新型三嗪环蕃的合成与应用及其中间体的应用探索
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摘要
近些年超分子化学领域中的大环化学发展迅速,具有分子识别能力的有机化合物的设计、合成与应用成为超分子化学和有机化学的研究热点之一。环蕃作为主-客体化学领域中非常具有代表性的主体化合物已经在诸多领域中取得了令人瞩目的成果。本论文以合成新型的氮杂环蕃为目标,通过用三聚氯氰和别的一些简单化合物在比较温和的条件下合成了三大类新型环蕃化合物。全文共分五部分,主要研究内容和结论如下：
第一部分简单介绍了超分子化学中的主体化合物冠醚、环糊精、杯芳烃、环蕃、葫芦脲、卟啉和酞箐、环肽等的基本概念和进展概况。较详细地介绍了环蕃的五种合成方法及其在应用方面的研究。
第二部分利用三聚氯氰、对硝基苯酚、苯酚、甲醇钠、4,4'-二氨基二苯甲烷和三乙胺合成了单环环蕃1-5a、1-5b、2-3a、2-3b、2-4、2-5a、2-5b。结果表明：在合成环蕃1-5a和1-5b时,硝基的还原是关键步骤；在合成2-3a、2-3b、2-4、2-5a、2-5b时,辅酸剂的选择非常重要。另外,所有成环步骤都需要在高度稀释下进行,否则得到的是链状高聚物。
第三部分以三聚氯氰、4,4'-二氨基二苯甲烷、邻苯二胺和1,6'-己二胺为原料合成了双环环蕃3-3和3-5。飞行质谱显示有目的产物的峰,证明的确合成出了该化合物,但是由于双环环蕃极难溶解,无法对其分离纯化,导致元素分析与理论值相差较大。如何能提高双环环蕃的溶解性是后续工作的重点和难点。
第四部分鉴于前面所合成的环蕃溶解性均比较差的特点,本部分的重点就是提高环蕃的溶解性,通过给环蕃引入活性基团,成功合成出了可溶性环蕃4-3、4-5、4-6、4-7。同时用水热法对它们进行了晶体培养,得到了4-3和4-6的晶体,并用X-射线单晶衍射对其结构进行了表征。
第五部分用环蕃中间体对枯草芽孢杆菌、金黄色葡萄球菌、大肠杆菌等三种细菌作了生物测试实验,发现用于生测的中间体均有灭菌或抑菌作用,其效果与分子中所含的氯原子个数有关,随着分子中氯原子个数的减少,它的杀菌或抑菌作用也在逐渐变弱；另外还对合成出的可溶性环蕃4-3和4-6进行了金属阳离子识别实验,紫外吸收谱图显示,对于不同族的金属离子,只有过渡金属中的一些离子能被识别。
In recent years, macrocyclic chemistry in the field of supramolecular chemistry has developed rapidly. In organic chemistry and supramolecular chemistry, the hottest studies are the design, synthesis and application of artificial organic compound which has molecular recognition properties. As the most representative host compound in host-guest chemistry, cyclophane have achieved remarkable achievement in many fields. In this thesis, we have synthesized three new classes of cyclophane compounds using cyanuric chloride and other relatively simple compounds under mild conditions. This dissertation divides into five chapters and the main contents and conclusions are listed as following:
The chapter 1:Briefly introduce the basic concepts and the progress of crown ethers, cyclodextrins, calixarenes, cyclophanes, cucurbituril, prophyrin, phthalocyanine, cyclic peptide in the supramolecular chemistry. And we described the five approaches of the synthesis of cyclophanes and their application research.
The chapter 2:Single-ring cyclophanes 1-5a, 1-5b,2-3a,2-3b,2-4,2-5a,2-6b are synthesized by using cyanuric chloride, p-nitrophenol, phenol, sodium methoxide, 4,4'-diaminodiphenyl methane and triethylamine, meanwhile they are characterized by Elemental analysis, IR, MALDI-TOF-MS and 1H-NMR. The results showed that:as the synthesis of cyclophanes 1-5a and 1-5b, the nitro reduction is a key procedure; in the synthesis of 2-3a,2-3b,2-4,2-5a,2-6b, the selection of the secondary acid agent is very important. In addition, all the procedures of cyclization should be operated under the highly diluted condition, otherwise it will produce polymer chain.
The chapter 3:Using cyanuric chloride, o-phenylenediamine,4,4'-diaminodiphenyl methane and 1,6'-hexanediamine as raw materials, we have synthesized bicyclic cyclophanes 3-3 and 3-5. MALDI-TOF-MS showed the peak of the target substance, which really proved that the target compound have been synthesized, but because of the bicyclic cyclophane is very difficult to be dissolved, it can not be isolated and purified, leading to the result of elemental analysis dose not match the theoretical value. So, how to enhance the solubility of bicyclic cyclophane is important and difficult aspect of following work.
The chapter 4:In view of the previously cyclophane relatively poor solubility characteristics, the focus of this section is to increase the solubility of cyclophane through the introduction of active groups to the cyclophane and successful in the synthesis of soluble cyclophane 4-3,4-5,4-6,4-7. At the same time, the perfect crystal of cyclophane 4-3 and 4-6 were gained, and their structures were characterized by the X-ray diffraction.
The chapter 5:Some experiments were carried out to the synthetic compounds and their intermediates. Bacillus subtilis, Staphylococcus aureus, Escherichia coli were used for biological testing laboratories, found that the sterilization or inhibition effect of the intermediates were related with the number of chlorine atoms, with the reduction of the number of chlorine atoms, the bactericidal or bacteriostatic effect is gradually weakened. We also used the metal cations to carry out the recognition experiment for the synthetic soluble cyclophane 4-3 and 4-6, UV absorption spectra showed that the metal ions for different families, only some of the transition metal ions can be identified.
第一部分简单介绍了超分子化学中的主体化合物冠醚、环糊精、杯芳烃、环蕃、葫芦脲、卟啉和酞箐、环肽等的基本概念和进展概况。较详细地介绍了环蕃的五种合成方法及其在应用方面的研究。
第二部分利用三聚氯氰、对硝基苯酚、苯酚、甲醇钠、4,4'-二氨基二苯甲烷和三乙胺合成了单环环蕃1-5a、1-5b、2-3a、2-3b、2-4、2-5a、2-5b。结果表明：在合成环蕃1-5a和1-5b时,硝基的还原是关键步骤；在合成2-3a、2-3b、2-4、2-5a、2-5b时,辅酸剂的选择非常重要。另外,所有成环步骤都需要在高度稀释下进行,否则得到的是链状高聚物。
第三部分以三聚氯氰、4,4'-二氨基二苯甲烷、邻苯二胺和1,6'-己二胺为原料合成了双环环蕃3-3和3-5。飞行质谱显示有目的产物的峰,证明的确合成出了该化合物,但是由于双环环蕃极难溶解,无法对其分离纯化,导致元素分析与理论值相差较大。如何能提高双环环蕃的溶解性是后续工作的重点和难点。
第四部分鉴于前面所合成的环蕃溶解性均比较差的特点,本部分的重点就是提高环蕃的溶解性,通过给环蕃引入活性基团,成功合成出了可溶性环蕃4-3、4-5、4-6、4-7。同时用水热法对它们进行了晶体培养,得到了4-3和4-6的晶体,并用X-射线单晶衍射对其结构进行了表征。
第五部分用环蕃中间体对枯草芽孢杆菌、金黄色葡萄球菌、大肠杆菌等三种细菌作了生物测试实验,发现用于生测的中间体均有灭菌或抑菌作用,其效果与分子中所含的氯原子个数有关,随着分子中氯原子个数的减少,它的杀菌或抑菌作用也在逐渐变弱；另外还对合成出的可溶性环蕃4-3和4-6进行了金属阳离子识别实验,紫外吸收谱图显示,对于不同族的金属离子,只有过渡金属中的一些离子能被识别。
In recent years, macrocyclic chemistry in the field of supramolecular chemistry has developed rapidly. In organic chemistry and supramolecular chemistry, the hottest studies are the design, synthesis and application of artificial organic compound which has molecular recognition properties. As the most representative host compound in host-guest chemistry, cyclophane have achieved remarkable achievement in many fields. In this thesis, we have synthesized three new classes of cyclophane compounds using cyanuric chloride and other relatively simple compounds under mild conditions. This dissertation divides into five chapters and the main contents and conclusions are listed as following:
The chapter 1:Briefly introduce the basic concepts and the progress of crown ethers, cyclodextrins, calixarenes, cyclophanes, cucurbituril, prophyrin, phthalocyanine, cyclic peptide in the supramolecular chemistry. And we described the five approaches of the synthesis of cyclophanes and their application research.
The chapter 2:Single-ring cyclophanes 1-5a, 1-5b,2-3a,2-3b,2-4,2-5a,2-6b are synthesized by using cyanuric chloride, p-nitrophenol, phenol, sodium methoxide, 4,4'-diaminodiphenyl methane and triethylamine, meanwhile they are characterized by Elemental analysis, IR, MALDI-TOF-MS and 1H-NMR. The results showed that:as the synthesis of cyclophanes 1-5a and 1-5b, the nitro reduction is a key procedure; in the synthesis of 2-3a,2-3b,2-4,2-5a,2-6b, the selection of the secondary acid agent is very important. In addition, all the procedures of cyclization should be operated under the highly diluted condition, otherwise it will produce polymer chain.
The chapter 3:Using cyanuric chloride, o-phenylenediamine,4,4'-diaminodiphenyl methane and 1,6'-hexanediamine as raw materials, we have synthesized bicyclic cyclophanes 3-3 and 3-5. MALDI-TOF-MS showed the peak of the target substance, which really proved that the target compound have been synthesized, but because of the bicyclic cyclophane is very difficult to be dissolved, it can not be isolated and purified, leading to the result of elemental analysis dose not match the theoretical value. So, how to enhance the solubility of bicyclic cyclophane is important and difficult aspect of following work.
The chapter 4:In view of the previously cyclophane relatively poor solubility characteristics, the focus of this section is to increase the solubility of cyclophane through the introduction of active groups to the cyclophane and successful in the synthesis of soluble cyclophane 4-3,4-5,4-6,4-7. At the same time, the perfect crystal of cyclophane 4-3 and 4-6 were gained, and their structures were characterized by the X-ray diffraction.
The chapter 5:Some experiments were carried out to the synthetic compounds and their intermediates. Bacillus subtilis, Staphylococcus aureus, Escherichia coli were used for biological testing laboratories, found that the sterilization or inhibition effect of the intermediates were related with the number of chlorine atoms, with the reduction of the number of chlorine atoms, the bactericidal or bacteriostatic effect is gradually weakened. We also used the metal cations to carry out the recognition experiment for the synthetic soluble cyclophane 4-3 and 4-6, UV absorption spectra showed that the metal ions for different families, only some of the transition metal ions can be identified.
引文
[1]龚汉元,王德先,黄志镗.基于Zn(Ⅱ)-甲基氮杂杯[4]吡啶复合物的氨基酸和阴离子识别[J].中国科学,B辑：化学,2009,39(10)：1194-1201
[2]Kuroda Y, Kato Y, Higashioji.Chiral amino acid recognition by a porphyrin-based artificial receptor[J]. American Chemical Society,1995,117:10950-10958
[3]Worm K, Schmidtchen F P.Molecular recognition of anions by zwitterionic host molecules in water[J]. Angew Chemi Int Ed Engl,1995,34:65-66
[4]昊世康.超分子光化学前景[J].感光化学与光化学,1994,12(4)：332-341
[5]孙得志,朱兰英,宋兴民.超分子化学、选择性分子间力和若干化学研究领域[J].聊城师范学院学报(自然科学版),1998,11(2)：27-33
[6]刘育.超分子化学：合成受体的分子识别与组装[M].天津：南开大学出版社,2001：1-624
[7]靳苏荣,姚礼峰.9-钨磷酸／结晶紫超分子化合物的合成及表征[J].合成化学,2001,9(3)：244
[8]孙晓红,刘源发,城邦.取代苯氧乙酸嘧霉胺盐的合成及杀菌活性[J].西北大学学报(自然科学版),2007,37(1)：55-58
[9]向智男,宁正祥.三种苯甲酸的抗菌剂的活性-结构关系研究[J].食品添加剂,2005,26(10)：159-162
[10]吉鹏举.新型多活性中心含氮杂环化合物的合成及生物活性研究[D].西安：西北大学2005
[11]Sun Xiaohong, Liu Yuanfa, Chen Bang, et al. Synthesis and Fungicidal Activities of Pyrimethanil Heterocyclic Acid Salt[J]. Chinese Journal of Chemistry.2007,25(1): 98-101
[2]Kuroda Y, Kato Y, Higashioji.Chiral amino acid recognition by a porphyrin-based artificial receptor[J]. American Chemical Society,1995,117:10950-10958
[3]Worm K, Schmidtchen F P.Molecular recognition of anions by zwitterionic host molecules in water[J]. Angew Chemi Int Ed Engl,1995,34:65-66
[4]昊世康.超分子光化学前景[J].感光化学与光化学,1994,12(4)：332-341
[5]孙得志,朱兰英,宋兴民.超分子化学、选择性分子间力和若干化学研究领域[J].聊城师范学院学报(自然科学版),1998,11(2)：27-33
[6]刘育.超分子化学：合成受体的分子识别与组装[M].天津：南开大学出版社,2001：1-624
[7]靳苏荣,姚礼峰.9-钨磷酸／结晶紫超分子化合物的合成及表征[J].合成化学,2001,9(3)：244
[8]孙晓红,刘源发,城邦.取代苯氧乙酸嘧霉胺盐的合成及杀菌活性[J].西北大学学报(自然科学版),2007,37(1)：55-58
[9]向智男,宁正祥.三种苯甲酸的抗菌剂的活性-结构关系研究[J].食品添加剂,2005,26(10)：159-162
[10]吉鹏举.新型多活性中心含氮杂环化合物的合成及生物活性研究[D].西安：西北大学2005
[11]Sun Xiaohong, Liu Yuanfa, Chen Bang, et al. Synthesis and Fungicidal Activities of Pyrimethanil Heterocyclic Acid Salt[J]. Chinese Journal of Chemistry.2007,25(1): 98-101