Organic reactions are generally inefficient, which means that crude reaction mixtures require work-up and purification to remove by-products and unreacted starting materials and/or catalysts. The goal in pharmaceutical research is to isolate the target compound with required purity and yield to be able to progress to the next synthetic sequence or biological testing with confidence. But the process of purification is viewed by synthetic chemists as a ‘means-to-an-end’ and the more rapidly and reliably the purification step can be performed the better. Easy enough to state, but hard to achieve when you need to be certain of purity and yield in a single, rapid purification attempt. As we will see here, flash column chromatography can help you achieve this.
The dark art of flash chromatography
Flash chromatography is a specialized technique that uses a low/medium pump to push solvent through a disposable flash column packed with stationary phase (often silica gel). This purification technique is particularly advantageous because it enables column chromatography methods to include faster solvent flow rates (in comparison to gravity flow) and compounds can be detected as they elute from the silica column, hopefully fully separated and collected into test tubes.
Modern chemists rely on flash column chromatography run with automated systems to get the job done, but seldom study the intricacies sufficiently to successfully control the separation. The result is less-than-pure compounds and poor yields. Automated flash separations are seen as more of a ‘dark art’, with success in purifying the target compound relying on luck versus know-how since most chemists cannot claim to be chromatography experts. Others may be overconfident that their separations will work out since they are convinced a favorite method will almost always work successfully at the first attempt. Some chemists just reason that it is just too challenging to learn how to use flash chromatography effectively or that it is not worth the time and effort to even try optimizing a flash separation.
Time to get control
The truth is, gaining control of the flash purification process will yield more predictable and successful separation outcomes in less time. In fact, modern flash systems equipped with high performance columns greatly reduce the risk of losing the target compound or inadequate sample recovery and get the job done fast. Added to that, chemists are appreciating the sophistication of platforms with built-in expert chromatography know-how that is easy to tap into, which boosts their chances of getting the job done right the first time.
In the next article in this series we will look at how you can gain control over your flash chromatography, including how to modify a column chromatography method to separate chemically similar compounds. We’ll demonstrate that with a few key choices in system design and control, you can greatly increase the certainty of your purification outcomes.
Stay current on what is possible with flash chromatography. Check out the Biotage flash purification blog.