Over the past several decades, the chemical industry has implemented process changes and updated practices in R&D and manufacturing in an effort to reduce liquid and solid lab waste. The pharmaceutical industry in particular has taken steps within their drug discovery labs to reduce solvent use by requiring their chemists to find and implement measures that achieve the corporate environmental goals without curtailing their productivity – quite the challenge.
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.
There are many factors which influence successful flash column chromatography. One of those factors is sample load, which itself is influenced by things like selectivity, efficiency, dissolution solvent, and load technique. Several of these factors I have addressed in previous posts. Of these, selectivity and efficiency are specific to a media's physical and chemical characteristics.
In this post I will show if particle size and/or particle shape can influence loading capacity. Additionally, I will show the positive impact that surface area has on flash column chromatography purification.
You have performed your synthesis and now it is time to purify the reaction mix. You have used thin-layer chromatography (TLC) and see a separation but when you try to purify with flash column chromatography, you can’t get the target compound separated from an impurity. So, what is happening (or isn’t happening)?
In this post I will give some input on why some separations are not transferable from TLC.
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.
Synthetic organic chemistry is the genesis of new pharmaceutical and commercial chemical products. In short, it is based on the idea that two or more carbon-based compounds can be forced to react using heat, or other energy source, to create a new, novel product – but this we already know.
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 preferring or needing to dry load their crude sample mixtures to get an acceptable flash purification result, using the right ratio of sample to sorbent can be quite important. Too much sample and solubility issues can ensue, too little sample and significant band broadening occurs, reducing the separation quality.
In this post, I propose an acceptable ratio range based on my own experimental data.
slash column chromatography has been practiced by chemists since the 1970s. That practice requires the silica in the column be properly wetted to remove trapped gasses and ensure uniform flow (remember those days of not letting air into the column?). Today, with automated flash chromatography systems and pre-packed columns as the norm, chemists ask me – do I really need to pre-equilibrate my column?
In this post I explore the impact on chromatography that equilibration, and lack thereof, has on separation performance.
Split peaks? Multiple peaks? Are they really a problem? What causes the issue?
In this post I will discuss what split peaks are and what to do to fix the problem.
Plate count is a theoretical number describing the separation efficiency of a chromatography column. In short, it is a measure an eluting compound's bandwidth at the time it elutes from a column, Equation 1.
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.