Transamination Mannich bases

Acdve methylene compounds ranging in acidity from -keto esters, malonates and nitroalkanes pK = 9-13) to ketones (pATa = 16-20) can be used in the Mannich reaction. The lack of examples using simple unactivated esters (p/iTa = 25) appears to be due to their weaker acidity or to transamination and/or hydrolysis side reactions. Enolizable aldehydes have also been used in certain instances however, side products arising from subsequent aldol condensation of the resulting -amino aldehyde often occur. Best results are achieved with a-branched aldehydes, which produce Mannich bases without enolizable protons. 

Tertiary and quaternary Mannich bases often undergo transamination readily and under mild conditions if the exchange amine is used in excess and the secondary or tertiary amine formed is sufficiently volatile (cf. reviews by Hellmann82,1126). Primary amines can also be prepared in this way, the amine group of the Mannich base being replaced by phthalimide1127 and the product then hydrolysed. 

Mannich bases, transamination with amidines, cyclic 18, 482 suppl. 21 Mannich reaction —, N-heterocyclics by — 21, 798 —, double, N-heterocycles by — 13, 775 suppl. 21 anfi-Markownikoff hydro-halogenation 14, 205 suppl. 21... 

Mannich bases and reactions have found new applications. Preparation of Mannich bases from ar. amines by transamination, transquaternization of quaternized Mannich bases reactions... 

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