Sciencemadness Discussion Board

Grignard Reagent Confusion

steadyhand - 26-4-2022 at 16:54

I've made myself some powdered bromine (NBS) from MSG and now I want to play. I see procedures for brominating all manner of carbons and forming Grignards. Sticking those onto carbonyls and alkyl bromides seems straightforward, but I'm confused what happens in mixed functional group situations.

For example, I could make a bromohydrin across an olefin bond. So I make a Grignard from 1-bromooctane and want to stick it to the Br carbon of the bromohydrin. What about that hydroxyl? I know I can protect carbonyls with a diol, but is the hydroxyl vulnerable?

On a side note, is the wiki wrong about Grignards not working with organic halides? Or should that say aryl halides?
https://en.wikipedia.org/wiki/Grignard_reagent
"Grignard reagents do not typically react with organic halides"

Lastly, is there a decent (pdf, free) writeup of Grignard procedures for a bunch of different use cases, protections, considerations? The wiki shows a lot of possibilities, but nothing really useful. Google searches almost always lead to some researcher's pet project with sonicated lithium-hafnium catalyzed special sauce behind a paywall.

njl - 26-4-2022 at 17:51

Except in the Kumada coupling, Grignard reagents do not generally react with alkyl halides so your idea to "stick it to the br carbon" won't work. The OH is vulnerable only to deprotonation, however this will destroy the grignard reagent.

steadyhand - 26-4-2022 at 19:33

I see now why the OH didn't show up on what needed to be protected because, well, it dings the Grignard instead. This dropped me into Greene's for protective groups which I take it is a must have. If I wanted an OH (not necessarily, just what comes from NBS on an -ene), mebbe tack on an ether, but then that needs to come off. Or not. That means MeI and a whole 'nother rat hole.

Kumada looks interesting. I suppose it needs anhydrous AlCl3 or Nickel. Of course it does because Grignard. But I like technique. I'm not much for dump and stir chemistry.

I suppose I should mention what I'm up to. Looking into chemo-receptors for an artificial nose. I'm musing in the direction of tacking something onto the middle of Oleic acid or such. Bromo chemistry caught my eye for constructing things on polystyrene and the like. That and the fond memories of high power rockets and all the pyrotechnical chemistry I got into in a former life.

DocX - 7-6-2022 at 22:19

Quote: Originally posted by steadyhand  

I suppose I should mention what I'm up to. Looking into chemo-receptors for an artificial nose. I'm musing in the direction of tacking something onto the middle of Oleic acid or such. Bromo chemistry caught my eye for constructing things on polystyrene and the like.


This sound like a truly awesome project! Do you have any literature you follow? Links?