Study On Synthesis Of Chromeno[2,3-b]pyridine Derivatives By Multi-component Reaction

Chromo[2,3-b]pyridine is a kind of key scaffolds in a deal of natural compounds with importantly biological activities,also is used as a significant pharmacophore of many drugs in clinical use.Thus,recently,the design and synthesis of new-type substituted chromo[2,3-b]pyridine derivatives have already gained a substantial amount of attention from synthetic chemists and pharmacologists.Worthy of mention are that,due to possessing an enol ether,enamine and vinylogous amide moieties,accessible 2-aminochromones as promising Michael addition donors played an important role in the efficient construction of polycyclic architectures via cyclization reactions with double electrophiles.Based on our previous research results,we successfully applied 2-aminochromones and malononitriles as key substrates through the multicomponent reactions as a versatile and highly efficient synthetic strategy for the preparation of diversely substituted 5H-chromeno[2,3-b]pyridines.The first part:Piperidine-promoted[3+3]cycloaddition reaction of substituted 2-amino-4H-chromen-4-ones and substituted 2-(benzylidene)malononitriles was developed to synthesize 2-amino-5-oxo-4-phenyl-5H-chromeno[2,3-b]pyridine-3-carbonitriles.Under the optimal reaction conditions,twenty-five new compounds were synthesized in 75-88%yields.The structures of all products were identified by nuclear magnetic resonance spectroscopy,infrared spectroscopy and high-resolution mass spectrometry,and the three-dimensional structures of three compounds were determined by single crystal X-ray diffraction method.The second part:A pseudo three-component reaction of substituted 2-amino-4H-chromen-4-ones and substituted β-nitrostyrenes promoted by DBU was investigated for the preparation of 2,4-diaryl-5H-chromeno[2,3-b]pyridin-5-one derivatives.Under the optimal reaction conditions,twenty-six substituted 2,4-diaryl-5H-chromeno[2,3-b]pyridin-5-ones were synthesized.Based on the above results,a new three-component reaction of substituted 2-amino-4H-chromen-4-ones,substituted β-nitrostyrenes and substituted benzaldehydes was developed to yield different 2,4-disubstituted aryl products.The three-component reaction conditions also were optimized.Under the optimal reaction conditions,eleven new compounds were synthesized in 47-60%.The structure of the product were characterized by nuclear magnetic resonance spectroscopy,infrared spectroscopy and high-resolution mass spectrometry,and the stereochemical structure of three compounds was determined by single crystal X-ray diffraction method.#12#12The third part:A pseudo four-component reaction of substituted salicylaldehydes,substituted β-nitrostyrenes and malononitrile was carried out in the presence of propionic acid as a promoter to synthesize substituted 5-amino-2-phenylchromeno[4,3,2-de][1,6]naphthalene-4-carbonitrile compounds.Under the optimal reaction conditions,nine new compounds were synthesized.The structures of all products were analyzed and identified by nuclear magnetic resonance spectroscopy,infrared spectroscopy and high-resolution mass spectrometry,and the three-dimensional structures of two compounds were confirmed by single crystal X-ray diffraction method.