【作者】 袁立丽；

【导师】 商永嘉； 王绍武；

【作者基本信息】 安徽师范大学 ， 有机化学， 2005， 硕士

【摘要】 近年来,可溶性聚合物支载的小分子有机化合物的合成技术已成功地应用于组合化学、平行合成等领域。这种液相合成技术兼具了传统的溶液相有机合成化学(如反应活性高、反应时间短、中间体容易鉴定等)与固相有机合成化学(如可使用过量的试剂使反应进行完全、产物分离纯化操作简便等)的优点,因而受到了合成化学家们重视。在本课题组以往研究的基础上,以可溶性聚合物聚乙二醇(PEG)为支载体,液相合成双异噁唑啉衍生物;以Baylis-Hillman 反应的产物与腈氧化物进行1,3-偶极环加成反应制备异噁唑类化合物;设计了以可溶性聚合物聚乙二醇(PEG)为支载体,液相合成1,3,4-噁二唑的新方法,并合成了其中的一些中间体。这些合成方法是操作简便,反应条件温和,产率良好的合成路线,适合于平行合成和组合化学技术制备杂环化合物库的基本要求。具体研究内容和结果如下: 1. 发展了用聚乙二醇4000 为支持树脂液相合成双异噁唑啉衍生物的新方法。聚乙二醇支持的丙烯酸酯和甲基丙烯酸酯与腈氧化物进行1,3-偶极环加成生成聚乙二醇支持的双异噁唑啉,用甲醇钠的甲醇溶液解脱,得到了二取代的异噁唑啉衍生物。产率达到90~92%。2. 发展了异噁唑啉衍生物的不对称液相有机合成的新方法。用聚乙二醇支持的丙烯酸酯与苯甲醛进行Baylis-Hillman 反应,得到的加成产物与腈氧化物进行1,3-偶极环加成反应,用甲醇钠的甲醇溶液解脱获得了异噁唑啉衍生物。3. 以α,α’-二氯-对二甲苯为连接分子设计了液相合成多取代1,3,4-噁二唑的合成路线,并合成了其中的一些中间体。更多还原

【Abstract】 Recently, the synthetic techniques of small molecule libraries using soluble polymer as support were applied successfully to combinatorial chemistry and parallel synthesis. The synthetic approaches have the advantages of homogeneous solution organic synthesis （high reactivity, lack of diffusion phenomena and ease of analysis） and those of solid phase methods （use of excess reagents and easy isolation and purification of products）, so the liquid-phase organic synthesis （LPOS） is more and more imported. A series of diisoxazolines were synthesized using poly （ethylene glycol）（PEG） as support in this paper. A series of isoxazolines were also synthesized by treating the PEG-supported Baylis-Hillman reaction products with in situ generated nitrile oxides through 1,3-dipolar cycloaddition. The liquid-phase synthetic methodology of 1,3,4-oxadiazoles using poly （ethylene glycol） as support were designed and some intermediate products were obtained. All reactions were highly efficient by simple operation, which suited with the demands of combinatorial chemistry and parallel synthesis of small molecule libraries. Firstly, PEG-supported acrylate or PEG-supported methyl acrylate reacted with in situ generated nitrile oxides through 1,3-dipolar cycloaddition, followed by cleavage from the resin by CH₃ONa / CH₃OH, to give diisoxazolines. The yields were in the range of （90⁹2%）. Secondly, PEG-supported acrylate reacted with benzaldehyde to give PEG-supported α,β-unsaturated ester through Baylis-Hillman reaction. The PEG-supported α,β-unsaturated ester reacted with in situ generated nitrile oxides through 1,3-dipolar cycloaddition, followed by cleavage from the resin by CH₃ONa / CH₃OH, to give isoxazolines. Thirdly, we designed a practice and efficient liquid-phase synthetic methodology of 1, 3,4-oxadiazoles using α,α’-Dichloro-p-xylene as a link and achieved some intermediate products.更多还原