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: email@example.com
Note: this was a post on my old blog site, and never made the migration over to the current "In the Pipeline". I was reminded of it this morning, and thought I'd bring it more out into the light.
There are reports (updated here - DBL) that Mars may have hexavalent chromium compounds in its surface dust, which is already being brought up as a concern for future human exploration. I agree with comments I've seen that this is putting the cart in front of the horse a bit, but it also means that I probably wouldn't be a good candidate for the expedition. I've already had my lifetime's exposure to Cr(VI).
Back in grad school, I had an undergraduate assistant one summer, a guy who was pretty green. I'll refer to him by an altered form of his nickname, henceforth as Toxic Jim. I shouldn't be too hard on him, I guess: I was a summer undergrad in my time, too, and I wasn't a lot of help to anyone, either. But TJ did manage to furnish me with some of my more vivid lab stories in his brief time in my fume hood.
One morning I showed him how to make PCC. That's pyridinium chlorochromate for the non-organic chemists out there, an oxidizing agent that doesn't seem to be used as much as it was 15 or 20 years ago. Even in '85, you could buy it, but the freshly-made stuff was often better. It certainly looked nicer. Like all the Cr(VI) salts, it has a vivid color, in this case a flaming orange. I shouldn't say "flaming;" that's getting ahead of the story. . .
It's not hard to make. You take chromium trioxide, a vicious oxidant in itself which comes as clumpy fine purple crystals, and dissolve it in 6N hydrochloric acid. That's an easy solution to whip up, since it's just concentrated HCl out of the jug cut 1:1 with water. I had Toxic Jim do all this - weighing out the chromium compound, making the HCl. During that part I couldn't resist quoting the ancient adage, which works well in the East Arkansas accent of my youth: "Do like you oughter, add acid to water." Most chemists either remember that one, or they remember the syrupy conc. acids splattering all over their arm when they did it (once!) the other way around.
We set up a three-neck flask with an overhead stirrer to run this in. That's just a motor mounted above the flask, turning a shaft with a paddle on the end of it. Works well for really thick mixtures, which this was supposed to turn into. As things turned out, it was even thicker than planned, for a brief exciting interlude.
In went the HCl, out of a big Erlenmeyer flask, and in went the chromium trioxide. Here's where the wheels began to come off. Instead of a vivid red-orange solution, the stuff got dark and began to thicken. I could tell it was getting hot, too, since you could see the clear wavery solvent vapors coming out of the open necks of the flask. And that was wrong, too - you don't get that so much with water vapor. It's the mark of organic solvent fumes, with their different density and refractive index.
And so it was. TJ had indeed grabbed the wrong Erlenmeyer. Not the one he'd just mixed up the HCl in, but one from another part of the bench that contained ethyl acetate from a big chromatography run the night before. Ethyl acetate is a pretty poor substitute for hydrochloric acid, most of the time, when you stop to think about it.
Then the overhead stirrer began to bog down, which takes a mighty thick mixture to achieve. I hadn't added up what had happened at this point, but I knew that things were going wrong in all directions at once. I pulled the glass hood sash down some more, saying "I think you better stand back -" WHOOOOMPH!
And there it went! The whole reaction went up in a big fireball, which filled a good part of the hood and came roaring out of the gap in the front sash. I felt the heat roll over me, yelled something incoherent, and bolted for the safety shower. I didn't have to run up Toxic Jim's back, either: he was making for the door in championship time. Pulling the chain of the shower dumped a hundred gallons of ice water on me immediately, not that I needed any more waking up.
When I opened my eyes and took inventory, things weren't as bad as I thought. Limbs and appendages all present, head and facial hair still attached - though lightly singed and frizzed - skin not even sunburnt, although it (along with my lab coat) was generously splattered with green. That was what remained of the chromium trioxide. It was now the Cr(III) oxide, having given up three oxidation levels by turning the ethyl acetate into carbon dioxide, most likely. There were a few orange-brown spots of the Cr(VI) stuff, but those were mostly confined to the front of the lab coat, in a vivid line that showed where the hood sash had gotten pulled down to.
My hood wasn't looking its best. There was smoke hanging in the air, although that was getting pulled out. There was a huge stain of the green and brown chromium mixture all over the inside, thickest in the directions of the three open necks of the flask. Which was still intact - if I'd been foolish enough to set this up in a closed system, the whole thing would have gone up as Pyrex shrapnel. Even the ceiling had a line of gunk on it, from the thin gap in the hood sash assembly.
While I was taking this in, wondering what the hell had gone wrong, and wondering what I could possibly do to TJ that was worse than what he'd just gone through, the emergency crews arrived. It was a Saturday morning, but Bob across the hall saw the explosion and immediately dialed 911. In came the fire crews, trying to talk through their breathing apparatus: "Mumph heff deff umphh cafulteff. . " "What?" "We hear there's a casualty up here"
I put my hands on my hips, and gave them the full effect of my green spots, frizzed hair, and soaking wet lab coat: "That would be me."
I have this from a lab-accidents-I-have-known discussion over on Reddit. It is, of course, unverified, but it's depressingly plausible. As a chemist, this one is guaranteed to make you bury your head in your hands - it's the second law of thermodynamics come to take vengeance, with the entropy increasing as you go along:
"A graduate student was constructing three solvent stills (dichloromethane, THF and toluene) inside a hood in Room XXXX. As a final step in this process, the student was cutting pieces of sodium metal to add to the stills. Once the sodium had been added, the student began to clean the knife used to cut the sodium. During the cleaning, a small particle of sodium was apparently brushed off the knife. The sodium landed in a drop of water/wet spot on the floor of the hood and reacted immediately making a popping sound. The graduate student was startled by this sound and moved away quickly.
In his haste to get away from the reacting sodium, he discarded the knife into a sink on the bench opposite the hood in which he was working.. Apparently, there was another piece of sodium still adhering to the knife since upon being tossed into the sink, a fire ignited in the sink, catching the attention of another student in the lab. As the flames erupted, the student noticed a wash bottle of acetone sitting on the sink ledge nearby. He immediately grabbed it to get it away from the flames, but in the process, squeezed the bottle, which squirted out some acetone which immediately ignited. The student immediately dropped the bottle and began to evacuate the lab. As he turned to leave, he knocked over a five gallon bucket containing an isopropanol/potassium hydroxide bath which also began to burn. This additional fire caused the sprinklers to activate and the fire alarm to sound which in turn resulted in the evacuation of the building.
When the sprinklers activated, water poured into the bulk sodium-under-mineral-oil storage bottle which had been left uncapped in the hood resulting in a violent reaction which shattered the bottle sending more sodium and mineral oil into the sprinkler water stream. This explosion also cracked the hood safety glass into numerous little pieces although it remained structurally intact. By the time the first-responders arrived on the scene, the fire had been extinguished by the sprinklers, but numerous violent popping sounds were still occurring. The first-responders unplugged the electrical cords feeding the heating mantles, shut off the electricity to the room at the breaker panel and waited until the Fire Department arrived. Eventually the popping noises stopped and sprinklers were turned off. The front part of the lab sustained a moderate amount of water damage The hood where the incident began also suffered moderate damage and two of the three still flasks were destroyed. The student, who was wearing shorts at the time of this accident, sustained second and third-degree burns on his leg as a result of the fire involving the isopropanol base bath.
There were some additional injuries incurred by the first-responders who unexpectedly slipped and fell due to the presence of KOH from the bath in the sprinkler water. These injuries were not serious but they do illustrate the need to communicate hazards to first-responders to protect them from unnecessary injury."
I doubt if the sodium was being added to the dichloromethane still; I've always heard that that's asking for carbene trouble. (Back in my solvent-still days, we used calcium hydride for that one). And it would take a good kick to knock over a KOH/isopropanol bath, but no doubt there was some adrenaline involved. I'm also sorry to hear about the burns sustained by the graduate student involved, but this person should really, really have not been wearing shorts, just as no one should in any sort of organic chemistry lab.
But holy cow. The mental picture I have is of Leslie Neilsen in a lab coat, rehearsing a scene for another "Naked Gun" sequel. This is what happens, though, when things go bad in the lab: we've all got enough trouble on our benches and under our fume hoods to send things down the chute very, very quickly under the wrong conditions. And were these ever the wrong conditions.
Via on Twitter (and that via C&E News), I bring you the definitive what-are-we-going-to-do-with-all-this-sodium video. The end of World War II brought all kinds of material disposal problems - you may have seen footage of virtually new airplanes being dumped into the sea and the like. Some of those disposal problems are still with us, like the unexploded ordnance that keeps turning up. But these barrels of sodium, no one ever had to worry about them again. . .
Via Sally Church on Twitter (and a post by Bethany Halford at C&E News), I bring you the definitive what-are-we-going-to-do-with-all-this-sodium video. The end of World War II brought all kinds of material disposal problems - you may have seen footage of virtually new airplanes being dumped into the sea and the like. Some of those disposal problems are still with us, like the unexploded ordnance that keeps turning up. But these barrels of sodium, no one ever had to worry about them again. . .
Well, since I was just talking about a reagent that can potentially take off without warning, I wanted to solicit vivid experiences from the crowd. What's a compound that you've made that did something violently unexpected? I can recall making some para-methoxybenzyl chloride in grad school (for a protecting group; I was running out of orthogonal protecting groups by that time). It's not hard - take the benzyl alcohol and some conc. HCl and swoosh 'em around. But the product you get by that method isn't the cleanest thing in the world, and on storage, well. . .a vial of it blew out in my hood after the acid had had a chance to work on it.
My most vivid reagent-gone-bad story is probably this one; that's a time I literally came down counting fingers. What other things have you had turn on you?
What do you have when a fire starts at a large chemical packing company, handling all sorts of oils, paints, coatings, and various industrial chemicals? Where they have hundreds of thousand-liter containers stored, surrounded by all the crates and packing material used to trans-ship them? You have this, at Chemie-Pack in the Netherlands yesterday:
And you have a black cloud that stretched across a significant part of the whole country:
Images are from Nufoto.nl, taken by people at the scene. A reader who lives 20km downwind writes me that he's been getting a pervasive smell of burnt plastic (which, he says, certainly makes a change). His main reason to be grateful is that this didn't spread to the Shell site nearby, which would have prompted an instant vacation to Germany. And then there are all the refineries 15 km to the west - if those ever go up, he tells me, "it'll look like the ending of Gulf War 1 - lowlands-style - with cows for camels".
Culturing bacteria is usually a pretty quiet affair. Bacteria aren't too noisy, and the equipment used to keep them happy isn't too dangerous. But there are exceptions. If you're going to culture anaerobes, you need somewhat more advanced technique, what with all that oxygen-is-deadly business. A professional-grade culture chamber for those beasts is usually filled with a mixture of about 80% nitrogen, 10% carbon dioxide, and 10% hydrogen. And those you'll be getting from three compressed gas cylinders, which is how they were doing it in a lab at the University of Missouri until Monday afternoon. . .
Well, regular readers will be expecting this to be a story of someone who did not remember to Treat Compressed Gases With Respect, but that's not the case. No, this is what happens when you don't Treat Hydrogen With Respect - and everyone in the audience who's had a hydrogenation reaction get frisky on them will be nodding their head in agreement at that thought. Somehow, enough hydrogen and enough oxygen got together around an anaerobic culture hood, and the mixture found an ignition source, and well. . .
Problem is, just about any hydrogen/air mixture will do. Anything from about 4% hydrogen in air to about 75% will ignite, and everything except the two ends of that range will go ahead and explode if given the chance. (Only acetylene is worse in that regard). And it doesn't take much to set it off, either, which is the other nasty thing about working with hydrogen. A static-electricity spark is plenty, as are the sparks generated by electrical switch contacts and the like.
As you can see, the lab was not improved by the resulting explosion. The latest report I have is that four people were injured, one seriously enough to still be in the hospital, although their condition has been upgraded to "good".
Initial reports were that this was due to human error, although everyone seems to be backing off that judgment until an official investigation is finished. At any rate, the local fire department stated Monday night that the problem was one or more people in the lab "not being familiar with the warning systems designed to alert them when the hydrogen level was approaching explosive limits (and) the gas was left on". If that was the case, then. . .you ignore a hydrogen level alarm at your peril. And here are seventeen blown-out windows, four people who are lucky not to have been killed, and one demolished lab as evidence.
Update: I had a link up to a commercial anaerobic culture chamber for illustration, but (as the manufacturer points out) these use cylinders of premixed gas with only 5% hydrogen which obviates this very problem. I thought it best to take down the link so that no confusion results - after all, it wasn't the model that was being used in this incident (and in fact would have avoided it completely). I should add that the email I received about this out was exactly the sort of courteous and informative request I have no problem responding to, as opposed to some others that have come in over the years.
(Photos are courtesy of the Missourian and the Columbia Fire Department).
For once, I'm going to farm out a "Things I Won't Work With" post to someone else. For those who missed it in the comments, here's the link to the PDF of Max Gergel's extraordinary memoir "Excuse Me Sir, Would You Like to Buy a Kilo of Isopropyl Bromide?" Gergel founded Columbia Organic Chemicals, and if you want to see how it was done in the Old Days, this is the place to go. A sample:
". . .As we chatted, as if the thought had struck him for the first time, the old rogue said, "You know Gergel, I have a prep you could run for us which would make you a lot of money." Now this was the con working on the con. When my mother told me that a gentleman had called from town asking to visit Dr. Gergel there was no one at the plant except the two of us; when Parry, whom I already knew by reputation, sauntered in disguised as a simple country bumpkin I knew he was the director of research for Naval Research Labs, and his mission was to find someone foolhardy enough to make pentaborane. News travels. I met him at the door and told him that I was simply a lab flunky but would fetch Mr. Gergel, that my boss was extremely smart but had been prevented by the war effort (in which he had served valiantly and with distinction) from getting a PhD; that right now Mr. Gergel was extremely busy with priority reaction but would be able to see him in ten minutes—which gave me time to change my clothes and wash my face. He never realized that we were the same person. Parry chatted with me in the breezy, confidential voice that has been used by every con man since Judas Iscariot and told me that the only reason that the Navy was willing to farm out this fascinating project was simply luck of qualified personnel. That my splendid contribution to Manhattan District was well known by the military, that people spoke of me as a true Southern prodigy. (The old devil was so good that I listened with gradually increasing preparedness to make pentaborane, although I had been forewarned that it was dog with a capital "D". . .
I came across the book in Duke's chemistry library in 1984, a few years after its publication, and read it straight through with my hair gradually rising upwards. Book 2 is especially full of alarming chemical stories. I suspect that some of the anecdotes have been polished up a bit over the years, but as Samuel Johnson once said, a man is not under oath in such matters. But when Gergel says that he made methyl iodide in an un-air-conditioned building in the summertime in South Carolina, and describes in vivid detail the symptoms of being poisoned by it, I believe every word. He must have added a pound to his weight in sheer methyl groups.
By modern standards, another shocking feature of the book is the treatment of chemical waste. Readers will not be surprised to learn that several former Columbia Organic sites feature prominently in the EPA's Superfund cleanup list, but they certainly aren't alone from that era.
For Friday lunchtime, I have a brief but alarming video clip from a 2007 incident in Dallas, where a fire started at a company supplying industrial gases to welding shops and the like. The incident was heralded, like so many others, by the simple but meaningful phrase "I hooked up something wrong". This as smoke began to emerge from the bed of a delivery truck full of aceylene cylinders.
If there's one thing to be learned from the whole "How Not to Do It" category on this blog, it is to treat pressurized gas containers with respect. Roasting them over an open fire does not qualify.
In case anyone missed it, a commenter on this post unearthed a really extraordinary find in the chemical literature. Here's an obscure isolation paper, from an obscure Chinese journal, reporting on a profoundly boring list of marine natural products.
What's so great, you ask? Well, take a look at the list. Dum de dum. . .hold on a minute, bis(2-ethylhexyl) phthalate? From Streptomyces, you say? When it's one of the most common plasticizers in the world, a bulk industrial chemical that, well, notoriously leaches out of labware under solvent exposure? Sure thing, guys. Sure thing.
We haven't had a How Not to Do It around here in a while, so here's a companion piece to the famous Sealed-Up Liquid Nitrogen Tank. This incident happened (as far as I can tell) about ten years ago. It's been used in a number of safety presentations then, thanks to the Airgas Corp., whose safety officer assembled a number of photos (and this is the time to emphasize that they had nothing to do with the accident itself, because people who work for a pressurized-gas company actually know how to handle pressure vessels.
As opposed to the two guys who scavenged a liquid oxygen Dewar from a scrap metal yard and decided to put it back into service. According to the most detailed report, they tried to rig up a connection to refill the cylinder, but found that it vented immediately through the pressure-relief valve. So. . .well, yeah, you know what's coming next: they took the darn thing off and plugged it shut. No more pesky venting! They filled up their cylinder, which was loaded on the back of their pickup truck, and went rolling down the interstate at lunchtime. Whereupon they had a flat tire, and pulled over for a while to fix things. . .
OK, you can look out from behind your hands now. Although I can't imagine how, neither of these two cowboys managed to get themselves killed, nor did they take out anyone else, through what appears to be sheer blind luck. According to the report, one member of the Cylinder Kings ended up being blown across five lanes of traffic, while his partner was launched forty feet in another direction. You can see from the photo how the truck weathered things. I can't imagine that a pressure wave of straight oxygen hitting tank of gasoline can end well; it's a perfectly reasonable mixture to put a payload into low-earth orbit.
Which is a good note on which to take inventory here. We have the owners of the oxygen cylinder accounted for, and their truck. What about the cylinder itself? Well, similar to the nitrogen tank referenced above, it had failed at the bottom weld and thus departed the scene of the accident like an artillery shell. It re-entered the affairs of the world a quarter of a mile away, plunging through the roof of an apartment, completely trashing the place (and severing a natural gas line in the process). As I said, how a dozen people didn't end up killed by all this is a complete mystery to me. (The red circle in that photo is where the pressure-relief device used to be. )
So the moral of this story is, I suppose, that Pressure Relief Devices Are There For A Reason. Or maybe it's "don't scrounge gas cylinders from the scrap yard and try to get them to work". Or perhaps "just because you haven't seen a pressure vessel explode yet, it doesn't mean that they can't". Or "Gegen der Dummheit kämpfen Götter selbst vergebens." Or something.
Some blogs run pictures of cats to give the readers a break from the ordinary. Around here, I thought that this might be appropriate. Here are the alkali metals, from top to bottom, differentiated in the most basic way possible. No, not by tasting them, sheesh: by tossing them into a dish of water:
(Courtesy of the Open University site in the UK). One thing they don't go into is the effect of density. Up to potassium, the metals are still light enough to float. But cesium drops like the rock it is, with depth-charge results.
I will consider running a photo of a cat, as long as he's working up a reaction.
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 watch 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.
Patent applications are no fun to write. You have to figure out just what you're trying to cover (and how wide a space around it you want to try to clear), and the lawyers have to whip up language that casts just the right legal spell. The chemists have to write up detailed experimental procedures for all the important compoun