[TheUnassuming]

Hello,
I am trying to synthesize a primary amine (R-CNH2) from a simple aldehyde (R-COH).  I will be reacting aldehyde with ammonia in methanol to form the imine and then reduce it using sodium borohydride or sodium cyanoborohydride.  There is just is one detail I am having a bit of trouble with, the ammonia.  I can not add water to this reaction with out negative consequences, so the NH3 would need to be in a form that does not have water.  My mind automatically jumps to various ammonium products, but I don't know that NH4+ would act in the manner needed to form the imine.  The reason the imine is formed to begin with is the nucleophillic nature of the ammonia.  The only literature I can find/have access to doesn't say anything beyond ammonia... does anyone have any thoughts or ideas?  It has to be a simple enough answer, my mind is just going in circles right now.

[macman104]

Either, you could possibly boil the methanol over?

Or, can you get ammonia gas?

[sjb]

A few ideas, I don't know what else you have in your molecule, so some may not be useful

RCHO -> RCHNHBenzyl, (just the imine), then hydrogenate both the double bond and the benzyl group off? Lots of choice with the initial amine there, and if you want to isolate the secondary to prove you have it you may be lucky with things like PMB amine, which you can oxidatively remove instead?

I seem to recall that primary imines of the form RCH=NH are rather prone to polymerisation - was looking into this a while back for aza-pinacol style couplings.

Can you form an aza-alkene? Sort of like RCH₂CHO -> RCH₂CH(OH)N₃ -> RCH=CHN₃ and reduce that?

S

[lavoisier]

I've recently found a procedure where you mix your carbonyl compound, methanol, 5 equivalents ammonium acetate and something less than 1 equivalent sodium cyanoborohydride, and heat to reflux under dry inert atmosphere.
It works well for my ketone; not sure about aldehydes, but I guess you can try on a small scale and see how it goes.

If you really can't use any hydroxylated solvents, you might try with a solution of ammonia in dioxane (very expensive though).
However, I think your product can't really be *that* sensitive to water, because already the first step of reductive amination produces water.

Using benzyl or PMB... yes, it has been done, but honestly, it's a pain in the ****

[sjb]

Could you form the oxime, and reduce that? RCHO -> RCH=NOH -> RNH₂ ??

[phil81]

Here's a reference for NH₄OAc / NaCNBH₃: J. Med. Chem. 2005, 48, 224. You'll find it on page 234. (Careful, they quench the reaction with acetic acid, releasing HCN!)