THE ALDOL CONDENSATION REACTION

An aldol condensation is a condensation reaction in organic chemistry in which an enol or an

enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone,
followed by dehydration to give a conjugated enone.

Aldol condensations are important in organic synthesis, because they provide a good way to
form carbon–carbon bonds. For example, the Robinson annulation reaction sequence features
an aldol condensation; the Wieland-Miescher ketone product is an important starting material
for many organic syntheses. Aldol condensations are also commonly discussed in university
level organic chemistry classes as a good bond-forming reaction that demonstrates important
reaction mechanisms. In its usual form, it involves the nucleophilic addition of a ketone enolate
to an aldehyde to form a β-hydroxy ketone, or "aldol" (aldehyde + alcohol), a structural unit
found in many naturally occurring molecules and pharmaceuticals.

The name aldol condensation is also commonly used, especially in biochemistry, to refer to
just the first (addition) stage of the process—the aldol reaction itself—as catalyzed by
aldolases. However, the aldol reaction is not formally a condensation reaction because it does
not involve the loss of a small molecule.
The reaction between an aldehyde/ketone and an aromatic carbonyl compound lacking an
alpha-hydrogen (cross aldol condensation) is called the Claisen-Schmidt condensation. This
reaction is named after two of its pioneering investigators Rainer Ludwig Claisen and J. G.
Schmidt, who independently published on this topic in 1880 and 1881. An example is the
synthesis of dibenzylideneacetone. Quantitative yields in Claisen-Schmidt reactions have been
reported in the absence of solvent using sodium hydroxide as the base and plus benzaldehydes.

Mechanism
The first part of this reaction is an aldol reaction, the second part a dehydration—an elimination
reaction (Involves removal of a water molecule or an alcohol molecule). Dehydration may be
accompanied by decarboxylation when an activated carboxyl group is present. The aldol
addition product can be dehydrated via two mechanisms; a strong base like potassium t-
butoxide, potassium hydroxide or sodium hydride in an enolate mechanism, or in an acid-
catalyzed enol mechanism. Depending on the nature of the desired product, the aldol
condensation may be carried out under two broad types of conditions: kinetic control or
thermodynamic control.
 Aldol Condensation Reactions

Aldol condensation reactions signify an essential class of reactions for the formation of
carbon-carbon bonds. An aldol reaction involves the condensation of two carbonyl
compounds to form a ß-hydroxyaldehyde or ß-hydroxyketone, the aldol product.

The typical aldol reaction involves self condensation of the reactant ketone or aldehyde
wherein one molecule adds to the other of the same type. An example of a self-condensation
aldol reaction is shown in Figure 1, with acetaldehyde as the sole reactant.

Here 3-hydroxybutanal is obtained by adding acetaldehyde to another acetaldehyde reactant

molecule to form the aldol (aldehyde-alcohol) product.

Figure 1. Aldol self-condensation of acetaldehyde

Under base-catalyzed conditions the aldol reaction proceeds through an enolate ion as shown
in Figure 2.

Figure 2. Base-catalyzed production of the enolate ion in the aldol self-condensation

reaction (R = H, alkyl, phenyl)
The resonance stabilized enolate is then subjected to nucleophilic addition to the carbonyl
carbon of another aldehyde or ketone molecule, forming a new C-C bond and an alkoxide ion
as shown in Figure 3.

Figure 3. Nucleophilic addition of enolate anion to the carbonyl group (R = H, alkyl, phenyl)

In the next step ß-hydroxy aldehyde or ketone is formed by reaction with water, and the
reaction is completed by dehydration of the alcohol group in a strong base, resulting in the
loss of water and the formation of an α,ß-unsaturated product as shown in Figure 4.

Figure 4. Formation of the aldol product and dehydration to an a,ß-unsaturated carbonyl

product

Similar self condensation reactions take place for ketones and derivatized ketones and
aldehydes as long as there is an enolizable proton at the a carbon position.

Crossed aldol reactions between ketones and aldehydes form mixed condensation products.
One compound’s enolate ion is subjected to nucleophilic addition to the carbonyl carbon of a
different compound. Normally crossed condensation products are not desirable as they cause
a mixture of products and bring down the yield of a desired product.
Figures 5 and 6 show a case where an aromatic benzaldehyde, aldehyde, is substituted for the
alkylaldehyde as a reactant.

Figure 5. Crossed aldol condensation reaction, producing the a,ß-unsaturated ketone

dibenzalacetone

Figure 6. Crossed aldol condensation reaction, producing the a,ß-unsaturated ketone

chalcone

Derivatives of the parent reactant molecules acetophenone and benzaldehyde can include a
range of R, R1 and R2 functional groups, such as methyl (-CH3), methoxy (-OCH3), chloro (-
Cl), bromo (-Br), amino (-NH2), hydroxy (-OH), nitrile (-CN), etc. and in a number of
positions round the phenyl ring. The hydroxy group will show concentration, temperature and
solvent polarity dependence that complicates interpretation.

Also there are complications in the amino group spectrum because of spin coupling of the
proton with the nitrogen nucleus, the varying exchange rate of the labile amino proton and the
electric quadrupole moment of the 14N nucleus.

A new peak in a proton NMR spectrum is not introduced by halogen substitution but will
impact splitting patterns and peak position on the aromatic protons. Only the methoxy and the
methyl groups introduce non-overlapping, new resonance lines in the parent molecule
spectrum enabling straightforward interpretation.

1H NMR – A Qualitative Lesson

It is a simple task to identify the key peaks in the 1H NMR spectra of the reactants in the aldol
reactions of Figures 5 and 6. Both the methyl ketone and aldehyde protons produce only one
resonance line each, hence making them easy to monitor. NMR spectra can be determined on
pure samples or by using using an aliquot of the reaction mixture.

The picoSpin 45 NMR spectrometer is suitable for initial qualitative analysis of neat mixtures
and samples providing students the chance to determine the quality of their starting materials,
establish the mixture’s stoichiometry, identify the main functional groups undergoing
chemical transformation and obtain valuable hands-on experience using NMR in the lab.

Since the capillary cartridge can be easily flushed and refilled, it can be used using a three to
four hour organic chemistry experiment. The reaction mixture of students can be sampled
several times at a number of stages through the experiment, obtaining spectra as the reaction
proceeds and determining a spectrum of the isolated product. 1H NMR spectra shown here
were obtained with a 90-degree pulse angle, 750 ms acquisition time, 10–20 s recovery delay,
and an average of 9 or 49 scans.

Figures 7 and 8 show spectra of reactants 4-methoxybenzaldehyde and 4-

methylbenzaldehyde. The aldehydic proton produces a lone signal because of a lack of the
neighboring proton. Diamagnetic anisotropy results by circulation of p electrons of the
carbonyl (C=O) bond induced along the transverse axis by the applied field, resulting in
strong e-shielding of this lone proton.
Figure 7. NMR spectrum of 4-methoxybenzaldehyde (neat, 25 scans)

Figure 8. NMR spectrum of 4-methylbenzaldehyde (neat, 25 scans)

Aldol Condensation reactions
Introduction
(a) Objectives
1. To synthesize Dibenzalacetone.
2. To synthesize Benzalacetophenone.
3. To measure the melting point of the sample.
4. To understand the mechanism of an Aldol Reaction.
(b) Theory

An Aldol condensation reaction is one in which an enol or an enolate ion reacts with a
Carbonyl compound to form £]-hydroxyaldehyde or a £]-hydroxyketone, hence a dehydration
gives a conjugate enone. In both parts of this practical experiment Benzaldehyde reacts with a
ketone in the presence of a base to produce £]-unsaturated ketones. The reaction that the
experiments follow is an example of a crossed aldol condensation reaction where the
intermediate in the reaction becomes dehydrated to produce the resonance- stabilised
unsaturated ketone. The ketone loses a proton from an alpha-carbon to then form an enolate
ion, which attacks the carbonyl carbon of the aldehyde to yield, after protonation alpha, beta-
hydroxyketone. The intermediate formed for the aromatic aldehyde is unstable and is
subjected to base-catalysed dehydration, until the unsaturated product is yielded. An
important point to note is that a crossed-aldol condensation leads to a number of different
products, unless one of the carbonyl compounds that is involved in the reaction cannot form
an enolate ion (meaning compound has no alpha-hydrogens). An aromatic aldehyde, such as
Benzaldehyde is sufficient for the reaction as only one enolate ion will form, which is from
the other carbonyl compound. Hence formation, the nucleophilic enolate ion attacks the
carbonyl carbon to form a £]-hydroxycarbonyl product. The £]-hydroxycarbonyl product then
eliminates a molecule of water to form a conjugated system composed of a double bond and
the carbonyl group. The elimination process with regards to part one of the experiment was
particularly fast as the alkene is stabilised by conjugation to not only the carbonyl but also
benzene. The theoretical melting point of Dibenzalacetone is 110-111¢XC. In theory, the
meltingpoint of Dibenzalacetone is 55-57¢XC.

Reference
1. Aldol Condensation, (2018), Libretexts, retrieve from
https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_
(Organic_Chemistry)/Reactions/Organic_Reactions/AldolCondensation
2. Understanding the Aldol Condensation Reaction Using Nuclear Magnetic Resonance
(NMR), (2013), Thermo Fisher Scientific – Materials & Structural Analysis, azom,
retrieve from https://www.azom.com/article.aspx?