A new one-pot synthesis of 1,2,3,4-tetrafluoroacridines and some 7-substituted derivatives

Article abstract of DOI:10.1016/S0022-1139(00)80058-5

1,2,3,4-Tetrafluoroacridine (1a) and a range of 7-substituted analogues can be synthesised by heating pre-formed Schiff bases (E)-C6F5CH=NC6H4R-p (3) (from C6F5CHO + H2NC6H4R-p) with the parent aniline H2NC6H4R-p (1:1 molar ratio) or by heating a mixture of the aldehyde C6F5CHO and the aniline H2NC6H4R-p (R=H, OMe, Me, Bu^t, F, Cl and Br) (1:2 molar ratio) in toluene or 1,2-dichlorobenzene under reflux.The mechanism has been deduced through the isolation in certain reactions of ortho-substituted Schiff bases 2-(p-RC6H4NH)C6F4CH=NC6H4R-p (6) (R=Cl or Br), which on acid catalysis (by p-RC6H4NH3(+)F(-)) undergo ring-closure with elimination of the aniline p-RC6H4NH2.Except where R=F, Cl or Br, substantial amounts of the corresponding 3-anilino-1,2,4-trifluoroacridines 5 are also formed; these arise via sequential para- and ortho-substitution of fluorine in the pentafluorophenyl moiety of the Schiff bases.The synthesis is capable of extension to other fluorinated aromatic aldehydes, e.g. the formation of 1-fluoro-7-methoxyacridine (9) from 2,6-difluorobenzaldehyde and p-anisidine.