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TMS Azide Explosions

There’s been a lot of safety on the blog this week. One recent accident I haven’t talked about is an azide explosion at Minnesota – C&E News, though, has plenty of coverage. Back in June, a grad student was injured when a batch of trimethylsilyl azide exploded – a 200 gram batch. As more details came out, it turned out that the student had reached in to adjust a thermometer on the reaction setup, and was wearing no protective gear:

More important than the reaction, Tolman emphasizes, is the deeper root cause of the incident: insufficient recognition of the reaction’s hazards. Warnings included with literature protocols were “pretty lame,” he says. He also thinks that the lab group became became complacent after doing the reaction several times without incident. “While they were aware of the hazards, concern about them became less up front,” he says.

Indeed. This just emphasizes the sort of thinking I was talking about the other day, the “What’s the worst that could happen?” exercise. In the case of two hundred grams of azide, the worst that could happen should be apparent to anyone who’s being let loose in a graduate chemistry lab: that thing could blow up. I notice that the student involved is quoted as saying that he’s learned that the hazards involved in running a reaction (even an Org. Syn. prep, which this was based on) are not necessarily made clear in the literature. While that’s true, the hazards of 200g of sodium azide going to the TMS azide should have been clear from the start. This, to me, was not a failure-to-warn; this was a failure-to-realize, as the department chair says in that quote above.
There was a lot of good discussion at Chemjobber’s blog when this happened (here as well), with one commenter noting that 200g of trimethylsilyl azide costs about $600. That, to me, illustrates another problem: it’s well worth six hundred bucks to keep someone from having to do an azide reaction of that size in your lab. I know that funding is tight and that academic labs can’t just trot out and buy all the reagents they need, but still.
More recently, a letter to C&E News mentions that no one at the university has been talking about blast shields. The response is that these things are sort of the last line of defense, and that a higher-level review (“Should we be doing this at all?”) would be a more general solution. That’s true, but people are going to set up reactions of all sorts, at all hours, especially in an academic lab. You can’t keep an eye on everyone, all the time, not even close. But even if the plan of a large-scale azide prep gets carried out, a general recognition that you shouldn’t be near the thing without barriers and PPE would be pretty useful. Now, it’s true that on that scale many blast shields are only going to be able to do so much, but they can at least soak up some shrapnel, and I’m just baffled by anyone setting up a reaction even remotely like this without having one in place.
It all gets back to thinking about what you’re doing, and there’s no form to fill and no box to check to make a person do that. Always think about what the most likely problem might be with a reaction, and what the worst problem might be. If you’re heating up two hundred grams of sodium azide and that answer to both questions isn’t “This could blow up and kill me”, then there are even bigger problems that need to be addressed.

37 comments on “TMS Azide Explosions”

  1. A. Nonny Mouse says:

    I wonder if there isn’t some connection between “failure-to-realize” and an increased emphasis on “CYA safety”, especially at the levels where you’re learning your habits, before you get into these situtations.
    I don’t work in labs, but I do see various industrial situations from time to time. And what I’ve seen more than I’d like, even in MSDSes and definitely in standard procedures, is a failure to provide calibrated risk warnings.
    There’s a difference between “it’s not a good idea to do this when you can avoid it, because there’s a .001 percent chance of it going badly wrong”, “it’s really stupid to do this, because there’s a 1 percent chance of it going very wrong indeed”, and “doing this is flat out suicide”.
    But you don’t get that information. What you get is “take precautions X and Y”, starting from your very first introduction to the environment. And sometimes X and Y are overboard, and sometimes they’re not, but you hear the same emphasis on both, and rarely do you get an explanation of why the rules are there. Often the person enforcing them doesn’t know, either.
    So you mostly go along, out of habit, and you get out of the habit of thinking. Sometimes you cheat, but you do OK, and your occasional slips don’t hurt you too much because most of the risks weren’t that big in the first place.
    Until you really blow it. Maybe because you suddenly got into a position where you really were expected to assess risk for yourself, but didn’t recognize that or didn’t have the habits.
    Do chemistry students normally get a “you’re doing original work now, so you’re expected to assess hazards for yourself” lecture? Is it formal? Is it beaten into them?
    Maybe even the first year undergrads ought to be assigned 500 word essays on why the safety precautions in their labs are what they are, what might happen if they weren’t followed, and why they are (or aren’t) adequate. If you teach awareness, you’ll get awareness.

  2. Thomas McEntee says:

    Complacency…can be a killer. In December 1974, I was called by the plant supervisor to come out to where the day shift was running another 2000-gal oxidation of tetrachlorocatechol using a process I’d developed for the production of high-purity o-chloranil. We had run this 15 or 20 times before without problems. The process involved use of considerably less than a stoichiometric quantity of nitric acid in hydrochloric acid under about 15 psig oxygen in the headspace. When the oxidation was complete, we centrifuged pure o-chloranil and washed the cakes with hexane..(uh oh). The problem I was presented with was that the reaction was not taking up oxygen. We checked the oxygen cylinders (OK), the dual manifold system (OK), and scratched our hard hats. 10 minutes later, the reactor exploded. Flames erupted from where the sight glass had been. Long story short, 3 of us nearly died and it was a week before I got out of the hospital.
    The graveyard shift had the job of cleaning the GL reactor, finishing the cleaning with water washes and a final spark test for explosivity. After months of denials, the truth came out that the reactor cleaning had not been done at all and that about 100 gallons of hexane were in the reactor when the day shift loaded it for the new run. The batch sheet had been filled in as if all the cleaning and spark testing had been done. Under the agitation conditions we used and in the presence of pure oxygen, the hexane auto-ignited. Critics will say ‘well, that should teach you…” but we had been able to bypass messy recrystallizations from carbon tet using this process. We had the forms and the boxes to check but the plant workers, all good guys but a tad lazy in those eerie hours after midnight, tried cutting some corners. As Derek wrote, it all gets back to people thinking about what they’re doing.

  3. annonie says:

    Universities continue to be lax on safety for such things. They leave it largely up to the individual dept, who sluffs it off to the professors, who are too busy to give proper oversight. The government continues to keep hands off too, like they to for other crimes on campus such as sexual assault. It’s all appalling. It’s criminal.

  4. A Nonny Mouse says:

    #1 is not me……

  5. Phil says:

    The argument against blast shields sounds a lot like the argument for abstinence. You’re not going to prevent every student from running a hazardous reaction, so give them training and access to all possible protection (including a blast shield).

  6. Nick K says:

    Azides are capricious and treacherous. Back in 1987 at Pfizer Sandwich they were making large batches of azidoethanol for the development of Amlodipine. The route had been run dozens of times without incident, until one evening, when a 1Kg batch exploded. It was a huge bang which shook the building, blowing out all the windows on that floor and doing structural damage. Had anyone been in that lab, he or she would certainly have been killed. No explanation for the incident was ever found. Nt surprisingly, a 10g limit was placed on azide reactions subsequently.

  7. David Borhani says:

    @2, Thomas: Out of curiosity, what are the uses for that large a quantity of o-chloranil?

  8. Anonymous says:

    “Blast shields are the last line of defense”?
    Great reason why we don’t need them! Not!
    I mean how stupid can someone be, with that kind of “logic”?

  9. Funny says:

    Did you guys go to grad school? You are completely on your own with regards to safety and protection. When faced with the option of ponying up 600 bucks for a compound – or having a grad student – someone whose labor is so cheap it’s almost free make it – what will every prof choose?
    I used liters of dimethyl sulfate in the early steps of a synthesis. Never once was I educated on the dangers of it. I had to learn as I went. What would happened if I spilled 100 ml on myself? I shudder to think. But, my advisor told me if I didn’t want to do the 100+ g preps – he’d find someone who would and I could forget about a good letter of recommendation. I did the preps – but the huge amounts of dimethyl sulfate I was using always made me nervous.
    Grad students dont think about the hazards of a large scale azide prep because they are under pressure to crank out results as quickly and cheaply as possible. To think that will ever change is a pipe dream.

  10. David Borhani says:

    Derek: Time for a new web host (cf. my unintentionally repeated comment)

  11. Anonymous says:

    My colleague had absolutely ordinary Schmidt reaction exploded – he did this reaction like hundred times before. Now even sodium azide is for small scale only.

  12. Slurpy says:

    This makes me think of Mike Rowe’s thing, “Safety Third.” Poorly paraphrased: the company is paying us to do this dangerous thing to make money. We are working for this company, doing this dangerous thing, to make money. Therefore:
    First: Money.
    Second: Money.
    Third: Something else (hopefully safety, but not necessarily).
    Feel free to substitute education/publication for 1 and 2, but it’s the same idea. Yelling “Safety First” everywhere is misleading, distracting and dishonest – accepting that you are doing dangerous things and understanding just what the risks are and what the consequences will be is far more useful than being afraid of everything to the point of complacency, as #1 said.

  13. Thomas McEntee says:

    @7 — oxidizing agent in an obsolete color film system for instant photography

  14. Academics says:

    For me it all goes back to the PI. If you are running the lab you are directly responsible for everything that occurs in that lab, no exceptions. I feel like too many PIs are too concerned with their own career growth that they don’t actually care how the lab runs on a day to day basis as long as they get their publications. To me it seems like they want all of the credit and none of the responsibility.

  15. Hap says:

    Safety isn’t really a goal (except in PR) – you do things that might have hazards for some reason (to make money, to have fun, to help others, or some combination), not to be safe, because if you wanted to be safe, you probably wouldn’t do those things at all. What you want from people is that they assess the risk as best they can (whether they should do what they’re doing at all or if it has too much risk for what they get), and to do what they have to as best they can and with as full awareness as possible of what they’re doing.
    Academia seems in lots of cases (I don’t know this one) like small businesses (*cough*T2*cough*), where doing things with any awareness of safety, or with an awareness of almost anything else other than getting things done and getting papers published is verboten. Universities charge for infrastructure (which in lots of cases includes safety provisions) but don’t want to spend the money on safety. (Also, since mindfulness is so hard, and they don’t care too much about safety because it doesn’t pay, they generally can only either let people do what they want or paper over the department to cover themselves.) Advisors get credit for papers, but not so much for teaching, and not much at all for teaching grad students, so guess where their efforts are directed…
    Risk/benefit assessment is hard because grad students don’t generally have that much experience with assessing risks, and grad school is not normally the healthiest place psychologically so risks and rewards may not be rationally determined.

  16. Tiger Chem says:

    I really wish that most PI’s would take safety more seriously but, with the precedent of Harran’s trial, it’s clear that they will not be held responsible. This is not to say that some don’t do this right (I’ve seen it firsthand, and it’s not that hard) but there is not a lot of incentive (other than the health and safety of grad students…)

  17. Featherson says:

    When I was in grad school in the late 70s, we had a hot shot group that shall remain unnamed next door to my lab. They actually took pride in doing stupid things-e.g. drinking coffee out of dewar flasks, smoking cigarettes while working up reactions, eyeballing a refluxing perchloric acid reaction from one inch away without safety glasses- all in the name of testosterone I guess. Plus they stole my calculator.

  18. Ted says:

    @2 – You obviously understand this, but it’s worth pointing out:
    (Glass or glass-lined reactors) + hexane + agitation = sparks.
    Freaked me out every time…
    -t

  19. agsone says:

    If I’d had a big accident in my group that was in the news I think I’d probably remove the 20+ photos of myself, past and current students taken in the lab while not wearing safety goggles from my website. They are clearly all portraits and not active chemistry but sheesh.

  20. Squib says:

    As someone who had had to create multiple >100g batches of an azide with only 5 other heavy atoms this year, I think one of the main problems can be complacency. The reaction had been run multiple times before and as we were scaling it up I’ve always been behind a safety shield. I’m always scared when I’m concentrating it down on the rotovap, but thats the way it should be. If you’re not scared of reactions like this you’re doing it wrong. At some point you’re going to be doing dangerous chemistry and there isn’t much you can do besides being as safe as possible. As someone who can be lax about lab glasses its amazing to thing you’d go to nudge the thermometer in this case without them at least protecting your eyes.

  21. bad wolf says:

    @17 Featherson: Were you at Sacramento State? When I was there there were still stories about the group that took out an entire floor of the building with a large scale perchloric acid reflux.

  22. Canageek says:

    Man, suddenly I’m glad I’m in a lab opposite of most: My prof would much rather pay $600 then risk an explosion. Heck, he doesn’t even like having a bottle of tBuLi in the lab, and to use it we need special permission from him, and proof that a) This is a *really* important reaction, and b) that higher conc. nBuLi or secBuLi won’t do it, and then he’ll think about it, and make sure the post doc is standing right there watching with a fire extinguisher, and probably a good chance he’d be there himself.
    That said, is there a big list of dangers you can consult? MSDS are great, provided anyone makes the stuff, but I bet there are a lot of chemicals known that people don’t know the dangers of, and it would be nice to check that without having to do a big literature search. I mean, I know sodium azide of course, but there are lots of metal salts and organic things out there that I might not know about.

  23. Jon says:

    The standard in the process world is probably Bretherick’s and there are other guidebooks out there as well. Of course, they’re still limited by what has been published, but such books are still a good starting point and will include incompatibilities you may not know of. Reasonably priced for a lab as well (under $500 on Amazon, although you could get a Kindle edition for about $300).

  24. Semichemist says:

    @ 18. Ted – Could you expand on that a bit? Why is it the glass in particular? Static charge?

  25. Anon says:

    @1, 22: I agree. It is frustrating that at the end of the day MSDS sheets are legal documents and are not the most informative. I prefer to look for SOP’s online (the Sarpong group website has a pretty comprehensive list).

  26. Anon says:

    @1, 22: I agree. It is frustrating that at the end of the day MSDS sheets are legal documents and are not the most informative. I prefer to look for SOP’s online (the Sarpong group website has a pretty comprehensive list).

  27. Jon says:

    Semichemist,
    Yes, it’s the static buildup. It’s a common problem with non-conductive solvents, especially in a non-conductive reactor. There are additives out there like StatSafe, which helps with the static electricity problem. Although I’m not sure anything would help in a kettle full of hexane and pure oxygen.

  28. philip says:

    In grad school a blast shield saved my undergrads life when my pressurized Wolff kisher reaction exploded due to flawed glass. Blast shields need to be reiterated in lab safety, they are indispensible

  29. Thomas McEntee says:

    We estimated that about 100 gallons of hexane were left in the reactor before roughly 1200 gallons of 10-percent hydrochloric acid containing the nitric acid were charged, followed by the tetrachlorocatechol. Quite different conditions than a reactor containing only anhydrous hexane (never mind the pure oxygen…) but Jon’s points are good ones.

  30. gippgig says:

    #22-23: What is needed is a public domain compilation, i.e. a reaction hazard wiki.

  31. Dirk says:

    #2 “After months of denials, the truth came out that the reactor cleaning had not been done at all … The batch sheet had been filled in as if all the cleaning and spark testing had been done.”
    The conclusion is to have check points in processes. Before the new reagents are added, the cleanness and spark test must be confirmed by the same operators adding the new reagents.

  32. dave w says:

    #29 – since hexane is much less dense than water and almost perfectly insoluble in it, adding 1200 gallons of dilute aqueous acid solution to 100 gallons of hexane would leave the hexane floating as a layer on top (and hence exposed to, and available to evaporate into, the oxygen-filled headspace – this would have explained why “the reaction was not taking up oxygen”: there was a layer of light hydrocarbon between the oxygen gas and the intended reaction mixture!)
    So the potentially explosive conditions would not actually have been so different from a “reactor containing only anhydrous hexane”…

  33. Thomas McEntee says:

    @32 — Yes, once the truth about the hexane became known to us, we completely understood the situation you describe…

  34. Thomas McEntee says:

    @31 — Yep

  35. Simon Higgins says:

    You learn something every day- as a small-scale synthesis person I’d never heard of the static electricity issue before.

  36. Simon Higgins says:

    You learn something every day- as a small-scale synthesis person I’d never heard of the static electricity issue before.

  37. Jim Bosley says:

    As someone who was injured in a lab explosion as an undergrad (not seriously – though I still have some glass shrapnel in my pectoral muscle), I can say from personal experience that safety is not addressed nearly enough in academia.
    I was injured by about about 8 g of benzoyl peroxide and an organic amine exploding in a glass bottle. 200 g? Half a pound? Wow. That’s a professor/advisor asleep at at the switch. No PPE? The university safety training was inadequate. So many failure modes here… Probably the major one is hammering it into students heads: “Some of the stuff we work with can explode, poison you, burn you and burn up the building, cause cancer in you or your yet-to-be-born offspring, and harm people and flora and fauna in the wider world. Know what you are working with, know the dangers, design experiments to eliminate/attenuate danger, wear appropriate PPE, work in hoods, have an escape route,.. ”

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