Mannich reaction

[2][3] The Mannich reaction starts with the nucleophilic addition of an amine to a carbonyl group followed by dehydration to the Schiff base.

[4]: 140 In the Mannich reaction, primary or secondary amines or ammonia react with formaldehyde to form a Schiff base.

The mechanism of the Mannich reaction starts with the formation of an iminium ion from the amine and formaldehyde.

[4]: 140 The compound with the carbonyl functional group (in this case a ketone) will tautomerize to the enol form, after which it attacks the iminium ion.

On methyl ketones, the enolization and the Mannich addition can occur twice, followed by an β-elimination to yield β-amino enone derivatives.

Scheme 1 – Ammonia or an amine reacts with formaldehyde and an alpha acidic proton of a carbonyl compound to a beta amino carbonyl compound.
Scheme 1 – Ammonia or an amine reacts with formaldehyde and an alpha acidic proton of a carbonyl compound to a beta amino carbonyl compound.
Scheme 4. Asymmetric Mannich reactions ref. Cordova (2002) and Mitsumori (2006)
Scheme 4. Asymmetric Mannich reactions ref. Cordova (2002) and Mitsumori (2006)