chromatography of sulfonamides - please help!

[asau09]

Hello fellow scientists,

 

A few days ago, I ran a reaction of an alkynyl tosylate (specifically ROTs, the R group being an internal alkyne) with p-toluenesulfonamide (TsNH2) in base (K2CO3) in hopes of alkylating the sulfonamide, and getting RNHTs out as the product. This reaction took much longer than I imagined, and I finally decided to work it up after 3 days of it running. When I took a TLC test of the crude, there was some starting material, the product spot, and p-toluenesulfonamide. From past experience (I ran this reaction before, except using 1-bromo-2-butyne), I had to use a 1:1 Hexane:EtOAc mixture to chromatograph this mixture, leaving me with ~50% yield of product. Last time, however, I had no starting material left over so chromatographing it was more simple compared to this time. I've been having issues trying to get the solids of the mixture (yes, the substrates and products are all solid) to dissolve in the Hex:EtOAc (4:1) system (this provided a better separation, as seen by TLC). I've tried dry-loading using silica, recrystallization from methanol and hexane, and so far nothing's working!! Please help me figure out how to solve this issue...

[hypervalent_iodine]

The obvious solution would be to try a different solvent system. Have you tried MeOH:DCM combinations? In my experience with nitrogen containing compounds, they are often the best systems.

[asau09]

The obvious solution would be to try a different solvent system. Have you tried MeOH:DCM combinations? In my experience with nitrogen containing compounds, they are often the best systems.

 

I have not, but I will test it out. Thanks for the reply! Just for clarification, how would the MeOH:DCM solvent mixture be different than using Hexane:EtOAc? Would it be because of the polarities of MeOH and DCM versus hexane and ethyl acetate?

[hypervalent_iodine]

I have not, but I will test it out. Thanks for the reply! Just for clarification, how would the MeOH:DCM solvent mixture be different than using Hexane:EtOAc? Would it be because of the polarities of MeOH and DCM versus hexane and ethyl acetate?

 

Well for one, you shouldn't have any problems with solubility and it won't stick so badly to the column. With nitrogen containing compounds, you also tend to get smearing as opposed to a nice clean spot on TLC and this is fairly representative of what happens in the columns. MeOH/DCM mixtures help with that. I would say this is definitely related to polarity.

 

Another thing to try is to flush your column with your solvent + 5% TEA and then run it with 1-2% TEA. If you do this, you'll also want to pre-wash your TLC plates with the 1-2% TEA/solvent mixture and play around with your solvents to figure out the optimal system. Then there is also basic alumina or alternatively, you could deactivate your silica gel by stirring it with bicarb for a few hours and then washing it through with water and acetone. I use the last method for my especially hard to purify amides.

[Horza2002]

Out ouf curiosity, why are you trying to make the sulphonamide that way? Surely it would be much easier to react the R-NH2 (amine) with tosyl chloride to give you the sulphonamide. I know this works great because I have actually just done the reaction 15 mins ago

[asau09]

Out ouf curiosity, why are you trying to make the sulphonamide that way? Surely it would be much easier to react the R-NH2 (amine) with tosyl chloride to give you the sulphonamide. I know this works great because I have actually just done the reaction 15 mins ago

 

I would have definitely used that approach, but I was trying to alkylate p-toluenesulfonamide with an alkyl group (butyne with an internal C-C triple bond), but we don't have butynyl amine in our lab (if it does exist at all).