导入含氮杂环的哒嗪酮衍生物的合成研究

【作者】 谭小华；

【导师】 安德烈；

【作者基本信息】 湖南大学 ， 有机化学， 2003， 硕士

【摘要】 本学位论文对具有生物活性的苯并含氮杂环化合物、哒嗪酮衍生物以及嘧啶类与苯并唑类化合物在医药和农药研究开发中的现状与发展趋势进行了综述。当今医药和农药研究中，哒嗪酮类化合物以其选择性好、生物活性高而成为一大研究热点。许多临床药物以及商品化的农药中都含有哒嗪酮结构。因而可以确信哒嗪酮类衍生物在发现和创造新的生物活性物质研究中，是一类很重要的前驱物质。 定量构效关系研究在预测化合物的生物活性、帮助了解药物的作用机制方面有一定的作用，能够指导目标分子设计。本学位论文通过对现有文献的研究，结合Free-Wilson模式的基本思想，设计了两类具有潜在生物活性的新型目标分子。 为了进行目标分子的合成，本学位论文首先研究了哒嗪酮化合物的合成，通过对它们不同合成方法的比较，结合本研究室的实际条件，成功地制备出2-苯基-4，5二氯-3(2氢)-哒嗪酮后，又研究并成功地制备了2-巯基嘧啶和2-巯基苯并唑类化合物。在碱性条件下，2-巯基嘧啶和2-巯基苯并唑类化合物通过硫醚键形式被引入到哒嗪酮结构中，合成了目标化合物M6～M9。 其次，本学位论文在成功地合成出2一苯基一4一氯一5一经基一3(2氢关哒嗦酮后，研究了苯并含氮杂环化合物的合成。通过对它们不同的合成方法的比较，结合本研究室以前的研究，优化和完善了这三种苯并含氮杂环化合物的合成方法，并合成了三个N-氯乙酞或从N，-二氯乙酞取代的苯并含氮杂环中间体。通过它们与2-苯基一4一氯一5一轻基一3(2氢升哒嚓酮的亲核取代反应被导入到哒嗓酮环结构中，合成了目标化合物M17一 M19。 目标化合物的结构经MS、IR、’HNMR和’3CNMR分析得到确证。更多还原

【Abstract】 This degree thesis shall make a comprehensive description of the current situation and development trend for the bioactive study of nitrogen-containing benzoheterocyclic compound, pyridazinone derivative, pyrimidine compound and benzoazole compound in the fields of medicine and pesticide. In current study of medicine and pesticide, pyridazinone compound has become a focus due to its excellent selectivity and high activity. Many clinical drugs and commercial pesticides contain pyridazinone structure. Therefore, we can firmly believe that pyridazinone derivative is a kind of very important precursor in the study and development of new bioactive compound.The research of Quantitative Structure-Activity Relationships(QSAR), which can predict compound’s bioactivity, helps to know the pharmaceutical effect and design target molecular. On the basis of study of existing literatures and Free-Wilson model’s basic thought, two kinds of target molecules owning potential bioactivity are designed.The synthesis of pyridazinones have been studyed firstly in this degree paper. Compared with different synthetic methods and based on the conditions of our laboratory, 2-phenyl-4,5-dihalo-3(2H)-pyridazinone were prepared firstly. Then, 2-mer capto-pyrimidines and 2-mercapto-benzoazoles have been studied and successfully synthesized. Under base condition, 2-mercapto-pyrimidines and 2-mercapto-benzoazol es compounds were introduced into pyridazinone by the formation of thioether. Target molecules M6-M9 were prepared.Secondly, after 2-phenyl-4-chloro-5-hydro-3(2H)-pyridazinone were successfully synthesized. The synthesis of nitrogen-containing benzoheterocyclic compounds has been done. Compared with different synthetic methods and based on the preceding researches in our laboratory, the synthesis method of these three nitrogen-containing benzoheterocyclic compounds was optimized. Three types of N-chloroacetyl and N,N’-dichloroacetyl substituted nitrogen-containing intermediate compounds were successfully synthesized. Target molecules M17-M19 were synthesized through nucleophilic substitution reaction between 2-phenyl-4-chloro-5-hydro-3(2H)-pyridazinone and nitrogen-containing benzoheterocyclic intermediate compounds.The structures of all target compounds were characterized by MS; IR ; 1HNMR and 13CNMR.更多还原