How can I improve my liquid-liquid extraction process?

In synthetic organic chemistry, post-reaction work-up using solvent extraction is almost routine. Solvent-solvent extractions using immiscible solvents can remove impurities from the product prior to the reaction mixture’s eventual purification either by flash chromatography or crystallization.

1. Solvent-solvent extraction has traditionally used a glass separatory funnel placed on a ring stand with denser solvent collected and either discarded or evaporated for further purification. While this methodology works well, it isn’t without its issues, namely…
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   1. 1. The separatory funnels need to be cleaned after use which involves removing the stopcock
3. 2. Before use, the separatory funnel needs reassembly, including the stopcock
4. 3. Most separatory funnels are glass meaning they can break
5. 4. Separatory funnels are not cheap and can cost several hundred dollars, depending on size and brand
6. 5. When not in use, separatory funnels need to be stored somewhere, taking up substantial lab cabinet or drawer space
7. 6. Extractions require the chemist to carefully read the meniscus or solvent interface to ensure only the denser solvent is collected, increasing the time required for each extraction
8. 7. When the extracting solvent is added to the reaction mixture, the solution must be mixed (stirred, not shaken) enough to get the organic components into the organic solvent and the polar components into the aqueous without creating an emulsion
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Seven drawbacks to a relatively simple procedure. I have found, however, a different, simpler, and more efficient way to perform these extractions. Instead of using a separatory funnel, you can use a device called a Biotage® Phase Separator. This is a disposable/recyclable polypropylene reservoir fitted with a very hydrophobic frit. Organic solvent, typically DCM or chloroform, passes through the frit while the aqueous portion remains in the reservoir. No meniscus or interface to watch. Nothing to clean afterwards. They use minimal space and are available in assorted sizes. Extractions, depending on the volume, take only a few minutes to complete.

I tried this in my lab extracting the organic product from a reaction I conducted in water (3 mL) - isatoic anhydride + benzylamine, 1 mM scale, using a Biotage® Initiator+ microwave reactor.

After the 10-minute synthesis, I placed a 15 mL volume Phase Separator on a 20-position Biotage® Gravity Rack. I then placed a 20 mL scintillation vial under the Phase Separator and poured the reaction vessel’s contents into another scintillation vial and added 5 mL of DCM. This mixture was thoroughly mixed and transferred into the Phase Separator where the denser DCM passed through the frit into the scintillation vial. I then added 2 x 2 mL more DCM to the Phase Separator with stirring and collected the extract. You can watch the process below

After evaporation on a Biotage® V-10 Touch, the product yield was 240 mg. The total extraction time was about 3 minutes and afterwards, I poured the aqueous portion into my hazardous waste container and the Phase Separator into the plastic recycling bin.

Quick, easy solvent-solvent extraction without the issues encountered using separatory funnels. If this has piqued your interest, learn more about them, click the link below.