Chemical Properties
White solid
Uses
4-Fluorosalicylic acid is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.
General Description
4-Fluorosalicylic acid can be synthesized from the following compounds:
- 4-fluorotoluene
- m-fluorophenol
- 4-aminosalicylic acid
Synthesis
General procedure for the synthesis of 4-fluorosalicylic acid from 2,4-difluorobenzoic acid: dimethylsulfoxide (DMSO, 4 L), 2,4-difluorobenzoic acid (500 g, 3.16 mol) and sodium hydroxide (NaOH, 253 g, 6.32 mol) were added to a dry 10 L four-neck flask. The mixture was heated to 130 °C and reacted for about 8 h, during which the progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction system was cooled to room temperature. Subsequently, the reaction solution was slowly poured into 40 L of ice water and the pH was adjusted to 23 with concentrated hydrochloric acid (care was taken that the temperature did not exceed 20 °C during the adjustment). At this time, a large amount of solid precipitated, continue to stir for 2 hours and then pump-filtered. The filter cake was washed with appropriate amount of water to obtain a white solid. The resulting solid was dried under reduced pressure at 60°C for 12 h. 450 g of 4-fluorosalicylic acid was finally obtained with a yield of 90% and a melting point of 184.9-185.2°C. The solid was dried at 60°C for 12 h under reduced pressure.
References
[1] Journal of Fluorine Chemistry, 2003, vol. 121, # 1, p. 97 - 99
[2] Patent: CN107501260, 2017, A. Location in patent: Paragraph 0030; 0031; 0033; 0034
[3] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 21, p. 5661 - 5675
[4] Patent: WO2013/148857, 2013, A1. Location in patent: Paragraph 00393; 00407; 00417
