A facile one-pot synthesis of 2-fluoroalkyl 1,3-imidazolines and 1,3-oxazolines through imidoyl halide intermediates

Abstract

A facile one-pot procedure has been developed for the synthesis of 1,3-imidazolines and 1,3-oxazolines bearing fluorinated alkyl groups at the 2-position. The reaction involves the condensation of N-monosubstituted ethane-1,2-diamines or 2-aminoethanols with a fluorinated carboxylic acid in the presence of PPh3/CX4. The proposed mechanism is that the amide intermediates were initially formed, and then converted to the imidoyl halide intermediates in the presence of PPh3/CX4, followed by rapid intramolecular cyclization to 1,3-diazoline products. This protocol allows for the synthesis of 2-bromodifluoromethyl-1,3-imidazoline, a useful CF2Br-heterocyclic building block, which can be used for the synthesis of gem-difluoromethylene linked compounds.