Reaction of pentafluoropyridine with lithium hydrazonides; competing monosubstitution at the 2- and 4-positions

Abstract

Treatment of pentafluoropyridine ( 1) in diethyl ether with approximately 1 M equiv. of the hydrazonides Ph 2C=NNHLi ( 3a) and Ph 2C=NNLiPh ( 3b) under mild conditions gives good yields (62% and 83%) of 4- and 2-(Ph 2C=NH)C 5F 4N ( 5a and 6a) and 4- and 2-(Ph 2C=NPh)C 5F 4N ( 5b and 6b), respectively, containing unusually large amounts of 2-substituted products ( 5a/6a = 50:50; 5b/ 6b = 65:35). The increased ease of displacement of a 2-F substituent from 1 (→ 6a and 6b) in these cases is ascribed to chelation of the lithium cation in the transition state involved in the rate-determining step leading to formation of an ortho-quinonoidal σ-complex. Catalytic hydrogenation of a 1:1 mixture of hydrazones 5a and 6a affords the corresponding hydrazines, 4- and 2-H 2NNHC 5F 4N ( 7 and 8) in good yield (78%); acidic hydrolysis (hot HCl aq.) of the 5a/6a mixture yields tetrafluoro-4-hydrazinopyridine ( 9) and, depending on the conditions, tetrafluoro-2-hydrazinopyridine ( 10) or 2-aminotetrafluoropyridine ( 11).