Nitroamines energy a much less explosive Sandmeyer response different

 

Researchers on the Chinese Academy of Sciences’ Hangzhou Institute for Advanced Study have provide you with a brand new technique to assist chemists get extra figurative bang from fragrant amine constructing blocks with much less probability of literal explosions.

Since 1884, the copper-mediated Sandmeyer response has been the established order for turning amines into bromides or chlorides. But the Sandmeyer methodology has a infamous draw back: the diazonium intermediates might be explosive. The response additionally makes use of massive quantities of copper salts as halide sources, thus resulting in substantial waste when the method is used on an industrial scale.

Xiaheng Zhang and his staff have found out an alternative choice to the Sandmeyer response that uses nitro groups instead of diazoniums (Nature 2025, DOI: 10.1038/s41586-025-09791-5). Because their methodology doesn’t use any steel, the merchandise might be funneled instantly into metal-catalyzed cross-couplings with out the necessity to run purification steps—saving chemists money and time.

“I think industrial people will really, really benefit with this chemistry,” Zhang says.

Zhang has been engaged on deamination chemistry since he began his unbiased profession in 2021. The nitro method is predicated on one thing his staff came across whereas making an attempt to connect electron-withdrawing teams to an aminopyridine spinoff within the hopes of weakening its C–N bond. Instead of attaching to a carbon atom within the ring, the researchers discovered that the nitro group ended up on the amine nitrogen.

Treating that N-nitroamine species with a chlorine supply gave the researchers the chlorinated product that they had been in search of. They discovered that the response works on many sorts of fragrant amines—even ones connected to rings with a number of heteroatoms, which usually don’t play properly with Sandmeyer chemistry. And they had been capable of set up a wide range of halides and different teams instead of the nitrogen, so long as they may discover a good nucleophile to react with the nitro intermediate.

The side Zhang was most enthusiastic about was with the ability to perform deamination adopted by cross-coupling in the identical response vessel with out worrying about residual steel, which might intrude with the response. He says that just about all of the basic coupling reactions are appropriate: Suzuki, Heck, Sonogashira—you title it. “Any reaction you can imagine, [it] can tolerate.”

This is a type of uncommon papers that “you know the second it’s published, people can and will use it,” says the Max Planck Institute for Kohlenforschung’s Tobias Ritter, who printed his personal safer tackle the Sandmeyer response in 2024. The beginning supplies in Zhang’s methodology are broadly obtainable, the process is simple, and the merchandise are the sorts of molecules that agrochemical and pharmaceutical corporations are curious about manipulating. It stays to be seen if this methodology will really unseat Sandmeyer chemistry because the go-to deamination approach, however “it just looks robust and very practical,” Ritter says.

Patrick Fier, a course of chemist at Merck & Co., who was not concerned within the work, says in an e mail {that a} extra rigorous security analysis is important to determine if this response would really be different on the method scale.

Zhang and his group are persevering with to work with native pharmaceutical and chemical corporations to develop this response. They’ve already demonstrated one instance that works at a kilogram scale and are planning to scale it up additional.