136491-17-3Relevant articles and documents
Synthesis of Novel Quinolone-Chemotherapeutics. V. Methodical Investigations on the Synthesis of Quinolone Chemotherapeutics
Jordis, Ulrich,Sauter, Fritz,Burkart, Michael,Henning, Hans-Georg,Gelbin, Anke
, p. 267 - 279 (2007/10/02)
The synthesis of 6,7-dihalogen-N-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acids (3a,b) from 3,4-dihalogen-anilines is a three-step processes: (a) N-ethylation, (b) reaction with orthoformic ester and Meldrum's acid, (c) intramolecular cyclization.An increase of the total yields in comparison with known methods is mainly connected with the third step.Here the Meldrum's method allows reactions in solution at temperatures 100 deg C.With application of special Lewis acids the 6,7-dihalogen-substituted products are formed in relatively high yields (6,7-difluoro-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (3a): 71percent; 7-chloro-6-fluoro-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (3b): 60percent) without impurities of the corresponding 5,6-dihalogen substituted isomers.Anhydrides (5) of 4-oxo-1,4-dihydro-quinolone-3-carboxylic acids with dibromo- and difluoro-boric acid were synthesized and shown to facilitate the aromatic nucleophilic substitution.The kinetics of two reactions (5a -> 6 and 3b -> 7) were determined and relative reaction rates established.
