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.

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.

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.

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.

Compounds precipitating during flash chromatography is at best an inconvenience when working up your crude reaction mixture.  Precipitation during purification typically happens in the column or in the tubing exiting the column.

In this post, I will propose a strategy that can minimize and perhaps prevent this issue from occurring.

For chemists needing to purify natural product extracts or synthesis reaction mixtures flash chromatography is typically the tool of choice. In previous posts I have discussed various ways to optimize the purification to obtain the highest purity compounds with maximum load in minimal time.

Sometimes, though, chemistry gets in the way in the form of solubility issues. When this happens most often dry loading is recommended for these sample types. In this post I will show the impact various dry load sorbent options have on chromatography.

One of the more challenging purifications is that of water-soluble, ionizable compounds. Typically, normal-phase with silica is not used because of the probable non-reversible interactions, especially between the ionized amines interacting and the ionizable silanols.  With normal-phase out of the purification solution that leaves ion exchange and reversed-phase as chromatographic options.

In this post I will discuss the use of reversed-phase and the influence pH and buffers have on the chromatography of some ionic, water soluble compounds.

In this post I will delve into six key factors that impact your purification success in flash column chromatography.

Previously, I have discussed the use of TLC for solvent scouting and method development and optimization. I have have also talked about cartridge size, particle size, and surface area and their impact on flash purification.  Here I integrate that information into the six factors below.

Many chemists today find they need to synthesize molecules at higher temperatures in order to force difficult reactions to proceed. Solvents such as DMF, DMSO, and NMP are commonly used in these reactions as they facilitate the use of the high reaction temperatures.  However, the same attributes that make these chemicals attractive as reaction solvents make compound recovery from them very difficult, including flash column chromatography.  These high boiling solvents are typically polar and pose a challenge if purification is to be accomplished with normal-phase silica.

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. 

How to choose between normal- and reversed-phase flash column chromatography is an excellent question and one that my readers often ask.  Those who use column chromatography know that as long as the reaction products or compounds are fairly non-polar and near neutral pH they will have successful purifications.  However, when your mixture's chemical characteristics are more challenging (polar, non-polar, basic, acidic) there are other options that are available to successfully separate pure compounds.

In this post, I will discuss the criteria you can use to guide your choice between normal- or reversed-phase flash chromatography.

Acetone, as you know, is a terrific solvent.  It dissolves many organic molecules, evaporates easily, is both water and organic soluble, and is cheap (relatively).  These attributes tell me it should be a good polar modifier for normal-phase flash chromatography.

In previous posts I have touched upon various sample loading options and how they impact flash chromatographic performance, primarily in normal-phase flash purification. As the use of reversed-phase flash chromatography has steadily increased over the past few years I thought it would be a good idea to discuss one of the most important factors impacting its success.

In this post I discuss the results of some of my original research studying the impact of injection solvent choice on reversed-phase flash separations.

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.