Studies in azide chemistry. Part V. Synthesis of 4-azido-2,3,5,6-tetrafluoro-, 4-azido-3-chloro-2,5,6-trifluoro-, and 4-azido-3,5-dichloro-2,6-difluoro-pyridine, and some thermal reactions of the tetrafluoro-compound

Abstract

4-Azido-2,3,5,6-tetrafluoropyridine can be prepared by nitrosation of 2,3,5,6-tetrafluoro-4-hydrazinopyridine or, preferably, treatment of pentafluoropyridine with sodium azide in acetonitrile, a reagent that converts 3-chloro-2,4,5,6-tetrafluoro- and 3,5-dichloro-2,4,6-trifluoro-pyridine into 4-azido-3-chloro-2,5,6-trifluoro- and 4-azido-3,5-dichloro-2,6-difluoro-pyridine, respectively. 4-Azido-2,3,5,6-tetrafluoropyridine decomposes smoothly into nitrogen and an intractable solid at temperatures above ca. 130 °C, undergoes the Staudinger reaction with tri-phenylphosphine at room temperature, reacts with dimethyl sulphoxide at elevated temperatures to give a sulphoximide, partakes in 1,3-dipolar cycloaddition reactions with benzyne, diphenylacetylene, phenylacetylene, cyclopentadiene dimer, and norbornene, yields 4-anilino-2,3,5,6-tetrafluoropyridine with benzene at 175 °C, and reacts with cyclohexane to give the C–H ‘insertion’ product 4-(cyclohexylamino)-2,3,5,6-tetrafluoropyridine and 4-amino-2,3,5,6-tetrafluoropyridine. Thermal decomposition of the azide in a mixture of cyclo-hexane, -heptane, and -octane reveals that C–H ‘insertion’ is encouraged by increase in ring size, and thermolysis experiments with cis- and trans-1,2-dimethylcyclohexane show that this type of reaction lacks stereospecificity. The results of reactions between the azide and trans-4-methylpent-2-ene at elevated temperatures indicate that 1,3-dipolar cycloaddition occurs before nitrene generation can be achieved. Authentic samples of the new amino-pyridines [PhNHpy_F, cyclo-C_nH_2n–1·NHpy_F(n= 6, 7, or 8), cis- and trans-cyclo-1,2-Me₂C₆H₉·NHpy_F, and cis- and trans-Prⁱ[graphic omitted]py_F(py_F= 2,3,5,6-tetrafluoro-4-pyridyl)] encountered in this work can be obtained via nucleophilic attack by the appropriate amines on pentafluoropyridine.