Dry Column Vacuum Chromatography
05 August 2004 (online)
Chromatographic purification is an integrated part of organic synthesis. The Dry Column Vacuum Chromatography presented here, has excellent resolving power, is easily applied to large scale chromatography (up to 100 g) and is fast. Furthermore, the technique is economical and environmentally friendly due to significant reductions in solvent and the amount of silica used. Therefore, it is an excellent alternative to the commonly used Flash Column Chromatography for purification in organic synthesis.
liquid chromatography - purification - large scale chromatography
KoshkinAA. SinghSK. NielsenP. RajwanshiVK. KumarR. MeldgaardM. OlsenCE. WengelJ. Tetrahedron 1998, 54: 3607
SinghSK. NielsenP. KoshkinAA. WengelJ. Chem. Commun. 1998, 455
StillWC. KahnM. MitraA. J. Org. Chem. 1978, 43: 2923
HarwoodLM. Aldrichimica Acta 1985, 18: 25
HarwoodLM. MoodyCJ. PercyJM. Experimental Organic Chemistry 2nd ed.: Blackwell Science; Oxford: 1999.
SharpJT. GosneyI. RowleyAG. Practical Organic Chemistry 1st ed.: Chapman and Hall; London: 1989.
ShustermanAJ. McDougalPG. GlasfeldA. J. Chem. Edu. 1997, 74: 1222
The inventors of Flash Column Chromatography stressed on the fact that Flash Column Chromatography is pressure- and not vacuum driven. 9
Although we have never experienced any problems, it is important to use precaution with evacuated glassware. Special care should be taken when using a separatory funnel as it is not designed for this purpose. All chromatography should be performed in a hood behind a safety shield.10
In general we have found that it is possible to load a mixture of up to approx. 500 mg on 1 cm2 of silica surface (e.g. approx. 40 g on a column with a diameter of 10 cm) and still achieve good separation of mixtures with a ΔRf ≅ 0.05 (by analytical TLC).11
For small columns (< 4 cm) it is usually easier to dissolve the mixture in a small volume of n-heptane and add it evenly onto the surface of the column with a pipette. If necessary a small amount of EtOAc can be added to dissolve more polar compounds. If the mixture is very polar, the pre-adsorbtion procedure is preferable as the use of too much EtOAc will compromise the resolution.