Protoberberines from <Emphasis Type="Italic">Reissert</Emphasis>-Compounds. Part IX [1]. An Alternative Approach to Dibenzoquinolizine- and Isoquinonaphthyridin-13a-carboxylic Acids,a Novel Synthesis of Alangimarine

Summary. 3,4-Dihydroisoquinoline-Reissert-compounds were alkylated to 1-benzyl- and 1-picolyl-derivatives, which in turn could selectively be hydrolized yielding various carboxylic acids, among others certain amino acids related to 3,4-deoxynorlaudanosoline carboxylic acid (DNLCA). These on treating with ethanolic KOH underwent cyclization to dibenzoquinolizine- and isoquinonaphthyridine-13a-carboxylic acids. Alternatively this cyclization also could be achieved by a more convenient one-pot procedure starting from the same dihydro-Reissert-compounds. Thermal decarboxylation afforded among others the alangia alkaloids alangimarine and dihydroalangimarine.Part of PhD thesis, LMU München, D     

Investigations of 2,3′-biquinolyl. 9. Reaction of 1′,4′-dihydro-2,3′-biquinolyl with organolithium compounds

The 1,4-dihydro-2,3-biquinolyl reacts with organolithium compounds to form the mixture of 4-R-1,4-dihydro-2,3-biquinolyls and 2-R-1,2-dihydro-2,3-biquinolyls in the ratio analogous to the conversion in the series of 2,3-biquinolyl. The utilization of the complex, the organolithium compound-TMEDA, in this process leads, after treatment of the reaction mixture with water, exclusively to 2-R-1,2-dihydro-2,3-biquinolyls. Treatment with methyl iodide leads to 1-methyl-2-R-1,2-dihydro-2,3-biquinolyls.     

Synthesis of 3-(3′-Acetyl-5′-aroyl-1′,3′,4′-oxadiazolyl-2′)-chromones

A general method has been proposed for synthesizing 3-(3-acetyl-5-aroyl-1,3,4-oxadiazolyl-2)-chromones that has been based on conversion of 3-formylchromones to acylhydrazones and of theacylhydrazones into the heterocyclic chromones.     

Untersuchung des Zerfalls verschiedener Azoinitiatoren in Lösung

The decomposition of various symmetric and unsymmetric azo-initiators (1,1-dichloro-1,1-diphenyl-1,1-azoethane, 2,2-dichloro-2,2-azopropane, 1,1-dichloro-1,1-azocyclohexane, 2,2-diacetoxy-2,2-azopropane, 1,1-diacetoxy-1,1-diphenyl-1,1-azoethane, 1,1-diacetoxy-1,1-azocyclohexane, 2,2-dipropionoxy-2,2-azopropane, 2,2-dicapronoxy-2,2-azopropane, 4,4-dimethyl-1,4-azobutyrolactone, azoisobutyronitrile, 2-t-butylazo-2-cyanobutan, 2-t-bytylazo-1-cyanocyclohexan) in solution was studied in dependence of temperature. Volumetry and differential-scanning-calorimetry (DSC) were used to determine decomposition rates; first order kinetics was found in all cases.

     

2-Spiroanellated 1,3-Benzodioxoles from the Reaction of 2,3-Dihydro-1 H-pyrrol-3-ones with Tetrachloro-1,2-benzoquinone

Novel spiro[1,3-benzodioxole-2,2-(2,3-dihydro-1H-pyrrol-3-ones)] were obtained from 2-aminomethylene-2,3-dihydropyrrol-3(1H)-ones and tetrachloro-1,2-benzoquinone in ethanol at room temperature. However, in addition, 3,4-dichloro-7-methoxy-5-(4-methoxyphenyl)-5,10-dihydrophenazine-1,2-dione was formed in the reaction of 1-(4-methoxyphenyl)-2-(4-methoxyphenylaminomethylene)-4,5-diphenyl-1,2-dihydropyrrol-3-one with tetrachloro-1,2-benzoquinone.     

Bisindoles. 26. Synthesis of 7,7-dichlorobis (5-indolyl) methane

7,7-Dichloro-2,2-dicarbethoxybis (5-indolyl) methane has been synthesized by cyclization of the 3,3-dichloro-4,4-diphenylmethanedihydrazone of ethyl pyruvate. Subsequent hydrolysis and decarboxylation of the corresponding diacid gave the unsubstituted 7,7-dichlorobis (5-indolyl) methane. The syn-syn, syn-anti, and anti-anti forms of 3,3-dichloro-4,4-diphenylmethanedihydrazone of ethyl pyruvate have been separated and characterized.For Communication 25, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1062–1065, August, 1988.     

ω,ω′-imino dicarboxylic acids and some of their derivatives

Summary Starting from the corresponding-chloro carboxylic acids we prepared, -imino dicarboxylic acids and their N- and O- derivatives; the products had the following structures:     

Synthesen in der Pyridazin-Reihe, 31. Mitt.: Über einige neue polycyclische Azolo- und Azinopyridazine

Zusammenfassung Synthesen von verschiedenen neuen polyazaheterocyclischen Systemen, wie 11H-Imidazo[1,22,3]pyridazino[6,1-b]-chinazolin-11-on (3), 11H-s-Triazolo[4,32,3]pyridazino[6,1-b]chinazolin-11-on (4), der Isomeren 4H-Pyrido[2,34,5]-pyridazino[6,1-c]-as-triazin (6) und 4H-Pyrido[3,24,5]-pyridazino[6,1-c]-as-triazin (9), Pyrido[3,24,5]pyridazino[1,6-b]benzimidazol (14) sowie Pyrido[3,24,5]-s-triazolo[4,32,3]pyridazino[1,6-a]benzimidazol (15) werden beschrieben.

---

Syntheses of pyridazines, XXXI: Some new polycyclic azolo and azino-pyridazines

Syntheses of several new polyazaheterocyclic systems are described, i.e. 11H-Imidazo[1,22,3]pyridazino[6,1-b]quinazolin-11-one (3), 11H-s-Triazolo[4,32,3]pyridazino[6,1-b]quinazolin-11-one (4), the isomeric 4H-Pyrido[2,34,5]pyridazino[6,1-c]-as-triazine (6) and 4H-Pyrido[3,24,5]pyridazino[6,1-c]-as-triazine (9), Pyrido[3,24,5]pyridazino[1,6-b]-benzimidazole (14) and Pyrido[3,24,5]-s-triazolo[4,32,3]pyridazino[1,6-a]benzimidazole (15).

---

---

Heterocyclen, 69. Mitt.     

Investigations of 2,3′-biquinolyl. 7. Thiolation of 1-alkyl-3-(2-quinolyl)quinolinium halides

Thiolation of 1-alkyl-3-(2-quinolyl)quinolinium halides by a mixture of sulfur with KOH in DMF leads to formation of 1-alkyl-1,4-dihydro-2,3-biquinolyl-4-thiones, rearrangement of which in boiling ethylene glycol makes it possible to obtain 4-alkylthio-2,3-biquinolyls.     

Fluorescence enhancement method for measuring anionic surfactants with a hydrophobic cyanine dye

A novel fluorimetric method based on use of a hydrophobic cationic cyanine dye has been developed for determination of the anionic surfactant sodium dodecylbenzenesulfonate (DBS). The method is based on the enhancement effect of DBS on the fluorescence of the hydrophobic cyanine dye 2-[-4-chloro-7-(1-ethyl-3,3-dimethylindolin-2-ylidene)-3,5-(propane-1,3-diyl)-1,3,5-heptatrien-1-yl]-1-ethyl-3,3-dimethyl-3H-indolium iodide. Under the optimum conditions the extent of fluorescence enhancement is proportional to the concentration of DBS in the range 0.05–5.0 mg L^–1; the detection limit is 0.014mg L^–1. The relative standard deviation for 0.35 mg L^–1 DBS was 1.1% (n=10). The proposed method, which avoided use of toxic solvents and tedious solvent-extraction, and was applied to the determination of DBS in natural water with recoveries between 99.9 and 107%. Preliminary research shows that the fluorescence enhancement is due to the formation of a dye aggregate facilitated by DBS.     

?-Methyl-2-amino-2,3-didesoxyribofuranoside, a Novel Building Block for Backbone Modified Antisense Oligonucleotides

A synthesis of the amino sugar 2-amino-2,3-didesoxyribose is described. Starting from D-glucosamine, -methylfuranoside was obtained in eight steps in 20% yield. This carbohydrate is a novel building block for nucleosides and for backbone modified antisense oligonucleotides with 2–5 amide linkages.     

Cobalt(II) and nickel(II) chloride and bromide complexes of 2-(2′-methyl-8′-quinolyl)benzoxazole and 2-(2′ or 4′-methyl 8′-quinolyl)benzimidazole

Summary Cobalt(II) and nickel(II) halide complexes of the ligands 2-(2-methyl-8-quinolyl)benzoxazole (mqbo), 2-(2-methyl8quinolyl)benzimidazole (mqbi) and 2-(4-methyl-8-quinolyl)benzimidazole (mqbi) were synthesized and characterized by analytical, thermogravimetric, conductivity and magnetic data, and i.r. and electronic spectra.The ligands are bidentate N-donors yielding complexes where the coordination geometry depends on the metal ion and steric hindrance. All the cobalt complexes have formula [CoL₂X₂] and distorted tetrahedral geometry. Different types of nickel compounds were obtained: i) complexes of formula NiLX₂ · n H₂O (or EtOH) (L = mqbo or mqbi; n=0–1.5) which arepseudo-tetrahedral or five-coordinate and ii) complexes NiL₂X₂ · n H₂O (L = mqbi, n=3 or 4) where the metal is bound to four nitrogen atoms and the overall coordination geometry is tetragonal. The structural changes occurring after removal of water or alcohol from the complexes are also reported.     

Über das Tetrahydrospiro [cyclohexan-1,2′(1′H)-chinazolin]-4′(3′H)-on

Zusammenfassung Das beim Erhitzen von Cyclohexanon und Harnstoff entstehende Produkt ist nicht als Cyclohexyliden-2-carbamylcyclohex-1-enylamin, sondern als 5, 6, 7, 8-Tetrahydrospiro-[cyclohexan-1,2(1H)-chinazolin]-4(3H)-on zu formulieren¹. Analog gebaute Verbindungen bilden sich aus Cyclopentanon bzw. Cycloheptanon und Harnstoff. Die genannten Kondensate sind als cyclische -Carbamylenamine aufzufassen; charakteristisch sind die Reaktivität der zur NH-Gruppe/1, in peri-Stellung befindlichen CH₂-Gruppe bzw. der Kernstelle 4a.

---

-Carbamoyl enamines: 5. 6. 7. 8-Yetrahydrospiro [cyclohexane-1,2 (1H)-quinazoline]-4 (3H)-one. (Heterocycles, XXIII)

The product obtained by heating cyclohexanone with urea has been found to be 5. 6. 7. 8-tetrahydrospiro[cyclohexane-1.2(1H)-quinazoline]-4(3H)-one, not cyclohexylidene-2-carbamoylcyclohex-1-enylamine, as was previously assumed¹. Compounds with analogous structures were formed by heating cyclopentanone or cycloheptanone with urea. Characteristic features of this class of compounds, i.e. -carbamoyl enamines, are the enhanced reactivities of the nuclear 4 a-position and of the methylene group in the peri-position to NH-1.

     

Transformation of batridene

Transformations of 1,1,6,6,7,7-hexahydroxy-3,3-dimethyl-5,5-diisopropyl-2,2-dinaphthylidene-8,8-dibarbituric acid (batridene) in DMSO are studied.     

Synthesis of 3′, 4′-dihydronaphth-1′, 2′ ∶ 5, 4-oxazole and its 2-aryl derivatives

From 2-amino-1-keto-1, 2, 3, 4-tetrahydronaphthalene, prepared by reduction of isonitroso--tetralone, a number of N-acyl derivatives are prepared, and these are converted further to 2-substituted 3, 4-dihydronaphth-1, 25, 4-oxazoles,     

Polarographic determination of some carcinogenic aminoazobenzenes

Summary The polarographic procedure can be used for the quantitative analysis of all the aminoazobenzenes tested in this study as indicated by proportionality between diffusion current and concentration. There is no significant correlation between the half-wave potential and carcinogenic potency for rat liver for three monosubstituted and seven disubstituted derivatives ofp-dimethylaminoazobenzene. These ring-substituted azocarcinogens rank from weak to very strong for carcinogenic potency against rat liver. Also aminoazobenzenes such as the noncarcinogenic 4-amino-4-dimethylaminoazobenzene and the carcinogenic N,N-dimethyl-4-amino-N-formyl-N-methyl-4-aminoazobenzene and N,N-dimethyl-4-amino-N-acetyl-N-methyl-4-aminobenzene have similar have-wave potentials. On the other hand, the noncarcinogenic 4-aminoazobenzene, 4-amino-N-methyl-4-aminoazobenzene and N-methyl-4-amino-N-methyl-4-aminoazobenzene have half-wave potentials that are about 100 mv more negative than that of all other aminoazobenzenes discussed in this report.

---

Zusammenfassung Die Proportionalität zwischen Konzentration und Stromdurchfluß bietet die Grundlage zur polarographischen Bestimmung aller in dieser Arbeit geprüften Aminoazobenzole. Zwischen dem Halbwellenpotential und der carcinogenen Wirkung gegenüber Rattenleber besteht bei drei monosubstituierten und sieben disubstituierten Derivaten desp-Dimethylaminoazobenzols keine signifikante Korrelation. Diese ringsubstituierten Azocarcinogene zweigen schwache bis sehr starke carcinogene Wirkung gegenüber Rattenleber. Aminoazobenzole wie das nicht-carcinogene 4-Amino-4-dimethylaminoazobenzol und die carcinogenen Verbindungen N,N-Dimethyl-4-amino-N-formyl-N-methyl-4-aminoazobenzol und N,N-Dimethyl-4-amino-N-acetyl-N-methyl-4-aminoazobenzol haben ähnliche Halbwellenpotentiale. Andrerseits ist das Halbwellenpotential der nicht-carcinogenen Verbindungen 4-Aminoazobenzol, 4-Amino-N-methyl-4-aminoazobenzol und N-Methyl-4-amino-N-methyl-4-aminoazobenzol ungefähr um 100 mV negativer als das aller anderen hier behandelten Aminoazobenzole.

     

Investigations in the field of oxygen-containing heterocycles

In the presence of stannic chloride, 2,3-dichlorotetrahydrofuran adds to isoprene with the formation of 3-chloro-2-(4-chloro-2-methylbut-2-enyl)tetrahydrofuran and to piperylene and bivinyl with the formation, predominantly, of 3-chloro-2-(4-chloropent-2-enyl)- and 3-chloro-2-(4-chlorobut-2-enyl)tetrahydrofuran, respectively, with their allyl isomers. The amount of the latter was estimated from the NMR spectra at 20–30%.For part VII, see [1].     

Nitration,amination, and halogenation of Di-O-methylphloracetophenone

Chlorination of the title compound gave 5- and 3-chloro-2-hydroxy-4,6-dimethoxyacetophenone. The nitration of its acetate, followed successively by reduction, diazotization, and reaction with cuprous chloride, gave the 3-substituted series, 2-acetoxy-4,6-dimethoxy-3-nitroacetophenone, 3-amino-2-hydroxy-4,6-dimethoxyacetophenone, and 3-chloro-2-hydroxy-4,6-methoxyacetophenone, respectively. The orientation of substituents in the products was proved. The amino and chloro members of the isomeric 5-substituted series were availablevia 2-hydroxy-4,6-dimethoxy-5-phenylazoacetophenone, the product of the reaction of the title compound with benzenediazonium chloride.

---

Nitrierung, Aminierung und Halogenierung von Di-O-methylphloracetophenon

Zusammenfassung Chlorierung der Titelverbindung gab 5- und 3-Chlor-2-hydroxy-4,6-dimethoxyacetophenon. Die Nitrierung des Acetats, gefolgt von Reduktion, Diazotierung und Reaktion mit CuCl ergab die 3-substituierte Reihe: 2-Acetoxy-4,6-dimethoxy-3-nitroacetophenon, 3-Amino-2-hydroxy-4,6-dimethoxyacetophenon und 3-Chlor-2-hydroxy-4,6-dimethoxyacetophenon. Die Orientierung der Substituenten wird diskutiert. Die Amino- und Chlorderivate der isomeren 5-substituierten Reihe sind über 2-Hydroxy-4,6-dimethoxy-5-phenylacetophenon zugängig, dem Produkt der Reaktion der Titelverbindung mit Phenyldiazoniumchlorid.