Generation of 1,2-Difluorobenzene via a Photochemical Fluorodediazoniation Step in a Continuous Flow Mode

• Kevin Simon^ab, Desiree Znidar^ab, Julien Boutet^c, Gérard Guillamot^c, Jean-Yves Lenoir^c, Doris Dallinger^ab, and C. Oliver Kappe^ab

• ^aCenter for Continuous Flow Synthesis and Processing (CCFLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, Graz 8010, Austria
• ^bInstitute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, Graz 8010, Austria
• ^cSeqens SAS, 21 Chemin de la Sauvegarde, 21 Ecully Parc, Ecully 69130, France

A proof-of-concept study for the synthesis of 1,2-difluorobenzene from 2-fluoroaniline via the Balz–Schiemann reaction using HF/pyridine as the fluorinating reagent is reported. Key to success for a fast reaction, a clean reaction profile─and thus high product selectivity─was a photochemically induced fluorodediazoniation of the in situ-generated diazonium salt performed in a continuous flow mode. A high-power 365 nm light-emitting diode provided a more robust and efficient irradiation system compared to a medium-pressure Hg lamp with respect to the reaction performance on scale-out runs and reaction time, allowing the generation of 1,2-difluorobenzene within a 10 min residence time and a product selectivity of ≥95% at full conversion.

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