新型含1，2，4-三氮唑类化合物的设计和合成

【作者】 杨德保；

【导师】 刘方明；

【作者基本信息】 杭州师范大学 ， 有机化学， 2009， 硕士

【摘要】 1,5-苯并硫氮杂卓是一类具有重要生理活性的七元杂环化合物,常用作镇静剂和治疗心血管病的药物,对其合成、结构和药理活性的研究一直倍受人们的关注。在以往的报道中,对于三号位含三唑基的1,5-苯并硫氮杂卓未见报道,鉴于此,我们将1,2,4-三唑基引入到三号位,期望得到一系列具有更高生理活性的化合物,然后,我们通过2+2环加成反应将β-内酰胺环这一具有强烈生物活性的结构单元合并到所合成的苯并硫氮杂卓母体分子中,合成了一系列结构新颖的衍生物,并且在此过程中意外的发现了多种反应途径。另外,1,3,4-噁二唑啉类化合物也是一类具有广泛的生物活性,如抗菌,消炎等,所以我们也尝试将1,2,4-三唑基引入到1,3,4-噁二唑啉类化合物中,成功的合成了一系列合成分子中既含有1,2,4-三唑,又含有1,3,4-噁二唑环的化合物2-(1-(1H-1,2,4-三唑)甲基)-3-乙酰基-2,5-二取代芳基-1,3,4-噁二唑啉。本论文分为以下四部分:第一章:1,5-苯并硫氮杂卓的文献综述。该部分是对1,5-苯并硫氮杂卓及其衍生物的重要合成方法、结构、化学改造等在国内外的研究状况作了比较系统的阐述。同时还简要介绍了1,2,4-三唑。第二章:新型含1,2,4-三唑基苯并硫氮杂卓类化合物的合成及其与氯乙酰氯的环加成反应研究,主要工作分为三部分:一、1,3-二芳基-2-(1H-1,2,4-三唑-1-基)-2-丙烯-1-酮的合成二、2-芳基-4-芳基-3-(1,2,4-三唑-1-基)-2,5-二氢-1,5苯并硫氮杂卓衍生物的合成三、2,4-二芳基-3-(1,2,4-三氮唑-1-基)-2,3-二氢-1,5-苯并硫氮杂卓与氯乙酰氯的环加成反应研究第三章:噁二唑啉等杂环化合物的文献综述。该部分是对1,3,4-噁二唑啉类化合物的重要合成方法、结构、化学改造等在国内外的研究进展。第四章:2-(1-(1H-1,2,4-三唑)甲基)-3-乙酰基-2,5-二取代芳基-1,3,4-噁二唑啉类化合物的合成和晶体结构。产物结构经过元素分析、IR、MS和HNMR得到确认,对其波谱性质进行了讨论,部分化合物进行了单晶结构确认。更多还原

【Abstract】 The 1,5-benzothiazepines are a kind of seven-membered ring heterocyclic compounds which possess many physiological properties. They are often used as tranquilizer and medicines for cardiovascular disease. Scientist shown great ardor in it’s synthesis, structure, and physiological properties research. In previous literatures, the research of 3 triazole substituted 1,5-benzothiazepines is seldom. Therefore, we expect to realize reinforcement of many physiological activities by introduction of 1,2,4-triazole ring into 1,5-benzothiazepine, and obtained a series of new compounds with stronger biological activities. In addition, we combined 1,2,4-oxodiazole which has strong biological activities with 1,5-benzothiazepines by 2+2 cycoladdition reaction respectively, and a series of derivatives with novel structures were synthesized. We discovered several unexpected reaction paths in the same course of reaction.1,3,4-oxadiazoles compounds are also well known to highly active, such as antibacterium, antiphlogosis. Therefore, we try to bring the 1H-1,2,4-triazole moiety into 1,3,4-oxadiazole compounds. We synthetize successfully a series of 2-(1-(1H-1,2,4- triazola) methyl)-3- acetyl-2,5-disubstituted aryl-1,3,4-oxadiazoline, which both contain 1H-1,2,4-triazole moiety and 1,3,4-oxadiazole moiey.The thesis includes four major parts:The first part is the literature review of 1,5-benzothiazepines. The important synthetic methods, structure and chemical transformation of l,5-benzothiazepine derivatives that have been studied in China and other countries were explicated systematically and briefly elucidated 1,2,4-triazole ring.The second part is synthesis and structure characterization of novel 2,3-dihydro-3-arylmethylene 4-aryl-1,5-benzo[b]thiazepine derivatives containing 1,2,4-triazole through 2+2 cycloaddition reaction.1. General procedure for synthesis of 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-one.2. General procedure for synthesis of 2,4-diaryl-3-(1H-1,2,4-triazol-1-yl)-2,5-dihydrobenzo[b][1,4]thiazepine.3. 2,4-diaryl-3-(1H-1,2,4-triazol-1-yl)-2,5-dihydrobenzo[b][1,4]thiazepine react with 2-chloroacetyl chloride through [2+2] cycloaddition reaction.The third part is the literature review of 1,3,4-oxadiazole compounds. The important synthetic methods, structure and chemical transformation of 1,3,4-oxadiazole derivatives that have been studied in China and other countries were explicated systematically.The forth part is synthesis and crystal structure of 2-(1-(1H-1,2,4 - triazola) methyl)-3- acetyl-2,5-disubstituted aryl-1,3,4-oxadiazoline.Above all, the structures of the new compounds were confirmed by elememtal analysis,IR, 1H NMR and MS spectral data, and discussed it’s spectral property. We give single crystal discussion to part of these compoundes.更多还原