新型苯甘氨酸衍生物“刷型”手性固定相的制备及其应用  

Preparation and Application of Novel Brush-type Chiral Stationary Phases Based on Phenylglycine Derivatives

作　　者：宾琴 付克勤[1] 张俊俊[1] 陈伟[1] 柏正武[1] 

机构地区：[1]武汉工程大学化学与环境工程学院,湖北武汉430073

出　　处：《合成化学》2015年第1期1-6,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(50973086)

摘　　要：以氨基酸(1a^1c)为原料,经两步反应合成了3个N-酰基-D-苯甘氨酸甲酯(4a^4c);D-2-氯苯甘氨酸和3,5-二甲基苯甲酰氯或D-4-氯苯甘氨酸和3,5-二硝基苯甲酰氯分别经缩合反应合成了N-3,5-二甲基苯甲酰基-D-2-氯苯甘氨酸(6)或N-3,5-二硝基苯甲酰基-D-4-氯苯甘氨酸(7)。其中4b,4c,6和7为新化合物,其结构经1H NMR,IR和元素分析表征。分别以胺-酯交换法和缩合反应将4a,4c,6和7固定在氨丙基硅胶表面,制得4种新型的"刷型"手性固定相4a',4c',6'和7'。研究结果表明,以缩合法制备的6'和7'的手性选择体负载量相对较高,分别为0.24 mmol·g-1和0.33 mmol·g-1。以胺-酯交换法制备的4a'和4c'的负载量分别为0.11 mmol·g-1和0.10 mmol·g-1。用4-二甲基氨基吡啶和1-羟基苯并三唑为催化剂能避免N-酰基-D-苯甘氨酸甲酯在固定化反应中的消旋化。初步评价了6'的分离性能,结果显示6'在以乙腈-水为流动相时有较好的对映体选择性。Three N-acyl-D-phenylglycine methyl esters（ 4a ～ 4c） were prepared by a two-step reaction with the amino acids（ 1a ～ 1c） as the raw materials. N-3,5-dimethylbenzoyl-D-2-chlorophenylglycine（ 6） or N-3,5-dinitrobenzoyl-D-4-chlorophenylglycine（ 7） was synthesized by condensation reaction of D-2-chlorophenylglycine and 3,5-dimethylbenzoyl chloride or D-4-chlorophenylglycine and3,5-dinitrobenzoyl chloride. 4a,4c,6 and 7 were new compounds and their structures were characterized by1 H NMR,IR and elemental analysis. Four novel brush-type chiral stationary phases（ 4a＇,4c＇,6＇and 7＇） were prepared by immobilizing 4b,4c,6 and 7 on 3-aminopropyl silica gel through a condensation or an amine-ester exchange reaction,respectively. The results indicated that 6＇ and 7＇which were prepared by a condensation reaction possessed comparatively higher loading capacities of chiral selectors that were 0. 24 mmol·g^-1and 0. 33 mmol·g^-1. The loading capacities of 4a＇ and4c＇ which were prepared by an amine-ester exchange reaction were 0. 11 mmol · g^-1and 0. 10mmol·g^-1. During the immobilization of N-acyl-D-phenylglycine methyl esters,the racemization could be avoided by using 4-（ N,N-dimethylamino） pyridine and 1-hydroxy-1,2,3-benzotriazole as the joint catalysts. The enantioseparation property of 6＇ was preliminarily evaluated,and the results revealed that 6＇ bear better enantioselectivity in the reversed-phase consisting of acetonitrile and water than in other mobile phase conditions.

关 键 词：苯甘氨酸衍生物 手性固定相 消旋化 固定化方法 制备 应用 

分 类 号：O623.736[理学—有机化学] O65[理学—化学]