June 18, 2021, 11:23:42 PM
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Topic: Hydrochloride Salt Deprotonation  (Read 325 times)

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Offline DoubleDisplacement

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Hydrochloride Salt Deprotonation
« on: May 11, 2021, 02:51:22 PM »
Hi all. Thanks for taking the time to read my post.

I have a methyl ester hydrochloride salt for use in a condensation reaction, but I need the free ester for the reaction instead of the salt. Typical deprotonation with an aqueous base is not suitable in this case as the ester is rapidly hydrolyzed by water. The ester salt is soluble in organic solvents, and attempts at bubbling dry NH3 gas into the solution seems to take a long time and provides incomplete conversion. I've also tried deprotonating with activated zinc with limited success (also seems to take significantly longer than literature).

Does anyone have any ideas on how I could approach/tackle this issue? Perhaps suggestions for an anhydrous acid form like tosic acid? Or even a strong organic base like DABCO or DBU? For reference, the ester in question in methyl l-prolinate. Thanks again for your help.

Offline Orcio_Dojek

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Re: Hydrochloride Salt Deprotonation
« Reply #1 on: May 11, 2021, 03:24:24 PM »
Maybe aluminium powder will be stronger reductant.

Offline Babcock_Hall

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Re: Hydrochloride Salt Deprotonation
« Reply #2 on: May 11, 2021, 08:23:40 PM »
Has anyone tried potassium tert-butoxide?  It's just a thought off the top of my head, and one would have one equivalent of KCl.

Offline Orcio_Dojek

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Re: Hydrochloride Salt Deprotonation
« Reply #3 on: May 12, 2021, 08:55:18 AM »
@Babcock_Hall
Neutralisation with KOC(CH3)3 will yield KCl and water and "ester is rapidly hydrolyzed by water".

Offline Babcock_Hall

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Re: Hydrochloride Salt Deprotonation
« Reply #4 on: May 12, 2021, 09:00:36 AM »
I don't see where the water would come from; it looks as if one mole of tert-butanol would be produced.  There are techniques to desalt amino acids, although I am not sure whether or not they are applicable here.  As for the question of rapid hydrolysis, I suspect that it depends on pH.

Offline Orcio_Dojek

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Re: Hydrochloride Salt Deprotonation
« Reply #5 on: May 12, 2021, 09:19:45 AM »
Right, I meant that (CH3)3COH can destroy the ester same as water will do.

Offline DoubleDisplacement

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Re: Hydrochloride Salt Deprotonation
« Reply #6 on: May 12, 2021, 02:27:32 PM »
I never considered (or handled) tert-butoxides before. That's something to consider, thank you.

I suppose I could also dissolve the ester in solvent, and add 1 eq of TEA (triethylamine), which would presumably yield the free ester and TEA-hcl which could be easily recovered by filtration, basified, and reused. Seems like an elegant solution being able to regenerate/reuse the amine, whereas zinc chloride (or aluminum chloride as suggested) can't be converted back into their respective metallic states with as much ease.

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