新型哒嗪酮甲酰肼的反应研究及其环合产物的生成
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摘要
哒嗪酮类化合物因其特有的生理活性而在医药、农药方面有广泛的应用，近年来已成为合成化学研究的热门课题。许多哒嗪类化合物具有良好的心血管药理作用，如抗血小板聚集和强心作用等。同时哒嗪酮类化合物在农药方面也有广泛的应用，如杀虫，杀螨，抗烟草花叶病毒等。1，3，4噻二唑，1，3，4-噁二唑，1，2，4-三唑-5-硫酮等杂环化合物也有明显的生物活性，如抗菌，除草，驱虫，消炎，调节植物生长等。糖类化合物是生物体内的可适性分子，是基本的生命物质之一，能以各种形式参与生命过程。
鉴于不同活性的分子片段在同一分子中聚集能明显改善化合物的生物活性这一特点，将哒嗪酮引入各种杂环化合物以及糖类化合物中，得到了系列含哒嗪酮的杂环化合物和一些N-糖基-2-取代氨基硫脲和糖腙。所有化合物均未见文献报道，中间体及目标化合物的结构经元素分析、IR、~1H NMR和MS谱得以证实。
本论文工作包括以下部分：
一、文献综述：对哒嗪酮、N-糖基-2-取代氨基硫脲的研究现状和发展进行了总结。
二、以α-酮戊二酸为起始原料合成哒嗪酰肼，将其与异硫氰酸芳基酯反应得到芳基氨基硫脲，并在不同条件下合环得到含哒嗪酮的杂环化合物。
三、用糖基异硫氰酸酯与哒嗪酰肼作用生成N-糖基-2-取代氨基硫脲。
四、由醛糖和哒嗪酰肼反应生成糖腙。
本论文的创新之处在于：
1．合成的1，4，5，6-四氢(及1，6-二氢)-6-哒嗪酮-3-甲酰肼尚未见文献报道；
2．将酰肼与异硫氰酸芳基酯反应得到12个芳基氨基硫脲，芳基氨基硫脲在不同条件下关环得到36个含哒嗪酮的1，3，4噻二唑，1，3，4-噁二唑，1，2，4-三唑-5-硫酮的杂环化合物；
3．将1，4，5，6-四氢(及1，6-二氢)-6-哒嗪酮-3-甲酰肼与糖基异硫氰酸酯反应，合成了8个N-糖基-2-取代氨基硫脲类化合物，将酰肼与醛糖反应合成了12个含哒嗪酮的糖腙。
Pyridazinone derivatives have been applied in field of pharmacy and agricultural chemicals due to their wide range of versatile, significant bioactivities and pharmalogical activities. In recent years synthetic work on pyridazinone derivatives have been become in synthetic chemistry. Many pyridazinones exhibited inhibition of platelet aggregation and treat congestive heart failure activities. In the same time, they were well-known compounds in agrochemical research, such as insecticides, acaridcides and show higher bioactivity against tobacco mosaic virus (TMV) etc. The heterocyclic compounds with 1,3,4-thiadiazole, 1,3,4-oxadiazole, and l,2,4-triazol-5-thione have significant biological activities as fungicides, insecticides, micribiocides, bactericides, anticunvulsants, antiviral, antibacterial etc. Carbohydrates are useful molecules to creatures and play important role in metabolizability.
In view of those observation and expect to realize the inforcement of many physiological activities by means of combining pyridazinone with different heterocycles and carbohydrates. The heterocyclic compounds of pyridazinone, N-glycosyl-2-substituted thiosemicarbazides and aldose hydrazones were obtained. The structure of intermediated and target compounds were conformed by elemental analysis, 'H NMR, IR and MS spectral date.
This work is composed of the follows.
1.Review on the development and actuality in pyridazinone and W-glycosyl-l-substituted thiosemicarbazide.
2. Hydrazides of pyridazinone were prepared from the starting materials a-ketoglutaric acid and hydrazine hydrate. Aryl thiosemicarbazides were synthesized from the reaction of aryl isothiocyanates with hydrazides, which cyclized under different conditions to give related heterocyclic compounds.
3..N-glycosyI-2-substituted thiosemicarbazides were synthesized using the reaction glycosyl isothiocyanates with hydrazides of pyridazinone.
4. Aldose hydrazones were obtained from the reaction of aldose with pyridazinone hydrazides.
The innovations of the thesis are based on the follows: 1. 1,4,5,6-tetrahydro (or 1,6-dihydro)-6-pyridazinone-3-hydrazides, which were synthesized unreported in the literatures; 2. 12 Aryl thiosemicarbazides have been synthesized from the reaction of thiosemicarbazides with hydrazide, and 36 pyridazinone heterocyclic compounds of 1,3,4-thiadiazole, 1,3,4-oxadiazole, and l,2,4-triazol-5-thione were obtained by cyclizing the aryl thiosemicarbazides in different conditions; 3. 8 A^-glycosyl-2-[l,4,5,6-tetrahydro(orl,6-dihydro)-6-pyridazione-3-carbonyl]thiosemicarbazides were synthesized by the reaction of l,4,5,6-tetrahydro(or 1,6-dihydro)-6-pyridazinone-3-hydrazides with glycosyl isothiocyanates. 12 Aldose hydrazones were obtained from the reaction aldose with pyridazinone hydrazides.
鉴于不同活性的分子片段在同一分子中聚集能明显改善化合物的生物活性这一特点，将哒嗪酮引入各种杂环化合物以及糖类化合物中，得到了系列含哒嗪酮的杂环化合物和一些N-糖基-2-取代氨基硫脲和糖腙。所有化合物均未见文献报道，中间体及目标化合物的结构经元素分析、IR、~1H NMR和MS谱得以证实。
本论文工作包括以下部分：
一、文献综述：对哒嗪酮、N-糖基-2-取代氨基硫脲的研究现状和发展进行了总结。
二、以α-酮戊二酸为起始原料合成哒嗪酰肼，将其与异硫氰酸芳基酯反应得到芳基氨基硫脲，并在不同条件下合环得到含哒嗪酮的杂环化合物。
三、用糖基异硫氰酸酯与哒嗪酰肼作用生成N-糖基-2-取代氨基硫脲。
四、由醛糖和哒嗪酰肼反应生成糖腙。
本论文的创新之处在于：
1．合成的1，4，5，6-四氢(及1，6-二氢)-6-哒嗪酮-3-甲酰肼尚未见文献报道；
2．将酰肼与异硫氰酸芳基酯反应得到12个芳基氨基硫脲，芳基氨基硫脲在不同条件下关环得到36个含哒嗪酮的1，3，4噻二唑，1，3，4-噁二唑，1，2，4-三唑-5-硫酮的杂环化合物；
3．将1，4，5，6-四氢(及1，6-二氢)-6-哒嗪酮-3-甲酰肼与糖基异硫氰酸酯反应，合成了8个N-糖基-2-取代氨基硫脲类化合物，将酰肼与醛糖反应合成了12个含哒嗪酮的糖腙。
Pyridazinone derivatives have been applied in field of pharmacy and agricultural chemicals due to their wide range of versatile, significant bioactivities and pharmalogical activities. In recent years synthetic work on pyridazinone derivatives have been become in synthetic chemistry. Many pyridazinones exhibited inhibition of platelet aggregation and treat congestive heart failure activities. In the same time, they were well-known compounds in agrochemical research, such as insecticides, acaridcides and show higher bioactivity against tobacco mosaic virus (TMV) etc. The heterocyclic compounds with 1,3,4-thiadiazole, 1,3,4-oxadiazole, and l,2,4-triazol-5-thione have significant biological activities as fungicides, insecticides, micribiocides, bactericides, anticunvulsants, antiviral, antibacterial etc. Carbohydrates are useful molecules to creatures and play important role in metabolizability.
In view of those observation and expect to realize the inforcement of many physiological activities by means of combining pyridazinone with different heterocycles and carbohydrates. The heterocyclic compounds of pyridazinone, N-glycosyl-2-substituted thiosemicarbazides and aldose hydrazones were obtained. The structure of intermediated and target compounds were conformed by elemental analysis, 'H NMR, IR and MS spectral date.
This work is composed of the follows.
1.Review on the development and actuality in pyridazinone and W-glycosyl-l-substituted thiosemicarbazide.
2. Hydrazides of pyridazinone were prepared from the starting materials a-ketoglutaric acid and hydrazine hydrate. Aryl thiosemicarbazides were synthesized from the reaction of aryl isothiocyanates with hydrazides, which cyclized under different conditions to give related heterocyclic compounds.
3..N-glycosyI-2-substituted thiosemicarbazides were synthesized using the reaction glycosyl isothiocyanates with hydrazides of pyridazinone.
4. Aldose hydrazones were obtained from the reaction of aldose with pyridazinone hydrazides.
The innovations of the thesis are based on the follows: 1. 1,4,5,6-tetrahydro (or 1,6-dihydro)-6-pyridazinone-3-hydrazides, which were synthesized unreported in the literatures; 2. 12 Aryl thiosemicarbazides have been synthesized from the reaction of thiosemicarbazides with hydrazide, and 36 pyridazinone heterocyclic compounds of 1,3,4-thiadiazole, 1,3,4-oxadiazole, and l,2,4-triazol-5-thione were obtained by cyclizing the aryl thiosemicarbazides in different conditions; 3. 8 A^-glycosyl-2-[l,4,5,6-tetrahydro(orl,6-dihydro)-6-pyridazione-3-carbonyl]thiosemicarbazides were synthesized by the reaction of l,4,5,6-tetrahydro(or 1,6-dihydro)-6-pyridazinone-3-hydrazides with glycosyl isothiocyanates. 12 Aldose hydrazones were obtained from the reaction aldose with pyridazinone hydrazides.
引文
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