Synthesis Of Isoxazole Derivatives Research Articles

Primary nitro compounds: progress in the synthesis of isoxazoles by condensation with aldehydes or activated ketones.

Among the known strategies directed towards the synthesis of isoxazole derivatives, the reactions of aldehydes with primary nitro compounds deserve a comprehensive treatment, including the historical development as well as the more recent applications. The reactions of aldehydes with primary nitro compounds in a 1 : 2 molar ratio have been shown to lead to isoxazoline-N-oxides or isoxazole derivatives, via β-dinitro derivatives. Several modifications of the process allowed the formation of products bearing substituents at various positions of the heterocyclic ring with control of regioselectivity. Ketones are reported to react with primary nitro compounds, only if activated (β-diketones, α-nitroketones, or strained ketones), to give isoxazole derivatives. Symmetric 2,4-dinitroglutarates formed from aromatic aldehydes and nitroacetate undergo ring closure to form isoxazole derivatives or, according to reaction conditions, 5-hydroxy-6-oxo-4-aryl-6H-1,2-oxazine-3-carboxylates ("oxazinones"), by loss of alcohol instead of water. Isoxazole-4-carbaldehydes are obtained by the reaction of 3-oxetanone with primary nitro compounds.

Synthesis, crystal structure and molecular docking study of novel isoxazole derivatives as CYP450 inhibitors in search of anticancer agents

Synthesis of some novel isoxazole derivatives and their molecular docking with enzymes from CYP450 family carried out using erlotinib, gemcitabine and ketoconazole as reference drugs are reported in this work. Eight isoxazole derivatives of 3,4-substituted phenyl 3-chloroacrylaldehyde and one isoxazole derivative of cinnamaldehyde were synthesized. A molecular docking study of all nine compounds shows good docking score compared to standard drugs erlotinib, gemcitabine and ketoconazole. 4-OH and 4-F derivatives were found to have strong affinity for all six CYP450 proteins under study in the present work. 4-F and 3-NO2 derivatives could be a suitable lead compound inhibitor to CYP1A2 followed by 4-OH derivatives. 4-OH derivative with significant binding affinity showed encouraging inhibition of CYP1A2, CYP2C9, CYP2C8, CYP2C19 and CYP2D6. The current predictions over these nine isoxazole derivatives of 3,4-substituted phenyl 3-chloroacrylaldehyde will be needed to be further investigated in vivo and in vitro conditions to identify the optimum therapeutic efficacy. Synthesis of the isoxazole derivatives is the first known report of the Knoevenagal condensation of acrylaldehyde derivatives to form isoxazole derivatives as per the literature survey. A detailed crystal structure study of five analogues gives insight into the solid-state structural features of this new framework with isoxazole moieties. Communicated by Ramaswamy H. Sarma

Recent Progress in the Synthesis of Isoxazoles

Isoxazole derivatives are aromatic five-membered ring heterocyclic compounds with one oxygen atom and one nitrogen atom at adjacent positions. These compounds have a broad spectrum of applications in medicinal chemistry, such as antimicrobial, anticancer, antitumor, antitubercular, analgesic, anti-inflammatory, antidepressant, and anticonvulsant activities and some of them are well-known drugs for the treatment of various diseases in the market. The use of this class of compounds in agriculture as herbicides, insecticides have been widely reported. In organic materials, these compounds have been applied as semiconductors, single-walled nanotubes, liquid crystals, chiral ligands, scaffolds for peptidomimetics, dyes, and high-temperature lubricants. Isoxazole derivatives also play an important role in organic synthesis because they can be converted into several important synthetic units such as β-hydroxy ketones, γ -amino alcohols, α,β-unsaturated oximes, β -hydroxy nitriles, α-hydroxy-β-diketones, and β - dicarbonyl compounds. Due to such a wide range of applicability, the synthesis of isoxazole derivatives has attracted intensive research from chemists. This review will focus on considerable studies on the synthesis of isoxazoles which date back from 2012.

Application, Reactivity and Synthesis of Isoxazole Derivatives

In this review article, we describe the application, reactivity and synthesis of isoxazole derivatives, more specifically, the application, reactivity, and synthesis of 3,5-disubstituted, 3,4- disubstituted, and 3,4,5-trisubstituted isoxazole using the green method. We review the application of isoxazole in material science, agriculture and pharmaceutical. In material science, isoxazole is used as a photochromic, electrochemical probe for Cu<sup>2+</sup> and, given its optical properties, in dye-sensitized solar cells, high energy material and liquid crystal. In agriculture, isoxazole is used as an insecticide for managing Callosobruchus chinensis, Acaricidal activity against T. cinnabarinus, and herbicidal activities of 2-cyanoacrylates containing isoxazole. In pharmaceutical, isoxazole shows anticancer, antituberculosis, anti-inflammatory, and acetylcholinesterase inhibitors. Further, we describe various reactions of isoxazole such as ring opens, bromination and iodination, thioynol ethers, intramolecular SEAr reaction, arylation, cycloaddition and photocycloaddition, photoisomerization, Domino transformation of isoxazoles to 2,4-dicarbonyl pyrroles and rearrangement. We also describe the synthesis of 3,5-disubstituted, 3,4-disubstituted and 3,4,5-trisubstituted isoxazole using different methods.

Application, Reactivity and Synthesis of Isoxazole Derivatives

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One-pot three-component synthesis of isoxazole using ZSM-5 as a heterogeneous catalyst

A mild and convenient route for the synthesis of isoxazole derivatives has been developed using ZSM-5 as a heterogeneous catalyst. The reaction was carried out under a solvent-free condition to afford the desired products in good yields. A variety of functional groups was tolerated under the reaction conditions employed. Moreover, the heterogeneous catalyst (ZSM-5) was recovered and reused several times without significant loss of its catalytic activity.

Continuous-Flow Microliter Microwave Irradiation in the Synthesis of Isoxazole Derivatives: An Optimization Procedure

An efficient method was developed for the synthesis of 3,4,5-trisubstituted and 3,5-disubstituted isoxazoles by using continuous-flow microwave-heated microreactors. A study on the separate effects of the temperature, continuous-flow regime, and microwave irradiation showed that the continuous-flow regime had important effects for less reactive diketones, where microwave heating enhanced the reaction, permitting the formation of 5-methyl-3-phenylisoxazole, which was not formed in the absence of microwaves.

3,4-Bis(4-fluorophenyl)-1,2,5-oxadiazole 2-oxide

The title compound, C14H8F2N2O2, also known as di(4-F-phen­yl)furazan N-oxide, was found as a side product in the synthesis of isoxazole derivatives. The are two molecules in the asymmetric unit. The bond length of the dipolar N—O unit is 1.107 (7) A. X-ray analysis confirmed the compound to have the desired structure

Synthesis of isoxazole derivatives by means of O-acylation of aliphatic nitro compounds in the presence of acetylenic compounds.

O-Acylation of some aliphatic nitro compounds or their alkali metal salts with acid chlorides in N, N-dimethylacetamide in the presence of acetylenic compounds afforded isoxazole derivatives in fairly good yield. The reaction is shown to arise from 1, 3-dipolar cycloaddition of acetylenic compounds to the nitrile oxide intermediates which would resulted from the fragmentation of the initially formed O-acylated product.

Synthetic Studies of the Derivatives of Nitroacetic Acid. II. The Synthesis of Isoxazolecarboxylic Acids from α,β-Unsaturated α-Nitroesters

Abstract 1) α,β-Unsaturated α-nitroesters react with n-butylamine to give 4-substituted isoxazole-3,5-carboxylic butylamides. This is a new synthesis of isoxazole derivatives. 2) The mechanistic features of the above reaction have been explained. 3) The mild alkaline hydrolysis of the above butylamides gave 4-substituted isoxazole-3,5-dicarboxylic acids.

Synthetic Studies of the Derivatives of Nitroacetic Acid. III. The Synthesis of Isoxazole-3,5-dicarboxylic Acids from Schiff Bases and Nitroacetic Ester

Abstract 1) Schiff bases react with ethyl nitroacetate in the presence of n-butylamine or benzylamine to give 4-substituted isoxazole-3,5-dicarboxylic amides. This is a new synthesis of isoxazole derivatives. 2) Twenty kinds of 4-substituted isoxazole-3,5-dicarboxylic amides, including aliphatic, aromatic and heterocyclic derivatives, have been prepared. 3) Seven of the above-mentioned amides have been hydrolyzed to give the corresponding 4-substituted isoxazole-3,5-dicarboxylic acids. 4) Some Schiff bases have been described.