【作者】 赵金武；

【导师】 江焕峰；

【作者基本信息】 华南理工大学 ， 应用化学， 2013， 博士

【摘要】 本论文有两部分组成，第一部分是2-氨基苯并噻唑的合成研究，第二部分是以二氧化碳为原料合成1,3-噁唑烷-2-酮的研究。2-氨基苯并噻唑是一类具有多种生物活性的杂环类化合物，如临床用于治疗肌萎缩性脊髓侧索硬化症的利鲁唑就属于2-氨基苯并噻唑类化合物，2-氨基苯并噻唑还广泛用于抗菌、抗病毒、抗癌、抗帕金森等药物的研发中。因此，2-氨基苯并噻唑在药物化学中占有非常重要的地位。本论文以环己酮类化合物和硫脲类化合物作为原料，在酸性条件下，以碘作为催化剂，以氧气作为氧化剂，在没有过渡金属参与的情况下，合成了各种2-氨基苯并噻唑。该反应是在30mol%碘和5当量对甲苯磺酸的作用下，在DMSO介质中75℃下反应24小时进行的。2-位、3-位和4-位取代的环己酮都可以得到相应的2-氨基苯并噻唑，无取代、单取代和N, N-二取代的硫脲也都能得到相应的2-氨基苯并噻唑产物。2-氨基萘[2,1-d]噻唑和2-氨基萘[1,2-d]噻唑的合成方法尚未有文献报道，而本论文所研究的合成2-氨基苯并噻唑的方法可以高产率的合成这两类新骨架化合物。该反应所用氧化剂为氧气，绿色环保，而且无需金属参与，所得产品无被金属污染的危险。二氧化碳既是地球上最为丰富的碳1资源又是主要的温室气体，以二氧化碳为原料合成有机小分子的研究对环境保护和碳1资源的充分利用都有十分重要的意义。本论文对以二氧化碳为原料合成1,3-噁唑烷-2-酮进行了研究。首先，二氧化碳与末端炔、酮类化合物及伯胺在碘化亚铜和氯化亚锡的催化下进行四组分的环综合反应得到1,3-噁唑烷-2-酮。该反应30mol%CuI和20mol%SnCl2的催化下，二氧化碳压力1.5MPa，在DMSO介质中70℃反应12小时以良好的产率得到相应的1,3-噁唑烷-2-酮。该反应是酮类化合物与末端炔、胺进行类似A3-Coupling反应的一个实例，直链的和环状的脂肪酮均能顺利进行反应，但空间位阻大的芳酮无法得到相应的1,3-噁唑烷-2-酮。在研究上述反应过程中，我们发现，当无酮类化合物存在时，二氧化碳也能与末端炔和伯胺进行三分子环缩合反应得到-1,3-噁唑烷-2-酮。反应是在10mol%CuI催化下，二氧化碳压力为2MPa，无溶剂条件下加热至90℃反应24小时进行的。亲核性强的脂肪伯胺和芳基末端炔均能以良好产率生成相应的-1,3-噁唑烷-2-酮。5-位亚烷基取代的-1,3-噁唑烷-2-酮通常由炔丙胺与二氧化碳反应得到，而本论文两种固定二氧化碳为5-位亚烷基取代的-1,3-噁唑烷-2-酮的原料则为较为廉价易得到的末端炔、伯胺和酮类化合物。更多还原

【Abstract】 This dissertation consists of part I and part II. Part I involves the reseach on thesynthesis of2-aminobenzothiazoles and part II involves the investigation on the synthesis of1,3-oxazolidin-2-ones using carbon dioxide as feedstock.2-Aminobenzothiazoles are an important class of heterocycle whose diverse biologicalactivities make them privileged scaffolds in drug discovery. For example, marketed Riluzoleis a2-aminobenzothiazole compound employed in the treatment of amyotrophic lateralsclerosis; They have also been widely used to develop anti-diabetic, anti-microbial, anti-viral,anti-cancer, anti-parkinsonian agents and so on. Therefore,2-aminobenzothiazole derivativesplay an important role in medicinal chemistry. In part I, it is presented that various2-aminobenzothiazole were metal-freely prepared from cyclohexanones and thioureas in theacidic conditions catalyzed by iodine with oxygen as an oxidant. This transformation wasconducted in DMSO at75oC for24hours by adding30mol%iodine and5equivp-toluenesulfonic acid.2-substituted,4-substituted,3-substituted cyclohexanones andnon-substituted, mono-substituted, N, N-disubstituted thioureas all went through the process.It is worth noting that2-aminonaphtho[2,1-d]thiazoles and2-aminonaphtho[1,2-d]thiazolescan be prepared via this method in satisfactory yield, whose practical synthetic processes havenot been reported. This strategy also employs oxygen as a green oxidant and avoids transitionmetals.Carbon dioxide is the major greenhouse gas as well as the most abundant carbonresourse in the earth. Chemical fixation of carbon dioxide is of great importance from theviewpoint of the protection environment and carbon resourse utilization. In part II, it wasinvestigated that carbon dioxide was chemically fixated into1,3-oxazolidin-2-ones. Firstly,CuI/SnCl2Co-Catalyzed four-component assembly of carbon dioxide, alkynes, amines andketones to afford1,3-oxazolidin-2-ones. This conversion was carried out in DMSO at70oCfor12hours under CO2pressure of1.5MPa by adding30mol%CuI and20mol%SnCl2togive1,3-oxazolidin-2-ones in good yield. This reaction is an example that ketones, terminalalkynes and primary amines can go across a A3-type coupling, and linear or cyclic aliphaticketones are good substrates while aromatic ketones are not due to its steric hindrance. In the course of the above research, it was found that carbon dioxide, terminal alkynes and primaryaimines could also reaction in the absence of ketones to produce another1,3-oxazolidin-2-ones. The three-component cycloaddition reaction was performed under CO2pressure of2MPa at90oC for24hours under solvent-free conditions using10mol%CuI ascatalyst. Primary aliphatic amine with strong nucleophilicity and aryl-substituted terminalalkynes were good substrates.5-Alkylidene-1,3-oxazolidin-2-ones are commonly synthesisfrom carbon dioxide and costly propargyl amines while they can be prepared for moreavailable alkynes, ketones, amines and carbon dioxde via the protocols in part II of thisdissertation.更多还原