DAST

  • A+

DAST室温下是黄色液体,在干燥情况下室温或冰箱能长期保存,DAST90oC会分解,处理不当会有爆炸的危险。但由于操作简单和通用性强,DAST是使用得最广泛的氟代试剂之一。这个试剂能将羟基化合物转化为单氟代化合物,醛和酮转化为二氟代化合物,而对羧酸及其衍生物的羰基则没有影响。

 

所以在羧酸及其衍生物如酯,内酯,酰胺,内酰胺等存在下,能选择性的取代羟基,醛和酮

 


 

脂肪族和芳香族的伯,仲,叔醇都能高产率的转化为相应的氟化合物。反应通常用二氯甲烷,一氟三氯甲烷等作溶剂,取代羟基通常在较低温度下反应(-78oC),取代羰基一般在0oC40oC反应。


 

反应示例

 



 

dry, 1-L, three-necked, round-bottomed flask is fitted with a 500-mL dropping funnelthermometer, a magnetic stirrer, and a reflux condenser protected from the atmosphere with a drying tube.  The apparatus is flushed with dry nitrogen, and 150 mL of dry dichloromethane and 21 mL (0.16 mole) of diethylaminosulfur trifluoride [Org. Synth.Coll. Vol. 6, 440 (1988)] are added to the flask.  The contents of the flask are cooled to 10°, and a solution of 23 g (0.150 mole) of 4-nitrobenzyl alcohol in 450 mL of dichloromethane is added dropwise at a fast rate (45 minutes).  The reaction mixture is allowed to come to room temperature and poured into a beaker containing 300 g of ice, decomposing any unreacted diethylaminosulfur trifluoride.  The organic layer is separated, and the water layer is extracted twice with 45-mL portions of dichloromethane.  The organic layer and extracts are combined, washed with 150 mL of water, and dried over anhydrous magnesium sulfate.  Evaporation to dryness under reduced pressure gives 20.9–22.1 g (90–95%) of crude product.  Recrystallization from 500 mL of pentane yields 15.5 g. (67%) of 4-nitrobenzyl fluoride as colorless needle-shaped crystals, m.p. 36–37°



The starting material (2.20 g, 9 mmol) in 15 mL of DCM was cooled to - 50 °C, then Et2NSF3 (2.47 mL,18.7 mmol) was added. After 10 minutes, the cooling bath was removed, and the mixture was stirred overnight. NaHCO3 solution was added slowly to the mixture and the mixture was extracted with dichloromethane (3X). The combined organics were dried with Na2SO4 and purified with flash chromatography (10percent ethyl ACETATE/HEXANE) to provide the difluoroester (1.81 g, 91percent). MS (CI) m/z 266 (M+H) +.(Patent; ABBOTT LABORATORIES; WO2005/23762; (2005); (A1) English)



Diethylaminosulfur trifluoride (32.10 mmol, 4.24 mL) was added drop-wise to a solution of 3- oxocyclobutanecarbonitrile (16.00 mmol, 1.52 g) in dichloromethane (50 mL) under N2 over 5 minutes. The mixture was allowed to warm to room temperature then stirred overnight. A further 2.12 mL of  diethylaminosulfur trifluoride was added then the mixture was heated at reflux for 4 hours then allowed to cool to room temperature. The mixture was poured into ice-cold saturated aqueous sodium bicarbonate solution with vigorous stirring. The organics were isolated by phase separator cartridge then concentrated under reduced pressure without external heating. The crude product was purified by column chromatography (silica gel, diethyl ether) to give the title compound as brown oil (1.72 g, 92percent).

[Patent; ONO PHARMACEUTICAL CO., LTD.; SAITO, Tetsuji; HIGASHINO, Masato; KAWAHARADA, Soichi; LEWIS, Arwel; CHAMBERS, Mark Stuart; RAE, Alastair; HIRST, Kim Louise; HARTLEY, Charles David;WO2015/115673; (2015); (A1) English]


本文内容编辑自网络。


weinxin
我的微信
关注我了解更多内容

发表评论

目前评论:0