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Author: Subject: Protecting groups for tertiary amines
zed
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[*] posted on 30-7-2021 at 22:20


As stated previously. Under some circumstances a protecting group is not required.

The molecule you are trying to synthesize bears some structural similarity to Codeine, and Chemists did spend many years perfecting that synthesis via the etherization of Morphine.

Eventually, they simply utilized a Quaternary Ammonium Salt, as the Methylating agent. Such a reagent will preferentially Methylate the hydroxy group.

https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bu...

I'll dig a little bit more. Yeah, I'm imagining Ethylation is not more difficult than Methylation, but I do not have a procedure.

The Ethyl Ether of Morphine (an analog to Codeine) is named Dionine. It is particularly useful for application to the eyes.
The preferred use of the Ethyl Ether rather than the Methyl Ether, might have to do with the toxic effect Methanol has on the optic nerve. I do not know that with any certainty though.

Dionine/Ethyl Morphine synthesis.... https://www.sciencedirect.com/science/article/abs/pii/S00959...

Sorry. No can open it, myself!

[Edited on 31-7-2021 by zed]

[Edited on 31-7-2021 by zed]
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[*] posted on 31-7-2021 at 07:24


Ethanol should work as a solvent. If you have more than one go at this, try both ways. The diethyl oxalate/carbonate way, and the protecting group + EtBr way.



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[*] posted on 31-7-2021 at 11:14


Acetic acid catalyzed ester aminolysis




Reflux condenser?? I barely know her!
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smile.gif posted on 7-8-2021 at 07:20


Quote: Originally posted by EverythingAl2O3  
Is there anything stopping you from doing an acid catalyzed ether synthesis? So you could use H2SO4 and ethanol to get your phenoxy group and avoid the overalkylation?


I'm not too familiar with this approach, but if this works for armatic OH groups, then of course this would solve the problem. Let me look into the exact reaction mechanism for this kind of ether-synthesis.

Thanks for the tip!
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[*] posted on 13-8-2021 at 22:49


Quote: Originally posted by zed  
As stated previously. Under some circumstances a protecting group is not required.

The molecule you are trying to synthesize bears some structural similarity to Codeine, and Chemists did spend many years perfecting that synthesis via the etherization of Morphine.

Eventually, they simply utilized a Quaternary Ammonium Salt, as the Methylating agent. Such a reagent will preferentially Methylate the hydroxy group.

https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bu...

I'll dig a little bit more. Yeah, I'm imagining Ethylation is not more difficult than Methylation, but I do not have a procedure.

The Ethyl Ether of Morphine (an analog to Codeine) is named Dionine. It is particularly useful for application to the eyes.
The preferred use of the Ethyl Ether rather than the Methyl Ether, might have to do with the toxic effect Methanol has on the optic nerve. I do not know that with any certainty though.

Dionine/Ethyl Morphine synthesis.... https://www.sciencedirect.com/science/article/abs/pii/S00959...

Sorry. No can open it, myself!

[Edited on 31-7-2021 by zed]

[Edited on 31-7-2021 by zed]


Very interesting that it contains a similar 3D moiety as Codeine! Just looked up the structure and there really is a similar one, but smaller, than that of the above compound. But as someone pointed out it also bears a semblance to noribogaine, the active metabolite of ibogaine, both of which are used to cure opiate addiction. But I guess in retrospect it isn't a surprise that a medication that addresses the symptoms of opiate withdrawal would have a similar structure to the later...

As for the difficulty of methylation vs. ethylation, I would actually imagine that ethylation is easier (if you're using an alkyl halide) since MeBr is a gas while EtBr isn't, so it's much easier to control the amount of reagent introduced to the reaction. (I'd guess that more than one molar equivalent of EtBr would inevitably lead to the formation of side products, where the amine is also alkylated).

Maybe you could use a tosylated methanol if you want to do a methylation? But honestly, I don't remember if that would even work for an ether synthesis. I'll look into it.

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