Method for synthesizing 3-aryl substituted indolizine

Abstract

The invention discloses a method for synthesizing 3-aryl substituted indolizine. The method comprises the following steps: in an ionic liquid medium, performing in-situ generation of a bromination aryl methyl substituted pyridine quaternary ammonium salt from pyridine and aryl methyl bromide, and further performing 1,3-dipolar-cycloaddition reaction with electron-deficiency alkyne under an alkali condition, so as to obtain a target product. Compared with a conventional synthesis method, the method has the remarkable advantages that firstly, reaction conditions are simple, and no transition metal catalyst is used; secondly, reaction conditions are gentle, and reaction reagents are relatively safe and cheap; thirdly, the solvent used in the reaction is an ionic liquid which has the advantages of being low in steam pressure, not liable to combustion or explosion, recyclable and the like.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method of 3-aryl substituted indolazines. Background technique [0002] 3-Aryl-substituted indoleazines have a wide range of pharmaceutical, biological and optical activities, and they are also important intermediates for the synthesis of many nitrogen heterocycles. Common methods for synthesizing 3-aryl substituted indoxazines mainly contain the following four types: (1) take 2-pyridine ethyl acetate and cinnamic acid as raw materials, prepare 3-aryl by copper-mediated free radical cyclization reaction Substituted indoleazines (Org.Biomol.Chem.2016,14,9966); (2) Preparation of 3-aryl substituted indole by cyclization reaction using ethyl 2-pyridine acetate and its analogues and aryne as raw materials Oxyzine (Tetrahedron Lett.2016,57,1074; Tetrahedron 2014,70,6717); (3) 3-aryl-substituted Indolezine (Org.Lett.2015,17,2404; Org.Lett.2015,17,3050); (4) Us...

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Problems solved by technology

[0003] But these four kinds of methods all have their own problems, as the raw materials used are relatively expensive, all need to be carried out in highly toxic, difficult to handle and reclaim organic solvents such as DMF, dichloroethane and NMP, and the reaction temperature is all very high (greater than 100°C), etc.

Most of the processes need to use a large amount of transition metal catalysts and oxidants, which further increases the synthesis cost and the difficulty of post-processing, and is also unfavorable to the environment.

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