【作者】 张慧丽；

【导师】 张越； 尚振华；

【作者基本信息】 河北科技大学 ， 药物化学， 2008， 硕士

【摘要】 具有生物活性的天然有机化合物大多数是杂环化合物,尤其是含氮、氧和硫杂原子的化合物在医药、农药、香料、电子材料等领域得到广泛应用。1,2,4-噻二唑和1,3,4-噁二唑等五元杂环化合物是杂环中的典型代表,具有多种显著的生物活性。论文第一部分研究2-(烷氧亚胺基)-(5-氨基-1,2,4-噻二唑-3-基)乙酸的合成;第二部分研究2,5-二取代-1,3,4-噁二唑类化合物合成的新方法。2-(烷氧亚胺基)-(5-氨基-1,2,4-噻二唑-3-基)乙酸类化合物多用于新型头孢菌素类药物的合成。论文确定了合理的工艺路线,即以氰基乙酰胺为起始原料,经肟化,烷基化,氨解,溴代,环合,碱性水解得到2-(烷氧亚胺基)-(5-氨基-1,2,4-噻二唑-3-基)乙酸。在获得目的化合物的基础上对反应条件进行了优化,其中2-乙氧亚胺基腈基乙酰胺的合成收率比文献高30%;对2-烷基丙二腈合成的后处理进行了简化,使产品的甲苯溶液直接进行下一步反应;2-氰基-2-烷氧亚胺乙脒的合成采用了盐析的方法,后处理变得简单,收率也由文献报道的57%增至62%;环和反应将反应温度由文献采用的-10～-5℃改为室温,使反应条件变得温和。最终产物的结构均通过红外光谱、核磁共振等分析方法进行结构确证。论文第二部分对2,5-二取代-1,3,4-噁二唑类化合物合成的新方法进行了研究。按照设计的合成路线,选取具有代表性的醛与酰肼合成出20个芳醛酰腙化合物,采用次氯酸钠作为新氧化剂实现芳醛酰腙的氧化关环反应,从而得到17个1,3,4-噁二唑类化合物。确定了氧化剂用量,反应溶剂和反应时间等因素;研究了不同取代基对产物收率的影响,并根据反应产物提出了较合理的反应机理,为具有多种生物活性的2,5-二取代-1,3,4-噁二唑类化合物的合成提供了合成方法上的选择。产物结构已由红外光谱、核磁共振、质谱等分析方法进行了确证。更多还原

【Abstract】 The natural organic compounds with biological activities are heterocyclic compounds, especially those containing N,O and S are applicated in many fields such as medicines, pesticides,perfurmes and electron materials.1,2,4-Thiadiazole and 1,3,4-oxadiazole are representives in five membered heterocyclic compounds which have multiple bioactivities. The synthesis of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(alkoxylimino)acetic acid was studied in the first part and the new preparation of 1,3,4-oxadiazole was successively studied in the second part.2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(alkoxylimino)acetic acid is applied in the preparation of novel cephalosprins.A reasonable synthetic route was designed in the paper, in which cyanoacetamide was starting marerial,then through oximation,alkylation, aminolysis,bromation,cyclization with postassium thiocyanate,hydrolysis in base environment to give 2-(5-amino-1,2,4-thiadiazol-3,yl)-2-(alkoxyimino) acetic acid.The reactive conditions were optimizated.For example,the yield of 2-cyano-2-(ethoxyimino)acetamide is 30%higher than literatures,the toluene solution of 2-(ethoxyimino)malononitrile was used directly and the yield of 2-cyano-2-(alkoxyimino)acetamidine is up to 62%from 57%of the literature and the workup is simpler with salting-out procedure and the last step-cyclization was realized at room temperature avoiding in lower temperature(-10～-5℃).The target compounds were confirmed by IR,NMR.The new method of preparation of 2,5-disubstituted-1,3,4-oxadiazole was studied in the second part of the paper.Twentyaromatic aldehyde N-acylhydrazones were synthezied from aldehydes and N-acylhyrazines according to the designed synthetic route. Seventeen oxadiazoles were obtained through oxidative cyclization with sodium hypochlorit as the new oxidant.The ratio between the substrate and the oxidant,the solvent,reaction time and the influence of the substitution of the moieties were respectively studied and the reaction mechanism was proposed.The new method applied choices in the preparation 2,5-disubstituted-1,3,4-oxadiazoles with biological activities and the products were confirmed through IR,NMR and MS.更多还原