2-Chloro-6-(trifluoromethyl)pyridine

Colorless to off-white liquid (or White to off-white crystal)

2-chloro-6-trichloromethyl pyridine (700 g, 3.03 moles, feed rate 1.24 g/min) and anhydrous hydrogen fluoride (936 g, 46.8 moles, feed rate 1.66 g/min) in the absence of inert gas were fed in to a tubular reactor packed with pre activated chromia- alumina catalyst (210 g) at 330°C. Reactor outlet material was collected in ice-cooled water and it was extracted with dichloromethane. Dichloromethane layer was washed with 10percent potassium hydroxide solution and the organic layer was separated out and it was concentrated to get 490.0 g of crude 2-chloro-6-trifluoromethypyridine. The purity of crude product was 95.03 percent by GC analysis. Reaction yield on the basis of crude product obtained is 89 percent. The crude product was purified by fractional distillation to obtain 2-chloro-6-trifluoromethlypyridine with the Purity (percent): 98.0 Yield (percent): 80.0(1), 2000 g of reaction flask A was charged with 700 g of concentrated hydrochloric acid at a concentration of 36percent by weight and 162.1 g2-amino-6-trifluoromethylpyridine was heated to 70 ° C, stirred for 1 hour, after the completion of the reaction to -2 to 2 ° C, 177.5 g of a sodium nitrite solution having a concentration of 40percentDropping the diazonium salt solution;(2), 500 ml of a hydrochloric acid solution having a concentration of 18percent by weight and 129.4 g of cuprous chloride were added to another reaction flask B, and the mixture was heated to 65C. The resulting diazonium salt solution was added dropwise, Reaction for 2 hours, After the completion of the reaction, the pH of the reaction solution was adjusted to 10 with a sodium hydroxide solution having a concentration of 46percent by weight. Then, 550 g of ethyl acetate was added thereto, followed by stirring. The organic layer was extracted and extracted twice, The organic layer was combined and the organic layer was distilled off to remove ethyl acetate to give a pale yellow liquid. The pale yellow liquid was cooled to room temperature to give 186.3 g of solid 2-chloro-6-trifluoromethylpyridine.A 300 ml high pressure reactor equipped with overhead condenser with controlled valve, mechanical stirrer and pressure gauge was charged with 2-chloro-6-(trichloromethyl)pyridine (231 gm) and ferric chloride (11 gm). The mixture was heated and anhydrous hydrogen fluoride was added into the reaction mixture under agitation. The temperatures of the mixture was maintained at 170±10 °C and at a pressure of 20±5 kg/cm for 18 hours with continuous feeding of anhydrous hydrogen fluoride at the rate of 20 gm/hr. Reaction mixture was maintained further for 4 hours. The excess HF and hydrochloric acid gas generated were vented, scrubbed and separated as per conventional method and recycled. The completion of reaction was monitored by gas chromatography. After the completion of reaction, the reactor was depressurized to atmospheric pressure and flushed with nitrogen. Reaction product was distilled, diluted with water, neutralized with 5percent aqueous solution of sodium carbonate, layer separated and analysed. The results obtained as per gas chromatography were: 2-fluoro-6- (trifluoromethyl)pyridine: 90.96 percent; 2-chloro-6-(trifluoromethyl)pyridine: 7.67 percent; 2-chloro-6- (trichloromethyl)pyridine: 0.001 percent. The obtained product was distilled to obtain 2-fluoro-6- (trifluoromethyl)pyridine with 85percent yield and 99.97percent GC purity. The distillation residue containing partially fluorinated chlorofluoropyridine compounds was recycled back. The product was confirmed by mass spectroscopy and 1HNMR.A 300 ml high pressure reactor equipped with overhead condenser with controlled valve, pressure gauge and mechanical stirrer was charged with 2-chloro-6-(trichloromethyl)pyridine (231 gm). The solution was heated and anhydrous hydrogen fluoride (260 gm) was added into the reaction mixture under agitation in approx 20 hours at 190±10 °C and 20-30 kg/cm pressure. Reaction mixture was maintained further for 8 hours. The excess HF and hydrochloric acid gas generated were vented, scrubbed and separated as per conventional method and recycled. The completion of reaction was monitored by gas chromatography. After the completion of reaction, the reactor was depressurized to atmospheric pressure and flushed with nitrogen. Reaction product was distilled, diluted with water, neutralized with 5percent aqueous solution of sodium carbonate and layer separated. The obtained product layer was analyzed by gas chromatography and the results obtained were: 2-fluoro-6- (trifluoromethyl)pyridine:- 51.87percent; 2-chloro-6-(trifluoromethyl)pyridine: 38.66percent; 2-chloro-6- (difluorochloromethyl)pyridine: 8.22percent. The obtained product was distilled to get 2-fluoro-6- (trifluoromethyl)pyridine with 99.97percent GC purity. The product was confirmed by mass spectroscopy and 1H NMR. The distillation residue containing partially fluorinated chlorofluoropyridine compound was recycled back.A 300 ml high pressure reactor equipped with overhead condenser with controlled valve, mechanical stirrer and pressure gauge was charged with 2-chloro-6-(trichloromethyl)pyridine (1 16 gm). The solution was heated and anhydrous hydrogen fluoride (55 gm) was added into the reaction mixture in one lot under agitation. The reaction was maintained at a temperature 150-175 °C under autogenously developed pressure for 12 hours. After the completion of reaction, the reactor was depressurized to atmospheric pressure and flushed with nitrogen. The reaction product was diluted in ice water, neutralized with soda ash aqueous solution, followed by steam distillation and analysed. The results obtained as per gas chromatography were: 2-fluoro-6-(trifluoromethyl)pyridine: 40.28percent; 2-chloro-6-(trifluoromethylpyriidne: 48.49percent; 2-chloro-6-(difluorochloromethyl)pyrdine: 10.22percent; 2-chloro-6- (0063) (trichloromethyl)pyriditte: 0.01 1percent. The product was confirmed by mass spectroscopy and 1H NMR.To a stirred solution of Representative synthesis of key intermediate 3-(5-chloro-6-(1122) ( trifluoromethyl)pyridin-2-yl)-l , 2, 3-oxathiazolidine 2, 2-dioxide : The mixture of

Molecular Weight:181.54
XLogP3:2.7
Hydrogen Bond Acceptor Count:4
Exact Mass:180.9906113
Monoisotopic Mass:180.9906113
Topological Polar Surface Area:12.9
Heavy Atom Count:11
Complexity:136
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes