We have learned that the reactions of aldehydes and ketones with alcohols and amines result in the formation of acetals, imines, and enamines, depending on the structure of the amine:

 

 

These reactions are reversible, and one application of this feature was the use of acetals as protecting groups for aldehydes and ketones:

 

 

The acetal group protects aldehydes and ketones in basic conditions during, for example, LiAlH₄ or NaBH₄ reduction or Grignard reactions, after which it is removed by hydrolysis.

Remember, the hydrolysis is in equilibrium with the alcohol reaction, and to move the process forward, a large excess of water is used.

The question is the mechanism of the hydrolysis of acetals, and that’s what we will be discussing in today’s post.

 

Acetal Hydrolysis Mechanism

The reaction starts by protonation of one of the oxygen atoms, converting the alkoxy group into a good leaving group, which is then kicked out by the other oxygen:

 

 

The resulting oxonium ion is very electrophilic and is attacked by water, forming a hemicacetal after a deprotonation:

 

 

In a similar manner, the second alkoxy group is protonated and expelled by the hydroxyl group, forming a new oxonium ion, which, this time, is a protonated ketone:

 

 

And in the last step, the final product, ketone, is formed by another proton transfer reaction:

 

 

Putting all this together gives us a summary for the acetal hydrolysis mechanism:

 

 

 

Is there an Easier Way To Predict the Products of Hydrolysis?

There are quite a few steps in this reaction, but fortunately, you don’t need to remember all the steps in order to predict the structure of the aldehyde and ketone of an acetal hydrolysis.

Here is the shortcut: draw a line between each oxygen and the carbon to which they are connected.

These are the bonds that are cleaved during the hydrolysis. Each oxygen is part of the  alcohol, and the carbon connected to them is the C=O carbon atom:

 

 

Additional examples of acetal, as well as imine and enamine hydrolysis, are covered in this practice problem set:

 

• Hydrolysis of Acetals, Imines, and Enamines-Practice Problems

 

 Check Also