How can I modify my flash chromatography method to separate chemically similar compounds?

The challenges organic, medicinal, and natural product chemists face are many: from designing reactions, to optimizing synthesis, work-up / extraction, and purification / isolation of the desired compound or compounds. Among those issues related to purification / isolation is the common problem of separating compounds with similar chemistry that either co-elute or separate poorly.

In this post I will discuss some tips on how to “resolve” this issue (yes, pun intended).

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Ionizable compound purification using reversed-phase flash column chromatography

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.

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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?

Does a longer flash column really provide better purification?

This is an interesting question that I am asked from time to time. There does seem to be two camps in which chemists reside – one believing longer and thinner columns provide better separations and the other preferring shorter and fatter columns to do the same chromatography.

Which is right? That is a question I will try to answer based on my own data. Continue reading Does a longer flash column really provide better purification?

When should I use dry loading instead of liquid loading with flash column chromatography?

Many microwave assisted organic synthesis (MAOS) reactions use polar solvents such as alcohols, DMF, DMSO, because they absorb and transfer microwave energy very efficiently.  However, the downside of using polar, microwave absorbing solvents is that they can interfere with the flash chromatography that follows it injected directly onto a flash cartridge.

In this post, I discuss why dry loading can be advantageous when purifying polar-solvated reaction mixtures.

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Using pH to optimize reversed-phase flash chromatography separations

I have previously posted on the topic of normal-phase optimization by evaluating different solvent blends or mixtures. I have also touched on reversed-phase method development as well suggesting chemists use HPLC to optimize their purification.

In this post, I will look at the impact modifying mobile phase pH can have on reversed-phase separations.

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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.

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Why is my UV baseline changing during flash column chromatography?

A baseline that rises or drops when using flash chromatography with a UV detector can be a problem, especially if you are trying to collect compounds with poor detectability or that exist in low quantities.

In this post I will talk about the causes and solutions for a rising (or even dropping) baseline. Continue reading Why is my UV baseline changing during flash column chromatography?