0.6 Aldol condensation  (Page 2/4)

Some important facts:

1. The reaction involves an enolate reacting with another molecule of the aldehyde.

2. Remember enolates are good nucleophiles and carbonyl C is electrophiles.

3. The products of these reactions are $\beta$ hydroxyaldehydes or aldehyde-alcohols = aldols.

4. The simplest aldol reaction is the condensation of ethanal.

Question: Why isn't the simplest example of an Aldol the condensation of methanal? 

Answer: These Aldol products can often undergo dehydration (loss of water) to give conjugated systems (an elimination reaction )

To recap, Aldol condensation depends mainly on two factors:

• Acidity ofα-H atom (hydrogen atom present next to carbonyl center)
• Reactivity of carbonyl compounds

Here is an example to explain the above facts:

In methyl cyclohexanone two different types of acidic proton is present next to carbonyl center. Due to steric and electronic reasons, one proton is more acidic than the other; whereas benzaldehyde doesn’t have any acidic proton. This is an example of Crossed aldol condensation. Depending on the position of hydroxyl group you can get a mixture of diastereomeric products. 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.

The condensation is usually pushed to completion by dehydration; in some contexts the dehydration may be assumed to be part of the aldol condensation itself.The base-induced elimination is normally not seen with alcohols other than with aldols. This reaction probably proceeds via formation of an enolate, followed by loss of water molecule; formation of the,ß-unsaturated ketone makes up for the poor leaving group ability of hydroxide. (Of course, with acid catalysis the dehydration follows the normal protonation/loss of water/loss of proton mechanism.) Either acid- or base-catalyzed dehydration is helped by increased temperature.

Several observations are necessary at this point.

1. All of the reactions shown above are reversible. You should be able, on your own to predict where each of the equilibria shown above should lie (is K>1 or is K<1?) 2. You should be able to predict how changes in structure will change the position of the equilibrium. (Examples: more or less bulky R groups in the ketone; ketones vs. aldehydes; electronic effects for electron-donating and electron-withdrawing groups.) 3. You should notice that the outcome of a mixture of carbonyl compounds depends on their structure: if there is no proton, no enolate can form and a cross-aldol condensation is possible. If both can form enolates, and both carbonyl groups are of similar reactivity, mixtures of products will result.

In this lab condensation between acetophenone and 4-nitrobenzaldehyde will take place. The reaction scheme as follows:

“Green Chemistry”is important from an environmental point of view. It requires fewer amounts of solvent and chemicals thought to be harmful to the environment. Though there are some possible drawbacks like (a) Low yield, (b) Slow reaction and (c) Increase in reaction cost, still we need to endeavor to keep our environment clean.