The introduction of trifluoromethyl groups into organic compounds can be useful, e.g., in pharmaceutical or materials chemistry. Trifluoroacetonitrile (CF₃CN), for example, can be used for the synthesis of trifluoromethylated nitrogen-containing heterocyclic compounds. However, CF₃CN is a hard-to-handle, toxic gas, which limits its use.

Yangjie Huang, Minjiang University, Fuzhou, China, Zhiqiang Weng, Minjiang University and Fuzhou University, China, and colleagues have synthesized a convenient precursor for generating trifluoroacetonitrile in situ under mild conditions. The team prepared a 2,2,2-trifluoroacetaldehyde O-(aryl)oxime (pictured) from commercially available O-(2,4-dinitrophenyl)hydroxylamine via a condensation with trifluoroacetaldehyde hydrate under acidic conditions.

The team found that the synthesized precursor released CF₃CN in quantitative yield under mildly basic conditions. The generated CF₃CN could be used, for example, to prepare different 5-trifluoromethyl-1,2,4-oxadiazoles via reactions with a range of in–situ-generated nitrile oxides. 3-Aryl-5-(trifluoromethyl)-2,3-dihydro-1,2,4-oxadiazoles were also prepared via reactions of CF₃CN with aryl-substituted N–tert-butyl nitrones.

• 2,2,2-Trifluoroacetaldehyde O-(Aryl)oxime: A Precursor of Trifluoroacetonitrile,
  Bo Lin, Yunfei Yao, Yangjie Huang, Zhiqiang Weng,
  Org. Lett. 2022.
  https://doi.org/10.1021/acs.orglett.2c00637