Glycerol → Quinoline, 7,8-Difluoro-

Participants

Reaction Conditions

Reaction Steps

In a 3 L eggplant-shaped flask containing a stir bar, 80% sulfuric acid (607.7 g, 49.57 mol) was introduced and cooled to 0° C., and then 2,3-difluoroaniline (160.0 g, 1.24 mol) was slowly added. After the addition, the mixture was stirred for 1 hour at room temperature, sodium iodide (1.85 g, 12.3 mmol) was further added thereto, and then the mixture was heated in an oil bath until the temperature thereof reached 150° C. (temperature of the bath). When it reached this temperature, glycerin (125.5 g, 1.36 mol) was added dropwise over a period of one hour, and the mixture was stirred for 1 hour at 150° C. The temperature of the bath was further elevated to 180° C., and the water was evaporated over a period of 2 hours using a distillation apparatus. After confirming that the starting material had disappeared, the mixture was neutralized using 10N aqueous sodium hydroxide while cooling with an ice-water bath (the inner temperature is 60 to 70° C.). After the neutralization, before the inner temperature returned to room temperature, the resultant was subjected to extraction with ethyl acetate, and the extract was dried with magnesium sulfate, filtered, and concentrated. The thus obtained crude product was purified by silica gel column chromatography (normal hexane:ethyl acetate) to obtain 185.5 g of 7,8-difluoroquinoline (91%) as a hazel solid.

Provenance & Evidence