Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability. Keywords: environmentally friendly; furoxans; 1,2,5-oxadiazole 2-oxides; trifluoromethyl-substituted isoxazoles

• with 95% yield (5% water, 95% methanol, room temperature, 2 hours; see Table 1, entry 15), which adds another method for the synthesis of furoxans to the current literature. The synthesis of furoxans or 1,2,5-oxadiazole-2-oxides was first reported by Kekulé in 1857 [36]. Since then, these nitric oxide

• for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked is our optimized reaction conditions for the dimerization of hydroximoyl chlorides to form furoxans or 1,2,5-oxadiazole 2-oxides, a class of structures with important biological