Two‐Step Continuous‐Flow Synthesis of Fungicide Metalaxyl through Catalytic C−N Bond‐Formation Processes

Metalaxyl, an acylalanine fungicide, was synthesized through catalytic continuous sequential‐flow reactions. Commonly used syntheses of this compound use batch systems and suffer from problems such as coproduction of halogen‐containing by‐products derived from acyl and alkyl halides in the substitution reactions of 2,6‐dimethylaniline. To minimize waste and enhance efficiency, a halide‐free approach including two continuous‐flow catalytic processes, heterogeneous Pt‐catalyzed reductive alkylation and homogeneous acid‐catalyzed amidation with an acid anhydride, was developed. Systematic examination of the two reactions in flow mode enabled a high‐yielding, two‐step sequential continuous‐flow process to be achieved.