[Honclbrif]

Anyone try Curly Arrow's dry column vacuum chromatography method? If so, is it worth it/any good?

http://curlyarrow.blogspot.com/2006/10/dry-column-vacuum-chromatography.html

https://www.thieme-connect.com/ejournals/pdf/synthesis/doi/10.1055/s-2001-18722.pdf

[Dan]

Looks interesting. It didn't catch on in the last decade though as far as I'm aware. I might give it a go sometime for large scale stuff (which I don't do much of these days) - I think in that case it could really save time and money.

We don't have sufficiently fine silica to hand, but I'm tempted to get some and have a go one day.

[Honclbrif]

Tried it, and it looks like it worked out fairly well.

I started with about 5 g of material¹ with three spots (Rfs around 0.7, 0.4, and 0.3). Using about 10 g of silica² and five 100 mL fractions³ and I actually got decent separation. This was also just using a regular filter flask and not their fancy setup.

Least polar component fell right off, got one slightly mixed fraction where delta Rf = 0.1, and one pure fraction. I'm tempted to try this again next time I go crazy and make a (relatively) huge amount of material. Beats buying a new column and cutting dozens and dozens of fractions.

¹biggest column I have can handle maybe 1 g
²regular grade, not that fancy stuff
³10% step gradient from 90:10 hexane:EtOAc to 50:50

[Dan]

What was the volume of a fraction (relative to the volume of silica used)?

What I normally do for a flash column is run a step gradient very similar to that used in the vacuum method described - something like 5-50% EtOAc in hexane, 5% step gradient, volume of solvent for each step of the gradient is equal to the volume of silica in the column. Each column volume is then collected over ~5 fractions.

I'm wondering if there's really any difference between the technique I use and this vacuum chromatography other than the grade of silica (and consequently the amount of silica) used.

Another question... Is the reason they use vacuum because the back pressure generated in a column using that finer silica too dangerous (or the column is too tedious at a safe pressure)?

[Honclbrif]

Volume fraction was about 1:1.

As for the final question, I also suspect that they're using vacuum for those reasons.

[nox]

Haven't tried it personally but a former grad student in the lab used this procedure to purify about ~500 g of stuff and it worked fairly well. (He was doing a 40 step total synthesis, and that was step 6 I believe)