Investigation On Palladium-catalyzed Functionalization Of Aromatic Ring C-H Bonds

Carbon-hydrogen bonds are widely found in various organic compounds. Theyhave a low reactivity activity, and are difficult to be converted to some other products.Thus it is of important theoretical significance and practical application value to searchfor the method for functionalization of carbon-hydrogen bonds and find the rule of thereaction. To some extent, transition metal-catalyzed functionalization of carbon-hydrogen bonds is accorded with the concepts of “green chemistry” and “atomeconomy”, so the formation of C-X （X=C, N, O and so on） via this method hasbecome one of focus in organic chemistry. To our knowledge, there is less example forthe formation of carbon-phosphorus. In the present thesis, the cleavage of carbon-hydrogen bonds of azole-based compound including benzothiazole and benzoxazolewas actualized to form carbon-phosphorus bonds, then the reaction mechanism wasinvestigated. In addition, palladium-catalyzed cyanation of₂-phenylpyridine wasactualized via the cleavage of carbon-hydrogen bonds with water as the solvent. Thedetailed results are as follows:The formation of carbon-phosphorus on the benzothiazole and benzoxazole wasactualized. The catalytic efficacy of various metal salts such as PdCl₂、Pd（OAc）₂、Pd（TFA）₂、Pd（COD）Cl₂、CuBr₂and CuI was investigated. Among them Pd（OAc）₂had a best efficacy. A series of ligands with nitrogen atom were optimized, and theexperimental results revealed that the presence of catalyst ligand is required tosmoothly performed the reaction. Of the screened ligands, L-Proline was mosteffective. The solvent had a significative effect on the reaction, and the best result wasobtained in the case of acetonitrile solvent. An oxidant was required due to that thereaction is a oxidating cross-coupling, but the experimental results showed that thepresence of the oxygen was adverse to the reaction. After various oxidant includingK₂S₂O8、I₂、Ag₂O、H₂O₂、Cu（OAc）₂etal., it was found that K₂S₂O8was the mosteffective one. In addition, the experimental results suggested that the addition of a base or acid is unnecessary.After the reaction conditions including reaction time, reaction temperature andcatalyst loading and so on were optimized, the optimal condition was found to be5mol%Pd（OAc）₂,30mol%L-Proline,1.5mmol K₂S₂O₈,3.0mL acetonitrile,₂4h,100℃, protection of inert gas. Under the optimal condition, a series ofbenzothiazolesand benzoxazoles was smoothly reacted to give the desired products in up to83%isolated yield.The reaction mechanism was investigated, and the results revealed that anaddition of radical scavenger had an less effect on the reaction. Two intermediates inthe catalytic cycle was detected by electron spray ionization mass spectrometry. Basedon the present results, a catalyzed mechanism was proposed.Palladium-catalyzed cyanation of₂-phenylpyridine was actualized via thecleavage of carbon-hydrogen bonds with water as the solvent. The presence ofpalladium salts and copper salts was required to smoothly performed the reaction. Theefficacy of CuI、 CuBr₂、 Cu（NO₃）₂·3H₂O、 Cu（OAc）₂·H₂O、 CuCl₂·₂H₂O andCuSO₄·5H₂O was investigated, and it was found that the reaction in the presence ofCuBr₂gave the best result. According to the related literatures, some couplingreactions were improved in the presence of the base while an addition of the base wasadverse to the reaction. The cyanation of0.4mmol₂-phenylpyridine was cyanated in₂8%GC yield （from the analysis method of internal standard） under the conditions of0.0₂mmol Pd（OAc）₂,0.4mmol CuBr₂,160℃and₂0h.