Uses
The 8-fluoroquinoline core serves as a ligand in palladium complexes, where the fluorine atom coordinates to the metal center and participates in nucleophilic substitution reactions or acts as a precursor for copper-free Sonogashira-type cross-coupling [3].
Synthesis
1. 85% sulfuric acid (623 g) was added to a 1 L reaction flask and o-fluoroaniline (133 g, 1.2 mol) was added slowly and dropwise.
2. The reaction mixture was heated to 130 °C and stirred at this temperature for 2 hours.
3. maintaining the reaction temperature at 130 °C, glycerol (121 g, 1.3 mol) and potassium iodide (3 g) were added slowly dropwise to the mixture.
4. After completion of the dropwise addition, the reaction mixture was continued to be stirred at 130 °C for 18 hours.
5. The reaction solution was cooled to room temperature and then slowly poured into ice water for quenching.
6. After quenching, aqueous sodium hydroxide solution was added dropwise to adjust the pH to 8-9.
7. Extraction was carried out with methyl tert-butyl ether, the oil layer was separated and concentrated.
8. The concentrate was distilled under high vacuum by means of a filled distillation column to give 8-fluoroquinoline (146 g) of high purity.
9. The yield was 83% and gas chromatographic analysis showed a purity of 99.7%.
References
[1] Patent: CN107698503, 2018, A. Location in patent: Paragraph 0061-0072
[2] Biological and Pharmaceutical Bulletin, 1997, vol. 20, # 6, p. 646 - 650
[3] Scharf, A., Goldberg, I., & Vigalok, A. (2012). Evidence for Metal–Ligand Cooperation in a Pd–PNF Pincer-Catalyzed Cross-Coupling. Journal of the American Chemical Society, 135(3), 967–970.
https://doi.org/10.1021/ja310782k
