Development of an Efficient and Sustainable Synthesis of 2-(3-Methyl-1H-1,2,4-Triazol-1-Yl) Acetic Acid Under Continuous-Flow Conditions

A novel, metal-free process for the challenging synthesis of 2-(3-methyl-1H-1,2,4-triazol-1-yl) acetic acid (1) is reported, which features an efficient condensation for the triazole build-up under flow conditions. This continuous, two-step method is atom economical, highly selective and environmentally benign, due to the avoidance of chromatography and isolation steps. Compared to the earlier batch synthetic routes, higher yields were achieved in a flow reactor. In addition, a highly energetic intermediate could be controlled and handled in a safe manner. To generalize the established route, several triazoles were finally prepared under the described conditions, confirming that the methodology could find useful applications for the rapid and sustainable construction of differentially functionalized 1,2,4-triazoles.