Synthesis Of Benzoxazoles Research Articles

Zirconium-catalyzed one-pot synthesis of benzoxazoles using reaction of catechols, aldehydes and ammonium acetate

In this study, an efficient method for the synthesis of benzoxazoles by coupling catechols, aldehydes and ammonium acetate using ZrCl4 as catalyst in ethanol is reported. A wide range of benzoxazoles (59 examples) are smoothly produced in high yields (up to 97%). Other advantages of the method include large-scale synthesis and the use of oxygen as an oxidant. The mild reaction conditions allowed late-stage functionalization, facilitating access to several derivatives with biologically relevant structures such as β-lactam and quinoline heterocycles.

One-Pot Synthesis of Benzoxazoles: A Promising Approach to Aromatic Heterocyclic Compounds Preparation

One-Pot Synthesis of Benzoxazoles: A Promising Approach to Aromatic Heterocyclic Compounds Preparation

Development of In-Water Scalable Process for the Preparation of [2-(3-Bromo-2-methylphenyl)-7-chloro-1,3-benzoxazol-5-yl]methanol, a Key Intermediate in the Synthesis of Potent PD-1/PD-L1 Inhibitors

AbstractWe propose a synthetic process for the preparation of a benzoxazole building block for a programmed death-ligand 1 inhibitor that is a candidate currently under clinical investigation for cancer treatment. Our research focused on searching for mild, scalable, and ecofriendly conditions for the synthesis of benzoxazoles. To reduce the use of toxic reagents or solvents and to minimize the production of organic wastes, the cyclization reaction was performed in an aqueous micellar medium. This in-water benzoxazole synthesis gave comparable yields to previously reported processes, and was applied to a broad range of benzoxazoles with various substitution patterns, showcasing its effectiveness in ecofriendly benzoxazole cyclization reactions.

Sustainable process intensification: Ultrasonic preparation of MIL-88A for benzoxazole synthesis

This study provides a biodegradable fumaric acid-based MIL-88A metal-organic framework, a cost-effective and non-toxic catalyst, for biologically active benzoxazoles synthesis. Initially, the ultrasonic approach is used for MIL-88A preparation at room temperature, significantly reducing the synthesis time compared to conventional heating protocols. The ultrasonic approach is once again used for the three-component production of benzoxazoles in the presence of MIL-88A catalyst. Subsequently, the benzoxazole reaction is accelerated and yields are also improved. Impressive yields ranging between 84 % and 96 % were obtained within one hour at room temperature for the three-component synthesis of benzoxazoles. Characterization techniques, including FT-IR, TEM, XRD, and SEM-EDS mapping, confirm the successful synthesis of MIL-88A. Moreover, a large-scale reaction for benzoxazole synthesis can be performed with minimal yield loss, indicating its practical application. Notably, fumaric acid, found in many fruits and vegetables, serves as the precursor for catalyst synthesis. Catechol, sourced from various plant sources, is employed for three-component production of benzoxazoles. By integrating sustainable techniques, including ultrasound-assisted synthesis and naturally available substrates, an innovative strategy was developed utilizing a renewable catalyst for an eco-friendly reaction.

Comparison of the effectiveness of two piperazine based nano-catalysts in the synthesis of benzoxazoles and benzimidazoles and use of the powerful one in the N-Boc protection of amines.

In this work, a comparison between the catalytic activity of two piperazine based ionic liquids immobilized on ZnO NPs and SiO2 NPs is presented in the synthesis of benzoxazoles and benzimidazoles. These reactions are performed under solvent free conditions during appropriate reaction times with high yields. The catalyst obtained from ZnO-NPs (PINZS), as the more efficient one, is used for the efficient promotion of the N-Boc protection of amines. High chemoselectivity, no by-products, facile separation of the catalyst, short reaction times and no need for volatile organic solvents are the best features of the proposed methods.

An atomically dispersed Co catalyst for efficient oxidative fabrication of benzoheterocycles under ambient oxygen conditions

The first Co1/NC SAC is reported to produce benzoheterocycles under oxygen conditions, and the yields of 2-PBO, 2-PBT and 2-PBM were 99%, 95% and 99%, respectively.

MgAl2O4 nanospinel: Green synthesis, characterization and effective heterogeneous catalyst for the photocatalytic degradation of carbol fuchsin dye and synthesis of 2-aryl substituted benzoxazole derivatives

In this study we report, plant extract mediated green, expedient, cost effective and environment friendly synthesis of MgAl2O4 nanospinel and their potential application in the field of photocatalytic degradation of organic contaminant and biologically active benzoxazole synthesis. The synthesized spinel material was characterized by XRD, TGA, FT-IR, FE-SEM, EDAX, TEM, UV–Visible spectra, XPS and BET for obtaining the structural, morphological, optical, and textural properties. Sunlight driven photocatalytic degradation efficiency of this catalyst was performed on a widely used industrial dye carbol fuchsin (CF) which is a major contaminant that is being mixed in water resources. The contamination could be degraded upto 96.84 % when its concentration is 30 ppm at pH 9, by the nanospinel of 0.6 g/L. Kinetic model of degradation follows pseudo- first order kinetic with rate constant of 0.043 min−1. Also the nanospinel has the key benefits in the synthesis of some benzoxazole derivatives as a catalyst, that its shorter reaction time, excellent yield, safety and moderate reaction conditions, non-toxicity and simple work up procedures.

One‐Pot Synthesis of Substituted Benzoxazoles Using Aminophenols and α‐Diazoesters via Annulation of Amide Intermediate Using Co2(CO)8 as a Solid Carbonyl Source

AbstractSynthesis of benzoxazoles via amide formation from amino phenols and α‐diazoesters using dicobalt octacarbonyl as a solid CO source is reported. Our methodology provides a strategy for synthesizing substituted benzoxazoles with methylene linker between the benzoxazole and aromatic ring systems. Substrates with different substituents were employed to produce corresponding benzoxazoles. The synthesized compounds were characterized by using standard spectroscopic and analytical techniques including single crystal XRD studies.

Application of Vitreoscilla Hemoglobin as a Green and Efficient Biocatalyst for the Synthesis of Benzoxazoles in Water.

We report an efficient and eco-friendly method for the Vitreoscilla hemoglobin (VHb)-catalyzed synthesis of benzoxazoles in water at room temperature. tert-Butyl hydroperoxide and 2,2,6,6-tetramethyl-1-piperidinyloxy were used as oxidant and radical scavenger, respectively. A total of 27 functionally diverse benzoxazoles were prepared in moderate to high yields (62 %-94 %) by the annulation reaction of phenols with amines in the presence of VHb in 1 h. Thus, this method is highly viable for practical applications. This work broadens the application of hemoglobin to organic synthesis.

Nanocatalyzed Synthesis of Benzoxazoles

AbstractNaturally, occurring as well as synthetic nitrogen and oxygen containing heterocyclic compounds like benzoxazoles and its derivatives have found to be playing a vital role in the Pharmaceutical, agriculture; polymer, material science and they also exhibits series of significant antimicrobial activities. In the last decade, an organic transformation has found abundant application of nanotechnology and nanoscience can aid design catalyst with excellent efficiency, selectivity and stability. Academics and industry have recently shown a lot of interest in the application of nanocatalysts, a field that is expanding significantly, to create sustainable and environmentally friendly processes for the synthesis of benzoxazole derivatives with multi‐component reactions (MCRs). Nanocatalyst reactions have advantages over conventional catalyst reactions because of the interaction of chemical reactants made possible by a high surface area ratio, simple purification, low catalyst loading, high atom economy, inexpensiveness, short reaction time, better yield, and recyclability of the nanocatalysts. In this review article, mainly focus is on the nanocatalysts fabrications, characterizations and their applications for the synthesis of benzoxazoles moiety during the last decennary (2011 to 2022).

F,O,S-Codoped Graphitic Carbon Nitride as an Efficient Photocatalyst for the Synthesis of Benzoxazoles and Benzimidazoles

Graphitic carbon nitride (g-C3N4) is a metal-free heterogeneous catalyst that has attracted attention because of its good chemical stability, cost-effectiveness, and environmental friendliness. In the work presented herein, F,O,S-codoped carbon nitride was synthesized by heating a mixture of melamine cyanurate and trifluoromethanesulfonic acid at 550 °C for 50 min. The obtained product was characterized by transmission electron microscopy, infrared spectroscopy, X-ray powder diffraction, CHNS elemental analysis, total combustion-ion chromatography, X-ray photoelectron spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy, and UV-Vis spectroscopy. Results point to an F,O,S-codoped g-C3N4. The material was applied as a photocatalyst for the formation of benzoxazoles and benzimidazoles by condensation–aromatization of 2-aminophenol or 1,2-phenylenediamine with suitable aldehydes (viz. benzaldehyde, 4-chlorobenzaldehyde, 2-naphthaldehyde, 2-hydroxybenzaldehyde, and 2-methoxybenzaldehyde), obtaining yields of up to 90% in 15 min under visible light irradiation, with good selectivity and reusability. Thus, the reported findings suggest that this F,O,S-codoped g-C3N4 may hold promise as a metal-free photocatalyst for the rapid synthesis of 2-arylbenzoxazoles and 2-arylbenzimidazoles.

Microwave-Assisted, [Bmim]PF6-Catalyzed Synthesis of Benzoxazoles Under Solvent-free Conditions

Background: An efficient and green strategy for the synthesis of 2-arylbenzoxazoles using [Bmim]PF6 ionic liquid as a catalyst has been investigated via the condensation of oaminophenol with aldehydes. The microwave-assisted synthesis features some advantages such as good yield of products, broad substrate scope, short reaction time, and absence of metal catalyst and solvent. Furthermore, the synthesis could be conveniently expanded to a gram scale. Methods: 2-arylbenzoxazoles were obtained from o-aminophenol with aldehydes using [Bmim]PF6 ionic liquid as a catalyst under microwave irradiation at 80ºC, 120 W. Results: Twenty-three 2-arylbenzoxazole derivatives were furnished in good to excellent yields under optimized conditions. The structures of these compounds were confirmed by analysis of NMR data. In addition, the method could be conveniently expanded to gram scale. Conclusion: An efficient and straightforward protocol for the synthesis of 2-arylbenzoxazoles catalyzed by [Bmim]PF6 ionic liquid has been demonstrated. The synthesis delivers several advantages such as short reaction time, broad substrate scope, scalability, solvent-free conditions, and high efficiency. The reaction mechanism and applications of this synthesis are currently ongoing in our lab and will be reported in due course.

Advances in the synthetic strategies of benzoxazoles using 2-aminophenol as a precursor: an up-to-date review.

Benzoxazole is a resourceful and important member of the heteroarenes that connects synthetic organic chemistry to medicinal, pharmaceutical, and industrial areas. It is a bicyclic planar molecule and is the most favorable moiety for researchers because it has been extensively used as a starting material for different mechanistic approaches in drug discovery. The motif exhibits a high possibility of broad substrate scope and functionalization to offer several biological activities like anti-microbial, anti-fungal, anti-cancer, anti-oxidant, anti-inflammatory effects, and so on. There has been a large upsurge in the synthesis of benzoxazole via different pathways. The present article presents recent advances in synthetic strategies for benzoxazole derivatives since 2018. A variety of well-organized synthetic methodologies for benzoxazole using 2-aminophenol with aldehydes, ketones, acids, alcohols, isothiocyanates, ortho-esters, and alkynones under different reaction conditions and catalysts, viz. nanocatalysts, metal catalysts, and ionic liquid catalysts, with other miscellaneous techniques has been summarized.

New iron(iii) complex of bis-bidentate-anchored diacyl resorcinol on a Fe3O4 nanomagnet: C-H bond oxygenation, oxidative cleavage of alkenes and benzoxazole synthesis.

We have synthesized a novel, bis-bidentate, covalently anchored, 4,6-diacetyl resorcinol (DAR) ligand on silica-coated magnetic Fe3O4 nanoparticles and the corresponding bi-metallic iron(iii) complex (Fe3O4@SiO2-APTESFe2LDAR). Both the chemical nature and the structure of the homogeneously heterogenized catalyst were investigated using physico-chemical techniques. The results obtained by XPS, XRD, FT-IR, TGA, VSM, SEM, TEM, EDX, ICP and AAS revealed a magnetic core, a silica layer and the grafting of a binuclear iron complex on the Fe3O4@SiO2-APTES, as well as its thermodynamic stability. Despite many reports of metal complexes on different supports, there are no reports of anchored, bi-metallic complexes. To the best of our knowledge, this is the first report of a bi-active site catalyst covalently attached to a support. This study focuses on the catalytic activity of an as-synthesized, bi-active site catalyst for C-H bond oxygenation, the oxidative cleavage of alkenes, and the multicomponent, one-pot synthesis of benzoxazole derivatives with excellent yields from readily available starting materials. Our results indicated high conversion rates and selectivity under mild reaction conditions and simple separation using a magnetic field. The leaching and recyclability tests of the catalyst were investigated for the above processes, which indicated that all the reactions proceed via a heterogeneous pathway and that the catalyst is recyclable without any tangible loss in catalytic activity for at least 8, 5 and 5 cycles for C-H bond oxygenation, C[double bond, length as m-dash]C bond cleavage and benzoxazole synthesis, respectively.

Synthesis of benzoxazoles via a silver mediated oxidation

A silver carbonate-based method to synthesize benzoxazoles from imines has been developed. The reaction is extremely mild, tolerates several heterocycles and functional groups, and provides highly functionalized benzoxazoles in modest to good yields. The reaction proceeds in an array of solvents and atmospheric conditions, demonstrating the robustness of this oxidation method and its ability to provide an alternative method for the easy preparation and isolation of these bioactive compounds.

Rapid and Simple Microwave-Assisted Synthesis of Benzoxazoles Catalyzed by [CholineCl][Oxalic Acid

Microwave irradiation has been used to enhance the reaction yields and selectivities for organic transformation. In this paper, microwave irradiation (MW) was investigated for the environmentally benign synthesis of benzoxazoles through the cyclization of 2-aminophenols and benzaldehydes using deep eutectic solvent (DES) as a catalyst. The [CholineCl][oxalic acid] was easily synthesized from choline chloride with oxalic acid and used without further purification. [CholineCl][oxalic acid] catalyzed the synthesis of benzoxazoles to produce the desired product in a good to excellent conversion and selectivity under MW irradiation. The presence of [CholineCl][oxalic acid] helps to promote the rapid heating transfer from microwave irradiation into the reaction mixture. The [CholineCl][oxalic acid] can be recovered and reused several times without a considerable degradation in catalytic activity.

Copper(II)-catalyzed Synthesis of Benzoxazoles from Inactive 2-chloroanilides.

Benzoxazoles are of great importance in natural products, pharmaceutical agents as well as synthetic intermediates. Although many works on the construction of benzoxazoles by Cu-catalyzed intramolecular O-arylation of ortho-haloanilides have been reported, only a few reports about transition metal-catalyzed synthesis of benzoxazoles from inactive 2-chloroanilides so far. This work aimed to explore a green and cheap protocol for intramolecular O-arylation of inactive 2-chloroanilides to prepare 2-arylbenzoxazoles. We found that Cu(acac)2/1,10-Phen complex was beneficial to intramolecular O-arylation of 2-chloroanilides using K2CO3 as a base in EtOH at 90 °C to prepare benzoxazoles. An efficient and green method was developed for Cu(II)-catalyzed intramolecular Oarylation of inactive 2-chloroanilides. In this way, many 2-arylbenzoxazoles were prepared in good yields.

TEMPO-Mediated Convergent Synthesis of Benzoxazoles from Primary Amines and Cyclohexanones

TEMPO-Mediated Convergent Synthesis of Benzoxazoles from Primary Amines and Cyclohexanones

Metal-Free Oxidative Annulation of Phenols and Amines: A General Synthesis of Benzoxazoles.

The ubiquity of benzoxazoles in natural products, drugs, and functional materials has stimulated numerous efforts toward their synthesis; however, the developed methods rely on prefunctionalized substrates and lack generality. Under metal-free conditions, a highly general synthesis of benzoxazoles direct from abundant and easily available phenols and amines is developed via a modular phenol functionalization controlled by TEMPO. In the reaction, various phenols and primary amines with a broad range of functional groups are compatible, producing structurally and functionally diverse benzoxazoles (64 examples) without or with trace observation of the byproducts of phenol transformation with amines. The practical synthesis, especially for drug tafamidis, demonstrates decisive advantages in generality, selectivity, efficiency, and atom- and step-economies over traditional methods, even in the cases of low yields. Mechanistically, the radical adducts of TEMPO with ortho-cyclohexa-2,4-dien-1-one radicals rather than the well-recognized cyclohexa-3,5-diene-1,2-diones may serve as intermediates.

Nanometric‐Thick Metal‐Free h‐Boron Nitride/Graphene Films as Base Catalyst for the Synthesis of Benzoxazoles

AbstractCatalysts are frequently used as pelletized powdered materials, but rarely as thin films. The present work reports the use of 2D h‐boron nitride on few layers defective graphene (h‐BN/fl‐G) films of about 10 nm thickness as base catalyst for the synthesis of benzoxazoles by coupling a 2‐amino‐phenol with p‐substituted benzaldehydes. The synthesis of benzoxazole derivatives has aroused much interest in the last decades due to their application as potent anticancer agents against MCF‐7 and MDA‐MB‐231 breast cancer cells. The results demonstrate that these nanometer‐thick films exhibit three orders of magnitude higher activity than K2CO3 taken as benchmark base catalyst. The activity and selectivity of h‐BN/fl‐G films depend on the nature of substituents on benzaldehyde, the solvent and reaction temperature.