Flash chromatography is the most commonly used purification tool for organic and medicinal chemists whose reaction scales typically range from milligrams to grams. The column size to be used for the purification of these reaction mixtures is selected either by using the 1% rule which states that for many reaction mixtures, a crude reaction mixture load equaling 1% of the column’s media weight often will provide the needed purity, assuming the right elution method is selected. While this strategy can work, often chemists either overload or underload the selected column resulting in low product purity which requires re-purification. In both situations, the chemists wastes time, solvent, and the cost of the column.
For many synthetic chemists the primary purification goal is to isolate as much synthetic product as possible with a minimum of 80% purity. The go-to technique for product isolation is flash purification (flash chromatography), especially for intermediates.
Scaling up reversed-phase flash chromatography methods is often necessary as reaction scale increases. This is especially true when other non-chromatographic purification techniques do not work or meet purity and/or yield needs.
This is an interesting question that I am asked from time to time. There does seem to be two camps in which chemists reside – one believing longer and thinner columns provide better separations and the other preferring shorter and fatter columns to do the same chromatography.
Which is right? That is a question I will try to answer based on my own data.
Chromatography is a common tool of the chemistry laboratory, and most chemists involved in synthesis have a good idea how automated flash purification system work on the lab bench. However, knowing how to take purifications from the laboratory to a manufacturing environment is a different question altogether.
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.
In all my years of working with medicinal and organic chemists, I have found that choosing how many grams of silica to use for purification by flash chromatography is something frequently guessed at. Getting the size of the column right is awfully important because using too few grams of silica will doom your purification to failure and using more an optimal mass of the stationary phase means the purification consumes excess silica, solvents, and a chemist's time.
Biotage®, a pioneer in Flash Purification, launched the unique, removable cap SNAP flash chromatography columns in 2007. This beneficial column design feature continues with the newest Biotage flash columns named Sfär columns.
For most synthesis and natural product chemists, flash chromatography is the primary tool for purification and isolation of compounds of interest. Purification methods include flash system defaulted linear gradients (e.g. 0-100%), active gradient modification (on-the-fly) during purification, and unique method creation based one either the chemist’s experience or TLC data (typically a linear gradient).
Sfär Stands for Spherical, Biotage® Stands for Quality
Biotage developed and introduced pre-packed columns for flash purification in 1994. Today our broad selection of columns enables professionals to choose the solution which best suits their purification needs.
Sfär is the Swedish word for "sphere", and the name of our columns reflects the fact that we have made spherical silica a standard due to its higher surface area and higher loading capacity. Reliable and flexible, Biotage® Sfär columns deliver larger loading capacities, tighter elution bands and purer fractions than traditional flash columns.
Biotage® Sfär is a complete portfolio of flash columns, available in a large variety of sizes from 5g to 350 g and in a range of media types, so you can purify milligrams to multi-grams of your valuable compounds quickly and easily.