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
- 1Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China
- 2China Chemical Technology Research Institute
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.
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BibTeX
@misc{lin2026modular,
title = {{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}},
author = {Ye Lin and Tianbo Wang and Wai Chung Fu},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010927/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010927/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - 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
AU - Ye Lin
AU - Tianbo Wang
AU - Wai Chung Fu
PY - 2026
DA - 2026/10/23
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010927/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010927/v1
AB - 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.
ER -