C-N/C-O Bond Coupling Reaction On Pyridine Ring Without Transition Metal Catalysis

The C_sp2-N bond and the C_sp2-O bond on the nitrogen heterocycle are important bonds in organic compounds.Nitrogen heterocycles are biologically active molecular skeletons and are found in a wide range of natural products and drugs.In the future,humans will conduct deeper research on drugs,so synthesis this class of compounds is also of great significance.The traditional coupling of C_sp2-N bond C_sp2-O bond requires transition metal catalysis.For example,Ullman reaction and Buchwald-Hartwig amination reaction have realized the construction of C_sp2-N bond,but there are some drawbacks,such as metal that is toxic and expensive which cannot be reused.The ligands that match the Pd metal are also extremely expensive,so it is necessary to find a clean and efficient method to synthesize C_sp2-N bonds and C_sp2-O bonds.In this thesis,the exchange reaction of methoxy group and the amination of demethoxy group were realized by using p-methoxypyridine as raw material under the action of two different organic bases.The advantages of these two methods are:?1?No metal catalysis,the green economy of the reaction,and the reaction conditions are mild.?2?The reaction yield is high,the atomic utilization rate is high,and the reaction substrate has good compatibility.?3?Applicable to some natural products and medicines.?4?The reaction is suitable for the gram-level reaction and has a good practical prospect.Details as follows:1.Exploring a simple method to achieve the ether exchange reaction of p-methoxypyridine to form a new C_sp2-O bond.This reaction uses p-methoxypyridine and alcohol as reactants,potassium tert-butoxide as a strong base,and 1,4-dioxane as a solvent,and stiring at 100?C for 16 hours.When p-methoxypyridine is used as a substrate,the product is substituted in the para position.With o-methoxypyridine as the substrate,the product is ortho-substituted,and the ortho-position yield is higher than the para-position yield,indicating that the ortho-activity of pyridine is greater than the para-activity in this reaction.We synthesized 23 reaction substrates with a yield of 50-99%.2.Investigating a new way to synthesis new C_sp2-N bond.Nitrogen heterocyclic compound containing a methoxy group and an aromatic amine as a substrate,using potassiumhexamethyldisilazane as a strong base,and tetrahydrofuran as a solvent,stirring at 100?C for 16 hours.Under the optimal conditions,the reaction can obtain better yield,and the yield can reach 54%-99%.The reaction produced a total of 28products.