《Table 1 Optimization of the reaction conditionsa》
本系列图表出处文件名:随高清版一同展现
《B_2pin_2参与的含硼酸酯的芳香胺和醛的一锅两步还原胺化反应(英文)》
The model reaction of 3-aminophenylboronic acid pinacol ester(1a,1.0 equiv.)and benzaldehyde(2a,1.0equiv.)was chosen to optimize the reaction parameters and the results are summarized in Table 1.Firstly,the reaction was kept in iPr OH at 25℃for 1 h under argon to obtain the intermediate(E)-N-benzylidene-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline.Secondly,B2pin2(3.0 equiv.)and tBu OK(2.0 equiv.)were added to the reaction and the mixture was stirred for 4 h at 110℃under argon(Table1,Entry 1).The desired reductive amination product 3a was observed in 32%yield in HPLC detection.Encouraged by this preliminary result,various reaction parameters,including bases,solvents and temperature were screened to optimize the reaction conditions.When a series of bases were studied,NaOH was found to be the best choice(Table1,Entries 1~6).The reaction did not work without base.It indicated that the base is essential for the reaction(Table 1,Entry 7).When the solvent was changed to EtOH,the yield improved to 77%.Whereas,other solvents such as MeOH,nPrOH,THF,dioxane and H2O were found to be less effective for the reaction(Table 1,Entries 8~13).The effect of temperature was also studied,and the best yield was obtained under 110℃(Table 1,Entries 14,15).When the amount of B2pin2 decreased to 2.0 equiv.,the yield of the desired product reduced to 66%(Table 1,Entry 16).Increasing the amount of 2a to 1.2 equiv.,the yield of the target product 3a improved to 82%(Table 1,Entry 17).Under air atmosphere,the desired product 3a was obtained in 76%yield(Table 1,Entry 18).Lowering the amount of base,the yield of 3a was slightly decreased(Table 1,Entries 19,20).Consequently,the optimized reaction conditions for the one-pot,two-step reductive amination were determined as follows:firstly,3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline(1a,1.0 equiv.)and benzaldehyde(2a,1.2 equiv.)were kept in EtOH at 25℃for 1h under argon.Secondly,B2pin2(3.0 equiv.)and NaOH(2.0equiv.)were added to the reaction and the mixture was stirred for 4 h at 110℃oil bath under argon.
图表编号 | XD00212951900 严禁用于非法目的 |
---|---|
绘制时间 | 2019.07.01 |
作者 | 刘雪滢、刘振伟、郭圆圆、李敬亚、邹大鹏、吴豫生、吴养洁 |
绘制单位 | 郑州大学化学与分子工程学院、郑州大学化学与分子工程学院、郑州大学化学与分子工程学院、郑州泰基鸿诺医药股份有限公司、郑州大学化学与分子工程学院、郑州泰基鸿诺医药股份有限公司、郑州大学化学与分子工程学院 |
更多格式 | 高清、无水印(增值服务) |