[OrganicDan96]

I have conducted a series of reactions between ethyl-3,4-dihydroxybenzoate and 2-(2-chloroethoxy)ethanol in MeCN where I varied the base, I tried Li2CO3, Na2CO3, K2CO3, LiOH, NaOH, KOH, NEt3. the only reaction that produces any yield after 7 days of reaction was K2CO3 (30%) I have since increased this to 83% (including some KI, Finkelstein reaction). I do not fully quite understand why only K2CO3 gave product. I think it may be because Li+ and Na+ are quite hard cations and coordinate strongly with the anion, resulting in a "masked" nucleophile. where as K+ is larger and softer therefore does not coordinate well to the anion and is better solvated by the MeCN solvent. may this be a similar reason as to why NEt3 did not work ether?. I think the hydroxides did not work as they are too nucleophilic resulting in some ester hydrolysis and attack of the 2-(2-chloroethoxy)ethanol.

 second reason i could think of is some sort of tamplate effect.

I do not know if either of these explanations are correct. If i am way off the mark I would like someone to help guide me to some sort of explanation.

[wildfyr]

Its curious that you're working on catechols at the same time as our other poster, now I see why you offered the benzoate as a substrate.

Anyways, when you say yield, do you mean conversion too? Catechols are unstable under basic conditions, so if they don't react quickly, they will oligomerize and produce crap via quinones that give both radical and Michael addition. I would expect all your carbonates to work somewhat, TEA to not work at all (too weak a base) and the metal hydroxides to produce chloro elimination and ester hydrolysis as you mentioned. What were the equivalents of base and 2-(2-chloroethoxy)ethanol? Were all these bases fully solubilized?

K₂CO₃ is the strongest base of the 3 (and also the most soluble), and for this reaction it might just be a case of goldilocks syndrone. I bet cesium carbonate would work nicely too , its an even stronger base with some very unique properties.

[OrganicDan96]

K₂CO₃ is the strongest base of the 3 (and also the most soluble), and for this reaction it might just be a case of goldilocks syndrone. I bet cesium carbonate would work nicely too , its an even stronger base with some very unique properties.

ahah, i knew this would come up, we have tried Cs2CO3, however we cannot use it as we are making caesium selective stuff, so we cannot have Cs contamination.

I used 3.5 eq of 2-(2-chloroethoxyethanol) and 5.6 eq of base (for carbonates) and 2 eq for hydroxides (as excess hydroxide would cause ester hydrolysis.

[opsomath]

I nearly always used 1 eq. of powdered KOH added to a DMF solution of the phenol (adding the phenol first, so my KOH didn't hydrolyse the DMF too badly) and stirred until completion. KI is a good idea. Once I tried NaOH instead and got almost zero conversion.

[OrganicDan96]

I nearly always used 1 eq. of powdered KOH added to a DMF solution of the phenol (adding the phenol first, so my KOH didn't hydrolyse the DMF too badly) and stirred until completion. KI is a good idea. Once I tried NaOH instead and got almost zero conversion.

i had to use 2 equivalents as it reacts twice as it's a catechol and i wanted to alkylate both OHs, i did do the reaction in DMF using potassium carbonate once i got the conditions locked down, although it improved the rate, the DMF was very hard to remove and would not scale well so i stuck with MeCN

[wildfyr]

KOH in DMF for Williamson ether is an old standby, maybe give it a check. Should be able to remove DMF by just dumping in DCM and washing with water 4-5 times.

Also, sometimes you can just add a bunch of water to a DMF reaction and the product that is organosoluble will crash out, then you can just filter and rinse the solid with water a few times. Is your product a solid or an oil with those oligo PEGs?

[OrganicDan96]

i have got this reaction working well with K2CO3/KI in MeCN, i was just asking for a bit of help to explain my observations.

[OrganicDan96]

Also, sometimes you can just add a bunch of water to a DMF reaction and the product that is organosoluble will crash out, then you can just filter and rinse the solid with water a few times. Is your product a solid or an oil with those oligo PEGs?

it's an oil> i diluted lots with water and added some LiCl to complex the DMF. extracted a few times into DCM, then washed a few times with water. there was still loads of DMF in my product, i did manage to rotorvap of most of it but i couldn't get all of it out.