Study On The New Synthetic Process Of 2, 3, 4, 5 - Tetrafluorobenzoic Acid

Quinolone antibacterial drugs are highly active and safe drugs with broad spectrum. 2,3,4,5- tetrafluorobenzoic acid is important intermediate for many quinolone antibacterial products. The tetrachlorophthalide- methylamine process was improved for the synthesis of 2,3,4,5- tetrafluorobenzoic acid, and the optimized process parameters were gained. The total yield was elevated, the producing cost was decreased and the waste compounds were reduced. The new process is expected to create good economic and social benefits.N-methyl tetrachlorophthalimide was synthesized by tetrachloro -phthalic anhydride and 40% methylamine. The optimized conditions were: The molar ratio was 1:1.2. They reacted at 120℃for 4 hours using DMF as solvent. The purity of N-methyl tetrachlorophthalimide was 98.5%, and the yield was 95.9%. Methylamine was easy to be reacted and removed, so the yield and purity were improved using methylamine instead of aniline which was used at traditional process.N-methyl tetrafluorophthalimide was prepared from N-methyl tetrachlorophthalimide by fluorinating. The optimized conditions were: The molar ratio between tetrachlorophthalimide and potassium fluoride was 1:5. They reacted at 150℃for 6 hours using PEG-6000 as catalyst and DMF as solvent. The purity of N-methyl tetrafluorophthalimide was 97%, and the yield was 85.2%. DMF was cheaper and have lower boiling point than sulfolane, so the producing cost and energy wastage were decreased using DMF instead of sulfolane which was used at traditional process.3,4,5,6-tetrafluorophthalic acid was prepared from N-methyl tetrafluorophthalimide by hydrolyzing. The optimized conditions were: 55% H2SO4 was used as catalyst and solvent. The reaction continued at 120℃for 10 hours. The purity and yield were 98% and 90% respectively.2,3,4,5- tetrafluorobenzoic acid was prepared from 3,4,5,6-tetra -fluorophthalic acid by decarbonating. The optimized conditions were: DMSO was used as decarbonating agent and solvent. The reaction continued at 100℃for 4 hours. The purity and yield were 98% and 92.6% respectively. Using DMSO instead of Bu₃N which was used at traditional process, the basification and acidification were cancelled, the yield was increased and the waste compounds were reduced.