具有哒嗪酮骨架结构类杂环化合物的合成研究
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摘要
哒嗪是一个有两个氮原子处于邻位的二嗪,是农药、医药等具有生物活性化合物的重要结构单元。哒嗪酮类化合物是一类具有良好生物活性的杂环化合物,在农药医药等研究领域中占有重要的地位。哒嗪酮类农药具有活性高、对环境友好等特点,在害虫综合防治和降低农药对环境污染方面发挥着重要作用。哒嗪酮类化合物还可以作为钙增敏剂用于治疗心功能障碍和心衰竭的强心药,另外在抗血小板聚集、降压以及抗炎、抗休克、抗惊厥等方面也有一定疗效。近年来对哒嗪酮类化合物的研究已成为一个重要的领域。为此我们开展了对哒嗪酮类化合物的合成研究,取得了一系列有意义的实验结果:
1、以顺丁烯二酸酐和苯肼为原料,先缩合得到哒嗪环,然后通过氯乙酸乙酯引入酯基,肼解后得到含哒嗪酮结构的酰肼,在此基础上合成了八个含哒嗪酮环的酰腙类化合物以及三个含吡唑基团的哒嗪酮类化合物。通过IR、1HNMR等方法进行了表征,并测定了其中三个化合物的单晶分子结构。
2、以2-苯基-3-哒嗪酮-6-氧乙酰肼为原料,通过在碱的作用下重排合成了2-苯基-6-肼基-3-哒嗪酮,并重点对该重排反应的机理进行了研究,初步得出了该重排反应发生对分子结构本身的要求。在此基础上合成了八个含哒嗪酮环的腙类化合物和七个含有二氢吡唑基团的哒嗪酮类化合物,通过IR、1HNMR、13CNMR等方法进行了表征,并测定了其中五个化合物的单晶分子结构。
3、通过研究3,6-二羟基酞嗪、2-苯基-3-酞嗪酮与氯乙酸乙酯在不同温度和不同比例下的酯基化反应,初步探索了3,6-二羟基酞嗪的互变异构化,证明了6-羟基3-酞嗪酮是其最稳定的构象。并在此基础上合成了两个含吡唑基的酞嗪酮类化合物,通过IR、1HNMR等方法进行了表征。
Pyridazine, being a triazine with two adjacent nitrogen atoms, is an important structural element in pesticides and pharmaceuticals with biological activity . Pyridazinones, being heterocyclic compounds with good biological activity, play an important role in the field of pesticides and medical research. The pesticides of pyridazinones play an important role in the integrated pest control and reducing environmental pollution of pesticides because of its activity and environment-friendly features. Pyridazinones can be used as calcium sensitizers for the treatment of heart dysfunction and heart failure in cardiac medicines. They also have a certain effect in the area of anti-platelet aggregation, hypotension, anti-inflammatory, anti-shock, anti-convulsion and so on.
In recent years, in the area of the pyridazinones has attracted many attentions. In this thesis, we have embarked on the synthesis of pyridazinones, and a series of significant results and developments have been achived, the main results are as follows:
1、Maleic anhydride reacted with phenylhydrazine to get to pyridazine ring, and then after esterification and condensation, we got eight acylhydrazone-pyridazinone compounds and three pyrazole - pyridazinones. Besides their structures were charactered by IR, 1HNMR ,and which of the three compounds charactered by X-ray diffraction.
2、Using 2 - phenyl -3 - pyridazinone -6 - oxyacetyl hydrazine for raw materials, through the rearrangement under base, we got the 2 - phenyl -6 - hydrazine--3 - pyridazinone .We Focued on the mechanism study of the rearrangement, and gave the preliminary draw of the rearrangement’s conditions . On the basis we synthesised eight pyridazinone-hydrazone compounds and seven dihydropyrazole-pyridazinones, Besides their structures were charactered by IR, 1HNMR , 13CNMR, and which of the five compounds charactered by X-ray diffraction methods.
3、Through the research to 3,6 - two hydroxyl phthalazine, 2 - phenyl -3 - phthalazinone reacted with ethyl chloroacetate at different temperatures and different ratios, we initially explorated the Tautomerism of 3,6-two hydroxyl phthalazine, and proved that 6-hydroxy-3-phthalazinone is the most stable conformation. On the basis, we synthesised two pyrazole-phthalazinones.which characterized by IR, 1HNMR,etc.
1、以顺丁烯二酸酐和苯肼为原料,先缩合得到哒嗪环,然后通过氯乙酸乙酯引入酯基,肼解后得到含哒嗪酮结构的酰肼,在此基础上合成了八个含哒嗪酮环的酰腙类化合物以及三个含吡唑基团的哒嗪酮类化合物。通过IR、1HNMR等方法进行了表征,并测定了其中三个化合物的单晶分子结构。
2、以2-苯基-3-哒嗪酮-6-氧乙酰肼为原料,通过在碱的作用下重排合成了2-苯基-6-肼基-3-哒嗪酮,并重点对该重排反应的机理进行了研究,初步得出了该重排反应发生对分子结构本身的要求。在此基础上合成了八个含哒嗪酮环的腙类化合物和七个含有二氢吡唑基团的哒嗪酮类化合物,通过IR、1HNMR、13CNMR等方法进行了表征,并测定了其中五个化合物的单晶分子结构。
3、通过研究3,6-二羟基酞嗪、2-苯基-3-酞嗪酮与氯乙酸乙酯在不同温度和不同比例下的酯基化反应,初步探索了3,6-二羟基酞嗪的互变异构化,证明了6-羟基3-酞嗪酮是其最稳定的构象。并在此基础上合成了两个含吡唑基的酞嗪酮类化合物,通过IR、1HNMR等方法进行了表征。
Pyridazine, being a triazine with two adjacent nitrogen atoms, is an important structural element in pesticides and pharmaceuticals with biological activity . Pyridazinones, being heterocyclic compounds with good biological activity, play an important role in the field of pesticides and medical research. The pesticides of pyridazinones play an important role in the integrated pest control and reducing environmental pollution of pesticides because of its activity and environment-friendly features. Pyridazinones can be used as calcium sensitizers for the treatment of heart dysfunction and heart failure in cardiac medicines. They also have a certain effect in the area of anti-platelet aggregation, hypotension, anti-inflammatory, anti-shock, anti-convulsion and so on.
In recent years, in the area of the pyridazinones has attracted many attentions. In this thesis, we have embarked on the synthesis of pyridazinones, and a series of significant results and developments have been achived, the main results are as follows:
1、Maleic anhydride reacted with phenylhydrazine to get to pyridazine ring, and then after esterification and condensation, we got eight acylhydrazone-pyridazinone compounds and three pyrazole - pyridazinones. Besides their structures were charactered by IR, 1HNMR ,and which of the three compounds charactered by X-ray diffraction.
2、Using 2 - phenyl -3 - pyridazinone -6 - oxyacetyl hydrazine for raw materials, through the rearrangement under base, we got the 2 - phenyl -6 - hydrazine--3 - pyridazinone .We Focued on the mechanism study of the rearrangement, and gave the preliminary draw of the rearrangement’s conditions . On the basis we synthesised eight pyridazinone-hydrazone compounds and seven dihydropyrazole-pyridazinones, Besides their structures were charactered by IR, 1HNMR , 13CNMR, and which of the five compounds charactered by X-ray diffraction methods.
3、Through the research to 3,6 - two hydroxyl phthalazine, 2 - phenyl -3 - phthalazinone reacted with ethyl chloroacetate at different temperatures and different ratios, we initially explorated the Tautomerism of 3,6-two hydroxyl phthalazine, and proved that 6-hydroxy-3-phthalazinone is the most stable conformation. On the basis, we synthesised two pyrazole-phthalazinones.which characterized by IR, 1HNMR,etc.
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