[Reddart]

Looking for acylation of alcohols in the presence of a phenol, or alternatively, selective deprivation of a phenylacetate over an alkylacetate.

Using a weak base (like pyridine) and acetic anhydride I would assume would accomplish the former if the phenol isn’t too acidic, and if the phenol is acidic  where the phenolate forms with a weak base, it should be easier to deprotect, no?

[wildfyr]

You'll have to selectively protect phenol. It is simply more reactive than an alkly alcohol. I think careful tbdms protection would work.

I'm not sure about your deacylation idea, but it may have legs.

[OrganicDan96]

what about exploiting the acidity of phenols. benzyl protecting the phenol might work, so need a week base like K2CO3 which will only deprotonate the phenol BnBr will only react with the anion.

[phth]

A soft lewis acid might work. I'd search for that.

[Reddart]

It appears that using the anhydride, for my particular phenol-alcohol, that the alcohol was favored using pyridine as the base. I think it helped that in my case the phenol ring was substituted ortho with a ketone, so it was somewhat hindered. I didn’t use much excess anhydride or base (1.1 excess) and let it go a few days. There were some very minor impurities visible on Tlc (the phenolic ester?) but was easy to separate on the column. The phenol proton is clearly visible on HNMR. About 68% recovered yield.

[rolnor]

If you have a ketone in orto-position the hydroxyl hydrogen might be hydrogen-bonded and therefore has very low reactivity.

[Reddart]

Yes I was thinking the hydrogen bonding, as well as conjugation would make the ketone planar to the ring and increase the steric hindrance of the phenol.

[Reddart]

So getting back on topic, does anyone have any recommended conditions for hydrolyzing a phenolic ester in the presence of an aliphatic ester? I know it "should" be more labile, though in my case there will be some steric hindrance (the phenol is substituded 2 and 6 to the phenol, with the aforementioned ketone and a straight alkyl chain). Though the column works well for the small scale, I'd like to be able to remove any phenolic ester without reacting with the aliphatic ester, and without a column in the large scale.

[wildfyr]

Ready to have your mind blown?

https://www.tandfonline.com/doi/abs/10.1080/00397910903068196?scroll=top&needAccess=true&journalCode=lsyc20

"Chemoselective Hydrolysis of Ester Bonds in the Presence of Baker's Yeast"

Procedure:

A mixture of fresh baker’s yeast (100 g) and sucrose (100 g) in distilled water
(200 ml) was stirred for 15 min, after which an ethanolic solution (5 ml) of 4-methoxyphenyl 40
-acetoxybenzoate (3.4 g, 11.8 mmol) or 4-cyanophenyl 4-acetoxybenzoate (1.8 g, 8.72 mmol) was added to it. The mixtures were stirred at room temperature for 5 days with TLC monitoring, and then 50 ml of chloroform were added to each of them and stirring was continued for another 24 h, after which the reaction mixtures were centrifuged.

A column is used but I think acid/base wash using ionization state of free carboxyl should be reasonable way to purify without one. I assume the bakers yeast doesn't leave too many impurities that won't be separated by filtration, centrifugation, organic/water exchanges .