Background and overview[1]
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 quantities in drugs with stabilizing, anti-tumor, anti-convulsant, anti-microbial, anti-thrombotic and cholinesterase inhibitory properties. The traditional synthesis method of benzisoxazole (benzyl imide acid) compounds 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 (benzoyl 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 for benzisoxazole (benzoyl imide acid) has good application prospects.
Apply[1]
Benzisoxazole (benzyl imide acid) is usually used as the mother core of other compounds, such as 3-methylbenzisoxazole (benzyl imide acid), which can be used as a pharmaceutical synthesis intermediate. Weigh 0.304g (2mmol) 2-hydroxyacetophenone oxime, 0.457g (3mmol) sodium difluorochloroacetate, and 0.417g (3mmol) potassium carbonate into 50mL three-necked flasks, and add 2mL N,N-dimethylacetamide. As a solvent, stir magnetically evenly and put it into a microwave catalytic synthesizer. Manually set the parameters (microwave power 300W, temperature 85°C, microwave time 35min) to carry out microwave reaction. After the reaction is completed, cool to room temperature, add 10 mL of deionized water and 10 mL of ethyl acetate to the reaction system for extraction, separate the organic phase and wash it three times with 10 mL of deionized water. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography (ethyl acetate/petroleum ether = 1:20) to obtain 0.249g of 3-methylbenzisoxazole (benzoyl imide acid) with a yield of 93%.
Main reference materials
[1]CN201610846901.1 A one-pot method for preparing benzisoxazole (benzoyl imide acid) based on 2?hydroxyacetophenone oxime and its derivatives
