Uses
4-(Trifluoromethyl)-3-Pyridinecarboxylic Acid is a useful synthetic intermediate. It can be used to prepare pyridine carboxamides as palm site inhibitors of HCV NS5B polymerase. It can also be used to synthesize pyrazolylcarboxanilides as Ca2+ release-activated Ca2+ (CRAC) channel inhibitors.
Application
4-(Trifluoromethyl)nicotinic acid is a trifluoromethyl-containing aromatic compound with unique biological activity, which can be used as a precursor material for the preparation of other pesticides or medicines. 4-(Trifluoromethyl)nicotinic acid is a key intermediate of flonicamid, a highly effective insecticide.
Definition
ChEBI: 4-(trifluoromethyl)nicotinic acid is a member of pyridines and an aromatic carboxylic acid.
Preparation
synthesis of 4-(Trifluoromethyl)nicotinic acid: add 5g (0.0192mol) Methyl 2,6-dichloro-4-(trifluoromethyl)nicotinate in turn to a 100mL three-necked flask, 0.3g of 10% Pd/C (water content 63.45%) ), 5.25g (0.0389mol) CH3COONa 3H2O and 20mL ethanol, after stirring and dissolving, nitrogen was replaced 3 times to discharge air, after hydrogen replacement 2 times, the reaction was stirred at room temperature for 8h under a hydrogen atmosphere until no hydrogen was absorbed to complete the reaction, and suction filtration was recovered. Palladium carbon, washed the filter cake 3 times with ethanol, the filtrate was rotary evaporated to remove the solvent, added 20 mL of water to the obtained solid, fully shaken to dissolve it, added hydrochloric acid to adjust pH=2～3, extracted 3 times with ethyl acetate, The organic phases were combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and rotary-evaporated to obtain 3.3 g of a pale yellow solid with a yield of 90.4%.
Synthesis
General procedure for the synthesis of 4-(trifluoromethyl)nicotinic acid from 4-(trifluoromethyl)nicotinamide: 9.5 g of 4-(trifluoromethyl)nicotinamide, 1.5 g of Pd/MCM-22 catalyst, and 40 ml of a 25% aqueous sodium hydroxide solution were added to a 250-mL flask at room temperature. The reaction mixture was heated to 100 °C and kept reacting for 4 hours until the solid was completely dissolved to form a light yellow transparent solution. Upon completion of the reaction, the mixture was cooled to room temperature, the pH was adjusted to 2 with concentrated hydrochloric acid, stirred and diafiltrated. The residue was washed with water and dried to give 4-trifluoromethylnicotinic acid as a white powdery solid.
References
[1] Patent: CN108586328, 2018, A. Location in patent: Page/Page column 4-7
[2] Patent: EP1460071, 2004, A1. Location in patent: Page 40
