Silica Prep LC

Flash Chromatography

"Flash Chromatography" is a rapid form of preparative column chromatography - Prep LC based upon "an air pressure driven hybrid of medium and short column chromatography optimized for rapid separation." This approach was pioneered by W.C. Still at Columbia University, and described in J. Org Chem 43, 2923 (1978). Separation was based upon the relatively inexpensive apparatus used.

Flash chromatography is typically used to prepare 0.1 - 10.0g of material in less than 15 minutes and is especially useful when the differences on TLC are greater than 0.15 Rf units. Clearly, Flash Chromatography is a simple and economical approach to Prep LC.

Results were less than acceptable when large 63-200 microns (70-230 mesh) material was used, but remarkably improved when a mean of 40 micron (32-63 micron) material was in the column. Equally important: particle sizes less than 40 microns offered no significant improvement in resolution in this system.

The column is a flat bottom 18 inch glass tube fitted with a Teflon stopcock and topped with 24/40 standard taper glass joint, "Columns without fritted glass bed are generally preferred because they have less dead volume than the standard fritted type." Stills' group described the flow controller as a "simple variable bleed device."

Sorbent Selection
Use an analytical TLC plate to scout for the best solvents and to optimize separations. The desired Rf of the component should be 0.35 with a delta Rf of 0.15. Use Scientific Adsorbents' TLC plate, Silica Gel, 20x20 (Cat# 84101), or Silica Gel F-254, 20x20 (Cat# 84111).

The following SAI "Flash" Silica Gel Sorbent Catalog #s are recommended:

CAT# Description
02745 SILICA, 18-32u, FLASH, 10g
02757 SILICA, 18-32u, FLASH, 100g
02830-05 SILICA, 18-32u, FLASH, 500g
02830-1 SILICA, 18-32u, FLASH, 1kg
02830-2 SILICA, 18-32u, FLASH, 2.5kg
02830-25 SILICA, 18-32u, FLASH, 25kg
02826-05 SILICA GEL, 40 MICRONS (FLASH), 32-63u, 500g
02826-1 SILICA GEL, 40 MICRONS (FLASH), 32-63u, 1kg
02826-5 SILICA GEL, 40 MICRONS (FLASH), 32-63u, 2.5kg
02826-25 SILICA GEL, 40 MICRONS (FLASH), 32-63u, 25kg
02749 SILICA, ACTIVE, 18-32u, FLASH, 10g
02805 SILICA, ACTIVE, 18-32u, FLASH, 100g
02750 SILICA, ACTIVE, 32-63u, 40 MICRONS (FLASH), 500g

Column Selection
Select a column that is 10, 20, 40 mm ID based upon preparative requirements. Indeed, Professor Still et al offered this selection table:

Column Diameter
Volume of eluant*
Sample Load (mg) Fraction Size
Rf > 0.2 Rf >0.1
10 100 100 40 5
20 200 400 160 10
30 400 900 360 20
40 600 1600 600 30
50 1000 2500 1000 50
* Typical Volume required for equilibrium of the column and elution.
Dry pack "Flash" Silica Gel into the appropriate column to a height of 6" - 10" depending upon the resolution required. Gently tap vertically to pack the gel. Clamp and assemble. Fill with solvent, pressure slightly to compress the silica gel and force solvent and air through the column. The top of the column should not be allowed to run dry. Apply the samples as a 20 - 25% solution and elute at a flow rate of 2 inches/minute.

Fast. Generally 5 - 10 minutes.

Gram quantities. Typically 0.5 - 2.0g. Can be increased to 10g if less resolution is required and/or larger columns are used.

Flash Chromatography is a fast, cost efficient Prep LC approach. Separations are based upon traditionally obtained TLC results which are simply extrapolated to prep scale. Best of all, elaborate equipment and the purchase of expensive equipment is not necessary.

"Flash" Chromatography | Dry Column Chromatography | Column Chromatography | HPLC