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Graduate School

Levoglucosan

Three days before: go to the local supermarket and ask to buy a case of corn starch. Ignore the puzzled looks, which come your way since you don’t look like you own a Chinese restaurant. Pay for the stuff out of your own pocket (this is grad school, y’know) and head back to the lab. Ignore the puzzled looks of colleagues who haven’t seen you walking around with boxes of corn starch before.
Two days before: mix up a kilo or two of the starch with some dilute acetic acid into a weirdly dilatant fluid. Hold on to the memory of it, unknowingly, for fifteen years or so until you have kids of nursery school age. In the meantime, pour the stuff into a cheap baking pan and put it into a drying oven that no one, since you started in on it, will use for anything else.
One day before: take the baking pan out of the oven, wheezing into the waiting faceful of acetic acid fumes if you try to rush the process. Break the cracked, slightly shrunken white cake into chunks small enough to be loaded into your apparatus. Wonder to yourself if this is how other famous scientists started during their doctoral work, and if it is, how come you never read about it.
Day of prep: load up the reactor, a metal box with a glass tube and ball joint poking out of it, with the chunklets of corn starch. Hook up to a connecting adaptor, with a vacuum take-off on it, which you’re going to need, big-time, and a large round-bottom flask at the bottom, ditto. Pour plenty of liquid nitrogen into the dual traps on the vacuum pump, regretting the day that you ever told your summer undergrad, who isn’t around, of the potential dangers of LN2 traps, because now he won’t get near one.
Hook up the vacuum line and pump down the system, and break out a Fisher burner, without realizing (naturally enough) that you won’t use one again for at least twenty years. (Not using corn starch as a starting synthetic reagent for at least twenty years, on the other hand, is something you actively yearn for). Take a deep breath and begin flaming the bottom of the metal box with the burner, making sure to get the whole surface and not to linger too long on any one spot. Moderation, moderation in all things.
Note the wisps of vapor flashing through the glass part of the apparatus, accompanied by a throatier note from the vacuum pump. As the heating continues, look for the appearance of an ever-darker flow of thick heterogeneous syrup. This sticky ooze with black flecks in it is your desired product, damn it all. Continue heating until the lava flow dwindles and its color becomes darker than you think you can ever lighten.
Cool down the apparatus, bleed in some air, pull the vacuum line and kill the pump – in that order, unless you really want to suck oil back into the traps, and you really don’t. Now would be a good time to lift those traps out of their liquid nitrogen Dewars, to guard against just that oxygen-condensing explosion risk you foolishly warned your undergraduate student about. Make sure that the pump system is open, though, and that the hose is draped into a fume hood, because some of that odd stuff that’s condensed in there is probably carbon monoxide and it will be evaporating shortly.
Turn your attention to your product, which has now cooled into a tarry reddish-brown glass. Dissolve it in water and transfer it to the three-foot-tall liquid-liquid extractor, which you will eventually describe to people who will look at you as if you are describing how you used to hunt mammoths. Start heating up a three-liter pot of ethyl acetate, make sure that all the hose fittings to the water condensor are tight (about three times should be enough to relieve your paranoia), and go to what passes, for now, for home. Your product will be ready for the next phase of its purification, which involves the irreversible blackening of a thick column of ion-exchange resin, in just under a week.
After that and all the rest of it (the evaporation, the decolorizing charcoal, the methanol, the crystallization), take a small sample of your product and put it in a glass vial, hanging a paper label around its neck. Pack it and take it with you on your every move over the next twenty years so that you have it, with its now-yellowed label with the faded ink structure on it, as you sit down at your computer.

7 comments on “Levoglucosan”

  1. Another Kevin says:

    OK, so why did you need levoglucosan so badly that you were doing pyrolysis on that scale to get it?
    I’m sure there’s another chapter to this story
    somewhere.

  2. Chrispy says:

    In undergraduate chemistry, we always used such a small volume in our reactions that we never got the thrill of recrystallization, etc. That’s too bad: it wasn’t until much later that I saw a gifted benchmate regularly apply recrystallization. (And no, he didn’t have a beard.)
    Actually, in industry it seems that people are pretty quick to do flash chromatography.

  3. Lucas says:

    Chrispy:
    Curious that you should mention recrystallization. Since starting in industry, I, too, have mostly used flash chromatography or simple precipitation (with heptane or the like) to isolate my products. The other day, however, I replicated a large-scale intermediate synthesis worked out by some of our European colleagues that involved nothing but extraction and recrystallization for the purification. As someone who has been doing organic chemistry for a relatively short time, it was amazing to me how quickly and easily I was able to obtain a high yield of remarkably pure product.
    The downside, of course, is that finding the right solvent system seems to be as much an art as it is a science. It kind of makes me wish I had been doing this earlier, when recrystallization was more fashionable (or maybe there were just fewer easy alternatives) and there would have been more mentors to help me figure it out.
    Then again, packing columns sucks. It’s hard to truly wish for a time when I wouldn’t have had my Isco system on hand to help me out 🙂

  4. Handles says:

    I love recrystallisation. My project last year (industry), we made a bunch of flat aromatic building blocks, and maybe 1/3 of them crystallised really well. It was heaps easier to do a quick recryst than to put them down the biotage. As far as choosing solvent systems go, my favourite is isopropanol/cyclohexane.

  5. Handles says:

    Oh, and Chrispy, you reminded me of doing small-scale recrystallisations in a Craig tube. Another thing I havent used for years; they are way cool though.

  6. Gerald says:

    Why didn’t you buy it from SIGMA? It’s # A8417. Or is the previous commenter wrong and it really is not Levoglucosan but something else?
    Gerald

  7. Derek Lowe says:

    As the time cues in the post suggest, grad school was a while ago for me. I was making lots of levoglucosan in 1985 or so, and at the time, the price was $27.00 / 100 milligrams. (I recall it well, because I used to look longingly in the catalog and wish that it was a “g” instead of an “mg”).
    And I was making it in 50 to 100 gram batches, over and over, because it was at the start of a roughly 30-step synthesis. You’re not going to get one of those going with stuff that you have to buy in 100-mg lots. Not with cheap grad-student labor around.
    Even now, looking at our ordering application, I see that its price is all over the place, anywhere from about $10/g to $100/gram, depending on who you order from. There are places that’ll really rip you off in 10 and 100 mg amounts, too, should you so desire.

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