u/1-MatjE

Background
I have been synthesising a series of vinylbenzene derivatives, all of which have been previously reported as solids in the literature. After purification by flash column chromatography, removal of solvent by rotary evaporation, and several hours under high vacuum, however, I am left with oils in some cases. The proton NMR spectra are clean apart from a small water peak (~1.55 ppm in CDCl3) and confirm that the oils are the desired compounds.

I am able to convert these oils into solid powders using the procedure I’ve outline below.

My questions are:

1. What is this process properly called (my lab mates call it freeze-drying, which I don’t think is right, since there is no solvent being sublimed) and; 2. How should I describe this concisely in an experimental? My PI and I have hopes to submit to Org. Left., JOC, or similar at the conclusion of this project and the procedure(s) will most likely appear in the SI.

Procedure
The RB flask containing the oil is placed under static vacuum on a Schlenk line and lowered into a liquid nitrogen bath. After around 5 minutes it is removed and allowed to warm to room temperature. After a further 30 minutes, the material is a powdery solid.

Any thoughts on the correct terminology, and on suitable wording for the SI, would be greatly appreciated.

Additional Note
No literature procedure I’ve come across for these compounds, or similar, describe anything like this.

I’ve noticed that there are a lot of different ways people go about running a column.

Interested to hear how you guys will tend to set up and run a column and the rationale (if any) behind why you do it that particular way. Any particular tips and tricks?

Hopefully the comments (and maybe my procedure – although it is in no way perfect nor do I claim it to be) can help serve as a guide to new researchers.

I pretty much exclusively do dry loads and my typical column procedure is as follows:

1. Add dry silica directly to the column (honestly I just eyeball how much).
   2 Add eluent. With isocratic elution the eluent will be the ‘ideal’ solvent system I selected based on TLCs. With gradient elution the eluent will typically be a system that gives my target compound spot (if I know which spot it is) an Rf of about 0.
2. Stopper the column and shake until I form a slurry.
3. Open the tap and turn on pump until the solvent is a couple of centimetres above the silica, wash down any silica stuck to the sides with eluent, then open the tap again and turn on pump until the solvent is pretty much level with the silica (ensuring I do not dry it though).
4. Add dry load using a solids funnel. Then, using a minimal amount of eluent, wash out the dry load RB and wash down any solids stuck on the sides of the column. I will give the column a couple of light taps to make sure the dry load is level.
5. Turn on pump until the solvent is level with the top of the dry load (I don’t think it matters if it goes below, just as long as you don’t dry the top of the silica).
6. Add a layer of sodium sulfate (again I just eyeball).
7. Add eluent (I should probably do this more slowly and carefully tbh to prevent any chance of disturbance), run the column, collecting the fractions in test tubes whose size was selected based on the crude mass, the closeness of spots on the TLC, and the availability of clean test tubes in our lab.

Some Notes
Pour silica, shake, and run the column inside a fume hood.

Wetting silica is exothermic and volatile solvents will build real pressure, so when stoppering and shaking, vent frequently by taking the stopper off, and point the column away from yourself and others while you do.

The dry load is usually prepared by adding an appropriate (I usually eyeball but ~2x the mass of the crude) amount of Celite (I should probably start using silica though, to be honest) to the crude, adding enough DCM to make a slurry, and finally removing the DCM by rotary evaporation. Always ensure it is completely dry (residual DCM can smear the bands).

In our lab we pretty much exclusively use columns with a sintered layer. Use cotton wool or glass wool and a layer of sand if you don’t have sintered columns.

Finally, don’t be afraid to ask a more experienced lab mate for advice if you’re unsure. You’ll pick things up much faster, and you’ll avoid mistakes that are easy to avoid once someone has pointed them out.