2-arylbenzoxazole Derivatives Research Articles

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.

Nickel/Copper Cooperative Catalysis Decarbonylative Heteroarylation of Aryl Anhydrides with Benzoxazoles via C-O/C-H Coupling.

A new strategy for the synthesis of 2-arylbenzoxazole derivatives via nickel-/copper-catalyzed decarbonylative heteroarylation of aryl anhydrides via C-O/C-H coupling has been developed. The reaction is promoted by a user-friendly, inexpensive, and air- and moisture-stable Ni precatalyst. A variety of 2-arylbenzoxazole derivatives have been successfully synthesized and have good functional group tolerance in this process, which afforded products in moderate-to-excellent yields.

A New Method for the Synthesis of 2-Substituted Benzoxazoles from 2-Nitrophenol Derivatives and Aldehydes

Benzoxazole derivatives are one of the compounds with many interesting biological activities. Conventional methods are often performed under complex conditions using strong acids, expensive metal catalysts, requiring high pressure, high temperature, and under microwave irradiation. In this study, we reported a new method of benzoxazole synthesis with redox catalyst using FeCl3.6H2O and sulfur. This is a suitable, efficient, readily available and environmentally friendly catalyst system for redox and condensation reactions in one step at 100 oC. Applying this new method, we have synthesized eight 2-arylbenzoxazole derivatives with high yields (calculated according to 2-nitrophenol). This research is an important step forward in the synthesis of biologically active compounds containing the benzoxazole framework from readily available starting materials in a single reaction.

New Method of 2-Arylbenzoxazole Synthesis from 2-Aminophenol Derivatives and Benzaldehyde Using Sulfur as an Oxidant

In previous studies, the synthesis of 2-arylbenzoxazole derivatives required strongly acidic conditions, prolonged heating at high temperatures and significant amounts of expensive/toxic transition metal catalysts. A major drawback of using oxygen as an oxidant is the risk of explosion of flammable organic substrates. Moreover, due to its gaseous state, exact stoichiometric control of oxygen amounts used in the reaction is not readily possible. Therefore, new methods of mellow conditions with eco-friendly agents is targeted by our team. In this study, sulfur (S8) is found as an effective oxidizer in the oxidation reaction condensation between 2-aminophenols with benzaldehydes to obtain different 2-arylbenzoxazole. In the presence of Na2S as catalysts and DMSO as an additive the reactions give good yield in only one step at the ambient temperature.

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.

Synthesis of o-Alkenylated 2-Arylbenzoxazoles via Rh-Catalyzed Oxidative Olefination of 2-Arylbenzoxazoles: Scope Investigation, Structural Features, and Mechanism Studies.

2-Arylbenzazoles are promising molecules for potential applications in medicine and material areas. Efficient protocols for direct regioselective functionalization of 2-arylbenzoxazoles are in high demand. Herein, we disclose a general method for selective ortho-olefination of 2-arylbenzo[d]oxazoles with alkenes enabled by versatile Cp*Rh(III) in high yields. This protocol features broad functional group tolerance and high regioselectivity. Intermolecular competition studies and kinetic isotope effect experiments imply that the oxidative olefination process occurs via an electrophilic C-H activation pathway. The molecular structure of the m-fluoro-substituted olefination product confirms regioselective C-H activation/olefination at the more hindered site in cases where the meta F atom or heteroatom substituent existed. Apparent torsion angles were observed in the structures of mono- and bis-olefination products, which resulted in distinct different chemical shifts of olefinic protons. Additionally, two gram-scale reactions and further transformation experiments demonstrate that this method is practical for synthesis of ortho-alkenylated 2-arylbenzoxazole derivatives.

BiCl3 – an eco-friendly catalyst for an efficient synthesis of benzoxazoles at room temperature

A simple and efficient protocol has been developed for the synthesis of 2-arylbenzoxazole derivatives of potential pharmaceutical interest. The method involves reaction between 2-aminophenol and substituted aromatic aldehydes in the presence of anhydrous bismuth trichloride as catalyst in acetonitrile. The use of eco-friendly bismuth trichloride, overall mild reaction conditions, and moderate to good yield of products are some attractive features of this methodology.

One-pot synthesis of 2-arylbenzoxazole derivatives via Cu(I) catalyzed C–N/C–O coupling of N-(2-chloro-phenyl)-2-halo-benzamides and primary amines

N-(2-Chloro-phenyl)-2-halo-benzamides (halo=I/Br/Cl) as substrates were used for the one-pot synthesis of 2-arylbenzoxazole derivatives via copper-catalyzed intermolecular C–N/intramolecular C–O couplings with primary amines. This aryl amination offers clean reaction conditions and easy work-up in good yields by using CuI as catalyst, readily available 8-hydroxyquinoline as ligand, K3PO4 as base, DMF as solvent.

(99m)Tc-labeled-2-arylbenzoxazole derivatives as potential Aβ imaging probes for single-photon emission computed tomography.

Four neutral (99m)Tc/Re-labeled 2-arylbenzoxazole derivatives conjugated to bis (aminoethanethiol) (BAT) chelating ligand via a short propoxy spacer were synthesized and evaluated. Invitro binding assay showed that they displayed binding affinities to Aβ1-42 aggregates (Ki=15.86-393.18nM). Invitro autoradiography studies further confirmed the high and specific binding of [(99m)Tc]20 to β-amyloid plaques on brain sections of transgenic mice. Biodistribution study of [(99m)Tc]17-20 in normal mice displayed moderate initial brain uptake (0.96-1.55%ID/g at 2min), and fast washed out from the brain (0.14-0.40%ID/g at 60min), especially for [(99m)Tc]20 with a brain2min/brain60min ratio of 8.86. Taken together, these preliminary data suggested that [(99m)Tc]20 may be a potential imaging probe for detecting amyloid plaques in the brain.

One-pot synthesis of 2-arylbenzimidazole, 2-arylbenzothiazole and 2-arylbenzoxazole derivatives using vanadium(IV)–salen complex as homogeneous catalyst and vanadium(IV)–salen complex nanoparticles immobilized onto silica as a heterogeneous nanocatalyst

The efficient synthesis of 2-arylbenzimidazole, 2-arylbenzothiazole and 2-arylbenzoxazole derivatives is described by condensation of aryl aldehydes and o-phenylenediamines, 2-aminothiophenol and 2-aminophenol in a single pot using a catalytic amount of vanadium(IV)–salen complex or vanadium–salen nanoparticles supported on silica (5.0 mol%) in excellent isolated yields. The immobilized catalyst was characterized by powder X-ray diffraction, scanning electron microscopy, atomic force microscopy, transmission electron microscopy, inductively coupled plasma analysis, thermogravimetric instrument for analysis of nitrogen adsorption and FT-IR spectroscopy.

Palladium-catalyzed direct arylation of benzoxazoles with unactivated simple arenes

Using CuBr(2) as an additive, the Pd-catalyzed intermolecular C-H-C-H cross-coupling between benzoxazoles and unactivated simple arenes has been developed. This protocol provides a straightforward approach for the biological activity of 2-arylbenzoxazole derivatives.

English

QSAR studies of thirty 2-arylbenzoxazole derivatives are carried out to probe their inhibitory activity against Cholesteryl Ester Transfer Protein (CETP). QSAR models have been obtained using multiple linear regression (MLR) analysis after manifestation of forward selection algorithm to cull significant descriptors out of descriptor’s pool. QSAR models are elected with adherent set of statistical parameters with R2=0.9431 and R2=0.9069. Validation of modeling includes method of Y-Scrambling and in addition to this, some other methods of validation. Moreover, QSAR approach of 2-arylbenzoxazoles are also attempted, supported and validated by flexible docking studies as well. The search strategies include evolutionary algorithm and edited form of Gehlhaar PLP scoring function. The same set of thirty candidates from 2-arylbenzoxazole derivatives is processed in molecular docking and their docking scores are found in agreement with QSAR studies reported. Remarkable CETP inhibitory activity is exhibited by a 2-arylbenzoxazole derivatives molecule 29C with most comprehensive set of interactions with rerank scores -102.167 and RMSD values 1.104. Hydrogen bond interactions along with hydrophobic and electrostatic interactions are mapped to confirm their potencies.

Zeolite‐catalyzed simple synthesis of different heterocyclic rings, part 2

AbstractA simple and environmentally friendly synthesis was developed for the preparation of 2‐arylimidazoline derivatives and 2‐arylbenzoxazole derivatives using a small pore size zeolite. The similar reaction was not applicable to the preparation of the sulfur‐containing analogs cysteamine or 2‐aminothiophenol, probably because of a disadvantageous reaction between the zeolite and the thio compound. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:428–431, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20036