Experiment: Aldol Condensation Reactions Using Unknown Reactants
The aldol reaction is particularly valuable to chemists as a carbon-carbon bond forming reaction.
This type of condensation is utilized in pharmaceuticals for the production of tetracycline
antibiotics, Lipitor, and a variety of other products. This reaction is also important to
biochemistry as an aldol condensation reaction is used in biological systems for the synthesis of
and breakdown of glucose. These reactions in nature, however, are catalyzed by enzymes.
In general, an aldol condensation joins two molecules together by the attack of a nucleophile on
a carbonyl carbon to form a β-hydroxy ketone or aldehyde. The nucleophile is normally an
enolate formed from an aldehyde or ketone that attacks another molecule of aldehyde or ketone.
For a standard aldol reaction, the aldehyde or ketone reacts with itself to form the new product.
In a crossed aldol, two different aldehydes or ketones are reacted together.
In this experiment you will perform a crossed aldol condensation, using an unknown aromatic
aldehyde reacting with an unknown ketone. Notice that the three possible aromatic aldehydes
(shown below) have no α hydrogens, therefore, they will not react with the base. This reduces
the possibility of self-condensation reactions.
The unknown aldehydes (labeled A, B, and C for convenience) are shown here:
CHO
benzaldehyde
CHO
CHO
CH3
OCH3
4-methylbenzaldehyde
B
A
4-methoxybenzaldehyde
C
You will react one of the above compounds with one of the possible ketones shown below.
O
O
cyclopentanone
cyclohexanone
2
3
O
acetone
1
The general form of these aldol condensation reactions can be written as shown. Notice the new
carbon-carbon bond formed in the reaction joining these two structures by the condensation
reaction. (Use your textbook to review the aldol reaction mechanism.)
O
O
O
H
2
NaOH
+
CH3CH2OH
R'
R
R'
R'
R'
R
R
+ 2 H2O
You will use the melting point of the product and its proton NMR and carbon NMR spectra to
determine the identity of the reactants and product.
The melting points (oC) of the aldol condensation products can be found in the following table.
compound
benzaldehyde (A)
4-methylbenzaldehyde (B)
4-methoxybenzaldehyde (C)
acetone (1)
113
175
129-130
cyclopentanone (2)
189
235-236
212
cyclohexanone (3)
118
170
159
Since the aldehydes and ketones differ slightly in structure, each possible product is different in
structure, melting point, and spectral data. In the proton NMR spectra of the possible products,
the vinyl hydrogens have a chemical shift around seven due to conjugation with the aromatic
ring. What that means is that in these spectra the aromatic hydrogens and vinyl hydrogens will
have nearly identical chemical shifts (or may overlap). This will make these hydrogens very
difficult to interpret. Instead, focus on the proton NMR signals that arise due to the R and
R’ groups, which will be different for each of the possible products. The number of signals
in the carbon NMR spectrum should be consistent with the structure you choose as your
product.
 Pre-lab Preparation
Before coming to lab, you need to complete the following:
1. Review the procedure used for recrystallization.
2. What are the properties of a good recrystallization solvent?
3. Why does the ketone react with two molecules of aldehyde?
4. Draw the resonance structures of the enolate ion formed from R’CH2COCH2R’.
5. Why is the aldol condensation product that is formed from two molecules of ketone a
minor product?
Experimental Procedure
! Safety Considerations
! The ketones are volatile. Transport them in closed containers and work in the hood.
! The aldehydes and products may be irritating to the skin. Wear gloves when working with
them.
You will be doing this experiment individually. You will be assigned an unknown ketone and an
unknown aldehyde.
1.
Dispense 0.50 mL of the assigned ketone into a 50 mL Erlenmeyer flask. Using a
graduated cylinder, add 2.0 mL of the assigned aldehyde. Then add 10 mL of 95%
ethanol and 8 mL of 2M sodium hydroxide solution.
2.
Swirl the flask for 15 minutes or as long as crystals continue to form. If the amount of
product is small, then place the flask into a hot water bath and continue to swirl for an
additional 15 minutes.
3.
Allow the solution to cool to room temperature before placing it into an ice-water bath
for 10 minutes.
4.
Filter the crystals with suction using a Buchner funnel. Wash any remaining crystals
from the Erlenmeyer flask into the funnel using a small amount of cold 95% ethanol.
Turn off the vacuum and pour 10 mL of a 4% acetic acid in 95% ethanol solution. Turn
on the vacuum to remove the liquid. (The purpose of this rinse with an acidic solution is
to remove any sodium hydroxide which can react with the product during the
recrystallization step.) Wash the crystals with a small amount of cold ethanol solution.
5.
In order to determine a good solvent for recrystallization, add around 1 mL of each of the
solvents provided to a small amount (20 – 30 mg) of the product in a test tube. If the
product does not dissolve at room temperature, heat the test tube in a hot water bath.
Look for dissolving at the higher temperature followed by recrystallization upon cooling.
Use the following solvents: 95% ethanol, toluene, 9:1 95% ethanol:acetone.
6.
Recrystallize your product from the solvent you chose. Note: If you are struggling to
dissolve your sample in the solvent you chose, review your test tube results and consider
adding a few drops of a solvent that dissolved the sample “too well” to the mixture until
the solid just dissolves. This creates a solvent-pair system, with the poorer solvent added
first, followed by the better solvent. Remember, you want just enough solvent to
dissolve all of the solid while at the boiling point. Cool and filter the crystals with
suction. Wash with a small amount of the cold solvent you used. Transfer the crystals to
a piece of dry, tared filter paper and allow to the sample to dry. Obtain a weight of the
dry product and measure its melting point.
7.
Check with your instructor to see whether you need to prepare an NMR sample. If so,
use 20 – 30 mg of your product and 1 mL of the designated solvent. Use a syringe filter
to filter your sample before transferring it to the NMR tube. Run a proton and carbon
NMR spectrum for your sample. If you are not asked to do this, you will be given a
previously run spectrum to interpret.
8.
Turn in the remainder of your product in a vial labeled with your name, the reactants
used, melting point and weight of product.
 Post-Lab and Report Requirements
1. Report the mass and melting point of your product. Include the letter and number used to
designate the reactants you used.
2. Identify the unknown aldehyde and ketone that you used. Explain how you used the
melting point and spectra to identify your unknown. For the proton NMR, include the
chemical shifts and areas of the hydrogens in your explanation. (Exclude the aryl and
vinyl hydrogens.) Explain the number of signals in the carbon NMR spectrum.
3. Write a balanced reaction equation for the aldol condensation that you performed.
4. Write a detailed mechanism for your condensation.