Electrochemical fluorination of hexahydroazepine, methylpiperidines and methyl 1-hexahydroazepine-acetate: the preparation of F-(1-hexahydroazepine-acetyl fluoride) and its derivatives

The electrochemical fluorination of hexahydroazepine (1), methylpiperidines (2) [2-methylpiperidine (2a), 3-methylpiperidine (2b), 4-methylpiperidine (2c)] and methyl 1-hexahydroazepine-acetate (3) was examined. An extensive cleavage of the C–N bond occurred in the fluorination of secondary cyclic amines (1, 2a–c) resulting in only a small yield of the corresponding F-(N-fluoro cyclic amines). F-(1-hexahydroazepine-acetyl fluoride) (4) was obtained in a fair yield from the fluorination of 3 along with F-[(methylpiperidino)-acetylfluoride] which was formed as a result of the isomerization of 3 during fluorination. In addition, several derivatives of 4 were synthesized. F-(1-iodomethyl-hexahydroazepine) (4a) was prepared by the reaction of 4 with anhydrous LiI. The compound 4 was converted into its potassium salt (4c) via methyl F-(1-hexahydroazepine-acetate) (4b), which upon pyrolysis in the presence or absence of ethylene glycol resulted in the formation of 1-difluoromethyl-dodecafluoro(hexahydroazepine) (4d) and F-(3,4,5,6-tetrahydroazepine) (4e), respectively. F-(1-hexahydroazepine-acetoamide) (4f), F-(1-hexahydroazepine-acetonitrile) (4g) and corresponding p-methoxyanilide (4h) were also derived from 4.