Courtesy of Steve Ley’s group, here’s a lab trick I’d never come across before. They were trying to purify a nasty mixture of closely related isomers, and found that the best chromatographic separation came from a long, long, run in ether/hexane. I’ve been in that situation myself, but it’s hard to have the patience to run a large column for such a long time, and it’s even harder to evaporate down the ridiculous amounts of solvent that you generate. (Even experienced organic chemists tend to underestimate how long that last part can take).
Ley’s group hit on an interesting solution. They loaded the crude material from a 42-gram reaction onto silica gel, and hooked a water-cooled condenser up to the top of the column. Under the condenser was a one-liter flask of 1:1 ether/pentane, heated to reflux. Those two solvents form an azeotropic mixture (about 1:1) that happens to match up well with the solvent brew needed for the column. This way, fresh solvent was continuously dripping down through the column, which was rigged to elute back into the flask of boiling solvent.
Chemists will recognize this as a variation of the Soxhlet extraction, and a rather ingenious one. To switch fractions, you turn off the heat, pour out the 1-liter flask, and charge it up with fresh pentane and ether. The solvents are so low-boiling that the material coming off the column doesn’t decompose while it’s cooking around in there in between. With one kilo of silica gel, they ran the column at about 80 mL per minute, and cut fractions about every 7 hours. (Told you it was a slow column!). After five days of this, they’d separated out their isomers. That took them out to 19 fractions, which seemed to be enough, but it turned out that washing the column with acetone furnished a pretty good amount of the final (most polar) component (which was presumably coming out very dilute by that point).
They used about 17 liters of solvent, which is a fair amount of rota-vapping, but is nothing compared to the 590 liters that would have been used under normal column conditions. (No one would have been able to put up with that). This idea will probably always have limited application – there are only so many solvents (or solvent mixtures) that can be used, for one thing. And in many cases people will grit their teeth and turn to large-scale HPLC when it’s available. (That’ll use more solvent than this, but less than an old-fashioned column, in most cases). But if someone had thought of this technique back in, say, 1955, it would have been everywhere.
And it could still be especially useful in academic labs, where labor is cheaper than solvent, and worth considering elsewhere. I’m always glad to see something new constructed out of the sort of equipment that’s in the drawers of every lab bench.