How to make an amide enolate.
Bert Kruiswijk
Does anyone know a good way to make an amide enolate? I could not find
anything in comprehensive org. chemistry.
Thanks,
Bert.
--
Paul J. Franklin (moderator - sci.chem.organic.synthesis)
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Atlanta, GA
Gabriel Tojo
>
> Hi everyone,
>
> Does anyone know a good way to make an amide enolate? I could not find
> anything in comprehensive org. chemistry.
The chemistry of enolates of Evan´s acyloxazolidones is very well
studied and used quite often, but they do not qualify as standard
amides.
Amide enolates are not used as often as ketone or ester enolates,
possibly because acidic free N-H´s would hinder its formation.
Nevertheless, as the protons alfa to an amide carbonyl are not as acidic
(pka about 34) as the ones alfa to esters or ketones (pka 26-31), the
corresponding enolates are much more reactive, and would work in cases
in which ester and ketones enolates would fail. Standard LDA/THF works
normally well.
Some references are:
Tetrahedron, 4733, 90; 2121, 91; 809, 94; JACS 5290, 90; 8258, 95:
Gabriel Tojo
Profesor Titular de Quimica Organica
Royal University of Santiago de Compostela
SPAIN
Uncle Al
Bert Kruiswijk wrote:
>
> Hi everyone,
>
> Does anyone know a good way to make an amide enolate? I could not find
> anything in comprehensive org. chemistry.
You will have to start by passivating the acidic N-H protons, if any.
As for dialkylamines, you use a strong base (stronger than for an
ester because electron donation by the amide reduces alpha-proton
acidity). If you really want to rip protons, pre-formed N-BuLi/TMEDA
- intensely powerful kinetic base, poor nucleophile. Note that THF
starts unzipping to acetaldeyde enolate at zero C here.
--
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Gabriel Tojo
>
> Bert Kruiswijk wrote:
> >
> > Hi everyone,
> >
> > Does anyone know a good way to make an amide enolate? I could not find
> > anything in comprehensive org. chemistry.
>
> You will have to start by passivating the acidic N-H protons, if any
Easely removable silicon works fine, and migrates to oxygen in reactions with
aldehydes, thus preventing retro-aldolic reactions (Tetrahedron, 2121, 91)
.
> As for dialkylamines, you use a strong base (stronger than for an
> ester because electron donation by the amide reduces alpha-proton
> acidity).
Yes, although the pKa of MeCONEt2 is 34.5. LDA is basic enough to take the
protons (Tetrahedron, 4733, 90)
If you really want to rip protons, pre-formed N-BuLi/TMEDA
> - intensely powerful kinetic base, poor nucleophile.
No need to kill flies with a gun. n耑uLi/TMEDA is a freak kinetic and
thermodinamic base able to deprotonate nude benzene.
Note that THF
> starts unzipping to acetaldeyde enolate at zero C here.
Yes, that愀 a nice way to prepare acetaldehyde enolate (acetaldehyde plus base
causes self-condensation). That愀 another reason to avoid killing flies with a
gun.
Cheers
--
Gabriel Tojo
Profesor Titular de Quimica Organica
Royal University of Santiago de Compostela
SPAIN