Hello all, I have a question regarding removal of lutidine from a reaction. I am using 2,6-lutidine as a base in a sulfinylation of an alcohol and I would like to remove it by washing or chromatography. At this point, I don't know enough about sulfinate esters to know whether or not they are labile during chromatography. In a test reaction with neopentyl alcohol, a sulfuric acid wash step removed the lutidine. However, my alcohol has an acid-labile protecting group elsewhere in the molecule, so this step would not work. When I have run sulfonylation reactions with triethylamine as a base in the past, I have used bicarbonate washes to remove the excess triethylamine successfully. However, bicarbonate did not remove the lutidine in our test reaction, based in H-1 NMR. Someone suggested that a copper sulfate wash can remove pyridine, and that it might work with lutidine also. Does anyone have any suggestions as to the removal of this base? Any input is appreciated, thank you.

Hi Sulfinator,

 

2,6-lutidine (pKa of BH+ = 6.65) is a much weaker base than TEA (pKa of BH+ = 10.75), and it's more lipophilic, too, that's why the bicarbonate wash can't remove it.

 

If your acid-labile group isn't exceedingly acid-sensitive (check in Greene's P.G.) you may want to try an acidic wash with something milder than H2SO4, maybe a buffered solution of some organic or weak inorganic acid. It only needs to have a pH lower than 6.65 (in practice say <5.65), so you have a huge choice.

I would also do a bicarbonate wash after that, just to make sure that no acid stays there and cleaves your group when you concentrate the organic extract (it happened to me!).

 

It's probably worth trying the simple option before turning to metals and the like.

 

Hope it helps.