Benzo Ring Research Articles

2-Oxochromen-4-yl 4-(dimethylamino)benzoate

In the title mol­ecule, C18H15NO4, the benzoate ring is oriented at a dihedral angle of 43.43 (6)° with respect to the planar [maximum deviation = 0.038 (2) Å] chromene ring. The crystal structure features R 2 2(12) centrosymetric dimers formed via C—H⋯O inter­actions and these dimeric aggregates are connected by C—H⋯π inter­actions.

Cyclopalladated Ferrocenylimine Catalyzed Chlorination of 2‐Arylbenzoxazoles

AbstractAn efficient and facile protocol for palladacycle‐catalyzed chlorination of 2‐arylbenzoxazoles was developed. The results represent the first examples involving the palladacycle as the catalyst for such chlorination. This chlorination was not a ligand‐directed ortho‐CH activation, but an electrophilic substitution process at the para‐position of the nitrogen atom in the benzo ring of benzoxazole moiety, the regiochemistry of which had been confirmed by HMBC spectral analysis. The catalytic system could tolerate various halogen atoms, such as F, Cl and Br, affording the corresponding products in moderate to excellent yields.

A macrocyclic ligand 5,14-dihydro-6,15-dimethyl-8,17-diphenyldibenzo-[b,i][1,4,8,11]tetraazacyclotetradecine and its nickel(II) complex: Syntheses, reaction mechanism and structures

Abstract The template reaction of o-phenylenediamine, 1-benzoylacetone and nickelous acetate tetrahydrate results in two structure isomers, 6,17-dimethyl-8,15-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecinatonickel (II) (2) and 6,15-dimethyl-8,17-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecinatonickel (II) (4). However, the latter has been neglected in the previous research because of its low yield in the template reaction. The mechanism of this template reaction is discussed. Though the steric hindrance between the phenyl ring and the benzo ring in 2 is greater than that in 4, the intermediate of the former shows better structural stability than that of the latter, leading to obviously higher final yield of 2 compared with that of 4. n-Butyl alcohol is used artfully to separate the crude product of the template reaction into almost pure 2 and a mixture of 2 and 4 in a mole ratio of 1:5. The free base of 2, 5,14-dihydro-6,17-dimethyl-8,15-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine (1), can be synthesized by demetalization of 2 with gaseous HCl. The same treatment to the mixture of 2 and 4 in a mole ratio of 1:5 leads to the free base of 4, 5,14-dihydro-6,15-dimethyl-8,17-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine (3). The neglected macrocyclic compounds 3 and 4 have been characterized unambiguously and their single-crystal structures have also been determined by X-ray diffraction analysis for the first time.

Ultrafast Intramolecular Energy Relaxation Dynamics of Benzoporphyrins: Influence of Fused Benzo Rings on Singlet Excited States

We have investigated the role of fused benzo rings on the electronic structures and intramolecular energy relaxation dynamics in a series of benzoporphyrins (Bp1, syn-Bp2, anti-Bp2, Bp3, and Bp4) by using time-resolved fluorescence measurements and theoretical calculations. Interestingly, even though anti- and syn-Bp2 have the same number of fused benzo rings, in the respective absorption spectra, anti-Bp2 shows an obvious splitting of B(x) (Q(x)) and B(y) (Q(y)) states, whereas syn-Bp2 exhibits degenerate B and Q bands. These features provide two dynamical models for the effect of the position of substituted benzo rings on the intramolecular energy relaxation dynamics. syn-Bp2 gives rise to similar intramolecular dynamics from the B state to the Q state in the case of ZnTPP having D(4h) molecular symmetry. On the other hand, anti-Bp2 shows split B and Q bands in the order B(y) > B(x) > Q(x) > Q(y), which leads a superimposition of the Q(x) (0,0) and Q(y) (1,0) bands. This overlap generates a strong coupling between these two states, which results in a direct internal conversion from B(x) (0,0) to Q(y) (0,0). This observation suggests that the anti-type fused position of benzo rings leads to a new mechanism in internal conversion from the B to the Q state. On the basis of this work, further insight was obtained into the effect of fused benzo rings on the photophysical properties of benzoporphyrins, providing a detailed understanding of the structure-property relationship in a series of benzoporphyrins.

Chlorination and ortho-acetoxylation of 2-arylbenzoxazoles

Efficient and facile catalytic protocols for chlorination and ligand-directed ortho-acetoxylation of 2-arylbenzoxazoles have been developed. The chlorination is not a ligand-directed ortho-functionalization, but an electrophilic substitution process in the benzo ring of the benzoxazole moiety. Meanwhile, the acetoxylation exhibited high regioselectivity for the substrates containing a meta-substituent and occurred at the less sterically hindered ortho-C-H bond of the directing group.

ChemInform Abstract: Synthesis of Novel Tetrahydrobenzazepinones.

Abstract The synthesis of novel tetrahydrobenzazepinones 1, 2, and 3 is described, as well as an improved synthesis of 4. The palladium catalyzed arylation approach to 1, 2, and 4 allows facile entry to benzazepinones lacking electron donating substituents on the benzo ring.

4-Methyl-2H-benzopyran-2-one 유도체들의 항산화 활성에 관한 Benzo 고리상 치환기들의 영향

The influences on antioxidant activities of the substituents () on benzo ring in 4-Methyl-2H-benzopyran-2-one analogues (1-23) were discussed quantitatively using three dimensional quantitative structure-activity relationships (3D-QSARs: Comparative molecular field analyses (CoMFA) and Comparative molecular similarity indice analyses (CoMSIA)) methods. The statistical qualities of CoMSIA models were better than those of CoMFA models and the CoMSIA 2 model was optimized model (

Structure-activity relationships of mono-substituted trisulfonated porphyrazines for the photodynamic therapy (PDT) of cancer

The impact of lipophilicity on biological parameters critical to photodynamic efficacy was analyzed for a new generation of trisulfobenzo(mononaphtho)porphyrazines. The porphyrazines were substituted on the naphtho ring with linear alkynyl side chains of various lengths. When compared to the analogous phthalocyanine structures, the added benzo ring in the porphyrazine structures increased the lipophilicity for analogs with short alkynyl chains, while this effect disappeared for analogs with longer side chains. In aqueous media, the analogous phthalocyanine series showed aggregation tendencies. In contrast, no correlation between aggregate formation and the length of the alkynyl side chain was evident in the porphyrazine series. At low concentrations, the length of the side chain did not affect cell uptake, while phototoxicity towards EMT-6 mouse tumour cells showed a parabolic relationship, where the hexynyl derivative showed the highest activity. The trisulfonated porphyrazines localized at intracellular organelles, plasma and perinuclear membranes, but could not be found in the nucleus. Total cell uptake of dye did not correlate with phototoxicity, suggesting that localization in certain intracellular organelles, and distribution into critical intracellular sites are important determinants of their photodynamic activity. The hexynyl trisulfonated zinc porphyrazine derivative (ZnNPcS(3)C(6)) showed the strongest in vitro photodynamic activity and therefore was further studied in an EMT-6 mouse tumour model. An i.v. dose of 1 micromol of ZnNPS(3)C(6) per kg, followed 24 h later by activation with light, induced 100% tumour necrosis within 24 h post-PDT. This treatment delayed tumour volume doubling time from 5 days to >2 weeks, and gave 41% tumour cure >3 weeks post-PDT. Applying the same light dose fractionated (5 min on, 2 min off), further improved tumour response, leading to a doubling time of 26 days and a 73% tumour cure. At the administered 1 micromol kg(-1) dye dose, no skin phototoxicity was observed and >90% blood clearance was observed within 5 h post-injection. Compared to the analogous trisulfo monohexynyl zinc phthalocyanine, the new trisulfobenzo(mononaphthohexynyl)porphyrazine provided a broader range of excitation wavelengths, and improved photodynamic potency, while apparently being free of unwanted systemic side effects.

Influence of Soil Factors on the Dissipation of a New Pyrimidynyloxybenzoic Herbicide ZJ0273

A novel pyrimidynyloxybenzoic herbicide (ZJ0273) uniformly labeled with (14)C on the benzoate ring was applied to soils under sterile and nonsterile conditions to understand the effect of soil microorganisms and selected properties on its dissipation and transformations to bound resides and (14)CO(2). A significant effect of soil microorganisms was found in an acidic soil, where sterilization significantly prolonged the half-dissipation time (DT(50)) of ZJ0273 from 15.57 to 34.31 days and decreased the total amount of mineralized (14)CO(2) from 19.91 to 0.43%. However, sterilization showed limited effect on the patterns of bound residue or extractable residue levels in soils having pH > or = 6.1. In addition, a significant suppression of high pH was found on the dissipation of extractable residues and formation of bound residues. The enhancement of bound residue formation by low soil pH was attributed to increased conversion of ZJ0273 to its intermediates, which were rapidly bound to soil organic matter.

2,2,7-Trichloro-3,4-dihydronaphthalen-1(2H)-one

The title compound, C10H7Cl3O, obtained as a major byproduct from a classical Schmidt reaction. The cyclohexyl ring is distorted from a classical chair conformation, as observed for monocyclic analogues, presumably due to conjugation of the planar annulated benzo ring and the ketone group (r.m.s. deviation 0.024 Å). There are no significant intermolecular interactions.

Knot-Isomers of Möbius Cyclacene: How Does the Number of Knots Influence the Structure and First Hyperpolarizability?

Four knot-isomers of Möbius cyclacene are composed of 15 nitrogen-substituted benzo rings. They are non-Möbius cyclacenes without a knot (0), Möbius cyclacenes with a knot (1), non-Möbius cyclacenes with two knots (2), and Möbius cyclacenes with three knots (3). Their structures and nonlinear optical properties are systematically studied. The order of first hyperpolarizability (β0) is 4693 (0) < 10 484 (2) < 25 419 (3) < 60 846 au (1). The β0 values of the knot-isomers with knot(s) are larger than that of the knot-isomer without a knot. It shows that the β0 value can be dramatically increased (13 times) by twisting the knot(s) to the cyclacene. Two noticeable relationships between the number of knots and the first hyperpolarizability have been observed: (i) the β0 values of one surface Möbius cyclacene (1 and 3) with an odd number of knots are larger than that of two-surface non-Möbius cyclacenes (0 and 2) with an even number of knots. (ii) For the one-surface Möbius cyclacenes, the β0 value for 1 with one knot is larger than that for 3 with three knots. On the other hand, the largest component of β0 is alternated for the four knot-isomers. The largest components are βz for the 0 and βy for the 1 and 2. The largest component turns back to the βz for the 3.

A molecular orbital study of the metabolism and carcinogenicity of the phenols of benzo(a)pyrene

Relative tendencies of the twelve isomeric phenol derivatives of benzo(a)pyrene to undergo specific metabolic chemical reactions have been examined using molecular orbital calculations. Considering presumed “activating” reactions alone, the calculations suggest that all the hydroxy derivatives except those substituted on the benzo ring should be capable of forming bay region carbonium ions via epoxide and dihydrodiol intermediates. Oxyradical formation provides a possible competing pathway. The tendency of benzo(a)pyrene phenols to form oxyradicals appears to be strongly influenced by the position of substitution: 6-hydroxybenzo(a)pyrene is calculated to have the highest tendency to undergo this transformation and 2-hydroxybenzo(a)pyrene the lowest tendency. It is suggested that the differing carcinogenic activities of the benzo(a)pyrene phenols may be related to their tendencies to form oxyradicals and that this reaction may provide a deactivating reaction pathway for these compounds.

Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors

Modification of the benzo rings of 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones into heteroaromatic systems was investigated to enhance physicochemical properties and potency profile of this class of inhibitors. The synthesis and biological activity of the derived compounds is discussed.

Hydrogen-bonded mononuclear nickel(II) benzoate complexes: synthesis and structural studies

[TpPh,MeNi(Cl)PzPh,MeH] (1) has been synthesized by the reaction of hydrotris(3-phenyl-5-methyl-pyrazol-1-yl) borate [TpPh,Me], NiCl2 · 6H2O and 3-phenyl-5-methyl-pyrazole [PzPh,MeH]. The reaction of 1 with variously substituted sodium p–X–benzoates resulted in the formation of complexes of the type [TpPh,MeNi(p–X–OBz)PzPh,MeH] (X = H for 2, F for 3, Cl for 4, NO2 for 5, Me for 6, OMe for 7, OH for 8, CHO for 9 and CN for 10). Single crystal X-ray studies suggest that all these complexes have a five-coordinate metal center and the benzoate groups are monodentate in a square pyramidal geometry. The X-ray studies also reveal that the uncoordinated oxygen atom of the benzoate forms intramolecular hydrogen-bonds with the NH group of the coordinated pyrazole. The substituents present on the benzoate ring are involved in different types of intermolecular interactions and the complexes exhibit different crystal packing. Complexes 2–10 were tested for superoxide dismutase activity.

2,4-Dichlorophenyl benzoate

The crystal structure of the title compound, C13H8Cl2O2, resembles those of 2,3-dichloro­phenyl benzoate, 2,4-dimethyl­phenyl benzoate and other aryl benzoates, with similar bond parameters. The plane of central –C(=O)—O– group is inclined at the angle of 9.1 (2)° with respect to the benzoate ring. The two aromatic rings make a dihedral angle of 47.8 (1)°. In the crystal structure there are no classical hydrogen bonds. The mol­ecules in the structure are packed into chains diagonally in the bc plane.

2,5-Dimethylphenyl benzoate

In the title compound, C15H14O2, the plane of the central –C(=O)–O– group is inclined at an angle of 3.7 (2)° with respect to the benzoate ring. The two benzene rings are almost perpendicular, making a dihedral angle of 87.4 (1)°. In the crystal, mol­ecules are packed into infinite chains through weak C—H⋯π inter­actions.

Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor γ Agonists

Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARalpha/gamma dual agonist 1 to selective PPARgamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARgamma receptor, with 80- to 100-fold PPARgamma selectivity over PPARalpha receptor. X-ray cocrystal studies in PPARgamma and modeling studies in PPARalpha give molecular insights for the improved PPARgamma potency and selectivity for 19 when compared to 1.

Octa- and Nonamethylfluorenyl Complexes of Zirconium(IV): Reactive Hydride Derivatives and Reversible Hydrogen Migration between the Metal and the Fluorenyl Ligand

Reaction of the zirconocene dichloride Cp′′Flu*ZrCl2 (Cp′′ = 1,3-(SiMe3)2C5H3, Flu* = C13Me9) with iBuLi (iBuLi = LiCH2CHMe2) resulted in elimination of isobutylene and formation of Cp′′(η5:η3-C13Me9H)ZrH (1-syn-1,2-DHF*D), possessing an η5:η3-dihydrofluorenediyl ligand derived from a metal-to-benzo ring hydride transfer. This species undergoes reversible hydride transfer and exists in equilibrium with only one of its three other possible isomers (1-syn-3,4-DHF*D). Compound 1-syn-1,2-DHF*D catalyzes the cyclization of 1,5-hexadiene to methylenecyclopentane, and its reaction with excess isobutylene leads to the elimination of isobutane and formation of the cyclometalated zirconocene isobutyl species (η5:η1-C5H3-1-SiMe2CH2-3-SiMe3)(η5-C13Me9)ZriBu (2). Reaction of Cp′′Flu′′ZrCl2 with iBuLi directly generated the cyclometalated zirconocene species (η5:η1-C5H3-1-SiMe2CH2-3-SiMe3)(η5-C13Me8H)ZriBu (3); however, reaction of the dichloride Cp′′Flu′′ZrCl2 with iBuLi in the presence of hydrogen generated the dihydrofluorenediyl monohydride derivative Cp′′(η5:η3-C13Me8H2)ZrH (4). Treatment of the cyclometalated isobutyl species 3 with H2 led to partial hydrogenation of the Flu′′ ligand and formation of the monohydride Cp′′(η5:η3-C13Me8H6)ZrH (5), which contains a hexahydrofluorenediyl ligand. Partial hydrogenation of the Flu′′ ligand proceeded exclusively via an intramolecular pathway, as evidenced by the all-exo configuration of the methyl groups on the saturated benzo ring. Structural characterization of 1-syn-1,2-DHF*D, 2, 3, and 5 revealed a highly strained η5:η3-coordination mode for the dihydro- and hexahydrofluorenediyl ligands.

Tricarbonylchromium Complexes of 1,2-Dihydro-1,2-benzazaborines

1,2-Dihydro-2-phenyl-1,2-benzazaborine reacts with Cr(CO)3(CH3CN)3 in THF at 140 °C to form complex 18, in which the phenyl is η6-bound to chromium. 1,2-Dihydro-2-methyl-1,2-benzazaborine reacts with Cr(CO)3(CH3CN)3 in THF at 60 °C to form complex 23, in which the benzo ring is η6-bound to chromium. Treating 23 with potassium bis(trimethylsilyl)amide in THF forms the corresponding potassium salt 25, which on heating undergoes haptotropic isomerization to complex 26, in which the anionic heterocyclic ring is η6-bound to the chromium.

Synthesis and X-ray crystal structures of metal complexes of three isomeric bibenzodiazines: Discrete and polymeric assemblies

Thirteen complexes of three isomeric bibenzodiazines were prepared and X-ray crystal structures were determined for seven of these. It is shown that 2,2′-biquinazoline prefers to form mononuclear complexes with chelation involving the less hindered nitrogen donors. Complexes of 4,4′-biquinazoline failed to provide suitable crystals for X-ray structure determination. 2,2′-Biquinoxaline is shown to offer two modes of coordination; in the first it acts as a “stepped-linear” bridging ligand using the two less hindered nitrogens, while in the second mode it chelates to copper(I) centres using its more hindered nitrogens. The presence of the fused benzo rings leads to a higher propensity for π–π stacking of the heterocyclic ligands within such complexes.