Rh(I)中间体及抗高血压药物用手性催化剂的合成及性能研究

Synthesis,characterization and catalytic performance of[Rh(COD)(S,S)-Meduphos)]in the antihypertensive drug Ramipril

在微压状态下,以95%的乙醇为溶剂,三氯化铑、乙烯等为原料,合成了Rh(I)中间体,产率85%;再以该中间体、1,5-环辛二烯、四氟硼酸银和(+)-1,2-双((2S,5S)-2,5-二甲基膦基)苯为原料,四氢呋喃为溶剂合成了Rh(I)手性催化剂,产率91.09%。采用元素分析、^(1)H-NMR、^(13)C-NMR、MS-ESI+和IR对其化学结构进行了表征。以合成抗高血压药物雷米普利为反应模型进行催化活性评价,结果表明,该手性催化剂与商业对照品的催化活性相当,转化率≥70%,产品光学纯度≥98%。

Under the condition of micro-pressure,the Rh(I)intermediate was prepared in one-step process from RhCl3·3H2O in 95%ethanol solvent by filling with ethylene gas.The ylied was≥85%.A quqntitative reaction of the Rh(I)intermediate with 1,5-cyclooctandiene,AgBF4 and(S,S)-meduphos in tetrahydrofuran produced the desired chiral catalyst[Rh(COD)(S,S)-Meduphos)]BF_(4) with a yield of 91.09%.The structrues were confirmed by means of elemental analysis,^(1)H-NMR,^(13)C-NMR,FT-IR and MS-ESI+.The catalytic activity in the preparation of Ramipril was found to be≥70%in terms of the conversion rate and optical purity of the product was 98%ee,comparable to the activity and selectivity obtained by using the commercially available catalyst.