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Topic: Flash Column Chromatography Problem - nothing eluting  (Read 464 times)

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Offline rarqorange

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Flash Column Chromatography Problem - nothing eluting
« on: January 29, 2022, 02:47:52 PM »
I have a simple biaryl I'm trying to purify by a flash column. I'm following a procedure from a paper (same exact product) on a 5 mmol scale, where they also purify this by silica gel column, using the same solvent system (just hexane). The product showed an Rf of about 0.3 on the TLC. I dry-loaded my sample and ran the column in hexane, but several column volumes later, NOTHING eluted.
I flushed with a polar solvent and got my crude sample.

More info about my columning technique to help get an answer:
 I have a set procedure for running columns following https://labs.chem.ucsb.edu/zakarian/armen/how-to-do-flash-column-3.pdf, but I use a slurry pack, and dry loading of the crude. After adding my dry load, I run through about half an inch of my solvent system to 'load' the sample into the silica. I then add sand, then the solvent system, then start the run. I collect a set amount of dead volume at the very beginning before collecting into fractions tubes, roughly 1 column volume worth, but don't throw it away until I am certain I have my product.
 I have run several columns using this procedure with good separations in short times so I'm very concerned about this problem.

In this particular case
- The fractions were not too dilute since I combined all of them, including the dead volume at the beginning, and evaporated the solvent to leave behind an empty flask. The flush at the end gave me back the same mixture I started with.
- I checked the recovered crude by NMR and the product did not decompose
- I double checked the solvent system by running another TLC of the crude in hexane

If anyone could tell me what they think went wrong I would be very grateful.




Offline Babcock_Hall

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Re: Flash Column Chromatography Problem - nothing eluting
« Reply #1 on: January 29, 2022, 03:27:13 PM »
I am not sure what is going on.  One thing you could try is a step gradient with increasing percentages of diethyl ether, DCM, or some other solvent in the hexane, as opposed to moving immediately to the flushing step.

Offline phth

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Re: Flash Column Chromatography Problem - nothing eluting
« Reply #2 on: January 29, 2022, 04:56:17 PM »
Probably TLC was too concentrated, and it smeared up the plate under non equilibrating conditions. Like Babcock_Hall said: always flush with polar solvent like 100% EtOAc or 100% acetone or 10% MeOH/DCM to elute it or decomp off the column. Could be a solid and it precipitated at the baseline therfore not moving far. These are common problems. Try TLC again with dilute sample.

Offline rarqorange

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Re: Flash Column Chromatography Problem - nothing eluting
« Reply #3 on: January 29, 2022, 05:18:07 PM »
Probably TLC was too concentrated, and it smeared up the plate under non equilibrating conditions. Like Babcock_Hall said: always flush with polar solvent like 100% EtOAc or 100% acetone or 10% MeOH/DCM to elute it or decomp off the column. Could be a solid and it precipitated at the baseline therfore not moving far. These are common problems. Try TLC again with dilute sample.

The TLC didn't have a smeared appearance so this didn't cross my mind, but it's definitely ssomething to consider. It is a solid yeah, so your idea that it precipitated at the top of the column seemes likely. I flushed with ethyl acetate to recover everything thankfully. I'll try with a different solvent system.
It's strange that the literature procedure states the same solvent system. I wonder what I was doing differently, or if they misreported.

Thank you very much for the advice. If anyone else has any thoughts please let me know. I am still very concerned and want to make sure I can avoid this in future.

Edit: typo

Offline rolnor

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Re: Flash Column Chromatography Problem - nothing eluting
« Reply #4 on: January 29, 2022, 11:49:17 PM »
Pure hexane is a poor solvent and as lipophilic as you can get so. Try to dissolve your material before loading. Toluene is a better solvent but usually dont impact on Rf

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