. Instead, you will be assigned a coded aldehyde and ketone to react
together. You will purify a small portion of the product by recrystallization, and determine the
melting point. You will demonstrate the purity of your product by TLC, and then obtain the NMR
spectrum of your product. From the NMR and melting point data, you should be able to deduce
what aldehyde and ketone you started with.
The reaction produces several intermediates before the final product is produced. These are
shown below. You can draw the arrows and supply the missing steps. The reaction is catalytic in
hydroxide. The ethanol solvent serves to keep the intermediate structures in solution so that the
final product can be formed.

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O

H
C
Ar

C
C

H
H

OH
C

Ar

C
H

C
Ar

C
C

H
H

H
H

C
Ar

Ar

Ar

HO

C
O

Ar

Ar

4-ethylbenzaldehyde is not in the CRC Handbook or in the Merck Index. The physical constants
you might want are given below.
Molecular weight:
Density:
Boiling Point:

134.18
0.979
221

General Procedure
In a 50 mL Erlenmeyer flask place in this order the ketone (0.5 mL), the aldehyde (2.0 mL), 95%
ethanol (12 mL), and 2M aqueous sodium hydroxide (10 mL). Stir or shake the reaction mixture
until no more precipitate is observed to form. Some reactions form precipitate almost
immediately; others require several hours. If no precipitate has formed after 15 minutes, you have
a slow-reacting mixture. You can either allow this sit until the next lab period, or heat the
reaction mixture on the steam bath for about 15 minutes, then allow the reaction to cool, and see
if crystals form. Magnetically stirring the reaction mixture also speeds up the rate of reaction.
Once crystallization is complete at room temperature, cool the reaction in an ice bath, and then
collect the product by suction filtration. Wash the product consecutively with ice-cold, 5 mL
portions of:
1. 95% ethanol,
2. 5% acetic acid in 95% ethanol,
3. 95% ethanol.
Recrystallize a small portion of your product from either 95% ethanol or toluene (whichever
solvent works the best). Check the purity of your crude and recrystallized products by TLC.
Dissolve tiny amounts of each in ethyl acetate in separate small test tubes, and spot each solution
on a small silica gel TLC plate. Use toluene as a developing solvent, and visualize the plate with
UV light to see the spots if needed. When you have demonstrated that your recrystallized product
is pure, you can obtain the NMR spectrum of your product from your lab instructor.
Hints on interpreting your NMR spectrum.

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A general structure of the Aldol product is shown below.
Hb
Hc

Ha

Hb
Hc

Ha

Hb

Hc

Hb

G
Hc

1.

The alkene hydrogens, Ha, usually show up in the aromatic region of the spectrum,
around 7.2-7.6 ppm. If your ketone is acetone, the R = H, and these hydrogens usually
show up close to 7 ppm. This is due to the C=C being conjugated to the C=O. If R = H,
it will couple with Ha with a large coupling constant, about 15-18 Hz.

2.

The aromatic hydrogens, Hb, appear about 7.3 ppm. Hc, on the other hand, may appear
between 6.7 and 7.3 ppm, depending upon what G is. Hb and Hc usually couple with
each other, so each appears as a doublet. However, if Hb and Hc are very close to one
another in chemical shift, the coupling patterns may be severely distorted. Ha may show
up in the same region these peaks, so the apparent coupling patterns may appear distorted,
due to the peak(s) for Ha.

3.

If G = H, then it will appear in the aromatic region of the spectrum, and could complicate
that region of the spectrum somewhat. If G = CH3 or OCH3, then it should appear as a
single peak in the appropriate region of the spectrum. If G = CH2CH3, then you should
see a triplet and a quartet at appropriate places in the spectrum.

4.

If you started with a cyclopentanone or cyclohexanone, then the R's are some number of
CH2 groups. You should see a peak for each type of CH2. These peaks often appear as
lumps, because coupling in cyclic compounds is more complex, so the N + 1 rule may not
apply. The peaks for the G groups may overlap the peaks for the CH2's, so be sure to use
the integration values to check the number of H's in each set of peaks, especially if the
peak looks distorted or unusual.

5.

If your ketone was 4-methylcyclohexanone, then the methyl group will be split by the
adjacent CH into a doublet. The CH and the CH2s are coupled to each other, and may
form some complex patterns, due to the CH2s not being free to rotate.

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The following table gives the reported melting points of the Aldol condensation products derived
from each combination of aldehyde and ketone.
Aldehydes

H
C

C
H

CH 3

H 3C

CH 2

O
H 3C

Benzaldehyde

p-tolualdehyde
(4-methyl
benzaldehyde)

4-ethyl
benzaldehyde

p-anisaldehyde
(4-methoxy
benzaldehyde)

113

175

125-127

129-130

189

235-236

147-148

212

118

170

124-125

159

98-99

133-135

115-116

141-2

Ketones
O
C
H3C

CH3

Acetone
O

Cyclopentanone
O

Cyclohexanone
O

H3C

4-methyl
cyclohexanone
For example, the product derived from the reaction of benzaldehyde with cyclohexanone is
reported to melt at 118C.

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Report Format
A.

Title Page
1.
2.
3.
4.

A descriptive title with between 10 & 20 words.

Course and section number.
Dates that the experiment was performed.
Your name.

Tape your TLC plate to the bottom of the page, labeled clearly so I know what is what.
B.

Body of the report.

1.
2.
3.
4.
5.
6.
7.

C.

A 2-3 sentence summary of your results (amount of product, melting point, identity
of starting aldehyde and ketone).
Balanced chemical equation, using the actual structures you used.
Important observations, and their interpretations, if possible. (colors of solutions &
solids, length of time until precipitate formed, etc.)
Weight of crude product.
Melting points of both crude and recrystallized products.
TLC data, and calculations of Rf values for all spots.
Calculations of theoretical and percent yields. Show calculations for the moles of
all reactants. Identify the limiting reagent.

Questions
1.

Explain in detail how you used all of the data you obtained to determine the
structure of your product. How did you distinguish between close choices? Did
all of your data point to the same structure? If not, how did you decide which
structure was correct? Include your NMR spectrum with your report. Interpret
your NMR spectrum by drawing the structure of your product on the spectrum,
and showing which H's in your structure give rise to which peaks in your
spectrum. Explain the coupling patterns and any unexpected peaks.

2.

What do your melting points tell you about the purity of your products? What do
your TLC data tell you about the purity of your products? How accurate do you
think these data are? Explain.

3.

What impurities are removed by the ethanol and acetic acid in ethanol washes?
Explain your reasoning.