pelnicki
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Separating an alkyl amine from an aryl amino alcohol (eg. methylamine v l-ephedrine)
Would anyone like to comment on an experiment currently underway, or suggest a better way? You can probably guess the exact reaction workup I'm
discussing (yes, I'm talking about hydroxyphenylacetone + methylamine(in excess) -> ephedrine).
L-ephedrine's solubility in water confounds traditional workup methods used after other ketone aminations.
So, given how volatile ephedrine is at high temperatures, steam distilling seems like a lovely way to recover the goods from an ugly witches brew of
amalgamated sludge.
But only some of the excess methylamine is lost to the atmosphere during steam distillation. The rest is hydrophillic similarly to ammonia, and winds
up in your distillate, giving a solution of aqueous methylamine and ephedrine freebase.
My idea to get around this process involves a lengthy reflux prior to any steam distilling. The idea is to drive off the gaseous methylamine from the
solution, without losing any of the rather volatile ephedrine freebase.
My first attempt involves refluxing through a graham condensor, which I thought could be even better than a vigreaux column in terms of allowing
methylamine to escape and forcing steam/condensate interactions through the spirals.
Am I fooling myself? Will I only get the same amount of methylamine liberated as if I simply heated the initial reaction to the vapor temperature at
the top of the condenser (which I am maintaining at ~25 deg. C, since practically zero ephedrine is lost at this temperature).
The answer would be obvious to anyone with a better knowledge re: hydrophillic gases heated in aqueous solutions
So far, it seems that methylamine and methylamine alone (and probably some water vapor with negligible ephedrine) is escaping.
The last thing I want to do is release anhydrous methylamine gas (which I know isn't going to happen in this case), but does venting water vapour
neccessarily carry ephedrine in the steam, even at low temps?
My room temp is ~13degC; escaping vapours ~25degC.
Perhaps a column would have been a better choice. I hate being stupid and having to unintelligently guess what's going to happen. Someone clever
please help. :-)
Love & Kisses,
Pelly
[Edited on 23-7-2006 by pelnicki]
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Nicodem
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I have never in my life seen such a lengthy consideration on how to separate a gas from a liquid. A gass that is furthermore even more soluble in
water than in organic compounds like ephedrine. 
Have you even bothered checking the physical properties of the two compounds in question? If you did you would have realized that the real problem
would be to isolate the mixture of ephedrine and methylamine. Don’t call for problems where there are none, when I’m sure you will have problems
elsewhere.
Edit: And to consider that you have chosen to make a problem out of this when I’m pretty sure steam distillation also carries over other stuff, like
unreacted 1-hydroxy-1-phenylacetone for example. And these might not prefer the aqueous phase like methylamine.
[Edited on 23-7-2006 by Nicodem]
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Organikum
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Actually one does the reductive amination of l-PAC with a slight excess of methylamine 1,2 to 1 or even with equimolar or less then equimolar ratios
if the sterochemistry is to be preserved.
And one extracts the product like any other product just salt it out. Never heard of this?
Steamdistillation is not really an option. Ephedrines don´t distill easily with steam.
/ORG
[Edited on 23-7-2006 by Organikum]
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pelnicki
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Thanks for the input!
D'oh! Yes, silly me, it seemed like a good idea at the time given that ephedrine freebase is rapidly volatile at 100degC.
"Salting it out", yes I have heard of this, thanks Org, does this involve adding solid NaCl (or CaCl2, MgSO4?) to the aqeous post-rxn layer until
saturated, and waiting for the freebase to be liberated (and solved in an organic layer)?
Are there any special tricks to this, and how long does it take for the salt to displace the ephedrine?
Also good was the suggestion to use a smaller molar excess during the amination. I've been using MeOH as a solvent for the reaction and a 1.5X molar
excess of methylamine (from nitromethane). Is there a problem with escaping methylamine, and should the rxn be pressurized?
And one final idiotic ask: Doesn't the organic layer also pick up methylamine, resulting in MeAm.HCl crytstals forming when later gassed?
EDIT: Regarding idiotic ask above^, methylamine prefers water, and won't get 'salted out' as does ephedrine.
PS. What does everyone use when they want to look up chemical properties? I tend to use either the Merck index for pharmaceutical compounds and the
online NIST chem webbook for any other chemical properties. Neither of these seem to be in any way an attempt at a 'complete' or canonical collection
of known compounds and physical data.
What's the best database to consult when you're seeking as much useful data as possible, for any compound?
Thanks for taking the time to read my verbose ramblings.
[Edited on 25-7-2006 by pelnicki]
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