# Reductive amination of phenyl-2-propanone with Sodium Cyanoborohydride (1kg scale)



## William Dampier (Jul 23, 2021)

*Reaction scheme:*​


​
*Synthesis:*
1. A mixture of phenyl-2-propanone (1000 g), ammonium acetate (6000 g), and sodium cyanoborohydride (600 g) in 15 liters of IPA was stirred at room temp for 48 h.
2. The pH of the mixture was maintained at neutrality by dropwise addition of concentrated HCl during the course of the reaction.
3. The reaction mixture was evaporated to dryness to yield a yellow semisolid that was suspended in water (25 ml) and then acidified to pH 1 by slow addition of concentrated HCl.
4. The acidic suspension was washed with methylene chloride, then made basic (pH 10) by the addition of NaOH pellets.
5. The resulting basic aqueous suspension was extracted with methylene chloride.
6. The combined methylene chloride extracts were washed with water, dried over magnesium sulfate, and evaporated to dryness to yield amphetamine as a yellow oil.
7. Dissolve oil in three amounts of acetone.
8. Dropwise sulfuric (or orthophosphoric) acid to pH - 6 when stirring.
9. Put in a freezer for 12 hours.
10. Filtrated and dried.​


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## caesare.robot

what are the yields of this method?


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## btcboss2022

William Dampier said:


> *Reaction scheme:*
> View attachment 1479
> 
> 
> ...



William DampierIs possible to replace sodium cyanoborohydride by NaBH4 in less amount? Sodium cyanoborohydride is a reducing agent weaker than NaBH4 if I'm not wrong.

Thanks.


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## caesare.robot

swim used methanol and nabh4. after vacuum distillation ~50% yielding


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## btcboss2022

caesare.robot said:


> swim used methanol and nabh4. after vacuum distillation ~50% yielding



caesare.robotIn what amounts did it?


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## Jamroz

In second step u mean that pH is changing for 48h when reaction is going and i need to control it? Or maybe its enough to make it neutral one time and it stay at neutral level when reaction is going.


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## caesare.robot (Nov 7, 2022)

btcboss2022 said:


> In what amounts did it?



btcboss202290g p2p.
reaction might be sensetive to water


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## btcboss2022

caesare.robot said:


> 90g p2p.
> reaction might be sensetive to water



caesare.robot90gr of P2P ok and the amounts of NaBH4 and Methanol? Same timing and process as posted?
Thanks.


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## caesare.robot

btcboss2022 said:


> 90gr of P2P ok and the amounts of NaBH4 and Methanol? Same timing and process as posted?
> Thanks.



btcboss202252g NaBH4 added in portions ca. 30min,
2 hours after on stirring 25°C.

while evaporation of methanol from RM a lots of salts are taking of?!? any suggestions.

and what is the point to keep reaction neutral?

swim is thinking about bubbling ammonia into iced and dried methanol and use it straight in reaction? using mollecular sieves? will it higher the yields?


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## caesare.robot

does anyone know the NH3 ratio to P2P in moles?


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## oscar412

caesare.robot said:


> does anyone know the NH3 ratio to P2P in moles?



caesare.robotIt will just be 1 mole NH3 to 1 mole p2p. Stoichiometric Ratio


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