| Transition metal catalysis to build carbon - carbon, carbon - miscellaneous bonds of coupling reaction is a hotspot of modern organic synthesis methodology, and is also an important method of organic synthesis. There are already a lot of reports about precious transition metal catalysis, like palladium, ruthenium, rhodium, and so on. But there are less reports about copper, iron, nickel, cobalt and other cheap transition metal catalyzed hydrocarbon activation coupling. In this paper, modern organic synthesis method has carried on the exploration of cheap metal catalytic hydrocarbon activation coupling reaction, and with copper salt as a promoter, through reasonable and effective design, a high rate, high selectivity synthesis reaction of constructing carbon - carbon bonds was developed. Such compounds have good physiological activities, and they are critical skeleton of many natural products and drug molecules.This paper mainly present the research of copper promote reaction based on 8-amino quinoline as bidentate ligand guiding of benzamide derivative reacting with nitro oxide through hydrocarbon activation to give a ring compound:3-methylene isoindole-1-one compounds, and it is a natural drug molecular skeleton. In terms of reaction conditions selection, through optimizing those factors like the promoter, alkali, solvent, temperature, additives and other factors, it was found that when using 1.0 equivalent of benzamide,10.0 equivalent nitroethane,2.0 equivalent copper acetate,3.0 equivalent potassium tert-butyl alcohol,2.0 equivalent tetrabutyl ammonium acetate,2 mL DMSO, reacting for 12 hours at 130℃ is the best reaction condition and with 82% yield.Through extending the substrate, the applicability of this reaction was tested. By choosing benzamide, which containing different substituents reacting with nitro ethane, the target product and good yield were achieved. When para- position has electron giving group or halogen replacing group, the activity of reaction is better, and it can get the target product better, and when para- position of benzamide contains strong pull electron group, both the activity and the yield of the reaction decrease, and in addition to that, the reaction can proceed better when the meta- position of benzamide contains replacing group. At the same time when ortho- position of benzamide contains substituents without affecting by steric hindrance, when expanding benzene ring to the heterocyclic such as pyridine, the reaction can be conducted, but the reaction activity will reduce.In terms of mechanism by capturing reaction intermediates and studying a large number of literatures about bidentate ligands guiding hydrocarbon activation and its related mechanism studying results, the possible reaction mechanism of copper promoting hydrocarbon activation catalysis was proposed, namely benzamide derivative induced by copper hydrocarbon activation coupling with nitro oxide, recurrence of Nef and cyclization reaction to get target compounds. |
