Home > Community > Counter ion effects in Sn2 reactions
Upvote

VOTE

Downvote
+ Organic
Posted by
Alan Murrie

Counter ion effects in Sn2 reactions

Austin Mccormack  Follow
Quote from:
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

More

Upvote

VOTE

Downvote
Alex Becker  Follow
Quote from:
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.

More

Upvote

VOTE

Downvote
Ben Warmus  Follow
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.

More

Upvote

VOTE

Downvote
Beth Goldowitz  Follow
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.

More

Upvote

VOTE

Downvote
Muhammad Zubair  Follow
Quote from:

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.

More

Upvote

VOTE

Downvote
Alex  Follow
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?

More

Upvote

VOTE

Downvote
Bernard Thompson  Follow
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.

More

Upvote

VOTE

Downvote