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2,4,5-Trifluorobenzoic acid
Release time：2019-10-09 17:49:26
Product introduction: 2,4,5-trifluorobenzoic acid is an important precursor for the synthesis of ciprofloxacin (CiproTM), norfloxacin (NoroxinTM) and pefloxacin (PeflacineTM), etc. It also has potential application value in the preparation of new materials such as diodes (OLEDs) and water tracers.
Existing processes and problems: The methods for synthesizing 2,4,5-trifluorobenzoic acid mainly include: 1) 2,4,5-trifluorobromobenzene is reacted with an excess of CuCN, and is hydrolyzed by an acid, and the method is produced. The highly toxic substance HCN is highly polluted by the environment; 2) the 1,2,4-trifluorobenzene and acetyl chloride are subjected to Friedel-Craft acylation under the action of AlCl3, and then an oxidation reaction is carried out in a NaClO/NaOH solution. A large amount of chlorine-containing waste is formed; 3) tetrachlorophthalic anhydride is hydrodechlorinated by metal zinc and NaOH to obtain 3,4,6-trichlorophthalic acid, and methylamine is used in glacial acetic acid. After protecting the carboxyl group, halogen exchange with KF in sulfolane is carried out, and after hydrolysis with H2SO4, 3,4,6-trifluorophthalic acid is obtained, and finally prepared under the action of DMSO. The reaction steps are many, and the total yield is only 60%. ; 4) 2,3,4,6-tetrafluorobenzoic acid is prepared by reacting with metallic zinc in a liquid ammonia environment, the process selectivity is only 50%, and the conditions are harsh; 5) 4,5-difluoro-2-amino Benzoic acid forms a corresponding ammonium salt under the action of strong acid (HCl, H2SO4, HBF4, HF), is diazotized with NaNO2 and 48% HBF4, and is prepared by heating and hydrolysis. , multiple temperature change operation, and waste acid is difficult to handle; 6) metallization reaction of 2,4,5-trifluorobromobenzene with butyl lithium or magnesium metal, and then the product is prepared by carboxylation with CO2, reaction selectivity ( 99%) and the yield (83%) are higher, but the reaction process is strongly exothermic, requiring ultra-low temperature, dripping operation, requiring multiple temperature changes to cause a long reaction cycle, and it is difficult to achieve process continuity.
The present technology and characteristics: the present technology on the basis of the method 6, using a common simple Grignard reagent and 2,4,5-trifluorobromobenzene to generate a Grignard exchange reaction, and then CO2 carboxylation to prepare 2,4,5- Trifluorobenzoic acid, combined with the advantages of the microreactor, enables the efficient and continuous preparation of 2,4,5-trifluorobenzoic acid under mild conditions. Its features include:
The reaction process achieves stoichiometric reaction and atomic economy;
The reaction time can be greatly shortened, and the conditions of the conventional Grignard reaction slow dropping and ultra-low temperature are exceeded;
The process is continuous and the intermediate (Gresh reagent) is sufficiently prevented from deactivating.
| 2,4,5-Trifluorobenzoic acid | Yield/% | time/min | temperature/oC |
| Microstructure reactor | 97 | 11 | 30~45 |
| Batch reactor with scheme 6 | 83 | ~300 | -40~-70 |