3(5)‐(2‐Hydroxyphenyl)‐5(3)‐styrylpyrazoles: Synthesis and Diels−Alder Transformations

Abstract

Reactions between cinnamoyl(2‐hydroxybenzoyl)methanes and hydrazine hydrate in acetic acid gave 3‐(2‐hydroxyphenyl)‐5‐styrylpyrazoles, while the corresponding reactions with phenylhydrazine yielded 5‐(2‐hydroxyphenyl)‐1‐phenyl‐3‐styrylpyrazoles as the major products and 3‐(2‐hydroxyphenyl)‐1‐phenyl‐5‐styrylpyrazoles as by‐products. The reaction mechanism of this transformation is discussed. The first cycloaddition reactions between ortho‐benzoquinodimethane and either 3‐(2‐hydroxyphenyl)‐5‐styrylpyrazoles or 5‐(2‐hydroxyphenyl)‐1‐phenyl‐3‐styrylpyrazoles afforded 5‐[2‐(3‐aryl‐1,2,3,4‐tetrahydronaphthyl)]‐3‐(2‐hydroxyphenyl)pyrazoles or 3‐[2‐(3‐aryl‐1,2,3,4‐tetrahydronaphthyl)]‐1‐phenyl‐5‐(2‐hydroxyphenyl)pyrazoles, respectively. These cycloadducts were converted into the corresponding naphthylpyrazoles by oxidation with DDQ in dry 1,4‐dioxane. The structures of all new derivatives have been established by NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Synthesis of 5‐Hydroxy‐2‐(naphth‐2‐yl)chromone derivatives

“…In order to improve the efficiency of the Diels-Alder reaction of 5-hydroxy-2-styrylchromones 3a-d with 2, we decided to use aluminum chloride as catalyst [42][43][44]. It was expected that it could form a chelate with the 5-hydroxy and carbonyl oxygen atoms and make the styryl double bond more reactive.…”

“…In this case 4a was obtained in 11% yield and 49% of 3a was recovered. Because none of these results were satisfactory, we decided to use 1,4-dioxane as solvent, since it has been successfully used in dehydrogenation reactions [44,46]. In that way, cycloadduct 3a was treated with DDQ in refluxing dry 1,4-dioxane for 24 hours.…”

Pyrazolylthiazole as ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator Correctors with Improved Hydrophilicity Compared to Bithiazoles

“…10 This general method often suffers from lack of regioselectivity in the production of substituted pyrazoles. 11 There are only sporadic reports addressing the synthesis of pyrazolylthiazoles by this condensation reaction. 12 However, none of these methods involve diversification of this heteroatom-rich bisazole or delineate routes to acquire both N -regioisomers of the pyrazole from a common intermediate.…”

Ru(II) trithiacyclononane 5-(2-hydroxyphenyl)-3-[(4-methoxystyryl)pyrazole], a complex with facile synthesis and high cytotoxicity against PC-3 and MDA-MB-231 cells

“…The syntheses of phpz and [Ru( [9]aneS 3 )(DMSO)Cl 2 ] were previously reported [13,14]. All other chemicals were purchased from Sigma-Aldrich (Poole, UK) and used as received.…”

“…As part of a study exploring new 3(5)-(2-hydroxyphenyl) pyrazole structures [13], this work presents the cytotoxicity against the PC-3 and MDA-MB-231 cell lines of 5-(2-hydroxyphenyl)-3-[(4-methoxystyryl)pyrazole] (phpz), both in its pure form and coordinated to ruthenium(II)trithiacyclononane.…”