Fluorocarbon derivatives of nitrogen. Part 13. Reaction of perfluoroalkanenitriles with pyridinium alkoxycarbonylmethylides: synthesis of perfluoroalkylated imidazo[1,2-a]pyridines (1-azaindolizines). X-Ray molecular structure of pyridinium 4,5-dihydro-4-oxo-2,6-bis(trifluoromethyl)pyrimidin-5-ylide

Abstract

Pyridinium t-butoxycarbonylmethylide, generated in situ by treatment of N-(t-butoxycarbonylmethyl)pyridinium perchlorate with sodium hydride (in acetonitrile) or triethylamine (in dichloromethane), reacts with trifluoroacetonitrile to yield 3-(t-butoxycarbonyl)-2-(trifluoromethyl)imidazo[1,2-a]pyridine, N-[2-amino-3,3,3-trifluoro-1-(t-butoxycarbonyl)prop-1-enyl]pyridinium perchlorate, and pyridinium 4,5-dihydro-4-oxo-2,6-bis(trifluoromethyl)pyrimidin-5-ylide. The corresponding heptafluoropropyl compounds can be prepared in the same way, starting from heptafluorobutyronitrile; in both cases, the relative yields of the three types of product can be varied by changing the reactant ratios. Treatment of N-[2-amino-3,3,3-trifluoro-1-(t-butoxycarbonyl)prop-1-enyl]pyridinium perchlorate with heptafluorobutyronitrile in the presence of triethylamine gives 2-(heptafluoropropyl)-4,5-dihydro-4-oxo-6-(trifluoromethyl)pyrimidin-5-ylide. Trapping of pyridinium ethoxycarbonylmethylide with trifluoroacetonitrile provides the known 3-(ethoxycarbonyl)-2-(trifluoromethyl)imidazo[1,2-a]pyridine, plus pyridinium 4,5-dihydro-4-oxo-2,6-bis(trifluoromethyl)pyrimidin-5-ylide. Reduction (zinc–acetic acid) of the latter, for which a detailed X-ray crystallographic analysis has been performed, gave 4-hydroxy-2,6-bis(trifluoromethyl)pyrimidine. A stepwise mechanism is proposed to account for the cycloaddition step involved in formation of perfluoroalkylated imidazo[1,2-a]pyridines from pyridinium alkoxycarbonylmethylides and the perfluoroalkanenitriles CF₃CN and n-C₃F₇CN.