Transition Metal Palladium-catalyzed Synthesis Of 2-arylacyl Indole Derivatives

As a nitrogen-containing heterocyclic compound,indole exists widely in all aspects of life.Among the many derivatives of indole,2-aroyl indole,as a molecule with special drug activity,shows excellent inhibitory activity on tumor cells.However,the reaction conditions of common synthesis methods require strict and complicate operation steps,such as: toxic gas CO needs to be added.Therefore,we hope to develop a mild,efficient,and environmentally friendly method for the synthesis of 2-aroyl indole.After controlling the reaction time,we explored the progress and trend of the entire reaction.Furthermore,we got insight into the reaction mechanism to obtained a more comprehensive and systematic understanding of this new synthesis pathway.On the basis of fully investigating the existing synthesis methods of 2-arylacyl indole,p-toluidine and ?-bromo ketone were used as raw materials in this subject.Firstly,the substrate ?-amino ketone was synthesized;then,under the synergistic effect of palladium acetate catalysis and oxidant oxidation,a new method for the synthesis of 2-aroylindole by tandem oxidation cyclization was explored.This subject conducted the following five aspects of research:1.Firstly,the synthesis of ?-amino ketone by p-toluidine and ?-bromo ketone was studied.After reacted with palladium acetate and oxidant,2-arylacyl indole was obtained.2.Optimization of the reaction conditions to achieved the goal of increasing the yield of the target product3.Substrate expanded.Under the best reaction conditions,2-arylacyl indole derivatives were synthesized by changing the substituents on the aromatic ring.4.Explore the reaction trend.Under the best reaction conditions,the reaction time was changed to analyze the amount of each compound in the system.5.Research on the reaction mechanism.Put forward the hypothesis of the possible mechanism of the reaction,and verify it through experiments.A new method for the synthesis of 2-arylacyl indole has been found in this work.Using aniline and aryl acetone as raw materials,we synthesized 26 2-aroyl indole derivatives with a maximum yield of 90%,and characterized these compounds by nuclear magnetic resonance(NMR).This method has the characteristics of mildness,high efficiency,and low environmental pollution,which provides a reference for the subsequent synthesis of such compounds.