Preparation and Reactions of Trichloromethyl-Substituted Pyridine and Pyrimidine Derivatives

The three-component reaction of lithiated methoxyallene, nitrites and trichloroacetic acid gave three model beta-keto enamides that were starting materials for the synthesis of trichloromethyl-substituted pyridine and pyrimidine N-oxide derivatives. Upon treatment with acetic anhydride, the methyl group of the prepared pyrimidine N-oxides was converted into an acetoxymethyl group by a Boekelheide rearrangement. A few typical experiments also revealed that the trichloromethyl group of the prepared pyrimidine N-oxides can be replaced by an alkoxy or a hydroxy group, or transformed into an arylthiomethyl group. An alternative approach to beta-keto enamides via the corresponding 13-keto enamines was also examined and provided the expected 4-hydroxy-6-(trichloromethyl)pyridine derivative in good yield.