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Synthesis of Pyrazoles Utilizing the Ambiphilic Reactivity of Hydrazones

Haruo Matsuzaki, Norihiko Takeda, Motohiro Yasui, Yuta Ito, Keiji Konishi, Masafumi Ueda

2020Organic Letters27 citationsDOI

Abstract

A Brønsted acid-mediated synthesis of pyrazoles from conjugated hydrazones through a β-protonation/nucleophilic addition/cyclization/aromatization sequence was developed. This protocol utilizing the ambiphilic reactivity of hydrazones enables not only self-condensation but also cross-condensation, affording multisubstituted pyrazoles in high yields, with a broad substrate scope. This sequential reaction proceeds under mild conditions via a simple operation. Moreover, the method can be applied to the synthesis of a nonsteroidal anti-inflammatory drug, Lonazolac.

Topics & Concepts

ChemistryAromatizationReactivity (psychology)Combinatorial chemistrySubstrate (aquarium)Conjugated systemProtonationNucleophileCondensationOrganic chemistryCatalysisPhysicsMedicineThermodynamicsOceanographyGeologyPathologyPolymerIonAlternative medicineClick Chemistry and ApplicationsSynthesis and Catalytic ReactionsChemical Synthesis and Analysis