Maybe it's just bad luck, or the fact I'm picking up synthesis again after a 4 month hiatus, but I've managed a week long streak of running crappy columns where stuff just co-elute all over the damn place.
And we're not talking about tight spots either, we're looking at things that have an Rf difference of at least 0.2. The separation looks so tantalizingly perfect on TLC, yet when I actually run the column, I get partial separation at best.
I slurry pack my column in whatever eluent I plan on using, and wet load my crude using toluene -- used to load with DCM until I had several bad experiences where it just flushed everything out within 5 fractions. After speaking to various people I've been told the following: pack column using hexanes only, do a gradient rather than an isocratic run, pack a longer column (I usually use about 6 inches of silica), and use dry loading rather than wet.
I usually get complete separation on running the 2nd column, only difference being I pack more silica and use a less polar system. I actually suspect it's what I use to load my column that's giving me these headaches. Right now my project involves making huge, greasy, polycyclic heterocycles, and I'm starting to think that these run merrily along with toluene. They dissolve in DCM just fine, but I get that flushing problem mentioned above.
For the record my columns usually use 5-15% EtOAc in Hexanes, and the Rf of the compound always runs around 0.3 on TLC in whatever system I'm running my column in.
Any insight is appreciated.