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?” For many years I have heard from organic and medicinal chemists as well as students of organic chemistry that silica is dissolved by methanol when running a DCM/MeOH gradient.
In this post I will share the results of some tests I performed that hopefully will help clarify what is happening to the silica when in contact with methanol.
Continue reading Does methanol really dissolve silica during flash column chromatography?
In many of my previous posts I have used the term column volume, typically abbreviated as CV, as a value used to help determine separation quality and loading capacity. However, I recently was asked a question about this topic from a chemist who understands the column volume concept but wanted to better understand its definition and how it is determined.
In this post I will explain what a column volume is and how it is determined empirically.
Continue reading So, what exactly is a column volume in flash column chromatography and how is it determined?
Flash column chromatography has been practiced by chemists since the 1970s. That practice required the silica in the column be properly wetted to remove trapped gasses to ensure uniform flow (remember those days of not letting air into the column?). Today, with automated flash chromatography systems and pre-packed cartridges as the norm, chemists ask me – do I really need to pre-equilibrate my cartridge?
In this post I explore the impact on chromatography that equilibration, and lack thereof, has on separation performance.
Continue reading Flash column equilibration – is it a waste of time or necessary step?
How does flow rate impact my flash column chromatography separation? This is the kind of question I frequently get. After all, we all know that high flow rates that are too high or too low mean bad prep HPLC chromatography. Well, this is not necessarily true in flash chromatography.
In chromatography there are three inter-related variables which impact your separation and are represented on the chromatographer’s triangle.
In practice only two of these variables can be optimized. Increasing flow rate decreases either load (if you need to maintain a purity level) or purity (if you need to maintain a throughput) because of increase sample dispersion and band-broadening. If you increase load, you need to decrease the optimal flow rate or purity will suffer. You get the idea.
In this post I will discuss the impact that flow rate has on flash chromatographic performance.
Continue reading Setting the Right Flow Rate for Flash Column Chromatography
Method transfer from reversed phase TLC (thin layer chromatography) to reversed phase flash column chromatography can be very challenging. Because of this, I often recommend using HPLC for reversed phase flash chromatography method development. This really is a straight-forward process if you start with the right HPLC column and know a little about your HPLC system’s detector.
In this post I will share some tips on how to develop a reversed-phase flash purification method using HPLC.
Continue reading How do I develop a reversed-phase flash column chromatography method?
I am often asked why reversed-phase TLC data does not translate well to reversed-phase flash column chromatography. There are several reasons for this and in this post I will attempt to explain the challenges associated with reverse-phase TLC as a method development tool for reversed-phase flash chromatography.
Continue reading Can I use TLC for reversed-phase flash column chromatography method development?
Applying green chemistry principals to flash purification is becoming increasingly important. In this post, I discuss ways to make flash column chromatography greener by reducing solvent use through optimization of gradient shape.
This is a follow-on to my earlier post where I presented some greener alternatives to DCM as a solvent in flash column chromatography.
Continue reading Can flash column chromatography be green? Part 2
Flash column chromatography is used by between 20 and 40 thousand organic synthesis chemists worldwide, an amazing number. For most of these chemists flash chromatography is an important part of their daily workflow but allocating time for good method development is often not considered, which can lead to less than ideal purification results.
In this post I focus on how allocating just 10 minutes on thin-layer chromatography (TLC) for method development can save you a lot of grief later on.
Continue reading Invest 10 minutes on TLC and save a day of grief
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…
1. Replacing chlorinated solvents with those considered more environmentally friendly
2. Reducing solvent use and waste generation with more thoughtfully applied chromatography principals
In this post I will discuss alternatives to chlorinated solvent-based flash column purification. In the future, look for a post on reducing solvent use (and its waste).
Continue reading Can flash chromatography be green? Part 1
For many chemists performing bench-scale organic synthesis flash column chromatography is the primary purification technique. When your synthesis needs scaling to multi-gram levels, so does the flash purification. The logical approach is to just increase the flash cartridge or column size, but this is only part of the solution.
In this post I discuss the process of simplified flash purification scale-up.
Continue reading Scaling-up flash purification – as easy as 1, 2, 3, 4