Synthesis of Trifluoromethylated Pyrazine-Containing Nitrogen Heterocycles from Trifluoropyruvaldehyde and Ortho-Diamines: Scope and Regiochemistry

Article abstract of DOI:10.1021/jo00256a034

The structures of the reaction products obtained from the condensation of trifluoropyruvaldehyde with a variety of ortho-diamines have been investigated in order to determine the scope of the reaction and also to investigate which of the structural isomers is formed in larger amount in cases in which two products are possible.As a result of intensive 13C, 19F, and 1H NMR studies, as well as X-ray analysis, it has been observed that in aqueous solution, the major product of the reaction is usually derived from reaction of the aldehyde carbonyl of trifluoropyruvaldehydehydrate (3) with the more reactive amino group of the diamine to give an intermediate imine (e.g.,28), which then dehydrates and cyclizes by reaction of the remaining amino group with the carbonyl adjacent to the trifluoromethyl group.