Intermediate considered ‘too reactive to isolate’ finally tamed

A chemical intermediate once considered too reactive to isolate has been stabilised in the laboratory for three days by researchers in Germany. The team’s techniques enabled studies that were previously impossible due to the nitrene species’ fleeting nature and could allow researchers to further harness the molecules’ potential in synthetic chemistry.

The importance of nitrenes – lone nitrogen atoms bonded to single substituents – in chemical reactions has been known for over a century. For example, a nitrene made of a nitrogen atom bound to a single hydrogen atom has been identified as an intermediate in ammonia synthesis. However, the vast majority of nitrenes have lifetimes in the nanosecond range.

‘In 1970 – my birth year – there was a book called Nitrenes, and in this book it’s stated that this compound class is too reactive ever to be isolated,’ says group leader Jens Beckmann at the University of Bremen in Germany. ‘Nevertheless people have used nitrenes prepared in situ to do chemical reactions.’

Chemists such as Guy Bertrand at the University of California, San Diego have successfully stabilised similar highly reactive compounds such as carbenes, and these have proved immensely useful in organic synthesis. Nitrenes, however, have proved trickier because they naturally have spin triplet ground states. ‘The two unpaired electrons are prone to all kinds of reactivity,’ explains team member Emanuel Hupf.

The researchers kinetically stabilised the nitrene molecule using a rigid substituent called M^SFluind. ‘The gold standard for kinetic stabilisation was the terphenyl family of substituents – but they are susceptible to electrophilic substitution,’ says Beckmann. ‘This particular family of fluind ligands was published for the first time in 2011 by Kohei Tamao’s group, but that was close to his retirement and he didn’t get the chance to explore [the ligands’] reactivity for himself.’ Beckmann says his postdoc Marian Olaru discovered Tamao’s research in 2021 during an ultimately successful quest to stabilise the phosphenium ion. Other groups subsequently used fluind substituents to stabilise bismuthinidene and stibinidene, which both have triplet ground states.

In the new work, Beckmann’s group irradiated M^SFluindN₃ with ultraviolet, leaving the nitrene M^SFluindN. Using magnetometry, the researchers confirmed that the species retained the spin triplet ground state. They also conducted x-ray crystallography, NMR spectroscopy and other imaging techniques for the first time on nitrenes. They now believe it should be possible to use it in the synthesis of bench-stable transition metal complexes. Beckmann notes that, since carbenes were first synthesised in the mid 1990s, the number of references in scientific journals has grown to over 2000 per year.

Bertrand, whose group previously stabilised the spin singlet state of nitrene using an electron-donating substituent, predicts the work will prove highly influential. He believes that the findings will draw significant attention to the fluind substituent’s intriguing ability to stabilise spin-triplet states. ‘If you talk about antimony or bismuth, only inorganic chemists are interested. But if you talk about carbon or nitrogen, inorganic, organic, physical … everybody is interested,’ he says; ‘What is so special about this substituent to stabilise diradicals? I don’t know. But it’s very surprising.’