含吡唑基的1，5-苯并硫氮杂卓及吡唑啉类衍生物的合成
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摘要
杂环化合物在医药和农药领域占有十分重要的地位,通过人工合成具有生物活性的杂环化合物是医药化学和农药化学的研究热点。实践证明,这方面的工作也为人类的健康和农业发展做出了巨大的贡献。此类合成工作是鉴于不同活性的杂环核在同一分子中聚集能明显改善化合物生物活性的这一活性叠加原理进行的。
吡唑是一类具有多种活性的含氮杂环化合物,它具有杀菌,止痛,抗病毒,杀虫,除草等活性,在农药和医药方面有着广泛的应用。自本世纪四十年代以来,就有人开始研究合成此类化合物,此后,许多化学工作者不断通过在吡唑环上引入新的具有活性的取代基,或者将吡唑环并入其它杂环的方法,开发出了许多具有更好生物活性的吡唑类衍生物,其中很多已经商品化。
1,5-苯并硫氮杂卓和1,2,4-噁二唑亦是具有很好生理活性的杂环化合物,其中1,5-苯并硫氮杂卓的一些化合物已成为治疗神经系统疾病,心血管病的良好药物。1,2,4-噁二唑也由于具有更多潜在活性如抗病毒,杀菌,杀虫和镇静等作用,引起了广泛的关注。本论文中通过一系列反应将这三种活性杂环组合于同一分子中,合成出一系列未见文献报道的化合物,化合物的结构经元素分析,1H NMR,IR谱确证。
本论文所做的工作为:
1.用1-苯基-3-甲基-5-芳氧基-吡唑甲醛与(对位取代)苯乙酮发生羟醛缩合反应制得五种α,β-不饱和酮,然后以此为原料与邻氨基苯硫酚反应合成出十种含1-苯基-3-甲基-5-芳氧基-吡唑基团的1,5-苯并硫氮杂卓类化合物,从而将吡唑这一活性基团引入到同样具有显著活性的苯并硫氮杂卓结构单元中。
2.将合成出的1,5-苯并硫氮杂卓继续与“现场”产生的氧化芳甲腈进行1,3-偶极环加成反应得到20种1,2,4-噁二唑与其并合的三环稠杂环化合物。
3.将生成的含1-苯基-3-甲基-5-芳氧基-吡唑基团的α,β-不饱和酮分别与水和肼,苯肼反应成了10种含吡唑基的吡唑啉类衍生物。
Heterocyclic compounds play an important role in the fields of medical and pesticides.It has been a hot topic to synthesize heterocyclic compounds containing bioactivities and pharmalogical activities by human synthsis in medical chemistry and pesticide chemistry. In fact, the works greatly contribute to human’s healthy and development of agriculture. The works go on in view of these observation and expect to realize the inforcement of many physiological activities by means of combining different heterocycles to one moleculer.
Pyrazole nitrogen-containing heterocycles is intensively applied in pharmaceutical and agrochemical industries due to their antipyretic, anti-inflammatory,herbicidal, insecticidal and fungicidal properties. In the beginning of this century, Somebody began to synthesize the compoud, then, many chemists develop lots of pyrazole derivatives containing more activities by introducing new substituent or combining the pyrazole heterocycle to other heterocycles, which also have good activities.
1,5-benzothiazepine and 1,2,4-oxadiazole heterocycles exhibit diverse biological activities. Of the two heterocycles, 1,5-benzothiazepine compounds have been used as anticonvulsants and tranquilizer drugs and drugs for cardiovascular disease. 1,2,4-oxadiazole also have attracted wide-spread attention due to their potent activities such as antiviral fungicide and anti-inflammatory. In the papers, I combine the aboved three heterocycles to one moleculer and synthesize a series of new heterocycles with a various structure by designing different synthetic procedures. the structures of intermediate and target compounds were estiblished by elemental analysis, 1H NMR, IR data.
The detail works in the paper:
1. 1-phenyl-3-methyl-5-aryloxyl-pyrazol-4-carboxaldehyde reacted with acetophenone or para-substituted acetophenones to formα,β-unsaturated ketone by condensation reaction And the reaction of theα,β-unsaturated ketone with 2-amino thiophenol gave 1,5-benzothiazepines containing 1-phenyl-3-methyl-5-aryloxyl-pyrazole.
2. 1,5-benzothiazepine synthesized underwent 1,3-dipolar cycloadditon reaction with aryl nitrile oxides″in situ″and a series of 1,2,4-oxadiazolo[4,5-d][1,5]benzothiazepine derivatives containing 1-phenyl-3-methyl-5- aryloxyl-pyrazol were obtained.
3. New pyrazoline deriravatives containing pyrazole have been synthesized whileα,β-unsaturated ketone containing 1- phenyl- 3- methyl- 5- aryloxyl- pyrazol react with hydrazine hydrate and phenyl hydrazine in glacial acetic acid under refluxing
吡唑是一类具有多种活性的含氮杂环化合物,它具有杀菌,止痛,抗病毒,杀虫,除草等活性,在农药和医药方面有着广泛的应用。自本世纪四十年代以来,就有人开始研究合成此类化合物,此后,许多化学工作者不断通过在吡唑环上引入新的具有活性的取代基,或者将吡唑环并入其它杂环的方法,开发出了许多具有更好生物活性的吡唑类衍生物,其中很多已经商品化。
1,5-苯并硫氮杂卓和1,2,4-噁二唑亦是具有很好生理活性的杂环化合物,其中1,5-苯并硫氮杂卓的一些化合物已成为治疗神经系统疾病,心血管病的良好药物。1,2,4-噁二唑也由于具有更多潜在活性如抗病毒,杀菌,杀虫和镇静等作用,引起了广泛的关注。本论文中通过一系列反应将这三种活性杂环组合于同一分子中,合成出一系列未见文献报道的化合物,化合物的结构经元素分析,1H NMR,IR谱确证。
本论文所做的工作为:
1.用1-苯基-3-甲基-5-芳氧基-吡唑甲醛与(对位取代)苯乙酮发生羟醛缩合反应制得五种α,β-不饱和酮,然后以此为原料与邻氨基苯硫酚反应合成出十种含1-苯基-3-甲基-5-芳氧基-吡唑基团的1,5-苯并硫氮杂卓类化合物,从而将吡唑这一活性基团引入到同样具有显著活性的苯并硫氮杂卓结构单元中。
2.将合成出的1,5-苯并硫氮杂卓继续与“现场”产生的氧化芳甲腈进行1,3-偶极环加成反应得到20种1,2,4-噁二唑与其并合的三环稠杂环化合物。
3.将生成的含1-苯基-3-甲基-5-芳氧基-吡唑基团的α,β-不饱和酮分别与水和肼,苯肼反应成了10种含吡唑基的吡唑啉类衍生物。
Heterocyclic compounds play an important role in the fields of medical and pesticides.It has been a hot topic to synthesize heterocyclic compounds containing bioactivities and pharmalogical activities by human synthsis in medical chemistry and pesticide chemistry. In fact, the works greatly contribute to human’s healthy and development of agriculture. The works go on in view of these observation and expect to realize the inforcement of many physiological activities by means of combining different heterocycles to one moleculer.
Pyrazole nitrogen-containing heterocycles is intensively applied in pharmaceutical and agrochemical industries due to their antipyretic, anti-inflammatory,herbicidal, insecticidal and fungicidal properties. In the beginning of this century, Somebody began to synthesize the compoud, then, many chemists develop lots of pyrazole derivatives containing more activities by introducing new substituent or combining the pyrazole heterocycle to other heterocycles, which also have good activities.
1,5-benzothiazepine and 1,2,4-oxadiazole heterocycles exhibit diverse biological activities. Of the two heterocycles, 1,5-benzothiazepine compounds have been used as anticonvulsants and tranquilizer drugs and drugs for cardiovascular disease. 1,2,4-oxadiazole also have attracted wide-spread attention due to their potent activities such as antiviral fungicide and anti-inflammatory. In the papers, I combine the aboved three heterocycles to one moleculer and synthesize a series of new heterocycles with a various structure by designing different synthetic procedures. the structures of intermediate and target compounds were estiblished by elemental analysis, 1H NMR, IR data.
The detail works in the paper:
1. 1-phenyl-3-methyl-5-aryloxyl-pyrazol-4-carboxaldehyde reacted with acetophenone or para-substituted acetophenones to formα,β-unsaturated ketone by condensation reaction And the reaction of theα,β-unsaturated ketone with 2-amino thiophenol gave 1,5-benzothiazepines containing 1-phenyl-3-methyl-5-aryloxyl-pyrazole.
2. 1,5-benzothiazepine synthesized underwent 1,3-dipolar cycloadditon reaction with aryl nitrile oxides″in situ″and a series of 1,2,4-oxadiazolo[4,5-d][1,5]benzothiazepine derivatives containing 1-phenyl-3-methyl-5- aryloxyl-pyrazol were obtained.
3. New pyrazoline deriravatives containing pyrazole have been synthesized whileα,β-unsaturated ketone containing 1- phenyl- 3- methyl- 5- aryloxyl- pyrazol react with hydrazine hydrate and phenyl hydrazine in glacial acetic acid under refluxing
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