Preparation and Antifungal Activity of 3-Iodo- and 6-Iodo-8-quinolinols

 3-Iodo- and 6-Iodo-8-quinolinols were prepared and tested against six fungi: Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes in Sabouraud dextrose broth. A comparison with the previously known 5-iodo- and 7-iodo-8-quinolinols showed that the 6-iodo isomer was the most active.     

Preparation of 6-Fluoro-8-quinolinol and Related 6-Fluoroquinolines

Summary.  6-Fluoro-8-quinolinol was prepared from 2-amino-5-fluorophenol by a Skraup synthesis. No synergism was observed between 5-fluoro- and 6-fluoro-8-quinolinols or between 6-fluoro- and 7-fluoro-8-quinolinols against any of the six fungi in our test system (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in Sabouraud dextrose broth. Unlike the fluoro-8-quinolinols, the 8-quinolinols comparably substituted with chlorine or bromine did form synergistic mixtures. This is attributed to steric factors. Corresponding author. E-mail: clarke@fordham.edu Received May 23, 2002; accepted May 29, 2002     

Preparation and fungitoxicity of 3,6-dichloro-and 3,6-dibromo-8-quinolinols

Summary 3,6-Dichloro- and 3,6-dibromo-8-quinolinols were prepared by direct halogenation of 8-nitroquinoline by N-halosuccinimide in acetic acid or by halogenation of the corresponding 6-halo-8-nitroquinoline prepared via aSkraup reaction. The nitro group was reduced to amino and the amine was hydrolyzed to the phenol in 70% sulfuric acid at 220°C. The fungitoxicity of 3,6-dichloro- and 3,6-dibromo-8-quinolinols, as well as intermediates in their preparation, againstAspergillus niger, Aspergillus oryzae, Myrothecium verrucaria, Trichoderma viride, andMucor cirinelloides was determined. 3,6-dichloro-8-quinolinol is the most fungitoxic analogue of this class of compounds observed to date.

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Herstellung und Fungitoxizität von 3,6-Dichlor- und 3,6-Dibrom-8-chinolinen

Zusammenfassung 3,6-Dichlor- und 3,6-Dibrom-8-chinoline wurden durch direkte Halogenierung von 8-Nitrochinolin mit N-Halogensuccinimid in Essigsäure oder durch Halogenierung der entsprechenden nachSkraup synthetisierten 6-Halogen-8-nitrochinoline hergestellt. Die Nitrogruppe wurde zum Amin reduziert und die Aminofunktion in 70% iger Schwefelsäure bei 220°C zum Phenol hydrolysiert. Die Fungitoxizität der 3,6-Dichlor- und 3,6-Dibrom-8-chinoline und jene der bei ihrer Herstellung auftretenden Zwischenstufen gegenAspergillus niger, Aspergillus oryzae, Myrothecium verrucaria, Trichoderma viride undMucor cirinelloides wurde bestimmt. 3,6-Dichlor-8-chinolin ist der derzeit stärkste bekannte fungitoxische Vertreter dieser Substanzklasse.

     

Intramolecular synergism,an explanation for the enhanced fungitoxicity of halo-8-quinolinols

Summary An antifungal study againstAspergillus niger,A. oryzae,Myrothecium verrucaria, andTrichoderma viride in Yeast Nitrogen Base supplemented with 1%D-glucose and 0.088%L-asparagine was carried out using 8-quinolinol and 3-, 5-, 6-, 7-, 3,6-, and 5,7-chlorinated and brominated-8-quinolinols. Binary mixtures of 3- and 6-halo- and 5- and 7-halo-8-quinolinols were intermolecularly synergistic. MICs of the monohalo synergistic mixtures admixed with a MIC of the corresponding dihalo-8-quinolinols were not synergistic. The dihalo-8-quinolinols with substituents in positions corresponding to those of the synergistic binary mixtures appeared to attack the same sites of action as the binary pairs. The enhanced activities of 3,6- and 5,7-dichloro-8-quinolinols and 3,6- and 5,7-dibromo-8-quinolinols are believed to be due to intramolecular synergism. The greater fungitoxicity of 5-, 6-, and 7-monohalo-8-quinolinols over 8-quinolinol can also be explained as due to intramolecular synergism. 3,6-Dihalo- and 5,7-dihalo-8-quinolinols formed synergistic pairs of compounds.

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Intramolekularer Synergismus als Erklärung für die erhöhte Fungitoxizität von halogenierten 8-Chinolinolen

Zusammenfassung 8-Chinolinol und verschiedene halogenierte 8-Chinolinole wurden auf ihre Fungitoxizität gegenüberAspergillus niger,A. oryzae,Myrothecium verrucaria undTrichoderma viride untersucht. Binäre Mischungen von 3- und 6-Halogen- bzw. 5- und 7-Halogen-8-chinolinol zeigten intermolekularen Synergismus, während bei Mischungen von mono- und dihalogenierten 8-Chinolinolen kein entsprechender Effekt beobachtet werden konnte. Die erhöhte Aktivität von 3,6-und 5,7-Dichlor-8-chinolinol und 3,6- und 5,7-Dibrom-8-chinolinol wird durch intramolekularen Synergismus erklärt, desgleichen die höhere Aktivität monohalogenierter 8-Chinolinole gegenüber 8-Chinolinol. 3,6-Dihalogenierte und 5,7-dihalogenierte 8-Chinolinole bilden synergistische Paare.

     

Preparation and Fungitoxicity of Some Trichloro-, Tribromo-, Tetrachloro-, and Tetrabromo-8-Quinolinols

Summary.  3,5,6-, 3,5,7-, 4,5,7-, and 5,6,7-trichloro- and -tribromo-8-quinolinols as well as 3,5,6,7-tetrachloro- and -tetrabromo-8-quinolinols were prepared and tested against six fungi (Aspergillus niger, Aspergillus oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in Sabouraud dextrose broth. The compounds strongly inhibit five fungi but not M. cirinelloides. They are less active than the related dichloro-8-quinolinols which is attributed to steric hindrance. Received April 3, 2001. Accepted April 10, 2001     

Preparation of 6-Fluoro-8-quinolinol and Related 6-Fluoroquinolines

 6-Fluoro-8-quinolinol was prepared from 2-amino-5-fluorophenol by a Skraup synthesis. No synergism was observed between 5-fluoro- and 6-fluoro-8-quinolinols or between 6-fluoro- and 7-fluoro-8-quinolinols against any of the six fungi in our test system (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in Sabouraud dextrose broth. Unlike the fluoro-8-quinolinols, the 8-quinolinols comparably substituted with chlorine or bromine did form synergistic mixtures. This is attributed to steric factors.     

Effect of Dimethyl Sulfoxide and Dimethylformamide on the Stability of 4-Halo-8-quinolinols

Summary. Polyhalo-8-quinolinols with chlorine or bromine in position 4 were not stable in DMSO or DMF. The degradation product from 4,5-dichloro-8-quinolinol was 5-chloro-4,8-quinolindiol and the major product from 4,5-dibromo-8-quinolinol was 3,5-dibromo-4,8-quinolindiol. 4,5,7-Trichloro- and 4,5,7-tribromo-8-quinolinols yielded similar hydrolytic products, and for the bromo compound, a rebrominated product in DMSO. In DMF rebromination did not occur. In pyridine-d₅ these reactions did not take place, indicating a special ability of DMSO and DMF to cause such hydrolysis at position 4 of 4-halo-8-quinolinols.Received December 13, 2002; accepted January 7, 2003 Published online June 23, 2003     

Evidence of steric factors in the fungitoxic mechanisms of 8-quinolinol and its 2-, 3-, 4-, 5-, 6-and 7-chloro and bromo analogues

Summary A study was made of the fungitoxicity of 2-, 3-, 4-, 5-, 6- and 7-chloro and bromo-8-quinolinols againstAspergillus niger,A. oryzae,Myrothecium verrucaria,Trichoderma viride andTrichophyton mentagrophytes in Sabouraud dextrose broth and in Yeast Nitrogen Base supplemented with 1%D-glucose and 0.088%L-asparagine. Based on the presence or absence of synergism between pairs of substituted 8-quinolinols and reversal or nonreversal of toxicity byL-cysteine or N-acetyl-L-cysteine, the following conclusions were reached: (1) substituents on the quinoline ring change the site(s) of action of the toxicant; (2) the sites of action of the 5-, 6-, and 7-chloro-8-quinolinols are different from each other and from 8-quinolinol and its 2-, 3-, and 4-chloro analogues, and the same is true for the corresponding bromo compounds; (3) 8-quinolinol and its 3- and 4-chloro and bromo analogues appear to share common sites of action; (4) for good antifungal activity the 2 position of the ring must not be substituted by sterically bulky groups; (5) the geometry of the binding sites of action are not so constrained that they cannot accommodate the analogously substituted chloro- and bromo-8-quinolinols.

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Nachweis sterischer Faktoren bei der Fungitoxizität von 8-Chinolinol und seinen 2-, 3-, 4-, 5-, 6- und 7-Chlor- und -Brom-Analogen

Zusammenfassung Es wurde eine Studie der Fungitoxizität von 2-, 3-, 4-, 5-, 6- und 7-Chlor- und-Brom-8-chinolinol gegenüberAspergillus niger,A. oryzae,Myrothecium verrucaria,Trichoderma viride undTrichphyton mentagrophytes in Sabouraud Dextrose Nährmedium und in Hefe-N-Base mit 1%D-Glucose und 0.088%L-Asparagin unternommen. Auf der Basis des Zutreffens oder der Abwesenheit eines Synergismus zwischen Paaren von substituierten 8-Chinolinolen und der Umkehrung oder Nichtumkehrung der Toxizität durchL-Cystein oder N-Acetyl-L-cystein wurden folgende Schlußfolgerungen abgeleitet: (1) Substituenten am Chinolin-Ring ändern die Aktionsstelle(n) des Toxikans; (2) Die Angriffsstellen der 5-, 6- und 7-Chlor-8-chinolinole sind untereinander und von 8-Chinolinol und seinen 2-, 3- und 4-Chlor-Analogen verschieden, wobei das auch für die entsprechenden Brom-Verbindungen gilt; (3) 8-Chinolinol und seine 3- und 4-Chlor- und -Brom-Analogen scheinen gemeinsame Aktionsstellen zu teilen; (4) für eine gute antifungale Aktivität darf die 2-Position des Rings nicht mit sterisch anspruchsvollen Gruppen besetzt sein; (5) Die Geometrie des Bindungsstellen der Wirkung ist nicht so gespannt, daß nicht sowohl analoge Chlor- oder Brom-8-chinolinole Platz finden.

     

1-Iodo-1-selenoalkenes as versatile alkene 1,1-dianion equivalents. Novel connective approach towards the tetrahydropyran subunit of polycavernoside A

syn-Hydroalumination of 2,4,6-triisopropylphenylselanyl-1-alkynes with DIBAL-H followed by Al/I exchange with I₂ afforded exclusively (E)-1-iodo-1-selenoalkenes in good yields. 1-Iodo-1-selenopropene 10 proved to be a convenient 1,1 dianion equivalent, leading to the stereodivergent synthesis of allylsilanes (Z)-6 and (E)-6. Adduct 3, an intermediate in the synthesis of the tetrahydropyran subunit of polycavernoside A, was efficiently synthesised from allylsilane (Z)-6 and aldehyde 7 via an intramolecular Sakurai cyclisation.     

Preparation and Fungitoxicity of Some Trichloro-, Tribromo-, Tetrachloro-, and Tetrabromo-8-Quinolinols

 3,5,6-, 3,5,7-, 4,5,7-, and 5,6,7-trichloro- and -tribromo-8-quinolinols as well as 3,5,6,7-tetrachloro- and -tetrabromo-8-quinolinols were prepared and tested against six fungi (Aspergillus niger, Aspergillus oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in Sabouraud dextrose broth. The compounds strongly inhibit five fungi but not M. cirinelloides. They are less active than the related dichloro-8-quinolinols which is attributed to steric hindrance.     

Preparation and fungitoxicity of 3-bromo-6-chloro- and 6-bromo-3-chloro-8-quinolinols

Summary 3-Bromo-6-chloro- and 6-bromo-3-chloro-8-nitro, -8-amino-, and -8-hydroxyquinolines along with 3-bromo- and 3-chloroquinolin-6,8-diols were prepared and tested for antifungal activity against six fungi (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, Trichophyton mentagrophytes) inSabouraud dextrose broth. Compounds with chlorine in the 3 position were generally more fungitoxic than the corresponding analogues with bromine. 6-Bromo-3-chloro-8-quinolinol inhibited four fungi at levels below 1 µg/ml andA. niger andM. cirinelloides at 2 µg/ml each.

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Synthese und Fungitoxizität von 3-Brom-6-chlor- und 6-Brom-3-chlor-8-chinolinolen

Zusammenfassung 3-Brom-6-chlor- und 6-Brom-3-chlor-8-nitro-, -8-amino- und -8-hydroxychinoline sowie 3-Brom- und 3-Chlorchinolin-6,8-diole wurden hergestellt und gegen sechs Pilzstämme (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, Trichophyton mentagrophytes) inSabouraud-Dextrosenährmedium auf lhre fungizide Aktivität untersucht. Verbindungen mit Chlor in Position 3 sind durchwegs fungitoxischer als die entsprechenden Bromanalogen. 6-Brom-3-chlor-8-chinolinol hemmt das Wachstum von vier Pilzen bei Konzentrationen unter 1 µg/ml und das vonA. niger undM. cirinelloides bei einer Konzentration von jeweils 2 µg/ml.

     

Utility of 5-Diazo-1,2,4- Triazol-3-Carboxylic Acid for Colorimetric Determination of Certain 8-Hydroxyquinolines

Abstract

A colorimetric method for the determination of certain 8-hydroxyquinolines has been developed. The method is based on the coupling of 8-quinolinols with diazotriazole carboxylic acid in the presence of sodium carbonate (0.5% w/v) at ambient temperature (around 30°C). The resulting azo dyes are stable and give intense absorption in the range of 486–540 nm. Beer's law is valid in the concentration ranges of 1 – 8, 2.5 – 17.5, 5 – 35, 2 – 20, and 2 – 20 mcg/ml for 8-hydroxyquinoline (HQ), 5,7-diiodo-8-hydroxyquinoline (DIQ), 5,7-dibromo-8-hydroxyquinoline (DBQ), 5-chloro-7-iodo-8-hydroxyquinoline (CIQ) and 8-hydroxy-7-iodo-5-quinoline sulfonic acid (SIQ), respectively. The proposed method has been successfully applied for the determination of the studied compounds in pure form and in commercial formulations. The obtained results are in good agreement with those obtained from reported methods.     

Spectrophotometry Studies of Uranyl Chelate of 7-Iodo-8-Hydroxyquinoline-5-Sulphonic Acid

Uranyl chelate of 7-iodo-8-hydroxyquinoline-5-sulphonic acid (ferron) has been studied spectrophotometrically in aqueous solution at 25° and at an ionic strength of 0.1 M. The formation of this chelate was pH dependent, and the optimum pH range was between 5.4 to 5.9, Its mole ratio of ligand to uranyl ion was found to be 2 to 1 stoichiometry and the stability constant, log K, was determined as 13.32±0.08. By using the wave-length of 365 mu, determination of trace amount of uranyl ion with the sensitivity of 0.54 γ/cm² was possible.     

Preparation and Fungitoxicity of Some Dibromo-8-quinolinols

Summary.  2,5-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6-, 5,7-, and 6,7-dibromo-8-quinolinols were prepared and tested against six fungi (Aspergillus niger, Aspergillus oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in Sabouraud dextrose broth. Most of the compounds were strongly antifungal, inhibiting five of the fungi below 1μg/cm³, but were somewhat less fungitoxic than the corresponding chloro analogues. M. cirinelloides was not inhibited by any of the compounds except 4,5-dibromo-8-quinolinol. This high level of fungitoxicity is attributed to intramolecular synergism. Received December 28, 2000. Accepted (revised) February 3, 2001     

Synthesis and crystal structure of mercury(II) chloride–ferron (7-iodo-8-hydroxyquinoline-5-sulfonic acid) adduct

A mercury(II) chloride adduct of ferron (7-iodo-8-hydroxyquinoline-5-sulfonic acid), [HgCl₂ (C₉H₆INO₄)·H₂O] has been synthesized and characterized by X-ray diffraction analysis and spectroscopic studies. The compound crystallizes in P2₁/c space group, a?=?8.919(3), b?=?23.216(3), c?=?7.714(3)?Å, β?=?95.79(3)°. The coordination geometry around mercury is distorted square planar [(2+2) coordination] with two short Hg–Cl bonds [2.308(2) and 2.309(18)?Å] and two long Hg–O(sulfonate) [2.738(4)?Å] and Hg–O(water) [2.889(4)?Å] bonds. The sulfonic group is deprotonated, the proton having migrated to the quinoline N atom that forms intermolecular hydrogen bonds. The inversion related organic ligands are stacked over one another. The crystal structure is further stabilized by a C–H···O, O–H···O and N–H···O hydrogen bonds.     

Spectrophotometric Studies of Cerium(III) Chelate of 7-Iodo-8-Hydroxyquinoline-5-Sulphonic Acid

Cerium(III) chelate of 7-iodo-8-hydroxyquinoline-5-sulphonic acid(ferron) has been studied spectrophotometrically in aqueous solution at 25°C and at an ionic strength of 0.1M. The formation of this chelate was pH dependent, and the optimum pH range was between 5.5 to 6.0. Its mole ratio of ligand to cerium(III) ion was found to be 2 to 1 stoichiometry and the formation constant, logK, was determined as 10.15. Enthalpy and entropy changes characterizing the formation of the chelate have been calculated as follows: ΔG° =-13.85kcal mole^-1, ΔH°= ?5.03 kcal mole^-1, ΔS°=29.56 eu mole^-1. By using the wavelength of 370 nm, determination of trace amount of cerium(III) ion with the sensitivity of 0.056 was possible.     

Preparation of Ethyl 5-Iodo-1H-indole- 2-carboxylate

Abstract

A facile, two step procedure for the preparation of ethyl 5-iodo-1H-indole-2-carboxylate (1) from commercially available ethyl 1H-indole-2-carboxylate is described herein, employing a regioselective C3, C5-bisiodination followed by zinc-mediated C3-dehalogenation.     

芳香碘基-Cu(Ⅱ)聚合配位引导组装的特殊层状超分子的晶体结构

近年来,有关无机碘(I2)及其相关化合物的溶液和晶态超分子结构的研究十分活跃,但对芳香碘基的超分子化学研究,特别是结构组装的应用研究尚未见报道．无机碘化物超分子结构组装的一个明显弱点是其对其它主体分子骨架的结构依附性和不稳定性．而芳香碘基通过共价键被固定于芳环     

Convenient Syntheses of Methyl 2-Bromo- and 2-Iodo-2,3-butadienoates

Syntheses of methyl 2-bromo- and 2-iodo-2,3-butadienoates 3 and 6 from readily available starting materials are described. 3 and 6 will be valuable building blocks for the synthesis of 2-aryl and 2-alkenyl substituted alka-2,3-dienoates via Palladium-catalyzed cross-coupling reactions.     

Synthesis of 2-Acetamido-5,6-dihalophenyl Acetates

Summary.  2-Acetamido-5,6-dihalophenyl acetates were synthesized as intermediates for the preparation of 6, 7-dihalo-8-quinolinols via the Skraup procedure. Received January 24, 2000. Accepted February 12, 2000