Dichloromethane unlocks metal-free amide formation
Korean researchers report that dichloromethane (DCM) can act as an amide-coupling reagent, enabling amide bond formation between carboxylic acids and alkyl amines using a basic salt, without metal catalysts, and scalable to more than 20 g per batch. While the method often preserves stereochemistry, it struggles with bulky or aromatic amines, and DCM’s health hazards pose potential industrial hurdles. Nevertheless, the inexpensive, simple protocol could offer a practical alternative to harsher, toxic reagents in suitable cases.