The Hive > Serious Chemistry

CTH compilation, questions, future directions

<< < (2/5) > >>

IMO a more intelligent way would bee to prepare your methylammonium formate without any Cl- or K+ ions involved, i.e. bubbling CH3NH2 into MeOH/H2O containing the correct amount HCOOH, or using an aeqous methylamine solution to neutralize a HCOOH/MeOH solution (maybe methanolic methylamine to aequous formic acid, even easier??), then bring back to room temp., add the ketone and catalyst and stir (at moderate speed, but with big stirbar) at 18°C for 48 hours. Use a fumehood (or vent the methylamine gas to the outside with a hose, and place the flask in such a position that it won't be warmed up by anything - placing it on a small mag.stirrer situated on a bookshelf is perfect...  :) ). Nothing else.

And please don't use IPA. It becomes reduced by the Pd/C and solvent proportions change. More percentual water will be present after a while, and this isn't good... just use MeOH. It strangely seems to be the only acceptable alcoholic solvent for this purpose.


Interesting about the IPA.  She was putting it in just incase it might donate protons as is the case with some other CTH versions. 

And yes, methanolic or ethanolic methylamine would bee the choice mainly for simplicity's sake (and beecause the salt supply is dwindling but the gas is plentiful.  Since you say MeOH and not EtOH, ok then, but I'm all for the K+ ions. Half methylamine formate, half potassium formate.

Indole: Why do you think the potassium and chloride ions disturbs the reaction? And no, IPA is not, to my experience anyway, acting as a hydrogen donor here. I have performed many CTH's using IPA and have never noticed any acetone during the removal of the solvent. Do you base your comments on experience or asre you just guessing?

Dopey: I would suggest to try to add formic acid dropwise to the pregenerated imine. Add 2 eq methylamine to your ketone of choice, add the catalyst and then start to add the formic acid dropwise. Check the reaction progress with TLC.

This way a excess methylamine is always present possibly preventing the formed amine to react with any ketone which may form from the hydrolysis of the imine. Doing it this way I don't think the water present from a ordinary 40% aq methylamine solution will cause any problems. Of you could of course make the methylamine in situ from methylamine chloride and KOH in MeOH to reduce the water content even further. Just a suggestion.

I could imagine that
a) potassium or chlorine ions *could* affect the catalyst reactivity in some way.. (poisoning or maybe even positive effects?)
b) if the acid is added to the ketone/imine/amine, "pockets" of acid could form due to insufficient mixing or too fast addition rate, resulting in temporary local overacidification. Not favorable. Surely nothing to bother with, but can be easily avoided by premixing amine and acid, mixing well (as Dope_amine said, one hour for paranoid bees  :) ) and then adding the ketone, followed by the catalyst.

About the water content: I don't know if reducing the amount of H2O is favorable; think 9:1 MeOH/H2O is the optimal proportion for this kind of red. amination with HCOOH... And I once read about a CTH using solely IPA as the hydrogen donor; but never about MeOH becoming reduced by Pd/C. And I know that this kind of reductive amination doesn't proceed through dehydrating the hemiaminal C(OH)-NHCH3 to the imine C=N-CH3 followed by hydrogen transfer to give amine C-NHCH3, but rather direct reduction of the hemiaminal to the amine being complexed with Pd and making some kind of hydrolysis necessary. With such amounts of water present, the imine formation is greatly disfavoured, in contrast to the following: the palladium(0) inserts into the formate ion, becomes oxidized to Pd(2) and causes a proton to be given off, which in turn causes dehydration of the hemiaminal and the formation of a H-Pd(II)amine complex with CO2 evolution. In easier words: the Pd destroys the formate moiety, and this initiates the reaction and drives it forward. The imine isn't formed by dehydration through water removal/absence alone but rather through the oxidative insertion of Pd into formate. Which happens favorably under slightly basic aequous conditions, as depicted in the article below... :)

Heterogenous Catalytic Transfer Hydrogenation and Its Relation to Other Methods for Reduction of Organic Compounds
(Robert A.W. Johnstone, Anna H. Wilby, Ian D. Entwistle)
Chemical Reviews 85 (1985), 129-170

EDIT: Of course uploading articles being already present is redundant; my fault, sorry. I have changed the link to the file being already present and have deleted the newer one...


indole_amine: It is completely unnecessary for you to upload articles already posted here - this one could for example be found in Post 455063 (Rhodium: "The Discovery of Catalytic Transfer Hydrogenation", Tryptamine Chemistry)


[0] Message Index

[#] Next page

[*] Previous page

Go to full version