Ortho Position Research Articles

Steric Bulk‐Dependent Photoresponse of Sulfonamide Azobenzene Ligand in Arene Ruthenium(II) Complexes

AbstractA series of sulfonamide azobenzenes bearing alkyl substituents of increasing steric bulk at the position ortho to the N=N bond and their corresponding chloro(hexamethylbenzene)ruthenium(II) complexes were synthesized. The latter bearing mono‐substituted ligands exhibited an exocyclic azo bond under the E configuration, and underwent reversible E→Z photoisomerization upon irradiation with visible light, followed by thermal Z→E back isomerization upon resting in the dark at 20 °C. In contrast, the corresponding 2,6‐dimethyl substituted azobenzene complex, while also exhibiting an exocyclic azo bond, was isolated as the Z‐isomer and underwent uncommon solvent dependent irreversible photodissociation of azobenzene ligand upon visible light irradiation. Valuable insights into the photophysical and structural properties of these complexes were gained by combination of computational and X‐ray diffraction studies.

Synthesis of Polysubstituted Naphthalenes by a Hydride Shift Mediated C-H Bond Functionalization/Aromatization Sequence.

A synthetic strategy for forming multisubstituted naphthalenes based on hydride shift mediated C(sp3)-H bond functionalization was developed. This strategy consists of three successive transformations: (1) an intramolecular hydride shift mediated C(sp3)-H bond functionalization; (2) a decarboxylative fragmentation; and (3) an oxidation reaction. When benzylidene malonates having a 2-alkoxyethyl group at the ortho position were treated with a catalytic amount of Al(OTf)3, the hydride shift/cyclization reaction proceeded smoothly to afford tetralin derivatives in good chemical yields. The resulting tetralins were easily converted into naphthalenes by exposing them to modified Krapcho decarboxylation reaction conditions (LiCl, DMSO, and heating under an O2 atmosphere). The one-pot operation of these two reactions was also realized.

Studies in synthesis of 6-aminocoumarin Schiff base derivatives as mesogens and their DFT approach

In first series, 6-amino coumarin Schiff base derivatives 10a-g were synthesized with alkoxy chain n = 6–18 and studied for their mesomorphic properties. In this series, compounds 10b with n = 8 showed monotropic nematic mesophase, while enantiotropic smectic A mesophase for higher analogues compounds 10c-g (with n = 10–18) was observed. In another series of Schiff base derivatives 12a-h additional ester linkage was introduced at the aldehyde end and were studied for their mesomorphic behavior. In second series, compounds 12a-c (with n = 4–8) showed enantiotropic nematic mesophase with very good thermal stability. Higher analogues of the second series with n = 12–18 showed stable enantiotropic smectic A mesophase. Compounds of both series were studied by DFT calculations. Different electronic parameters such as dipole moment, polarizability, molecular electrostatic potentials, frontier molecular orbitals, and thermodynamic variables were calculated and compared with the observed mesomorphic trends in both the studied series. Further, electronic parameters of compounds 10b and 12c and that of reference compound 4 were calculated and discussed to understand the effect of the removal of a hydroxyl group on the ortho position of the aldehyde part.

Sustainable and Environmentally Friendly Approach for the Synthesis of Azoxybenzenes from the Reductive Dimerization of Nitrosobenzenes and the Oxidation of Anilines.

This study demonstrates a comparative synthesis of azoxybenzenes through the reductive dimerization of nitrosobenzenes and the oxidation of anilines. Utilizing the cost-effective DIPEA catalyst at room temperature with water as a green solvent, the one-pot procedure involves in situ generation of nitrosobenzene derivatives from anilines in the presence of oxone, followed by DIPEA addition. Both methods yield azoxybenzenes with high selectivity, showcasing the versatility of DIPEA in facilitating the synthesis of azoxybenzenes with various substituents in ortho, meta, and para positions, encompassing electron-donating and electron-withdrawing groups. The use of DIPEA proves pivotal in achieving moderate to high yields, emphasizing its significance in this environmentally friendly synthesis.

Electrochemical Dearomatizing Methoxylation of Phenols and Naphthols: Synthetic and Computational Studies.

The electrochemical oxidative dearomatizing methoxylation of phenols and naphthols was developed. It provides an alternative route for the preparation of methoxycyclohexadienones, important and versatile synthetic intermediates, that eliminates the need for stoichiometric high-energy chemical oxidants and generates hydrogen as a sole by-product. The reaction proceeds in a simple constant current mode, in an undivided cell, and it employs standardized instrumentation. A collection of methoxycyclohexadienones derived from various 2,4,6-tri-substituted phenols and 1-substituted-2-naphthols was obtained in moderate to excellent yields. These include a complex derivative of estrone, as well as methoxylated dearomatized 1,1'-bi-2-naphthols (BINOLs). The mechanism of the reaction was subject to profound investigations using density functional theory calculations. In particular, the reactivity of two key intermediates, phenoxyl radical and phenoxenium ion, was carefully examined. The obtained results shed light on the pathway leading to the desired product and rationalize experimentally observed selectivities regarding a side benzylic methoxylation and the preference for the functionalization at the para over the ortho position. They also uncover the structure-selectivity relationship, inversely correlating the steric bulk of the substrate with its propensity to undergo the side-reaction. Moreover, the loss of stereochemical information from enantiopure BINOL substrates during the reaction is rationalized by the computations.

An Alternative Method for the Selective Synthesis of Ortho-nitro Anilines Using Bismuth Nitrate Pentahydrate.

Nitroaromatic compounds are important scaffolds used for the syn-thesis of a variety of compounds, such as explosives, herbicides, dyes, perfumes and phar-maceuticals. Bismuth nitrate pentahydrate is a widely used reagent in organic synthesis; how-ever, its utility as a nitrating agent for anilines is underexplored. The aim of this work is to propose and find the proper reaction conditions of an alternative nitrating agent constituted by a mixture of bismuth nitrate / acetic anhydride in DCM with a series of substituted anilines under mild reflux. Several anilines having both activating and deactivating substituents in the ortho, meta and para positions were the substrate for the nitration reaction. Experimental conditions were performed in "one-pot" conditions before product purification. Bi(NO3)3•5H2O demonstrated to be effective and somehow regioselective when it came to the nitration of anilines in the ortho position. Although other products were also identified under these conditions, in most cases, the ortho derivative was the major or even the only product obtained with moderate to high yields in the range of 50% - 96%. Bi(NO3)3•5H2O is an efficient and safe nitrating agent since the use of concen-trated and corrosive acids like sulfuric and nitric is avoided; furthermore, bismuth nitrate is low-priced and no special care nor equipment is required.

Sublimation enthalpies of organic compounds by isothermal thermogravimetry

AbstractAn improved method has been developed to determine the sublimation enthalpies of solid organic compounds using thermogravimetric analysis and applying an isothermal methodology with a TA Instruments® SDTQ600 equipment. This was achieved by measuring the rate of mass loss as a function of the temperature from isothermal experiments in an interval of temperature of 10 to 20 K below the melting temperature of the sample. The resulting rates of mass loss were used by applying the Pieterse and Focke equation, then combined with the integrated Clausius–Clapeyron equation to calculate the heat of sublimation at the experimental temperature and it was corrected to T = 298.15 K. In order to demonstrate the reliability of this methodology, the results for benzoic acid, pyrene and phenanthrene are presented, which are respectively primary, secondary, and tertiary reference compounds in the measurement of enthalpies of sublimation, along with the sublimation enthalpies of picolinic acid, nicotinic acid and isonicotinic acid which are three pyridinecarboxylic acids isomers with the carboxyl group in the ortho, meta and para position, respectively, to the nitrogen of the pyridine.

A Fluorescent Probe with Zwitterionic ESIPT Feature for Ratiometric Monitoring of Peroxynitrite In Vitro and In Vivo.

Peroxynitrite (ONOO-), as a short-term reactive biological oxidant, could lead to a series of effects in various physiological and pathological processes due to its subtle concentration changes. In vivo monitoring of ONOO- and relevant physiological processes is urgently required. Herein, we describe a novel fluorescent probe termed HBT-Fl-BnB for the ratiometric detection of ONOO- in vitro and in vivo. The probe consists of an HBT core with Fl groups at the ortho and para positions responding to the zwitterionic excited-state intramolecular proton-transfer (zwitterionic ESIPT) process and a boronic acid pinacol ester with dual roles that block the zwitterionic ESIPT and recognize ONOO-. Thanks to the specificity as well as low cytotoxicity, success in imaging of endogenous and exogenous ONOO- in living cells by HBT-Fl-BnB was obtained. Additionally, the applicability of HBT-Fl-BnB to tracking the abnormal expression of ONOO- in vivo induced by inactivated Escherichia coli was also explored. This is the first report of a fluorescent probe for ONOO- sensing via a zwitterionic ESIPT mechanism.

Modular Synthesis of 1,2-Benzothiazines and 1,2-Benzothiazine 1-Imines via Palladium-Catalyzed C-H/C-C Activation Reactions.

In this study, a modular approach toward cyclic sulfoximines and sulfondiimines via palladium-catalyzed intramolecular C-H/C-C activation reactions was reported. Various 1,2-benzothiazines including bicyclic, tricyclic, highly fused ones, ones of the seven-membered ring, along with 1,2-benzothiazine 1-imines were accessed in good yields. KIE experiment demonstrated that the C-H bond cleavage at the position ortho to the sulfoximine group is not the rate-determining step in the coupling reaction.

The Pseudo Symmetric Crystal Structure of 1,4-Diazabicyclo[2·2·2]octane-1,4-diium bis(5-hydroxy-2,4-dinitrophenolate)

Reaction of 4,6-dinitroresorcinol (1) and the nitrogen base 1,4-diazabicyclo[2·2·2]octane (2) affords the 1:2 salt and proton-transfer compound 1,4-diazabicyclo[2·2·2]octane-1,4-diium bis(5-hydroxy-2,4-dinitrophenolate) (3). Compound 3 crystallizes in the triclinic crystal system (space group P-1) with a = 8.3242(5) Å, b = 11.9915(7) Å, c = 12.4595(7) Å, α = 116.282(2)°, β = 100.576(3)°, γ = 101.051(2)°, 1042.30(11) Å3 and Z = 2. The dication 2-H22+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{H}}_{2}^{2+}$$\\end{document} forms charge assisted donating bifurcated N+−H⋅⋅⋅O− hydrogen bonds to the phenolate moieties of two monoanions of 1. The latter exhibit an intramolecular O−H⋅⋅⋅O hydrogen bond between the hydroxy group and the nitro group in ortho position. The crystal structure of 3 features pseudo B-centering of the lattice, which relates the two crystallographically distinct monoanions of 1 by a pseudo translation. The possible B-centring is broken by the ethylene groups of 2-H22+, which are related in neighbouring molecules by centres of symmetry.Graphical The 1:2 proton-transfer compound 1,4-diazabicyclo[2.2.2]octane-1,4-diium bis(5-hydroxy-2,4-dinitrophenolate) features pseudo B-centering of the lattice.

Substitution and Orientation Effects on the Crystallinity and PFAS Adsorption of Olefin-Linked 2D COFs.

Solid phase adsorbents with high removal affinity for per- and polyfluoroalkyl substances (PFAS) in aqueous environments are sought. We report the synthesis and investigation of COF-I, a new covalent organic framework (COF) with a good affinity for PFAS adsorption. COF-I was synthesized by the condensation reaction between 2,4,6-trimethyl-1,3,5-triazine and 2,3-dimethoxyterephthaldehyde and fully characterized. In addition to the high crystallinity and surface area, COF-I showed high hydrolytic and thermal stability. Further, we converted its hydrophobic surface to a hydrophilic surface by converting the ortho-methoxy groups to hydroxyl derivatives and produced a new hydrophilic olefin-linked two-dimensional (2D) COF. We experimentally measured the crystallinity of both COFs by X-ray diffraction and used atomistic simulations coupled with cross-polarization/magic angle spinning solid-state nuclear magnetic resonance (CP/MAS ssNMR) to determine the relative amounts of AA-stacking and AB-stacking present. COF-I, with its hydrophobic surface and methoxy groups in the ortho positions, showed the best PFAS adsorption. COF-I reduced the concentration of perfluorooctanoic acid from 20 to 0.069 μg L-1 and to 0.052 μg L-1 for perfluorooctanesulfonic acid. These amounts are lower than the U.S. Environmental Protection Agency advisory level (0.070 μg L-1). High efficiency, fast kinetic adsorption, and reusability of COF-I are advantages of COF-I for PFAS removal from water.

Investigating the Effects of Fluorine Substituents on Organic Dyes in Dye-Sensitized Solar Cells

We synthesized and evaluated five organic dyes that featured both mono- and di-substituted fluorine atoms for application in dye-sensitized solar cells (DSSCs). The dye structure was designed with N, N-dimethylaniline as a donor, fluorophenyl as an π-conjugated bridge, and cyanoacetic acid as an anchoring and acceptor group. The fluorine substituents are strong electron-withdrawing groups, introducing different numbers and positions of fluorine atoms (ortho and meta) that were expected to the ability of the acceptor parts of the dye. The results showed that adding the fluorine mono-substitution in the ortho position can enhance the efficiency of the solar cells in comparison with the meta-substitution and unsubstituted one. However, the di-substitution by fluorine atoms in two ortho positions and ortho, meta positions reduced the performance of the solar cells. The reason was related to the effect of π-conjugation between the fluorine substituent and the carbonyl group of the carboxylic acid. The DSSCs based on dye 14 achieved the best results with power conversion efficiency (PCE) = 3.33%, (Jsc = 5.43 mA cm-2, Voc = 0.81V and FF = 75.85%) under standard conditions with I3-/I- as the electrolyte.

Synthesis and Butyllithium-Induced Cyclisation of 2-Benzyloxyphenylphosphonamidates Giving 2,3-Dihydrobenzo[d][1,3]oxaphospholes

A series of fourteen O-ethyl-N-butylphenylphosphonamidates with benzyl ether substituents at the ortho position was prepared and fully characterised. Upon treatment with n-butyllithium in THF at RT, they underwent cyclisation in eight cases to give the novel 2,3-dihydrobenzo[d][1,3]oxaphospholes in moderate to low yield as a single diastereomer, for which the relative configuration was determined by X-ray diffraction in one case.

BPy][OH] Immobilized Hydrotalcite Clay Catalytic System for 1,2-dihyd-roquinazolines Synthesis

Abstract: We easily synthesized two ionic liquids, [BMIM][OH] and [BPy][OH], with high yield. We found that hydrotalcite clay, mediated by these ionic liquids, is a highly effective catalyst for synthesizing biologically active 1,2-dihydroquinazoline derivatives. Using a simple reaction protocol and easy product isolation steps, we successfully synthesized 18 different 1,2-dihydroquinazoline derivatives and were able to recycle the catalysts up to 8 times. Overall, the use of hydrotalcite and [BPy][OH] catalysts provide a more efficient and environmentally friendly method for synthesizing quinazolines compared to traditional methods that often require harsh conditions and toxic reagents. Background: 1,2-Dihydroquinazolines are an important class of heterocyclic compounds with diverse biological activities, including anticancer, antifungal, and antibacterial properties. They also exhibit other pharmacological activities such as antihypertensive, anti-inflammatory, and antiviral effects. The synthesis of 1,2-dihydroquinazolines dates to the early 20th century when they were first synthesized by Pictet and Huber in 1911 by the condensation of anthranilic acid with aldehydes or ketones in the presence of strong acids. Since then, numerous methods have been developed for their synthesis, including the cyclization of o-aminobenzamides, the reaction of o-aminoaryl ketones with aldehydes or ketones, and the use of catalysts such as Lewis acids and transition metals. In recent years, the development of new synthetic methods for the efficient and selective synthesis of 1,2-dihydroquinazolines has been of great interest to synthetic chemists, particularly in the pharmaceutical industry. These methods include the use of microwave irradiation, ultrasound, and ionic liquids as green solvents. : Overall, the synthesis of 1,2-dihydroquinazolines has been an active area of research, and new methods continue to be developed to improve their synthesis and properties for various applications. Methods: We easily synthesized two ionic liquids, [BMIM][OH] and [BPy][OH], with high yields. We found that hydrotalcite clay, mediated by these ionic liquids, is a highly effective catalyst for synthesizing biologically active 1,2-dihydroquinazoline derivatives. Results: Overall, our results provide insights into the development of efficient and sustainable methods for the synthesis of 1, 2-dihydroquinazolines. Conclusion: In summary, our studies demonstrated that the [BPy][OH] ionic liquid and hydrotalcite clay catalytic system could be used for the synthesis of various 1, 2-dihydroquinazolines using different aromatic carbonyl compounds, amino benzophenone derivatives, and heterocyclic aldehydes. The presence of electron-donating substituents in the phenyl group provided higher yields than electron-withdrawing groups, and the para position of the aldehyde group had a more significant effect than the ortho or meta position. Our catalytic system was also found to be recyclable for up to eight runs without significant loss of catalytic activity. Overall, our results provide insights into the development of efficient and sustainable methods for the synthesis of 1, 2-dihydroquinazolines.

Molecular Docking and Molecular Dynamic Investigations of Xanthone-Chalcone Derivatives against Epidermal Growth Factor Receptor for Preliminary Discovery of Novel Anticancer Agent

Epidermal growth factor receptor (EGFR) is found to be overexpressed in cancer cells as it controls angiogenesis, cell signaling, and proliferation mechanisms. Therefore, EGFR has been known as a common target for the initial screening of new anticancer agents. Either xanthone or chalcone has been evaluated as the anticancer agents, and their activity strongly depends on the type and position of the attached functional group. Therefore, molecular hybridization between xanthone and chalcone could yield novel anticancer agents through the EGFR inhibition mechanism. Herein, a series of xanthone-chalcone derivatives with hydrogen-bond-acceptor or hydrogen-bond-donor substituents at ortho, meta, and para positions was evaluated as the EGFR inhibitor. Thirty-seven xanthone-chalcones were designed and docked in the active site of EGFR. Compared to the native ligand, pristine xanthone-chalcone gave a 1.215× stronger binding energy and a 13.97× lower binding constant. Compound 3SH was found to be the most promising candidate due to its strongest binding energy (−9.71 kcal/mol) and the lowest binding constant (0.08 µM). Furthermore, molecular dynamic studies demonstrated that complex EGFR-3SH was stable for 100 ns simulation. These in silico investigations show that the xanthone-chalcone derivative is a promising novel anticancer agent to be examined through in vitro and in vivo assays.

Investigation of the correlation between the substituent effect of ligands and the catalytic activity/magnetic properties in fine-tuned rare-earth complexes

Amine-bis(benzothiazole phenol) ligands, C1NNBiBTHP-H2 and CLNNBiBTHP-H2 ligands, were designed for yttrium complexes with analogous structures. A series of nitrophenolate (NP)-type of ligands possessing R substituents with variable electronic properties (R = NO2, Cl, H, CH3) on ortho and/or para position attached to the phenolate rings have been selected as secondary ligands for complexes syntheses. Ten novel yttrium complexes have been synthesized, [Y(C1NNBiBTHP)(NP)(MeOH)] (1–5) and [Y(CLNNBiBTHP)(NP)(MeOH)] (6–10) where the secondary ligand NP = 2,4-dinitrophenol(1 and 6), 2,5-dinitrophenol (2 and 7), 2-nitrophenol (3 and 8), 4-chloro-2-nitrophenol (4 and 9) and 4-methyl-2-nitrophenol (5 and 10), as well as the structures and catalytic properties for lactide (LA) polymerization were both studied. All the core structures and coordination geometries for complexes 1–10 were isostructural. All complexes were demonstrated to be active catalysts for LA polymerization, and the catalytic performance for these complexes was compared. The dysprosium analogues (11, 12 with C1NNBiBTHP-H2 and 13, 14 with CLNNBiBTHP-H2) also been synthesized and the magnetic properties of these compounds are fully studied. Comparing a series of nitrophenolate co-ligands in two different ligand systems, we presented the first example to study the correlation between electronic effect of the ligands and catalytic properties for mononuclear rare-earth complexes.

Interfacial electron transfer of perylenes: Influence of the anchor binding mode.

Interfacial electron transfer (IET) through saturated single-linker and dual-linker groups from a perylene chromophore into nanostructured TiO2 films was studied by ultrafast spectroscopy. Perylene chromophores with one and two propanoic acid linker groups in the peri and ortho positions were investigated. In comparison to previously studied perylenes bound via unsaturated acrylic acid linkers, the chromophores with saturated linkers showed bi-exponential IET dynamics. Two distinct transfer times were observed that indicate the presence of two concurrent binding modes. A comparison between ortho- and peri-substituted sensitizers resulted in slower IET dynamics and weaker electronic coupling for ortho substitution. Finally, IET from sensitizers with saturated linker groups is neither promoted nor hindered by a second linker group. This indicates that only one of the two linkers binds covalently to the surface. This study reveals the importance of the anchor-binding mode and design considerations of the linker for regulating IET.

Synthesis, antioxidant and neuroprotective analysis of diversely functionalized α-aryl-N-alkyl nitrones as potential agents for ischemic stroke therapy

Herein, we report the synthesis, antioxidant and biological evaluation of 32 monosubstituted α-arylnitrones derived from α-phenyl-tert-butyl nitrone (PBN) in the search for neuroprotective compounds for ischemic stroke therapy, trying to elucidate the structural patterns responsible for their neuroprotective activity. Not surprisingly, the N-tert-butyl moiety plays beneficious role in comparison to other differently N-substituted nitrone groups. It seems that electron donor substituents at the ortho position and electron withdrawing substituents at the meta position of the aryl ring induce good neuroprotective activity. As a result, (Z)-N-tert-butyl-1-(2-hydroxyphenyl)methanimine oxide (21a) and (Z)-N-tert-butyl-1-(2-(prop-2-yn-1-yloxy)phenyl)methanimine oxide (24a) showed a significant increase in neuronal viability in an experimental ischemia model in primary neuronal cultures, and induced neuroprotection and improved neurodeficit score in an in vivo model of transient cerebral ischemia. These results showed that nitrones 21a and 24a are new effective small and readily available antioxidants, and suitable candidates for further structure optimization in the search for new phenyl-derived nitrones for the treatment of ischemic stroke and related diseases.

Tuning the Structure of 4‐Aminopyridine Catalysts for Improved Activity and Selectivity in Functionalization of Alcohols

AbstractSeeking to improve the site selectivity in the catalytic phosphorylation and acylation of a model amphiphilic substrate, further increasing the preference for the apolar domain, which we recently disclosed, we attempted to augment the nucleophilicity of the 4‐aminopyridine core unit used in our catalysts, while simultaneously preserving or even increasing the density of their lipophilic outer‐sphere components. Of the three approaches to the new catalyst design, the most promising, in the case of phosphorylation, was that placing two benzyl moieties, substituted with long apolar alkoxy groups in the ortho positions, on the amine nitrogen of the core. This modification also substantially improved the activity of the catalyst in both reactions. Although this approach reduced the selectivity in the acylation reaction, we demonstrated that by altering the geometry of the benzyl substituents (e. g., by restricting the degree of their freedom), the higher selectivity can be regained.

Chiral 1‐Phosphabarrelene‐Pyridines as Suitable Ligands for the Rh/Ir‐Catalyzed Asymmetric Hydrogenation of Olefins

AbstractHerein, we report the synthesis of chiral phosphabarrelene‐pyridine ligands. Their synthesis benefit from modified reaction conditions to overcome the low yields normally associated with the [4+2] cycloaddition reaction of phosphinines with hexafluoro‐2‐butyne, which is a key to install the P‐stereocenter in the phosphabarrelene. Their potential as chelating ligands in asymmetric catalysis was assessed in the Rh‐ and Ir‐catalyzed hydrogenation of cyclic β‐enamides and β‐dehydroamino acid derivatives. The catalytic system containing a tert‐butyl substituent at the ortho position of the phosphabarrelene moiety successfully hydrogenates a range of cyclic β‐enamides (ee's between 92% to 94%) and β‐dehydroamino acid derivatives (ee's between 93% to 95%). Moreover, the reactions can be carried out in the environmentally friendly 1,2‐propylene carbonate as solvent with no loss of enantioselectivity. Mechanistic studies with the Rh/P,N catalytic systems agree with the Landis‐Halpern mechanism and explain the influence of the substituent at the phosphabarrelene on enantioselectivity. Finally, the hydrogenation reactions can be carried out at large scale maintaining high enantioselectivities.