June 20, 2021, 08:42:48 AM
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Topic: Chemoselective cleavage of aryl methyl ethers  (Read 200 times)

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Offline columbo123

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Chemoselective cleavage of aryl methyl ethers
« on: June 09, 2021, 02:54:52 AM »
Hello everybody.
Recently, I am struggling with following reaction (attempt). I have a molecule which contains both, a methyl phenyl ether group and an aliphatic ether chain. For subsequent reactions, I would like to cleave the aryl methyl ether group to obtain a phenol.
So far I tried cleavage with a) high excess AlCl3 in DCM anh. at RT, and b) 1.1 eq AlCl3 with 3 eq NaI in MeCN anh. at RT. However, neither pathway worked. Since the aliphatic ether oxygen atoms are more basic, I suspect them to form Lewis acid-base complexes R2O->AlCl2 first. That is also, why I haven't tried the classic BBr3 so far, in fear of it cleaving the aliphatic ether already at RT.

Do you have experience/suggestions with selective ether cleavage reactions? Greetings.

 

Offline rolnor

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Re: Chemoselective cleavage of aryl methyl ethers
« Reply #1 on: June 09, 2021, 06:17:00 AM »
BBr3 will cleave the alkyl ethers faster than the aryl ether. You can use NaSMe in high-boiling solvent, not 100% sure what solvent exactly, collidine? You can find this in Greens protective groups in organic synthesis under protection of phenols, methyl ether.

Offline columbo123

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Re: Chemoselective cleavage of aryl methyl ethers
« Reply #2 on: June 10, 2021, 01:15:04 PM »
Thank you, great suggestion. I will try that right away.

Offline rolnor

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Re: Chemoselective cleavage of aryl methyl ethers
« Reply #3 on: June 10, 2021, 02:19:02 PM »
You need to degass the solvent and  run under N2 or argon, the phenolate product will easily oxidize att high temp.

Offline BobfromNC

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Re: Chemoselective cleavage of aryl methyl ethers
« Reply #4 on: June 10, 2021, 04:39:23 PM »
You can also try MeI in pyridine, but not sure if that will be very selective.   The NaSMe should be pretty good, so that makes sense to try first.

Offline rolnor

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Re: Chemoselective cleavage of aryl methyl ethers
« Reply #5 on: June 11, 2021, 05:32:42 AM »
Do you mean LiI?

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