0.6 Aldol condensation

Experiment 2: aldol condensation reaction

Objective

The purpose of this laboratory exercise is to introduce the concept of the Carbon-Carbon bond forming reaction and the basic mechanism of the aldol condensation reaction.

Background information

A useful carbon-carbon bond-forming reaction is known as the Aldol Reaction or Aldol Condensation. It is an example of electrophilic substitution at the alpha carbon in enols or enolate anions. Traditionally, it is the acid- or base-catalyzed condensation of one carbonyl compounds with the enolate/enol of another, which may or may not be the same, to generate aβ-hydroxy carbonyl compound—an aldol. It is reversible in nature. The reaction may occur between two molecules of aldehyde, two molecules of ketones or one molecule of aldehyde and a molecule of ketone. When two different carbonyl compounds react, it is known as mixed aldol/ Crossed aldol condensation.

Reactions in which a larger molecule is formed from smaller components with the elimination of a very small by-product such as water are termed Condensations. Hence the following examples are properly referred to as aldol condensations. The dehydration step of an aldol condensation is also reversible in the presence of acid and base catalysts. Consequently, on heating with aqueous solutions of strong acids or bases, manyα,β-unsaturated carbonyl compounds fragment into smaller aldehyde or ketones, a process known as the retro-aldol reaction. Below, a few examples of aldol condensation reaction are:

The product has both a carbonyl and an alcohol group; since the chemistry was initially developed with aldehydes the name "Ald-ol" (aldehyde-alcohol) was coined and has been applied to the reaction that forms it. For aldol condensation, the presence ofα-H (acidic hydrogen atom) atom is necessary. In the absence ofα-H atom, it can undergo the Cannizaro reaction. Aldol condensation involves the following steps in the mechanism:

1. Addition phase:

(a) Formation of an enol or enolate anion.

(b) Nucleophilic addition

(c) Proton transfer

2. Dehydration phase (If strong base/acid or some heat is applied)

Using acetone as an example:

Step 1: An acid-base reaction occurs first. Ethoxide functions as a base and removes the acidic-hydrogen giving the reactive enolate.

Step 2: The nucleophilic enolate attacks another molecule of acetone at the electrophilic carbonyl C in a nucleophilic addition type process giving an intermediate alkoxide.

Step 3: An acid-base reaction. The alkoxide deprotonates a solvent molecule (here ethanol) creating hydroxide and the $\beta$ hydroxyaldehydes or aldol product is formed.

There is little difference mechanistically between an acid or base catalyzed mechanism but examples of both have been given for completeness.

In next figure, the actual carbon-carbon bond formation has shown in different color for simplicity.

Acid catalyzed reaction mechanism:

Base catalyzed reaction mechanism:

From the mechanism it is clear that presence of electron withdrawing group in acceptor molecule facilitates the reaction and vice versa.