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In a chemistry version of whipping up a delicious dinner from pantry staples, researchers in Korea have found a recipe for forging amide bonds using inexpensive chemicals stocked in nearly any organic laboratory: dichloromethane (DCM)—also called methylene chloride and best known as a workhorse polar aprotic solvent—and a basic salt (J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.6c05971).

“It’s something that most people could walk in their lab and do without even bothering to buy anything,” says Tom Sheppard, an organic chemist at University College London who was not involved in the work.

Amide linkages are important structural motifs in organic chemistry; they appear in the backbones of proteins, polymers, small-molecule drugs, and more. New ways to make them more inexpensively and efficiently have a lot of potential for impact.

Chonnam National University’s Sunwoo Lee, who led the work, says his graduate student Nithin Pootheri discovered the reactivity while working on an iridium-catalyzed decarboxylation reaction with DCM as the solvent. The intended reaction failed but produced chlorinated molecules that could undergo substitution with an amine to make an amide, the researchers found. The amide formation happened even without the metal catalyst, thus indicating that DCM was responsible for the reaction.

“At the beginning, I didn’t believe the result,” Lee says. It seemed almost unthinkable that nobody had noticed this behavior from DCM before, but further investigations into the mechanism convinced him.

The researchers found that the reaction works on a moderate variety of carboxylic acid and alkyl amine starting materials. It usually preserves the starting materials’ stereochemistry, though amino acids showed a slight tendency to scramble under the basic conditions. The reaction also struggles with sterically bulky amines and doesn’t work at all with aromatic amines, which Lee says he and his team are working to remedy.

DCM has a number of health hazards, including cancer from long-term exposure, that have led to the solvent being tightly regulated in the US and European Union. Many companies are phasing it out of their processes. Lee acknowledges this as a potential obstacle for future industrial applications, but he says that the DCM method could still have process advantages over existing amide synthesis routes that generate toxic gases or high-molecular-weight by-products.

“Some coupling reagents provide higher yield than our method. But if [people] want to try just a simple method that’s not expensive,” they can easily try this protocol before turning to fancier reagents, Lee says.