Chemical Properties
white to light yellow crystal powder, solubility in water, ethanol, and methanol, as well as high solubility in organic solvents.
Uses
2-Fluoroisonicotinic acid is a catalyst in organic reactions and serves as a starting material for the synthesis of fluorinated compounds. Furthermore, it plays a role in the synthesis of dyes, pigments, and various other organic compounds.
Synthesis
General procedure for the preparation of 2-fluoroisonicotinic acid:
1. 5.00 g (45 mmol) of 2-fluoro-4-methylpyridine and 1.00 g (17 mmol) of KOH were added to a reaction flask followed by 50 ml of pyridine as solvent.
2. The reaction mixture was heated to reflux.
3. 20.00 g (127 mmol) of potassium permanganate was added in batches over 30 minutes at reflux temperature.
4. After addition, the reaction mixture was continued to be heated at reflux for 1.5 hours.
5. Upon completion of the reaction, the mixture was cooled to room temperature in an ice bath.
6. 100 ml of water was added to the cooled mixture and the pH was subsequently adjusted to 1 with concentrated hydrochloric acid.
7. 100 ml of ethyl acetate was added and the insoluble material was removed by filtration.
8. The aqueous phase was extracted twice with ethyl acetate, 100 ml each time.
9. Combine all ethyl acetate phases and dry with magnesium sulfate.
10. The dried organic phase was concentrated under pressure to give 2.70 g of 2-fluoroisonicotinic acid.
Yield: 42%.
References
[1] Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 2745 - 2766
[2] Patent: US6358978, 2002, B1
[3] Journal of Medicinal Chemistry, 1990, vol. 33, # 6, p. 1667 - 1675
[4] Chemical and Pharmaceutical Bulletin, 1990, vol. 38, # 9, p. 2446 - 2458
[5] Journal of the American Chemical Society, 1949, vol. 71, p. 4152
