无需催化剂,5分钟室温下实现氨酯交换得到酰胺

chem 化学亮点 6.2K+ 0

酰胺键是一种非常常见的一种化学键,广泛存在于天然产物和工业产品中,例如多肽蛋白、农药、高分子材料和药物,制备酰胺最重要的有机反应之一。目前酰胺的最常见合成方法就是羧酸和胺的脱水缩合,这就需要另外加入缩合剂或脱水剂。直接由酯和胺进行胺酯交换制备酰胺是最理想的方法,但是这种转化通常条件苛刻,反应时间长。

最早在上世纪30年代,有文献报道酯与氨直接氨解得到伯酰胺。后来不断改进并广泛用于合成化学和药物合成,通常情况下此反应非常缓慢,但在某些反应中可以使用NaNH2代替NH3直接在液氨中与酯反应或者AlMe3等路易斯酸促进的胺酯交换制备酰胺取得很好的效果。

近期在 nature communications上报道了一篇,利用氨基硼烷钠 (NaNH2BH3 , NaAB )与酯反应制备伯酰胺和仲酰胺的方法,在室温下, 5分钟内定量形成相应的伯酰胺,无需任何催化剂。此外,NaMeNHBH3 (NaMeAB) 也可用于在相同条件下合成N-Me 仲酰胺【 Nat. Commun. , 2021, 2, 5964】。

无需催化剂,5分钟室温下实现氨酯交换得到酰胺   第1张

无需催化剂,5分钟室温下实现氨酯交换得到酰胺   第2张

反应机理

反应操作

General method for the synthesis of primary or secondary amides. Under N2 atmosphere, NaRNHBH3 (R = H, Me) (1.20 mmol) was put into a 10 mL flask which was connected to a Schlenk line and then 5 mL of THF was added. Then 0.5 mmol of substrate ester was added. The reaction mixture was stirred at room temperature and monitored by 1H NMR spectroscopy or TLC. After 5 min, the substrate ester was consumed, and then the solvent was pumped out. Next, the mixed solvent of CH2Cl2 and n-hexane (volume ratio of 10:1) was added to extract RNH2BH3, while Na[R’CONRBH3] (R’ = alkyl, aryl; R = H, Me) and other boroncontaining compounds are left in the residual. Then, add 15 mL water into the flask and stir for 15 min. Addition of ethyl acetate extract the product (7–8 times) and the organic phases are collected and dried. The amide products with high purity and yield were obtained.

参考资料

Efficient synthesis of primary and secondary amides via reacting esters with alkali metal amidoboranes;Yu Guo , Ruo-Ya Wang, Jia-Xin Kang , Yan-Na Ma, Cong-Qiao Xu , Jun Li✉ & Xuenian Chen✉; Nat. Commun. 2021, 2, 5964


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