[insertwittyname]

I've synthesized the compound 3-(4-chlorophenyl)-3-(trifluoromethyl)isochroman-1-one . When I run a TLC of the crude product in 10% DCM in n-pentane, I get quite a good separation, yet when I do a silica column, it looks like the compound just sticks to the silica and nothing shows up in the collected fractions. Any ideas/suggestions which might help?

[OrganicDan96]

did you flush the column at the end with very polar solvent like EtOAc and check the contents of that? are the factions very dilute?

[insertwittyname]

did you flush the column at the end with very polar solvent like EtOAc and check the contents of that? are the factions very dilute?

I flushed with EtOAc thrice, and still did not manage to get all the stuff that I had loaded onto the column.
I also thought that the fractions might be dilute and thus spotted them 15-20 times before visualizing (or trying to visualize) under UV.

[kriggy]

Maybe the lactone opened on silica and gets stuck there. Maybe try bit of acetic acid in the mobile phase

[pgk]

I am afraid of something else.
Fluorine atoms form strong hydrogen bonds with dichloromethane and form dimer, trimer,….., polymer H-adducts of your molecule, with variable polarity and which are present in almost all fractions in very high dilutions.
This doesn’t extensively happen in TLC because the development-surface/distance ratio is different than the chromatographic column.
If this happens, it can be avoided by using eluent solvents that are free of hydrogen bond donors, like e.g. acetone or ethyl acetate in pentane or hexane.
Question: In the initial TLC, do the spots have a tail and “comet-like” appearance?

[wildfyr]

Pgk this is the first I've heard of this phenomenon on a column. People do columns on CF3 compounds all the time with nothing fancy. I am MUCH more in the corner of the lactone opening causing the problem. That quaternary carbon is pretty hot.

[clarkstill]

Maybe the lactone opened on silica and gets stuck there. Maybe try bit of acetic acid in the mobile phase

Or triethylamine? If the lactone opening happens on SiO2 then it must be acid-catalysed, so adding AcOH might add fuel to the fire... admittedly it could also be base-catalysed.

insertwittyname - have you tried a 2D TLC to check whether your compound is stable on silica?

[rolnor]

Could the compound crystalize on the column? Use a better solvent like DCM/EtOAc as mobile phase.

[pgk]

Crystallization in the column is also possible and especially, if the solute crystallizes in the eluent solvent at temperatures that are little lower than room temperature.
On the other hand and concerning the intermolecular H-bonding in the column, I don’t see the “why not?” because fluorine group is H-bond acceptor and dichloromethane is H-bond donor. Besides, the presence of a non-polar solvent like pentane, favors the intermolecular H-bonding:

How good is fluorine as a hydrogen bond acceptor?, Tetrahedron, 52(38), 12613-12622, (1996)
https://www.sciencedirect.com/science/article/pii/0040402096007491
Fluorine as a Hydrogen‐Bond Acceptor: Experimental Evidence and Computational Calculations, Chemistry, 20(35), 11058-11068, (2014)
https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201402858
Weak Intermolecular Hydrogen Bonds with Fluorine: Detection and Implications for Enzymatic/Chemical Reactions, Chemical Properties, and Ligand/Protein Fluorine NMR Screening, Chemistry, 22(22), 7592-7601, (2016)
https://www.ncbi.nlm.nih.gov/pubmed/27112430
IR study on double hydrogen bonding in dichloromethane, Journal of Molecular Structure, 275, 203-210, (1992)
https://www.sciencedirect.com/science/article/abs/pii/002228609280195N
Role of chloroform and dichloromethane solvent molecules in crystal packing: an interaction propensity study, Acta Crystallographica B, B69, 379-388, (2013)
http://scripts.iucr.org/cgi-bin/paper?S2052519213015078

[wildfyr]

Well he could not use DCM and see if that helps. Just use ethyl acetate, or even a low alcohol or MeCN.

I also noticed another issue. Pentane is very low boiling. I would never run a column with it. Use hexane or heptane.

I once tried and it was evolving enough gas that bubbles disturbed my silica pack.