Acetal hydrolysis: practice and mechanism
Acetals are stable to base but are cleaved in aqueous acid. The original ketone or aldehyde and the diol (e.g. ethylene glycol) are released.
Example
Acetals are stable in base but cleaved by aqueous acid, giving back the carbonyl compound and the alcohol (here ethylene glycol). This is how the protecting group is removed at the end of a synthesis.
Mechanism step by step
- 1
The acid protonates one acetal oxygen; the C–O bond breaks and an oxocarbenium ion forms.
- 2
Water attacks the cation; after deprotonation a hemiacetal forms.
- 3
The second O is protonated and released: the carbonyl group and the diol are free again.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Background
Conditions
Acetals are cleaved with aqueous acid, for example dilute HCl, aqueous acetic acid or p-toluenesulfonic acid in acetone/water. Plenty of water shifts the equilibrium back to the aldehyde or ketone and the alcohol or diol.
Acetals as protecting groups
Acetals survive bases, nucleophiles, Grignard reagents and hydrides, but not acid. So aldehydes and ketones are protected as acetals (often with ethylene glycol), the reaction is done at the other end of the molecule, and the acetal is removed with acid at the end.
Glycosides
Glycosidic bonds in carbohydrates are acetals too. Starch and sucrose are therefore split into their sugars by acid (or enzymes) but are fairly stable to bases.
Typical mistakes
- The hydrate (two OH on the same carbon) is unstable and loses water at once. The final product has a C=O group.
- No alcohol forms: the carbonyl carbon is not reduced, the acetal is only hydrolysed. The ketone or aldehyde comes back.
- The ring does not open to an ether. Both C–O bonds to the acetal carbon are cleaved and the carbon becomes a carbonyl group again.
Often confused with: Acetal formation (protecting group)
Frequently asked questions
Why form and cleave acetals?
As a protecting group: the acetal survives bases, Grignard reagents and LiAlH₄. Afterwards dilute acid cleaves it and returns the carbonyl group.
How do you steer formation versus cleavage?
It is an equilibrium. Removing water (Dean–Stark) drives formation; plenty of water drives cleavage.