Abstract

AbstractIn the pursuit of clean pharmaceutical production, chemists in medicinal industry require access to new sustainable methodologies to reduce and even eliminate pollution, which is mainly produced by the overuse of organic solvents during chemical synthesis of active pharmaceutical ingredients (APIs). In this context, the solvent‐free/less mechanochemical functionalization of small molecules has gradually emerged as a powerful strategy for the green synthesis and modification of APIs, bioactive compounds, and functional materials. In this review, we present an overview of mechanochemical C−X/C−H functionalization applications to medicinal chemistry, involving cross‐coupling, cross‐dehydrogenative coupling, oxidative coupling (via C−H activation pathway), and direct coupling (via radical pathway) as key steps for the preparation of APIs and bioactive compounds.

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