Base-Mediated Reaction of Hydrazones and Nitroolefins with a Reversed Regioselectivity:  A Novel Synthesis of 1,3,4-Trisubstituted Pyrazoles

Abstract

A regioselective synthesis of 1,3,4-tri- or 1,3,4,5-tetrasubstituted pyrazoles by the reaction of hydrazones with nitroolefins is described. Mediated with strong bases such as t-BuOK, the reaction exhibits a reversed, exclusive 1,3,4-regioselectivity. Subsequent quenching with strong acids such as TFA is essential to achieve good yields. A plausible stepwise cycloaddition reaction mechanism is proposed.

Synthesis of Nanostructured sawdust-BF3: An efficient reagent for synthesis of 2,3,5-substituted-2H-pyrazole derivatives

“…The recent success of pyrazole based COX-II inhibitors and their applications in medicinal chemistry have amplified the importance of pyrazoles to even a greater extent [2]. Several pharmaceutical drugs including celecoxib [2] and rimonabant [3] utilize the pyrazole as their core molecular entity [4,5], Pyrazoles are often synthesized by the 1,3-dipolar cycloaddition reaction of nitrilimines with alkynes [6], alkyne surrogates [7],or alkenes [5,6], pyrazoles also can be synthesized via 1,3-dipolar cycloadditions of diazo compounds [8], reaction of chalcones [9] and hydrazines, a four-component coupling of terminal alkynes, hydrazine, carbon monoxide, and aryl iodides [10], and the direct condensation of 1,3-diketones and hydrazines in the presence of an acidic catalyst [11]. The last one is the simplest and most straightforward procedure for the synthesis of pyrazoles.…”

Friedel-Crafts chemistry: Part 41. A new facile synthesis of indeno[1,2-c] pyrazoles, 2H-benzo[g]indazoles and benzo[6,7]cyclohepta[1,2-c]pyrazoles via Friedel-Crafts ring closures

“…The synthesis of pyrazoles and their condensed scaffolds have been a subject of consistent interest because of their long history of application in pharmaceutical [1][2][3] and agrochemical [4][5][6] industries.…”

One-pot easy conversion of Baylis-Hillman adducts into arylpyrazoles under ultrasound irradiation

“…9,10 In recent years extensive studies have been devoted to the synthesis of arylpyrazoles. [11][12][13] Usually they can be prepared from the venerable Konor reaction involving condensation of hydrazine derivatives with 1,3-dicarbonyls, 12,14a 1,3-dipolar cycloaddition of diazoalkanes or nitrile imines with olefins or alkynes, 14b use of BaylisHillman adducts, 6 palladium catalyzed arylation of hydrazones, solid-phase combinatorial approaches, zinc-catalyzed synthesis via hydrohydrazination and condensation of α,β-unsaturated ketones with phenylhydrazine. 9,[15][16][17] However most of these syntheses suffer from multi-step reactions, low yields of products and low regioselectivity, and there is still a lack of general and efficient method for the synthesis of arylpyrazoles.…”