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     

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     

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 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.

     

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.

     

The elimination of small neutral molecules and fragments in mass spectra—II: 2-substituted 8-hydroxyquinolines

The mass spectra of a series of 2-substituted 8-hydroxyquinolines and related compounds are reported. Fragmentation pathways based upon interpretation of spectra and metastable transitions for 8-quinolinol; 2-methyl-8-quinolinol; 4-methyl-8quinolinol; 2-hydroxymethyl-8-quinolinol; 2-aminomethyl-8-quinolinol; 8-quinolinol-2-carboxaldehyde; 8-quinolinol-2-carb-oxaldehyde oxime; and 8-quinolinol-2-carboxaldehyde tert-butylimine are discussed, as are dissociations in the related compounds 2-hydroxymethyl quinoline and quinoline-2-carboxaldehyde oxime. It is suggested that the molecular ions of 2-substituted-8-quinolinols undergo rearrangement to a substituted azatropylium ion prior to dissociation. An ion of m/e 89 has been observed in these spectra and is considered to be characteristic of the quinoline nucleus bearing an X-substituent in any position, where X ? OR, SR, NH₂ etc. (R ? H, CH₃, etc).     

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.     

Quantum-chemical study of 4- and 8-element-substituted tetrahydro-sym-indacenes

Energies, geometries, and electronic structures of structural isomers of 4,4,8,8-tetramethyl-4,8-disila-3a,4,4a,8-tetrahydro-sym-indacene as well as some transition states for the intramolecular metallotropic rearrangements of these compounds were calculated using the semiempirical quantum-chemical INDO and MNDO methods. The applicability of the MINDO/3, INDO, and MNDO methods for describing ^l-silyl derivatives of cyclopentadienes was tested on model compounds R₃SiC₅H₅, where R is Me or H.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 859–865, May, 1993.     

Improved syntheses of some monochloro- and monobromo-8-quinolinols

Summary Procedures were developed for the preparation of the 2-, 3-, 4-, and 6-monosubstituted chloro and bromo 8-quinolinols which afforded greater yields and/or reduced the number of steps in the preparation. 100 MHz¹H-NMR spectra for the 12 possible monochloro and monobromo analogues are given.

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Verbesserte Synthese von Monochlor- und Monobrom-8-chinolinolen

Zusammenfassung Es wurden Verfahren entwickelt, um 2-, 3-, 4- und 6-Chlor bzw. -Brom-8-chinolinole in besseren Ausbeuten und/oder bei reduzierter Anzahl von Synthesestufen herzustellen. Die¹H-NMR-Spektren der 12 möglichen Monochlor- und Monobromverbindungen werden angegeben.

     

Synthesis of novel pyridocoumarins and benzo-fused 6-azacoumarins

Benzo[7,8]-fused 6-azacoumarins are prepared from 4-quinolinol by treatment with PPh₃ and DMAD, or from 3-formyl-4-quinolinol by Wittig reaction with carbalkoxyalkylidene(triphenyl)phosphoranes. Angular pyridocoumarins are prepared from 8- or 6-quinolinols with PPh₃ and DMAD, or from the reactions of 5,6- or 7,8-quinolinediones with carbalkoxymethylene(triphenyl)phosphoranes.     

Synthesis and Tautomeric Equilibrium of Polyfluoroacyl-Containing 1,5-Benzodiazepines

Summary. The reaction of bis(polyfluoroalkyl)-containing 1,3,5-triketones with o-phenylenediamine yielded 2-polyfluoroacylmethylene-4-polyfluoroalkyl-1,3- or 1,5-dihydro-1,5-benzodiazepines. The tautomeric equilibrium of the obtained benzodiazepines in CDCl₃, CD₃CN, DMSO, and DMF solution was studied.     

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.     

A Convenient Route for the Synthesis of 4-Aryl- and 4-Aminopyrimidines

Summary. A series of ureidopropenenitriles were synthesised by Knoevenagel condensation of ArCOCH₂CN and HC(OEt)₃ in presence of ureas in a one pot reaction. These ureidopropenenitriles were cyclised to 4-aryl-5-cyano-3-substituted pyrimidines (in acid) or to 4-amino-5-benzoylpyrimidines (in base) in 60–70% yields. The amine pyrimidine derivatives were further converted to substituted uracils by hydrolysis with isopentyl nitrite in DMF. Alkylation of uracils furnished 1,3-dimethyluracil derivatives with DMS in alkali. All new compounds were characterised by spectral and analytical methods.     

Efficient synthesis of brominated tetrathiafulvalene (TTF) derivatives: solid-state structure and electrochemical behaviour

An efficient synthesis is reported for 4,5-dibromo-[1,3]dithiole-2-thione (1) and 4-bromo-1,3-dithiole-2-thione (7) by bromination of lithiated vinylene trithiocarbonate. Compound 1 acts as a convenient precursor to a number of asymmetric electron donors. This is exemplified by the formation of 4,5-dibromo-4′,5′-bis(2′-cyanoethylsulfanyl)TTF (3) by cross-coupling methodology and subsequent conversion into 4,5-dibromo-4′,5′-ethylenedithioTTF (4) by reaction with caesium hydroxide and 1,2-dibromoethane. The new donor 4,5-dibromo-4′,5′-ethylenedithiodiselenadithiafulvalene (5) was prepared by cross-coupling of 1 and 4,5-ethylenedithio-1,3-diselenol-2-one (6). The X-ray structures of 3 and 5 are reported.     

Stereochemistry of nitrogen heterocycles. 66. Synthesis and x-ray diffraction analysis of C(4)-epimeric 1-methyl-trans-decahydro-4-quinolinols

C₍₄₎-Epimeric 1-methyl-trans-decahydro-4-quinolinols, which are of interest as model compounds for stereochemical investigations, were obtained. It was shown by means of x-ray diffraction analysis that the crystalline compound that we synthesized and not the liquid compound described in the literature is the actual 1-methyl-trans-decahydro-4-quinolinol with an axial hydroxy group. Different pathways of weakening of the OH/H 1,3-syn-peri-planar repulsive interactions were observed: torsional twisting of the cyclic system for the equatorial alcohol and an increase in the O-C₍₄₎-C₍₁₀₎ and C₍₄₎-C₍₁₀₎-C₍₅₎ bond angles. The previously unknown isomorphic forms of equatorial trans-decahydro-4-quinolinol and 1-methyl-trans-decahydro-4-quinolinol were obtained.See [1] for Communication 65.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 642–651, May, 1988.     

Synthesis of imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridones and imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridines as potential antibacterial agents

Abstract  New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug. Graphical abstract        

Synthesis of 4-Octuloses from a Derivative of d-Fructose

Abstract

Reaction of 2,3:4,5-di-O-isopropylidene-β-d-arabino--hexos-2-ulo-2,6-pyranose (1) with (methoxycarbonylmethylene)triphenylphosphorane in either dichloromethane or methanol gave methyl (E)-2,3-dideoxy-4,5:6,7-di-O-isopropylidene-β-d-arabino-oct-2-ene-4-ulo-4,8-pyranosonate (2) or a 1:2.3 mixture of 2 and its Z-isomer (3), respectively. Bishydroxylation of 2 with osmium tetraoxide gave a mixture of methyl 4,5:6,7-di-O-isopropylidene-β-d-glycero-d-galacto- (4) and -d-glycero-d-ido-oct-4-ulo-4,8-pyranosonate (5) which were carefully resolved by column chromatography. Compound 4 was transformed into its 2,3-di-O-methyl derivative (6) which was deacetonated to 7 and subsequently degraded to dimethyl 2,3-di-O-methyl-(+)-L-tartrate (8). On the other hand, acetonation of a mixture of 4 and 5 gave the corresponding tri-O-isopropylidene derivatives (9) and (10). Compounds 4 and 5 were reduced with LiAlH₄ to the related 4,5:6,7-di-O-isopropylidene-β-d-glycero-d-galacto- (11) and β-d-glycero-d-ido-oct-4-ulo-4,8-pyranose (12). Treatment of 11 and 12 with acetone/PTSA/CuSO₄ only produced the acetonation at the C-2,3 positions. Finally, compounds 11 and 12 were deacetonated to the corresponding D-glycero-d-galacto- (15) and D-glycero-d-ido-oct.-4-ulose (16).     

Synthesis and some properties ofN-polynitromethyl derivatives of fused benzotriazoles

The procedures for the synthesis ofN-polynitromethyl derivatives of benzo[1,2-d;4,5d]ditriazole-4,8-dione are described. Some chemical properties of the compounds obtained are investigated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1623–1625, September, 1993.     

Synthesis and Tautomeric Equilibrium of Polyfluoroacyl-Containing 1,5-Benzodiazepines

The reaction of bis(polyfluoroalkyl)-containing 1,3,5-triketones with o-phenylenediamine yielded 2-polyfluoroacylmethylene-4-polyfluoroalkyl-1,3- or 1,5-dihydro-1,5-benzodiazepines. The tautomeric equilibrium of the obtained benzodiazepines in CDCl₃, CD₃CN, DMSO, and DMF solution was studied.