Sciencemadness Discussion Board

Replacing halogen by hydrogen

Monoamine - 30-7-2021 at 13:55

I've been looking far and wide for a method to perform the following reaction:

R-O-CH2-X -> R-O-CH3

In other words, all I'm trying to do is get rid of a Cl- and replace it with an H-.

Classical reducing agents such as NaBH4 or Li AlH4 were never mentioned as a means to achieve this reaction.

On the other hand, would't it just be as simple as using LiH or NaH so that the Na+ undergoes nucleophilic attack by Cl- and, while the resulting carbon cation undergoes nucleophilic attack by H-, yielding:

R-O-CH2-X -> (NaH) -> R-O-CH3 + NaCl

Would this work, or is there maybe a much more streight forward way to achieve this?

Texium - 30-7-2021 at 14:32

I’m not sure what the scope is (I’ve only used it on chlorines that are alpha to a ketone) but at work I’ve de-chlorinated compounds using chromium(II) chloride. Downsides are the chromium(II) chloride is not too easy to come by or make, and you have to use a stoichiometric amount. Really, a considerable excess if you want to ensure it goes to completion.

unionised - 30-7-2021 at 15:16

Quote: Originally posted by Texium  
you have to use a stoichiometric amount. Really, a considerable excess


Pick one.

unionised - 30-7-2021 at 15:21

Quote: Originally posted by Monoamine  
I've been looking far and wide for a method to perform the following reaction:

R-O-CH2-X -> R-O-CH3

In other words, all I'm trying to do is get rid of a Cl- and replace it with an H-.

Classical reducing agents such as NaBH4 or Li AlH4 were never mentioned as a means to achieve this reaction.

On the other hand, would't it just be as simple as using LiH or NaH so that the Na+ undergoes nucleophilic attack by Cl- and, while the resulting carbon cation undergoes nucleophilic attack by H-, yielding:

R-O-CH2-X -> (NaH) -> R-O-CH3 + NaCl

Would this work, or is there maybe a much more streight forward way to achieve this?

If there's nothing else that would react (that's a big if) I think you can go via a Grignard reagent or some such.

Monoamine - 30-7-2021 at 17:05

Ah cool, Grignard may be the way to go then. Thanks for the tip!

Basically, I was hoping to make a methyl ether, but the problem is that methyl halides tend to be gasses, so I don't know if I would have enough...


methyl ether.png - 237kB

I guess I could try to reflux some MeOH and HBr and bubble the fumes through the deprotonated phenol, but not really sure how efficient that would be..., hence the roundabout route.

I've been meaning to get some practice with Grignard reagents anyway, so this also seems a good way to practice.


[Edited on 31-7-2021 by Monoamine]

Oxy - 30-7-2021 at 17:14

Methyl iodide has a boiling point of 42oC

Here you can find some info about alpha-haloalkyl ether's chemical properties


Attachment: summers1955.pdf (3.2MB)
This file has been downloaded 244 times

[Edited on 31-7-2021 by Oxy]

Bedlasky - 30-7-2021 at 17:32

SmI2 in THF or THF/HMPA can reduce alkyl halides to hydrocarbons.

https://sci-hub.se/https://pubs.acs.org/doi/10.1021/ja00528a...

https://books.google.cz/books?id=QUfQamGsEgwC&printsec=f...

Texium - 31-7-2021 at 13:37

Quote: Originally posted by unionised  
Quote: Originally posted by Texium  
you have to use a stoichiometric amount. Really, a considerable excess


Pick one.
Fine: an excess. Either way, my point was that you have to use at least a stoichiometric amount of something that is not so easy to come by, and if you want it to work really well, you'll need to use an excess. So although it is a cool reaction, it is likely not viable in the home lab.

If it was possible to use a catalytic amount of CrCl2 with an excess of a secondary reductant like zinc metal, that would be a different story, but I don't think that works.

[Edited on 7-31-2021 by Texium]

karlos³ - 31-7-2021 at 14:52

You could react that stuff with borohydride and CuCl2, that would dehalogenate it.
I don't know about other function groups in your molecule though.

clearly_not_atara - 31-7-2021 at 19:03

Quote: Originally posted by unionised  
Quote: Originally posted by Texium  
you have to use a stoichiometric amount. Really, a considerable excess


Pick one.

Remember that a stoichiometric amount of CrCl2 for this rxn is two molar equivalents!

Bedlasky - 1-8-2021 at 02:34

Monoamine: If you want to make anisole from phenol, you can use dimethyl oxalate as methylating agent:

http://www.sciencemadness.org/talk/viewthread.php?tid=86622