Abstract
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.
Key words
liquid chromatography - purification - large scale chromatography
References
<A NAME="RZ09601SS-1">1</A>
Koshkin AA.
Singh SK.
Nielsen P.
Rajwanshi VK.
Kumar R.
Meldgaard M.
Olsen CE.
Wengel J.
Tetrahedron
1998,
54:
3607
<A NAME="RZ09601SS-2">2</A>
Singh SK.
Nielsen P.
Koshkin AA.
Wengel J.
Chem. Commun.
1998,
455
<A NAME="RZ09601SS-3">3</A>
Still WC.
Kahn M.
Mitra A.
J. Org. Chem.
1978,
43:
2923
<A NAME="RZ09601SS-4">4</A>
Harwood LM.
Aldrichimica Acta
1985,
18:
25
<A NAME="RZ09601SS-5">5</A>
The inventors of Flash Column Chromatography stressed on the fact that Flash Column
Chromatography is pressure- and not vacuum driven.
[3]
<A NAME="RZ09601SS-6">6</A>
Harwood LM.
Moody CJ.
Percy JM.
Experimental Organic Chemistry
2nd ed.:
Blackwell Science;
Oxford:
1999.
<A NAME="RZ09601SS-7">7</A>
Sharp JT.
Gosney I.
Rowley AG.
Practical Organic Chemistry
1st ed.:
Chapman and Hall;
London:
1989.
<A NAME="RZ09601SS-8">8</A>
Shusterman AJ.
McDougal PG.
Glasfeld A.
J. Chem. Edu.
1997,
74:
1222
<A NAME="RZ09601SS-9">9</A>
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.
<A NAME="RZ09601SS-10">10</A>
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).
<A NAME="RZ09601SS-11">11</A>
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.
