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Updated: Apr 10, 2026

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Published on: November 15, 2017

Safe by Design Flow Technology for Diazoacetonitrile Generation and Direct Conversion to Pyrazoles

Dušan Bošković¹, Stefan Loebbecke¹, Calogero Giancarlo Piscopo¹

¹Energetic Materials Department, Fraunhofer Institute for Chemical Technology ICT, Pfinztal, Germany.

|April 9, 2026

Abstract

None:

Diazo compounds enable short and efficient synthetic routes but their broader adoption is limited by hazards associated with their preparation, storage, and handling. Here, a safe by design continuous flow process is presented in which diazoacetonitrile (DAN) is generated in aqueous solution, transferred into an organic phase with minimal hold up, and immediately consumed in a telescoped [3 + 2] cycloaddition with activated alkynes to obtain 3 cyano 1H pyrazoles. Operating windows for solvent choice, temperature, residence time, and pressure are established, and the influence of added HCl on nitrosation efficiency and DAN decay is observed. Dichloromethane and benzonitrile are compared as extraction and reaction media: benzonitrile enables higher organic phase DAN concentrations, whereas dichloromethane facilitates isolation. Under optimized conditions, NMR yields of ∼60%-80% are obtained for reactions with methyl propiolate, and a 2 h telescoped run affords a 37% isolated yield after recrystallization. The workflow prevents isolation or accumulation of DAN, improving the safety of processes involving this energetic intermediate and illustrating how continuous flow and biphasic extraction can support greener synthesis by avoiding reaction steps.

Keywords:

continuous flow diazoacetonitrile green methods hazardous chemistry pyrazole

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