Leuckart variation

[patrick]

Hello,
Have somebody encountered some sucess using the Leuckart variation synthesis proposed by Psyloxy in Post n° No 61613.
What kind of yield was obtained ?

Patrick

[terbium]

You might want to try reading the FAQ on posts so that you would know how to refer to a post in a way that enables people to easily access it.

Post 61613

(psyloxy: "Re: Leukard scaleable ?", Methods Discourse)

[PolytheneSam]

I wonder how that microwave process would work here with acetic acid. 

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdp2p.leuckart.txt

http://www.geocities.com/dritte123/PSPF.html

[foxy2]

Sam
I have been wondering the same thing.

I was recently thinking of posting a compilation of the microwave Leuckart information in hope of prompting someone to try it.
Foxy
I hate my government, does this mean I'm a terrorist??

[psychokitty]

One idea is to use dimethylformamide as the amide source.  One could then react this with PMPA (para-methoxy-phenyl-acetone; formed by reacting oxone with anethole) to form the intermediate dimethylamide which could then possibly be hydrolyzed in situ to the amine by reacting the amide with a high-boiling alcohol and base (sodium hydroxide?)

One way to do this would be to place in an unmodified microwave oven (domestic) a beaker of water to act as a heat sink.  DIRECTLY INTO this, one would place the reaction vessel.  This way, the microwave power could be set on high.  The water would absorb all of the excess microwave energy while at the same time maintain the reaction temperature at 100 C.  If much of the water evaporates, simply add more.  Although Loopy's original paper indicates 180 C or so as the necessary temperature, I have no doubt that increasing the reaction from 20 minutes to 1 to 2 hours might bypass this complication.

This reaction has great potential.

[psychokitty]

By DIRECTLY INTO THIS, I mean that the reaction vessel is sitting right smack in the middle of the heat sink so that it is surrounded by water.

[Ritter]

What's up Psychokitty?

I may be wrong but I believe the product from the Leuckart reaction with DMF and ketone would be the N,N-Dimethylamine.  As far as I remember, no amide forms with DMF directly resulting in the tertiary amine.

[patrick]

Do you mean that this procedure will simply result in a complete failure on MDA synthesis?

[terbium]

Do you mean that this procedure will simply result in a complete failure on MDA synthesis?
It depends on what procedure you are talking about - one using formamide or one using dimethylformamide.

[patrick]

It depends on what procedure you are talking about - one using formamide or one using dimethylformamide.
[/blue]
Formamide.

[terbium]

Yes, formamide will work to produce MDA.

[patrick]

Why do all the people prefer to deal with NaBh3CN. It seems that sodium cyano create some nasty cyanide acide and that the yield with this kind of synthesis is approx. the same as with the modified Leuckart (according to TSII). This modified Leuckart seems to be much quicker and doesnt generate any strongly toxical products.

[terbium]

The yield for the Leuckart is the question. I am not convinced that there are any reliable reports of yields better than 30-40%. My yields when I used the Leuckart to make methamphetamine were in the 30-40% range.

[psychokitty]

Ritter:  You may be right.  I'll have to double-check that one. 

The only reason I suggested using dimethylformamide is just to practice the reaction.  Formamide is rather hard to get for most bees, unless they make it themselves.

[sunlight]

I used Leuckart for amphetamine, and yields were low as well, around 30 %, sometimes a bit more.

[patrick]

Can somebody confirm that acetic acide will be a nice substitut to formic acid in this synthesis. I think that the original paper makes use of formic acid (obtained in-situ from formamide).

[terbium]

Can somebody confirm that acetic acide will be a nice substitut to formic acid in this synthesis.
I can disconfirm this. Acetic acid cannot replace formic acid in the Leuckart reaction.

[twodogs]

In US patent 3852352 the authors conduct a number of Leuckart reactions and in Example 6 react acetamide,formic acid and ketone instead of formamide to get the acyl derivative which is then hydolysed to the amine. They claim 64% yield based on ketone.