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.

Purifying polar organic compounds can be very challenging. In a previous post I have discussed using reversed-phase flash chromatography to retain and purify ionizable and ionic compounds.  My colleague, Dr. Elizabeth Denton, has also posted a blog on purifying very polar peptides as well.  Sometimes, however, despite all your efforts with reversed-phase, success is elusive. When this happens, what do you do?

Recently, one of our readers wrote and asked how to determine solvent strength in normal-phase flash chromatography. This is an excellent question because solvent strength is one of several factors impacting flash chromatography performance.

In this post I will explain how solvent strength can easily be determined.

In our more environmentally aware climate, chemical and pharmaceutical companies now prioritize reducing organic solvent use in chemistry labs. Employees and shareholders alike are pushing their companies to become greener which impacts how chemistry, both synthesis and purification, is performed.

If you synthesize organic amine compounds, especially heterocyclic, secondary, or tertiary amines, you likely have encountered problems with their chromatography using silica columns. With the amine groups being basic and silica being acidic, there is a natural attraction between the two. This sometimes strong attraction often requires the use of a competing amine in the solvent system. Modification of the mobile phase with the addition of a solvent like triethyl amine can provide a successful purification. Often times the use of an amine-modified stationary phase can provide the needed conditions to avoid the acid-base interaction that can interfere with a successful flash chromatography purification.

This is an age-old question that has been around a long time, perhaps as long as me (and I have been around a while) –  “Does silica dissolve in methanol?”