4-Amino-3-fluorobenzoic acid

Chemical Properties

Fine Needles

Uses

4-Amino-3-fluorobenzoic acid serves as a synthetic precursor for the preparation of 3-fluoro-4-acetamidobenzoic acid via acetylation with acetic anhydride, and reacts with 2-ethylbutyryl chloride to yield 4-(2-ethyl-butyramido)-3-fluorobenzoic acid. Its reaction with 1-piperidinecarbonyl chloride produces either piperidino aryl anhydride or N-aroyl-piperidine, depending on the workup conditions. In the synthesis of benzothiazole derivatives, it condenses with 2-aminothiophenol in polyphosphoric acid to generate 2-(4-amino-3-fluorophenyl)benzothiazole. Additionally, it functions as a monotopic linker in the construction of the metal-organic framework B-MV-PCN-521-R[4-8].

Synthesis

In a 1000 mL round-bottomed single-necked flask, 3-fluoro-4-nitrobenzoic acid (30 g, 190 mmol) was dissolved in 300 mL of a solvent mixture of methanol and tetrahydrofuran, and carbon-loaded palladium (2 g) was added as a catalyst. The reaction system was charged with hydrogen and the reaction was stirred at room temperature for 15 hours. Upon completion of the reaction, the reaction mixture was filtered through diatomaceous earth and the filtrate was collected. The filtrate was dried to give a white solid product. The white solid was further dried in an oven to finally obtain 3-fluoro-4-aminobenzoic acid (24.86 g, 98.6% yield).

References

[1] Patent: CN105294567,  2016,  A. Location in patent: Paragraph 0033-0036
[2] Tetrahedron,  2018,  vol. 74,  # 47,  p. 6795 - 6803
[3] Journal of the American Chemical Society,  1944,  vol. 66,  p. 1631
[4] Bioorganic and Medicinal Chemistry,  2016,  vol. 24,  # 12,  p. 2697 - 2706
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[6] Borišek, J., Vizovišek, M., Sosnowski, P., Turk, B., Turk, D., Mohar, B., Novič, M. (2015). Development of N -(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors. Journal of Medicinal Chemistry, 58(17), 6928–6937. https://doi.org/10.1021/acs.jmedchem.5b00746
[7] García-Báez, E. V., Padilla-Martínez, I. I., Tamay-Cach, F., Cruz, A. (2021). Benzothiazoles from Condensation of o-Aminothiophenoles with Carboxylic Acids and Their Derivatives: A Review. Molecules, 26(21), 6518. https://doi.org/10.3390/molecules26216518
[8] Chen, W., Li, S., Yi, L., Chen, Z., Li, Z., Wu, Y., Yan, W., Deng, F., Deng, H. (2024). Precise Distance Control and Functionality Adjustment of Frustrated Lewis Pairs in Metal–Organic Frameworks. Journal of the American Chemical Society, 146(17), 12215–12224. https://doi.org/10.1021/jacs.4c03133