Specific solvent issues with Reductive Amination/Alkylation
A recent review on the reductive amination of aldehydes revealed that many reactions were run in dichloromethane, 1,2-dichloroethane, CHCl3 and DMF. The authors demonstrate that many of these reductive aminations could be run in much more environmentally acceptable solvents such as EtOAc. In particular those utilising reagents like STAB.
Alcohols are generally regarded as one of the greenest solvent classes but caution needs to be exercised if running a reductive amination with H2 and a metal catalyst in a neat or mixed alcohol solvent. More reactive primary and secondary alcohols can undergo oxidation on the catalyst surface and generate aldehydes/ketones which can then take part in the reductive amination reaction generating undesired alkyl amine impurities, reducing yield and complicating product isolation.