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Topic: Flash Chromatography  (Read 4701 times)

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Offline Dea

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Flash Chromatography
« on: August 06, 2007, 08:31:42 AM »
Does anyone have some tips how to pack a column really good, for flash chromatography?
For example, does it pack better if you let solvent running through it for some time?
Thank you!!

Dea

Offline Dan

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Re: Flash Chromatography
« Reply #1 on: August 06, 2007, 11:04:40 AM »
I usually mix up the silica gel with cyclohexane to form a slurry, quite runny otherwise you get air bubles, and push the solvent throught to the level of the silica. Then I push through another column volume of cyclohexane, and it always seems well packed after that. You can of course re-use that extra cyclohexane you push through.
I know people who swear by putting the silica gel in dry, and then running solvent through to pack it. I often get air bubbles when I do this and so tend to stick to using a slurry.
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Offline Custos

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Re: Flash Chromatography
« Reply #2 on: August 08, 2007, 07:37:41 PM »
I suggest you have a read of the original article from Clark Still of Columbia University (W.C. Still, M. Kahn and A. Mitra, J. Org. Chem. 1978, 43, 2923-2925) -- or here is a good summary, which includes the original paper. I've always found that dry packing the column was best and easiest (as per the original paper) but the three critical issues are the silica gel used, the amount of silica, and the Rf difference for the compounds you are trying to separate.

1. You should use 250-400 mesh, anything bigger will not work properly.

2. Try to use only around 30 times (by weight) the amount of silica to the amount of compound. Most people use far too much, like when they run gravity-fed columns. If you have 250 mg of compound to purify I can guarantee that 7.5 g of silica doesn't look like enough but it is!

3. The Rf ratio is much more important than the absolute difference in Rf. As an example, say you are trying to separate compound A from B. In one solvent system you get Rf values for A and B of 1.5 and 3.0 respectively. In another solvent system you get 4.0 and 6.5 respectively. On TLC the separation looks better for the second system because the Rf "gap" is 2.5 as opposed to 1.5, but that's the wrong way of looking at it. In the first solvent system compound B moves twice as fast as compound A (3.0 is twice 1.5) , while in the second system B moves only 1.6 times as fast (6.5/4.0).

A bit of work with TLC to find the best system (I like to run through a variety of hexane/ethyl acetate mixtures) for separation with low Rfs will pay off with better separation.

Of course if you can get your supervisor to spring for a chromatotron...  :)

Offline Dea

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Re: Flash Chromatography
« Reply #3 on: August 09, 2007, 04:34:56 AM »
Thank you guys, very much!! I wish I found this forum earlier!

I have some experience with flash chromatography, it's just that I'd like to get to the performance of an HPLC (he he - the arrogance of a chemist :-) )

I also mix the silica with the solvent before, but sometimes I cannot avoid the preferential running "routes" of the solvent.

I've been thinking of ways to apply the reaction mixture in an as thin as possible layer. I've tried once to impregnate a filter paper with the diameter of the column....I don't really remember how it worked...:-)

Wouldn't be great is someone came up with an (practical) idea of some thin absorbant silica gel "tablets" to be packed on the top of the column?

Offline russellm72

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Re: Flash Chromatography
« Reply #4 on: August 09, 2007, 07:23:12 AM »
Loading your material onto silica or sodium sulphate followed by r/e can give you a nice powder to load on to your column. This is most practical when your sample doesn't dissolve easily.

I have used Biotage equipment in the past (google it) with which one can load his sample onto a sample module and evaporate off the solvent in vacuo. This is then attached to the top of the column and hay presto.

R.

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