Anhydrous reductive amination in IPA

[Bandil]

In

this

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/meth-nabh4.html) document, labtop describes an reductive amination of P2P using methylamine and borohydride in methanol.

Is the same scheme applicable in IPA? Perhaps the reaction times should be extended a bit?

Comments?

Regards
Bandil

[starlight]

As far as I remember, NaBH4 does not work as well with IPA in this situation. Edit: Although my memory may be incorrect here.

You could always do it wet as in

Post 458857

(Barium: "Improved "wet" reductive alkylation", Novel Discourse)

[Bandil]

Yes, but the whole idea here was to improve the yields of the wet red. amination by using 3A mol. sieves on the wet stuff  

Didnt have any methanol around however. Does the water actually help the reaction?

Regards
Bandil

[Smilaxium]

according to a friend of SWIM who has been making MDMA through what he calls "a cold method". And he didn´t use molecular sieves to get rid of the water. He states that yields are around 75-80%. Besides the IPA (solvent), he uses a methanol solution of methylamine... The only disadvantage of this method is the relatively large amount of boro you should use.

[starlight]

The reaction obviously does work in not-so-wet IPA and the yields are improved over the wet version. Well done to Bandil for trying this out and finding the answer for himself. For the proof, look here:

Post 503533

(Bandil: "Pseudo-"wet"- BH4 amination BH4", Methods Discourse)

[Bandil]

Actually, I have during the past days developed a fondness of doing reductive aminations in dry IPA, instead of methanol. The reaction is so suitably slow, that all the borohydride¹ can be added in one portion. In methanol this will cause a wild volcano reaction.

The reaction (with all the NaBH₄ added in one portion) has been attempted safely at 0.5 mole scale, without any heat / hydrogen problems. Plug the flask loosely with some paper or similar, and let the reaction run overnight. The yields will go through the roof as described earlier.

Notes:
1:
0.5 molar eq. borohydride is quite sufficient for excellent yields. No difference between 1 and 0.5 eq. has been noted.

[ADDkid]

Hey a much easier method which applies to MDA, MDMA, Amphetamine and methamphetamine.  Use Al/Hg, if using P2P Ammonia will give amphetamine, Nitro methane will give you methamphetamine.  With MDA, ammonia is used, and Nitro methane when making MDMA. So far I have read many options, and did plenty of research, and this seems by far the best when dealing with easiness and yield. ADDkid

[Bandil]

Al/Hg and ammonia will give you shitty yields(10-20%) with any ketone.

Other than that, the gigantic amount of work involved in a Al/Hg reduction is not even comparable to this method. borohydride sludge is alot nicer to work with than Al sludge - thats for sure.

But no - Al/Hg is not easier, nor higher yielding than this method!

Regards
Bandil

[XrLeap]

The reaction is so suitably slow, that all the borohydride1 can be added in one portion

Hi Bandil,

SWIM is trying to get his amination working correctly, and would like to get the sam yield as you.
In the above statement, what was the temperature that you encountered? Did it go near to IPA's boiling point?

And, did you just add the pallets/powder into the IPA solution?

What was the largest rxn that you have tried with no problem adding NaBH4 in 1 go? Can 5 mol scale be used and still add the NaBH4 in 1 go?

[armageddon]

Hi!

I think that the reason behind the slow rxn as stated by you:

The reaction is so suitably slow, that all the borohydride¹ can be added in one portion. In methanol this will cause a wild volcano reaction

is the following: the borohydride first needs to react with lower alcohols (MeOH or EtOH) or water to form an intermediate, which then reduces the imine. In this case (with this molarities used) this slowed reaction is of course favorable. But maybe a compromise between faster rxn and still manageable exotherm/H2 evolution could bee found by adding very small amounts of lower alcohols?  

(sorry, can't come up with details for this; it's already very late/early and I'm a little tired by now - but I'm very sure I once read about it somewhere in a different context, but with NaBH4/IPA alone giving low yields, until small amounts of either EtOH/MeOH or water were added, which improved yield w/using same rxm time... was it a thread about nitropropene-nitropropane  maybe? Dunno..)

I'll better get some sleep and maybe check my personal reference collection "tomorrow"/later...

Greetz, A