May 25, 2019, 09:31:08 AM
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Topic: Acylation of alcohols over phenols.  (Read 321 times)

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Offline Reddart

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Acylation of alcohols over phenols.
« on: April 26, 2019, 12:05:51 AM »
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?

Offline wildfyr

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Re: Acylation of alcohols over phenols.
« Reply #1 on: April 26, 2019, 08:15:49 AM »
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.

Offline OrganicDan96

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Re: Acylation of alcohols over phenols.
« Reply #2 on: April 26, 2019, 11:31:26 AM »
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.

Offline phth

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Re: Acylation of alcohols over phenols.
« Reply #3 on: May 02, 2019, 12:13:51 AM »
A soft lewis acid might work. I'd search for that.

Offline Reddart

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Re: Acylation of alcohols over phenols.
« Reply #4 on: May 10, 2019, 04:49:15 PM »
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.

Offline rolnor

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Re: Acylation of alcohols over phenols.
« Reply #5 on: May 11, 2019, 05:41:15 AM »
If you have a ketone in orto-position the hydroxyl hydrogen might be hydrogen-bonded and therefore has very low reactivity.

Offline Reddart

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Re: Acylation of alcohols over phenols.
« Reply #6 on: May 13, 2019, 05:57:35 PM »
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.

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