Mannich Reaction Alkylation of Enols by Iminium Ions

MANNICH REACTION ALKYLATION OF ENOLS BY IMINIUM IONS 

In the aldol reaction, an enolate ion attacks the carbonyl group of an aldehyde or ketone (Section 18-5) to furnish a j8-hydroxycarbonyl product. A process that is quite analogous is the Mannich reaction. Here, however, it is an enol that functions as the nucleophile and an iminium ion, derived by condensation of a second carbonyl component with an amine, as the substrate. The outcome is a j8-aminocarbonyl product. 

To differentiate the reactivity of the three components of the Mannich reaction, it is usually carried out with (1) a ketone or aldehyde (2) a relatively more reactive aldehyde (often formaldehyde, CH2=0, see Section 17-6) and (3) the amine, aU in an alcohol solvent containing HCl. These conditions give the hydrochloride salt of the product. The free amine, called a Mannich base, can be obtained upon treatment with base. 

we depict only the mechanism that leads to product. You can formulate multiple alternative reactions steps (protonations enol, hemiacetal, and heminaminal formations aldol additions), all of which are reversible dead ends, making the Mannich reaction possible. 

2-Methyl-2-(iV-methyl-aminomethyl)propanal Mannich base 

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