In a previous post I shared results of experiments where I evaluated selected organic solvents for sample dissolution and injection for reversed-phase flash purification. I demonstrated that DMF and DMSO both are excellent solvents for this purpose and actually provide better chromatography than methanol, acetonitrile, and acetone.
In all my years of working with medicinal and organic chemists, I have found that choosing how many grams of silica to use for purification by flash chromatography is something frequently guessed at. Getting the size of the column right is awfully important because using too few grams of silica will doom your purification to failure and using more an optimal mass of the stationary phase means the purification consumes excess silica, solvents, and a chemist's time.
When it comes to the purification of polar organic compounds many chemists turn to normal-phase flash chromatography with dichloromethane and methanol as the mobile phase. This solvent system often can be challenging to optimize due to methanol’s high polarity and protic chemistry.
I have found that acetonitrile can often replace methanol as the polar modifier in DCM-based solvent systems. In this post I will show an example where this is true.
In this article I discuss the optimization of solvent ratios to generate ideal Rf (retention factor) values on TLC plates. Then I show how maximizing efficiency of flash chromatography achieves higher loading with rapid and reliable isolation of compounds, reduced solvent use and improved separation.
Challenging separations, we all have faced this vexing problem. You synthesized your compound, analyzed it, and know your molecule is in there, based on LC-MS or TLC. Then, you do some method development using a silica TLC plate and see a major spot with some minor, early-eluting impurities. You think that the purification will be easy only to find that your “purified” compound has some co-eluting impurities. Now what? Should you change solvents or change stationary phase?
In this post, I will show how changing the column media but keeping the same solvents removed a co-eluting impurity in one of my reaction mixes.