[foxthreefour]

When using sodium cyanoborohydride for reductive amination, does water in the the methanol substrate affect formation of the imine?

I’m performing the reaction at a ph of ~6 for 48hrs in MeOH and workup is consistently recovering starting material with no reaction taking place.

[rolnor]

It is impossible to comment this if you dont give details, are you making a primary or secondary amine etc.

[rolnor]

It seems you need pH 7-10?

https://en.wikipedia.org/wiki/Sodium_cyanoborohydride

[hollytara]

Depends on the imine structure as well. 

Aromatic imines can be formed in water.  But all aliphatic hydrolyze readily.  So if you have a lot of water and aliphatic structures you will shift the equilibrium and have a lower concentration of imine and therefore slower reaction.

[rolnor]

I think if you have the imine in a equilibrium you will reduce it with NaBH3CN, you dont need to shift it completely.

[foxthreefour]

The compound is cyclic, is the timing of the reductive agent addition important here? I’ve seen written examples at ph 7-10, 6 and 5-7. My understanding is that at lower ph the reduction will occur without substitution.

[hollytara]

Can you test it at different pHs small scale?