I wanted to do a follow-up to this post, about a reaction that removes nitrogen atoms from heterocyclic rings. Some readers took issue with the paper in the comments, pointing out that a mechanistically similar transformation had been published in 2017. The group that did the earlier work has a new paper on the subject out in Angewandte Chemie, so I thought it might be a good time to take a look.
Both of these papers eventually go through an isodiazene intermediate; that’s the species that turns into nitrogen gas and takes the existing ring nitrogen with it. But they get there in different ways. The paper I blogged on earlier (Mark Levin’s group at Chicago) uses a N-benzyloxy N-pivaloyloxy amide reagent, while the other group (Hongjian Lu at Nanjing) uses sulfuryl azide reagents to get there. The Levin paper references the 2017 work in passing, noting how they were “circumventing the laborious and undesirable features of existing protocols“. As mentioned, some readers took exception to what they saw as shade-throwing.
The problem is, any reaction protocol that calls for sulfuryl diazide is something I’m going to have to think about very hard before trying. Here’s a 2011 paper from Helge Willner’s group in Wuppertal that describes it in detail, but from the structure you probably already know what you’re looking at. Chemist Nick Chiappini noticed the new Angew. Chem. paper on Twitter, and directed people to this 2011 work as well. Sulfuryl diazide is described as having “exceedingly explosive, unpredictable properties”, and I can believe it. It’s not a compound that appears in the literature very often, but it always comes with phrases like this attached to it. Now, I don’t know what the pivaloyloxy reagent from Levin’s group is like, either (you don’t see many N,N-dioxy amides), but at least so far I have no reason to think that it’s as hazardous as sulfuryl azide.
And as Chiappini mentions in another tweet in his thread, another problem is that the azide work in the new paper is being done in dichloromethane. That’s not a good combination: if you have any azide anion around, it can react with dichloromethane to form diazidomethane, and you truly do not want any amount of that whatsoever. Now, the Nanjing authors describe using and storing the sulfuryldiazide in solution and say that they experienced no explosions, and I’m glad to hear it. But they do strongly recommend safety precautions and I wish what they’d said something about the azide/dichloromethane combination as well.
So overall, even though this is an interesting reaction and does something that’s very hard to do otherwise, I don’t really want to do it with with the sulfuryl azide protocol. There are quite a few reactions in this category, though!