The term “Green Chemistry” has become a major part of the science community’s lexicon. When I think about green chemistry and its relationship to flash column chromatography I think of two specific areas where it applies...

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.

An interesting question, at least to me. Depending on the detector brand, some mass spectrometer manufacturers recommend acetonitrile while others recommend methanol. Is there a real difference between these solvents?

In this post I look at how acetonitrile and methanol compare when used with an APCI source.

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.

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.

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.

Organic chemistry syntheses often use polar, high boiling point solvents to facilitate high temperature reactions. However, these solvents also can complicate down-stream compound purification, either by evaporation, crystallization, or even flash 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.

Recently, I posted an article explaining why high performance TLC plates are not needed for method development for high-performance flash chromatography.  Based on some excellent feedback, I see a need to discuss silica chemistry and its impact on chromatography.

For many chemists using generic linear gradients and even gradients based on TLC the purification results often are not selective enough to separate all of the compounds in their mix.  This is especially true if your target has a closely eluting impurity. One method used to try and increase resolution is the use of an isocratic hold or gradient pause during purification.

In this post I examine the use of the isocratic hold to determine how well it works and when/if it should be inserted into a gradient method.

The products of organic synthesis are designed with specific functional groups in order to possess desired properties. Depending on the compound’s functionality, it can be neutral, acidic, or basic as determined by a compound measurement called pKa or acid dissociation constant. Compounds with low pKa are typically acidic while those with high pKa tend to be basic. Compounds with a pKa near 7 are deemed neutral.

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).

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. 

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.

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.

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.