Does methanol really dissolve silica during flash column chromatography?

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.

For as long as I have been involved in the field of flash column chromatography I have heard stories about chemists finding white powder in their purified product which has been verified to be silica. The only time this is seen, that I know of, is with gradients of DCM and methanol. The conclusion that is drawn is that silica is dissolving in the methanol.

Until now I never tested this theory. When I have asked those who are more knowledgeable in silica chemistry, the answer is always, “no, silica cannot be dissolved by methanol.” However, being the inquisitive scientist that I am I wanted to determine this on my own. So, I finally was able to set aside some time in the lab to perform my own experiments to hopefully shed some light on this topic. After all, you know the old saying which says “where there is smoke there is fire” meaning that there may be some truth to what these medicinal chemists have been telling me all of these years.

I decided to test for dissolution of standard granular flash-grade silica (your typical 40-63 µm, 60Å, 500 m2/g silica) and spherical silica of similar particle size and porosity (Figures 1 and 2). For the former I used a 5 gram cartridge packed with granular silica. For the latter I used a 5 gram Biotage® ZIP-Sphere cartridge packed with spherical silica (60 um, 50Å, 750 m2/g). The reason I chose two types of silica is that granular and spherical silica are both frequently used in flash chromatography and it would be unfare to test only one silica type and draw a scientifically valid conclusion. My logic being that if methanol dissolves silica then its physical shape and other characteristics should not matter.


Very interesting, let us know what you find!

I was a synthetic chemist for 15 years and worked with DCM/Methanol gradients regularly. I never observed silica in my samples. That being said we didnt try to detect the presence of silica in our samples.

I am definitely interested in the results. How are you planning to detect the silica?


To dissolve Silica, you need boiling caustic soda (NaOH) or HF (Hydrofluoric acid)