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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: Twitter: Dereklowe

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August 26, 2004

Things I Won't Work With: Polyazides

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Posted by Derek

The azide group (three nitrogens bonded together in a row, for the non-chemists in the crowd) has several personalities. Unfortunately, most of them are hostile. Azide anion, as you find in sodium azide, is pretty toxic. It shuts down several important enzymes, and it's often used in biology labs as a general metabolic poison.

Covalent azides are a different sort of beast. Having something directly bonded to the group stops it from being an enzyme-killer, for the most part, but you have a new problem to worry about: explosiveness. In general, reasonably high molecular weight azides are OK to handle (e.g., the early anti-HIV drug azidothymidine). I've made some of that sort, since azide displacement is a classic (and useful) way to get a nitrogen into your molecule. But the smaller ones aren't worth the risk.

That's because the higher the percentage of nitrogens in the formula, the more you have to worry. Thermodynamically, nitrogens bonded to each other are always regarded as guilty until proven innocent - there's always the fear that they're going to find a way to throw off their civilized clothes and revert to wild nitrogen gas. That's a hugely stable compound. If your structure goes that route, all that extra bonding energy it used to have ends up diverted into flying shrapnel and loud noises.

A few years ago I saw some Israeli escape artists has prepared triazidomethane, which I wouldn't touch with somebody else's ten-foot titanium pole. One carbon, one hydrogen, and nine nitrogens - look at the time! Gotta run! But there's always worse. Just today I was reading a soon-to-be-published paper in Angewandte Chemiefrom some daredevils at USC. They've prepared titanium tetraazide, of all things. One titanium and twelve nitrogens: whoa! Podiatrist appointment! See you later!

You can isolate the stuff, it seems, as long as you handle it properly. It turns out that brutal treatments like, say, touching it with a spatula, or cooling down a vial of it in liquid nitrogen - you know, rough handling - make it detonate violently. I think that staring hard at it is OK, though. The authors recommend using everything you have for protection if you're zany enough to follow their lead: goggles, blast shield, face shield, leather suit (!) and ear plugs. Those last two suggestions are unique in my experience, and quite. . .evocative of what you have to look foward to with these compounds. (We don't have any leather suits around where I work, although I'm sure I'd look dashing in one.)

Some of the folks on the paper have a joint appointment with an Air Force missile propulsion research lab. They've found a home. Me, I'll be way over here.

Comments (7) + TrackBacks (0) | Category: Things I Won't Work With


1. The Novice Chemist on August 26, 2004 9:49 PM writes...

I had a co-worker who once claimed to prepare the tetra-azide derivative of erythritol. Apparently, other chemists were never able to prepare it (it was always a different color each time) and he made it and it was crystal clear.

It was in a scintillation vial and he set it down on a stirplate; it blew glass into his back (fortunately he turned), glass into the door six feet away and the blast was heard over the phone at the other end of the building. I kinda thought that would have been cool to see, but not to experience.

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2. Jake McGuire on August 26, 2004 10:55 PM writes...

Speaking of rocket propulsion types, I suspect you'd enjoy reading Ignition! An Informal History of Liquid Rocket Propellants, by John Clark, apparently now back in print in facsimile form from

Not that organic chemists don't have their share of lab explosions, but when you're talking bulk quantities of liquid ozone or chlorine pentaflouride, things are bound to be colorful.

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3. Dawn B. on August 27, 2004 1:44 PM writes...

Great way of putting it. Bertozzi recently reported in Nature about using azides on sugars for chemical reactions in biology. Link

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4. Derek Lowe on August 27, 2004 2:20 PM writes...

There are some erythritol tetra-azides reported in a 1984 JOC reference (49, 5150). Naturally enough, it's one of those papers from the Naval Weapons folks at China Lake, another great source for alarming structures.

What on earth was your colleague doing making the stuff? Just for the sake of the name, I'd like to think that someone would do cycloadditions with that compound to make a tetratetrazole.

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5. The Novice Chemist on August 27, 2004 3:18 PM writes...

As I recall, it was a possible coating for the "spinning fiber" technology that my old company was up to at the time. Basically, it was to be a coating for some sort of membrane filtration system. He told me that the he heard that the Army had worked with it and decided that it was too sensitive to work with for explosives. (Imagine that!)

It never ceases to amaze me what people used to do in "the old days." I'm still in graduate school and it stuns me when people talk about "cowboy chemistry" It must have been a lot of fun, if not entirely safe. That JOC reference has procedures that seem entirely mundane; one wonders if you're nervous about taking the flask off the rotovap once everything's concentrated down. Maybe the leather suit helps.

Bertozzi, for a lack of a better term, rocks.

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6. Daniel Newby on August 29, 2004 4:28 PM writes...

At work we recently had a visit from an explosives chemist. His stories were real eye openers. Since he was from Africa, they didn't have a big pile of DoD money and had to be creative. He said they did a lot of work in plastic bags instead of glassware: shrapnel is far more lethal than the blast overpressure. If the bag got hot as you kneaded it, you dropped it and ran... [sigh] Almost makes me wish I was a chemist instead of a EE, so I'd have an excuse to play with things that go bang.

My favorite energetic compound is octanitrocubane: a cube of carbon with a nitro group hanging on each corner. It looks very unhappy for a molecule. Remarkably it is stable enough to make a practical explosive.

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7. The Novice Chemist on August 29, 2004 8:57 PM writes...

Best T-shirt ever (if a little bit over used):

Bomb technician -- If I'm running, try to keep up.

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