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Graduate School

In Which I Reminisce About the Prins Reaction, Chemical Abstracts, and John Keats

Well, this post needs updating. In it I mentioned never running a Prins reaction again since the 1980s, nor any photochemistry, and today what do I find myself doing? Both of them, although not at the same time.
I am, fortunately, not running the Prins this way. But even bringing it up at all recalls to me a key part of my education. When I first joined my graduate school research group, I was put to making some tetrahydropyran systems. I was handed a synthesis, drawn up before my arrival, of how to make the first one, and like most first-year grad students, I gamely dug and and started to work on it.
I should have devoted a bit more thought to it. I won’t go into the details, but it was a steppy route that relied, in the final ring-closure step, on getting the cyclic ether to form where one of the partners was a neopentyl center. The organic chemists in the audience will immediately be able to guess just how well that went.
So I beat on it and whacked at it, getting nowhere as I used up my starting material, until I was finally driven to the library. In the spring of 1984, that was a different exercise than it is now, involving the 5-year Chemical Abstracts indices and an awful lot of page flipping. (I haven’t so much as touched a bound volume of CA in I don’t know how many years now). If you were a nomenclature whiz, you could try looking up your compound, or something like it, in the name index, but a higher-percentage move was often to look up the empirical formula. That gave you a better shot, because (if it was there at all) you could see how CA named your system and work from there.
To my great surprise, the second set of collective indices I checked (the good ol’ 9th), yielded a direct hit on an empirical formula, and the name looked like exactly what I had been trying to make. The reference was in Tetrahedron, which we most certainly had on the shelf, and I zipped over to see if there was any detail on how to make the stuff.
There was indeed. A one-stepper Prins cyclization gave just the ring system I’d been trying to make, and that was one step from the intermediate I needed. I just stared at the page, though. I honestly couldn’t believe that this was real (as I mentioned, I was in about my second month of grad school lab work). Surely the synthesis I’d been given was the way to make this stuff? Surely the people responsible for it had checked the literature before drawing it up? (After all, it had only taken my a few minutes to find the stuff myself). Surely I couldn’t just make the ring in one afternoon using two starting materials I could buy cheaply from Aldrich?
Well, surely I could. And that’s just what I did, and got my project moving along until the next interesting difficulty came up a couple of months later. But I still recall standing there in the Duke chemistry library, looking at that journal article “with a wild surmise” that perhaps I should check things out for myself next time instead of just taking everyone else’s word. It took a couple more lessons for me to really grasp that principle (Nullius in verba!, but it’s helped me out a great deal over the years. I have the 27-year-old photocopy I made that afternoon in front of me now. It’s a good reminder.

15 comments on “In Which I Reminisce About the Prins Reaction, Chemical Abstracts, and John Keats”

  1. myma says:

    I asked a client recently if he had checked his junior scientist’s math for setting a crucial and hard to hit spec in manufacturing. His answer was that he had full faith that the junior had done the math right. Oh, really?

  2. You're Pfizered says:

    You sure it wasn’t a test to see how long you’d flail away before going to the library? 😉

  3. Derek Lowe says:

    I only wish it had been a test. When I came back with the one-step route, the reaction was “Huh – who knew?”

  4. Industry Guy says:

    If you still have 27 yrd old photocopies lying around after all the moving from company to company, time to let someone else clean up your office my friend to remove emotional attachment to journal articles. Recycle em so Starbucks can make some new cups would ya!

  5. RB Woodweird says:

    Graduate school: Two weeks in the lab will save you an hour in the library.
    Real world: Two weeks direct labor and overhead and waste charges will save you ten minutes on STN.

  6. PharmaHeretic says:

    A bit off topic for this post, but very relevant to the whole pharma job loss, outsourcing and management debacles.

    Bill Moyers on October 29, 2010 as part of the Howard Zinn Lecture Series at Boston University

  7. Anonymous says:

    Thanks for the bad CAS memories! I remember long hours of flipping too. I try to look at the experience A’s a ‘right of passage’.
    Grad students have it much easier today with online Beilstein/SciFinder. If they are really lucky their profs can afford an ISCO too. It’s not fair!!!

  8. DLIB says:

    Invaluable lesson and lucky that first reaction failed in that way so soon for you. Some grad students don’t learn that lesson for years into their studies and are far worse off.

  9. Sleepless in SSF says:

    Oh man, I remember sitting in the chemistry library at the University of Toronto in the fall of ’83 doing pretty much exactly the same thing. I cursed every individual volume that wasn’t in the most recent CI and bemoaned the fact that I’d have 5 years of individual volumes to sort through before the next CI came out.
    A friend’s lab had online access (at exorbitant rates!) and oh how I envied him. In one of those small world things, he landed at Gross Chem probably just after Derek finished up and has been there ever since. And as an aside, I was on the Duke campus for the first time in about ten years last month and was slightly aghast to find that Gross Chem is shuttered and they can’t figure out how to get it running again. Odd to see a building that size basically derelict.

  10. Hap says:

    #1: Maybe I’m being cynical, but perhaps he doesn’t want to be responsible if the process fails (he’s hoping that he can blame it on his junior rather than himself) or he can’t do the calculations himself?
    The term might be “strategic incompetence”.

  11. Harry says:

    My rule of thumb: An hour in the library will save you a week (or more) in the lab.
    Never known it to fail. I’ve chased stuff back to 1898 and had get the library to dig journals out of storage, but it’s amazing what is there!

  12. Vader says:

    Beauty is truth, truth beauty; that is all
    Of Keats’ poem many can recall.
    –Richard Armour

  13. Vader says:

    Beauty is truth, truth beauty; that is all
    Of Keats’ poem many can recall.
    –Richard Armour

  14. Wheels17 says:

    This article reminded me of a library reference issue when I was a Chemical Engineering undergrad taking organic chemistry with the Chemistry majors. The assignment was to identify structures of 20 or so compounds based on the IR spectra of the compound. The spectra were taken from a book in the library, and the professor pulled the book from the library so that students couldn’t just look them up.
    My buddy and I went over to the library of the major chemical manufacturer that employed his dad, and used their copy of the book. Seemed like a good engineering solution. The professor found out and canceled the whole assignment after everyone had turned it in. I know why at least a few chemists dislike chemical engineers….

  15. petros says:

    funnily enough several of us oldies were reminiscing about the delights of ploughing through CA and Beilstein in hard copy the day you wrote this!

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