Which Reductive Amination Would You Choose....

[Bwiti]

What's up folks!? Before I ask this question, I want to let you know that I don't really care if a psychedelic substituted compound is an amphetamine or a methylamphetamine; I love them either way.. With that in mind, I have a question about reductive amination.. In my dreams, I'm trying to decide which reductive amination I should use on a methylenedioxyphenylacetone; The Ammonium Chloride/Titanium(IV)Isopropoxide/Sodium Borohydride process at

https://www.thevespiary.org/rhodium/Rhodium/chemistry/redamin.titanium.ammonia.html

, or the Al/Hg done with methylamine? I'm very familiar with the Al/Hg, but that Titanium(IV)Isopropoxide reductive amination sounds sweet, because only ammonium chloride is required, and anything that saves me from the time put into making methylamine is cool. Anyone have experience with that? Peace!

[Rhodium]

It depends on your resources, if you can aquire Titanium(IV)Isopropoxide/Sodium Borohydride, then by all means use that method, as it uses less amine (nice if you are going the methylamine route), it can use any amine (imperative for MDA) and it also runs cooler, which means no fumes. It also is nicer to use on a small scale (<5g). On the other hand, the Al/Hg is cheaper and more OTC.

[SPISSHAK]

Like the ones barium and sunlight posted, SWIM is working on a CTH with Potassium Formate as the hydrogen source to reduce an imine swim will tell you how it goes when swim gets all the materials.

[Bwiti]

Thanks for the input, folks.

[roger2003]

Reductive Amination with good yield:

Patent DE865599

:

[Rhodium]

Yes, but they are alkylating amphetamine with acetone and L-phenylacetylcarbinol (L-PAC) with cyclohexylamine, and the intermediate imines are much more stable than the ones gotten from phenyl-2-propanones and NH₄Cl or CH₃NH₃Cl. You can see that the yield directly falls to sixty-something when using formaldehyde and a secondary amine. In addition to that they make use of Pt/H₂ as reducing system, and that is much more cumbersome than either Al/Hg or NaBH₄.

[roger2003]

Yes, but i think, the idea of the patent was to use the amine as hydrochloride

[Rhodium]

That is possible both in the Ti(iPrO)₄/NaBH₄ and Al/Hg reductive aminations too, you simply add one equivalent of base to deprotonate the salt.

[Bwiti]

I seem to remember a reference to increasing yields for the Al/Hg reductive amination by putting the reaction under pressure? Anyone know what the hell I'm talking about? Maybe a push-pull type of device could be rigged to it.
  Just like with borohydrides, I'd prefer to store titanium(IV)isopropoxide in a freezer, surrounded by a larger container to keep out moisture.. Besides that, the only other downside to using Ti(iPrO)4/NaBH4 is that you need triethylamine, but that isn't watched..

  Btw, I found a patent that involves Ti(iPrO)4/NaBH4;

Patent US2001031498

"Various articles from Bhattacharyya et al. (J. Org. Chem., 1995, 60, pp. 4928-4929; Synlett, 1995, pp. 1079-1080; J. Chem. Soc., Perkin Trans. 1, 1998, pp. 2527-2531) have disclosed the process below for preparing amines from ketones or aldehydes, blah, blah"

[Acme]

One would think that PtO2 (Adam's Catalyst) would hypothetically work marvelously, with methylamine(g) (condensed to a liquid a suitably low temp) in MeOH (1/1/1 v/v/v) at 40 psi H2 for 1 hour

[Bwiti]

The thing that I'm not clear on is, after ammonium hydroxide's added to quench the Ti(iPrO)4/NaBH4 reaction mixture, can one just extract out the product amine, or does that triethylamine have to be distilled out first?