title: Multistep flow synthesis of 5-amino-2-aryl-2H-[1,2,3]-triazole-4-carbonitriles.
abstract: 1,2,3-Triazole has become one of the most important heterocycles in contemporary medicinal chemistry. The development of the copper-catalyzed Huisgen cycloaddition has allowed the efficient synthesis of 1-substituted 1,2,3-triazoles. However, only a few methods are available for the selective preparation of 2-substituted 1,2,3-triazole isomers. In this context, we decided to develop an efficient flow synthesis for the preparation of various 2-aryl-1,2,3-triazoles. Our strategy involves a three-step synthesis under continuous-flow conditions that starts from the diazotization of anilines and subsequent reaction with malononitrile, followed by nucleophilic addition of amines, and finally employs a catalytic copper(II) cyclization. Potential safety hazards associated with the formation of reactive diazonium species have been addressed by inline quenching. The use of flow equipment allows reliable scale up processes with precise control of the reaction conditions. Synthesis of 2-substituted 1,2,3-triazoles has been achieved in good yields with excellent selectivities, thus providing a wide range of 1,2,3-triazoles.
authors: UCB Biopharma, Avenue de l'Industrie, 1420 Braine l'Alleud (Belgium).
authors: Jérôme
authors: J
authors: Jacq
authors: Patrick
authors: P
authors: Pasau
mesh_terms: D000147:Acids, Heterocyclic / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003979:Diazonium Compounds / Q000737:chemistry*; D005434:Flow Cytometry; D014230:Triazoles / Q000138:chemical synthesis*
chemical_list: D000147:Acids, Heterocyclic; D003979:Diazonium Compounds; D014230:Triazoles; D003300:Copper
keywords: diazonium ions; flow chemistry; heterocycles; library synthesis; triazoles