Preparation method of benzyl imide acid_Kain Industrial Additive

Overview^[1][2]

Benzisoxazole (benzyl imide acid) is a type of benzoheterocyclic compound containing adjacent oxygen atoms and nitrogen atoms, which has high biological activity and pharmaceutical properties. Benzisoxazole (benzyl imide) is found in large amounts in pharmaceuticals with neuroleptic, antineoplastic, anticonvulsant, antimicrobial, antithrombotic, and cholinesterase inhibitory properties. The traditional synthesis method of benzisoxazole (benzyl imide acid) requires a strong acidic environment and the use of a large amount of organic bases. The experimental operation is complicated, and the post-processing process causes great environmental pollution. In 2010, Larock’s research group used chlorooxime and o-trimethylsilyl aryl trifluoromethanesulfonate as raw materials and cesium fluoride as the inducer to generate benzyne and cyano oxide on site, and [3+ 2] Cycloaddition reaction prepares benzisoxazole (benzyl imide acid) compounds. Although this method can obtain benzisoxazole (benzyl imide acid) compounds in higher yields, the raw materials used in the reaction are complex and require multi-step synthesis, thus limiting its practical application value. As mentioned in the review, the research and development of low-value and simple preparation methods of benzisoxazole (benzoyl imide acid) has good application prospects.

Structure

Preparation method^[1]

A one-pot method for preparing benzisoxazole (benzoyl imide acid) based on 2-hydroxyacetophenone oxime and its derivatives, which is carried out according to the following steps: 2-hydroxyacetophenone oxime and its derivatives, fluorine-containing accelerator and alkali are added to the organic solvent, heated to 70-100°C and reacted for 20-240 minutes. After the reaction is completed, water and ethyl acetate are added for extraction, the solvent is evaporated from the organic phase, and the remaining crude product is Silica gel column chromatography was used to separate and obtain substituent-containing benzisoxazole (benzoyl imide acid). The method for synthesizing benzisoxazole (benzyl imide acid) of the present invention has rich sources of raw materials, short synthesis steps, simple operation, high product yield, with a maximum yield of 93%, and has potential application value.

Main reference materials

[1]CN201610846901.1 A one-pot method for preparing benzisoxazole (benzoyl imide acid) based on 2-hydroxyacetophenone oxime and its derivatives