多氟烷基和联苯取代噁二唑类的合成及活性研究
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摘要
含氟有机化合物得到广泛的应用,这主要是因为氟原子或含氟链段导致化合物物理、化学和生物学性质产生很大的变化。而1,3,4-噁二唑-2-硫酮具有广谱的生物活性如抗HIV病毒,抗细菌及防止低血糖昏迷等。关于它们唑环NH上的氢原子的反应已有较多的研究,比较典型的就是Mannich反应,但是对于该氢原子被多氟烷基取代的化合物,却未有文献报道。本文第二章设计合成了一系列多氟烷基乙基取代的1,3,4-噁二唑-2-硫酮类化合物;1H-NMR, 19F-NMR, IR和MS谱以及元素分析表征了它们的结构,并选取部分化合物进行了除草活性测试。
含有联苯的衍生物,由于其高效的降压活性而引起国内外化学家的极大关注。它们一般由含氮杂环部分和联苯环部分组成,前者变化较多,而后者相对稳定。1,3,4-噁二唑-2-硫酮是一类用途十分广泛的有机五元杂环化合物,不仅在染料、光敏物质及电子材料等方面有广泛的应用,而且还具有杀菌、抗低血糖、利尿、抗病毒、降压等医药活性。若将联苯环引入到含1,3,4-噁二唑-2-硫酮的分子中有望实现其生物活性叠加和拓宽抗菌谱。鉴于此,本文设计并合成了几个新型联苯杂环化合物,其结构经过1H-NMR, IR和MS谱以及元素分析确证。
实验开发了一个沙坦联苯的高效的两步合成工艺,总产率达67%。这条工艺具有以下几个特点:(1)使用MnCl2为偶联反应的催化剂,避免了昂贵的钯催化剂的使用,大大降低了成本;(2)MnCl2催化的偶联反应可以使带活化基团(CN,CH=NR)的氯代芳烃顺利的发生偶联反应,并可有效的保护-CN;(3)通过对反应中各种副产物成因的分析,有依据的对反应条件进行了了优化;(4)对产品的纯化工艺做了改进,提出了一个分步结晶法的提纯工艺,此方法避免了成本较高的柱色谱纯化,以及能耗较高的减压蒸馏方法。
Fluorinated functional compounds have gained to chemist’s attentions since it was found that the introduction of fluorine atoms or fluorous alkyl into organic molecules could lead to significant changes in biological activities. And 1,3, 4-oxadiazole-2-thiones with a broad spectrum of biological activity such as anti-HIV-virus, anti-bacteria and to prevent low blood sugar coma.There a few papers reported the reactivity of the hydrogen of NH group in heterocycle, for example, Mannich base reaction. However, the same hydrogen substituted by perfluoroalkyl is not reported in the literature. A series of N-perfluoroalkylethyl-substituted 1,3, 4-oxadiazole-2-thiones were synthesized in the second chapter this paper and their structures were confirmed by 1H-NMR, 19F-NMR, IR, mass spectra and elemental analysis, And select the part of the herbicidal activity of compounds tested.
Containing biphenyl derivatives in recent years because of its high efficiency step-down activity chemists caused great concern at home and abroad. They are generally part of the nitrogen-containing heterocyclic ring and the biphenyl components, the former is much more varied, while the latter is relatively stable. If the introduction of biphenyl ring containing 1,3,4-oxadiazole-2-thione molecule is expected to achieve its biological activity and broaden the antibacterial spectrum superposition. In view of this, the paper design and synthesis of several new heterocyclic compounds biphenyl, and their structures were confirmed by 1H-NMR, IR, mass spectra and elemental analysis.
A highly efficient 2-step synthesis of the Sartanbiphenyl was developed by Losartan experiment, 68% of total yield. The most important features are the following: (1) using MnCl2 as a catalyst for cross-coupling reaction, have avoid the use of the palladium catalyst and reduced the cost greatly; (2) in the presence of MnCl2, Grignardreagents can easy react with aryl chlorides which has an electron withdrawing activating group(CN,CH=NR,oxazoline),and can effectively protect CN group; (3) The possible origins of by-product were discussed, and the reaction condition were optimized; (4) the purified process of the products has been improved, and we describe a step-by-step crystallization of the purification process. This process to avoid expensive chromatographic purification and vacuum distillation.
含有联苯的衍生物,由于其高效的降压活性而引起国内外化学家的极大关注。它们一般由含氮杂环部分和联苯环部分组成,前者变化较多,而后者相对稳定。1,3,4-噁二唑-2-硫酮是一类用途十分广泛的有机五元杂环化合物,不仅在染料、光敏物质及电子材料等方面有广泛的应用,而且还具有杀菌、抗低血糖、利尿、抗病毒、降压等医药活性。若将联苯环引入到含1,3,4-噁二唑-2-硫酮的分子中有望实现其生物活性叠加和拓宽抗菌谱。鉴于此,本文设计并合成了几个新型联苯杂环化合物,其结构经过1H-NMR, IR和MS谱以及元素分析确证。
实验开发了一个沙坦联苯的高效的两步合成工艺,总产率达67%。这条工艺具有以下几个特点:(1)使用MnCl2为偶联反应的催化剂,避免了昂贵的钯催化剂的使用,大大降低了成本;(2)MnCl2催化的偶联反应可以使带活化基团(CN,CH=NR)的氯代芳烃顺利的发生偶联反应,并可有效的保护-CN;(3)通过对反应中各种副产物成因的分析,有依据的对反应条件进行了了优化;(4)对产品的纯化工艺做了改进,提出了一个分步结晶法的提纯工艺,此方法避免了成本较高的柱色谱纯化,以及能耗较高的减压蒸馏方法。
Fluorinated functional compounds have gained to chemist’s attentions since it was found that the introduction of fluorine atoms or fluorous alkyl into organic molecules could lead to significant changes in biological activities. And 1,3, 4-oxadiazole-2-thiones with a broad spectrum of biological activity such as anti-HIV-virus, anti-bacteria and to prevent low blood sugar coma.There a few papers reported the reactivity of the hydrogen of NH group in heterocycle, for example, Mannich base reaction. However, the same hydrogen substituted by perfluoroalkyl is not reported in the literature. A series of N-perfluoroalkylethyl-substituted 1,3, 4-oxadiazole-2-thiones were synthesized in the second chapter this paper and their structures were confirmed by 1H-NMR, 19F-NMR, IR, mass spectra and elemental analysis, And select the part of the herbicidal activity of compounds tested.
Containing biphenyl derivatives in recent years because of its high efficiency step-down activity chemists caused great concern at home and abroad. They are generally part of the nitrogen-containing heterocyclic ring and the biphenyl components, the former is much more varied, while the latter is relatively stable. If the introduction of biphenyl ring containing 1,3,4-oxadiazole-2-thione molecule is expected to achieve its biological activity and broaden the antibacterial spectrum superposition. In view of this, the paper design and synthesis of several new heterocyclic compounds biphenyl, and their structures were confirmed by 1H-NMR, IR, mass spectra and elemental analysis.
A highly efficient 2-step synthesis of the Sartanbiphenyl was developed by Losartan experiment, 68% of total yield. The most important features are the following: (1) using MnCl2 as a catalyst for cross-coupling reaction, have avoid the use of the palladium catalyst and reduced the cost greatly; (2) in the presence of MnCl2, Grignardreagents can easy react with aryl chlorides which has an electron withdrawing activating group(CN,CH=NR,oxazoline),and can effectively protect CN group; (3) The possible origins of by-product were discussed, and the reaction condition were optimized; (4) the purified process of the products has been improved, and we describe a step-by-step crystallization of the purification process. This process to avoid expensive chromatographic purification and vacuum distillation.
引文
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