Synthesis of 3,4-diaryl-5-carboxy-4,5-dihydroisoxazole 2-oxides as valuable synthons for anticancer molecules

Comparison of Substituting Ability of Nitronate versus Enolate for Direct Substitution of a Nitro Group

“…This result prompted the study of α-nitrocinnamate 1b reactions with other active methylene compounds such as 1,3-dicarbonyl compounds, because the nucleophilicity of the enolate ion is considered to be lower than that of the nitronate ion. There have been several studies of the formation of isoxazoline N-oxides from α-nitro-α,βunsaturated esters with C-H acids such as secondary nitroalkane [15], (ethoxycarbonylmethyl)dimethylsulfonium salt [16], (ethoxycarbonylmethyl)ammonium salt [17], (ethoxycarbonylmethyl)pyridinium salt [18], α-halomalonate [19], and α-iodo aldehyde [20]. β,β-Dimethoxynitroethene is also usable as a nucleophile in this protocol [21].…”

Effective Synthesis of 3,4‐Diaryl‐isoxazole‐5‐carboxamides and their Antiproliferative Properties

“…To confirm this synthetic scheme the reactivity of esters 9 in different conditions was studied. Ester 9a in acidic media (aqueous HCl in dioxane) was hydrolyzed almost quantitatively into 3,4‐diaryl‐5‐carboxy‐isoxazoline N‐oxides 12a in 98 % yield (Scheme ) . In contrast, in ethanolic NaOH the rearrangement of both esters 9 and acids 12 afforded mainly 3,4‐diaryl‐5H‐isoxazoles 15 with small amounts of isoxazole‐5‐carboxylic acids 11 (0–9 %).…”

“…General Procedure for the Preparation of 3,4‐Diarylisoxazoles (15) and 3,4‐Diarylisoxazole‐5‐carboxylic Acids (11) . A mixture of the corresponding 5‐(ethoxycarbonyl)‐4,5‐dihydroisoxazole N‐oxides 9 (1.5 mmol), 2 % ethanolic NaOH solution (10 mL) and water (2 mL) was stirred at 60 °C for 5–6 h, then ethanol was removed in vacuo. The residue was suspended in dichloromethane (100 mL) and the aqueous alkaline layer was separated.…”

“…In our previous work, starting 3,4‐diaryl‐isoxazoline N‐oxide‐5‐carboxylic esters were synthesized in high yields . Unfortunately, their subsequent rearrangement was not selective, giving decarboxylated 3,4‐diaryl‐5H‐isoxazoles as the main products with only negligible amount of the required 3,4‐diarylisoxazole‐5‐carboxylic acids .…”

Synthesis of 4‐Hetarylisoxazoles from Amino Acid‐Derived Halogenoximes and Push‐Pull Enamines

“…The known methods for the synthesis of 4‐(het)arylisoxazoles include palladium‐catalyzed C–C couplings,, , various heterocyclizations and recyclizations, diazotative deamination of the corresponding 5‐aminoisoxazoles, and formal [3+2] cycloaddition of alkynes, electron‐deficient enamines or their synthetic equivalents with halogenoximes , . The latter approach can be considered as the most convenient since generally, the target products are obtained in good yields with high regioselectivity.…”