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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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In the Pipeline

« A Real Periodic Table - With Real Elements | Main | When Reagents Attack! »

February 16, 2012

Imidazole-1-Sulfonyl Azide HCl: Look Out

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Posted by Derek

I don't know how many of you out there like to form azides, but if you do, you've probably used (or thought about using) imidazole-1-sulfonyl azide hydrochloride. This reagent appeared in Organic Letters a few years ago as a safe-to-handle shelf-stable azide transfer reagent, and seems to have found popularity. (I've used it myself).

So it was with some alarm that I noted this new paper on the stability and handling characteristics of the reagent. It's a collaboration between the University of Western Australia (where the reagent was developed, partly by the guy whose lab bench I took over in grad school back in 1983, Bob Stick), the University of British Columbia, and the Klapƶtke group at Munich. That last bunch is known to readers of "Things I Won't Work With", as experts in energetic materials, and when I saw that name I knew I'd better read the paper pronto.

As it turns out, the hydrochloride isn't quite as optimal as thought. It's impact-sensitive, for one thing, and not shelf-stable. The new paper mentions that it decomposes with an odor of hydrazoic acid on storage - you don't want odors of hydrazoic acid, believe me - and I thought while reading that, "Hmm. My bottle of the stuff is white crystalline powder; that's strange." But then I realized that I hadn't looked at my bottle for a few months. And as if by magic, there it was, turning dark and gooey. I had the irrational thought that the act of reading this paper had suddenly turned my reagent into hazardous waste, but no, it's been doing that slowly on its own.

So if you have some of this reagent around, take care. The latest work suggests that the hydrogensulfate salt, and especially the fluoroborate, are less sensitive and more stable alternatives to the hydrochloride, and I guess I'll have to make some at some point. (They also made the perchlorate - just for the sake of science, y'know - and report, to no one's surprise, that it "should not be prepared by those without expertise in handling energetic materials"). But it needs no ghost come from the grave to tell us this.

So, back to my lab and my waste-disposal problem! And here's a note on the literature. We have the original prep of the reagent, a follow-up note on stability problems, and this latest paper on alternatives. But when you go back to the original paper, there is no mention of the later hazard information. Shouldn't there be a note, a link, or something? Why isn't there? Anyone at Organic Letters or the ACS care to comment on that?

Update: I've successfully opened my bottle, with tongs and behind a blast shield, just to be on the safe side, and defanged the stuff off by dilution.

Comments (17) + TrackBacks (0) | Category: Chemical News | Safety Warnings | The Scientific Literature


COMMENTS

1. Martyn on February 16, 2012 9:46 AM writes...

Be sure not to accidentally work it up with 6N HCl:

http://cen.acs.org/articles/90/i2/Chemical-Safety-Benzotriazole-1-sulfonyl.html

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2. swissboy on February 16, 2012 10:20 AM writes...

Thank you for the warning, Derek.
Mine turned completely black in a year as well.

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3. Curryworks on February 16, 2012 10:46 AM writes...

I had done a prep of that compound a few years back and made a stock solution of I1SA in water. The solution wound up detonating in my hand and I wound up in the hospital for a few hours with glass in my hand and face. Needless to say full goggles my eyes (I still have the pair).

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4. Seth on February 16, 2012 11:52 AM writes...

I've synthesized and used this reagent in ~12g scale batches several times without incident. My samples did eventually decompose to the aforementioned black goo regardless of storage conditions, which was disposed of without incident. This is not to downplay the very real danger that has been described.

I do wonder how many close calls I've had with azides as they were a prominent feature of my dissertation. I recall a rather interesting violent result after adding Cu(I) to neat tripropargylamine and an alkyl azide and making various organic azides with ratios of C+O/N = 0.75

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5. ScientistSailor on February 16, 2012 12:33 PM writes...

What's wrong with the smell of HN3? I think it smells a lot like HCN...

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6. gippgig on February 16, 2012 2:23 PM writes...

ALL azides should be handled as potentially explosive (hmm, I wonder about zidovudine).

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7. PhilaChem on February 16, 2012 3:59 PM writes...

I just made a 10 g batch of this stuff about 2 weeks ago. It still is a white solid, but I will get rid of it. Any idea on just how long the stuff can be stored before degradation begins?

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8. Jose on February 16, 2012 5:02 PM writes...

"Any idea on just how long the stuff can be stored before degradation begins?"

Young grasshopper! If there is a question, there is no question.

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9. coprolite on February 17, 2012 11:15 AM writes...

I'm assuming you did some shrapneliferousness calculations beforehand which allowed you to forgo the leather suit.

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10. metaphysician on February 18, 2012 9:57 AM writes...

This might be a silly question, but are there any azides that aren't explosive at all? ( IE, can't even be detonated by gross abuse including blasting cap )

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11. Paul on February 18, 2012 12:37 PM writes...

#10: I imagine if the azide group is part of a sufficiently large molecule, there wouldn't be enough energy released to sustain a detonation wave.

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12. Curryworls on February 18, 2012 8:32 PM writes...

Guy I know made some small molecule azide monomers-the polymers turned out to be inert but wow the monomers were unstable to even slight heating.

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13. Josh on February 23, 2012 11:17 AM writes...

I've made recently made a series of a huge macromolecules with azide groups decorating them (during my PhD). I've built them up from smaller fragments - I've always beenn told and assumed that the bigger the azide to everything else ratio, the more dangerous the molecule.

However - I've never ever had any problems with them. I normally make them on a small scale first, spot them onto paper and then hit them with a hammer / heat them up mega hot with a heat gun to see what happens.

It's irritating that these compounds are so unpredictable, as I'm sure this experience has made me more complacent than I should be about these guys.

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14. Sebastian on February 29, 2012 6:18 AM writes...

Finally the authors released the new salts details! Yay!

Honestly I hope I don't ever have to make this compound again but I probably will have to, and this time hopefully it won't end up with bits of roundbottom flask embedded in my face.

Kind of sad when your first step into the realm of scientific publications is an addition/correction about how you blew yourself up making it. :(

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15. Sebastian P. on February 29, 2012 6:23 AM writes...

Oh, just a quick amendment - I have had Immi-N3.HCl compound for well over a year now, in an isolated dessicator, and it has been fine. The compound is fine as long as it's dry and by itself. As soon as it gets wet, get rid of it. Never had a problem during azido transfer rxn or during workup. Only the actual synthesis of it.

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16. Biochem undergrad on March 8, 2013 10:00 PM writes...

ScientistSailor - off the top of my head, because azide is an ass-kicker of an electron transport chain inhibitor.

You DO like your cells to have ATP, right? :P

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17. Anonymous on June 21, 2014 10:51 AM writes...

Apologies for commenting on an old post but....

A colleague of mine recently synthesized 100g of this and put in in a hot vac oven to dry overnight. The outcome is that we no longer have a vac oven (well, we have pieces of one now) and there's a departmental ban on making this compound plus any other azides require departmental approval.

Wish they had done a little bit of reading! I mean just googling the name of it comes up with several safety warnings.

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