Synthesis Of The Active Substances Containing Arylimidazoles Structures In Traditional Chinese Medicine Catalyzed By Palladium-N-Heterocyclic Carbene(Pd-NHC) Complexes

The structure of arylimidazoles widely consisted in the active substances of traditional Chinese medicine, natural products and their derivatives. As it can efficiently and quickly to construct the C-C bond intramolecular or intermolecular, C-H direct arylation reaction is broadly used in the synthesis and structural modifications of the active substances in traditional Chinese medicine, natural products. The catalysis system based on transition metal determined the reaction conditions and the conversion rate and so on, is the key to the reaction. The palladium-N- heterocyclic carbene(Pd-NHC) complexes with effective catalytic activity play an important role in various catalysis systems. Ⅰ, The purpose of the studyTo provide a method for synthesis and structural modification of the active substances containing arylimidazoles structures in traditional Chinese medicine and natural products. In this stuy, we try to develop highly efficient and stable catalysts, and then apply them to C-H drict arylation of imidazoles compounds. Ⅱ,The methods of the studyA series of palladium-N- heterocyclic carbene(Pd-NHC) complexes were designed, C-H arylation reaction of N- substituted imidazoles and andalkyl bromides would be catalyzed by these complexes after they were synthesized. The relationship between conversion rate of these reaction and complexes’ structures, reaction conditions would be determined. Differences in reactivities among different substrates would be also investigated. Ⅲ, The experimental results8 palladium-N- heterocyclic carbene(Pd-NHC) complexes(C1~C8) were synthesized and determined successfully. Studies showed these complexes could effectively catalyze the C-H direct arylation reaction of N- substituted imidazoles and alkylbromides in 1mol % of the amount, and the complexe C8 showed the best catalytic activity. The most effective reaction condition were also selected out: by using K2CO3 as the base, pivalate as the acid, solvent were N, N- dimethylacetamide, under aerobic the reaction systems were heat to 130 oC for 12 hours. Investigation also showed 1- methylimidazole and 1, 2-dimethylimidazole performed higher reactivity in the reaction than 1-benzylimidazole and 1- phenylimidazole. The alkyl bromides with electron-withdrawing groups had a higher reactivity, the conversion rates were 46%~98%, while the alkylbromides with electron donating groups showed rather lower reactivity, the conversion rates were only 5%~62%. In this reaction condition, alkyl chlorine almost had no reactivity. All the C-H arylation reaction had a good regioselectivity in C-5 of N- substituted imidazoles. Most of the coupling products were separated and determined by NMR. Ⅳ, Conclusions8 new palladium-N- heterocyclic carbene(Pd-NHC) complexes(C1~C8) were synthesized. These complexes could effectively catalyze the C-H direct arylation reaction of N- substituted imidazoles and alkylbromides.