Preparation methods and applications of 3-chloro-2-fluoropyridine_Industrial additives

Preparation method, application background and overview of 3-chloro-2-fluoropyridine

3-Chloro-2-fluoropyridine is an organic intermediate that can be obtained from 2-nitro-3-chloropyridine or 2,3-dichloropyridine through one-step fluorination. 3-Chloro-2-fluoropyridine can be used to prepare 3-chloro-2-hydrazinopyridine. 3-Chloro-2-hydrazinopyridine is an important intermediate in the synthesis of new fish-acceptor insecticides chlorantraniliprole and cyantraniliprole. This type of insecticide mainly acts on the insect’s calcium ion channel, causing the insect’s muscles to relax and anesthetize.

Preparation method and application of 3-chloro-2-fluoropyridine

Preparation method and application report 1 of 3-chloro-2-fluoropyridine,

General procedure E: In a dry bismuth borate drying oven, combine anhydrous NMe₄F (18.6 mg, 0.2 mmol, 2 equivalents) and an appropriate aryl chloride or nitroarene substrate. (0.1 mmol, 1 equivalent) was weighed into a 4 mL vial equipped with a micro stirring rod. DMF (0.5 mL) was added, the vial was removed from the dry box and stirred at room temperature for 24 hours unless otherwise stated. The reaction was cooled to room temperature and the internal standard (1,3,5-trifluorobenzene, 100 μL of 0.5 M in toluene) was added. Aliquots were taken for analysis by 19F NMR spectroscopy and GCMS.

Following general procedure E, using 2-nitro-3-chloropyridine (15.8 mg, 0.1 mmol, 1 equiv) afforded 3-chloro-2-fluoropyridine in 94% yield as obtained from the crude reaction mixture Determined by 19FNMR spectral analysis. The product showed a 19F NMR signal at -72.54 ppm in DCM (-73.03 ppm in DMSO in the literature) (same source as above). The identity of the product 3-chloro-2-fluoropyridine was further confirmed by GCMS analysis, where the product peak was observed at 5.48 min. The yield (94%) represents the average of two runs of experiments ([94% ​​(above) and 94%).

Preparation method and application report 2 of 3-chloro-2-fluoropyridine,

Cesium fluoride (2.053 g, 13.51 mmol) was added to a solution of 2,3-dichloropyridine (1.00 g, 6.76 mmol) in dimethyl sulfoxide (33.8 ml) at room temperature. The mixture was stirred in air at 110°C for 20 hours. The mixture was quenched with water at room temperature. The reaction mixture was extracted with EtOAc. Separate the organic layer. The organic layer was washed with water and brine. The organic layer was dried over anhydrous sodium sulfate. The organic layer was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluting with ethyl acetate in hexane) to give 3-chloro-2-fluoropyridine.

Preparation methods and applications of 3-chloro-2-fluoropyridine

CN201310471317.9 discloses a synthesis method of 3-chloro-2-hydrazinopyridine, which is characterized by mixing 3-chloro-2-fluoropyridine and hydrazine hydrate evenly, adding ethanol solvent, and reacting at room temperature for 3-5 After an hour, the solvent was dried and evaporated to obtain 3-chloro-2-hydrazinopyridine. The preparation method of 3-chloro-2-hydrazinopyridine of the present invention has a simple operation process and can obtain a high-yield and high-quality product without heating and refluxing. The product yield can reach 99.53%, and the product purity can reach 99.95%.

Reference text Hexahydroxypentacobalt dicarbonate

[1][Chinese invention] CN201680052780.1 Method for fluorinating compounds

[2] Taisuke, Katoh. Facile Preparation of 3-Substituted-2,6-difluoropyridines and Application to the Synthesis of 2,3,6-Trisubstituted Pyridines for PKCθ Inhibitors[J]. Journal of Synthetic Organic Chemistry, Japan , 2020, 78(2):121-129.

[3] CN201310471317.9 A synthesis method of 3-chloro-2-hydrazinopyridine