The Aldol Reaction

An ‘aldol reaction’ is named for the reactions’ products, which contain a beta-hydroxy aldehyde. The reaction is our first example of a self condensation reaction where two molecules of the same compound react with each other to make something new.

It’s common for many students to find the aldol reaction really confusing. Make sure you understand what’s going on before we move on to new subjects.

The aldol can be catalyzed by acid or base.

Acid catalyzed:

In the presence of acid, a little bit of enol and a little bit of protonated aldehyde are formed.

The nucleophilic enol and the electrophilic protonated aldehyde can react together to make a beta-hydroxy aldehyde. The driving force for the reaction is the creation of a new carbon-carbon bond at the expense of a carbon-oxygen pi bond.

Base Catalyzed:

Basic conditions also work for the aldol reaction. In the presence of base a little bit of enolate is formed.

The nucleophilic enolate and the aldehyde can react together to make a beta-hydroxy aldehyde.

Q: How many stereoisomers are possible in the above aldol reactions?

Q: What happens when two different aldehydes are used? An aldehyde and a ketone? Two different ketones?

The Aldol Reaction: Dehydration

The aldol reaction may not stop at the beta-hydroxy aldehyde, but lose water (dehydration) to form an alpha,beta-unsaturated aldehyde. Dehydration is much faster under acidic conditions, but can happen under basic conditions too.

Acidic Conditions:

Protonation of the alcohol makes it a better leaving group.

Basic Conditions:

Recall that hydrogen bonding makes the hydroxide not such a bad leaving group.

The aldol reaction is reversible. (See Michael Reaction). Try drawing the mechanism for a ‘retro-aldol’. That is, start with a beta-hydroxy aldehyde and end up with two aldehydes. You should be able to do this with acidic or basic conditions. After we discuss the ‘Michael reaction’ determine the retroaldol mechanism again, but this time start with an alpha,beta-unsaturated aldehyde.

Variations on the Aldol Reaction

The aldol reactions also work with other carbonyl groups such as ketones and esters. In these cases the reaction is still called an ‘aldol’ even though the product doesn’t contain an aldehyde.

Q: What structural requirements are there for a molecule to participate in an aldol reaction?