Aldol Condensation
Aldehydes having α-hydrogen(s) undergo self-condensation on warming with dilute or mild base to give β-hydroxy aldehydes, called aldols (aldehyde + alcohol). This reaction is known as aldol condensation. A typical example is the reaction of acetaldehyde with base under mild condition.
Various basic reagents such as dilute sodium hydroxide, aqueous alkali carbonate, alkali metal alkoxides, etc., may be used. The reaction is not favourable for ketones.
Aldol condensation has broad scope. It can occur between
(i) two identical or different aldehydes,
(ii) two identical or different ketones and
(iii) an aldehyde and a ketone.
When the condensation is between two different carbonyl compounds, it is called crossed aldol condensation.
Mechanism of Aldol Condensation
Step: 1 The first step involves the formation of a resonance-stabilized enolate anion by the removal of an α-hydrogen from the aldehyde by the base.
Step: 2 In the second step the enolate anion attacks the carbonyl carbon of the second molecule of the aldehyde to form an alkoxide ion.
Step: 3 The latter then takes up a proton from the solvent to yield aldol in the third step.
Thus, the overall reaction is an addition of enolate anion to the carbonyl double bond.
Usually aldol as such is not isolated, e.g., acetaldol is isolated as a cyclic hemiacetal.
Aldol is isolated under reasonable mild condition, i.e., using aqueous K2CO3 as base.
The reaction between two ketones is not very successful. The equilibrium is not favourable and lies far to the left.
This is because the carbonyl carbon of ketone is less positive (due to +I effect) and more sterically hindered relative to aldehydes. This reduces the nucleophilic attack on the carbonyl carbon. However, it is possible to prepare diacetone alcohol in reasonable good yield by boiling acetone with solid Ba(OH)2 in a specially devised apparatus.
Salient features of Aldol Condensation
(a) Aldols are easily dehydrated to α,β-unsaturated compounds on heating alone or with acid or base.
(b) When aldol condensation is carried out in the presence of strong alkali, repeated condensation and dehydration results in the formation of resins.
(c) The condensation is promoted by –I effect and reduced by +I effect on the carbonyl carbon.
(d) The reaction equilibrium is favourable for aldehydes but much less favourable for ketones.
Crossed Aldol Condensation
When the condensation is between two different carbonyl compounds, it is called crossed aldol condensation.
(i) Crossed aldol condensation between two different aldehydes
When both the aldehydes have α-hydrogen(s) both can form carbanions and also can act as carbanion acceptors. Hence a mixture of four products are formed which has little synthetic use. If one of the aldehydes has no α-hydrogen then it can act only as a carbanion acceptor. In such case two products are formed, e.g.,
However, a good yield of the crossed product is obtained by slowly adding the aldehyde having α-hydrogen to a mixture of the aldehyde having no α-hydrogen and the catalyst, e.g.,
Formaldehyde having no α-hydrogen is a reactive carbanion acceptor due to the absence of steric hindrance and +I effect. Hence, when acetaldehyde is treated with excess of formaldehyde in the presence of Ca(OH)2, crossed aldol condensation continues (three times) until trihydroxymethyl acetaldehyde, (HOCH2)3CCHO(I) is formed. The latter having no α-hydrogen undergoes crossed Cannizzaro reaction to form pentaerythritol.
(ii) Crossed aldol condensation between two different ketones
Due to poor reactivity of carbonyl carbons (+I effect and crowding) of ketones, a poor yield is obtained and so it is rarely attempted.
(iii) Crossed aldol condensation between an aldehyde and a ketone
(a) When an aldehyde and a ketone both having α-hydrogens are condensed, two products are obtained. This is because ketones are poor carbanion acceptors and so cannot undergo self-condensation. Aldehydes being more reactive than ketones act as carbanion acceptors and the ketones provide the carbanions.
Usually, the crossed product is the predominant product. The formation of acetaldol can be minimized by slowly adding the aldehyde to the mixture of ketone and the catalyst base.
(b) When the addition is between a ketone and an aldehyde with no α-hydrogen, only one product is obtained. This is because the ketones are less reactive and cannot undergo self-condensation and the aldehyde does not undergo Cannizaro reaction which is slower than aldol condensation. Hence, the ketone provides the carbanion and the aldehyde acts as the carbanion acceptor. Thus,
The reaction (iii) is difficult to stop at this stage and proceeds further till all the hydrogens of the ketone have been replaced by hydroxymethyl group to give (HOCH2)3C-CO-C(CH2OH)3.
Dehydration of Aldols
Aldols can be easily dehydrated to α,β-unsaturated compounds in the acidic or basic medium and sometimes on simple heating.
