Mannich reaction

Schematic of the Mannich reaction. Reagents: primary or secondary amine, non-enolizable and enolizable carbonyl compound, acid or base catalyst. Product: beta-amino carbonyl compound (Mannich base).

The Mannich reaction is an organic reaction used to convert a primary or secondary amine and two carbonyl compound (one non-enolizable and one enolizable) to a β-amino carbonyl compound, also known as a Mannich base, using an acid or base catalyst. In the acid catalyzed mechanism both carbonyl compounds get protonated at the oxygen. The enolizable carbonyl compound, which has an α-hydrogen, then gets deprotonated to form an enol intermediate. The non-enolizable carbonyl compound reacts with the amine to form an iminium ion. The enol intermediate then attacks the iminium ion which after deprotonation provides the final Mannich base product.[1]


Mechanism of the Mannich reaction. The Acid catalyzied Mechanism includes proton transfer steps, acid-catalized enol formation, an enolized carbonyl compound and an iminium ion.


Mannich, C.; Krösche, W. Arch. Pharm. Pharm. Med. Chem. 1912, 250, 647–667.