4221-96-9Relevant academic research and scientific papers
Chemoselective N-Difluoromethylation of Functionalized Tertiary Amines
Zafrani, Yossi,Amir, Dafna,Yehezkel, Lea,Madmon, Moran,Saphier, Sigal,Karton-Lifshin, Naama,Gershonov, Eytan
, p. 9180 - 9187 (2016)
A practical, convenient, and general method for the difluoromethylation of tertiary amines, using diethyl bromodifluoromethylphosphonate and fluoride, is described. This commercially available phosphonate smoothly reacts with a fluoride ion to liberate a difluorocarbene intermediate that in the presence of a proton source and a tertiary amine generates the corresponding α-difluoromethylammonium compound in good to excellent yields. Despite the involvement of a difluorocarbene intermediate, this difluoromethylation occurs almost exclusively on the nitrogen atom with diverse molecular structures, including drugs, surfactants, chiral phase transfer catalysts, polymers, ionic liquids, and other fine chemicals. A preliminary assessment of the effects that an α-difluoromethyl groupT has on hydrogen bonding and logP of quaternary ammonium salts is also described.
