Synthesis of Tri- and Tetrasubstituted Pyrazoles via Ru(II) Catalysis: Intramolecular Aerobic Oxidative C–N Coupling

Abstract

An unprecedented ruthenium(II)-catalyzed intramolecular oxidative C-N coupling method has been developed for the facile synthesis of a variety of synthetically challenging tri- and tetrasubstituted pyrazoles. Dioxygen gas is employed as the oxidant in this transformation. The reaction demonstrates excellent reactivity, functional group tolerance, and high yields.

Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

“…As shown in Scheme 2 , key intermediate 9 was synthesized by the nitration of the commercially available 2,6-di- tert -butylphenol ( 7 ) with aqueous HNO 3 in hexane to give 2,6-di- tert -butyl-4-nitrophenol ( 8 ), which was then reduced with Sn/HCl under reflux conditions with a 70%–80% yield. Another key intermediate, 4-aminosulfonylphenylhydrazine hydrochloride ( 12 ), was prepared according to a similar method reported previously 22 , 23 . Commercially available sulfanilamide ( 10 ) was converted into its diazonium salt by reaction of the amine with in situ generated nitrous acid.…”

A Convenient Approach to CF3‐Containing N‐Heterocycles Based on 2‐Methoxy‐2‐methyl‐5‐(trifluoromethyl)furan‐3(2H)‐one

“…General: All reagents and solvents were obtained from the commercial suppliers and dried by the standard procedures before use. [4‐(Aminosulfonyl)phenyl]hydrazine monohydrochloride ( 15e ), 4‐methylbenzenesulfonohydrazide ( 17c ) were prepared according to the reported procedures 20,21. 2‐Methoxy‐2‐methyl‐5‐(trifluoromethyl)furan‐3(2 H )‐one ( 11 ) was obtained according to the method earlier reported 9 .…”

Ruthenium‐Catalyzed Synthesis of Heterocycles via CH Bond Activation

“…The synthesis of a variety of high diversified tri-and tetrasubstituted pyrazoles was achieved by ruthenium(II)-catalyzed intramolecular oxidative C-N coupling from easily accessible starting materials (Eq. (7.4)) [9]. The C-H/N-H coupling transformation proceeded with excellent reactivity and high tolerance of functional groups.…”