For medicinal chemists, maximizing the synthetic yield of their newly created intermediate compound is their priority. More times than not, flash chromatography is used to purify these intermediate compounds to at least 80% purity. Final compounds, however, not only require high yield but maximum attainable purity, typically in excess of 95%. For this purity level, chemists will either send the reaction mixture to an in-house prep HPLC lab or perform their own preparative HPLC compound purification, if it is available in the lab.
In a previous post I talked about column size, specifically long-thin versus short-fat and the impact of the cartridge’s dimensions on purification performance. With that comparison I showed that in preparative chromatography, purification efficiency is more about the amount of silica than column dimensions. Cartridges of different dimensions containing the same amount of the same media will provide the same separation efficiency.
Yes, the title is a bit salacious but it got your attention, didn’t it? I believe this is a topic worthy of discussion as it relates to flash chromatography for purification because many chemists believe longer but thinner columns perform better than short, wide columns. The facts of the matter may surprise you.
In this post I discuss the impact that cartridge dimensions have on purification performed using flash purification.
A question I hear a lot from chemists is “how much can I load”. The answer is always “it depends on your separation quality”. At that point I begin asking about the TLC data and purification goals. Purification goal setting should be your first step and the question to answer is – what do I need this purification to achieve? Is the goal high purity, high yield, or some combination. Remember, you will typically sacrifice purity for high yield and yield for high purity so optimization is an important consideration.