Oxidative alpha-Amination of 4-methylpropiopnenone with Ammonium iodide

[WillD]

Reaction scheme:

Synthesis:
1. NH4I (15 g) was added to a mixture of sodium percarbonate (200 g), 4-methylpropiophenone (100 g), and methylamine (200 ml 40%) in DMF (600 ml) at room temperature.
2. The reaction was stirred at 50 *C 18 hours.
3. The reaction mixture was then allowed to cool to room temperature, dilute water (1500 ml).
4. Extracted with benzene (500 ml).
5. Acidified 5:1 solution conc. HCl in IPA to pH=5.
6. Crystallisation in cold 12 hours and filtered in vacuum, washing cold acetone and dry.

 

[ADATA]

This way directly 4MMC without bromination?
Are there any other alternatives to DMF?
acetone?

 

[G.Patton]

methylamine will react with acetone

 

[ADATA]

Are there any other options besides DMF?

 

[WillD]

DMSO and acetonitrile maybe.

 

[w2x3f5]

I found the original source, it states that DMSO is not suitable as a solvent, DMF, dichloroethane or acetonitrile are used

 

[ADATA]

I will try the 4MMC harvested from this program
How much output can 1KG produce?

 

[WillD]

For some reasons, the reaction poorly scale, start with a small scale

 

[ADATA]

Is 1000G scale possible?

 

[WillD]

Maybe, but start with smaller quantities. In general, the synthesis of the intermediate and its subsequent use is the best option than this synthesis.

 

[karamelosanto]

Hi, I have a few questions about this route.
Methylamine 40% solution is in water or methanol ?
Can benzene be replaced with hexane or DCM or another solvent?
For scale this down like on the range of 10g 4-mpf. Is correct to scale down all the others reagents in the same 10/1 way?
Thanks

 

[G.Patton]

water
yes, you can all of them. Also can use Petroleum ether
dev 10

 

[zyuxo0]

Is this a good procedure to start my adventure with organic chemistry? Or should I start with classic halogenation?

I will do only nano scale. And I want to try because it looks like I can make a lot of experimental cathinones and this turns me on haha

What are the disadvantages of this procedure?

I know these are dumb questions for pros but anyways...

 

[Mellym]

I guess this should work with carbamide peroxide (hydroperite) instead of sodium percarbonate.
Overall this scheme looks quite messy to me..

 

[w2x3f5]

it is most likely better to use pre-prepared n-iodamine in this reaction

 

[w2x3f5]

clarified, this makes no sense, since the reaction follows the path of halogenation and further amination. the reaction does not proceed through iodamine