Flash column chromatography equilibration speed – how fast can you go?

Equilibrating silica flash chromatography columns is something I always do.  There are chemists who see this as an unnecessary, time-and-solvent-wasting step.  Because getting consistent, predictable results is a priority, I equilibrate to remove the variability that can be caused by heat generated as solvent initially contacts the silica. Consistency is really important when running flash column chromatography because re-runs are time consuming and may put your compound at risk.

In this post, I examine the role of equilibration speed and duration to show its impact, or lack there of, on purification performance.
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How can I perform normal-phase and reversed-phase column chromatography on one flash system?

For chemists, flash chromatography is part of their everyday synthesis workflow. For most syntheses, crude reaction mixtures are purified by normal-phase (aka adsorption) chromatography.  There are times; however, where the crude mixture’s complexity and polarity make normal-phase chromatography very challenging.  For these situations, reversed-phase (aka partition) chromatography may be a preferred option.

But, if you have only one flash system available, can you, should you, and how do you efficiently switch from non-polar, normal-phase solvents to polar, reversed-phase solvents – and back again without issues? In this post I’ll attempt to shed some light on the topic. 

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How do particle size and flow rate affect normal-phase flash column chromatography?

Media particle size and solvent flow rate play major roles in chromatographic separations including flash purification.  This is true in both reversed-phase chromatography (aka partition chromatography) as well as normal-phase chromatography.

The roles played are related to the overall compound mass-transfer kinetics and diffusion/dispersion as they migrate through the column.  Smaller particles reduce sample dilution by reducing interstitial volume, while flow rate impacts the ability of molecules to efficiently pass through the porous particles.

In this post, I will show how both particle size and flow rate impact flash chromatography.

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How many times can I reuse my flash chromatography column?

Flash chromatography – a purification tool for both organic chemists and natural product researchers.  This tool is essential when you need to remove impurities from your targeted product, or products, in order to get them pure.  To reduce the costs associated with flash chromatography, some chemists try reusing the same column over and over, not always with success.

A question I am frequently asked is “how many times can I reuse my flash column?” Although I have previously addressed this topic, I feel it is worth another look. In this post, I will attempt to address this question by providing a bit more science behind the cartridge reuse question.

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