Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide.

This article describes the detailed analysis of the reaction between arylamines, such as aniline, o-anisidine, and methyl anthranilate, with selenium dioxide in acetonitrile. A systematic analysis of the reaction products with the help of 77Se NMR and single-crystal X-ray crystallography revealed that the reaction progress follows three major reaction pathways, electrophilic selenation, oxidative polymerization, and solvent oxidation. For aniline and o-anisidine, predominant oxidative polymerization occurred, leading to the formation of the respective polyaniline polymers as major products. For methyl anthranilate, the oxidative polymerization was suppressed due to the delocalization of amine lone pair electrons over the adjacent carboxylate function, which prompted the selenation pathway, leading to the formation of two of the isomeric diorganyl selenides of methyl anthranilate. The diaryl selenides were structurally characterized using single-crystal X-ray diffraction. Density functional theory calculations suggest that the highest occupied molecular orbital of methyl anthranilate was deeply buried, which suppressed the oxidative polymerization pathway. Due to solvent oxidation, oxamide formation was also noticed to a considerable extent. This study provides that utmost care must be exercised while using SeO2 as an electrophile source in aromatic electrophilic substitution reactions.

Amino-λ3 -iodane-Enabled Electrophilic Amination of Arylboronic Acid Derivatives.

In this report, we describe the use of amino-λ3 -iodanes in the electrophilic amination of arylboronic acids and boronates. Iodine(III) reagents with transferable amino groups, including one with an NH2 group, were synthesized and used in the amination, allowing the synthesis of a wide range of primary and secondary (hetero)arylamines. Mechanistic studies by DFT calculations indicate that the reaction proceeds through an electrophilic amination process from a tetravalent borate complex with a B-N dative bond.

Preparation of Carbazoles Involving 6π-Electrocyclization, Photoredox-, Electrochemical-, and Thermal Cyclization Reactions: Mechanistic Insights.

Carbazole is a heterocyclic motif that can be found in a diverse array of natural and unnatural products displaying a wide range of biological and physiological properties. Furthermore, this heterocycle is part of electronic materials like photoconducting polymers and organic optoelectronic materials owing to its excellent photophysical characteristics. Consequently, the development of synthetic strategies for carbazole scaffolds holds potential significance in biological and material fields. In this regard, a variety of preparation methods has been developed to exploit their efficient and distinct formation of new C-C and C-heteroatom bonds under mild conditions and enabling broad substrate diversity and functional group tolerance. Therefore, this review focuses on the synthesis of a set of carbazole derivatives describing a variety of methodologies that involve direct irradiation, photosensitization, photoredox, electrochemical and thermal cyclization reactions.

Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles.

The global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.

Catalyst-free synthesis of acenaphthoindolopyrimidine derivatives.

A one pot three component reaction of acenaphthoquinone, barbituric acid/thiobarbituric acid/N,N-dimethyl barbituric acid and arylamines in ethanol for the synthesis of acenaphthoindolopyrimidine derivatives is reported. The reactions take place without a catalyst and gentle conditions. This method is facile and has some benefits such as, readily available starting materials, green solvent, catalyst-free, no column chromatographic purification and good to high yields.

Disperse azo dyes, arylamines and halogenated dinitrobenzene compounds in synthetic garments on the Swedish market.

BACKGROUND: Azobenzene disperse dyes (azo DDs) are well-known as textile allergens, but the knowledge of their occurrence in garments is low. The numerous azo DDs and dye components found in textiles constitute a potential health risk, but only seven azo DDs are included in the European baseline patch test series (EBS). OBJECTIVES: To investigate non-regulated azo DDs and dye components in synthetic garments on the Swedish market. METHODS: High-performance liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and computerized data mining. RESULTS: Sixty-two azo DDs were detected, with Disperse Red 167:1 occurring in 67%, and 14 other DDs each found in >20% of the garments. Notably, the EBS dyes were less common, three even not detected, while arylamines were frequently detected and exceeded 1 mg/g in several garments. Also, halogenated dinitrobenzenes were identified in 25% of the textiles. CONCLUSION: Azo DDs and dye components, in complex compositions and with large variations, occurred frequently in the synthetic garments. The arylamines were shown to occur at much higher levels compared to the azo DDs, suggesting the former constitute a potentially higher health risk. The role of arylamines and halogenated dinitrobenzenes in textile allergy has to be further investigated.

A One-Pot Approach for Bio-Based Arylamines via a Combined Photooxidative Dearomatization-Rearomatization Strategy.

The synthesis of arylamines from renewable resources under mild reaction conditions is highly desired for the sustainability of the chemical industry, where the production of hazardous waste is a prime concern. However, to date, there are very few tools in chemists' toolboxes that are able to produce arylamines in a sustainable manner. Herein, a robust one-pot approach for constructing bio-based arylamines via a combined photooxidative dearomatization-rearomatization strategy is presented. The developed methodology enables the synthesis of structurally complex amines in moderate-to-good isolated yields using biomass-derived phenols, natural α-amino acids, and naphthols under remarkably mild reaction conditions. For the photooxygenation of phenols, a novel chrysazine-based catalyst system was introduced, demonstrating its efficiency for the synthesis of natural products - hallerone, rengyolone, and the pharmaceutically relevant prodrug DHED.

Novel aminoarylcysteine adducts in globin of rats dosed with naphthylamine and nitronaphthalene isomers.

Novel aminonaphthylcysteine (ANC) adducts, formed via naphthylnitrenium ions and/or their metabolic precursors in the biotransformation of naphthylamines (NA) and nitronaphthalenes (NN), were identified and quantified in globin of rats dosed intraperitoneally with 0.16 mmol/kg b.w. of 1-NA, 1-NN, 2-NA and 2-NN. Using HPLC-ESI-MS2 analysis of the globin hydrolysates, S-(1-amino-2-naphthyl)cysteine (1A2NC) together with S-(4-amino-1-naphthyl)cysteine (4A1NC) were found in rats given 1-NA or 1-NN, and S-(2-amino-1-naphthyl)cysteine (2A1NC) in those given 2-NA or 2-NN. The highest level of ANC was produced by the most mutagenic and carcinogenic isomer 2-NA (35.8 ± 5.4 nmol/g globin). The ratio of ANC adduct levels for 1-NA, 1-NN, 2-NA and 2-NN was 1:2:100:3, respectively. Notably, the ratio of 1A2NC:4A1NC in globin of rats dosed with 1-NA and 1-NN differed significantly (2:98 versus 16:84 respectively), indicating differences in mechanism of the adduct formation. Moreover, aminonaphthylmercapturic acids, formed via conjugation of naphthylnitrenium ions and/or their metabolic precursors with glutathione, were identified in the rat urine. Their amounts excreted after dosing rats with 1-NA, 1-NN, 2-NA and 2-NN were in the ratio 1:100:40:2, respectively. For all four compounds tested, haemoglobin binding index for ANC was several-fold higher than that for the sulphinamide adducts, generated via nitrosoarene metabolites. Due to involvement of electrophilic intermediates in their formation, ANC adducts in globin may become toxicologically more relevant biomarkers of cumulative exposure to carcinogenic or non-carcinogenic arylamines and nitroarenes than the currently used sulphinamide adducts.

Direct Amination of Aromatic C-H Bonds with Free Amines.

Aromatic amines belong to a highly important class of organic compounds which are found in various natural products, functional materials, and pharmaceutical agents. Their prevalence has sparked continuing interest in the development of highly efficient and environmentally benign synthetic strategies for the construction of these compounds. Cross-dehydrogenative coupling reactions between two unmodified C(X)-H bonds have recently emerged as a versatile and powerful strategy for the fabrication of new C(X)-C(X) bonds. In this context, several procedures have been reported for the synthesis of aromatic amines through the direct amination of aromatic C-H bonds with free amines. This review highlights recent advances and progress in this appealing research arena, with special emphasis on the mechanistic features of the reactions.

Fluorescent recognition and selective detection of nitrite ions with carbon quantum dots.

The nitrite ion (NO2-) is a vital inorganic species that occurs both in natural ecological systems and human bodies. The high concentration of NO2- can be harmful for animal and human health. It is important to develop a simple, sensitive, reliable, and economic methodology to precisely monitor NO2- in various environmental and biological fields. Thus, a novel nitrite biosensor based on carbon quantum dots (PA-CDs) has been constructed and prepared via a high-efficiency, one-pot hydrothermal route using primary arylamines (PA) such as m-phenylenediamine. The device exhibits bright green fluorescence and a high quantum yield of 20.1% in water. In addition, the PA-CDs also possess two broad linear ranges: 0.05-1.0 µM and 1.0-50 µM with a low detection limit of 7.1 nM. The classical diazo reaction is firstly integrated into the PA-CD system by primary arylamines, which endows the system with high sensitivity and specific selectivity towards nitrite. Importantly, the nanosensor can detect NO2- in environmental water and serum samples with high fluorescence recoveries, demonstrating its feasibility in practical applications. This work broadens a new method to fabricate novel nanosensors and provides a prospective application for fluorescent carbon quantum dots (CDs). Graphical abstract.

2-[(3-Aminoalkyl-(alkaryl-,aryl-))-1H-1,2,4-triazol-5-yl]anilines: synthesis and anticonvulsant activity.

The presented work is devoted to the development of synthesis methods for novel 2-[(3-aminoalkyl-(alkaryl-, aryl-))-1H-1,2,4-triazolo]anilines. Abovementioned compounds were obtained via hydrazinolysis (Ing-Manske procedure) and acid hydrolysis of corresponding N -acylated{([1,2,4]triazolo[1,5-c]quinazolin-2-yl)alkyl-(alkaryl-, aryl-)}amines. The regioselectivity of hydrazinolysis and hydrolysis were established. The features of spectral characteristics werestudied and discussed. Characteristic patterns of protons signals splitting in 1H NMR of the synthesized compounds were established. The effect of the synthesized compounds on the pentylenetetrazol seizures was studied. It was found that according to some indicators, anticonvulsant activity of 2-[(3-aminoalkyl-(alkaryl-, aryl-))-1H-1,2,4-triazolo]anilines superior or comparable with effect of the reference drug "Lamotrigine". It is a valid argument for their further structural modification, in-depth study of activity mechanisms and further study of anticonvulsant activity on other experimental seizures models.

Synthesis and Characterization of Copper (II) and Nickel (II) Immobilized on Silica- Coated Copper Ferrite: As Novel Magnetically Reusable Nano Catalysts Towards Reduction of Nitroarenes with NaBH4.

AIM AND OBJECTIVE: Nowadays, the design, synthesis and application of magnetically nanocomposite systems have attracted the attention of numerous scientists. The huge surface area and magnetic characteristic of nanoparticles as well as the inherent potentiality of the used metal species, makes them susceptible to have different reactivity in chemical reactions. In this context, we therefore encouraged to prepare a new design of magnetic nanocatalysts as CuFe2O4@SiO2@AAPTMS@Ni(II) and CuFe2O4@SiO2@AAPTMS@Cu(II) followed by monitoring of their catalytic activities towards reduction of nitroarenes with NaBH4. MATERIALS AND METHODS: Magnetically nanoparticles of CuFe2 O4@SiO2@AAPTMS@Ni(II) and CuFe2O4@SiO2@AAPTMS@Cu(II) were prepared through a four-step procedure: i) preparation of CuFe2O4 MNPs, ii) coating of CuFe2O4 nucleus by silica-layer using tetraethyl orthosilicate (TEOS), iii) layering of CuFe2O4@SiO2 MNPs with [3-(2-aminoethylamino)propyl] trimethoxysilane (AAPTMS), and iv) the complexation of CuFe2O4@SiO2@AAPTMS MNPs with an aqueous solution of Ni(OAc)2·4H2O or Cu(OAc)2·H2O. RESULTS: The catalytic activity of CuFe2O4@SiO2@AAPTMS@Ni(II) and the Cu(II)-analogue towards reduction of nitroarenes with NaBH4 was studied. The examinations resulted that using a molar ratio of 1:2 for ArNO2 and NaBH4 in the presence of 20 mg of nanocomposites in H2O under reflux conditions reduces various aromatic nitro compounds to arylamines in high yields. CONCLUSION: The immobilization of Ni(II) and Cu(II) species on silica-layered CuFe2O4 was investigated. Magnetically nanoparticles of CuFe2O4@SiO2@AAPTMS@Ni(II) and the Cu(II)-analogue showed the perfect catalytic activity towards reduction of nitroarenes with NaBH4 in H2O. All reactions were carried out within 2- 15 min to afford aniline products in high yields.

Regiospecific N-Arylation of Aliphatic Amines under Mild and Metal-Free Reaction Conditions.

A transition metal-free N-arylation of primary and secondary amines with diaryliodonium salts is presented. Both acyclic and cyclic amines are well tolerated, providing a large set of N-alkyl anilines. The methodology is unprecedented among metal-free methods in terms of amine scope, the ability to transfer both electron-withdrawing and electron-donating aryl groups, and efficient use of resources, as excess substrate or reagents are not required.

A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination.

Despite significant recent progress in copper-catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N-arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N-arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1-disubstituted olefins, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under the reported method.

The N-butyl-N-4-hydroxybutyl Nitrosamine Mouse Urinary Bladder Cancer Model.

Urinary bladder cancer (UBC) is a common and complex malignancy, with a multifactorial etiology, like environmental factors, such as cigarette smoking, occupational exposure, and genetic factors.UBC exhibits considerable genotypic and phenotypic heterogeneity. Among all UBC lesions, urothelial carcinoma is the most frequently observed histological type. Despite all the developments made in urologic oncology field, therapeutic options remain inadequate. There is urgency for the identification and development of new antineoplastic drugs to replace or improve current protocols and in vivo models have been proven to be essential for this step. There are different animal models of UBC: Spontaneous and experimentally induced models (genetically engineered, transplantable-xenograft and syngeneic animals- and chemically induced models). N-butyl-N(4-hydroxybutil)nitrosamine (BBN) is the most suitable reagent to generate chemically induced in vivo models of UBC and to study bladder carcinogenesis. BBN has proven, over the years, to be very realistic and reliable. It is bladder specific, and induces high tumor incidence.

Synthesis and characterization of NiFe2O4@Cu nanoparticles as a magnetically recoverable catalyst for reduction of nitroarenes to arylamines with NaBH4.

In this research, a simple and efficient method for synthesis of magnetically separable NiFe2O4@Cu nanocomposite under co-precipitation conditions was described. X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic absorption spectroscopy (AAS), Brunauer-Emmett-Teller (BET) and vibrating sample magnetometer (VSM) analyses confirmed the construction of NiFe2O4@Cu nanoparticles. The prepared core-shell nanocomposite showed a satisfactory catalytic activity for NaBH4 reduction of nitroarenes to arylamines. All reactions were carried out in a mixture of H2O-EtOH (1.5:0.5mL) within 1-12min under reflux conditions. The Cu nanocatalyst can be easily separated by a magnet and reused seven consecutive runs with no obvious loss of activity.

9,10-Diaminoanthracenes Revisited: The Influence of N-Substituents on Their Electronic States.

The electronic and molecular structures of 9,10-diamino-substituted anthracenes with different N-substituents have been re-examined. In particular, different N-substituents influence both the electronic and molecular structures of the oxidized species of 9,10-diaminoanthracenes. The anthrylene moiety of 9,10-bis(N,N-di(p-anisyl)amino)anthracene retains its planarity during the course of two successive one-electron oxidations, whereas 9,10-bis(N,N-dimethylamino)anthracene and 9,10-bis(N-p-anisyl-N-methylamino)anthracene undergo a substantial structural change to a butterfly-like structure through a two-electron oxidation process. The structural changes observed for the oxidized states are ascribed to significant differences in the frontier molecular orbitals of the above-mentioned three kinds of 9,10-diaminoanthracenes due to different extents of mixing between the amine-localized and anthrylene-localized orbitals.

Isotypic crystal structures of 2,6-di-bromo-N,N-bis-(4-nitro-phen-yl)aniline and 2,6-di-chloro-N,N-bis-(4-nitro-phen-yl)aniline.

In the mol-ecules of the two isotypic title compounds, C18H11Br2N3O4 (I) and C18H11Cl2N3O4 (II), the tri-phenyl-amine N atoms show no sign of pyramidalization, with marginal displacements of the N atoms from the mean plane of the three connecting C atoms: 0.0058 (13) Šfor the Br compound (I) and 0.0074 (9) Šfor the Cl compound (II). In the crystals, mol-ecules are linked through C-H⋯O hydrogen bonds between phenyl rings and nitro groups and by X⋯O (X = Br, Cl) inter-actions, that are shorter than the sum of the van der Waals radii, leading to a three-dimensional network.

C-H oxygenation and N-trifluoroacylation of arylamines under metal-free conditions: a convenient approach to 2-aminophenols and N-trifluoroacyl-ortho-aminophenols.

Direct ortho-hydroxylation through C-H oxygenation and N-trifluoroacylation of anilines was achieved in a single step under metal-free conditions by using a combination of TFA and oxone. The method allowed the formation of functionalised amino phenolic compounds such as ortho-hydroxy-N-trifluoroacetanilides in good yields with broad substrate scope.

Variations in CYP isoforms and bladder cancer: a superfamily paradigm.

OBJECTIVES: The objective of this study is to examine our current understanding of molecular mechanisms involved in regulation of CYP genes to induce bladder cancer by endogenous and exogenous chemicals and to analyze the respective polymorphisms in various isoforms of xenobiotic-metabolizing gene involved in bladder cancer. METHODS: Studies revealed the molecular mechanisms of CYP genes and respective polymorphisms to demonstrate the association between xenobiotic-metabolizing gene polymorphisms and bladder cancer published from 1996 through 2012 were retrieved from MEDLINE, EMBASE and PUBMED databases. RESULTS: 22 studies met our criteria of CYP polymorphism and bladder cancer. We found that a large proportion of the published studies were small and population-based. CONCLUSION: We conclude that large, well-designed studies of common polymorphisms in CYP genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures.