基于二氧化碳与端炔的羧化反应构建含氮稠杂环

发布时间：2018-01-04 12:40

本文关键词：基于二氧化碳与端炔的羧化反应构建含氮稠杂环　出处：《南开大学》2016年硕士论文　论文类型：学位论文

【摘要】：二氧化碳是温室气体的主要成分,同时也是分布最广、储量丰富的碳一资源。作为一种廉价易得、安全的可再生碳一合成子,二氧化碳资源化利用的有效途径之一就是将其转化为具有高附加值的精细化工产品。目前,工业生产所消耗的二氧化碳已经取得一定的规模,但由于二氧化碳分子热力学稳定性和动力学惰性的限制,化学利用二氧化碳的量还远远不能与化石原料的消耗量相比。除此之外,二氧化碳资源化利用产品结构不够丰富,其中90%以上是用于生产尿素、无机碳酸盐、碳酸酯、聚碳酸酯和水杨酸等,仅有小部分二氧化碳用于其它高附加值化学品的制备。从有机合成的角度来看,拓展二氧化碳应用范围,提高二氧化碳应用规模的有效策略分为两方面,一是通过调控金属、配体等设计更高效的催化剂或采用高能态的原料,降低二氧化碳的转化能垒,从而实现温和条件下二氧化碳的化学转化;二是设计更为绿色、实用的反应路径,提高反应的选择性和步骤经济性,从而有效地将二氧化碳“固定”在有机分子中。实现温和条件(低压)下二氧化碳的转化可以降低能耗、减少设备消耗,有利于实验室基础研究结果快速应用于工业生产。炔酸酯是一类缺电子炔烃,常常作为迈克尔加成反应的受体广泛应用于构筑杂环化合物。我们课题组在金属催化二氧化碳的化学转化方面积累了大量经验,在此基础上,我们开展了常压二氧化碳化学利用的研究:1)炔酸酯在杂环化合物合成中的应用非常广泛。从商品化的末端炔烃出发,以二氧化碳作为碳一合成子通过C(sp)-H键直接羧化的方法制备炔酸酯是最具优势的合成路线。使用新型的铜基离子液体[Cu(Im12)2][CuBr2]为催化剂,高效实现了末端炔烃的羧化酯化反应。催化剂合成简单,且不需要使用额外的配体,在室温、常压二氧化碳下就可实现端炔羧化反应。底物适用面较广,带有吸电子取代基和给电子取代基的底物均能以高收率(70~96%)转化为相应炔酸酯产物。通过13C NMR检测到了铜催化剂对底物炔烃的活化,催化剂中包含的长烷基链取代的咪唑配体使催化剂具有更高的溶解性、疏水性和稳定性,增强了中心铜原子的电子云密度,使得反应可以在温和条件下高效进行。2)异吲哚酮并异VA唑类稠环化合物广泛存在于天然产物和药物活性成分中,吲哚酮结构具有良好的抗菌、抗炎活性,而异VA唑类衍生物也是一类具有良好杀虫、抗菌、抗炎生物活性的杂环有机化合物。我们使用CuCl/PPh3催化端炔与二氧化碳的羧化反应制备炔酸酯,随后向反应体系中直接加入N-羟基邻苯二甲酰亚胺(NHPI),通过一锅两步法成功地实现异吲哚酮并异VA唑类稠环化合物的合成(收率65~96%)。该体系的优点在于以羧化反应促进环化反应,无需分离中间产物炔酸酯,三苯基膦即作为羧化反应的配体,同时也用作催化剂促进第二步的环化反应。经过羧化酯化环化反应,同时构建了两个C-C键和两个C-O键,将二氧化碳分子拓展到药物分子中的合成中。3)作为由二氧化碳制备的高附加值产品,炔酸酯的应用也是二氧化碳资源化利用的更进一步体现。我们以炔酸酯和NHPI为原料,使用廉价易得的NaOAc·3H2O为催化剂,合成具有潜在生物活性的异吲哚酮并异VA唑类稠环化合物。该方法只需10 mol%的催化剂用量便可实现该[3+2]环化反应高效进行。另外,通过设计控制实验,认为NHPI盐作为真正的催化中心,促进该反应以类似oxa-Michael-aldol的反应机理进行。
[Abstract]:Carbon dioxide is the main component of greenhouse gases, but also the most widely distributed and abundant carbon resources. As a kind of cheap, renewable carbon synthon safety, one of the effective ways of resource utilization of carbon dioxide is converted into high value-added fine chemical products. At present, the consumption of industrial production carbon dioxide has a certain scale, but because the carbon dioxide molecular thermodynamic stability and kinetic inertia constraints, compared to chemical consumption by the amount of carbon dioxide is far from fossil raw materials. In addition, CO2 utilization structure of the product is not rich, of which more than 90% is used in the production of urea, inorganic carbonate, carbonate, polycarbonate salicylic acid and etc., only a small part of the carbon dioxide used for other high value-added chemicals. The preparation of organic synthesis from the angle of extension. The application scope of exhibition of carbon dioxide, improve carbon dioxide effective strategy application scale is divided into two aspects, one is through the regulation of metal catalyst, ligand to design more efficient use of raw materials or energy state, reduce carbon dioxide conversion barrier, so as to realize the two chemical oxygen carbon conversion under mild conditions; the two is to design more green. The utility of the reaction path, improve the reaction selectivity and the steps of economy, thus effectively carbon dioxide will be "fixed" in organic molecules. Mild conditions (low pressure) conversion of carbon dioxide can reduce energy consumption, reduce equipment consumption, is conducive to the laboratory study results rapidly applied in industrial production. Propargyl ester is a kind of electron deficient alkyne, often as the Michael addition reaction of receptor is widely applied to the construction of heterocyclic compounds. The chemical area in metal catalyzed carbon dioxide into our research group Tired of a lot of experience, on this basis, we carried out research on atmospheric chemistry of carbon dioxide by: 1) propargyl ester is widely used in the synthesis of heterocyclic compounds. Terminal alkynes from commercialization of carbon to carbon dioxide as a synthesis by C (SP) for direct carboxylation of -H bond with method of preparing alkyne ester is the most advantage of the synthetic route. The use of copper based ionic liquid type [Cu (Im12) 2][CuBr2] as catalyst, the efficient implementation of carboxyl esterification reaction of terminal alkynes. The catalyst synthesis is simple, and does not need to use additional ligands, at room temperature, atmospheric CO2 can achieve the alkyne carboxylation reaction substrates. Wide, with electron withdrawing substituents and electron donating substituents are substrates with high yield (70~96%) into the corresponding Alkynoates products. Through the 13C NMR detected the activation of copper catalyst to substrate catalyst containing alkynes. Long alkyl chain substituted imidazole ligand of the catalyst has higher solubility, hydrophobicity and stability, enhance the electron density of central copper atom, the reaction can be efficiently.2 under mild conditions) isoindolones and ISO VA azole fused ring compounds exist widely in natural products and active pharmaceutical ingredients in indole, ketone structure has good antibacterial, anti-inflammatory activity, different VA azole derivatives are a kind of good insecticidal, antibacterial, anti-inflammatory and biological activity of heterocyclic organic compounds. We use CuCl/PPh3 and carbon dioxide catalyzed alkyne carboxylation reaction preparation of propargyl ester, then directly added to the reaction system of N- hydroxy two methyl benzene imide (NHPI), the two step is achieved successfully by one pot synthesis isoindolones and ISO VA azole fused ring compounds (yield 65~96%). The advantages of this system is to promote the cyclization reaction to carboxylation reaction, no The need to separate the intermediate product of propargyl ester, three phenyl phosphine ligands as carboxylation reaction, but also used as a catalyst to promote cyclization reaction in second steps. After carboxylation esterification cyclization, and constructed two C-C bonds and two C-O bonds, will be extended to the synthesis of.3 in carbon dioxide molecules in drug molecules) as a high value-added products from carbon dioxide preparation, further reflect the Alkynoates application is carbon dioxide utilization. We use Alkynoates and NHPI as raw materials, the use of cheap NaOAc 3H2O as catalyst, synthesis of isoindolone potential biological activity and different VA azole fused ring compounds. This method only needs a catalyst dosage of 10 mol% can achieve the [3+2] cyclization reaction efficiently. In addition, through the design of control experiment, NHPI salt as the catalytic center of the real, to promote the reaction to oxa-Michael-aldol like reaction The mechanism is carried out.

【学位授予单位】：南开大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：X701;O626

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