PPA from LPAC

[Chewbacca]

could an NH3 soln substitute CH3NH2 in the reductive amination of l-phenylacetylcarbinol via Ag/Hg to ephdrine to produce phenylpropalonamine instead?

[Novice]

No, ammonia sucks for reductive aminations.

[Chewbacca]

Damn, how irritating- not that i doubt your response, but would you mind explaining why this cannot be achieved considering phenylacetone can be reductively aminated with ammonia to yield non-methylated amphetamine?

do PPA and ephedrine differ more so in molecular structure than a methyl group attatched to the amine group?

thanks

[foxy2]

If I were to attemp this, I would go the oxime route.  See MDA synth's @ Rhodium.

The reductive amination is the boring part, lets hear about how the L-PAC is successfully made.

[Novice]

Generally speaking ammonia is an inadequate nucleophile for aminations, the yield would be low, and it gives rise to byproducts in form of secondary- and tertiary amines. It CAN be used but is often avoided.

From Advanced Organic Chemistry, 4th ed. p. 899, on reductive amination: "When the reagent is ammonia, it is possible for the initial product to react again and for this product to react again, so that secondary and tertiary amines are usually obtained as side products."

Of course you can prevent it by using a large excess of ammonia, but there would still be the problem of ammonias lousy properties as a nucleophile.

I would employ the Leuckart reaction if I was going for PPA from L-PAC, but that's just me.

[Organikum]

Look here:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/alhg-pressure.txt

and read at the end the translation of the french patent, where it is told:

It's already known that reducing hydroxyketones or polycarbonylic compounds
with activated aluminum and ammmonia (derivates) leads to formation of the
corresponding aminoalcohols. This reaction is favored because of the fact that
hydroxyketones and polycarbonyls are apt to form relatively stable imines.

And l-PAC is the hydroxyphenylacetone and norephedrine is the corresponding aminoalcohol.

I would suggest to use the procedure as described in the patent above but to use an about 1 to 3,5 molar ratio of l-PAC to ammonia. An advantage of the Al/Hg red. amination is that the raw ether extract from the fermentation can be used without any further purification, "as is". The reaction conditions and the superior properties of hydroxyketones in imine formation will compense for the drawbacks ammonia has as reagent in this kind of reactions.
What wont work with MDP2P or P2P might very well work for l-PAC.

Though this is just my opinion on this.
Not more.
Not less.

take it or leave it.
 ORG


A lil´ -OH group, have or not have, may actually change the properties of compounds fairly, dont we have a whole forum which is just about this......?

[Chewbacca]

Many thanks for your contributions guys, I was actually about to consult you Org regarding this procedure, I guess you picked up on my thought wavelength before I could log in

Novice, SWIC was intent on performing a Leuckart, but he figured that NH3 being more readily avaliable than formamide, that the NH3 route was worth considering.

I'm assuming that a 10% aqueous ammonia solution is inapropriate under these circumstances and it would be more viable producing a concentrated (30$?) NH3/CH3CH2OH solution from NH4 salt + base...

any links to "activated aluminium" preparations including patents would bee greatly appreciated!

[Organikum]

"activated aluminium" is Al/Hg - all on this is covered on Rhodiums page.

Ammonia is easily driven out of an aqueous (28%) solution by gentle heating. If done slowly, bubbling the ammonia into cold alcohol you will get what you need - NH3 in alcohol. The ammonia is not dry of course but as water is needed anyways in this reaction the small amounts driven over with the NH3 wont hurt. This is no BIRCH.   .
Cant get much easier. As a large molar excess of ammmonia is to be used it is not necessary to determine the exact amount of NH3 in solution - 3,5 fold molar excess or more.

[Novice]

Well what do you know - way to go Organikum :-)

If you were to perform a Leuckart you'd only have to make some ammonium formate, IIRC it gives even better yields than with formamid.

https://www.thevespiary.org/rhodium/Rhodium/pdf/leuckart.pdf

[Organikum]

I remember the Leuckard is somehow high on temperatures. This will not be appreciated by the l-PAC I guess, it is told to be a compound more favoring lower temperatures, thats why a real good vacuum is needed for distillation and also then some l-PAC will be lost I guess.
Stereospecifity will be lost I guess, razemisation, also this is not important if 4-MAR is the desired endresult.
Its worth a try of course, nobody knows by now how and if l-PAC will stand the conditions of the Leuckard.