Tags
columns week, dry column vacuum chromatography, Flash chromatography, medium pressure liquid chromatography, reverse phase flash chromatography
*To bring Columns Week to a close, here’s some additional reading*
The techniques outlined in the last few posts should be enough for the majority of chemists. But, I like to be thorough. So for those with special considerations, here are a few of my favourite modifications to standard flash chromatography.
Reverse Phase Silica
Dichloromethane/methanol mixtures can only take you so far in terms of polarity. True, “so far” generally encompasses all compounds with one or fewer free amines, but I’ve spent a fair bit of time purifying peptides and aminoglycosides. When your compound is that polar flash silica just won’t do, and it’s time to set up a reverse phase flash column. The alternative to an HPLC, gross separation of highly polar compounds is quite feasible. Unfortunately you’ll probably be stuck using NMR to identify your fractions, if there aren’t clear break points.
Medium Phase Liquid Chromatography
The little brother of HPLC, MPLC offers far better separation than a standard flash column, at about 1% the price of a full-fledged HPLC. Kyle Finchsigmate did the bulk of his PhD using one of these, and has spoken their praises at length (Build order, FAQ). Note: Most of the components will have to be purchased from used lab equipment websites. The hardest piece to acquire will be the automated sample changer, which (finally) frees you to do other things while your compounds purify.
Dry Column Vacuum Chromatography
At normal research scales flash is quite inexpensive, but offers little to no economy of scale. By the time you’re dealing with multi-gram quantities you’ll have swapped your wash bottles for 4L/gallon containers, and will be scrambling to find forty medium Erlenmeyer flasks (try not to think about the cleanup afterwards). The answer is dry vacuum column chromatography, which strangely has not really gained mainstream exposure. Daniel Sejer of the Curly Arrow Blog is a major fan of this technique, and has both a published methods paper on the topic and offered his personal tweaks (initial setup, improvements).
And there we go! That ends columns week at Chemtips. If you have any questions on what I’ve written, or are having some particular trouble with your experiments, let me know in the comments.
Chemtips 
For cationic complexes, I’ve used normal silica with an acetonitrile:water:sodium perchlorate 85:10:5 mobile phase. Isolation of the product from the salt can be tricky, but it’s usually just a matter of precipitation/filtration.
I second the DCVC method, especially as the mass of what you are trying to separate increases. I have even used it successfully in liquid/liquid mode, modeling silica gel TLC with a n-butanol-acetic acid-water mobile phase. I experimented and settled on n-propanol as a butanol substitute for easier removal. The column was eluted with decreasing amounts of propanol relative to a acid-water (1:1)