An Synthesis Of Substituted Quinoline-2-carboxylates Through The Potassium Persulfate-mediated Cross-dehydrogenative Coupling

Persulfate oxidation system has been developed to efficiently promote direct coupling of substituted quinoline-2-carboxylates with simple olefins via oxidative C-H bond activation, which can afford the corresponding products in good yields. Persulfate has long been known to oxidize hydrocarbons initiated by a single electron transfer process.The oxidant is inexpensive, less toxic, and easily handled, and the byproduct can be easily removed with a simple filtration over Celite or by washing with H2O.Therefore, the synthesis of substituted Q2Cs through the persulfate mediated CDC of glycine derivatives with olefins would be attractive based on economic and environmental factors. The theme of the article is about the research of the system.By the literature research and results of laboratories, we basically determine the research direction and goals, and then began to experiment. Initially, the CDC of glycine ester with styrene was chosen as a model reaction for optimization. Then, we studied the main aspects:the reaction catalyst, kind of solvent, oxidant species and temperature. In the case of the main factors identified, the kinds of catalyst, solvent, oxidant, substrate and oxygen effects were studied. Finally, the optimal reaction conditions:glycine ester (1.0eq), styrene (2.0eq), CuBr (10mol%), acetonitrile (1ml), K2S2O8 (1.0eq), the reaction temperature is 40℃-60℃, and reaction time 16-24h. With the optimal reaction conditions we get, the range of oxidation system of nucleophiles have been studied. Different types of electronic olefins were chosen as nucleophiles. We found that they can adapt to the reaction conditions to obtain the desired product with a high yield, which verify the scope of the oxidation system. Then We choosed styrene as a nucleophile, and N-substituted aryl glycine derivatives as substrates, which could also obtain the desired product with a high yield. Since quinoline-2-carboxylate derivatives having an important role in modern pharmacology and organic synthesis, traditional synthetic method also has many drawbacks. Quinoline derivatives can be synthesized efficiently and highly selective in this method.After the study of the reaction conditions, substrates and nucleophiles, the reaction mechanism of oxidation system has been studied, and two different reaction mechanisms were envisaged. We have proposed two mechanisms for potassium persulfate-mediated cross-dehydrogenative coupling and done some research on them. The first pathway proceeds through an initial hydrogen atom abstraction from glycine ester to the SO4 radical anion giving free radical, which then undergoes one electron oxidation by Cu(Ⅱ) to afford intermediate. Alternatively, an initial electron transfer from glycine ester to the SO4 radical anion provides the radical cation, which then proceeds through a proton abstraction followed by a second electron transfer to generate intermediate. In the presence of Cu(Ⅱ), intermediate reacts with styrene to a□ord intermediate that was further oxidized and aromatized to quinoline. In this process, we synthesized the idea of intermediates and achieved the target product.