[orgstudy]

Hi all

I need help in following conversion (pic)

OH to be replaced by CH₃ if X is highly deactivating

... i thought of treating with Zn and the Friedel craft ... but as benzene is highly deactivated so it wont work ... any help

[Honclbrif]

Is that ring supposed to be a benzene?

Straight up replacing an -OH with anything is tricky. You will have to activate it first.

[orgstudy]

Oh yes ... sorry ...  its benzene ...

[jake.n]

I think Friedel-Craft makes sense for this reaction.  Even with the deactivators, you could force the reaction to completion as the EAS product of ipso attack eliminates water which will either condense or could be boiled out, depending on solvent system.

There may be a more efficient way to do it, but FC seems possible for this system if enough energy is added over a long enough period.

[orgstudy]

I told my teacher about FC but he said there is another better way ...

[hobobot]

O-chem isn't my strong suit, but out of curiosity: why can't you just add HCl and do a SN2 type reaction? with the OH turning into an OH₂+ and then the Cl- replacing it? Then FC becomes easier?

[Mikez]

this is perfect because since its deactivating the methyl will only be ADDED ONCE rather than multiple times

[nox]

This is a crazy idea, but thought I'd throw it out there:

1. Add triflic anhydride to make the phenyl triflate
2. Do a Suzuki coupling with methyl boronic acid

[jake.n]

I like Nox's Suzuki route.  I've attached another mechanism that looks like it would work conceptually.  Because this generates an intermediate dianion, I don't know how reasonable it really is, but the dianion should still be less basic than the Grignard reagent.

[Honclbrif]

@jake.n

I'm not crazy about the intermediate dianion either.

However, if the X's are pi-withdrawing (which I think is reasonable to assume since it is claimed they are "highly deactivating"), and the -OH is suitably activated, this is a great candidate for S_NAr.