Mechanochemical Amidation Mediated by 1,1'-Oxalyldiimidazole for the Synthesis of Agrochemicals

The synthesis of amide moieties, essential components in both pharmaceuticals and agrochemicals, traditionally involves environmentally hazardous and polluting processes. This study presents a novel mechanochemical method to form amide bond using 1,1'-oxalyl diimidazole (ODI) as activating agent, and evaluates its applicability in synthesizing agrochemicals such as Mepronil, Flutolanil, and Fluxapyroxad at gram-scale. The mechanochemical kinetics underlying the synthesis of the three mentioned compounds was also investigated. The new method was compared with the similar 1,1'-carbonyl diimidazole (CDI)-mediated mechanochemical amidation previously reported. Results demonstrate that ODI-mediated synthesis outperforms in the case of deactivated acids. Energetic considerations and technical process parameters are also discussed to provide quantitative technology assessment. A comprehensive analysis by green chemistry metrics with CHEM21 and DOZN^TM 3.0 toolkits, underscores the potential benefits of the mechanochemical approach, compared with the solvent-based protocols for the preparation of marketed agrochemicals.