2,2-Difluoroethylamine

1.9 g (0.01 mol) CuI and 1.8 g (0.01 mol) D-glucosamine were added to a reactor containing N,N-dimethylformamide. 4.3 g (0.25 mol) liquid ammonia was introduced into the high-pressure reactor, and the temperature was raised to 90°C. 14.5 g (0.1 mol) 2,2-difluoro-1-chloroethane was then introduced into the high-pressure reactor at a molar ratio of 1:2.5 to liquid ammonia over 30 minutes. After the introduction was complete, the reactor was kept at the desired temperature for 3 hours. After the reaction was complete, the reactor was cooled, filtered, and excess ammonia was purged with nitrogen. The resulting product was then distilled to obtain 6.6 g (99% purity) of 2,2-difluoroethylamine.

Liquid

2,2-Difluoroethylamine (DFEA) is an ESI-compatible buffering reagent whose conjugate acid has a pKa of 7.2, providing buffering capacity at physiological pH[1]. 2,2-Difluoroethylamine serves as a nucleophile in Ni-catalyzed C–N cross-couplings with aryl electrophiles, including N-arylation of fluoroalkylamines and competition studies against other heteroatom-containing nucleophiles[2].

[1]Davis, B. T. V., Velyvis, A., & Vahidi, S. (2023). Fluorinated Ethylamines as Electrospray-Compatible Neutral pH Buffers for Native Mass Spectrometry. Analytical Chemistry, 95(48), 17525–17532. https://doi.org/10.1021/acs.analchem.3c02640
[2]McGuire, R. T., Yadav, A. A., & Stradiotto, M. (2020). Nickel‐Catalyzed N‐Arylation of Fluoroalkylamines. Angewandte Chemie International Edition, 60(8), 4080–4084. https://doi.org/10.1002/anie.202014340