Amphetamine via P2P + Ammonia NaBH4 reductive amination?

[ItsMee]

Hello,

P2P + Methylamine reductive amination with NaBH4 is pretty common, in either wet, or for better yield, dry conditions.

But i never heard of P2P + ammonia reductive amination.

I know that imine formation with ammonia is very water sensitive and difficult.

But isn't it possible to run this reaction in anhydrous conditions to get amphetamine?

For example:

Mixing and stirring P2P and dry ammonia in methanol, ethanol or IPA,
Adding some drying agent, molecular sieves etc. to catch up all water which is produced during imine formation
and then adding NaBH4 for reduction.

Would this be possible, and what yield could be expected?

 

[Ihml]

There’s a video somewhere, I think it was on YouTube, where they did it with Na[BH3(CN)]. You might find it with some digging.

 

[Ihml]

“Synthesis of 2-amino-1-phenylpropane by Reductive Amination of 1-phenyl-2-propanone with NaBH3CN” on youtube.

 

[OrgUnikum]

No matter if NaBH3CN or STAB or NaBH4 plain is used, it only works if you add a stochiometric amount of titanium(IV)isopropoxide. Otherwise almost all or all product will be the di-alkylated compound, Dialkylamphetamie.

 

[Ihml]

Alkyls groups are methyl, ethyl etc… Do you mean that the product would be methylated (or ethylated, etc) twice? If so then why and how would that be?