α,α-Difluorobenzylamines Deoxofluorination

Excerpt

α,α-Difluorobenzylamines are an important class of “N-CF₂R” type deoxofluorination reagents. Among various α,α-difluorobenzylamines with different substitution groups, α,α-difluorobenzyl(dimethyl)amine (DBDA) was first used for the deoxofluorination of simple alcohols and carboxylic acids [1]. However, the deoxofluorination property of DBDA has not been systematically studied, and the thermal stability of DBDA was also not shown. In 2004, N,N-Diethyl-α,α-difluoro(meta-methylbenzyl)amine (DFMBA) was first reported as a deoxofluorination reagent by Hara and coworkers [2]. In the next few years, the deoxofluorination property of DFMBA was well studied. DFMBA is a commercially available colorless liquid with boiling point of 81–83 °C/4 mmHg. Accelerating rate calorimetry analysis (ARC) showed that it is stable at temperatures up to 180 °C and decomposes gradually at 210 °C [3]. However, DFMBA can be destroyed gradually by moisture in air; thus, it must be stored in the refrigerator under inert atmosphere. Among a series of α,α-difluorobenzylamine reagents, only DFMBA has been commercialized probably due to the ready availability of its starting material, N,N-diethyl-meta-toluamide (DEET), which is a widely used pesticide. Another reason may be its higher hydrophobicity than nonsubstituted α,α-difluorobenzylamines, which can slow down the hydrolysis by water. …