p2p to amphetamine?

[Grignard]

What would be the the best method for the formation of amphetamine (not meth) from p2p? I have tried the utfse but i dont manage to get good result. Higest yielding method? would Al/Hg/NH3 work on p2p, and what is the expected yield from this reaction?

[Osmium]

> Higest yielding method?

H2/NH3/Ni high pressure catalytic hydrogenation. Yields should be around 85%.

> would Al/Hg/NH3 work on p2p,

Poorly.

>and what is the expected yield from this reaction?

20% tops. Probably less.

[Grignard]

Thank you.. do you got a link to a procedure on that hydrogenation? vould 10% Pt on C work?

[Bandil]

I'd rather go for P2P + hydroxylamine -> oxime. The oxime is easily formed if you have pure enough P2P. The oxime can be reduced in high yields to amphetamine using the standard Al[Hg] reducion method.

How come you want to make plain amphetamine anyway? (just curious)

Regards
Bandil

[Lego]

Why not prepare the oxime and then reduce it with zinc and ammonium chloride?

Post 477266 (missing)

(Lego: "Reduction of oximes with zinc/ammonium formate", Novel Discourse)
This does not need toxic mercury salts and less solvent


All you need for this is OTC, except the P2P   .

[stratosphere]

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mda.nabh3cn.html

discusses cyanoborohydride route to mda (towards bottom of article). would presumably be the same for non-meth-amp.
unfortunatly i did not see the reported yield anywhere on there.

[WizardX]

Don't forget the Leuckart reaction. 

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0503

[stratosphere]

here is an article about a chirally selective reductive amination for S-fenfluramine

Post 339141

(Rhodium: "Revolutionary novel subst. amphetamine synthesis!", Novel Discourse):
its some rather heavy reading, im not 100% it will be applicable to your desired product, plus im doubtful that its clandestine friendly (i.e. may require alot of hard to get chems) but if possible a chirally selective reaction would assumably be what you want, as d-amp is most likely what your after.

what would really be wonderful is a biosynthetic (and hence most likely chiral) method of reductive amination, there must be some friendly bacteria or plant enzyme out there that would do our dirty work for us, this is the only article that came up when I ran "biosynthetic reductive amination" through TFSE.

Post 187244

(Teonanacatl: "Re: Biosynthetic Pathway", Serious Chemistry)

[callen]

[dioulasso]

This red. amination could also be considered:

Post 435995

(gabd: "Patent  FR971429", Chemistry Discourse)

Post 470154

(Antoncho: "Direct Zn-Ni amination of ketones in 70% yield", Novel Discourse)


But indeed the most established way is through oxime formation and subsequent reduction (plenty of methods).

And also the Leuckart:
1. The above mentioned conventional one w/ Formamide
2.

Post 302161 (missing)

(Antoncho: "Leuckart with 92%+ overall yield", Methods Discourse)
w/ Ammonium formate
3.

Post 326428 (missing)

(zealot: "Äàëüíåéøåå óëó÷øåíèå ðåàêöèè Ëåéêàðòà-zealot’a", Russian HyperLab)
a variation of the previous

[armageddon]

Hi!

There are MANY possibilities starting from P2P, as already said - here are a few more routes:

The cheap ones: make the oxime with NH2OH, reduce with zinc/NH4Cl (or a simple ammonium formate leuckart of course)

The more stylish ones: React P2P with borohydride/NH3... or do a NH3/formic CTH with Pd/C...
(maybe reduce P2NP with borohydride, then aminate nitropropane with Pd/C and KCOOH)

...or hydrogenate with H2/NH3 over RaNi...

..use LiAlH4...


...maybe read

Post 499607

(armageddon: "different routes starting from nitropropenes", Methods Discourse)...


Greetz A