7.0 Aldol Condensations

  Aldehydes and Ketones

Two molecules of an aldehyde or a ketone undergo condensation in the presence of a base to yield a $\beta $-hydroxyaldehyde or a $\beta $-hydroxyketone. This reaction is called the aldol condensation which may be exemplified by the reaction of acetaldehyde to give acetaldol (3-hydroxybutanal).

Since aldehydes and ketones lacking a-hydrogens do not undergo aldol condensation, a key step of the reaction is the formation of the enolate anion (carbanion) by removal of an a-hydrogen by base. Like other nucleophiles, the carbanion then attacks the carbonyl carbon of the second molecule and the anion so formed accepts a proton from the solvent molecule to yield the product.

Step I:

Crossed aldol condensation between two different carbonyl compounds – both having $\alpha $-hydrogen – yields a mixture of four possible products. For example, the condensation of acetaldehyde and propionaldehyde may occur in the following manner:

In addition, the reaction will also yield both, the dimmer of acetaldehyde and the dimmer of propionaldehyde by self-condensation of the reactants.

However, when one of the reactants has no a-hydrogen (e.g., benzaldehyde and formaldehyde) and therefore cannot form an enolate, mixed aldol condensation can be of some synthetic utility. For example.

Aldol condensations are also catalysed by acids. The reaction of benzaldehyde with acetophenone in the presence of acid was found to be first-order in both the reactants and it appears quite reasonable to believe that acid catalyses the conversion of acetopheone into the enol when they reacts with the protonated benzaldehyde.

Usually the aldol products are easily dehydrated under acidic conditions.

The appearance of dehydrated product is not only confined to acid-catalysed reactions, but many aldol condensations employing strong bases, such as alkoxide or hydroxide ions also yield the dehydrated products. Their mechanism of formation involves an enolate ion which subsequently eliminates a hydroxide ion.

This forms the basis of the Claisen-Schmidt reaction which may be defined as a base-catalysed condensation of an aldehyde or ketone to form an $\alpha ,\beta $-unsaturated aldehyde or ketone.

Mesityl oxide (III) is thermodynamically favoured product and hence lies at a lower energy level than either acetone or diacetone alcohol (II).

It becomes apparent from an inspection of figure that dehydration of the initially formed aldol product is an extremely facile process in the presence of acids.