The Chemistry of α,β-Ditosyloxy Ketones: A New and Convenient Route to 4,5-Diarylisoxazoles from α,β-Chalcone Ditosylates

Abstract

The reaction of α,β-chalcone ditosylates with hydroxyl­amine hydrochloride under suitable conditions leads to a 1,2-aryl shift, thereby providing a new route to 4,5-disubstituted isoxazoles.

α,β-chalcone dibromides - α,β-chalcone ditosylates - hydroxy(tosyloxy)iodobenzene - 4,5-diarylisoxazoles

References and Notes

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Experimental procedure used to prepare α,β-chalcone ditosylates 1: Prepared from the corresponding chalcones^¹7-²² 3 using a procedure similar to that reported previously by our research group. Compounds 1a-c,g,i-j,l were previously reported, whereas 1d-f,h,k,m-o are novel compounds. Spectroscopic data of the latter compounds are given in the Supporting Information.

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Experimental procedure used to prepare 4,5-diaryl-isoxazoles 4: A mixture of chalcone ditosylate (1a; 0.550 g, 0.001 mol), hydroxylamine hydrochloride (0.138 g, 0.002 mol) and sodium acetate (0.164 g, 0.002 mol) in EtOH (25 mL) was heated at reflux for approximately 3 h. The reaction mixture was then poured onto ice-cold water. The resulting mixture was extracted with CH₂Cl₂ (3 × 50 mL) and the combined organic extract was dried over anhydrous Na₂SO₄ and filtered. Evaporation of CH₂Cl₂ in vacuo gave the crude product, which was purified by column chromatography on silica gel (100-200 mesh; PE-EtOAc) to give pure pyrazole 4a (72%, 0.159 g). Other derivatives were prepared in a similar manner. Compounds 4e,g,h,j,k,m-o are novel. Spectroscopic data of these compounds are given in the Supporting Information.

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