基于2-炔基苯甲醛合成异喹啉类化合物的研究
发布时间：2018-10-08 11:28
【摘要】：含有异喹啉、二氢异喹啉骨架结构的天然产物和药物分子大都具有较好的生物活性。异喹啉类化合物不仅是许多天然分子和合成小分子的亚结构单元,同时也是生物碱全合成的重要中间体。基于此,本论文主要研究通过多米诺反应合成几类异喹啉骨架化合物。1.研究了CuI催化的邻炔基苯甲醛与邻氨基苯甲醇多米诺反应构筑了苯并VA嗪并异喹啉类化合物,采用微波辐射加热方式,相比传统的油浴加热方式,反应时间短,操作简便,底物适应性好,收率中等到良好。2.发展了两种合成异喹啉类化合物的方法。其一,在硝酸银的催化下,利用NH4HCO3产生氨源的方法与邻炔基苯甲醛发生串联反应合成异喹啉类化合物。在该反应的优化条下进行底物扩展,均能以中等至良好的收率得到各种取代的异喹啉。其二,通过硝酸银催化/N-N键直接断裂的方法合成异喹啉化合物:邻炔基苯甲醛与NH2NH2反应得到腙,在硝酸银的催化下发生成环反应,继而在硝酸银的作用下发生N-N断裂而芳构化生成异喹啉类化合物。3.发展了一种基于同一1,3-偶极子底物通过不同条件得到两种不同产物的[3+2]环加成反应。邻炔基苯甲醛在银的催化下得到1,3-偶极中间体,然后与乙酰乙酸乙酯在DMF/Li2CO3和MeCN/K2CO3体系中,分别得到吡唑并异喹啉甲酯与吡唑并异喹啉乙酯化合物;并且,在DMF/Li2CO3反应体系中,由于锂离子在中间过渡态的络合作用,得到了单一的反应产物,产物的构型通过X-ray单晶衍射得到了确证。
[Abstract]:Most natural products and drug molecules containing isoquinoline and dihydroisoquinoline skeleton have better biological activity. Isoquinoline compounds are not only substructural units of many natural molecules and synthetic small molecules, but also important intermediates for the total synthesis of alkaloids. Based on this, this paper mainly studied the synthesis of several isoquinoline skeleton compounds. 1 through domino reaction. CuI catalyzed domino reaction of o-alkynyl benzaldehyde with o-aminobenzyl methanol was studied in this paper. The benzo VA azide isoquinoline compounds were constructed by microwave irradiation. Compared with the traditional oil bath heating method, the reaction time was shorter and the operation was simple. The substrate has good adaptability and the yield is medium to good. 2. Two methods for the synthesis of isoquinoline compounds have been developed. First, isoquinoline compounds were synthesized by series reaction of o-alkynyl benzaldehyde with o-alkynyl benzaldehyde by using NH4HCO3 to produce ammonia under the catalysis of silver nitrate. When the substrate was expanded under the optimized strip, various substituted isoquinoline could be obtained in moderate to good yield. Secondly, isoquinoline compounds were synthesized by direct breaking of N-N bond catalyzed by silver nitrate: o-alkynyl benzaldehyde reacted with NH2NH2 to obtain Hydrazone, which formed a ring reaction under the catalysis of silver nitrate. Then N-N breaks under the action of silver nitrate and aromatization to form isoquinoline compounds. 3. A [32] cycloaddition reaction based on the same 1n 3- dipole substrate was developed to obtain two different products under different conditions. In the system of DMF/Li2CO3 and MeCN/K2CO3, pyrazolyl isoquinolinyl methyl ester and pyrazolium isoquinolinyl ethyl ester were obtained respectively, and in the system of DMF/Li2CO3, in the system of DMF/Li2CO3 reaction, the intermediate was obtained from o-alkynyl benzaldehyde under the catalysis of silver, and then with ethyl acetoacetate in the system of MeCN/K2CO3 and pyrazolyl isoquinolinyl methyl ester. Due to the complexation of lithium ions in the intermediate transition state, a single product was obtained. The configuration of the product was confirmed by X-ray single crystal diffraction.
【学位授予单位】：湖南科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626.323
本文编号：2256578
[Abstract]:Most natural products and drug molecules containing isoquinoline and dihydroisoquinoline skeleton have better biological activity. Isoquinoline compounds are not only substructural units of many natural molecules and synthetic small molecules, but also important intermediates for the total synthesis of alkaloids. Based on this, this paper mainly studied the synthesis of several isoquinoline skeleton compounds. 1 through domino reaction. CuI catalyzed domino reaction of o-alkynyl benzaldehyde with o-aminobenzyl methanol was studied in this paper. The benzo VA azide isoquinoline compounds were constructed by microwave irradiation. Compared with the traditional oil bath heating method, the reaction time was shorter and the operation was simple. The substrate has good adaptability and the yield is medium to good. 2. Two methods for the synthesis of isoquinoline compounds have been developed. First, isoquinoline compounds were synthesized by series reaction of o-alkynyl benzaldehyde with o-alkynyl benzaldehyde by using NH4HCO3 to produce ammonia under the catalysis of silver nitrate. When the substrate was expanded under the optimized strip, various substituted isoquinoline could be obtained in moderate to good yield. Secondly, isoquinoline compounds were synthesized by direct breaking of N-N bond catalyzed by silver nitrate: o-alkynyl benzaldehyde reacted with NH2NH2 to obtain Hydrazone, which formed a ring reaction under the catalysis of silver nitrate. Then N-N breaks under the action of silver nitrate and aromatization to form isoquinoline compounds. 3. A [32] cycloaddition reaction based on the same 1n 3- dipole substrate was developed to obtain two different products under different conditions. In the system of DMF/Li2CO3 and MeCN/K2CO3, pyrazolyl isoquinolinyl methyl ester and pyrazolium isoquinolinyl ethyl ester were obtained respectively, and in the system of DMF/Li2CO3, in the system of DMF/Li2CO3 reaction, the intermediate was obtained from o-alkynyl benzaldehyde under the catalysis of silver, and then with ethyl acetoacetate in the system of MeCN/K2CO3 and pyrazolyl isoquinolinyl methyl ester. Due to the complexation of lithium ions in the intermediate transition state, a single product was obtained. The configuration of the product was confirmed by X-ray single crystal diffraction.
【学位授予单位】：湖南科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626.323
【参考文献】
相关期刊论文 前1条
1 高鹏;韩家军;朱永明;张翠芬;李宁;;金属锂二次电池锂负极改性[J];化学进展;2009年Z2期
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