[washtin]

Recently, i am running one reaction for TMS-ethers,To a solution of the iodolphenol and triethylamine (2 eq) stirring in CH2Cl2(DCM)at 0° under an inert atmosphere, is added drop wise TMS-Cl (10 eq).  The result was allowed to warm to room temperature and stirred overnight.After microwork up,I detected it by TLC, and there is no reaction happened because of the same moving pot in TLC as start material.What should i do?

[agrobert]

This protection should work and the conditions are fine.  Either the product is being deprotected in your work-up or on your silica.  Try spoting without work-up and running 1% TEA in your TLC eluent to prevent deprotection.

[washtin]

Thanks,i did not run work up this time and there are two pionts in TLC. one pot is definitely start material.The other one i think maybe is product. i try to seperate these two materials but eluent which is from EA:HEX 4:1 to EA:HEX 20:1 can not work well. these two materials have weak polarity ,and are so easy &quick to wash that each tube also has two materials.
Did you think whether i should change my base to stronger one such as imidazole or pyridine.

[macman104]

If they have a weak polarity, you're using a fairy polar eluting mixture.  Why not try something as non-polar as just hexane, or you can still do something like, 1:7 EA/HEX.  Anyway, I would try something much more non-polar.

[Dan]

A quick point, you are using 2 eq of triethylamine and 10 eq TMSCl. Are you taking further precautions in the workup to keep the pH up? If you don't add any more base, aqueous workup will generate alot of HCl unchecked, and this may be causing your TMS groups to fall off.

I would personally use an excess of triethylamine over TMSCl, or actually just run the reaction in neat pyridine.

If deprotection is a problem you could also use a more robust silyl group, like TBDMS.

As far as the column goes try,  as macman104 suggested, EA/HEX systems where hexane is the major component. If that's still too polar you could use ether instead of EA as your strong solvent.

[washtin]

Sorry, i wrote wrong in here about  EA:HEX 4:1 to EA:HEX 20:1.It should be EA:HEX 1:4 to EA:HEX1:20, thank you everyone.

[washtin]

anyway, in my first time i tried Et3N  with 3 eq and TMSCl 1.5eq, but the reaction showed nothing happened. So, i thought maybe this is silyl ethers , i need much more TMS- group to make something happened. Then, i increased TMSCl amount to 10 eq.
Maybe Et3N is not a strong base or something i should change.

[macman104]

Sorry, i wrote wrong in here about  EA:HEX 4:1 to EA:HEX 20:1.It should be EA:HEX 1:4 to EA:HEX1:20, thank you everyone.

Is this another typo?  You are running from a more polar solvent, to a less polar solvent?

I would say, try eluting it very slowly with the 1:20 EA/HEX, and see if you can get a good separation over a longer column.  I had two very similar spots, that required elution in pure hexane (downside is that it took a large amount of solvent, ~3L of hexane )

Alternatively, do you have access to HPLC or something that may be more efficient and better at separating your compounds?

EDIT:  I'm only commenting on the separation process, since I have no experience working with silyl ethers, so I can't really comment on that part.

[agrobert]

The separation should not be a problem.  You should be confident in your reaction before stopping it.

[washtin]

Sorry, i wrote wrong in here about  EA:HEX 4:1 to EA:HEX 20:1.It should be EA:HEX 1:4 to EA:HEX1:20, thank you everyone.

Is this another typo?  You are running from a more polar solvent, to a less polar solvent?

i know what you mean, i just try it in TLC from EA:HEX 1:4 to 1:20 because i  want left my start material in Si column, but when i use 1:20 to seperate ,each tube also has two materials..

[phil81]

Maybe your silyl group falls off on the column, leaving you with a mixture of product and SM... You might try a mild work-up without running a column if the TMS group is so unstable.

[agrobert]

Preparing your column with 1% TLC in your eluent will also prevent deprotection.