Arene Oxides Research Articles

Photo-tunable oxidation of toluene and its derivatives catalyzed by TBATB

In this report, tetrabutylammonium tribromide (TBATB) was introduced as an efficient visible light active catalyst to carry out the aerobic oxidation of toluene, its derivatives, and some of methyl arenes to benzaldehydes, benzoic acids and ketones in good to high yields. All the oxidation reactions were performed under mild conditions using oxygen as a green oxidant, a catalytic amount of TBATB under blue (460 nm), royal blue (430 nm), and violet LED (400 nm) irradiation. It was found that the reactions selectivity was significantly affected by changing the solvent (from CH3CN to EtOAc) and LED wavelength (from blue to violet). In the following, our mechanistic studies revealed that the visible light oxidation of toluenes and methyl arenes over TBATB could be following a benzyl peroxy radical intermediate.

Additive-free aerobic C-H oxidation through a defect-engineered Ce-MOF catalytic system

Ce-UiO-66 MOF, namely cerium-organic framework was prepared through a fast and efficient method under ultrasonic radiation. After preparation, it was identified using some different microscopic and spectroscopic techniques such as PXRD, FT-IR, TG/DTA, BET, BJH, and FE-SEM. The catalytic activity of Ce-UiO-66 MOF was checked in aerobic oxidation of methyl arenas, alcohols and styrene derivatives in a sustainable circumstance with no additives. Moreover, its catalytic activity was surveyed influenced by a number of variables in the ultrasonic synthesis method. Some parameters such as solvent, base, temperature, amount of the catalyst and time were also tested to optimize the aerobic oxidation reaction. After the 10th run, the recycled Ce-MOF showed an acceptable efficiency, which proved its high reusability and stability under optimized conditions. Furthermore, the Ce-UiO-66 was investigated structurally by PXRD method which demonstrated the catalyst stability after the aerobic oxidation reaction. • Aerobic oxidation of methyl arenes, alcohols, and styrene derivatives. • Simple and efficient synthesis method for defect-engineered Ce-MOF preparation. • Using a non-precious metal catalyst for the aerobic oxidation process. • Air as a green oxidant for the oxidation process. • Using inert solvents to increase oxygen solubility and efficiency.

Arene Amination Instead of Fluorination: Substitution Pattern Governs the Reactivity of Dialkoxybenzenes with Selectfluor.

Arene substitution patterns are well-known to affect the regioselectivity of a given transformation but not necessarily the type of reactivity. Herein, we report that the substitution pattern of alkoxyarenes dictates whether a putative one-electron or two-electron reaction predominates in reactions with Selectfluor. A series of amination products is presented, resulting from the single-electron oxidation of electron-rich arenes followed by direct C-H to C-N bond formation. We demonstrate the ability of this transformation to synthesize medicinally and biologically relevant nitrogen heterocycles. Lastly, this unusual "mechanistic switch" is probed with computational chemistry and competition experiments.

Aromatic C−H Hydroxylation Reactions with Hydrogen Peroxide Catalyzed by Bulky Manganese Complexes

AbstractThe oxidation of aromatic substrates to phenols with H2O2 as a benign oxidant remains an ongoing challenge in synthetic chemistry. Herein, we successfully achieved to catalyze aromatic C−H bond oxidations using a series of biologically inspired manganese catalysts in fluorinated alcohol solvents. While introduction of bulky substituents into the ligand structure of the catalyst favors aromatic C−H oxidations in alkylbenzenes, oxidation occurs at the benzylic position with ligands bearing electron‐rich substituents. Therefore, the nature of the ligand is key in controlling the chemoselectivity of these Mn‐catalyzed C−H oxidations. We show that introduction of bulky groups into the ligand prevents catalyst inhibition through phenolate‐binding, consequently providing higher catalytic turnover numbers for phenol formation. Furthermore, employing halogenated carboxylic acids in the presence of bulky catalysts provides enhanced catalytic activities, which can be attributed to their low pKa values that reduces catalyst inhibition by phenolate protonation as well as to their electron‐withdrawing character that makes the manganese oxo species a more electrophilic oxidant. Moreover, to the best of our knowledge, the new system can accomplish the oxidation of alkylbenzenes with the highest yields so far reported for homogeneous arene hydroxylation catalysts. Overall our data provide a proof‐of‐concept of how Mn(II)/H2O2/RCO2H oxidation systems are easily tunable by means of the solvent, carboxylic acid additive, and steric demand of the ligand. The chemo‐ and site‐selectivity patterns of the current system, a negligible KIE, the observation of an NIH‐shift, and the effectiveness of using tBuOOH as oxidant overall suggest that hydroxylation of aromatic C−H bonds proceeds through a metal‐based mechanism, with no significant involvement of hydroxyl radicals, and via an arene oxide intermediate.magnified image

Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides.

Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective cis-dihydroxylation of carbocyclic rings and formation of isolable cis-dihydrodiol metabolites. These in silico docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated cis-dihydroxylation of electron-deficient pyridyl rings, to give transient cis-dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline cis-dihydrodiol metabolites were used as precursors in the chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives of quinoline, in the context of its possible mammalian metabolism and carcinogenicity.

Benzylic C(sp3)-C(sp2) cross-coupling of indoles enabled by oxidative radical generation and nickel catalysis.

A mechanistically unique functionalization strategy for a benzylic C(sp3)–H bond has been developed based on the facile oxidation event of indole substrates. This novel pathway was initiated by efficient radical generation at the benzylic position of the substrate, with subsequent transition metal catalysis to complete the overall transformation. Ultimately, an aryl or an acyl group could be effectively delivered from an aryl (pseudo)halide or an acid anhydride coupling partner, respectively. The developed method utilizes mild conditions and exhibits a wide substrate scope for both substituted indoles and C(sp2)-based reaction counterparts. Mechanistic studies have shown that competitive hydrogen atom transfer (HAT) processes, which are frequently encountered in conventional methods, are not involved in the product formation process of the developed strategy.

DRESS Sendromu: Bir Olgu Sunumu

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome is a rare, life-threatening drug reaction characterized by acute onset of fever, skin rash, and multisystemic involvement. Although the pathophysiology is not exactly known, slow detoxification of arene oxide bioactive metabolites of drugs and viral coinfections are blamed in people with genetic predisposition. A 17-year-old male patient was admitted to our clinic with a rash covering his entire body for 5 days. The patient, who stated that he had been using carbamazepine for 4 months due to epilepsy, had fever reaching 38.5°C at the time of admission, impaired liver function tests, high CRP, leukopenia, thrombocytopenia and eosinophilia. The patient, who was hospitalized, developed sudden vision blurriness and the cranial MRI result was reported as normal. It was thought that the blurriness in the vision could be caused by drug-induced eosinophil infiltration. This case is presented as a rare case of DRESS syndrome with blurred vision. Keywords: drug-induced hypersensitivity syndrome, anticonvulsant treatment, blurred vision

Visible-light assisted of nano Ni/g-C3N4 with efficient photocatalytic activity and stability for selective aerobic C−H activation and epoxidation

A selective, economical, and ecological protocol has been described for the oxidation of methyl arenes and their analogs to the corresponding carbonyl compounds and epoxidation reactions of alkenes with molecular oxygen (O2) or air as a green oxygen source, under mild reaction conditions. The nano Ni/g-C3N4 exhibited high photocatalytic activity, stability, and selectivity in the C−H activation of methyl arenes, methylene arenes, and epoxidation of various alkenes under visible- light irradiation without the use of an oxidizing agent and under base free conditions.

Preparation and characterization of p-sulfonated calix[4]arene functionalized chitosan hydrogel beads and their preliminary adsorption study towards removal of lead(II) and zinc(II) ions

p-sulfonated calix[4]arene functionalized chitosan hydrogel beads have been successfully prepared by mixing p-sulfonated calix[4]arene and chitosan in dilute acetic acid solution (1% v/v), followed by dropping the mixture into sodium hydroxide solution to form beads with diameters of ~0.1 cm. The presence of the active sulfonate groups and the unique structure of calixarene render the material useful as an adsorbent for heavy metal ions. Metal adsorption on p-sulfonated calix[4]arene is possible through a combination of physical and ionic interactions. Atomic Absorption Spectroscopy (AAS) results showed that the amount of adsorbed metal ion is optimum at 10 ppm for all samples. The overall percentage of metal ion removal shows that p-sulfonated calix[4]arene modified chitosan is the best adsorbent with up to 98% removal achieved for Pb(II) and 90% removal for Zn(II). This is followed by p-sulfonated calix[4]arene and graphene oxide (GO) modified chitosan with up to 90% removal for Pb(II) and 89% removal for Zn(II) and pure chitosan hydrogel beads with up to 60% removal for both Pb(II) and Zn(II). The results clearly prove that the presence of p-sulfonated calix[4]arene can enhance the adsorption of heavy metal ions. In addition, the adsorbent shows higher Pb(II) removal compared to Zn(II).

Исчерпывающее окисление декагидроксипиллар[5]арена нитратами меди(II) и железа(III)

Pillar[n]arenes are suitable synthetic platforms for synthesis of functionalized p-cyclophanes, versatile building blocks for creating supramolecular polymers and (pseudo)rotaxanes. The presence of hydroquinone fragments in unsubstituted pillar[n]arene derivatives opens wide opportunities for their application in electrochemical sensors and for their use as reducing agents for synthesis of hybrid materials. Macrocyclic cavity plays the key role in molecular recognition, supramolecular self-assembly of pillararenes, and therefore possibility of switching electron donor properties of aromatic moieties, forming macrocyclic cavity presents specific interest. Synthesis of pillar[n]quinones is non-trivial goal, usually, it requires expensive reagents (сerium(IV) ammonium nitrate). As an oxidized compound alkoxy-derivatives of pillararenes are used. While possibility of red-ox transitions of decahydroxypillar[5]arene are well known, to the date in literature there are no examples of total oxidation of decahydroxypillar[5]arene. We have studied interaction of decahydroxy-pillar[5]arene with a row of inorganic oxidants: catalytic oxidation with air oxygen in presence of copper(II) and iron(III) nitrates, and oxidation with ammonium persulfate. In order to find the optimal conditions for oxidation of pillar[5]arene the series of solvents were tried (proton donor alcohols and acetic acid, proton acceptor dimethylformamide and dimethylsulfoxide). It was established that using glacial acetic acid as a solvent with ultrasonication leads to total oxidation of pillar[5]arene to pillar[5]quinone. This fact is explained by strong proton-donor properties of glacial acetic acid, to prevent formation of insoluble quinhydrone complexes of pillar[5]arene oxidation products. Using ammonium persulfate does not lead to the product of total oxidation.

Metal- and Reagent-Free Electrochemical Synthesis of Alkyl Arylsulfonates in a Multi-Component Reaction.

This work presents the first electrochemical preparation of alkyl arylsulfonates by direct anodic oxidation of electron‐rich arenes. The reaction mechanism features a multi‐component reaction consisting of electron‐rich arenes, an alcohol of choice and excess SO2 in an acetonitrile‐HFIP reaction mixture. In‐situ formed monoalkyl sulfites are considered as key intermediates with bifunctional purpose. Firstly, this species functions as nucleophile and secondly, excellent conductivity is provided. Several primary and secondary alcohols and electron‐rich arenes are implemented in this reaction to form the alkyl arylsulfonates in yields up to 73 % with exquisite selectivity. Boron‐doped diamond electrodes (BDD) are employed in divided cells, separated by a simple commercially available glass frit.

Synthesis of Stilbenes by Rhodium-Catalyzed Aerobic Alkenylation of Arenes via C-H Activation.

Arene alkenylation is commonly achieved by late transition metal-mediated C(sp2)-C(sp2) cross-coupling, but this strategy typically requires prefunctionalized substrates (e.g., with halides or pseudohalides) and/or the presence of a directing group on the arene. Transition metal-mediated arene C-H activation and alkenylation offers an alternative method to functionalize arene substrates. Herein, we report a rhodium-catalyzed oxidative arene alkenylation from arenes and styrenes to prepare stilbene and stilbene derivatives. The reaction is successful with several functional groups on both the arene and the olefin including fluoride, chloride, trifluoromethyl, ester, nitro, acetate, cyanide, and ether groups. Reactions of monosubstituted arenes are selective for alkenylation at the meta and para positions, generally with approximately 2:1 selectivity, respectively. Resveratrol and (E)-1,2,3-trimethoxy-5-(4-methoxystyryl)benzene (DMU-212) are synthesized by this single-step approach in high yield. Comparison with palladium catalysis showed that rhodium catalysis is more selective for meta-functionalization for monosubstituted arenes and that the Rh catalysis has better tolerance of halogen groups.

Chemical Equivalent of Arene Monooxygenases: Dearomative Synthesis of Arene Oxides and Oxepines.

Direct epoxidation of aromatic nuclei by cytochrome P450 monooxygenases is one of the major metabolic pathways of arenes in eukaryotes. The resulting arene oxides serve as versatile precursors to phenols, oxepines, or trans-dihydrodiol-based metabolites. Although such compounds have an important biological and chemical relevance, the lack of methods for their production has hampered access to their utility. Herein, we report a general arenophile-based strategy for the dearomative synthesis of arene oxides. The mildness of this method permits access to sensitive monocyclic arene oxides without any noticeable decomposition to phenols. Moreover, this method enables direct conversion of polycyclic arenes and heteroarenes into the corresponding oxepines. Finally, these studies provided direct connection between simple aromatic precursors and complex small organic molecules via arene oxides and oxepines.

Oxidation of Electron-Rich Arenes Using HFIP-UHP System.

The straightforward oxidation of electron-rich arenes, namely, phenols, naphthols, and anisole derivatives, under mild reaction conditions, is described by means of the use of an environmentally benign HFIP-UHP system. The corresponding quinones or hydroxylated arenes were obtained in moderate to good yields.

Advances in Rhodium-Catalyzed Oxidative Arene Alkenylation.

ConspectusAlkyl and alkenyl arenes are of substantial value in both large-scale and fine chemical processes. Billions of pounds of alkyl and alkenyl arenes are produced annually. Historically, the dominant method for synthesis of alkyl arenes is acid-catalyzed arene alkylation, and alkenyl arenes are often synthesized in a subsequent dehydrogenation step. But these methods have limitations that result from the catalytic mechanism including (1) common polyalkylation, which requires an energy intensive transalkylation process, (2) quantitative selectivity for Markovnikov products for arene alkylation using α-olefins, (3) for substituted arenes, regioselectivity that is dictated by the electronic character of the arene substituents, (4) inability to form alkenyl arenes in a single process, and (5) commonly observed slow reactivity with electron-deficient arenes. Transition-metal-catalyzed aryl-carbon coupling reactions can produce alkyl or alkenyl arenes from aryl halides. However, these reactions often generate halogenated waste and typically require a stoichiometric amount of metal-containing transmetalation reagent. Transition-metal-catalyzed arene alkylation or alkenylation that involves arene C-H activation and olefin insertion into metal-aryl bonds provides a potential alternative method to prepare alkyl or alkenylation arenes. Such reactions can circumvent carbocationic intermediates and, as a result, can overcome some of the limitations mentioned above. In particular, controlling the regioselectivity of the insertion of α-olefins into metal-aryl bonds provides a strategy to selectively synthesize anti-Markovnikov products. But, previously reported catalysts often show limited longevity and low selectivity for anti-Markovnikov products.In this Account, we present recent developments in single-step arene alkenylation using Rh catalyst precursors. The reactions are successful for unactivated hydrocarbons and exhibit unique selectivity. The catalytic production of alkenyl arenes operates via Rh-mediated aromatic C-H activation, which likely occurs by a concerted metalation-deprotonation mechanism, olefin insertion into a Rh-aryl bond, β-hydride elimination from the resulting Rh-hydrocarbon product, and net dissociation of alkenyl arene with formation of a Rh hydride. Reaction of the Rh hydride with Cu(II) oxidant completes the catalytic cycle. Although Rh nanoparticles can be formed under some conditions, mechanistic studies have revealed that soluble Rh species are likely responsible for the catalysis. These Rh catalyst precursors achieve high turnovers with >10,000 catalytic turnovers observed in some cases. Under anaerobic conditions, Cu(II) carboxylates are used as the oxidant. In some cases, aerobic recycling of Cu(II) oxidant has been demonstrated. Hence, the Rh arene alkenylation catalysis bears some similarities to Pd-catalyzed olefin oxidation (i.e., the Wacker-Hoechst process). The Rh-catalyzed arene alkenylation is compatible with some electron-deficient arenes, and they are selective for anti-Markovnikov products when using substituted olefins. Finally, when using monosubstituted arenes, consistent with a metal-mediated C-H activation process, Rh-catalyzed alkenylation of substituted arenes shows selectivity for meta- and para-alkenylation products.

Palladium Catalyzed Stereoselective Arylation of Biocatalytically Derived Cyclic 1,3-Dienes: Chirality Transfer via a Heck-Type Mechanism

Microbial arene oxidation of benzoic acid with Ralstonia eutropha B9 provides a chiral highly functionalized cyclohexadiene, suitable for further structural diversification. Subjecting this scaffold to a Pd-catalyzed Heck reaction effects a regio- and stereoselective arylation of the cyclohexadiene ring, with 1,3-chirality transfer of stereogenic information installed in the microbial arene oxidation. Quantum chemical calculations explain the selectivity both by a kinetic preference for the observed arylation position and by reversible carbopalladation in competing positions. Further product transformation allowed the formation of a tricyclic ketone possessing four stereogenic centers. This demonstrates the capability of the method to introduce stereochemical complexity from planar nonchiral benzoic acid in just a few steps.

A Remote 'Imidazole'-Based Ruthenium(II) Para-Cymene Pre-catalyst for the Selective Oxidation Reaction of Alkyl Arenes and Alcohols.

Herein we disclosed the use of a remote 'imidazole'-based precatalyst [(para-cymene)RuII (L)Cl]+ , C-1 where L=2-(4-substituted-phenyl)-1H-imidazo[4,5-f][1,10] phenanthroline) for the selective oxidation of a variety of alkyl arenes/heteroarenes and alcohols to their corresponding aldehydes or ketones in presence of tert-butyl hydroperoxide (TBHP). The remote 'imidazole' moiety present in the complex facilitates the activation of oxidant and subsequent generation of active species via the release of para-cymene from C-1, which in-turn was less effective without the 'imidazole' moiety. The mechanistic features of C-1 promoted oxidation of alkyl arenes were also assessed from spectroscopic, kinetic, and few control experiments. The substrate scope for C-1 promoted oxidation reaction was assessed based on the selective oxidation of 27-different alkyl arenes/heteroarenes and 25 different alcohols to their corresponding aldehydes/ketones in moderate to good yields.

Iodine(III)-catalyzed benzylic oxidation by using the (PhIO)n/Al(NO3)3 system

The first iodine(III)-based procedure for the benzylic oxidation of different arenes is described by using the (PhIO)n/Al(NO3)3 system under catalytic conditions leading to the formation of the corresponding carbonyl derivatives. The method proceeds under mild, operationally simple, room temperature, short reaction times, and open flask conditions. In light of the organocatalysis relevance and the novelty of our protocol, we wish to communicate our initial results of this novel oxidation.

An 8-hydroxyquinoline-proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes.

Herein the design and synthesis of a new 8-hydroxyquinoline derivative, (S)-5-chloro-7-((proline-1-yl)methyl)8-hydroxyquinoline (HQCl-Pro), with good water solubility and multidrug resistance reversal activity are reported. In this work the proton dissociation processes of HQCl-Pro and its complex formation with [Rh(η5-C5Me5)(H2O)3]2+, [Ru(η6-p-cymene)(H2O)3]2+ and [Ru(η6-toluene)(H2O)3]2+ were investigated by the combined use of pH-potentiometry, UV-visible spectrometry and 1H NMR spectroscopy. Our results revealed the prominent solution stability of the complexes in all cases. The lipophilicity of the complexes increased with the chloride ion concentration, and the complexes showed moderate log D values (-0.8 to +0.4) at pH 7.4 at all tested Cl- concentrations. The formation of mixed hydroxido complexes from the aqua complexes was characterized by relatively high pKa values (8.45-9.62 in chloride-free medium). Complexation processes are much slower with the Ru(η6-arene) triaqua cations than with [Rh(η5-C5Me5)(H2O)3]2+. Both the pKa values and H2O/Cl- exchange constants of the Ru-complexes are lower by 0.5-1.0 orders of magnitude than those of the Rh analogue. Arene loss (p-cymene and toluene) and oxidation were found in the case of Ru-complexes when an excess of HQCl-Pro and aromatic (N,N) bidentate ligands was added. The cytotoxicity and antiproliferative effect of HQCl-Pro and its complexes were assayed in vitro. In contrast to the structurally familiar 8-hydroxyquinoline, HQCl-Pro and its Rh(η5-C5Me5) complex were somewhat more effective against drug resistant Colo 320 adenocarcinoma human cells compared to the drug sensitive Colo 205 cells. The Ru- and Rh-complexes showed a similar metal uptake level after 4 h, while a longer incubation time resulted in higher cellular Rh concentration.

Photocatalytic Oxidative Iodination of Electron‐Rich Arenes

AbstractA visible‐light‐mediated oxidative iodination of electron‐rich arenes has been developed. 2.5 mol% of unsubstituted anthraquinone as photocatalyst were used in combination with elementary iodine, trifluoroacetic acid and oxygen as the terminal oxidant. The iodination proceeds upon irradiation in non‐ or weakly‐electron donating solvents (DCM, DCE and benzene) wherein a spectral window in strongly coloured iodine solutions can be observed at around 400 nm. The method provides good to excellent yields (up to 98%) and shows excellent regioselectivity and good functional group tolerance (triple bonds, ketone, ester, amide). Moreover, the photo‐iodination was also upscaled to a 5 mmol scale (1.1 g). Mechanistic investigations by intermediate trapping and competition experiments indicate a photocatalytic arene oxidation and the subsequent reaction with iodine as a likely mechanistic pathway.magnified image