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.

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

When should I add acid to my detector make-up solvent when using mass-directed flash chromatography?

Increasingly, organic and medicinal chemistry labs use mass-directed flash chromatography to isolate synthesized compounds. Mass-directed flash chromatography benefits are many, including collecting only the targeted molecule(s) in the reaction mixture. This approach simplifies compound purification since you know what you have made and it’s associated mass.

However, there are mass detection nuances that can be challenging. One of these is to know when an acid should be added to the mass detector’s make-up solvent to protonate targeted molecules. In this post, I will provide some insight on this topic.

Continue reading When should I add acid to my detector make-up solvent when using mass-directed flash chromatography?

Why do I see more peaks than I expect with flash column chromatography?

Are you observing more chromatographic peaks than you expect compared to TLC or other assessment data?  Well, it could be that your method is separating some isomers or, it could be that there is an actual method issue.

In this post I will discuss what could cause a method issue and suggest some ideas as to how to fix it. Continue reading Why do I see more peaks than I expect with flash column chromatography?

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.

Continue reading Using pH to optimize reversed-phase flash chromatography separations

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?