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Murphy Barrett

How to chose methylating agent?

Bill Gillooly  Follow
Methylation in textbook or Wikipedia may be a good starting point.

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And Esco  Follow
Quote from:
Quote from:
Methylation in textbook or Wikipedia may be a good starting point.

Could not find anything related on wikpedia.
If there's a website I can learn more about this I would really appreciate if you could link it.
I know there are a lot of websites comparing Sn2/Sn1/E1/E2 rxn but havent seen any of the like for methylating agents.

How to chose a proper methylating agent so to speak. Depending on substrate that will be methylated and solvent of choice or if there's a solvent free rxn.
English Wikipedia under "Methylation" contains quite useful information.
Solvent free means also an excess of methylating agents. Sometimes you can get only side products.

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Demi Blye  Follow
Check methyl iodide or dimethylsulfate

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Andrew Kiener  Follow
Diazomethane.

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Avery Stablegenius  Follow
Quote from:

Quote from:
IMO you may want to differentiate between cases in which the methyl carbon is electrophilic versus nucleophilic.  Also, have you thought about the reactivity-selectivity principle?

I haven't given it much thought to be honest, but I will consider it during the weekend and get back you guys here when I know a bit more on the subject!
What got me thinking about the first issue is that Grignard reagents are nucleophilic, whereas methyltosylate is electrophilic.  The reactivity-selectivity principle is not really much of a principle (it might qualify as a generalization).  However, there are times when it is useful.

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Chaw Tin Zar Maung  Follow
Quote from:
Methylation in textbook or Wikipedia may be a good starting point.

Could not find anything related on wikpedia.
If there's a website I can learn more about this I would really appreciate if you could link it.
I know there are a lot of websites comparing Sn2/Sn1/E1/E2 rxn but havent seen any of the like for methylating agents.

How to chose a proper methylating agent so to speak. Depending on substrate that will be methylated and solvent of choice or if there's a solvent free rxn.

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David Newberry  Follow
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It sounds like a very open-ended question. Methylation of aromatic rings will be different than methylation of proteins or DNA. You will need to limit your scope.

This review paper covers methylation in medicinal chemistry: The Methylation Effect in Medicinal Chemistry

Geez, thanks for that. It will keep me busy for the weekend for sure. Appreciate it!  :)

Quote from:
IMO you may want to differentiate between cases in which the methyl carbon is electrophilic versus nucleophilic.  Also, have you thought about the reactivity-selectivity principle?

I haven't given it much thought to be honest, but I will consider it during the weekend and get back you guys here when I know a bit more on the subject!

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Brian Maina  Follow
Methyl tosylate should be on the list too.

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Andrew White  Follow
IMO you may want to differentiate between cases in which the methyl carbon is electrophilic versus nucleophilic.  Also, have you thought about the reactivity-selectivity principle?

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Charlie  Follow
Quote from:
Check methyl iodide or dimethylsulfate

Thanks!
I see that dimethylsulfate is very limited in use today due to its toxicity, from wikipedia.
Wikipedia also suggests that trifluoromethanesulfonic acid and Methyl trifluoromethanesulfonate would be "the next best thing" but how can one reason around that?
What should I look for (properties) in methylating agents so to speak.

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Bill Welden  Follow
It sounds like a very open-ended question. Methylation of aromatic rings will be different than methylation of proteins or DNA. You will need to limit your scope.

This review paper covers methylation in medicinal chemistry: The Methylation Effect in Medicinal Chemistry

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Armand Wong Sr.  Follow
"Magic" methyl aka methylfluorosulfonate  :o hideously toxic and volatile. Mostly outdated by methyl triflate.

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