Chromics Al/Hg

[El_Zorro]

I've been looking over Chromic's peracetic writeup at Rhodiums. 

https://www.thevespiary.org/rhodium/Rhodium/chemistry/peracetic.chromic.html

In it, he's got the sections called "Typical run reductively aminating MDP2P to form MDMA.HCl"  And he says that he adds the HgCl to the Al, and waits 'till he sees a faint bubbling, then adds the methylamine solution along with the MDP2P. 

1. So is this all wholesale, just dumping it in, and adding the condensor?

2. Could yeilds be improved by making the methylamine solution with methanolic or ethanolic NaOH or KOH and MeAm*HCl, then adding the MDP2P dissolved in alcohol, and letting sit over night, maybe chilled, before it's put through the amalgum?  My thoughts are that if someone could get 78% yeild y just dumping everything into the flask that's already got a running amalgum going, without giving the imine any time to form beforehand, could yeilds be drastically improved by taking steps to form the imine completely?  The only other major product of the Al/Hg is MDP2Pol, which is no doubt formed by the ketone being reduced before it has a chance to form the imine.  Am I far off on this?  Has anyone tried to let the imine form separately before they ran the Al/Hg?

[Antibody2]

my understanding was that the imine is not very stable.

[El_Zorro]

please forgive my long-winded post, but i'm up at 1:30 in the morning with nothing to do but ponder this little question.


OK, so the imine might not be very stable, so i guess getting it in as fast as possible would be a good idea.  But in the procedures for the borohydride reduction, the MDP2P is mixed with a methanolic solution of methylamine, and stirred with silica gel.  My understanding was that the silica gel was only there to remove formed water because of the belief that removing water drove the reaction farther to the right.  But then I saw some thoughts posted here that removing the water was not really necessary.  But the procedure does call for forming the imine beforehand, then reducing, and the yeilds are close to quantitative.  The Al/Hg is not all that harsh of a reaction.  It does not leave tar or polymerization afterwards.  Pretty much the only two products are the amine and the alcohol, with the alcohol only being formed because the imine did not fully form.  So just how redily does MDP2P form the imine with methylamine?  and when it does, how stable is it?

Now for a few clarifications on my thoughts on the Al/Hg.  The methylamine solution is normally made as an aqueous solution.  So i'm just asking what everyone's thoughts are on making it in a solution that MDP2P is also soluble in?  And if you used methanolic NaOH or KOH to basify the MeAm*HCl, then you wouldn't have to mess with bubbling dry MeAm gas into anything.  The only thing you'd have to worry about is the NaCl or KCl that would precipitate from the alcohol.  But that has no effect at all on the reaction, so it wouldn't even be worth the trouble to remove.  Then the MDP2P could be added to the solution and sat aside for a length of time in order to let the imine form, then the amalgumation could be started.  And I also read in the borohydride procedure that some literature suggested that cold temps also drove the imine formation forward.  So how hard would it be to set a solution of methanolic MDP2P and MeAm in the freezer overnight, the running the reaction?  Would this help?  Any thoughts?



And I'm sorry for not providing any sources for what I'm saying, but right now I'm just kinda musing.

[GenericVersion]

SWIM would think that the imine would want to be used relativly quickly (less than ~3 or 4 hours perhapsa freezer will work SWIM doesnt know) as far as the water question SWIM will quote from the brightstar writeup


"This reaction actually has two parts. First, there is the ketone -> imine condensation. This reaction reacts the ketone with methyl-amine to form an imine - water is produced as a product. Second, the imine is reduced (Hydrogen is added across the double bond) to the amine. The condensation really needs anhydrous (no water) conditions, and the reduction actually needs water - so there is a fine balance here."

a small amount of H2O helps yields in the final reduction other than that anhydrous is best.

[raffike]

Water is only needed for Al/Hg reduction,for borohydride or catalytic stuff,less water the better.If water is removed constantly during imine formation,imine can't go back to ketone+amine as there's no water for that.

[El_Zorro]

So maybe just adding the MDP2P to a methanolic solution of methylamine, adding silica gel, and stirring overnight, maybe with some form of cooling?  The amount of silica gel would probably have to be higher than the amount used in the borohydride procedures, because if one were to make the methylamine solution with methanolic NaOH and MeAm*HCl, then water is going to be formed anyway.  Then just filter everything out the next morning and run the amalgum.  Would it be worth the extra trouble for only maybe a 10-15% increase in yeild?  Or would it even increase the yeild at all?

[raffike]

How do you run Al/Hg without water?I don't think it will increase yields.

[ja304]

Abacus's method results in 2.5-3.0mol MeNH2 in 1400mL of methanol.

Argox reports success forming the imine with 1.2mol MeNH2 to 1 mol of ketone.
 
I would assume that if you take 4 hours to make MeNH2 via abacus, you could form 2 moles of imine.

Maybe strip some of the methanol (post-imine formation) under reduced pressure and throw that into the Al/Hg flask to start the reaction.

Seems that if one forms the imine first, rather than reacting 1mol of ketone, you could react 2mols.

Or maybe i dont have a clue to what is going and i need to stop posting.

[El_Zorro]

Dammit, that really fucks up the plan.  I forgot that the water formed by the imine formation is what drives the Al/Hg.  So i guess trying to remove the water from a solution of methylamine and MDP2P wouldn't help the reaction.  But i don't really see how letting a solution of MDP2P and methylamine sit in the freezer overnight or for even a few hours would hurt anything.  Maybe I should try it sometime.

[LaBTop]

Post 440288

(Barium: "PTC - imine reduction", Novel Discourse)
Please read the last lines from the Notes also. LT/

[El_Zorro]

That's very interesting.  It looks like they just let the imine form for one hour and then ran the reaction and got 92% yeild.  Not bad.  And they made no effort to remove water formed during the imine formation, either.  That says to me that the imine forms fairly redily, at least up to 90%+ without steps having to be taken to favor the reaction.  And in the notes section he just talks about how they took steps to make the methylamine available to the organic phase so that it could be in the same solution as the ketone, which would make it much easier and faster to react.  That's all I was saying to do with the methanolic solutions of MDP2P and MeAm, just so that they are both dissolved in the same phase, which would greatly increase the reaction rate of the two.

[scram]

"Argox reports success forming the imine with 1.2mol MeNH2 to 1 mol of ketone.

I second this comment. I have to say that when less MeAm was used yields were consistently higher. Even though my data is far from scientific I would guess my ratios were best with 1.33 to 1.66 moles MeAm per mole ketone. I think too much MeAm eats up the al too fast due to it's alkaline nature.