Reductive amination

Reductive amination, also called reductive alkylation, is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde.

Mechanism

The amine first reacts with the carbonyl group to form a hemiaminal species, which subsequently loses one molecule of water in a reversible manner by alkylimino-de-oxo-bisubstitution, to form the imine. The equilibrium between aldehyde/ketone and imine can be shifted toward imine formation by removal of the formed water through physical or chemical means. This intermediate imine can then be isolated and reduced with a suitable reducing agent (e.g., sodium borohydride). This method is sometimes called indirect reductive amination.

In a separate approach, imine formation and reduction can occur sequentially in one pot. This approach, known as direct reductive amination, employs reducing agents that are more reactive toward protonated imines than towards the ketone/aldehyde precursors. These hydride reagents also must tolerate moderately acidic conditions. Typical reagents that meet these criteria include sodium cyanoborohydride and sodium triacetoxyborohydride.

See also

• Leuckart reaction

References

Relevant Sciencemadness threads

• Conditions for reductive amination