Synthèse de dérivés O-substitués du (dihydroxy-3′,4′ phényl)-2 indole par utilisation de groupes protecteurs sulfonylés

O-Substituted derivatives of 2-(3,4-dihydroxyphenyl)indole have been synthesized from acetovanillone by various methods using hydroxyl protective groups such as benzene sulfonyl and methylsulfonyl. Thus these groups facilitate Fischer and Bischler indole synthesis. Moreover, selective O-demethylation and O-alkylation reactions are allowed. Finally, the already quoted protective groups may be easily removed to yield back the 2-(4-hydroxy-3-alkyloxyphenyl)indoles.     

Synthèse de nouveaux hétérocyeles indoliques

In this work we present a new aproch for the synthesis of tri aned tetracyclic heterocycles in the indole series.     

Synthèses d'hétérocycles indoliques à partir de dérivés carbonylés de l'indole et du pyrrole

The reactions of ethyl azidoacetate with 1-methylindole-2-3-dicarboxaldehyde (1) and its monoacetal 2 afforded β and γ carbolines. The regioselectivity of condensation of ethy6l aminoacetate with 1 was investigated and yields a γ-carboline. Derivatives of a new heterocycle, the thiepino[4,5-b]indole and its application of the synthesis of some carbazoles are described.     

Cycloadditions dipolaires-1,3 II. Addition des diarylnitrilimines au N-methyl-indole. Etude expérimentale et essai d'interprétation

The reactivity of N-methylindole towards diarylnitrilimines has been studies. The cycloadducts are 8-methyl-3a,8a-dihydro-pyrazolo[3,4-b] indole derivatives. The structure reported was assigned on the bases of satisfactory analytical, spectroscopic and chemical data. An interpretation based on the second order perturbation method of frontier orbitals is in agreement with the observed regiospecificity.     

Facile synthesis of 6‐aryl‐5H‐8‐oxa‐4b, 7‐diaza‐benzo[a]azulen‐9‐one derivatives,new tricyclic heterocycles

8‐Oxa‐4b,7‐diaza‐benzo[a]azulene‐9‐one system, a new tricyclic heterocyclic framework is designed through a simple and convenient synthetic sequence. Its 6‐aryl derivatives are synthesized starting from ethyl indole‐2‐carboxylate. Reaction of differently substituted phenacyl bromides with ethyl indole‐2‐carboxylate, treatment of the resultant N‐substituted indole‐2‐carboxylates with hydroxylamine hydrochloride to provide corresponding oximes, subsequent ester hydrolysis followed by dehydrative cyclisation furnished the desired compounds 5 a‐g .     

Azaindoles. V. Pyrido(4,3-b]indoles (γ-carbolines) fonctionnalisés sur leur sommet 4: Synthèse en une seule étape

In boiling diphenylether phenylhydrazine reacts with 1,2-dihydro-2-oxo-4-hydroxypyridines to give 3,4-dihydro-4-oxo(9H)-pyrido[4,3-b]indoles (γ-carbolines) in one step. Nucleophilic displacement of their 4-chloro derivatives by secondary amines affords both 3,4-disubstituted γ-carbolines and chlorination of 2,3-dimethyl-4-oxo(9H)pyrido[4,3-b]indoles, as well as methylation of 2-methyl-4-chloro-(9H)pyrido[4,3-b]indole leads to derivatives in the (3H)4-substituted pyrido[4,3-b] indole series.     

Réarrangements en milieu acide trifluoroacétique de deux alcaloïdes indoliques: la desformocorymine et la dihydrocorymine

The rearrangement in trifluoroacetic acid of two indole alkaloids of the echitamine series, desformocorymine (14) and dihydrocorymine (9) , has been investigated. Desformocorymine (14) was tranformed into a mixture of carbinolamines 17a , b , with the akuammiline skeleton, which were reduced (Et₃SiH, CF₃CO₂H) into an isomer 12 of cathafoline (6). This sequence constitutes the first example of an interconversion of the corymine skeleton into the akuammiline skeleton (Scheme 2). In the case of dihydrocorymine (9) , the rearrangement followed a different pathway owing to the formation of a hemiacetal between the primary alcohol CH₂(17)-OH and a carbonyl formed at C(3). Treatment of this hemiacetal 26 with aqueous base led to its opening with concomitant formation of a lactam. ¹³C-NMR seems to indicate that this lactam exists under a hydrated form 27. This highly unstable intermediate was cleanly transformed (MeONa-MeOH) into a 2-acyl indole 30 (Scheme 4), the structure of which was determined by X-ray crystallography. The formation of this acylindole involves the rupture of the C(7)? C(16) bond; it is the reverse of the reaction generally postulated as occurring in the biogenesis of the pentacyclic alkaloids. The structure of a by-product 34 was established as 17-hydroxymethylvincoridine by X-ray crystallography. The acid-catalyzed rearrangements involve the rupture of the Ph-N? C? N chromophore, with formation of a carbonyl at C(3). The reversibility of these steps is used in an easy correlation of dihydrocorymine and of 3-epidihydrocorymine via their trifluoroacetates.     

Synthesis of Some New Spiro,Isolated and Fused Heterocycles Based on 1H‐indole‐2‐One

The reaction of 3‐benzoylcyanomethylidine‐1(H)‐indole‐2‐one ( 1 ) with a variety of active methylene compounds, thioglycolic acid, glycine, hydrazine hydrate and phenyl hydrazine led to the formation of compounds 4a‐d‐10 . 3‐Thiosemicarbazide‐1(H)‐indole‐2‐one 2 on reaction with α‐halocarbonyl compounds gave compounds 11a‐c, 12a‐c . The latter compounds on heating with phosphoryl chloride, cyclization takes place via losing water to give the angular tetracyclic compounds 13a,b and 14a‐c . Cyanoacetic hydrazone derivative 3 readily cyclized upon heating in triethyl orthoformate to give the tricyclic system, oxopyridazino indole 15 . On the other hand, the reaction of 3 with benzylidine malononitrile and benzylidene ethylcyanoactate gave the pyranyl hydrazone derivatives 16a,b .     

Spectres photoélectroniques He(I) et He(II) du benzo[b]sélénophène et du benzo[b]tellurophène

He(I) and He(II) photoelectron spectra of benzo[b]selenophene and benzo[b]tellurophene The photoelectron spectra of benzo[b]selenophene ( 2 ) and benzo[b]tellurophene ( 1 ) have been recorded with He(I) and He(II) radiation and been compared to those of benzo[b]thiophene ( 3 ), benzo[b]furan ( 4 ), indole ( 5 ) and indene ( 6 ). The first four bands are correlated with π-orbitals, of which the highest occupied one is strongly localized on the heteroatom in the case of 1 . The results are in agreement with semi-empirical PPP-calculations.     

UPLC‐HR‐MS/MS‐based determination study on the metabolism of four synthetic cannabinoids,ADB‐FUBICA,AB‐FUBICA,AB‐BICA and ADB‐BICA,by human liver microsomes

Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and have gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB‐FUBICA [N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐1‐(4‐fluorobenzyl)‐1H–indole‐3‐carboxamide], AB‐FUBICA [N‐(1‐amino‐3‐methyl‐1‐oxobutan‐2‐yl)‐1‐(4‐fluorobenzyl)‐1H–indole‐3‐carboxamide], AB‐BICA [N‐(1‐amino‐3‐methyl‐1‐oxobutan‐2‐yl)‐1‐benzyl‐1H‐indole‐3‐carboxamide] and ADB‐BICA [N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐1‐benzyl‐1H‐indole‐3‐carboxamide] were detected in China recently, but unfortunately no information about their in vitro human metabolism is available. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by ultra‐performance liquid chromatography–high resolution–tandem mass spectrometry. Metabolites generated by N‐dealkylation and hydroxylation on the 1‐amino‐alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N‐dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake.     

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.     

Réactions de Transposition Ionique et de Rétrocycloaddition de Dihydro-3a, 8a Pyrazolo (3,4-b) Indoles Sous l'Impact Electronique

Three isomeric compounds, one having a 3a,8a-dihydropyrazolo (3,4-b) indole, the second an aryl-indolyl-ketone-hydrazone and the third a 1,3,4-triarylpyrazole structure give the same mass spectrum, which results from the superposition of the corresponding spectra of the first two compounds, which equilibrate after ionization. The 3a,8a-dihydropyrazolo (4,3-b)indoles proceeding from the second method of cycloaddition, also have the same fragmentation pathway. This makes a determination of the structure of the compounds formed by the cycloaddition reaction impossible by mass spectrometry.     

1,3‐Dichloro‐tetra‐n‐butyl‐distannoxane: a new application for catalyzing the direct substitution of 9H‐xanthen‐9‐ol at room temperature

1,3‐Dichloro‐tetra‐n‐butyl‐distannoxane was firstly used to catalyze the direct substitution of 9H‐xanthen‐9‐ol with indoles at room temperature to afford a class of 3‐(9H‐xanthen‐9‐yl)‐1H‐indole derivatives in good to excellent isolating yield. Moreover, other nucleophiles (such as diketone and pyrrole) could also proceed smoothly in this methodology. Copyright © 2012 John Wiley & Sons, Ltd.     

N‐Methyl‐N‐(1‐phenyl­sulfonyl­indol‐2‐ylmethyl)­aniline

In the title compound, 2‐[(methylphenylamino)methyl]‐1‐(phenylsulfonyl)indole, C₂₂H₂₀N₂O₂S, the indole system is not strictly planar and the dihedral angle between the fused rings is 2.7 (1)°. The angles around the S atom of the sulfonyl substituent deviate significantly from the ideal value for tetrahedral geometry. The pyramidalization at the indole N atom is very small. Of the two C—H?O interactions, one influences the orientation of indole with respect to the sulfonyl group and the other determines the orientation of the phenyl bound to sulfonyl. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 89.6 (1)° with the best plane of the indole. The molecular packing is stabilized by C—H?π and C—H?O hydrogen bonds.     

(Z)‐2‐(1‐Benzyl‐5‐nitro‐1H‐indol‐3‐ylmethyl­ene)‐1‐aza­bicyclo­[2.2.2]octan‐3‐one

In the title compound, C₂₃H₂₁N₃O₃, the indole ring is planar and the phenyl ring of the benzyl group makes a dihedral angle with the best plane of the indole ring of 73.77 (4)°. The double bond connecting the aza­bicyclic and indole moieties has Z geometry.     

1,2,3,9a-Tetrahydro-9H-imidazo[1,2-a]indoles

When derivatives of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one or 1-carbamoylmethyl-2-methylene-2,3-dihydroindole are reacted with lithium aluminum hydride, derivatives of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole are formed. Under the same conditions 1-(N-phenylcarbamoylmethyl)-2-methylene-2,3-dihydroindole is not cyclized to an imidazo[1,2-a]indole. WHen treated with proton acids imidazo[1,2-a]indoles are converted to 3H-indolium salts. Opening of the imidazolidine ring is also found when imidazo[1,2-a]indole is acylated with benzoyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 227–230, February, 1987.     

Nickel‐catalyzed Buchwald–Hartwig amination of pyrimidin‐2‐yl tosylates with indole,benzimidazole and 1,2,4‐triazole

Nickel‐catalyzed Buchwald–Hartwig amination of pyrimidin‐2‐yl tosylates with indole and benzimidazole was achieved using Ni(dppp)Cl₂ as catalyst, yielding a variety of novel C2‐substituted pyrimidine derivatives in good yields. This reaction proved to be tolerant of various pyrimidin‐2‐yl tosylates bearing either electron‐donating or electron‐withdrawing groups as well as nucleophiles including indole, benzimidazole and 1,2,4‐triazole. Copyright © 2016 John Wiley & Sons, Ltd.     

Palladium‐Catalyzed One‐Pot Three‐ or Four‐Component Coupling of Aryl Iodides,Alkynes, and Amines through CN Bond Cleavage: Efficient Synthesis of Indole Derivatives

An efficient synthesis of N‐substituted indole derivatives was realized by combining the Pd‐catalyzed one‐pot multicomponent coupling approach with cleavage of the C(sp³)?N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene–phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1‐bromo‐2‐iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4‐methylpiperidine, 1‐methylpiperazine, 2‐methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3‐b]indole.     

Synthesis and autoxidation of new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-ones.

The new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-one derivatives (7a-d, 7ea, 7eb) have been synthesized by modified Fischer indole synthesis from the enol ether of 2,5-dihydroxy-7-methyl-6-cyano-indolizine (3) and arylhydrazines (4a-g). Attempted N-methylation of 7a-d produced a series of autoxidized products including 10-hydroperoxy-1-methoxyindolizino[1,2-b]indole (9a-d) as the major product accompanied with methylperoxides (10a-d and 11a-d) and 2-formyl-3-(pyridine-2-yl)indole (12a, 12c) derivatives as the minor products. A plausible mechanism of the autoxidation is postulated based on the isolation of some intermediates. The reaction is thought to proceed through azaenolate/enamine intermediates following a novel type of autoxidation.     

Synthesis and Photochromic Behaviour of Novel 2H‐1‐Benzopyrans (=2H‐Chromenes) Derived from Carbazololes

The synthesis and photochromic properties of new 2,2‐diphenyl‐2H‐1‐benzopyrans, fused to an indole moiety, are described. All compounds exhibit photochromic behaviour in solution at room temperature. The heteroanellation effects are variable and depend on the position and geometry of the fused indole moiety. A general bathochromic shift in the spectra of the open forms is observed. The presence of a N‐methyl group prevents the broadening of the absorption spectra and promotes the instability of some photoinduced forms of compounds with the indole moiety fused at the 5,6 positions of the 2H‐1‐benzopyran skeleton. The enhanced photocolouration efficiency in the near‐UV and the kinetics of thermal bleaching indicate that the novel compounds with an indole moiety fused at the 6,7 positions, particularly those with a linked thiophene moiety, are very interesting molecules for applications in the field of variable optical absorption systems.