Fluoroquinolone 항생제의 중요한 중간체인 2,3,4,5-tetrafluorobenzoic acid를 tetrachloride phthalic anhydride에서 출발 하여 imidation, fluorination, hydrolysis과 decarboxylation단계를 거쳐서 합성하였다. Imdation 단계에서는 상전이 촉매를 이용하여 98.2%의 수율로 합성하였으며, fluorination 단계에서는 81.3%, 가수분해 단계에서는 88.6%, 마지막으로 decarboxylation단계에서는 81.6%의 수율로 합성하였다.
2,3,4,5-Tetrafluorobenzoic acid, an important intermediates of fluoroquinolone antibiotics, was synthesized from tetrachloride phthalic anhydride through imidation, fluorination, hydrolysis and decarboxylation. The effects of phase transfer catalyst on imidation and fluorination reaction and the effects of surfactants on the hydrolysis reaction were studied, respectively. Experimental results showed that the imidation reaction time was greatly reduced in the presence of a phase transfer catalyst, hexadecyltrimethyl, resulting in imidation yield as high as 98.2%. The fluorination yield reached 81.3% when tetrabutylammonium bromide was chosen as a phase transfer catalyst. The hydrolysis reaction time was also decreased by adding hexadecyltrimethyl while increasing the yield to 88.6%. In the post-processing, the sublimation method was used to purify the product, and ideal effect was obtained. In the decarboxylation reaction, tetrafluoride phthalic acid was obtained by decarboxylation in the solvent of tri-n-butyl amine and decarboxylation yield reached 81.6%. Compared with the literature method, the overall reaction time of the improved method decreased from 53 h to 20.5 h and the total yield increased from 47.3% to 57.4%.
