[Babcock_Hall]

doi:10.1016/j.bmc.2007.06.016
http://dx.doi.org/10.1016/j.ejmech.2014.05.014

We are attempting to acetylate a quinol bearing an aldehyde.  The acetylation conditions that we are using come from two nearly identical procedures.  Both use potassium carbonate, acetic anhydride, and are in diethyl ether.  We are not see any reaction by TLC after about 90 minutes, whereas the papers we are following suggest that the reaction is finished in 2-3 hours.  I was thinking of letting it run overnight.  If that does not lead to a complete reaction, the only other thing that I can think of is to add a small amount of DMAP.  I have not seen DMAP used as a catalyst in this sort of reaction in my searches so far, although I have seen it used in esterifications involving DCC, and I have seen it used stoichiometrically in one acetylation.  Any ideas or thoughts about a good way to proceed?
EDT

We took one more time point, and there is still little evidence of a reaction.  One supposes that the product will have a larger value of R_f than the reactant.

[Babcock_Hall]

All of the reagents except the potassium carbonate come from unopened containers.  The solid settled less quickly this morning when I briefly discontinued stirring the reaction.  Yet the TLC this morning gave only a hint of a product and mostly starting material.  I wonder whether or not the K_2CO3 should have been ground to make a finer powder.  I am also thinking about checking the starting material by NMR.  One other problem may be in discriminating between mono- and di-acetylation.
EDT
The only not-fresh reagent was potassium carbonate, and it is possible that water in this reagent was the problem.

[rolnor]

If the compound is identical with the one in the paper then maybe ground K2CO3 might be important. If not I wonder why this strange conditions are used, ether seems like a unusual solvent? Why not use 2eq. Ac2O+pyridine in DCM?

[Babcock_Hall]

Our substrate is strictly identical to the one in the two papers.  I like the idea of grinding dry potassium carbonate, and I am concerned that the potassium carbonate we used might not have been dry.  I have also heard that people sometimes substitute in cesium carbonate, but I am unsure whether or not this would be a good idea.

[rolnor]

I wonder if maybe one of the OH-groups is hydrogenbonded to the aldehyde carbonyl? This would explain why K2CO3 is used?

[Guitarmaniac86]

I'd try the reaction in dry THF and warm it up and see if anything happens.

If not, I would try DMAP, triethylamine and THF.

On the note of cesium carbonate, I have found it to be a much better base and use it in place of pot carb now.

[kriggy]

We had a tricky acetylation and we used neat Ac2O and DMAP to make it work. The workup was painful though.
Also, the procedure described in the paper seems weird to me. First of all, the deprotonated quinone will be hardly soluble in ether so maybe that is the issue?
I would try Ac2O+DMAP in DCM or  acetonitrile/THF..

[Babcock_Hall]

Thank you.  Would you use a catalytic amount of DMAP?  Would you use a base?

[wildfyr]

Whats wrong with neat acetic anhydride? Its pretty common. BP is 140, or you can stir it with a bunch of water (keep it cold!) to remove the Ac₂O after the reaction.

Some DMAP wouldn't hurt either to hedge your bets. I guess 1.1 eq since it would be acting as a base and catalyst.

[rolnor]

I agree with wilfyr, just reflux with Ac2O, I have done that, then just evaporate with aspirator vacuum.

[kriggy]

Thank you.  Would you use a catalytic amount of DMAP?  Would you use a base?

We used over 2 eq because it acted as a base as well and we needed to do bis-acetylation otherwise we got a mixture of compounds

Whats wrong with neat acetic anhydride? Its pretty common. BP is 140, or you can stir it with a bunch of water (keep it cold!) to remove the Ac₂O after the reaction.

Some DMAP wouldn't hurt either to hedge your bets. I guess 1.1 eq since it would be acting as a base and catalyst.

Nothing wrong with it but required excessive amount of water/base in workup. We did like 500 mg reaction but ended up using almost 500 mL of water/base to quench the acid which worked but was bit too much for me based on the amount of product we were getting in the end.
Also, adding water to Ac2O takes time, I just perfomed acetylation with it in aq. NaHCO3 as a solvent so it probably takes quite some time to decompose.

[Babcock_Hall]

We tried one suggestion (Reddit/Chempros), which was to use cesium carbonate (sealed bottle).  We are still not seeing anything by TLC.  It was suggested to me that the product might have the same R_f as the starting material in EtOAc/hexanes and that I might try DCM with a small percentage of EtOAc or acetone.  Thoughts?

[rolnor]

You can evaporate the excess A2O on rotavapor, just turn up the heat in the water-bath.

[Babcock_Hall]

Funny you should mention that.  We hoped to recover the unreacted aldehyde from the first reaction.  After acidifying, we removed the solvent from the first reaction, the one performed with potassium (not cesium) carbonate.  I noticed that I could still smell acetic acid or possibly the anhydride, even being at 40 °C bath temperature with a moderate vacuum.  I can go a bit higher in vacuum and in temperature.

I have not yet had the chance to try a different TLC solvent, but possibly tomorrow.

[rolnor]

Is it possible for one if the hydroxyl groups being hydrogen-bonded to the aldehyde carbonyl? If so the acetylation is much more difficult.