酰胺脱水制备腈.docx

酰胺脱水制备腈 2016-07-14 javascript:void(0);有机合成 有机合成 酰胺可在P2O5、POCl3、SOCl2、PCl5等脱水剂存在下进行脱水反应生成腈，此为实验室合成腈的方法之一。将酰胺与P2O5的混合物加热，反应毕将生成的腈蒸出可得到良好的收率。SOCl2最适宜于处理高级的酰胺，这是由于副产物均为气体，易于除去，因而减少精制腈的困难。同时，以上这些脱水试剂多在酸性条件下反应，对于酸敏感的底物是不实用的，因此人们也开发了许多更加温和的方法用于酰胺的脱水，如：Burgess reagent [Et3N+SO2N-COOMe]，三氟醋酸酐(TFAA)－三乙胺，(COCl)2-NEt3-DMSO等条件可以在低温和几乎中性的条件下反应。还有甲烷磺酰氯(CH3SO2Cl)，四氯化钛(TiCl4) 等等。反应实例1.用P2O5为脱水剂的反应实例A solution of 35g (0.16 mol) of 2-(2-ethyl-3-benzofuranyl)-propionamide in 500ml of toluene was refuxed for 18 hours in the presence of P2O5.?The organic phase was decanted off and the residue was carefully decomposed with ice-water and extracted with ether.?The organic phase was washed with water, dried over sodium sulphate and added to the toluenic phase.?The solvent was?evaporated off under reduced pressure and the residue was fractionated to give 23.8g of 2-(2-ethyl-3-benzofuranyl)-propionitrile?(yield 74.4%, boiling point: 105.deg. C. at0.2 mmHg).Reference:?US4124710 ?A1?(1978/11/07)2.用POCl3为脱水剂的反应实例 A mixture of 2-chloro-1,3,4-thiadiazole-5-carboxamide (1.4 g) in 17 ml?of POCl3 is heated at reflux for 18 hours.?The reaction mixture is concentrated and the residue is suspended in 25 ml?of ethyl acetate.?The suspension is cooled in an ice bath and neutralized with saturated, aqueous NaHCO3 (to pH 7). ?The phases are separated and the aqueous phase is extracted with 20 ml?of ethyl acetate. ?The combined organic phases are dried over MgSO4, filtered and concentrated.?The residue is purified by column chromatography (using 30?percent ethyl acetate?/?hexane as eluent) to afford 0.832 g of 2-cyano-5-chloro-1,3,4-thiadiazole. MP: 65-67.?deg.CReference: Patent; EP883611 ?B1?(2002/07/31)?3.用SOCl2为脱水剂的反应实例A solution of thionyl chloride (7.70 g, 0.065 mol) in dry DMF?(10 ml) was added dropwise to a stirred solution of compound?13 (4.20 g, 0.013 mol) in dry DMF (25 ml) at room temperature.?The stirred mixture was heated at 120C for 3 h and poured?into ice–water. The product was extracted into et