4-CHLORO-2,5-DIFLUOROBENZONITRILE synthesis
- Product Name:4-CHLORO-2,5-DIFLUOROBENZONITRILE
- CAS Number:135748-35-5
- Molecular formula:C7H2ClF2N
- Molecular Weight:173.55
508203-26-7
135748-35-5
The general procedure for the synthesis of 4-chloro-2,5-difluorobenzonitrile from 4-chloro-2,5-difluorobenzamide was as follows: a mixture of 4-bromo-2,5-difluorobenzoic acid (11a, 53.28 g), thionyl chloride (165 mL), and N,N-dimethylformamide (DMF, 0.87 mL) was stirred for 1.5 hr at 80 °C, and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in chloroform (300 mL). To this solution, 28 wt% ammonia (300 mL) was slowly added dropwise at 5 °C and stirred for 0.5 h at the same temperature. After completion of the reaction, the mixture was extracted with chloroform, the organic layers were combined and dried over anhydrous sodium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure to give a pale yellow solid. The solid was mixed with phosphoryl chloride (195 mL) and stirred at 80 °C for 2 h. After completion of the reaction it was cooled to room temperature. The reaction mixture was concentrated under reduced pressure and the residue was treated with ether (500 mL) and ice water (300 mL) followed by stirring for 0.5 h at room temperature. The mixture was extracted with ether and the organic layer was washed sequentially with saturated aqueous sodium bicarbonate and brine, then dried over anhydrous sodium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure to afford the target product 4-chloro-2,5-difluorobenzonitrile (9h, 41.57 g, 85% yield) as a light yellow solid.
508203-26-7
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135748-35-5
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Yield:135748-35-5 41.57 g
Reaction Conditions:
with trichlorophosphate at 80;
Steps:
5.5 4-Bromo-2,5-difluorobenzonitrile (9h)
General procedure: A mixture of 4-bromo-2,5-difluorobenzoic acid (11a, 53.28 g), thionyl chloride (165 mL) and DMF (0.87 mL) was stirred at 80 °C for 1.5 h, and cooled down to room temperature. The mixture was evaporated in vacuo, and the resulting residue was dissolved in chloroform (300 mL). To the solution was added dropwise 28 wt % aqueous ammonia (300 mL) at 5 °C, and the mixture was stirred at 5 °C for 0.5 h. The mixture was extracted with chloroform, and the organic layer was dried. The desiccant was removed by filtration and the filtrate was evaporated in vacuo to obtain a pale yellow solid. The mixture of the obtained solid and phosphoryl chloride (195 mL) was stirred at 80 °C for 2 h, and cooled down to room temperature. The mixture was evaporated in vacuo, and the resulting residue was treated with diethyl ether (500 mL) and ice-water (300 mL), then stirred at room temperature for 0.5 h. The mixture was extracted with diethyl ether and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine, and then dried. The desiccant was removed by filtration and the filtrate was evaporated in vacuo to obtain 9h (41.57 g, 85%) as a pale yellow solid.
References:
Negoro, Kenji;Yonetoku, Yasuhiro;Misawa-Mukai, Hana;Hamaguchi, Wataru;Maruyama, Tatsuya;Yoshida, Shigeru;Takeuchi, Makoto;Ohta, Mitsuaki [Bioorganic and Medicinal Chemistry,2012,vol. 20,# 17,p. 5235 - 5246]
132794-08-2
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135748-35-5
131 suppliers
$14.00/250mg
132794-07-1
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$5.00/1g
135748-35-5
131 suppliers
$14.00/250mg