Mannich reaction: practice and mechanism
Formaldehyde and dimethylamine form an iminium ion. The ketone enol attacks it: a CH₂–N(CH₃)₂ group is then attached to the α-carbon (Mannich base, β-amino ketone).
Example
Formaldehyde and the secondary amine form an iminium ion. The enol of the ketone attacks it, giving a β-amino carbonyl compound (Mannich base). A CH₂–NR₂ group is attached to the α carbon.
Mechanism step by step
- 1
Formaldehyde and dimethylamine form an iminium ion (CH₂=N⁺(CH₃)₂) under acid.
- 2
The ketone is partly present as the enol; the enol attacks the iminium carbon.
- 3
Deprotonation gives the Mannich base, a β-amino ketone.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Typical mistakes
Often confused with: Aldol addition · Enamine formation
Frequently asked questions
Why formaldehyde?
It is very reactive and has no α-H, so it cannot form its own enol. The iminium ion is a better electrophile than the ketone.
What are Mannich bases good for?
After methylation and elimination of the amine they give α,β-unsaturated ketones (e.g. for Michael additions). Many alkaloids are biosynthesised similarly.