Monday, May 11, 2009

If I were working with tert-butyllithium...

 I've pretty obsessively covered the UCLA/Sheharbano "Sheri" Sangji case with two hats: as a blogger who sees this as a tragic consequence of some of the deficits in academic chemistry lab safety and as a working synthetic chemist who desperately wants to avoid bodily injury*. As time grows, I've thought about what I would do the next time I use tert-butyl lithium. Here are my thoughts on the precautions I would take:

No matter the scale of the t-butyllithium reaction: 
  • Full PPE: For me, this goes without saying. But let's make it really clear: Lab glasses (with side shields), lab coat (I even have access to a couple Nomex ones, but a regular lab coat will do.) Gloves at the right size -- not too small (they'll split at the wrong time) and not too large (overly bulky is uncomfortable and maybe clumsy.) The right kind of gloves (latex or nitrile.) No shorts or sandals. 
  • Avoid synthetic clothing: Neal Langerman has made it clear -- no synthetics, down to the underwear. Ladies, that means your upper undergarments, too. (This is a family blog and I'm a prude Baptist.)
  • Hood sash down as far as you can comfortably deal. 
  • A full and complete understanding of your nitrogen line system (with bubbler.) You are going to use a SureSeal bottle, right? Make sure you understand how much pressure you need to make sure the bottle has an inert atmosphere and that you're not overpressuring your system. I speculate this may be another hidden reason for the accident in the Sangji case. 
  • A clean hood. No bottles of flammable waste knocking around, no glassware to get in the way. 
  • A mind free of distraction: Quit worrying about how your boyfriend's ticked at all the time you're spending in the lab, quit being annoyed at your boss and his stupid questions at group meeting. Get your mind in the hood. 
A small-scale reaction (less than 10 mls of tBuLi):
  • Clean needles: Chances are, you're not using a disposable needle. Chances are, you're using metal needles. Make sure they're clean, unclogged, dry and working. 
  • Making an airlock?: This is an interesting idea that I've never tried: Plug both ends of a short length of glass tube with septa, flush with Ar, then use it as a needle "air lock" pushing the needle through both septa, then into the BuLi bottle. Take what you need then withdraw the needle through the first septa only - if this is pressed up against the septa of the bottle then the tip shouldn't catch fire.
A larger-scale reaction (more than 10 mls of tert-butyllithium):
  • Think ahead of time: Pre-plan. It might seem a little silly, but let's face it -- someone died doing what you're about to do. Think about scale of flasks, needles, syringes ahead of time. 
  • Have patience: Don't have the right equipment? Don't do the reaction yet! Don't feel safe? Don't do the reaction yet! 
  • Don't do this alone: First couple of times, have someone looking over your shoulder while you're doing this. Everytime you do it, make sure someone knows what you're up to, the very second you start. Which brings me to the next point...
  • Not in the middle of the night! Don't do this in the middle of the night, when there's nobody around and you're all alone. You'll be more likely to be tired and make a mistake. 
  • Learn your equipment: Make sure you're comfortable with the syringes you're using (and that you don't withdraw too quickly). Note: Milkshake (probably one of the more experienced bench chemists in the blogosphere) says that the 50 and 60 mL syringes stink. Go with multiple draws on a 20 mL syringe, he says. 
  • Leather gloves: Going to be working with a lot of tBuLi? Try leather gloves. From the accident reports, it sounds like the nitrile gloves may have caught fire. A pair of leather gardening or work gloves (make sure there's no synthetic fabric pieces) may make your life easier. 
  • Consider cannulation?: Cannulation always makes me nervous, as it's easy to overpressure your system and get jumping reflux condensers and the like. But IF you know your nitrogen line well, it may be a good idea to consider. 
  • A blast shield?: If you can't get your hood sash down (maybe you need access to the vacuum manifold in the back of the hood?), a safety or blast shield might be a good way to avoid the flames that may happen. 
A couple more resources: Lots of people have pointed to the Aldrich bulletin on handling air-sensitive reagents. There's lots of good advice (and some hairy stories) in these two In the Pipeline threads.  

I'm sure that others will have good advice on how to handle tBuLi. Please, I ask you, put your good advice in the comments to this thread. 

*After all, I have a wife and daughter to feed and hands I'd like to keep. 


  1. If faced with transferring a large volume of pyrophoric solution, consider using a system of cannula (cannulae?) and a graduated cylinder with a 24/40 top. It will take only a minute to diagram a system that pushes solution from container into cylinder for measurement and then into reaction vessel using a balloon hooked to a needle as the driving force.

  2. So Anon12:08 -- a question. Is it possible to use only balloon pressure for cannula systems? I was under the impression that you needed the raging force of a N2 tank for it; is that wrong?

  3. Balloon pressure is not enough; you'll have extremely slow transfer.

  4. I usually use a syringe and pull from the other side of the cannulae, not quite as efficient but it works well when getting things started.

    Also since when has Bra been a forbidden baptist word?

  5. Not that I'm aware of, but the fact that I'm uncomfortable writing about it is a sign of my innate puritanical nat- er, religious upbringing.

  6. Actually, I hate to disagree with Anon but I've used balloons with cannulae several times. the trick I always found was to ensure you transfer "downhill". Almost as if you're siphoning. Worked for me on 100 mL tBuLi reactions and with other equally exciting reagents. Oh, and the sirlock idea is a winner by the way. Avoids the "panic flamethrower" effect you can get the first time.

  7. Former EHS DIrectorMay 23, 2009 at 11:37 AM

    I was the former director of EH&S (until 4/1/09) of a very successful pharma R&D company with more than 600 researchers that shall remain nameless. Yes, EH&S is the "police," and yes, university settings are likely less safe than private industry. However, I can assure you that my group took safety very seriously and attempted to work collaboratively with researchers to make sure they understood their legal and personal responsibilities to work safely. That didn't keep a PhD (group lead) from propping a heat gun in a hood to melt some tert-butyl to soften it for an experiment while he left the building to have a smoke which even my 11 yr old knew was not a good idea.

    Ironically, his hood caught on fire while he was outside. Though we had strong EH&S policies and procedures in place (from my end), he didn't receive so much as a reprimand from the company's management and senior management. I can't help but conclude that many companies consider these sorts of incidents collateral damage in the interest of getting the research done. And, that said, there are many, many private companies and other organizations that take safety VERY seriously.

    The UCLA researcher appears to me to be one of those rebels not following the rules, or someone whose management didn't demonstrate through the willingness to take punitive actions with those who break the rules. Either way, she is now no longer with us because of some very simple rules that were broken: know what you are working with, take necessary precautions, and always, always wear the PPE.

  8. Note to readers, especially novice chemists:

    I welcome the comment from "Former EHS director". However, I believe that the compound that the group lead was using was tert-butanol, NOT tert-butyl lithium.

    The appropriate (and common) way to heat a bottle of t-butanol is to place the bottle on top of a hot oven or (better yet) in a warm water bath.

  9. >>Read your bottles!

    oh yeah, nitrogen line and vacuum manifold,
    would be nice. but then I'm not using BuLi, and it limits my scope a little

  10. then again, maybe the problem with organic chemistry in academics is you are in an underfunded lab without lots of people with advanced training to man the fortress.

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  13. All in all a very sad story.

    Something I like to remind people of is that they should use 100% cotton labcoats (which may char, but do not melt and stick to your skin) that are sized correctly.

    Also, I really recommend glove-liners; either cotton or Kevlar based since 1.) they do not burn well, 2.) they insulate your hands so you don't accidently burn yourself by touching a hot flask or heating fluid line, 3.) they provide a modicum of slice/slash resistance. I've saved my hands many a cut from a broken piece of glass as well as what could have been a nasty burn from my nitrile gloves.

    Cannula technique can be just as dangerous to the inexperienced graduate student as anything they will do. Many seem to think that a lot of pressure is needed, when just 1 or 2 PSI will do the trick.

    It all comes down to proper manifold design, maintenance, and training on it. Each and every PI should take the time to teach proper Schlenk technique (since some of the comments here show an obvious lack of knowledge!).

  14. @Fleaker: You are welcome to add your thoughts and corrections on proper Schlenk technique -- please do!

  15. Focus on the goal of the synthesis and find an alternative way to make the product. Thinking outside the box is very often a good safety practice.

  16. Strive, stongly, to NOT use pentane solutions of pyrophrics, if hexane or heptane solutions are available. You not only have the pressure of N2 to deal with, but the vapor pressure of the solvent. Pentane basically boils (that's 15 psi) at the temperature of your hands. SO if you put your warm nervous hands around a syringe full of pentane and t-BuLi, guess what it going to happen after that.


looks like Blogger doesn't work with anonymous comments from Chrome browsers at the moment - works in Microsoft Edge, or from Chrome with a Blogger account - sorry! CJ 3/21/20