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.

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Published by

Bob Bickler

Technical Specialist, Biotage

9 thoughts on “Does methanol really dissolve silica during flash column chromatography?”

  1. Thank you so much about your informative article . I would like to ask if it is possible to use water in normal silica gel column and which the strong polar solvent that i use with column chromatography.

    1. Yes, water (neutral or acidic) is fully compatible with water. However, I have not found many applications where water is a suitable strong solvent. For what sample types do you use water with silica?

  2. Hi Bob,

    Nice article. However I have two questions which are normally asked by the chemists.

    1. ACN is more expensive than methanol. Hence the users try to use Methanol as far as possible while refraining from using ACN. Also most of the users move to C18 if their Polar compounds don’t separate well on normal phase.

    2. Most of the companies try to go green in their MedChem or Impurity Isolation processes. Hence use of ACN is most of the times avoided.

    1. Hi Aniruddha,

      Many thanks for your input on this topic. Yes, acetonitrile is more expensive than methanol but if you have a sample for which methanol does not work well and you do not have reversed-phase flash columns at your disposal, acetonitrile may be the only suitable alternative.


  3. I would often run MeOH/DCM columns and was mindful of “dissolved silica” so post-column, would then re-dissolve isolated product in 100% MeOH or DCM and pass through a 0.45 um syringe tip filter. It would be interesting to see if this procedure removed the fines under your test conditions.

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