Org Prep Daily

March 25, 2008

Bleak chemistry

Filed under: industry life — milkshake @ 1:38 am


Last week I run a reaction in molten imidazole without a solvent, at 240C in a pressure vessel. This reminds me – in Prague we would heat quantities of beta naphtol with neat hydrazine hydrate in a “Bombenrohr” in the electrical oven at 150C, and we were taking that alarming thing periodically out and giving it a hard shake while hot. (Bombenrohr is a fancy German word for a pipe bomb, a steel  tube with screws at ends).  The resulting ooziness was then poured and spooned out into vats of boiling water, to extract away the unreacted hydrazine, naphtol and the sideproduct – betanaphtylamine (I know how it smells so I am gonna die) – and the leftover slime was then repeatedly precipitated as HCl salt, to get 1,1′-binaphtyl-2,2′-diamine. We were making 50 g batches of the racemic stuff that way and we were then resolving them with CSA.

The meanest reaction I did was melting binaphtol with 3 equivalents of Ph3PBr2 without solvent, to get binaphtyl dibromide. The procedure called to “dilute the melt with equal volume of dry Celite, cool the mixture to solidification, break the flask and peal off the glass, crush the solidified reaction mixture into half-inch sized chunks and extract them in Soxhlet” – which I managed, except that hammering the mean black 250mL tar-ball into chunks produced lots of corrosive bits flying everywhere while I was choking on the HBr fumes.

There is no moral to this sad story.


  1. I think the moral is “there is something seriously wrong with eastern europe.”

    Comment by excimer — March 25, 2008 @ 3:06 am

  2. You sir… are a badass.

    I am not worthy.

    Comment by milo — March 25, 2008 @ 8:32 am

  3. Yikes, that’s seriously nasty. I ruined a few flasks pyrolyzing corn starch to make levoglucosan, that’s for sure, but at least that didn’t produce beta-napthylamine as a byproduct. Sheesh.

    Comment by Derek Lowe — March 25, 2008 @ 10:27 am

  4. awesome

    Comment by pi* — March 25, 2008 @ 2:50 pm

  5. Cue James Brown singing “It’s a Man’s World”. Wow.

    Comment by Klug — March 25, 2008 @ 3:49 pm

  6. Sweet jesus.

    Comment by Jose — March 25, 2008 @ 7:02 pm

  7. haha, i just looked up beta-napthylamine in aldrich and it’s categorized under “carcinogens.” Rest in peace.

    Comment by excimer — March 25, 2008 @ 7:56 pm

  8. (molten imidazole rocks!)
    um, wow. you ARE a badass. so tell us, how does beta-naphthylamine smell?

    Comment by Ψ*Ψ — March 25, 2008 @ 9:07 pm

  9. When you take 1,3,5-difluorobromobenzene and melt it with an excess of imidazole at 240C you get 1,3,5-bis(N-imidazolyl)bromobenzene in about 50% yield and it is not too nasty mess to work up because the product crystallizes out quite nicely. (Monoimidazolyl product stays in supernatants). The only trouble is that the glass flask gets somewhat etched by the produced imidazole hydrogenfluoride. Biotage microwave reactor makes these inquisition reactions quite easy.

    Betanaphtol has an acrid naphthalenish-phenolic smell but betanaphtylamine is actually somewhat sweeter (but still nasty and aromatic)

    Comment by milkshake — March 26, 2008 @ 5:50 am

  10. OMG…

    I once vacuum distilled nitrobenzyl bromide, which exploded. I was hospitalised for a month while all the skin on my face, scalp, ears, chest and arms slowly peeled off. There is still glass in my right hand, which the doctors did not want to remove because they could end up maiming me. Fortunately, I did not have mutant children later on. My PhD advisor got away scott free because he told the bosses that I did the experiment without telling him. Which was a lie. Such is life…

    Comment by dilutedmagnetics — March 26, 2008 @ 8:53 am

  11. I am sorry to hear this one – your advisor should have known, about nitro compounds exploding when distilled to dryness and about the extreme nastiness of benzyl bromides. The only consolation I can think of is that at least your eyes were not damaged in the mishap/

    Comment by milkshake — March 26, 2008 @ 10:52 am

  12. It is very sad to hear that. Most chemistry teachers at Uni are not familiar with safety issues. We all were horrified to know that certain operations we did at Uni were not safe at all and the whole building could have blown up. But maybe, due to use small quantities or to luck accidents are not so frequent as one may think, afterwards.

    Comment by vasili — March 26, 2008 @ 1:55 pm

  13. In the group that I had my post-doc, graduate student A asked graduate student B how to dry a large sample of AsCl3. Graduate student B suggested refluxing it from sodium. At about the melting point of sodium it blew up, pulverizing the apparatus and depositing a thin film of arsenic oxides and chlorides over the entire lab. This happened at the end of the day and my supervisor was extremely motovated to get the mess cleaned up so I went in with him and we cleaned through the night. They monitored my arsenic levels by hair analysis and they were still elevated a year later.

    Comment by Liberal Chemist — March 26, 2008 @ 10:16 pm

  14. Jesus, some of the stories here!!!

    betanaphthylamine was responsible for a cancer outbreak in dye factory workers somewhere IIRC.

    Comment by TWYI — March 28, 2008 @ 4:11 am

  15. Dude you rock!!!

    Comment by KATS — April 1, 2008 @ 4:05 pm

  16. A few good ones come to mind- Sodium thiolates in HMPA, and using neat MeMgBr slurry (160 deg C fuming madness)to deprotect Ar-OMe.

    Comment by Jose — April 1, 2008 @ 7:41 pm

  17. Brian Stoltz started his thesis synthesis of Staurosporine by melting o-toluidine bisamide of oxalic acid with excess of tBuOK, neat, at 320C, to make 2,2′-bis-indolyl.

    Comment by milkshake — April 1, 2008 @ 8:51 pm

  18. I have done that very reaction like Stoltz.

    Only time I have used a Metal bath for anything. Works very well too!

    Comment by TWYI — April 1, 2008 @ 10:52 pm

  19. “…while I was choking on the HBr fumes.”

    Smart boy works inside fumehood :o)

    Comment by Mary — April 2, 2008 @ 7:05 am

  20. And even smarter boy does not run this reaction.

    In Prague we had only one large hood for the entire lab and it did not work so great. Some time after I left, the boss got eventually upset about the hood exhaust performance and climbed into the old building attic and then on the roof, to investigate. He found out that few feet of pipe between the exhaust fan and our hood was missing, probably knocked off by winds, without anyone noticing. All these years the sole hood was working without any functioning exhaust – except for a chimney effect…

    Comment by milkshake — April 2, 2008 @ 1:35 pm

  21. In our lab, the chimney effect was the only effect that dispersed the noxious H2S fumes that enveloped the whole room.

    Comment by Wavefunction — April 2, 2008 @ 10:46 pm

  22. Elaborate stories with “no moral”.. always funny, though dangerousIt ranks right up there with scratching azides off of a metal surface. Unfortunately, that poor sap lost a finger. Glad to see no one was seriously injured.

    Comment by J — April 24, 2008 @ 4:59 pm

  23. omg Is there much suing going on then I wonder? ;¬) Very funny stories. I love this blog btw

    Comment by Minty — May 19, 2008 @ 11:55 am

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