Syntheses Of Trifluoromethyl Ketones Of Pyridines And Other Heteroarenes By Regioselective Lithiation

In this thesis, the reactions of2,2,2-trifluoro-l-morpholinoethanone, as a trifluoroacetyl-containing reagent, were studied and the corresponding trifluoromethyl ketones of pyridine and other heteroarene derivatives were successfully synthesized by regioselective lithiation.1. The selection of trifluoroacetylation reagentThe organolithium intermediates (5-bromopyridin-2-yl)lithium was obtained by the selective monolithiation of2,5-dibromopyridine, after reacted with various trifluoroacetylation reagents to give compound1. The results indicate that2,2,2-trifluoro-l-morpholinoethanone is the optimal trifluoroacetylation reagent.2. The synthesis of heteroaryl trifluoromethyl ketonesFirstly, six trifluoromethyl ketones of pyridine derivatives were generated normally by the reaction of bromine-lithium exchange. The regioselective monolithiation of dibromopyridines were achieved by using different solvent. Reactions of lithio reagents thus obtained with2,2,2-trifluoro-l-morpholinoethanone successfully furnished the corresponding trifluoromethyl ketones1-6in30-83% Secondly, seventeen heteroaryl trifluoromethyl ketones were obtained by directed ortho-lithiation reaction. The corresponding sustitutied pyridine, pyrimidine, pyridazine, coumarone and benzothiophene trifluoromethyl ketones7-23were obtained in25-86%yield followed by the literature procedure.Finally, four trifluoromethyl ketones of pyridine derivatives were obtained by C-2lithiation reaction. References to the C-2lithiation reaction of chloropyridines, we offered the corresponding trifluoromethyl ketones24-27in32-88%yield.