Skip to main content

How Not to Do It

Manfred Christl Rides Again (Bonus Idiotic Lab Accident, Too)

Readers may remember the incident a couple of years ago where a paper was published claiming the synthesis of some very odd-looking 12-membered ring compounds. Prof. Manfred Christl of the University of Würzburg noticed something odd about this reaction, though, namely that it had already been run over a hundred years ago and was known to give a completely different product. (As I pointed out here, though, you didn’t need to unearth the ancient literature to know this; ten minutes of looking through the modern stuff would have done the trick, too).

Well, Christl’s back with another takedown of some improperly assigned weirdo 12-membered rings. This time, it’s Cheryl Stevenson of Illinois State that gets the treatment, with this paper from last year that claims several interesting ring structures from 1,5-hexadiyne and base. Christl had trouble believing the mechanism, and on closer inspection had trouble believing the NMR assignments. Then, on even closer inspection, he assigned the structure as a simple isomerization of one of the triple bonds, and found that this exact reaction (and product) had first been reported in 1961 (and several times afterwards). Not good.

As it turns out, I almost certainly made some of the compound myself, by mistake, back in mid-1983. That was the summer before I started my first year of grad school, and I was doing work in Ned Porter’s lab at Duke. One of the starting materials I needed was. . .1,5, hexadiyne, which you couldn’t buy. So I made it, in real grad-school fashion. I homocoupled allyl Grignard to get the 1,5-hexadiene (which even if you could buy back then, we didn’t). Then I reacted that with bromine and made the only six-carbon molecule with four bromines on it that I ever hope to make. Reacting that with freshly prepared sodium amide in ammonia gave the smelly di-yne, in crappy yield after distillation. I can still see it: me heating up a column full of glass beads, then turning to Steve, the postdoc in the next hood, and making a bad joke about Herman Hesse while David Bowie’s “Modern Love” played on the radio. . .ah, those days, they will not come again.

At any rate, I went on to react the compound with bases under different conditions, trying (in vain) to alkylate both of those terminal alkynes, and thus passed the last of my summer, in exactly the way my two previous summers of research had passed: unsuccessfully. This latest paper, though, makes me think that I was probably turning my starting material instead into exactly the diene that Christl is talking about. I should have hit the library harder myself, although (to be fair) there are references that tell you that you can do that alkylation, and digging through the literature was a good deal more time-consuming back then that it is now.

That lab accident, you say? Well, that happened when I was making a big batch of sodium amide. You start that prep off like a Birch reduction – condense a bunch of liquid ammonia into a flask, and start chucking sodium metal into it. The big difference is that you add a bit of ferric chloride to the mix, which kicks things over at the end. After you’ve dissolved your sodium, to give you the bronzy purple-blue of solvated electrons, you take the flask out of the cold bath to let the ammonia reflux. At that point, the whole thing suddenly clears, dramatically revealing grey lumps of sodium amide rolling around on the bottom of a pond of plain ol’ ammonia, without a solvated electron in sight. (I have, in years since, seen a couple of people refer to the blue stage of the reaction as sodium amide, which it ain’t, and I can get quite cranky and pedantic about it).

One afternoon I was whipping up a batch of this stuff, when something starting going on inside the flask. I don’t recall what made me take a look at the ammonia solution, but since there was so much bronze gorp on the side of the one-liter three-neck, I had to lean in and look down near the central joint. Whereupon my hair wound itself immediately around the greased shaft of the overhead stirrer, pulling my head in toward the whole setup and jamming my nose into the side of the flask. I fumbled for the switch of the stir motor, feeling like George Jetson as I shouted for someone to give me a hand, and watched with interest as the dry ice bath bubbled along an inch away from my face.

Steve the postdoc came to my aid, shutting off the grinding motor which was doggedly trying to wind me headfirst around the stirrer shaft. We unreeled my hair from the whole contraption, with me cursing foully and Steve merrily making jokes of the “Hair today, gone tomorrow” kind, with side comments about me getting too wrapped up in my work. Those days, as I said, will not come again.

35 comments on “Manfred Christl Rides Again (Bonus Idiotic Lab Accident, Too)”

  1. Sili says:

    I used to have a spindly ponytail halfway down my back. Good thing I wasn’t in the lab more, I guess. (Did you have to wear a hairnet afterwards?)
    Interesting – I did terribly in the lab as well, but it sounds like you soldiered on, while I took the easy (and unemployable) route of crystallography – as I was told at my supervisor’s funeral last week: “They have robots for that now.”
    Christl sounds like someone I’d love to meet.

  2. anchor says:

    When it comes to acetylenic compounds even before you start to do something, one should look for two guys who are legendary in these area. They are Franz Sondhimeir (UK and then later Israel) and Reppe (Germany). They have done everyting imaginable (base isomerization, Zipper reaction, oxidative coupling etc. It seems like Dr. Manfred Christl has made his mission to scout out for those suspicious reaction akin to a grave digger, I guess.

  3. darwin says:

    Reading chemist’s lab blunder blogs somewhat reminds me of the scene from Jaws when Capt Quint and Cooper where comparing tales of their sharkbite scars-only much, much more lame.

  4. Nick K says:

    How did Stevenson et al make such an egregious error – didn’t they characterise their supposed macrocycles by mass spec?
    BTW, Thanks Derek for the account of your accident. It made my day!

  5. petros says:

    Interesting to see that, yet again, the offending article is in Agnew Chem

  6. Martyn says:

    The original offending article is JACS, 2005, 127, 16143. Angewandte have at least published this rebuttal from Christl.

  7. Hap says:

    ACIEE isn’t alone – I guess that’s a comfort. Or not.

  8. Hap says:

    The mechanism in the original article for the formation of the title compounds would have not gotten me far in a cume.
    Maybe that’s the key – if it looks like something that a professor, post-doc, or grad student would give no credit for on a cume or an undergrad organic exam, then there ought to be either a boatload of characterization data of the product or good kinetic and mechanistic studies (“no, we were not on crack while making this – here’s why.”) I’m not seeing a whole lot in the JACS, for example – where are the downfield/upfield shifts (even with conformational flexibility, they ought to be present in some amount – the peak positions don’t at first look much different than alkene positions)?

  9. nitrosonium says:

    Do you really miss doing lab work in Gross Chem?

  10. Derek Lowe says:

    Nitro, I have to admit that I truly hated the P. M. Gross building, and would buy a ticket to watch it implode. Parts of my grad school experience were (perhaps unavoidably) no fun whatsoever, and the windowless labs (and horrible “graduate student lounge”) did not add to the festive mood.
    That said, I did have some good experiences there, mostly having to do with people I worked with. Who knows, if things had been in a better environment, the whole experience could have been nearly enjoyable.

  11. RB Woodweird says:

    You are in luck. In A Novel And Efficient Synthesis of Cadaverine (, you can vicariously experience the implosion of what was to be the Dalyrumple Chemistry Building. Not to mention its explosion and replosion. It may have been gross Newtonian-level quantum accumulation. Or it may have been the ghost.

  12. Hap says:

    Windowless labs seem like a recipe for graduate student insanity, with all sorts of unfortunate consequences.
    Perhaps the architects just hated graduate students – that would also explain my dorm in graduate school, designed by Groepius.

  13. retread says:

    Too bad Dr. Stevenson isn’t a climate scientist. She never would have been required to release the spectra. Moreover, she would have had defenders who would argue that people wanted her spectra only to attack it (see some of the commentary to Derek’s post on Climategate).

  14. riboiron says:

    Hap –
    Was your dorm Child or Richards (I think that was the name…)? Nothing was as bad as Richards during a heatwave in the summer…

  15. Retread says:

    Let us further assume that computational chemistry is quite good, so that Dr. Stevenson could calculate the MRI peaks and splittings of the structure given in her paper. Then she could have had a program to ‘adjust’ the actual MRI data to the calculated one. As a climate scientist in good standing she could have refused to release both the program or the original data. The same crew would have sprung to her defense.

  16. Hap says:

    a) Richards, I think. It could have been worse – the women’s bathrooms were on the first and third floors in the winter/spring, and the women’s-only floor had their bathroom combination locked (of course, they all had the combination, anyway, so it was just spite, mostly). The lobby looked like it was finished with castoffs from a prison. It was designed with light from the rooms lighting the hallways – but of course, that would mean that the rooms were open to view. Oops.
    I think they should have sentenced Groepius to live in his own darn building for life – of course, there’s the 8th Amendment to worry about.
    b) If a JACS and an ACIEE paper were the only evidence for AGW, that would hold more water, but, alas…

  17. Jose says:

    “Having been deemed nearly unobtainable, our poor understanding of [12]annulene was not born from a lack of interest.”

  18. milkshake says:

    I was in Child for one year. Oh horror. Only one bathroom per entire long floor, and I happened to be at the exact opposite end of the long hallway and on a floor which had only women bathroom. My room faced a construction site – they buldozers and ground-compacting machines started under my window every workday at 8 am. At least once a month some absend-minded early bird burned a toast in the kitchinette at about 7am while walking away – this triggered smoke alarm and the evacuation and we were shivering there in pajamas until the building was checked by the firemen. Ah, those days will not come again

  19. Hap says:

    b) That’s not really fair or relevant. Sorry.

  20. TOSG says:

    Wow – I had no idea that Gropius designed Richards Hall. One of my friends lived there last year – it’s such a dismal building that it was almost painful just to visit. He should have his famous architect card revoked.

  21. excimer says:

    So let me get this straight. Christl publishes a correspondence in ACIE on a paper that is solely on the NMR analysis of a compound he apparently did not bother to make. He apparently didn’t bother to communicate with the authors of the paper; if he did, he didn’t state so. He did not see if the experimental conditions which he claims generate the EPR spectra central to the papers in question. Now the original authors of the paper aren’t off the hook completely, but this has to be the laziest “response” I have ever seen to a paper. Who among you would publish this without actually doing the chemistry?

  22. S Silverstein says:

    In my former (i.e., pre-medical informatics) role as Occupational and Industrial physician, I used to treat industrial workers who’d had “incidents” as you described. Your recollection brought back some (bad) memories, so: please keep your nose & other parts out of the reaction vessels!

  23. leftscienceawhileago says:

    RB Woodweird,
    I’ll admit, I fell for your schtick and bought the book.
    Just wanted to let you know it sucks. It wasn’t worth the 10 bucks.
    Chemistry needs a book like it (and there is a brilliant passage or two in there), but I don’t think I’ve ever bought a piece of writing that was horrible…until your book. I am being honest.
    You can keep it crude, but at least make it funny.

  24. Jose says:

    This ACIE bit makes me imagine a scene…
    First year grad student working for an almost-emeritus prof at a sleepy off-the-beaten-track Uni. Left mostly to his/her own devices, with prof looking things over only once in awhile. Student needs to do some rose bengal photochem, or maybe finds a reference to “Ag2O in paraffin” and thinks, “huh, cool, Angewandte, and just the chemistry I need!” and then spends, 4, 5, 6 weeks monkeying with it. Prof, whose focus is more on golf than current lit, gives kind encouragement. More time goes by, and finally someone clues Jr into the whole hexacyclinol debacle. The 2006 ACIE paper has not a single note, asterisk, or any notice whatsoever that something is very, very wrong. And if that paper isn’t flagged, then what ??

  25. sjb says:

    Shocking lack of labcoats in evidence at , too, or does this tie in with the hair-jamming problem?

  26. RB Woodweird says:

    Thanks leftscienceawhileago. Now more detail. Was it, in your opinion, third-rate or fourth-rate? Plus, for $10 it looks like you bought the ebook at Scribd ( rather than the paperback at Amazon ( Too bad, as the actual book has some heft to it and might be useful to squash bugs or thump unruly children. It is also thick enough to use as a sturdy prop under a wavering pile of journals or an unsteady table.
    leftscienceawhileago, why did you leave science? Were you in a graduate program? What, as they say in actual bonafide surveys, is your highest level of degree attained? Just curious.

  27. Hap says:

    If someone can look at your NMR and question your assignments (like where the hell is the upfield/downfield shifts you expect from an antiaromatic ring system), let alone compare your NMR to a literature compound that looks nothing like what you proposed, then it seems that someone ought to have asked (and answered) those questions long ago.
    I don’t know if it’s worth an ACIEE, or why you wouldn’t ask the author first, but if it’s a lazy ACIEE, then what the heck are the ACIEE and JACS that the original author got?

  28. Hap says:

    Oh, and the phrase “broadened to oblivion” is one I need to read more often in papers.

  29. AnotherCMC Guy says:

    Derek, I too will buy a ticket if and when Gross Chemistry implodes. Miserable building in an otherwise nice setting. The people were great, but no one spent time in there unless they had to.

  30. Hap says:

    The “Ag2O in paraffin” part came from Taber – it’s one of the things (let’s be optimistic) tt might actually work, or barring that, at least the student could find someone who knew about it. Now, the [2+2+2] reaction with singlet oxygen, or the Mitsunobu at a tertiary alcohol…good luck with those.

  31. alig says:

    Interesting that the correspondence was submitted in March, but not published until December. Was Angew. asking the original author for a response?

  32. Anonymous BMS Researcher says:

    I don’t recall whether I ever set foot inside the Gross Chem building at Duke, but I certainly walked past it many times while Derek was working there because I got my doctorate from Duke in Zoology, and the Biosci building was just down a big hill from Gross Chem.
    As for the Andromeda Strain, I’ve not seen the movie versions but have read the novel many times, and even recommended it to Duke undergraduates when I was a Physiology TA because it’s the only best-selling novel I know of where a key plot point turns on acid-base physiology. Crichton wrote it while at Harvard Medical School.
    As for decent movie portrayals of scientists, Contact is better than most. Of course Apollo 13 is about astronauts and engineers rather than about scientists, but I do treasure the scene when a bunch of engineers get together in a conference room figuring out how the astronauts could kludge together an adapter for CO2 canisters from random stuff known to be aboard the spacecraft — including duct tape! At least Apollo 13 does make it clear that all the heroics of the astronauts would have accomplished nothing without the help of many nerds on the ground.

  33. leftscienceawhileago says:

    My dear Dr. Woodweird,
    Your feigned interest is obviously an attempt to bait me into a discussion which would only further the aims you pursue by shameless self promotion, and only inflict suffering upon more individuals who were foolish enough to buy a copy of your miscarried opus.
    The few good passages in your book must feel like a proper synthetic organic chemist at a peptide meeting, surrounded by crap.
    I recommend you look outside your field for inspiration, so that the next book you write will redeem you from this one. Please use the proceeds that you gained from my purchase on this book:
    I believe I have answered all of your questions.
    Good day.

  34. Hap says:

    Sevenson’s group got MS of their products, and they give an NMR with very high and very low field peaks that doesn’t make sense for the ynediene that Christl says is formed. (No alkyne C-H is noted, either, and if the ynediene is right there should be two different alkyne C’s in C13, rather than the one that Stevenson’s group says they see). On the other hand, the NMR of the mixture has some peaks in typically aromatic positions that might fit the antiaromatic ring, but the rest of the peaks don’t look much different from standard alkene peaks.
    I don’t know what’s going on, and I have to say that I can’t fault the reviewers for not understanding the paper (or not rejecting it) because I don’t understand it well myself.

  35. Design Monkey says:

    18. milkshake on December 15, 2009 3:08 PM writes…
    I was in Child for one year. Oh horror. Only one bathroom per entire long floor, and I happened to be at the exact opposite end of the long hallway
    There is saying form Russian chemists:
    Real chemists drink government issued alcohol and pee into lab sinks.
    It sounds better in original, but you get the idea..

Comments are closed.