Extremophile
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Aliphatic alcohol activation orthogonal to primary amide
Hello everyone. I am a PhD student with not much experience. I hope to be able to compensate for it by the valuable comments on this wonderful site.
Unsurprisingly, my first post has turned out to be a question.
I want to activate the aliphatic alcohol on my compound for a preceding coupling reaction which is moisture sensitive. So, phase transfer conditions
with aqueous medium will not do the job. Beside the alcohol, the compound also contains a primary amide, which has a very close pKa to the alcohol.
So, NaH will abstract both amide and alcohol protons.
1)The question is how to activate the aliphatic alcohol orthogonal to the primary amide?
2) Just for curiosity, how to activate the primary amide orthogonal to the aliphatic alcohol?
Thanks.
[Edited on 23-2-2013 by Extremophile]
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ash
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what kind of coupling reaction do you want to conduct? change OH to what?
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Nicodem
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Extremophile, your question is too vague. What kind of activation? Do you want to make the alcohol group nucleophilic or electrophilic? Activation
with which reagent? What kind of an alcohol group is it: primary, secondary, tertiary, allylic, homoallylic, benzylic, etc.? What is the geometrical
relation between the amide and alcohol group? What kind of a primary amide is it (RCONH2: what is R)?
All this is very important, if you truly want a meaningful answer. Better yet, post the exact structure.
Welcome to the forum, but please acknowledge that this forum is for amateur chemistry and is not supposed to be a support for students unless the
exchange is mutual. Also, open threads without references only in the Beginnings section. Please read the forum guidelines for more information.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Nicodem
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Thread Moved
23-2-2013 at 05:31 |
Extremophile
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OK, i will read the guidelines and post accordingly from now on. Actually amide is a secondary one, my apologies and the alcohol is primary aliphatic
alcohol.
I want to answer your question by a retro-question. How do you guys think an aliphatic alcohol is activated by NaH, which I gave as an example in my
post? Have you guys really read my post thoroghly?
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Extremophile
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OK, I have attached the scheme.
I used NaH / DCM(dry) with the hope of getting only 2 but, I realized that 2,3,4
all may well be present in the solution.
Then, I tried CsCO3 / DCM(dry) which didn't work either.
Therefore,
1) what can be (?) (Reagent/solvent/conditions) in order to get exclusively 2 ?
2) (just for curiosity) In order to get exclusively 3 and 4?
[Edited on 23-2-2013 by Extremophile]
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Nicodem
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Transprotonations like this are equilibrium reactions - there are no paths for these equilibriums. Since you can not obtain exclusively one
form of the anion, your questions 1 and 2 are nonsense from the scientific perspective. Utmost you can obtain tight ion pairs under certain conditions
(counterion and solvent dependent), but these will not behave as you want them to, instead they will partially reverse the selectivity. What you want,
from the synthetic perspective, is to find conditions where the selectivity of the reaction is optimal. This obviously cannot be answered unless you
first describe the reaction. All we can deduce up to know, is that you want to make the alcohol group in 2-(acetylamino)etanol nucleophilic. We don't
know what you want to do with it, so how can anybody give you anything but the most general and therefore useless answer?
I can only comment the little information that you gave up to now:
Dichloromethane is not a proper solvent for deprotonation of alcohols, because it is moderately electrophilic. It is also unable to solvate cations
and thus the concentration of the alcoholate anions remains low even after the NaH fully deprotonate the substrate.
Why don't you do the most obvious thing and check the literature for examples of related reactions on 2-(acetylamino)etanol?
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Extremophile
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Thank you very much for the response, sir. I understand that the answer depends on the conditions for the reaction. I thought there might be a
straightforward answer (reagents, conditions, ...etc) to this selectivity problem that I wouldn't know about. I did search the literature but couldn't
find what I am looking for. I will definitely search the literature more. Regards.
Extremophile
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