Organic synthesis usually requires organic solvents to dissolve reactants or catalysts for reaction, but this leads to serious waste of solvents and environmental pollution. The solvent-free organic synthesis reaction method can effectively avoid resource waste and environmental pollution caused by the use of solvents, and without the use of solvents, the concentration of reactants is the highest, it has significant advantages over reactions in solution in terms of reaction speed, reaction operation, yield, etc. Therefore, solvent-free organic synthesis reaction is favored by organic synthesis chemists as a cleaner and more sustainable synthesis reaction method. However, skeleton structures containing N—N bonds are a very important class of structural units, such as azo compounds, hydrazine derivatives, pyrazole, indazole, triazole derivatives, etc. that exist in various natural products, functional drug molecules, and organic materials. Currently, more than 300 drug molecules have been reported to contain N—N bonds. Especially N,N-disubstituted hydrazine has a wide range of physiological and pharmacological activities, such as antihypertensive, anticancer, and antibacterial. Therefore, we reported using iodobenzenediacetic acid (PIDA) as an oxidant, N-alkoxyamide compounds underwent N—N self coupling reaction at room temperature and solvent-free conditions. This method not only has a simple and easy to operate system, high reaction efficiency, and can prepare products at the gram level, but also has good functional group compatibility, suitable for various substituted benzene rings, aromatic heterocycles, and aliphatic amide substrates. This provides a simple, mild, efficient and potentially useful preparation method for N—N self-coupling of N-alkoxyamide compounds with different substituents. Under this condition, 28 coupling products were prepared with a maximum yield of 96%. The typical procedure is as follows: the mixture of N-alkoxyamide (0.2 mmol, 1 equiv.) and oxidant PIDA (0.15 mmol, 0.75 equiv.) is stirred under a magnetic stirrer until the starting material is completely consumed under thin layer chromatography monitoring. After the reaction, the N—N coupling product was purified by silica gel chromatography.

Key words: N-alkoxyamide, N—N coupling reaction, solvent-free reaction, solid state reaction, hydrazine derivatives