How does media pore size impact small-molecule flash column chromatography?

For most chemists, flash purification is a means to an end. In other words, it is a tool needed to purify and isolate one compound from a mixture of compounds so that the next reaction can occur with reduced by-product formation. Other than choosing between normal– or reversed-phase, there typically is not much thought put into cartridge selection, especially not related to stationary phase media porosity.

For most small molecules, this approach makes sense, but for larger molecules and very lipophilic compounds, factoring for media porosity should be included.  In this post, I will discuss the impact media porosity can have on chromatographic performance.

Continue reading How does media pore size impact small-molecule flash column chromatography?

How to prevent compound precipitation during flash column chromatography

Compounds precipitating during flash chromatography is at best an inconvenience when working up your crude reaction mixture.  Precipitation during purification typically happens in the column or in the tubing exiting the cartridge.

In this post, I will propose a strategy that can minimize and perhaps prevent this issue from occurring.

Continue reading How to prevent compound precipitation during flash column chromatography

When should I use a pH modifier in flash column chromatography gradient?

Have you ever experienced compound tailing or streaking on your TLC plate or flash chromatography results and wondered what in the world is going on here? Well, there can be multiple reasons for this problem including poor mass-transfer kinetics, secondary solute-sorbent interactions, or unstable compound chemistry.

In this post, I will discuss one technique that has been shown to work time and time again to address the issue.

Continue reading When should I use a pH modifier in flash column chromatography gradient?

When should I use a “high-performance” flash chromatography column?

The evolution of flash column chromatography has brought chemists many new and exciting options for crude mixture purification. Among them are so-called high-performance flash columns or cartridges.  These high-performance purification tools are typically filled with silica or other media 15 to 30 microns in particle diameter (versus 40-63 micron for standard flash media) and provide the expectation of better separations and higher purity fractions.  That’s really enticing but how often do you need these types of columns especially since they are, of course, more expensive?  Well, that question is what I address below. Continue reading When should I use a “high-performance” flash chromatography column?

So, how does an ELSD work?

Evaporative Light-Scattering Detection, or ELSD for short, is a technology used with liquid chromatography to see UV-transparent (and UV-absorbing) compounds. In a previous post I talked about some applications where ELSD is not only useful, but required.

In this post, I will explain how an ELSD is configured and functions. Continue reading So, how does an ELSD work?

Why does my silica flash chromatography column get hot?

Silica is the most commonly used sorbent for flash column chromatography. When solvent is pumped through a column packed with dry silica you may notice it gets warm and sometimes down right hot!

In this post I will attempt to explain why this phenomena occurs. Continue reading Why does my silica flash chromatography column get hot?

Why is TLC Rf important for flash column chromatography optimization?

Many chemists I talk to understand that TLC data is useful for flash chromatography method development. Most also know that they should try to get their target compound to elute with an Rf between 0.15 and 0.4 by adjusting TLC solvent strength. Have you ever wondered why this is important and how Rf values impact flash chromatography results?

In this post I will explain the relationship between TLC Rf and flash elution volumes (CV) and why having your target compound elute in the Rf range is needed. Continue reading Why is TLC Rf important for flash column chromatography optimization?

Determining solvent strength in flash column chromatography

Recently, one of our readers wrote and asked how to determine solvent strength in normal-phase flash chromatography. This is an excellent question because solvent strength is one of several factors impacting flash chromatography performance.

In this post I will explain how solvent strength can easily be determined. Continue reading Determining solvent strength in flash column chromatography

Are reversed-phase flash chromatography columns designed for aqueous solvents necessary?

When it comes to the purification of polar, water-soluble compounds reversed-phase chromatography is the most commonly used approach. However, because of strong stationary phase – mobile phase repulsion forces, the use of highly aqueous (90-100% water) solvent systems has been shown to provide less retention than needed.  This issue has led to the development of “aqueous compatible” reversed-phase media.

In this post I explore if these types of phases are actually needed by looking at the separation of some very polar and low log P compounds using a “traditional” C18-bonded silica.

Continue reading Are reversed-phase flash chromatography columns designed for aqueous solvents necessary?

How does solvent choice impact flash column chromatography performance?

Selectivity and solvent strength are the most important factors that determine success or failure of a chromatographic separation. These two independent dynamics apply to both normal- and reversed-phase chromatography and should be optimized, especially when high fraction purity is needed.

In this post I will discuss the impact that elution solvent choice has on both normal- and reversed-phase purification. Continue reading How does solvent choice impact flash column chromatography performance?