We said that a solution of acetaldehyde in methanol contains a new compound: a hemiacetal. We’ve also said that the rate of formation of hemiacetals is increased by adding an acid (or a base) catalyst to the alcohol plus aldehyde mixture. But, if we add catalytic acid to our acetal dehyde–methanol mixture, we find not only that the rate of reaction of the acetaldehyde with the methanol increases, but also that a different product is formed. This product is an acetal; the hemiacetal is half-way there.

In the presence of acid (but not base!) hemiacetals can undergo an elimination reaction (different from the one that just gives back aldehyde plus alcohol), losing the oxygen atom that once belonged to the parent aldehyde’s carbonyl group.

The stages are:

1-Protonation of the hydroxyl group of the hemiacetal.

2-Loss of water by elimination. This elimination leads to an unstable and highly reactive oxonium ion.

3-Addition of methanol to the oxonium ion (breaking the π bond and not the σ bond, of course).

4-Loss of a proton to give the acetal.

Oxonium ions

Oxonium ions have three bonds to a positively charged oxygen atom. All three bonds can be σ bonds, as in H3O+ or Meerwein’s salt, trimethyl oxonium fluoroborate, a stable (though reactive) alkylating agent, or one bond can be a π bond as in the acetal intermediate. The term ‘oxonium ion’ describes either of these structures. They are like alkylated ethers or O-alkylated carbonyl compounds.

Just as protonated carbonyl groups are much more electrophilic than unprotonated ones, these oxonium ions are powerful electrophiles. They can react rapidly with a second molecule of alcohol to form the new, stable compounds known as acetals. An oxonium ion was also an intermediate in the formation of hemiacetals in acid solution. Before reading any further, it would be worthwhile to write out the whole mechanism of acetal formation from aldehyde or ketone plus alcohol through the hemiacetal to the acetal, preferably without looking at the fragments of mechanism above or the answer overleaf.

● Formation of acetals and hemiacetals

Hemiacetal formation is catalysed by acid or base, but acetal formation is possible only with an acid catalyst because an OH group must be made into a good leaving group.

The mechanism is the most complex you have met and it will help you to recall it if you see it in two halves, each very similar to the other. The reaction starts with a protonation on car bonyl oxygen and addition of an alcohol to the C=O π bond. When you get to the temporary haven of the hemiacetal, you start again with protonation of that same oxygen then lose the OH group by breaking what was the C=O σ bond to form an oxonium ion. Each half goes through an oxonium ion and the alcohol adds to each oxonium ion. The last step in the for mation of both the acetal and the hemiacetal is the loss of a proton from the recently added alcohol. From your complete mechanism you should also be able to verify that acetal forma tion is indeed catalytic in acid.

●Remember the oxonium ion!

When you wrote out your mechanism for acetal formation, we hope you didn’t miss out the oxonium ion! It’s easy to do so, but the mechanism most definitely does not go via a direct displacement of water by alcohol.

If you wonder how we know this, consult a specialized book on organic reaction mechanisms. After you have read Chapter 15 in this book, you will be able to spot that this substitution step goes via an S_N1 and not an S_N2 mechanism.

مواضيع ذات صلة

Amines react with carbonyl compounds

Modifying reactivity using acetals

Cyclic acetals are more stable than acyclic acetals

Acetals hydrolyse only in the presence of acid

Amines from imines: reductive amination

Making acetals

Acid or base catalysts increase the rate of equilibration of hemiacetals with their aldehyde and alcohol parents

Aldehydes can react with alcohols to form hemiacetals

Making the products less reactive

Making the starting materials more reactive

A bit of shorthand

Making alcohols instead of ketones