[OrganicDan96]

I don't know if this is the right place to ask this, i'm sorry if it isn't

I am doing a Wiliamson ether synthesis between ethyl (3,4-dihydroxy)benzoate and 2-(2-chloroethoxy)ethanol to give ethyl 3,4-bis(2-(2-hydroxyethoxy)ethoxy)benzoate as shown in the scheme below. so I am trying to find a suitable TLC system for monitoring and later column chromatography. the problem is that the product is incredibly polar and will not move f the baseline, the starting material has no problem moving. I have tried the following solvent systems, 100% chloroform (nothing moved off the baseline) 60:40 DCM/Acetone (starting material give Rf of 0.55 but product stuck on the baseline), 40:60 DCM/Acetone (same as previous) 60:40 Acetone/EtOAc (same as previous), 100% EtOAc (same as previously), 90/10 DCM/Methanol (same still) ether (same as previous and very reliable results) 50:50 EtOAc/MeCN (product sticks at the bottom but an impurity moves up the plate slightly (Rf about 0.15). does anyone know of a solvent system which may move the product of the baseline? also each sample was spotted by taking a sample of the reaction and doing a little acid workup to protonate the starting material.

[wildfyr]

Whooeee you got a real polar one if 90:10 DCM/methanol won't shift it. I've seen some strange polar eluents out there, you might want to think about including a few % water in these tests. Like 90:7:3 MeCN/methanol/water. Its just TLC, throw convention out the window and try anything that comes to mind! Avoid DMSO/DMF thought, they suck to remove. and CS₂ is rather expensive, smelly, and toxic for my taste. There alre also exotics like dimethoxyethane that have structural similarities that could help you elute the product.

Keep in mind when reporting results, if its been sitting on the bench for weeks, a lot of your polar solvents already have a few % water in them. Might want to sieve dry them to achieve consistency.

And this is certainly the right place to ask this .

Here is a nifty list of solvents, maybe youll get some ideas here: http://www.mjlphd.net/solvent-of-the-week.html (scroll down for property descriptions)

[OrganicDan96]

Thanks for the Quick reply, I forgot to add that i tried 4:1 MeCN:H20 which just shifted everything to the top, also my solvents are not sitting around for very long as I am constantly trying new ones, but they may when i find a good system, I will try the system you recommended and i will try DME as well as soon as possible.

[wildfyr]

If 4:1 MeCN:H2O put everything to the top, why not try 9:1 MeCN:H2O? Or pure MeCN? Pure acetone is a similar to MeCN as well.

[rolnor]

I have used EtOAc-MeOH-H2O. 7:2:1. for nukleosides.

[kriggy]

What about pure methanol? Moves everyhing, and IMO easier to work with than the water based mobile phases

[OrganicDan96]

so i tried 95:5 MeCN:H2O which gave me a second spot with Rf of 0.2 but i still have a spot on the baseline. also the orange colour stays on the baseline. the product should not be coloured.

[rolnor]

You could have a mixture of the two possible mono-substituted products and the wanted di-substituted. Also this phenol can easily oxidase if you run the reaction long time, that could be the colored material. I would try running in degassed DMF with NaI as catalyst and use nitrogen or argon atmosphere.

[OrganicDan96]

yeah i know this was determined a few weeks ago when i was using carbonate bases, this week i have used hydroxides and i am doing the reaction under nitrogen this time, the colour is still persisting. also when i worked up the last lot of reactions the colour came out in the aqueous phase. I always suspected that the baseline spot would  consist of other products.