In continuation of our interest in long-range "through-space" H-F and C-F spin-spin coupling in planar aromatic molecules,we desired to explore the presence (or absence) of such coupling between the fluorine and the methyl group as possibly mediated via the nitrogen lone pair in 4-fluoro-5-methylacridine (1). Some examples of through-space H-F and C-F coupling from our laboratory are shown in Figure 1. The subject of "through-space" H-F and C-F spin-spin coupling has been reviewed " and several recent examples have been described.9"14 However, to our knowledge, no H-F or C-F spin-spin coupling via a nitrogen lone pair of electrons has been reported. Our synthesis of this new compound 1 is shown in Scheme 1 and extends from a modification of a reported preparation of 4-methyl-5-aminoacridine (7).15 The commercially available 3-methyl-2-nitrobenzoic acid (2) was hydrogenated to afford 2-amino-3-methylbenzoic acid (3) (93%), which was coupled with 2-bromonitrobenzene under Ullmann copper coupling conditions to give 2-methyl-2'-nitrophenylamine-6-carboxylic acid (4) (78%). Ring closure of 4 to 4-methyl-5-nitroacridin-9-one (5) was accomplished with hot cone, sulfuric acid (quant.). Reduction of the nitro group in acridinone 5 with SnCl2, HC1 gave 4-amino-5-methylacridin-9-one (6) in low yield after recrystallization from EtOH (18%). However, reduction of the carbonyl group in 7 with sodium/mercury amalgam gave 4-amino-5-methylacridine (7) in 50% yield. Diazotization was carried out using nitrosylsulfuric acid, followed by fluoboric acid to afford 4-(5-methylacridino)dia-zonium tetrafiuoroborate (8) in 88% yield. Heating salt 8 at 180 °C afforded the desired 4-fluoro-5-methylacridine (1) in low yield (21%).
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