A scalable and safe continuous flow procedure for in-line generation of diazomethane and its precursor MNU

Abstract

Diazomethane is a valuable C₁-building block for organic synthesis. Due to its intrinsic reactivity and instability, handling of this reagent is associated with serious safety hazards. Herein we present a simple and robust continuous flow process, allowing a safe and on-demand generation of diazomethane with a productivity of 95–117 mmol h⁻¹. The developed two-step process starts from non-hazardous N-methylurea, and generates and consumes N-methyl-N-nitrosourea (MNU) and diazomethane, thus enabling a safe and convenient scale-up to a multi-gram scale in a conventional synthesis laboratory.