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.
Continue reading How can I perform normal-phase and reversed-phase column chromatography on one flash system?
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.
Continue reading How do particle size and flow rate affect normal-phase flash column chromatography?
The bane of organic synthesis for most chemists is purification rather than synthesis. Synthetic reaction mixtures are rarely devoid of impurities so some type of purification is necessary. Most often flash chromatography is used but for many chemists, it is less well understood than their chemical reaction and provides some level of anxiety.
In this post, I will summarize the five most important steps to creating a successful flash chromatography method and thus the anxiety associated with it.
Continue reading 5 Steps to successful flash chromatography
I have recently posted on how solvent choice influences the separation of hard to resolve compounds using normal-phase flash chromatography. As a chemist with an inquiring mind, I thought I would expand my research beyond normal-phase and see what happens in reversed-phase.
In this post, I share my results.
Continue reading How does solvent choice impact reversed-phase flash chromatography separations?
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.
Continue reading How many times can I reuse my flash chromatography column?
With most chromatographic purifications, only two solvents are needed to adequately separate compounds from each other. Unfortunately, there are instances where the separation is either poor or cannot be accomplished with “normal” elution conditions such as those with ionic or very polar organic molecules.
In this post I offer some solutions to this issue.
Continue reading Ionizable compound purification using reversed-phase flash column chromatography
Organic and medicinal chemists frequently utilize flash chromatography to purify their reaction mixtures. Normal-phase flash chromatography is most often used but may not the best methodology, especially when the compounds are quite polar and/or ionizable.
For these molecules, reversed-phase flash chromatography is preferred but often is not used due to an uncertainty regarding the best solvent choices and the reversed-phase mechanism. In this post, I will discuss how organic solvent choice in reversed-phase chromatography can influence the chromatographic separation.
Continue reading How does mobile phase organic solvent choice impact reversed-phase flash column chromatography?
In this post, I will look at the impact modifying mobile phase pH can have on reversed-phase separations.
Continue reading Using pH to optimize reversed-phase flash chromatography separations
Have you ever run flash column chromatography with mass detection (Flash-MS) and observed the total ion current or TIC increase during the purification only to find that there was no discernible compound contributing to the effect?
In this post I discuss how I came across this issue and the solution I found to work.
Continue reading How do I remove an annoying MS TIC background?