Fluorous Solid Phase Extraction (FSPE)

Features of Fluorous Solid Phase Extraction (FSPE)

  • Excellent choice for intermediate purification or biological sample enrichment
  • Good choice with C8F17 tags

Fluorous Solid Phase Extraction (FSPE)

Fluorous Solid Phase Extraction (FSPE) utilizes fluorous silica as the fluorous stationary phase to quickly separate all fluorous molecules from all non-fluorous molecules.

Fluorous Solid Phase Extraction is a powerful technique that can be used with just a single fluorous chain over a wide variety of molecular classes including small molecules, peptides, oligonucleotides and carbohydrates. For synthetic applications, FSPE can be used to isolate a fluorous molecule from non-fluorous impurities. For life science applications, FSPE can enrich a biological mixture for a class of compounds (e.g. fluorous cysteinyl peptides).

Simple Procedure

The solid-liquid extractions are operationally filtrations and they are easy to conduct in parallel either manually (see the manual solid-phase extraction apparatus above) or by using various automated techniques. In addition to the operational convenience, solid-liquid extractions succeed with many fewer fluorines in the fluorous domain compared to liquid-liquid extractions. For this reason, solid-liquid extractions are especially useful when the desired product of the reaction bears a fluorous tag. The solid phase extraction is applicable in essentially all areas from traditional synthesis through parallel synthesis, and is especially useful for parallel synthesis of intermediates.

Fluorous Solid Phase Extraction is generally a three-step process. The mixture is loaded onto the silica gel using a minimum of organic solvent. A fluorophobic wash, like 20% Water in Methanol, washes away all of the non-fluorous molecules while the fluorous molecules are retained on the silica gel. A fluorophilic wash, such as methanol or THF, is then used to wash the fluorous molecules from the stationary phase.

Example FSPE


The sequence below shows the separation of a fluorous dye (F-orange, FTI) from a non-fluorous one (Solvent Blue-35, Aldrich) by Fluorous SPE over a 2 gram FluoroFlash® silica gel cartridge. These aminoanthraquinone dyes have about the same polarity and cannot be separated by regular or reverse phase silica gel. The cartridges can be reused. For detailed instructions, along with a list of frequently asked questions, please download the F-SPE application notes from the links in the left section.

Automated and Parallel FSPE Methods

Now available from Fluorous Technologies are 24, 48, 96-well F-SPE plates (with 3g, 1g, 0.5g FluoroFlash® silica in gel each well, respectively) for parallel purification and high throughput purification of fluorous reaction mixtures.  These separations use either vacuum or positive pressure and procedures have been developed using commercially available manifolds. Other fluorous solid phase extraction options include gravity-driven plate-to-plate FSPE using larger particle size FluoroFlash® silica and automated serial FSPE using a RapidTrace® workstation. All of these options are used in conjunction with our fluorous reagents, tags, and scavengers to provide fast and effective purifications to increase your productivity.


Our FluoroFlash® line of tags, reagents and separation media are specifically designed to help you apply FSPE. For your convenience, we have listed additional materials about FSPE in the left column.

Solid-liquid extraction over FluoroFlash® silica is currently the most general and most easily implemented fluorous-organic phase separation technique. It is useful for the gamut of fluorous methods. Fluorous solvents are rarely needed for the extractions, and they are used only to wash the silica prior to reuse, if desired.

Selected References

  • "Synthetic applications of fluorous solid-phase extraction (F-SPE)" Zhang, W.; Curran, D. P. Tetrahedron Report No. 777, Tetrahedron 2006, 62, 11837-11865.