Adsorptive/Extractive Stripping Voltammetry of 1,2,3,4-Tetrahydrocarbazole

Abstract

Adsorptive/extractive accumulation of 1,2,3,4-tetrahydrocarbazole at a carbon paste electrode is used to improve the subsequent voltammetric measurement with respect to sensitivity and selectivity. By simply immersing the electrode in the 1,2,3,4-tetrahydrocarbazole solution for a given period of time, and then transferring it to a blank solution, high degree of selectivity is achieved. After 10 min preconcentration, a detection limit near 1.4×10^-8M 1,2,3,4-tetrahydrocarbazole is obtained. Cyclic voltammetry is used to aid understanding the nature of the accumulation process. Applicability to measurements of other indole alkaloids and to analysis of urine samples is illustrated.     

The synthesis of propellance compounds from 2,3-disubsituted indoles and o-benzoquinones

The reaction of 2,3-dihydro-1H-cyclopent[b]indole 3 and 1,2,3,4-tetrahydrocarbazole 4 with substituted o-benzoquinones yielded [4.3.3]- and [4.4.3]propellanes, respectively. The physical and chemical properties of the propellane compounds were investigated and a mechanism for the formation of the propellane compounds was discussed.     

Die massenspektrometrische Retro-Diels-Alder-Reaktion: 1,2,3,4-Tetrahydrocarbazol. 30. Mitteilung über massenspektrometrische Untersuchungen

The mass spectral retro Diels-Alder-reaction: 1,2,3,4-tetrahydrocarbazole 1,2,3,4-Tetrahydrocarbazole undergoes a retro Diels-Alder-reaction under electron impact. C(2) and C(3) are eliminated as ethylene. This is shown by measuring the deuterated derivatives 1a , 1b and 1c . Furthermore the oxo-1,2,3,4-tetrahydrocarbazole derivatives 3 and 4 are investigated in respect to the mass spectral retro Diels-Alder reaction too.     

Partially flourinated heterocyclic compounds. Part 19 [1]. The formation of fischer indole products from a series of hydrozones derived from pentaflourophenylhydrazine and 1,3,4,5,6,7,8-heptaflouro-2-naphthylhydrazine. The surprising loss of o-flourine

The pentafluorophenyl and 1,3,4,5,6,7,8-heptafluoro-2-naphthylhydrazones of a variety of aldehydes and ketones give 4,5,6,7-tetrafluoroindole and 4,5,6,7,8,9-hexafluorobenz[e]indole derivatives when heated under reflux in tetralin. These products are typical Fischer indole products — yet the substrates all have fluorine atoms in positions $\text{ortho}$ to the nitrogen rather than hydrogen which is a pre-requisite in the conventional reaction. Acetaldehyde (10) and cyclohexanone(11) pentafluorophenylhydrazones give 4,5,6,7-tetrafluoroindole(8) (1.5%) and 5,6,7,8-tetrafluoro-1,2,3,4-tetrahydrocarbazole(9) (18%) respectively. 4-Methylacetophenone- (12) , propiophenone- (13) , 1,2-diphenylethanone- (14), acetone-(15) and phenylacetaldehyde-1,3,4,5,6,7,8-heptafluoro-2-naphthylhydrazones give 4,5,6,7,8,9-hexafluoro-2-(4-methylphenyl)- (16)(41%), -2-phenyl-3-methyl-(17) (34%), -2,3-diphenyl-(18) (42%), -2-methyl-(19) (20%), and-3-phenyl-(20) (24%) -benz[e]indoles respectively.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-Tosylates of 4-Methoxy-1,2,3,4-tetrahydrocarbazole and 2-(6-Methoxy-1-cycloalken-1-yl)anilines

The reaction of N-tosylates of 2-(1-cycloalken-1-yl)anilines and 2,3,9a,9-tetrahydro-1H-carbazole with methanol in the presence of CuBr₂ proceeds with high regioselectivity leading to the corresponding tosylates of 2-(6-methoxy-1-cycloalken-1-yl)anilines and 4-methoxy-1,2,3,4-tetrahydrocarbazole. The latter as well as N-mesyl-1,2,3,4-tetrahydrocarbazole showed moderate cytotoxic activity with respect to HEK293 cell line.     

Dehydrogenation of 1,2,3,4-tetrahydroquinoline and its related compounds: comparison of Pd/C-ethylene system and activated carbon-O2 system

Dehydrogenation of substituted 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, and 1,2,3,4-tetrahydrocarbazole proceeded using Pd/C-ethylene system (method A) or activated carbon-O₂ system (method B) to give the corresponding heteroaromatic compounds.     

Synthesis of heterocycles on the basis of iminotetrahydrocarbazoles. 1. 3-Benzyl-8-methyl-2-oxo-2,3,3a,4,5,6-hexahydro-1H-pyrazino[3,2,1-j,k]-carbazole

The reaction of 6-methyl-1-oxo-1,2,3,4-tetrahydrocarbazole and benzylamine gave 1-benzylimino-6-methyl-1,2,3,4-tetrahydrocarbazole, which was converted by two methods to a pyrazinocarbazole derivative. The promising character of the use of iminotetrahydrocarbazoles for the synthesis of more complex heterocyclic systems was thereby demonstrated.Translated from Khimiya Geterosiklicheskikh Soedinenii, No. 12, pp. 1632–1635, December, 1987.The authors thank L. M. Alekseeva for investigating the PMR spectra and N. M. Rubtsov and V. V. Chistyakov for investigating the IR and mass spectra.     

Synthesis of heterocycles from 1,5-diketones. 3. Alicyclic 1,5-diketones in reaction with phenylhydrazine

8-R-7aH-5,6,7,8,9,10,11,12-Octahydroindolo[3.2.1-d,e]acridines, 1,2,3,4-tetra-hydrocarbazole, 9-R-sym-octahydroacridines, and 9-R,10-phenyl-sym-octahydroacridinium salts are formed by the action of phenyl-hydrazine on alkylidene-2,2-dicyclohexanone or the corresponding 8-R-tricyclo(7.3.1.0^2,7)tridecan-2-ol-13-ones in an acid medium. Postulations were made for the paths of formation of these compounds.2,2-Dimethyl-3-oxa-4a-(2,2-dimethyltetrahydropyran-4-on-5yl-methyl)-4aH-1, 2,3,4-tetrahydrocarbazole, 3,3,14,14-tetramethyl-2-oxa-5a,10b-(methanoxyisobutane)-1,2,3,4,5a,10b,11,11a-octahydroquinindoline, 2,2-dimethyl-3-oxa-1,2,3,4-tetrahydrocarbazole and 3,3,6,6-tetramethyl-2,7-dioxa-sym-octahydroacridine were obtained by the reaction of methylene-3,3-di(6,6-dimethyltetrahydropyran-4-one) with phenylhydrazine in acetic acid. The quinindoline structure was confirmed by the synthesis of this compound from 2,2-dimethyl-3-oxa-4a-(2,2-dimethyl-tetrahydropyran-4-on-5-ylmethyl)-4aH-1,2,3,4-tetrahydrocarbazole by the action of ammonia.For article 2, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 46–52, January, 1986.     

Synthesis of novel 3‐ and 5‐substituted indole‐2‐carboxamides

The preparation of several novel 3,5‐substituted‐indole‐2‐carboxamides is described. A 5‐nitro‐indole‐2‐carboxylate was elaborated to the 3‐benzhydryl ester, N‐substituted ester, and carboxylic acid intermedi ates, followed by conversion to the amide and then reduction of the 5‐nitro group to the amine. Indole‐2‐carboxamides with 3‐benzyl and 3‐phenyl substituents were prepared in four steps from either a 3‐bromo indole ester using the Suzuki reaction or from a 3‐keto substituted indole ester. N‐Alkylation of ethyl indole‐2‐carboxylate, followed by amidation and catalytic addition of 9‐hydroxyxanthene gave a 3‐xanthyl‐indole‐2‐carboxamide analog and a spiropyrrolo indole as a side product.     

Regio‐ and Chemoselective N‐1 Acylation of Indoles: Pd‐Catalyzed Domino Cyclization to Afford 1,2‐Fused Tricyclic Indole Scaffolds

A concise method for the synthesis of 1,2‐fused tricyclic indole scaffolds by domino cyclization involving a Pd‐catalyzed Sonogashira coupling, indole cyclization, regio‐ and chemoselective N‐1 acylation, and 1,4‐Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2‐a]indole and hexahydro[1,5]diazocino[1,2‐a]indole scaffolds.     

Synthesis and properties of [1,4]diazepino[6,5-b]indoles

1-Aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxides were synthesized based on 3-(N"-aryl-N"-chloroacetyl)amino-2-formylindoles. Deoxidation of 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxide afforded 1,2,3,6-tetrahydro- and 1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole derivatives. A new approach to the synthesis of pyrido[3,2-b]indole and pyrimido[5,4-b]indole derivatives was developed.     

Anodic hydroxylation of 1-carbomethoxy-1,2,3,4-tetrahydrocarbazoles

1-Carbomethoxy-1,2,3,4-tetrahydrocarbazole (1) and its 7-methoxy derivative (2) were oxidized at carbon felt anodes in acetonitrile containing 0.2 M LiClO₄ and 2-17 M water at potentials on the rising portion of the primary oxidation peak to yield products formed by formal substitution of the C-1 H atom with hydroxide. The resulting 1-hydroxy-l-carbomethoxy-1,2,3,4-tetrahydrocarbazole and its 7-methoxy derivative were isolated in 44 and 22% yields, respectively, when sodium bicarbonate was used to control acidity of the medium. Structures were elucidated by NMR, IR, elemental analysis, and mass spectrometry. Voltammetry at carbon-paste and glassy carbon electrodes showed that the oxidations proceed by an ECE or DISPI pathway. The rate-determining step is the reaction of water with a cation radical electrochemically generated from 1 or 2, involving either proton abstraction or nucleophilic addition.     

Cyclization of 2- and 3-indolythioalkanoic acids to novel indole-containing tricyclic ring systems

A series of 2- and 3-indolylthioalkanoic acids of various chain lengths were cyclized under dehydrative conditions affording tricyclic indole-containing ring systems wherein the third ring contains a sulfur atom attached to the 2- or 3-position of the indole ring. This methodology affords entry into the novel thiepino[3,2-b]indole, thiocino[2,3-b]indole and thiocino[3,2-b]indole ring systems.     

Synthetic studies on indoles and related compounds. XXXI. Chemical confirmation of the synthetic route for the benz[f]indole skeleton and its application

To confirm the structure of ethyl 9-methoxybenz[f]indole ( 8a ) prepared from ethyl pyrrole-2-carboxylate ( 4 ) via a new synthetic route, the following chemical correlation work was performed. Ethyl 9-methoxybenz[f]in-dole ( 8a ) was converted to 1-benzyl-3-methyl-5,6,7,8-tetrahydrobenz[f]indole ( 25 ), which was alternatively and authentically synthesized from ethyl 3-methylpyrrole-2-carboxylate ( 11 ). On the basis of the established route to the benz[f]indole nucleus, two representative benz[f]indoles, benz[f]indole ( 1 ) and 4,9-dioxobenz[f]indole ( 26 ) were synthesized.     

The reaction of N-Acylpyridinium salts with indole

Depending on the solvent used and the ratio of the reactants, N-acylpyridinium salts condense with indole to give 3-(N-acyl-1,4-dihydro-4-pyridyl)indole ( 1 ) or 4-(N-acyl-3-indolyl)pyridinium chloride ( 3 ). Compound 1 is an intermediate in the formation of compound 3 . The reaction mechanism has been studied, and a hydrogen transfer reaction is suggested as a key step. Alkaline hydrolysis, e.g., of 4-(N-acetyl-3-indolyl)pyridinium chloride ( 3a ), gave 3-(4-pyridyl)indole ( 2a ). The reaction of α-chlorosubstituted acyl halides with indole, in the presence of pyridine constitutes a convenient synthesis of 3-chloroacylindoles.     

Thermodynamics and kinetics of indole oligomerization: Preliminary results in aqueous sulfuric acid

Reaction rates and equilibrium constants of indole dimerization and trimerization in aqueous sulfuric acid at 298 K are reported. The equilibrium of oligomerization is attained in about 4–5 h, and formation of oligomers with more than three monomeric unit is not observed. The equilibrium of formation of the indole dimer is influenced by the protonation equilibrium of indole, which means the pK_IH values of indole strongly influences equilibria and kinetics of the whole process. In the evaluation of the kinetic constants, the pK_IH values of indole have been taken into account; in this way, the kinetic constant of formation of the dimer (k_D) results almost four order of magnitude larger than that of the trimer (k_T), suggesting a higher electrophilicity of the 3H‐indolium cations with respect to the protonated dimer (which is an aliphatic ammonium salt). Further indole addition to the trimer, which is a protonated 2‐alkyl‐aniline, does not occur, since the anilinium ion is ineffective as an electrophile. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 107–112, 2009     

Targeted quantitative analysis of monoterpenoid indole alkaloids in Alstonia scholaris by ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry

Monoterpene indole alkaloids exhibit structural diversity in herbal resources and have been developed as promising drugs owing to their significant biological activities. Confidential identification and quantification of monoterpene indole alkaloids is the key to quality control of target plants in industrial production but has rarely been reported. In this study, quantitative performance of three data acquisition modes of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry including full scan, auto-MS² and target-MS², was evaluated and compared for specificity, sensitivity, linearity, precision, accuracy, and matrix effect using five monoterpene indole alkaloids (scholaricine, 19-epi-scholaricine, vallesamine, picrinine, and picralinal). Method validations indicated that target-MS² mode showed predominant performance for simultaneous annotation and quantification of analytes, and was then applied to determine monoterpene indole alkaloids in Alstonia scholaris (leaves, barks) after extraction procedures optimization using Box-Behnken design of response surface methodology. The variations of A. scholaris monoterpene indole alkaloids in different plant parts, harvest periods, and post-handling processes, were subsequently investigated. The results indicated that target-MS² mode could improve the quantitative capability of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for structure-complex monoterpene indole alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, quadrupole time of flight mass spectrometry, qualitative and quantitative analysis, ultra-high-performance liquid chromatography     

The Effect of Bacterial Signal Indole on the Electrical Properties of Lipid Membranes

Indole is an important biological signalling molecule produced by many Gram positive and Gram negative bacterial species, including Escherichia coli. Here we study the effect of indole on the electrical properties of lipid membranes. Using electrophysiology, we show that two indole molecules act cooperatively to transport charge across the hydrophobic core of the lipid membrane. To enhance charge transport, induced by indole across the lipid membrane, we use an indole derivative, 4 fluoro‐indole. We demonstrate parallels between charge transport through artificial lipid membranes and the function of complex eukaryotic membrane systems by showing that physiological indole concentrations increase the rate of mitochondrial oxygen consumption. Our data provide a biophysical explanation for how indole may link the metabolism of bacterial and eukaryotic cells.     

Indole and quinoline derivatives of 2,3-dihydro-l-benzothiepin-4(5H) one

By application of the Friedlander synthesis on 2,3-dihydro-l-benzothiepin-4(5H) one (4), the corresponding [4,5-b]quinoline derivatives 5a and 5b were obtained. Starting from the ketone (4) and by application of the Fischer indole synthesis, 1-benzolhiepino[4,5-b ]indole (6) and 1-benzothiepino[4,5-b]benzo[g]indole (7) were obtained. When β-naphthylhydrazine was used in the indolisation reaction, a mixture of 1-benzothiepino[4,5-b]benzo[e]indole ( 8 ) and 1-benzothiepino[4,3-b]benzo[e] indole (9) was obtained.     

Synthesis of novel 1-phenyl-1H-indole-2-carboxylic acids. II. Preparation of 3-dialkylamino, 3-alkylthio, 3-alkylsulfinyl,and 3-alkylsulfonyl derivatives

The synthesis of novel indole-2-carboxylic acids with amino- and sulfur-containing substituents in the indole 3-position is described. An Ullmann reaction with bromobenzene converted 1H-indoles with 3-(acetylamino)- and 3-(diethylamino)-substituents into 1-phenyl-1H-indoles. Reaction of 3-unsubstituted indoles with thionyl chloride provided indole 3-sulfinyl chlorides, which reacted with alkyl and aryl Grignard reagents to form the corresponding sulfoxides. The indole sulfoxides thus obtained were reduced to sulfides or oxidized to sulfones.