stoichiometric_steve
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amine salt formation in ketones as solvents
in several procedures laying out the making of amine salts, especially with phosphoric acid, acetone is used as the solvent for freebase amines.
i was under the impression that acetone easily forms an imine with amines, which is even more stable when protonated.
isnt it thus likely that not the ammonium salt, but an iminium salt is isolated when using ketones as solvents?
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Boomer
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You mean the procedures where you dissolve the amine freebase in acetone, then add alcoholic acid solution (e.g. 1:5 conc. H2SO4:IPA) till either
neutral or till precipitation stops. I guess acetone is used due to lower solubility of the fromed salts in it compared to alcohols, and I doubt an
imine forms *that* easily if you keep it cold.
Silly me once tried to use acetone *only*. The freebase was waiting in one pot, already dissolved in acetone, while I tried to prepare the sulfuric
solution by mixing acetone and conc H2SO4. It got hot and yellow quite fast. Congrats stupid, you just invented mesitylene!
OTOH it *does* work also with the FB in toluene, then adding the acid in alcohol. Easier than gassing, good for 'non-gassable' acids, and if you
*have* to make the hydrochloride, you can simply buy alcoholic HCl.
Personally, when people insist on the HCl salt even though it's more hygroscopic, I suspect not chemical interest but a smoking habbit... 
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stoichiometric_steve
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well thanks for your reply, but it wasnt really helpful. i already knew that acetone is a no-no with sulfuric acid. anyways, i was talking about
phosphoric acid and acetone in particular.
the formation of an imine is much more likely when keeping the solution cold - ever mixed benzaldehyde with methylamine? the reaction is exothermic
and thus favored if the generated heat is dissipated.
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Sergei_Eisenstein
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When you want to make a salt of an amine, you usually create the salt in a solvent that can dissolve it. Afterwards, you decrease the solubility by
adding a second solvent in which the salt is insoluble. You should not choose solvents which can react with your product, and as such should not
believe everything they put in the patent literature. In case the imine formation is a disturbing factor, the contaminant can still be washed out with
e.g. ether.
damnant quod non intelligunt
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contrived
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continuing this thread in a slightly different direction ...
suppose the amine is a heterocylce made from say cyclohexyldiamine with phenethyl at one end and phenyl or pyridyl at the other...its made in
suspension that becomes cloudier as the reaction completes ..
the published procedure says to dilute with chlorinated solvent wash with base; wash with water .. then wash with 2N HCl solution .. save the organic
layer, extract the aqueous layer with another aliquot of chlorinated solvent .. combine the organic layers and flash off the solvent collecting the
HCl salt.
I did and no cigar .. I suspect the second alkylation reaction as not having gone as planned but I wanted to ask, is the final workup right?
The Sergei guy seems to be pretty hip...
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stoichiometric_steve
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| Quote: | | Originally posted by contrived .. then wash with 2N HCl solution .. |
this is where you lost your product. byebye!
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contrived
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Yeah, I hear that. Damned thing is I've read this approach with other syns. The HCl is made by washing the solution with the base in it with 2N HCl.
An alternate is supposed to be wash the mixture with base and water and then strip down the solvent and treat the residues with con HCL. These two
are for the cases where the HCl salt is totally soluble in the organic side. I wonder if there are other approaches to this situation.
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stoichiometric_steve
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i think you should read up on acid-base extraction. the reason why you failed is easily explained by chemical common sense. there are numerous
suggestions about proper salt formation on this board - hit SEARCH to continue.
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