Hello,
I have done a mesylation reaction on some diol I made but I keep getting so many side products. I recently purified a new set of diols using FCC to try the mesylation reaction with MSCl and DMAP, but on integrating the NMR of my diols, I can notice a little single peak at 0.07ppm (CDCl3) corresponding to that of a silanol. From NMR integration, I would say this is about 10% of what I have as my diol.
Will SIlanol from Silical gel affect my mesylation reaction and whats the best way to get the silanols off my product?
Thanks.
I would suggest using triethylamine (Et3N) with your mobile phase while running the FCC. This would prevent the side reactions.
Is your mesylate to act as a leaving group or protecting group? If leaving group, the compound may not be very stable and it may be better to just do the next reaction. If it is a PG, then you may have to consider changing the PG
I didn't see what solvents were used to elute the compound from the flash column. Polar, basic solutions will dissolve silica gel. An example is dichloromethane/methanol with ammonia or ammonium hydroxide added. This starts dissolving the silica somewhere greater than 10% methanol. Perhaps that is what you see in the NMR.
You could also try alumina. If your compound is decomposing, try a bonded phase such as diol or cyano. These can both be run as normal phase. For an example, see:
http://www.teledyneisco.com/en-us/liquidChromatography/Chromatography%20Documents/Application%20Notes/Purification%20of%20Delicate%20Compounds%20with%20RediSep%20Rf%20Gold%20Diol%20and%20Cyano%20Columns%20App%20Note.pdf#search=diol
As Jack points out, methanol in the eluant will leach silicic acid from a silica column. If your diol is a 1,2- or 1,3- diol, you could easily end up with cyclic siloxy ethers. Use alternative solvents and/or column packing.
Also, rather than DMAP, you should use Et3N or (i-Pr)2NEt as the base in the mesylation reaction. The intermediate, when using these stronger bases, is the sulfene, CH2=SO2, and you can run the reaction at a considerably lower temperature. Neutralize before warming, and work up normally.
Just one minor addition to the answer above- neutral or acidic solutions are OK with silica gel. It is possible (and fairly common) to run methanol/water gradients with silica. The technique is called HILIC and is applicable to a number of normal phase chromatographies, including silica.
An example is here: http://www.teledyneisco.com/en-uk/liquidChromatography/Chromatography%20Documents/Posters/Strategies%20for%20Flash%20Purification%20of%20Highly%20Polar%20Compounds%20Poster.pdf#search=HILIC
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