Background and overview[1][2]
Fluorobenzoic acid is an important fine chemical intermediate and is widely used in the synthesis of medicines, pesticides, dyes, liquid crystal materials, etc. For example, in pesticides, it can be used to synthesize herbicides, insecticides, fungicides, etc.; in medicine, it can be used to synthesize antibacterial drugs, cardiovascular and cerebrovascular and nervous system, antipyretic, analgesic, anti-tumor drugs, etc., using it as a matrix. Synthetic fluorine-containing pesticides and medicines have the advantages of high physiological activity, high efficiency and low toxicity (low side effects). The new fluoropolymer synthesized from it has the characteristics of high thermal stability and good mechanical properties, and can produce high-strength and high-toughness fiber and membrane materials.
At present, there is a huge demand for fluorobenzoic acid products at home and abroad, but there are few manufacturers that can mass-produce such products. Therefore, it is particularly urgent to find a new method suitable for industrial production.
Physical and chemical properties and structure[1]
Fluorine-containing aromatic compounds are fine chemicals that are growing rapidly. They are widely used in medicine, pesticides, dyes and other fields, and have broad development prospects. Compared with non-fluorine aromatic compounds, fluorine-containing aromatic compounds not only have stronger stability and biological activity, but also have higher fat solubility and hydrophobicity. They have low toxicity and low toxicity in the field of pharmaceutical applications. It has the characteristics of low dosage, high efficacy and strong metabolism. Therefore, the development and application of fluorine-containing aromatization and compound synthesis technology have attracted more and more widespread attention from the domestic and foreign chemical circles.
Me-fluorobenzoic acid appears as leaf-shaped crystals or white powder. Melting point (℃): 122~124. m-Fluorobenzoic acid is an important intermediate for the synthesis of pesticides, medicines, dyes and other fine chemicals. It is especially used for the synthesis of loratadine, nolinatadine and bupropion and other drugs. Synthesis of phenylene ether herbicides.
m-Fluorobenzoic acid
Preparation[2]
The main preparation methods for m-fluorobenzoic acid include arylamine diazotization (classic Balz-Schiemann reaction) thermal decomposition method, halogen exchange method and direct fluorination method. The diazotization method used earlier in the industry uses 3-aminobenzoic acid as raw material, diazotizes it with nitrous acid, and then reacts with fluoroboric acid to form an insoluble fluoroboric acid diazonium salt, which is then filtered, washed, and dried. After heating and decomposition, the corresponding fluorine-containing compounds are obtained. This method has high raw material cost and complicated steps, and when the diazonium salt is heated and decomposed, the toxic gas boron trifluoride will be produced to pollute the environment.
Simultaneous reaction itself has many limitations. For example, aromatic amines with electron-donating groups on the benzene ring (aniline, p-methoxyaniline, p-toluidine) have higher yields, but when the substituents on the benzene ring are carboxyl, hydroxyl, or sulfonic acid groups, the yield will increase. The water solubility of the fluoboric acid diazonium salt greatly reduces the yield.
1. Improved Balz-Schiemann method
The Balz-Schiemann method is improved by using anhydrous hydrogen fluoride instead of fluoroboric acid to react with sodium nitrite for diazotization. However, because hydrogen fluoride has the disadvantages of low boiling point, easy volatility (19.54°C), high toxicity, strong corrosiveness, and difficulty in control, a complex solution based on hydrogen fluoride has been continuously developed as a substitute for hydrogen fluoride.
Practice has proven that hydrogen fluoride pyridine complex solution is an excellent fluorinating agent. The characteristic is that the complexed hydrogen fluoride is difficult to volatilize, and its diazonium salt can be directly fluorinated without separation, reducing operating steps. Nowadays, a complex solution composed of 30% pyridine and 70% anhydrous hydrogen fluoride is generally called Olah’s reagent (PPHF). The complex solution will not suffer any loss when heated to 50°C. The reaction conditions are mild, the post-processing is convenient, the cost is low, and it can be recycled and reused.
Using m-aminobenzoic acid as the raw material and hydrogen fluoride pyridine reagent as the reaction solvent and fluorination reagent, the important fine chemical intermediate m-fluorobenzoic acid is prepared through a one-pot diazotization reaction.
2. One-step synthesis of m-fluorobenzoic acid by electrochemical method
Using fluorochlorobenzene as raw material, o- (m-, p-) fluorobenzoic acid was synthesized by electrochemical method. The effects of electrode material, reaction temperature, current and reactant concentration on the reaction were investigated. In this reaction, metallic magnesium acts as a supply source of metal ions to generate the magnesium salt of carboxylic acid, which is acidified to obtain the corresponding carboxylic acid. The reaction yield is related to the electrode material. In this article, magnesium metal is used as the anode, and galvanized stainless steel is used as the cathode. The solvent is an aprotic solvent and a small amount of supporting electrolyte needs to be added.
The reaction temperature needs to be below 10°C, constant current electrolysis, and the energization amount is 2.2F/mol. Using galvanized stainless steel as the cathode and magnesium as the anode, the reaction temperature is controlled at about 5°C, the initial concentration of fluorochlorobenzene is 0.50~0.70mol/L, and the yields of o-, m- and p-fluorobenzoic acid are 80%, 75% and 75% respectively. 82%. The small test of the electrolytic cell with a volume of 50mL and the expansion test of 15L have been completed. The pilot test of 100L is currently in progress. Fluorobenzoic acid is synthesized by electrocarboxylation using the consumption of magnesium anode method. The reaction selectivity is good, the yield is high, the reaction conditions are mild and easy to control, the equipment is simple, easy to operate, and the production cost is low. A set of equipment can produce different products according to different needs. Products, industrial production is easy to implement.
Main reference materials
[1]Zhang Kaili, Du Xiaohua. Synthesis process of 3-fluorobenzoic acid[J]. Pesticides, 2018(2):90-92.
[2]Mao Zhen, Yu Chengguang, Zhang Jinjun, et al. One-step synthesis of o-, m- and p-fluorobenzoic acid by electrochemical method [J]. Fine Chemicals, 2007, 24(6):584-586.
