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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.
Sorbent
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.
Apparatus
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
(mm) |
Volume of eluant*
(ml) |
Sample Load (mg) |
Fraction Size
(ml) |
| 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. |
|
 |
Technique
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.Time
Fast. Generally 5 - 10 minutes. |
Results
Gram quantities. Typically 0.5 - 2.0g. Can be increased to 10g if less resolution is
required and/or larger columns are used.
Summary
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 |
