Synthesis And Derivatization Of4-3,5-Dimethylpyrazolyl Isoxazolines

Isoxazoline is a class of five-membered heterocyclic structural framework that occupies a prominent position in natural products and medicinal chemistry.The research on the synthesis methods of isoxazolines and their derivatives has been a hot research topic for synthetic chemists.Currently,most of the derivatization reactions using isoxazoline as the parent nucleus are focused on the ring-opening reaction of isoxazoline.It is an important basis for exerting its application value.In this paper,taking advantage of the excellent reactivity of 3,5-dimethylpyrazolyl,using diarylnitrones and electron-deficient 3,5-dimethylpyrazolyl olefins as raw materials,and using Ni（Cl O₄）₂ as catalyst,4-3,5-dimethylpyrazolyl isoxazoline was prepared,and a series of isoxazoline derivatives were prepared from this type of material.The specific research contents are as follows:Synthesis of 4-3,5-dimethylpyrazolyl isoxazolines by the reaction of diarylnitrone with 3,5-dimethylpyrazole olefins catalyzed by Ni（Cl O₄）₂,The results showed that Ni（Cl O₄）₂ resulted in 100%regioselectivity and diastereoselectivity of the reaction;Electronic and space effects of the nitrone substituents are key factors affecting the yield of isoxazoline,and the donating electron group significantly improves the yield of the product,and the product yield can reach 99%,absorbing electron groups and bulky groups,resulting in significantly lower outcomes of 70-85%of the product.The ring-opening reduction reaction of 4-3,5-dimethylpyrazolyl isoxazolines for the preparation ofβ-amino alcohols was investigated.The results showed that 60%-95%ofβ-amino alcohols could be obtained by using 5%mmol Pd/C as the catalyst and reacting at room temperature for 1-8h.The effect of substituents on the nitrone on the reaction was investigated.The Construction methods for other functional groups at the 4-position of the isoxazoline ring was investigated by using 4-3,5-dimethylpyrazolyl isoxazoline as a raw material.The results show that 3,5-dimethylpyrazolyl is an excellent auxiliary group.Its efficient reactivity can be used to construct five active functional groups,namely,primary hydroxyl[-CH₂OH],tertiary hydroxyl[-C（CH₃）₂OH],acetyl[-COCH₃],ester[-COOC₂H₅),and hydrazine[-CONHNH₂],in high yield under mild conditions,which providing systemic methodological support for the high-level construction of the 4-substituted isoxazolyl ring framework.