建立苯乙烯环氧化反应的筛选方法及烯丙醇环氧化反应研究

发布时间：2018-06-19 09:09

本文选题：苯乙烯 + 环氧化　；参考：《泸州医学院》2014年硕士论文

【摘要】：目的：手性环氧化合物具有重要的生理活性，许多重要的医药中间体可由其选择性开环反应和官能团转化获得，其中备受关注的是作为医药和精细化工品中间体的手性环氧苯乙烷。对于手性环氧化物的测定通常采用手性高效液相色谱法或气相色谱法，但应用于苯乙烯环氧化反应的分析检测未见系统研究报道。本文对苯乙烯不对称环氧化反应混合物的高效液相色谱分析和气质联用分析法进行研究，建立苯乙烯不对称环氧化反应的筛选方法，并结合正交试验，筛选优化苯乙烯不对称环氧化反应的条件。基于苯乙烯的不对称环氧化反应及建立的筛选方法，扩展不对称环氧化反应的范围，对肉桂醛和1-辛炔的不对称加成反应及其产物的环氧化反应进行探索。方法：采用手性高效液相色谱法(HPLC)和气质联用/选择离子法(GC-MS/SIM)，，通过内标法分析测定苯乙烯环氧化反应混合物，并利用正交实验对苯乙烯环氧化反应进行筛选；同时，采用BINOL/Ti(OiPr)体系不对称催化辛炔与肉桂醛的加成，并利用Sharpless环氧化催化体系对其加成产物进行环氧化反应研究。结果：利用HPLC法分析测定时，苯乙烯及(R)/(S)-环氧苯乙烷的标准曲线线性关系良好，相关系数分别为0.9983、0.9996、0.9995；方法检测限低，分别为0.02、0.10和0.13μg/mL；该方法低、中、高三个浓度水平的回收率为100.2%~100.8%；以相对标准偏差表示的精密度分别为0.86%、1.52%和1.80%。采用气质联用法分析测定时，苯乙烯及(R)/(S)-环氧苯乙烷标准曲线的相关系数分别为0.9997、0.9932和0.9963，检测限为1.3、1.1和0.7μg/L；方法的低、中、高三个浓度水平的回收率为98.2%~116.1%；以相对标准偏差表示的精密度分别为3.57%、3.08%和2.80%。获得了肉桂醛与1-辛炔的不对称加成产物-烯丙醇类物质，产率最高可达70%，对映异构体过量（ee值）为80%；对该烯丙醇进行环氧化反应，以20%的产率获得了环氧化产物。结论：应用HPLC法和气质联用/选择离子法均能很好的分离苯乙烯及对映异构的环氧苯乙烷，且能实现环氧苯乙烷产率及(R)/(S)-环氧苯乙烷对映异构体过量的测定，两种方法的准确度和精密度高，可应用于苯乙烯及同系物的不对称环氧化反应混合物的分析测定及反应筛选。利用Sharpless环氧化反应体系可成功合成手性环氧醇，但其产率的提高及对映选择性有待进一步探索。
[Abstract]:Objective: chiral epoxides have important physiological activity. Many important pharmaceutical intermediates can be obtained by selective opening reaction and conversion of functional groups. The most important thing is the chiral epoxide as the intermediate of medicine and fine chemicals. The chiral high performance liquid phase color is usually used for the determination of chiral epoxides. There is no systematic study on the analysis and detection of styrene epoxidation reaction by spectrum or gas chromatography. This paper studies the high performance liquid chromatography analysis and GC-MS analysis of styrene asymmetric epoxidation reaction mixture, and establishes a screening method for asymmetric epoxidation of styrene. The conditions of asymmetric epoxidation of styrene were optimized. Based on the asymmetric epoxidation of styrene and the screening method established, the range of asymmetric epoxidation was extended, the asymmetric addition reaction of Cinnamaldehyde and 1- ocyne and the epoxidation reaction of the products were explored. The reaction mixture of styrene epoxidation was determined by GC-MS / GC-MS/SIM, and the epoxidation reaction of styrene was screened by orthogonal experiment. At the same time, the addition of symoxyne with cinnamaldehyde was catalyzed by BINOL/Ti (OiPr) system, and the addition product of Sharpless epoxidation catalyst system was used. Study on the reaction of epoxidation. Results: the standard curve of styrene and (R) / (S) - Epoxy benzene ethane has good linear relationship, and the correlation coefficient is 0.9983,0.9996,0.9995, and the detection limit is low, 0.02,0.10 and 0.13 u g/mL respectively. The method is low, and the recovery rate of the middle and high levels is 100.2%~100.8% The relative coefficient of the standard curve of styrene and (R) / (S) - Epoxy ethylbenzene was 0.9997,0.9932 and 0.9963 respectively when the precision of the relative standard deviation was 0.86%, 1.52% and 1.80%. were determined by GC-MS. The detection limit was 1.3,1.1 and 0.7 mu g/L, and the recovery of the three concentrations of the method was 98.2%~116.1 %, the precision of the relative standard deviation was 3.57%, 3.08% and 2.80%. obtained the unsymmetrical addition product of Cinnamaldehyde and 1- ocyne - allyl alcohol, the highest yield up to 70%, the enantiomer excess (EE value) 80%, and the epoxidation of the allyl alcohol by 20% yield. Conclusion: application of HPL The C method and GC-MS / GC-MS can well separate styrene and enantiomer epoxide, and can determine the yield of epoxide and (R) / (S) - Epoxide enantiomer overdose. The accuracy and precision of the two methods are high, and can be applied to the asymmetric epoxidation of styrene and their homologues. The synthesis of chiral epoxy alcohols can be successfully synthesized by the Sharpless epoxidation reaction system, but the increase of the yield and the enantioselectivity of the enantiomer need to be further explored.
【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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