Nanocatalyst-Fe3O4@SiO2 mediated efficient isoxazole cyclization and bulk synthesis

Abstract

Isoxazoles are found to be key components in the area of medicinal chemistry and agriculture. Reaction yields of cyclized derivatives is low (∼30%) and when reaction temperature goes beyond ambient temperature, decomposition reactions lead to further reduction in yield. Herein, we report silica functionalized magnetic nanomaterials as an inert catalyst for isoxazole cyclization. The model system chosen is 1, 2-benzisoxazole. The key role of Fe3O4@SiO2 particles was to provide inert surface as well as lower the cyclization temperature. The present protocol does not include any column purification and 1,2-benzisoxazole are obtained in good yield. Silica surface interacts with lone pairs present on oxygen. In this work we found that acidic surface of silica has additional role for cyclization under basic conditions. In this protocol, the reaction of hydroxylamine-o-sulphonic acid with salicylaldehyde results in the formation of N-O bond followed by ring cyclization with the assistance of acidic surface of Fe3O4@SiO2. The 40 nm sized Fe3O4@SiO2 favoured the maximum yield attributed to the density of active sites. Conceivably reported work results significant improvement in yield (60 %), which is substantial in bulk scale production of drugs.