Can reversed-phase flash chromatography purify better than normal-phase?

The answer to this question is yes, reversed-phase can sometimes provide a better separation and thus better purification than normal-phase.  When is reversed-phase likely to be the better choice is a different, and likely better, question.

In this post I will try to demonstrate when reversed-phase is likely the better purification mode.

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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 to efficiently scale-up flash column chromatography

For synthesis and medicinal chemists, compounds are typically made only once en route to a final product. Once that compound shows activity toward a particular target, then the synthesis is scaled up meaning that purification too requires scaling. The same is true in natural product research where once a high-value compound is isolated at small scale, there is a need to isolate it at larger scale.

Both of these scenarios can be problematic to scale-up/ process chemists when other, non-chromatographic purification techniques are not successful. When this happens, either a different synthetic route or extraction process is needed or large scale chromatography is employed. In this post, I will explain how flash chromatography can be successfully scaled while minimizing time and solvent consumption. Continue reading How to efficiently scale-up flash column chromatography

How do I purify ionizable organic amine compounds using flash column chromatography?

For most organic reaction mixture purifications the process is fairly straightforward. Use hexane/ethyl acetate or, for polar compounds, DCM/MeOH.  But what do you do if this doesn’t work and your compounds are basic organic amines?

In this post, I re-examine the options available to achieve an acceptable organic amine purification when typical separation methods are insufficient. Continue reading How do I purify ionizable organic amine compounds using flash column chromatography?

What do I do if a 2-solvent gradient will not separate my sample?

Usually, a 2-solvent or binary gradient will separate your desired compound from the by-products and impurities. Sometimes though, you can encounter a mixture in which some compounds co-elute and are not separable with any binary gradient you try.

I encountered this situation recently while trying to purify a lavender essential oil and have dedicated this post to how I solved the problem.  Continue reading What do I do if a 2-solvent gradient will not separate my sample?

How does mobile phase organic solvent choice impact 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?

How do I remove an annoying MS TIC background?

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?

Using TLC to Scout Flash Chromatography Solvents

TLC is the tool most used for normal-phase flash chromatography method development. For many chemists, a solvent system of hexane (or heptane) + ethyl acetate is the first, and sometimes only, solvent system evaluated. Though often useful, ethyl acetate may not always provide the optimal purification conditions.

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