N-酰基戊二酰亚胺开环/选择性水解制备伯酰胺

近期高雄医学大学医药暨应用化学系的Wei-Yu Lin和Karthick Govindan报道了N-酰基戊二酰亚胺开环/选择性水解可以制备得到伯酰胺。

此方法利用两个当量的氢氧化锂作为碱在室温下反应，戊二酰亚胺首先开环，接着选择性C-N键断裂得到伯酰胺。此方法可以高产量高选择性的制备各种芳基和脂肪酰胺，另外可以利用流动化学方法实现克极制备伯酰胺。反应利用水作为溶剂，环境友好。

反应机理

羟基负离子首先亲核进攻戊二酰亚胺开环，然后通过两种路径进行水解C-N键：一种是另外一个当量的羟基负离子直接水解得到伯酰胺和戊二酸；另外开环的戊二酸进行分子内的亲核进攻，生成伯酰胺和戊二酸酐。

操作步骤：

To a vial was charged with starting material 1a-z & 1aa-ag (0.3 mmole) and LiOH.H2O (0.6 mmole) at room temperature, and H2O (3ml) was added. The reaction was stirred for 2 h. The reaction was diluted with ethyl acetate (15 mL), washed with brine (5 mL × 2). The organic layer was dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude product was triturated with hexane.

【Org. Lett. 2021, 23, 1600–1605】