| Nitrogen-containing heterocyclic compounds are widely used in medicine, pesticides, natural products fields, and so on. So the synthesis of such compounds is a hot area in the field of organic synthesis and the copper catalytic Ullmann reaction is one of the most effective methods to build the C-N bond. But the traditional Ullmann reaction needs quite harsh reaction conditions, such as equivalent copper catalysts, high reaction temperatures and long reaction time, limiting the scope of application of the reaction. With further research, the chemists found that addition of a suitable ligand in the catalyst system can improve the reaction efficiency and need relatively mild reaction conditions. Therefore, the current research about Ullmann reaction focuses on the design and optimization of the copper-ligand aspect.Based on the previous studies, this paper is committed to the development of new and efficient "copper-ligand" catalyst system, and further optimize the copper-catalyzed C-N coupling reaction. The specific tasks include the following several parts:In the first part, we designed and synthesized a series salicylic hydrazide compound as the ligand of copper catalyst, then we established a catalytic system of CuSO4 / hydrazide ligand to achieve the Narylation reaction between imidazole and other nitrogen-containing heterocyclic in the aqueous phase. Under the preferred reaction conditions [CuSO4(10 mol%), 2-hydroxy-N’-methylbenzohydrazide(L4, 20 mol%), TBAB(20 mol%), NaOH(2 equiv.), H2O(1.0 mL), 120 ℃, 24h], the reaction yields of 4-Iodotoluene and imidazole reached 87%, which is the model reaction. Under the optimal reaction conditions, the research about the applicability of the substrate catalytic systems were expanded. The results showed that this catalytic system have high catalytic activity for the coupling reaction about different aryl iodide and aryl bromine with nucleophiles such as indole, benzyl amine. Finally we get 23 kinds of target products in the yield of between 25-94%, and the products were characterized by 1H NMR.In the second part, in order to expand the range of copper / hydrazide ligand catalytic system application, we established the CuI / hydrazide ligand catalytic system to achieve the Sonogashira coupling reaction of halogenated aromatic with aryl alkyne in the organic phase. Under the optimal reaction conditions [L4(20 mmol%), CuI(10 mmol%), K2CO3(1.0 mmol), DMF(1.0 mL), 120℃, 24 h], the reaction yields of 1-methoxy-4-methylbenzene withethynylbenzene reached 86%,which is the model reaction. Under the optimal reaction conditions, the research of the applicability of the substrate catalytic systems was expanded. The results showed that this catalytic system have high catalytic activity for different aryl iodides. Finally we get 10 kinds of target products in the yield of between 34-86%, and the products were characterized by 1H NMR.In the third part, recycled catalyst or ligand is the important means to achieve green catalytic systems, based on this, we carried out the immobilization and recycling of the salicylic hydrazide. Firstly, through the click chemistry reaction make the salicylic hydrazide attached to the chloromethyl polystyrene resin, and the product was characterized by FI-IR. Subsequently, we selected 4-iodotoluene and imidazole’ coupling reaction as the model reaction. Unfortunately, the results is 20%, which is not satisfactory. The reason may be the steric hindrance, which hindered the coordination of copper and ligand, thereby reducing the reactivity.In summary, in this paper we established a copper / hydrazide catalytic system which realized Ullmann C-N coupling reaction in the aqueous phase. The catalytic system needs relatively mild reaction conditions and has high catalytic activity for different aryl iodide and aryl bromine. Then we use it for Sonogashira coupling reaction and it can catalyze the reaction of aryl iodide with aryl alkyne. Finally, we get immobilized ligand but its catalytic effect is not ideal. |
PDF Full Text Request