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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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March 1, 2007

How Not to Do It: Tertiary Butyllithium

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Posted by Derek

Over here at scenic Lowe Manor (otherwise known as the House that Pharma Has Paid And Will, With Any Luck, Continue Paying For), the dinner table conversation sometimes runs to things like the proper handling of flaming t-butyllithium. Well, OK, the conversation is a bit one-sided, since I'm the only one in the house who's used the darn stuff. My wife has done a lot of bacteriology and molecular biology, fields that don't find much use for pyrophoric organometallics, and I'll keep my kids a good distance from any bottles of butyllithium, thanks.

But I was speaking to the them the other night about the value of experience. Tertiary butyllithium catches on fire, and there's nothing you can do about it. Your best course is to be aware of that, and to expect it. That way, you won't be shocked when you put your syringe into a bottle of the stuff and withdraw it only to find a merry orange flame burning from the tip of the needle. That's a good sign - it shows that your bottle of butyllithium is still good, as opposed to the cloudy, wimpy, hydrolyzed stuff that you should carefully leave sitting in someone else's hood when they're not around.

This pilot light will do you no harm, and will extinguish itself once you put your syringe needle through the next rubber septum. But if you're not expecting it, the sight can come as a bit of a jolt. The consequences are generally not good. There's almost always a tensing of the hand and arm muscles, which tends to depress the syringe plunger a bit, and whooomph: instant flamethrower. I've heard of several completely needless fires that started this way, invariably at the hands of someone who wasn't psychologically prepared to wield some (temporarily) flaming lab equipment with the needed aplomb.

As I mentioned here before, I've had still more practice with fiery glassware. I can attest that a butyllithium flame from the pure substance has a more noble purple color to it than the common orange of the commercial hexane solutions. That magenta hue is from the emission spectrum of lithium itself, and (at least in my case) it did not have a calming effect.

There are, regrettably, even more stupid things to be done with t-BuLi. I'm not sure if I've told this one here before - it's not in the archives at right, so here goes: a friend of mine in grad school was showing a summer undergrad student (hear the chairs of the experienced chemists draw closer) how to do cannula transfers of air-sensitive materials. (This involves hooking up a hose system with needles and tubing, with dry nitrogen or argon gas bled in at the front end of the system to force the stuff over into another waiting flask). There was a double manifold set up in the hood, as usual, to allow a vacuum pump out to remove air from reaction flasks and let nitrogen in to replace it. Somehow, this summer student got the vacuum and nitrogen setting all hosed around when trying to cannulate a whacking load of t-BuLi, and reported back a few minutes later that (although everything was set up perfectly) no butyllithium was appearing.

Feeling the hair raise up on his arms, my friend came to look things over, and saw that indeed, no t-BuLi was showing up in the receiving flask. But there was nitrogen pressure going in, so surely something had to be going somewhere, right? He looked up. . .and realized with a sinking heart that the vacuum manifold at the top of the hood was inexorably filling with the stuff. Now what? I always think in that kind of situation that it's time for lunch, no matter what the clock says.

Comments (26) + TrackBacks (0) | Category: How Not to Do It


COMMENTS

1. molecularArchitect on March 2, 2007 4:00 AM writes...

That incident reminds me of another. I was the TA for an advanced organic synthesis lab. The prof in charge decided that, rather than do pointless experiments producing compounds which would not be used, the students would do scale up synthesis of intermediates needed by graduate students in the department. One of the procedures was a large scale prep using n-BuLi. The student set up the cannula between the bottle and the flask, inserted the nitrogen needle into the bottle, a vent line into a septum on the flask, and pressurized the system. Nothing came over, so he increased the pressure. Still nothing, increased more. He then walked across the room to ask me what to do, without turning off the nitrogen.

Turned out that he had inserted the vent needle into the thick edge of the septum and it had not pierced through. Suddenly, the septum with the cannula popped off the flask and started rotating wildly about in the hood, spraying n-BuLi everywhere which promptly caught fire. The student stood there, with his mouth open, staring at the spectacle. I'm racing across the room yelling for someone to turn off the nitrogen. Luckily, I got there and turned off the gas which extinguished the flame with no major damage but what fun!

This particular student was so incompetent that his first name soon became a synonym for a screw-up. Even professors started to say "I did a (his name)" when they made a mistake.

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2. JamesB on March 2, 2007 6:25 AM writes...

One way to avoid the flaming tip of death: 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.

Undergrads need not bother - they're going to have a fire no matter what they do.

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3. Russ on March 2, 2007 8:46 AM writes...

JamesB: Cool trick - I hadn't thought of that (well, I've never actually used tBuLi, so haven't really needed to...)

Not too long ago, I had occasion to see an undergrad's hybroboration reaction catch fire. That particular incident produced beautiful green flames, and promptly went out (100% conversion!).

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4. Jal-Frezi on March 2, 2007 8:56 AM writes...

Prior to my studies there, the department I did my PhD in lost an entire lab due to a cowboy postdoc not respecting tBuLi.

Adding it dropwise to his reaction at -78 was too slow and boring and he figured the whole process could be speeded up if only his tBuLi was at -78 as well. So he sets up a second acetone/dry ice bath and submerges his bottle of tBuLi in it.

Of course, the bottle shatters, fire ensues, consuming not only both acetone baths, but the two winchesters of flammable waste he had in his hood as well......

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5. Derek Lowe on March 2, 2007 10:03 AM writes...

There's a penetrating intelligence at work, all right. I guess it didn't occur to him either that at that temperature, his BuLi would have the vicosity of pancake syrup and would cannulate accordingly.

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6. milkshake on March 2, 2007 10:03 AM writes...

We had a brilliant guy who thought that if his metallation did not work at RT, he would reflux his material in neat 10M n-BuLi, about 100mL of it.
Things progresses without anybody noticing what he was p to, until the point when he tried to take the condenser off and found the joint to be glued. Like an aspiring Jedi, he used the Force.

He had couple of acetone/dry ice baths around, and a full waste container. The rest of his hood was a history, too.

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7. TNC on March 2, 2007 10:36 AM writes...

J-F: That's a brilliant story, if not sad for the loss of the lab.

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8. syregnask on March 2, 2007 10:52 AM writes...

I guess I'd like to first point out that the flammability of tBuli is dependent on your general air humidity and if you work in arid regions the flame is not guaranteed.

On the notion of respecting the stuff, one postdoc around here was particularly notorious for his carelessness (not that he ever had any incidents with BuLi). You might have seen how doctors flip bottles upside down when drawing liquids out into a syringe to eliminate air pockets. He used a related technique with his BuLi, no Ar line to even the pressure, holding the flask and syringe preferably above his head, no safety goggles.

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9. Petros on March 2, 2007 11:05 AM writes...

Takes me back.

Gave me a shock the first time I had to use t-BuLi, as n-BuLi was rarely a problem, but at least Aldrich supplied it in SureSeal bottles. It must have been horrendous to make your own.

Have also had the delights of destroying quantities in the past. First time as a consequence of a building fire that had knocked out all power. Second time in disposing of all such reagents when our part of the Wonder Drug Factory was shut down. We ahd rather more to dispose of that time.

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10. RET on March 2, 2007 11:26 AM writes...

Personally, I am a bit surprised that the bottle shattered when cooled to -78C and remind me of a story from my postdoc days.

Large-scale lithium halogen exchange reaction going on and first liter bottle of tBuLi went in fine, color looks good. The rookie is sent to the fridge for the second bottle. During his return a crash is heard and at is feet is the shattered bottle. Luckily, for his future as well as the labs, the polymer coating around the bottle held and protected the tBuLI so it could be used in the reaction. 80% yield.

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11. Outofthelab... on March 2, 2007 11:34 AM writes...

Quench day in graduate school - where all of the bottles that no one will use any more are gotten rid of (hopefully safely). All group members were required to take care of 3-4 bottles. When I was not paying attention, the very green first-year next to me chose 3 bottles of tBuLi. Before disaster ensued, I was able to replace them with 1M borohydrides. Not sure what became of the tBuLi but the building is still standing.

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12. wrw on March 2, 2007 11:50 AM writes...

Hmm:

As a Winchester, I have to wonder what is meant by
"two winchesters of flammable waste "....

As far as refluxing t-buLi goes, I point out that the prep for
(tbu)3SiH calls for mixing (tbu)2SiF2 with t-buli (xs) and stirring, then adding a still head and some highboiling alkane and distilling out the pentane and heating at reflux overnight. Really. I have seen it done, it isn't as evil as you seem to think.

No, more interesting is when you need n-buli6 for NMR studies and so you need to make your own buli from bucl and li6 and you first need to add the .5% Na amalgam that one usually gets with li, which means heating the li/Na mix until it is molten. Don't do this in glass.

Did you know you can distill buli? You can. I have. Or I think I have, it was a while ago...

Permalink to Comment

13. dearieme on March 2, 2007 3:05 PM writes...

OT, but I thought you might be interested in this obit of Cotton:-
http://www.telegraph.co.uk/news/main.jhtml?view=DETAILS&grid=&xml=/news/2007/03/02/db0203.xml

Permalink to Comment

14. Hap on March 2, 2007 5:10 PM writes...

SM: I think your labmate was simply looking to win a Darwin Award. I don't know whether I would be happy or not that he didn't succeed - at least my outbreaks of stupidity were unlikely to kill me or others.

Why didn't he try the Schlosser conditions (organolithium and potassium tert-alkoxides)? They might deprotonate some (lots of) other things, but functional group compatibility probably isn't an issue in refluxing 10M BuLi.

Permalink to Comment

15. milkshake on March 2, 2007 11:09 PM writes...

He did not try them cuz he did not know them. i mean - Why spending time in library (or asking anyone) if a quick experiment can settle the question permanently? (oh, did I mention he had his compound attached on Rink resin on polystyrene beads? The guy was quite an acqusition to the already technically-challenged combichem group)

We did BuLi/tBuOK mixtures in Prague - I and can confirm that this stuff deprotonates everything. We used it to metalate unsunstituted naphtalenes and binaphtyls. (Gray-black aryl potassium compound precipitating from the mic). I still remember shaking pentane - used as a solvent - with sulfuric acid, and than distilling it from P2O5, to get all the olefins out.

Permalink to Comment

16. eugene on March 3, 2007 1:10 AM writes...

I did reactions with tBuLi at reflux on the mole scale as a first year grad student. And the reaction wasn't for the purpose of deprotonation (well, in a way). It was to introduce a tBu group into a tricky position. You just have to know what you're dealing with and take it easy. Although, one time I did add four drops of water/methanol instead of three while quenching... I still recovered most of the product though.

Anyways, I can proudly say that transferring 800ml - 1L of tBuLi to the ginormous reaction flask via cannula did not result in even a small visible fire. Of course, this is probably, because I am the 'Master Of Refluxing tBuLi'!

Well... it is Friday... (gets coat and walks out the door)

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17. Liquidcarbon on March 4, 2007 10:02 AM writes...

I guess not many people work with cesium metal, but I heard about it. You crack the tube open, nevermind the fire and pour the metal in your reaction.

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18. Esteb on March 5, 2007 4:57 AM writes...

This also reminds me one of the biggest thrill I had, although retrospectively:
I have experienced an earthquake while doing some benchwork, ran out of the lab after quickly stopping some heaters and -only after few minutes- consider that the 5 l flask containing freshly prepared BuLi could have fallen or get broken.........brrrrrr
Still scares me!

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19. bcpmoon on March 5, 2007 11:05 AM writes...

As I used tBuLi for the first time (late in my PhD) I was rather disappointed - I was used to Diethylzinc... ;) For very unacademic purposes I wanted to prepare some 2 mL vials with Et2Zn and I was able to do so without any flames using several funnels connected to N2, more or less flooding the hood with nitrogen.
Btw, we called tBuLi "Männer-BuLi".

Permalink to Comment

20. ZAL on March 5, 2007 11:06 AM writes...

Hey,
my entire undergraduate work was about superbasic mixtures of BuLi, or LDA, and tBuOK! Thanks for reminding me of the good old days!

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21. Jeff Karenovics on April 19, 2007 3:46 PM writes...

I studied chemistry at the Albert-Ludwig-University (Freiburg/Breisgau, Germany). I was lucky to do my Diplome work in Analytical Chemistry, where I only handled sub-microgram amounts of metal ions to be determinated by their catalytic effect on exothermal indicator reactions.

But a co-student of mine was working at the same time in the Institute for Macromolecular Chemistry. He had built up a quite sophisticated glass apparatus for doing reactions with perchloryl fluoride at -78 degrees Celsius.

One day he added about 50 milligrams of BuLi (I don't know whether tert- or n-) to perchloryl fluoride at this deep temperature - and the whole lab was atomized with a huge, sharp bang which let him deaf for 3 months. After that his hearing came back very slowly...

One week after this big bang a warning was published in the "Angewandte Chemie" to avoid reactions of this kind, alas, it came too late.

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22. whiskeysoda on January 8, 2009 3:37 PM writes...

Though it would otherwise go without saying - in light of a recent and unfortunate incident involving a green RA using tBuLi - it is good practice to MAKE SURE THE SYRINGE IS FIRMLY ATTACHED TO THE NEEDLE BASE when not using a cannula.

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23. Andrew on January 26, 2009 2:37 PM writes...

In my experience, the "pilot" light may ususally be avoided if one draws a little (inert) headspace into the syinge from the BuLi bottle ('blanket' it with N2 or Ar) before removing the needle. That said, knowing what to expect (i.e., being prepared for a small fire) is critical when handling highly pyrophoric materials like t-BuLi.

While in gard school I received an excellent piece of advice on handling pyrophorics for the first time - intentionally "spill" a tiny amt of the pyrophoric material under controlled conditions (i.e., away from other flammables). This gives one a feel for how long of a 'fuse' they've got before there's a fire situation.

Permalink to Comment

24. r keen on December 6, 2010 9:30 PM writes...

Hi,
I work in a chemical disposal plant and butyl lithium is my next goal. The comments posted give me little confidence. Does anyone have any sensible and safe way to destroy the stuff?

Permalink to Comment

25. JK on April 1, 2011 12:35 AM writes...

I'm just coming up to the end of my first research project now (In fact i'm procrastinating by posting here), and have recently been availed to the wonders of transfering bu-li by syringe whilst surrounded by clumsy people...

The high vac supply to our lab died earlier in the year, so all air-sensitive reactions have to be flushed with a constant positive pressure of dry nitrogen, ruling cannula transfer right out. With some trepidation I parafilm a large balloon to a syringe body and fill it with argon, whack a fin gauge needle on and stab it into the buli bottle to provide possitive pressure, and then thankfully prepare a quench bath just in case.

I then start filling a 50cc syringe with bu-li which is a painfully slow process to do safely, and our resident clumsy masters student (with whom i share a hood) comes over weilding a lab stool (held at head height for some unknowable reason) and hits me square in the shoulders by accident. Result: I stumble and pull the (cheap luer-slip) syringe out of the needle and the balloon's pressure propells buli up and all over the hood screen, he panics and I have grab the (now very hot, flame tipped) needle and with draw it and stick it in the quench bath before dumping the whole (still full) syringe in there with it for good measure. Luckily no-one got hurt (though i could happily of bludgeoned him unconcious with that infernal lab stool).

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26. Penney Namsaly on July 20, 2012 1:31 AM writes...

It’s actually a nice and helpful piece of information. I’m happy that you just shared this helpful info with us. Please stay us up to date like this. Thank you for sharing.

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