Advances in Safe Handling and Synthetic Applications of Diazomethane (CH 2 N 2 )

ABSTRACT Diazomethane (CH 2 N 2 ) is a highly versatile C1 building block in organic chemistry, but its practical use is significantly limited by its extreme toxicity and explosive properties. This review systematically evaluates methodologies developed for the safe application of diazomethane as a key reactive intermediate. In this context, we categorize these strategies into four paradigms: (1) the structural evolution of stable diazomethane precursors, (2) the optimization and limitations of traditional batch preparation processes, (3) the application of continuous‐flow and membrane separation technologies, and (4) the strategies in a one‐pot and in situ manner for the use of CH 2 N 2 . By emphasizing the safety profiles, feasibility, and scalability of each methodology, this review aims to facilitate the broader and safer application of diazomethane in both the milligram‐scale synthesis of complex target molecules and industrial‐scale manufacturing.