Photoinduced C-F Bond Cleavage in Some Fluorinated 7-Amino-4-quinolone-3-carboxylic Acids

J Org Chem. 1999 Jul 23;64(15):5388-5395. doi: 10.1021/jo982456t.

Abstract

The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water. All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution. 6-Fluoro derivatives such as norfloxacin (Phi(dec) = 0.06) and enoxacin (Phi(dec) = 0.13) give the corresponding phenols. Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Phi(dec) = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain). With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (Phi = 0.55) and selective for position 8. Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N-ethyl group rather than solvent addition (a carbene-like chemistry). With all of the above fluoroquinolones an intensive triplet-triplet absorption is detected and is quenched by sulfite (k(q) = (1-5) x 10(8) M(-)(1) s(-)(1)). Under this condition, reductive defluorination via the radical anion takes place. The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.