Synthesize Polysubstituted Pyrroles And Pyridines From1,4-disubstituted-1,3-butadiynes

Pyrroles and pyridines are two classes of important heterocyclic compounds. Many functionalized pyrroles and pyridines possess bioactivity and vital physiological action, Pyrroles and pyridines widely exist in various natural products and synthetic compounds. They are applied in numerous aspects, including pharmaceuticals, pesticides, dyes and materials. Organic synthetic chemists have advanced a great many of methodologies to construct multisubstituted pyrroles and pyridines. This dissertatation describes the ways to efficiently synthesize trisubstituted pyrroles and trisubstituted pyridines from1,3-butadiynes and primary amines through cycloaddition. It mainly consists of following three parts:(1)We employ more stable cuprous iodide to activate alkynes, following by [4+1] type annulation reactions of1,3-butadiynes with primary amines to efficiently construct1,2,5-trisubstituted pyrroles. The reaction combines a catalytic amount of cuprous iodide, five equivalent amines, and DMF as solvent, which enhance the reaction economy to avoid the disadvantage of excess primary amines in traditional synthetic methods.(2)We firstly report more stable copper acetate monohydrate activate alkyne, following by cycloaddition of1,3-butadiynes with primary amine to effectively present1,2,5-trisubstituted pyrroles. The reaction combines catalytic amount of copper acetate monohydrate, five equivalent primary amine and solvent of ethyl glycol, which increase the reaction economy instead of use of excess amine. Copper acetate monohydrate in solvent of ethyl glycol display highly catalytic activity, making the reaction advisable.(3)Potassium carbonate as a base can effectively promote course of reaction to synthesize2,3,5-trisubstituted pyrridines between1,3-butadiynes and primary amines. Under the optimized condition, the reaction combines one equivalent base and oxidant of DMSO, product of2,3,5-triphenyl pyridines are selectively obained. The reaction sequence consists of including intermolecular nucleophilic addition, isomerisation, intramolecular nucleophilic addition and aromatization from starting materials to desired product. A radical inhabit experiment is carried out to exclude the reaction process of free radical.