Arylation Of Benzoxazoles Research Articles

Facile and an efficient one-pot synthesis of 2-arylbenzoxazoles promoted by transition metal oxide nano catalyst

The advantages and an efficient path way of process for 2-arylbenzoxazole can be obtained by transition metal oxide Nano catalyst. The transition metal nano TiO2 catalysed and a tandem reaction between substituted 2-aminophenols and substituted aromatic aldehydes to produces scaffold series of 15 smoothly forming benzo heterocycles with good to excellent yields (80-94%). The synthesized benzoxazole compounds were confirmed by FT-IR, 1H, 13CNMR, and mass spectroscopy. This article describes a one-stage coupling technique that provides a unique way to access variously functionalized benzoxazole scaffolds. This methodology consists of a one-pot combination of condensation followed by oxidative addition reactions. It was shown that nano TiO2 in ethanol encouraged the formation of 2-aryl benzoxazole scaffolds and this catalyst quickly boosted the cascade reaction that produced a variety of collections of named derivatives. These protocols are atom-economic, efficient, reusable and modular means of accessing restricted named derivatives that have a substantial substrate tolerance and over ten points of diversity.

Synthesis and Characterization of Pd(0) Complexes with Electronically Differentiated Ferrocene Diphosphane Ligands

AbstractThe strategy of modifying phosphane ligands through substituent variation has been widely applied in coordination chemistry and catalysis. This contribution focuses on unsymmetric ferrocene diphosphanes with electronically distinct phosphane moieties, Ph2PfcCH2PAr2 (Ar=Ph, 1; 3,5‐C6H3Me2, 2; and 3,5‐C6H3(CF3)2, 3; fc=ferrocene‐1,1′‐diyl), which were synthesized and converted to the corresponding selenides (1Se–3Se) and Pd(0) complexes [Pd(L‐κ2P,P′)(η2‐ma)] (5–8 for L=1–3 and dppf, ma=maleic anhydride). All compounds were characterized by NMR spectroscopy, ESI MS and elemental analysis, and the structures of 2, 1Se ⋅ CHCl3, 2Se and 5 ⋅ PhMe were determined by X‐ray diffraction analysis. In addition, the redox behavior of 1–3 and 5–8 was studied by cyclic voltammetry and rationalized through DFT calculations. The prepared Pd(0) complexes and their model compound [Pd(dppf‐κ2P,P′)(η2‐ma)] were employed in Pd‐catalyzed C−H arylation of benzoxazole with chlorobenzene in n‐butanol in the presence of K3PO4 as the base, and the catalytic results were compared with the collected characterization data, including the 1JPSe coupling constants determined for 1Se–3Se, as a measure of ligand basicity.

Identification of α-Synuclein Proaggregator: Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson's Disease.

We report the discovery of two compounds, TKD150 and TKD152, that promote the aggregation of α-synuclein (aSN) using a real-time quaking-induced conversion (RT-QuIC) assay to detect abnormal aSN. By utilizing a Pd-catalyzed C–H arylation of benzoxazole with iodoarenes and implementing a planar conformation to the design, we successfully identified TKD150 and TKD152 as proaggregators for aSN. In comparison to a previously reported proaggregator, PA86, the two identified compounds were able to promote aggregation of aSN at twice the rate. Application of TKD150 and TKD152 to the RT-QuIC assay will shorten the inherent lag time and may allow wider use of this assay in clinical settings for the diagnosis of α-synucleinopathy-related diseases.

Synthesis of 2-Aryl Benzoxazoles from Benzoxazoles and α-Ketoic Acids by Photoredox Catalysis

Synthesis of 2-Aryl Benzoxazoles from Benzoxazoles and <i>α</i>-Ketoic Acids by Photoredox Catalysis

Life cycle assessment of multistep benzoxazole synthesis: from batch to waste-minimised continuous flow systems

A comprehensive life cycle assessment of different 2-aryl benzoxazoles routes was performed to a flow chemistry approach, its batch equivalent, and other batch approaches to show how innovations in green chemistry and circularity result in real sustainability benefits.

Stable Pd(0) Complexes with Ferrocene Bisphosphanes Bearing Phosphatrioxaadamantyl Substituents Efficiently Catalyze Selective C‐H Arylation of Benzoxazoles by Aryl Chlorides

AbstractVersatile applications and unique performance of 1,1’‐bis(diphenylphosphanyl)ferrocene (dppf) in coordination chemistry and catalysis prompted the search for its analogs. This contribution describes the synthesis of the first donor‐unsymmetric dppf congeners bearing bulky and rigid 1,3,5,7‐tetramethyl‐2,4,6‐trioxa‐8‐phosphaadamantyl (CgP) donor groups, viz. Ph2PfcPCg (1) and Ph2PfcCH2PCg (2; fc=ferrocene‐1,1’‐diyl). Bis‐phosphanes 1 and 2 were converted into air‐stable Pd(0) complexes, [Pd(ma)(L^L)] (L^L=1 and 2; ma=maleic anhydride). Together with [Pd(ma)(dppf)], these complexes were applied as catalysts in Pd‐catalyzed C−H arylation of benzoxazoles with aryl chlorides in n‐butanol as an environmentally benign solvent. Among all catalysts tested in this study, complex [Pd(ma)(2)] performed the best, providing a high‐yield and selective synthesis of 2‐arylbenzoxazoles from a range of the generally less reactive chloroarenes at low catalyst loading (typically 1 mol.%). Under similar conditions, the structurally related heterocycles (e. g., 1‐methylbenzimidazole and benzothiazole) did not react.

Delivering 2-Aryl Benzoxazoles through Metal-Free and Redox-Neutral De-CF3 Process.

An unexpected cleavage of the Csp3-CF3 bond of CF3-hydrobenzoxazoles has been disclosed, affording a range of 2-aryl benzoxazoles under metal-free and redox-neutral conditions. This transformation has demonstrated broad substrate scope and good compatibility of functional groups. 2-Aryl benzothiazole and 2-aryl benzoimidazole could be smoothly assembled in the same manner. On the basis of preliminary mechanistic studies, base initiated and aromatization driven β-carbon elimination was considered to be the key step for the formation of 2. This reaction offers an alternative, facile, and sustainable route to access important 2-aryl benzoxazole motifs.

TEMPO-mediated aerobic oxidative synthesis of 2-aryl benzoxazoles via ring-opening of benzoxazoles with benzylamines

A simple and efficient TEMPO-mediated system for aerobic oxidative synthesis of 2-aryl benzoxazoles from readily available benzoxazoles and primary benzylic and hetero benzylic amines is presented in one pot. The reaction proceeds through the ring-opening of benzoxazoles and is followed by oxidative condensation with benzylamines. These metal-free, straightforward reactions worked well with a wide range of substrates, yielding moderate to good yields under mild conditions using air as an external green oxidant.

A new synthesis of tafamidis via zinc-MsOH mediated reductive cyclisation strategy

A practical zinc-MsOH mediated intra-molecular reductive cyclisation and its application in the synthesis of tafamidis is presented starting from the readily available 3-hydroxy-4-nitrobenzoic acid as a precursor. The key reductive cyclization step involves the use of a combination of the readily available zinc and MsOH as the catalyst system. This methodology provides an attractive route to 2-aryl benzoxazoles from ortho-nitro phenols under mild reaction conditions. This methodology is developed on a multi-gram scale and without the need for column chromatography. A new and alternative zinc-MsOH mediated intra-molecular reductive cyclisation and its application in the synthesis of tafamidis is reported starting from the readily available 3-hydroxy-4-nitrobenzoic acid as precursor. This method provides an attractive route to 2-aryl benzoxazoles from ortho-nitro phenols under mild reaction conditions.

Phosphine-phosphonium ylides as ligands in palladium-catalysed C2-H arylation of benzoxazoles

As balanced electron-rich P,C-chelating ligands, phosphine-phosphonium-ylides are considered for their ability to in situ promote palladium-catalysed direct C(sp2)H arylation. Using methyl phosphonium salts of 2,2'-bis(diphenylphosphino)-1,1'-binaphtyl ("methyl-BINAPIUM") as ylide precursors under optimized reaction conditions, arylation of benzoxazole was found to proceed in moderate to high yield to give functional 2-aryl benzoxazoles. A strong anion effect of the non-salt free ylide was evidenced (TfO− > I− > PF6− ≈ salt-free). This first example of phosphonium ylides as ligands in catalytic C–H activation extends the prospect of their general implementation in homogeneous transition metal catalysis.

Synthesis and X-ray crystal structures of three new nickel(II) complexes of benzoylhydrazones: Catalytic applications in the synthesis of 2-arylbenzoxazoles

Three new complexes of nickel(II), having general formula [Ni(L1)(PPh3)] (1), [Ni(L1)(4-picoline)] (2), and [Ni(L2)(4-picoline)] (3) were synthesized by the reaction of Ni(OAc)2·4H2O with corresponding benzolyhydrazine-derived Schiff base ligands i.e. [4-(diethylamino)-2-hydroxybenzylidene]-benzohydrazonic acid (H2L1) or [2-(hydroxynaphthalen-1-yl)methylene]-benzohydrazonic acid (H2L2) and PPh3/4-picoline as co-ligand in 1:1:1 ratio in methanol. All the three complexes were air-stable, isolated as reddish brown solids and characterized by Elemental analysis, FT-IR, 1H, 13C{1H}, 31P{1H} NMR spectroscopy and mass spectrometry. The structures of all three complexes were determined by single crystal X-ray diffraction studies which revealed the distorted square planar geometry of the complexes. In these complexes, three coordination sites were occupied by ONO pincer type Schiff base ligand and the fourth site was blocked by phosphorus (P) or nitrogen (N) atom of the co-ligand. The catalytic potential of all three complexes was explored in the synthesis of a series of 2-arylbenzoxazoles from aldehydes and 2-aminophenol, using low catalyst loading (0.5 mol%). Complex 1 was found to be the best catalyst among three complexes, for the synthesis of a series of 2-aryl benzoxazoles. The ease of synthesis, air-stability and robustness of the catalyst, and good TONs are some of the key characteristics of the described catalytic system.

Magnetic Nanoparticle Decorated N-Heterocyclic Carbene–Nickel Complex with Pendant Ferrocenyl Group for C–H Arylation of Benzoxazole

Magnetic nanoparticle decorated N-heterocyclic carbene–nickel complex with pendant ferrocenyl group has been prepared by multi-step procedure. The formation of complex was confirmed on the basis of analytical techniques such as Fourier transform infrared (FT-IR), Fourier transform Raman (FT-Raman) and X-ray photoelectron spectroscopy (XPS) as well as by X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM) analysis. The complex proved to be an efficient heterogeneous catalyst for C–H arylation of benzoxazole with aryl boronic acids. The recycling studies revealed that complex could be reused for six times without significant decrease in catalytic activity.

Heteroleptic palladium(II) complexes containing N-heterocyclic carbenes and 4-phenyl-1H-1,2,3-triazole: Synthesis, characterization, and catalytic application

Reaction of the dimeric N-heterocyclic carbene (NHC) palladium compounds [Pd(μ-Cl)(Cl)(NHC)]2 with 4-phenyl-1H-1,2,3-triazole gave four mono- and dinuclear complexes 1–4. Mononuclear complexes 1 and 2 [(NHC)PdCl2(4-phenyl-1H-1,2,3-triazole)] were obtained when the reactions were performed in CH2Cl2, whereas dinuclear complexes 3 and 4 [Pd2(μ-Cl)(μ-4-phenyl-1H-1,2,3-triazole)Cl2(NHC)2] were obtained when the reactions were performed in THF in reflux with Et3N as the base. Further explorations of the catalytic properties of 1–4 for Pd-catalyzed transformations have been performed and these complexes exhibited moderate to high catalytic activities for Suzuki–Miyaura coupling and arylation of benzoxazoles with aryl bromides.

Facile Protocols towards C2-Arylated Benzoxazoles using Fe(III)-Catalyzed C(sp 2-H) Functionalization and Metal-Free Domino Approach

Considering their growing attention in the field of medicinal chemistry and drug-discovery research, the facile and convenient approaches towards the preparation of 2-aryl benzoxazole derivatives have been described. The transformation is accomplished by using Fe(III)-catalyzed C–H activation of benzoxazoles with boronic acids to obtain a wide range of C2-arylated benzoxazoles in high yields. The developed method excludes the formation of self-coupling compounds as side products. On the other hand, the synthesis of the products is also achieved via a metal-free domino protocol by the reaction between 1-nitroso-2-naphthol and acetophenones using catalytic amounts of CBr4 in the presence of Cs2CO3 as base. The devised tandem method avoids the use of pre-activated α-haloketones as substrates. Due to their immense impact in marketed drugs and molecules under clinical trial, the described method can be a powerful tool for their synthesis which ­restricts the use of precious metals as catalyst.

Unsymmetrical Pincer N-Heterocyclic Carbene–Nitrogen–Phosphine Chelated Palladium(II) Complexes: Synthesis, Structure, and Reactivity in Direct Csp2–H Arylation of Benzoxazoles

An unsymmetrical pincer N-heterocyclic carbene–nitrogen–phosphine (CNP) and its palladium complexes PdCl2(κ2-CP) (4) and [PdCl(κ3-CNP)]PF6 (5·PF6) were synthesized. NMR spectra disclosed that the transformation of complex 4 structure occurred in the solution. Further NMR experimental and single crystal structure analysis of complex 4 provided unequivocal and structural evidence for the formation of complex [PdCl(κ3-CNP)]Cl (5·Cl) in the solution of complex 4. The catalytic performance of palladium complexes 4 and 5·PF6 was investigated with the direct Csp2–H arylation of benzoxazoles with aryl bromides. Notably, aryl bromides could give up to 97% arylation products in the presence of 0.5% complex 4. For ortho-substituted substrates, the steric hindrance had a significant impact, but product yields could be improved remarkably by extending reaction time. This result implied the catalytic active species in this system was stable and kept in a long lifetime. The flexible backbone and unsymmetrical pincer str...

Transition-metal-free arylation of benzoxazoles with aryl nitriles

Transition-metal-free arylation of benzoxazoles with aryl nitriles has been developed to afford important 2-aryl benzoxazoles under simple reaction conditions.

Synthesis of 2-Aryl Benzoxazoles from Aldoximes

Synthesis of 2-Aryl Benzoxazoles from Aldoximes

Sonocatalyzed facile synthesis of 2-aryl benzoxazoles using MnO2 nanoparticles as oxidant agent under mild conditions

ABSTRACTNano MnO2 was found to be an efficient oxidant agent for the synthesis of 2-substituted benzoxazoles through one-pot reaction of o-aminophenol and different aromatic aldehydes in acetonitrile under ultrasonic irradiation. This method was performed under mild conditions with high yields, inexpensive and readily available oxidant agent, facile and easy experimental procedure, simple purification of final products, and short reaction times. The prepared nano MnO2 has been characterized by FTIR, XRD, and SEM techniques. The pure products were identified and characterized by physical and spectroscopic data such as; melting point, IR, 1H NMR, and 13C NMR.

Lewis-Acid-Mediated Benzotriazole Ring Cleavage (BtRC) Strategy for the Synthesis of 2-Aryl Benzoxazoles from N-Acylbenzotriazoles.

A Lewis-acid-mediated ring cleavage of acylbenzotriazoles (RCOBt) followed by cyclization to corresponding benzoxazoles was achieved in good to excellent yields. The reaction was found consistent with the milligram to gram scale.

Nickel-Catalyzed Coupling of Azoles with Aromatic Nitriles.

This manuscript describes the Ni-catalyzed coupling of azoles with aromatic nitriles. The use of BPh3 promotes these arylations with electronically diverse azoles and benzonitriles. While the nickel catalyst is necessary for the arylations of phenyl oxazoles, arylation of benzoxazoles with some nitriles affords the arylated products even in the absence of the Ni catalyst albeit in lower yield than the catalyzed process. The Ni-catalyzed process exhibits higher rates and a broader scope than the uncatalyzed transformation.