A practical base mediated synthesis of 1,2,4-triazoles enabled by deamination annulation strategy

A rapid and efficient base mediated synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from annulation of nitriles with hydrazines, which can be scaled up to a wide range of triazoles in good to excellent yields. Ammonia gas is liberated during the reaction, and halo, hetero functional groups as well as free hydroxyl, amino are tolerated in this transformation. A variety of alkyl, aryl-substituted nitriles can be functionalized with aromatic and aliphatic hydrazines employing this procedure. This finding provides a practical and useful strategy for synthesis of various of 15N-labeled 1,2,4-triazole derivatives and two type of mGlu5 receptor pharmaceuticals can be easily assembled in a one-pot manner.