A Modular Continuous Flow Platform for Safe, On-demand Generation of HCF 2 N 3 from R-22 Gas and Access to N -CF 2 H Triazoles
Year: 2026
Type: preprint
Abstract: The N -CF 2 H motif recently emerges as a promising pharmacophore but modular and general strategy to access this scaffold remains scarce. Although difluoromethyl azide (HCF 2 N 3 ) constitutes an ideal aminodifluoromethyl surrogate in this case, its exceptionally low ratio of C to N atoms (0.33), high volatility (b.p. = 8 o C), and heat/shock sensitivity render it particularly unsafe to handle and use in batch. On the other hand, R-22 (ClCF 2 H gas) is a phased-out refrigerent due to its ozone depletion potential and high global warming potential, and valorization of the reclaimed R-22 is highly desirable. Here, we report a modular continuous flow platform to efficiently enable a safe, on-demand generation of HCF 2 N 3 from R-22 gas and its direct in-line utilization. Two HCF 2 N 3 generation modules are developed to operate under aqueous or organic reaction conditions for accommodating diverse downstream reactions. The freshly generated HCF 2 N 3 is immediately intercepted by downstream base-mediated or copper tube-catalyzed cycloadditions to yield a wide range of valuable N -CF 2 H triazoles using easily available alkynes, aldehydes and β -ketoesters. Our method completely circumvents isolation hazards, mass transfer limitations in batch, and enables previously improbable gas-to-gas transformation and multiphasic conditions.
Source: ChemRxiv
Authors: Ye Lin, Tianbo Wang, Wai Chung Fu
Institution: City University of Hong Kong
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: G1261735317, G7165543787
OpenAlex ID: W7223373370