T+:Very toxic;932-98-9Relevant articles and documents
Continuous Flow Synthesis of Azoxybenzenes by Reductive Dimerization of Nitrosobenzenes with Gel-Bound Catalysts
Schmiegel, Carsten J.,Berg, Patrik,Obst, Franziska,Schoch, Roland,Appelhans, Dietmar,Kuckling, Dirk
, p. 1628 - 1636 (2021/03/15)
In the search for a new synthetic pathway for azoxybenzenes with different substitution patterns, an approach using a microfluidic reactor with gel-bound proline organocatalysts under continuous flow is presented. Herein the formation of differently substituted azoxybezenes by reductive dimerization of nitrosobenzenes within minutes at mild conditions in good to almost quantitative yields is described. The conversion within the microfluidic reactor is analyzed and used for optimizing and validating different parameters. The effects of the different functionalities on conversion, yield, and reaction times are analyzed in detail by NMR. The applicability of this reductive dimerization is demonstrated for a wide range of differently substituted nitrosobenzenes. The effects of these different functionalities on the structure of the obtained azoxyarenes are analyzed in detail by NMR and single-crystal X-ray diffraction. Based on these results, the turnover number and the turnover frequency were determined.
Understanding Mechanistic Differences between 3-Diazoindolin-2-Imines and N-Sulfonyl-1,2,3-Triazoles in the Rh2(II)-Catalyzed Reactions with Nitrosoarenes
Bao, Xiaoguang,Fu, Rui,Gao, Ke,Kou, Luyao,Zhou, Shaofang
supporting information, p. 1565 - 1572 (2021/05/28)
The employment of α-iminometallocarbenes to construct valuable N-containing compounds has attracted significant research interest. Herein, the nucleophilic addition of nitrosoarenes with the α-imino rhodium carbene species (I), which is derived from Rh2(II)-catalyzed denitrogenation of 3-diazoindolin-2-imines, to produce synthetically useful 2-iminoindolin-nitrones is described. Mechanistically, the N-attack of nitrosoarenes with the carbene site of I is proposed. For the analogous Rh2(II)-catalyzed reaction of nitrosoarenes with N-sulfonyl-1,2,3-triazoles reported by Li and co-workers (Org. Lett. 2014, 16, 6394), however, the O-attack of nitrosoarenes with the carbene site of α-imino rhodium carbene species (II) is more favorable to occur than the N-attack. The subsequent transformation to yield the product of N-acylamidines is rationalized based on computational studies. The mechanistic differences for the reactions of nitrosoarenes with α-imino rhodium carbene species I and II are discussed.
Pt nanoparticles on Ti3C2T: X -based MXenes as efficient catalysts for the selective hydrogenation of nitroaromatic compounds to amines
Chen, Qian,Fan, Guangyin,Jiang, Weidong
supporting information, p. 14914 - 14920 (2020/11/11)
The development of Pt nanocatalysts for the selective hydrogenation of nitroaromatic compounds to the corresponding amines is of great significance to solve the drawbacks associated with a low reserve of Pt. Herein, we develop a protocol for the preparation of a Pt/titanium carbide-based MXene heterostructure for the selective reduction of nitroaromatic compounds. In the heterostructure, well-defined and nano-sized metallic Pt crystallites are uniformly decorated on Ti3C2Tx nanosheets using a mild reducing agent of ammonia borane without additional stabilizing agents. The selective hydrogenation of p-chloronitrobenzene (p-CNB) to p-chloroaniline (p-CAN) was employed as a model reaction to investigate the catalytic performance of the as-synthesized heterostructure, denoted as Pt/Ti3C2Tx-D-AB. Notably, this catalyst can catalyze the complete conversion of p-CNB to p-CAN with 99.5% selectivity, superior to that of Pt/Ti3C2Tx-D-SB synthesized with sodium borohydride. The high performance of the present catalytic system can be ascribed to the well-dispersed Pt nanoparticles, the abundant surface electron-efficient Pt(0), and the synergistic catalysis between Pt/Ti3C2Tx-D-AB and water. This catalyst also shows generality toward the selective hydrogenation of a series of nitroaromatic compounds to the corresponding amines with high efficiency. The present study provides a strategy to synthesize efficient catalysts for catalytic applications.
Tungstate-supported silica-coated magnetite nanoparticles: a novel magnetically recoverable nanocatalyst for green synthesis of nitroso arenes
Jadidi Nejad, Masoume,Yazdani, Elahe,Kazemi Miraki, Maryam,Heydari, Akbar
, p. 1575 - 1583 (2019/09/09)
Tungstate ion was heterogenized on the silica-coated magnetite nanoparticles and applied for the selective oxidation of anilines to nitroso arenes—with hydrogen peroxide/urea as oxidant in dimethyl carbonate as solvent—in moderate–good yields (40–96%). The catalyst was characterized using different techniques including Fourier-transform infrared spectroscopy, X-ray powder diffraction, vibrating sample magnetometry, scanning electron microscopy, energy dispersive X-ray and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The catalyst was easily recovered using an external magnet and reused for six times.
A Photoswitchable Agonist for the Histamine H3 Receptor, a Prototypic Family A G-Protein-Coupled Receptor
Hauwert, Niels J.,Mocking, Tamara A. M.,Da Costa Pereira, Daniel,Lion, Ken,Huppelschoten, Yara,Vischer, Henry F.,De Esch, Iwan J. P.,Wijtmans, Maikel,Leurs, Rob
supporting information, p. 4531 - 4535 (2019/03/07)
Spatiotemporal control over biochemical signaling processes involving G protein-coupled receptors (GPCRs) is highly desired for dissecting their complex intracellular signaling. We developed sixteen photoswitchable ligands for the human histamine H3 receptor (hH3R). Upon illumination, key compound 65 decreases its affinity for the hH3R by 8.5-fold and its potency in hH3R-mediated Gi protein activation by over 20-fold, with the trans and cis isomer both acting as full agonist. In real-time two-electrode voltage clamp experiments in Xenopus oocytes, 65 shows rapid light-induced modulation of hH3R activity. Ligand 65 shows good binding selectivity amongst the histamine receptor subfamily and has good photolytic stability. In all, 65 (VUF15000) is the first photoswitchable GPCR agonist confirmed to be modulated through its affinity and potency upon photoswitching while maintaining its intrinsic activity, rendering it a new chemical biology tool for spatiotemporal control of GPCR activation.
Novel Phenyldiazenyl Fibrate Analogues as PPAR α/γ/δ Pan-Agonists for the Amelioration of Metabolic Syndrome
Giampietro, Letizia,Laghezza, Antonio,Cerchia, Carmen,Florio, Rosalba,Recinella, Lucia,Capone, Fabio,Ammazzalorso, Alessandra,Bruno, Isabella,De Filippis, Barbara,Fantacuzzi, Marialuigia,Ferrante, Claudio,MacCallini, Cristina,Tortorella, Paolo,Verginelli, Fabio,Brunetti, Luigi,Cama, Alessandro,Amoroso, Rosa,Loiodice, Fulvio,Lavecchia, Antonio
supporting information, p. 545 - 551 (2019/03/19)
The development of PPARα/γ dual or PPARα/γ/δ pan-agonists could represent an efficacious approach for a simultaneous pharmacological intervention on carbohydrate and lipid metabolism. Two series of new phenyldiazenyl fibrate derivatives of GL479, a previously reported PPARα/γ dual agonist, were synthesized and tested. Compound 12a was identified as a PPAR pan-agonist with moderate and balanced activity on the three PPAR isoforms (α, γ, δ). Moreover, docking experiments showed that 12a adopts a different binding mode in PPARγ compared to PPARα or PPARδ, providing a structural basis for further structure-guided design of PPAR pan-agonists. The beneficial effects of 12a were evaluated both in vitro, on the expression of PPAR target key metabolic genes, and ex vivo in two rat tissue inflammatory models. The obtained results allow considering this compound as an interesting lead for the development of a new class of PPAR pan-agonists endowed with an activation profile exploitable for therapy of metabolic syndrome.
Easily Accessible, Highly Potent, Photocontrolled Modulators of Bacterial Communication
Hansen, Mickel J.,Hille, Jacques I.C.,Szymanski, Wiktor,Driessen, Arnold J.M.,Feringa, Ben L.
supporting information, p. 1293 - 1301 (2019/05/06)
External control of bacterial communication—quorum sensing—allows for the regulation of a multitude of biological processes. Herein, we describe the development of a new synthetic methodology, as well as the characterization, photoisomerization, and biological evaluation of a privileged series of novel photoswitchable quorum-sensing agonists and antagonists. The presented method allows for the rapid and convenient synthesis of previously unknown photoswitchable agonists with up to 70% quorum-sensing induction and inhibitors reaching up to 40% inhibition, which significantly extends the level of photocontrol over bacterial communication achieved before. Remarkably, for the lead photoswitchable agonist, a >700-fold difference in activity was observed between the irradiated and non-irradiated forms, which allows for antagonism-to-agonism switching upon exposure to light, showing levels of control unprecedented in photopharmacology. Finally, utilizing this system, we were able to regulate toxin production in Pseudomonas aeruginosa with light. Photopharmacology is an emerging approach aimed at the regulation of biological function with light. Herein, the application of molecular photoswitches allows for the reversible switching between two distinct structural states of bioactive compounds. Bacterial communication (quorum sensing) is an interesting target for photopharmacology, from the perspective of both clinical and basic research, because of its implications for pathogenicity of bacteria and complex biological mechanism of action. By the novel synthesis and application of photoswitchable modulators, we were able to reversibly control bacterial communication with light. Remarkably, one of our lead compounds allows the control of bacterial communication with very high selectivity, switching from a quorum-sensing inhibitor to a quorum-sensing activator upon irradiation with light, which was further exemplified by the control of quorum-sensing-regulated toxin production in Pseudomonas aeruginosa. By applying the photopharmacological approach, bacterial communication can be controlled with light through the application of photoswitchable modulators. Interestingly, one of the lead photoswitchable modulators of bacterial communication, presented herein, shows a remarkable (>700-fold) difference in activity between the non-irradiated and irradiated states. The photoresponsive quorum-sensing modulators can be used to control toxin production in Pseudomonas aeruginosa and have a promising outlook as next-generation research tools.
Enantioselective Oxidative Coupling of β-Ketocarbonyls and Anilines by Joint Chiral Primary Amine and Selenium Catalysis
Chen, Wanting,Wang, Yanni,Mi, Xueling,Luo, Sanzhong
supporting information, p. 8178 - 8182 (2019/10/16)
An enantioselective primary amine-catalyzed total N-selective nitroso aldol reaction (N-NA) was achieved through the oxidation of primary aromatic amines to the corresponding nitrosoarenes catalyzed by selenium reagents and 30% H2O2. This protocol provides a facile and highly efficient access to α-hydroxyamino carbonyls bearing chiral quaternary centers under exceedingly mild and green reaction conditions with high chemo-and enantiocontrol.
A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light
Gómez-Santacana, Xavier,De Munnik, Sabrina M.,Mocking, Tamara A.M.,Hauwert, Niels J.,Sun, Shanliang,Vijayachandran, Prashanna,De Esch, Iwan J.P.,Vischer, Henry F.,Wijtmans, Maikel,Leurs, Rob
supporting information, p. 2509 - 2523 (2019/12/11)
We report a detailed structure–activity relationship for the scaffold of VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were used to guide the design iterations. Investigations of positional and substituent effects reveal that halogen substituents on the ortho-position of the outer ring are preferred for conferring partial agonism on the cis form of the ligands. This effect could be expanded by an electron-donating group on the para-position of the central ring. A variety of efficacy differences between the trans and cis forms emerges from these compounds. Tool compounds VUF15888 (4d) and VUF16620 (6e) represent more subtle efficacy switches, while VUF16216 (6f) displays the largest efficacy switch, from antagonism to full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling.
Metal-Free Sequential C(sp2)-H/OH and C(sp3)-H Aminations of Nitrosoarenes and N-Heterocycles to Ring-Fused Imidazoles
Purkait, Anisha,Roy, Subhra Kanti,Srivastava, Hemant Kumar,Jana, Chandan K.
supporting information, p. 2540 - 2543 (2017/05/24)
Hydrogen bond assisted ortho-selective C(sp2)-H amination of nitrosoarenes and subsequent α-C(sp3)-H functionalization of aliphatic amines is achieved under metal-free conditions. The annulation of nitrosoarenes and 2-hydroxy-C-nitroso compounds with N-heterocycles provides a facile excess to a wide range of biologically relevant ring-fused benzimidazoles and structurally novel polycyclic imidazoles, respectively. Nucleophilic aromatic hydrogen substitution (SNArH) was found to be preferred over classical SNAr reaction during the C(sp2)-H amination of halogenated nitrosoarenes.
