Simple preparation method of isoxazoline

Abstract

The invention discloses a simple preparation method of isoxazoline. The simple preparation method is characterized in that a series of isoxazoline compounds are efficiently synthesized by using aldehyde, p-toluenesulfonhydrazide, olefin and tert-butyl nitrite as substrates, copper chloride as a catalyst and tetramethylethylenediamine (TMEDA) as alkali through the one-pot two-step method. The method has the advantages that the catalyst is cheap, reaction is economical, good substrate universality is achieved, the raw materials are easy to obtain, later-stage functionalization is more convenient, reaction conditions are mild, and gram-level scale reaction is good; and especially, the compounds with medium yield can be obtained without the catalyst, post-treatment is simple and convenient, the application of the compoumds in drug molecule synthesis and large-scale industrialization is facilitated, and the requirements and trends of modern green chemistry and medicinal chemistry are met.

Description

technical field [0001] The invention relates to a method for preparing isoxazolines, belonging to the technical field of organic synthesis. Background technique [0002] Isoxazolines are the core skeletons that widely exist in natural products, drug molecules, bioactive molecules, pesticides and functional materials. Alternatively, it is also used as a ligand for transition metal catalysis. Chemists have developed a series of methods for preparing isoxazolines, but all of them have obvious disadvantages, such as: a large excess of oxidizing agent or dehydrating agent is required; raw materials are expensive or the preparation is cumbersome; reaction conditions are harsh; expensive and harmful transition metals are required, etc. . For example: (1) The in situ generation of nitrile oxide intermediates from alkynes and copper nitrate and further preparation of isoxazolines by dipolar cycloaddition with alkenes, but the reaction must be under a nitrogen atmosphere to have a h...

AI Technical Summary

Problems solved by technology

Chemists have developed a series of methods for preparing isoxazolines, but all of them have obvious disadvantages, such as: a large excess of oxidizing agent or dehydrating agent is required; raw materials are expensive or the preparation is cumbersome; reaction conditions are harsh; expensive and harmful transition metals are required, etc.

For example: (1) The in situ generation of nitrile oxide intermediates from alkynes and copper nitrate and further preparation of isoxazolines by dipolar cycloaddition with alkenes, but the reaction must be under a nitrogen atmosphere to have a higher yield At the same time, this method inevitably needs to use an equivalent amount of transition metal copper nitrate (expensive and toxic), which is not suitable for the synthesis of drug molecules (see: Angew. Chem., Int. Ed. 2015 , 54, 8795); (2) The three-component reaction of diazo compounds and alkenes to prepare isoxazolines initiated by tert-butyl nitrite

However, tedious and dangerous diazonium compounds need to be prepared in the reaction, which limits its application in the preparation of biologically active molecules (see: Chem. Sci., 2021, December, 774)

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