Turning nitroarenes into aromatic amines is a bread-and-butter organic chemistry reaction. And although there are many ways to do this transformation—commonly used to make aromatic amine motifs in drug candidates—there are drawbacks to all of them. Some require high temperature and hydrogen gas under pressure; some use precious metal catalysts and complex ligands; some leave behind metal salt sludge; and most of them aren’t compatible with other substituents, particularly halogens.
Now, chemists at Queen’s University in Canada, led by P. Andrew Evans and Gregory Jerkiewicz, have developed a simple reaction that uses inexpensive nickel foam to do these reduction reactions. The transformation takes advantage of a form of nickel that’s cheap and readily available because it’s used in mass-produced batteries. The reaction tolerates air and moisture, and its discerning reducing power leaves a large number of other functional groups, including halogens, untouched (J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.5c19584).
Evans tells C&EN that he thinks the reaction will be particularly useful to medicinal chemists who need to incorporate an aromatic amine into a molecule but also want to maintain a halogen handle for a chemical coupling later in their synthesis. “It’s a genuinely simple, easy, practical method for doing something that’s often quite hard,” he says.
The process hinges on a sequential two-electron reduction. The hydrogen in the reaction comes from hydrogen chloride generated from acetyl chloride. HCl converts nickel(II) on the surface of the nickel foam—which forms naturally in the presence of air—to Ni(0), which does the reduction. Normally, using Ni(0) requires the use of a glove box.
“Here, what we’re doing is an in situ etching without taking any real precautions to get the Ni(0) to do the two-electron chemistry,” Evans says. He adds that any nickel foam that doesn’t get used can be recovered with a magnet.
“It’s a genuinely simple, easy, practical method for doing something that’s often quite hard.”
The chemists show that they can make expensive aromatic amines with a multitude of functional groups from inexpensive nitroaromatics on gram scale. They also use the reaction en route to several drugs, including the antibiotic linezolid (Zyvox), the HIV drug rilpivirine (Edurant), and the cancer drugs enzalutamide (Xtandi) and apalutamide (Erleada).
The reaction does have some limitations, Evans says. It doesn’t work well with nitro heteroaromatics and doesn’t reduce alkyl nitro groups.
Angie Angeles, head of process chemistry at Vertex Pharmaceuticals’ San Diego site, points out that aromatic amines are widely used in pharmaceuticals, agrochemicals, polymers, and fine chemicals, so a simple and environmentally responsible route for making them is important. The fact that the nickel foam “is inexpensive, bench-stable, and compatible with many functional groups makes it especially attractive compared to traditional methods that often require harsher reagents and generate more waste,” she says in an email. “Overall, this looks like a scalable and easy-to-implement method with real potential beyond the academic laboratory.”
Next, Evans says he’s looking to scale up the transformation. He adds that metal foams have largely been used in the domain of electrochemistry, but he expects that after other chemists see this paper, they will start trying them out in reactions.
2026 American Chemical Society
