Pumukli
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O-methylation in acid
I have accidentally found something at OrgSyn which really intrigued me and I could not explain. I'm calling our experts to shed light on this
reaction and possible uses -if any- for us, amateurs, who are looking for safer methylating agents/methods.
There is a synthesis of 6-methoxy-2-naphthol at the above mentioned website (vol. 49, p. 90, 1969.) - which is not really interesting at the moment.
The interesting thing is hidden in the "Notes" section of the paper, under section 2. paragraph 2.
It suggests that after brominating 2-naphthol the product 6-bromo-2-naphthol should be mixed with sulphuric acid and methanol and refluxed for a few
hours. After workup it yields 6-methoxy-2-bromo-naphthalene. (See the attached .pdf)
The yield is (very) good.
The methylating agent is sulphuric acid/methanol mixture.
The O-methylation takes place in a strongly acidic environment, not with the help of a base.
I tried to use the above method on hydroquinone.
Guess what? It failed. All I got was a reddish liquid with a strong, unpleasant phenolic smell. What I could recover by chloroform extraction was only
around 10-15% of the starting hydroquinone - as a deep red goo. I think the rest remained dissolved in water as -suspected- sulphonic acid derivative.
Probably the sulphuric acid concentartion was too much for this really activated phenol.
Then I tried a less active phenol: methyl-paraben. (P-hydroxy-benzoic acid methyl ester)
Guess what? It failed. :-) The paraben quickly dissolved in sulfuric acid / methanol, but failed to do anything beyond that.
Then I realized that it probably never would work on such a substrate because what I did was basically the "continuation" of the esterification
process of p-hydroxy-benzoic acid with methanol/sulfuric acid. I mean, if I had started with p-hydroxy.benzoic acid and had wanted to make its methyl
ester, I'd have used methanol/ sulfuric acid reflux. From such a mixture only the ester could be isolated, but not the ether.
TLC confirmed this: no reaction.
I doubt that only naphthols could be used as substrate. What's your opinion?
Edit: forgot to attach the relevant article.
[Edited on 19-5-2019 by Pumukli]
Attachment: methylatingwithacid.pdf (324kB)
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AvBaeyer
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Pumukli,
It is my recollection that the methylation reaction you describe is pretty specific for 2-naphthols (and perhaps some electronically related
compounds). The reaction that you found interesting was described by Gilbert Stork many years ago. The reaction is not a true methylation but relies
on the transient ketonic character of 2-naphthol induced in a strong acid environment. Think of 2-naphthol as the enol. Now move the phenolic hydrogen
to the 1-position and write the previous phenolic oxygen as a ketone. The "methylation" can now be envisaged as proceeding through a hemiketal
(addition of methanol to the ketone) followed by loss of water resulting in the phenol OH being replaced by methoxy.
There may be other phenolic compounds which undergo this type of reaction if a transient ketonic function can be induced. Others may be able to
provide real examples. However, it appears from your report that neither of your substrates can be induced into a transient ketonic state.
I hope that what I have said is reasonably clear.
AvB
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Pumukli
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AvBaeyer,
Thanks for the clarification!
Now I have at least a name (Stork) and a keyword (2-naphthol) to start digging up more info on this reaction.
I tend to think that maybe hydroquinone can participate in this reaction but cc sulphuric acid is a bit too much for him/her. :-)
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AvBaeyer
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Attached is the Stork reference which is a bit hard to find since the reaction in question is buried in the paper.
Also attached is an older review article on phenol tautomerism which will give you some insight into the general subject.
I hope you find these useful
AvB
Attachment: Base Effect in Catalytic Hydrogenation stork1947.pdf (483kB)
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Attachment: PHENOL TAUTOMERISM thomson1956.pdf (1.2MB)
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