The planet’s population is growing, its resources are dwindling – this is a problem. On top of that environmental contamination from myriad sources is only compounding the issue of available clean food and water.
As chemists, we contribute to this issue, to some degree, by performing reactions that generate chemical waste in the form of unwanted by-products and excess solvents from work-up and purification. What can we, as chemists, do to help reduce our so-called “carbon footprint”?
In this post, I discuss some ways to improve flash chromatography resource utilization, especially for hard separations.
Preparative scale chromatography, whether it be prep HPLC or flash chromatography, contributes its fair share to this issue. I have previously blogged on using various techniques to reduce solvent consumption without sacrificing isolated product yield or purity.
To me, step gradients are the best for minimizing solvent consumption. In fact, I have found experimentally that step gradients (developed from TLC data) increase a column’s loading capacity up to 2x over what a linear gradient can provide, while reducing solvent consumption by as much as 50%. This is significant – doubling load and halving solvent consumption actually creates a solvent savings of 4x. But if your flash system does not have the software to create the step gradient, what can you do?
Well, you can consider changing flash columns. For a rather challenging purification a while ago, I looked at the impact of column media (silica particle size and surface area) on this sample’s purification. Choosing columns packed with smaller particles with higher surface area can really reduce solvent usage. In fact, these are two most important parameters regarding both loading capacity and separation efficiency.
Using smaller particles gets you part of the way there, increasing load capacity up to about 40% (if you use media with 1/2 the particle size of what you normally would use). Increasing surface area allows a doubling (or even tripling) of loading capacity while improving separation efficiency. For really challenging purifications, this is an excellent approach.
As an example, I purified a mixture of 4 pyrazines using a linear gradient of 12% to 100% ethyl acetate in hexanes with a 10 gram, 15-40 µm, high performance silica column (surface area ~500 m²/g) and also with a 10 gram, 25 µm, high performance column (surface area ~750 m²/g).
The TLC data showed a relatively tight separation with ΔCV values of 0.25, 0.30, and 0.71, Table 1. Low ΔCV values indicate a small separation and therefore, small load.
Even with as little a 20 mg, the column with 15-40 µm particles was unable to perform a complete separation of the middle two compounds, Figure 1. In order to perform this purification with the same media and method, a much larger column is required, likely a 50 gram column. Larger columns consume much more solvent – not efficient and certainly not green. In this case, the 10 gram column consumed 195 mL; the 50 gram would require 975 mL!
However, the high surface area column (a Biotage® SNAP Ultra), easily separates all four compounds at the same load, Figure 2. Consuming only 221 mL, the high surface silica column is much more efficient providing a complete separation with room for more than 20 mg of sample!
So, if you have a difficult purification and are environmentally conscious, I recommend using small particle, high surface are silica columns.
For more information on flash chromatography, I invite you to listen to my webinar on this subject.
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