Photo-induced molecular transformations. Part 123. One-step synthesis of 1H-benz[f]indole-4,9-diones by a new regioselective photoaddition of 2-amino-1,4-naphthoquinone with various alkenes and its application to one-step synthesis of kinamycin skeleton

2,3-Dihydro-1H-benz[f]indole-4,9-diones are formed in one-step in 45–82% yields by an unprecedented [2+3]-type regioselective photoaddition of 2-amino-1,4-naphthoquinone with various electron-rich alkenes and the [2+3] adducts derived from ammonaphthoquinone with vinyl ethers and vinyl acetate to give 1H-benz[f]indole-4,9-diones including a benzindole-dione with a kinamycin skeleton in 33–72% yields. A probable pathway leading to the formation of the dihydroindole-dione involving air oxidation of an intermediary hydroquinone is proposed.     

Synthesis of 4,9-dimethoxy-1H-benz[f]indole

A three-step synthesis of 4,9-dimethoxy-1H-benz[f]indole (4) starting from 1,4-dimethoxy-2-aminonaphthalene (1) is described. Compound 1 was condensed with epichlorohydrin in acidic methanolic solution and the crude reaction product, purified by column chromatography, was cyclized to compound 3 by reflux heating in bromobenzene solution in the presence of excess diethylaniline. Appropriate oxidization with periodate in alkaline solution produced the title compound 4.     

Synthesis of Pyrrolo [3,4-c] [1] benzazepine-4, 10 (2H, 5H)-dione,a Model System Useful for the Design of 11-Oxosibiromycinone Analogues

The synthesis of pyrrolo[3,4-c] [1] benzazepine-4,10(2H, 5H)-dione, a compound related to 11-oxosibiromycinone, is described. 2-Methyl-, 5-methyl- and 2,5-dimethylpyrrolo[3,4-c] [1] benzazepine-4, 10 (2H, 5H) - dione have been also prepared. The title compound has been synthesized either by ring enlargement of 2H-benz [f] isoindole-4,9-dione or by TosMIC addition to 1H-1-benzazepin-2,5-dione.     

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.     

Photoinduced Molecular Transformations. Part 142. One-step syntheses of 1H-benz[f]indole-4,9-diones and 1H-indole-4,7-diones by a new regioselective photoaddition of 2-amino-1,4-naphthoquinones and 2-amino-1,4-benzoquinones with alkenes

The 2,3-dihydro-1H-benz[f]indole-4,9-diones 3a–d , h were formed in a one-step reaction in 13–82% yield by an unprecedented [3 + 2] regioselective photoaddition of 2-amino-1,4-naphthoquinone ( 1 ) with various electronrich alkenes 2 (Scheme 1, Table). The [3 + 2] photoadducts derived from 1 with vinyl ethers and vinyl acetate gave 1H-benz[f]indole-4,9-diones 4e , f , i , in 33–72% yield, by spontaneous loss of the corresponding alcohol or AcOH from the resulting adducts; 4i has a kinamycin skeleton. The [3 + 2] photoaddition also took place on irradiation of the differently substituted amino-1,4-benzoquinones 6 , 7 , and 12 and excess alkenes 2 in benzene, giving 1H-indole-4,7-dione derivatives 13 and 14 (Scheme 3), 15a and 16 (Scheme 4), and 18 (Scheme 4), respectively. The initial products in these photoadditions were proved to be hydroquinones, the air oxidation of which yielded the heterocyclic quinones; 2,3-dihydro-2-methoxy-2-methyl-5-phenyl-1H-indole-1,4,7-triyl triacetate ( 19 ) was isolated after treatment of the crude photoaddition mixture obtained from 2-amino-5-phenyl-1,4-benzoquinone ( 7 ) and 2-methoxyprop-1-ene ( 2f ) with Ac₂O and pyridine under N₂. A pathway leading to the annelated hydroquinones involving ionic intermediates arising from an electron transfer in these photoadditions is proposed (Scheme 5).     

Synthesis and demethylation of new 5,6,7,8-tetrahydro-4,9-dimethoxy-1H-benz[f]indole

The title compound 17 was prepared in good yield starting from 5,6,7,8-tetrahydro-l-naphthol ( 9 ) by an advantageous synthesis route consisting of eight steps, as indicated in Scheme 2. Demethylation by reflux heating with anhydrous aluminium chloride in dry benzene furnished 4,9-dihydroxy- and 4,9-dioxo-5,6,7,8-tetrahydro-1H-benz[f]indoles (compounds 18 and 19 , respectively). All new products were identified on the basis of spectral and analytical data.     

2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indoles. II. Reversible transformation of 1-alkyl-2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)cyclohexanol into 1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles

Treatment of 2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)-1-methylcyclohexanol ( 2a ) with acetic anhydride or methyl isocyanate gave 2-acetyl-2,3,4,9-tetrahydro-1-(6-oxoheptylidene)-1H-pyrido[3,4-b]indole ( 3 ) or 1,3,4,9-tetrahydro-N-methyl-1-(6-oxoheptylidene)-2H-pyrido[3,4-b]indole-2-carboxamide ( 4 ), respectively. Simpler analogues, 1-alkyl-4,9-dihydro-3H-pyrido[3,4-b]indoles, 7 , subjected to identical reaction conditions, gave 2-acetyl-1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles 8 and 1,3,4,9-tetrahydro-N-methyl-1-alkyli-dene-2H-pyrido[3,4-b]indole-2-carboxamides 9 , respectively. A limited lanthanide shift reagent study to determine stereochemical assignments was also performed.     

Synthesis and structures of benzo[<Emphasis Type="Italic">cd</Emphasis>]furo[2,3-<Emphasis Type="Italic">f</Emphasis>]indol-4(5<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A procedure was developed for the synthesis of derivatives of the new heterocyclic system, benzo[cd]furo[2,3-f]indole, based on the cyclodehydration of 6-acylmethyloxy-1-alkyl-benzo[cd]indol-2(1H)-ones. Either 7- or 8-aryl derivatives of benzo[cd]furo[2,3-f]indol-4(5H)-ones can be prepared depending on the reaction conditions. The molecular and crystal structures of 7- and 8-phenylbenzo[cd]furo[2,3-f]indol-4(5H)-ones were established by X-ray diffraction.     

A simple synthesis of 4‐chloro‐5‐hydroxy‐1H‐benzo[g]indoles

The reaction of methyl 2‐(3‐chloro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)propenoate ( 2a ) with primary amines gave 4‐chloro‐5‐hydroxy‐3‐methoxycarbonyl‐1H‐benzo[g]indoles 5a‐f as major compounds and 3‐methoxycarbonyl‐4,9‐dioxo‐2,3,4,9‐tetrahydro‐1H‐benzo[f]indoles 6a‐d as minor ones. Whereas the reaction of 3‐(3‐chloro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐3‐buten‐2‐one ( 2b ) with primary amines afforded the corresponding 1H‐benzo[g]indoles 5g‐i as major products and 3‐acetyl‐4,9‐dihydro‐4,9‐dioxo‐1H‐benzo[f]indoles 7g, h as minor products.     

Synthesis of 6,7,8,9-tetrahydro-N,N-di-n-propyl-1H-benz[g] indol-7-amine,a potential dopamine receptor agonist

In this work, the synthesis of 6,7,8,9-tetrahydro-N,N-di -n-propyl-1H-benz[g]indol-7-amine (1) is described. This compound was designed as an indole bioisostere to the known dopamine receptor agonist 5-OH-aminotetraline 2 . The key step of the synthesis was a Mukaiyama type aldol condensation between the dimethyl acetal of 1-(p-toluenesulfonyl)pyrrole-3-acetaldehyde ( 4 ) and 4-di-n-propylamino-1-trimethylsilyloxycyclohexene ( 8 ) followed by cycloaromatization to afford 1-p-toluenesulfonyl-6,7,8,9-tetrahydro-N,N-di-n- propyl-1H-benz[g]indol-7-amine ( 10 ). Scission of the sulfonamide bond in 10 gave the target compound 1 . A byproduct which was isolated was assigned to the structure of 1-(p-toluenesul-fonyl)-6-[3-[1-(p-toluenesulfonyl)]pyrrolyl]indole ( 11 ). This compound was also synthesized in good yield by an acid catalyzed dimerization of the dimethyl acetal of 1-(p-toluenesulfonyl)pyrrole-3-acetaldehyde ( 4 ). Preliminary screening of 1 indicated that it possesses central dopamine receptor agonist properties.     

Synthesis of novel methoxy and hydroxy derivatives of 2-phenyl-1H-benz[g]indoles

The synthesis of novel methoxy-derivatives of 2-phenyl-1H-benz[g]indole 3 by condensation of α-naphthyl-amines 1 with N-phenacyl-pyridinium salts 2 is described, as well as their conversion into the corresponding hydroxy-derivatives 5 . Unexpected quinoxaline derivatives 4 were obtained when in the condensation reaction the N-nitrophenacylpyridinium salts 2d,e have been used.     

Heterocyclische und carbocyclische 12-π- and 14-π-Molekülsysteme, 47. Mitteilung. Herstellung von 7, 9-Dimethyl-4, 5-dihydro-3 H-benz [cd]- azulen-3-on and 7,9-Dimethyl-3H-benz [cd]azulen-3-on. Eine einfache Synthese eines Azulenopseudophenalenons

Heterocyclic and Carbocyclic 12-π-and 14-π-Systems, 47th Commnunication¹. Synthesis of 7,9-Dimethyl-4,5-dihydro-3H-benz[cd]azualene-3-one and 7,9-Dimethyl-3H-benz[cd]azulene-3-one. A Simple Synthesis of Azulenopseudophenalenons 4, 6, 8-Trimethylazulene ( 3 ) reacts after metalation with lithiumdiisopropyl-amide in ether with bromoacetic acid to the 6, 8-dimethylaltulene-4-propionic acid ( 4 ), which undergoes cyclization to the 7, 9-dimethyl-4, 5-dihydro-3H-benz [cd]-azulene-3-one ( 5 ) in the presence of p-toluenesulfonic acid; oxidation of 5 with 2, 3-dichloro-5, 6-dicyanobenzoquinone yields 7, 9-dimethyl-3H-benz [cd]azulene-3--one ( 1b ). Alkylation of 1b with triethyloxonium tetrafluoroborate in CH₂C1₂ gives the 3-ethoxy [cd]benzazulenium tetrafluoroborate ( 6 ).     

The schmidt reaction on 3a,4,5,6-tetrahydrosuccinimido[3,4-b]-acenaphthen-10-one and its alkylated derivatives

The rearrangement of 3a,4,5,6-tetrahydrosuccinimido[3,4-b]acenaphthen-10-one and two methylated derivatives using Schmidt conditions is described. The ratio of the major product, 2,3,8,9-tetrahydro-3-oxo-1H-benz[de]isoquinoline-1,9a-(7H)dicarboximide, to the minor product, 2,3,6,7-tetrahydro-3-oxo-4H-benz[ij]-isoquinoline-4,4a-(5H)dicarboximide, under different acidic conditions is given. The ratios of analogous products from the methylated derivatives are similar under similar conditions.     

Beiträge zur Chemie schwefelhaltiger Heterocyclen, 4. Mitt.: 6H-Benz[b]indeno[1,2-d]thiophen und 10H-Benz[b]indeno-[2,1-d]thiophen

Zusammenfassung Intramolekulare Cyclisierungsreaktionen von 3-Phenyl-benzo[b]thiophen-2-carbonsäurechlorid und von 2-Phenyl-benzo[b]thiophen-3-carbonsäurechlorid lieferten 6-Oxo-6H-benz[b]indeno[1,2-d]thiophen bzw. 10-Oxo-10H-benz[b]indeno[2,1-d]thiophen.

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Contributions to the chemistry of sulfur containing heterocycles, IV.: 6H-Benzo[b]indeno[1,2-d]thiophene and 10H-benzo-[b]indeno[1,2-d]thiophene

Intramolecular cyclization reactions of 3-phenyl-benzo[b]thiophene-2-carbonyl chloride and of 2-phenyl-benzo[b]-thiophene-3-carbonyl chloride gave 6-oxo-6H-benz[b]indeno-[1,2-d]thiophene and 10-oxo-10H-benz[b]indeno[2,1-d]thiophene, respectively.

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3. Mitt.:F. Sauter, Mh. Chem.99, 2100 (1968).     

Identification of a 4H-benz[f]indole by-product from the friedel-crafts-based synthesis of benzoylpyrrole calcium channel activators

9,9a-Dihydro-2,9a-dimethyl-4-oxo-4H-benz[f]indole-3-carboxylic acid, methyl ester was formed in varying amounts from the Friedel-Crafts-based synthesis of benzoylpyrrole calcium channel activators. The structure of this by-product was determined using two-dimensional long-range ¹H-¹³C heteronuclear correlated and INADEQUATE nmr techniques.     

A three-component domino reaction of 2-tetralone, hydroxylamine and acetylene: a one-pot, highly regioselective synthesis of 4,5-dihydrobenz[e]indoles

2-Tetralone, hydroxylamine and acetylene react in the system MOH/DMSO to give 4,5-dihydrobenz[e]indole and its N-vinyl derivatives in up to 41% and 75% (in the case of excess acetylene) yields, respectively. The amount of the alternative regioisomer, N-vinyl-4,9-dihydrobenz[f]indole, does not exceed 2% (GLC-MS), while the corresponding regioisomer of 4,5-dihydrobenz[e]indole is not detectable.     

Synthèses de la benzo[b][1,4]diazocino[7,6-f]indole,de pyrrolo[f]phtalazines et réactions de cycloadditions

From l-methyl-5,-dibenzoyl-1H-indole two new ring system, mainly a benzob[b][1,4]diazocino[7,6-f]indole and a pyrrolo[2,3-f]phthalazine are obtained. From 2-methyl-5,6-dibenzoyl-2H-isoindole a pyrrolo[3,4-f]phthalazine is obtained and the cycloaddtion reations with electron deficient dienophiles have been investigated.     

K-region oxides and imines of benzo[b]phenanthro[2,3-d]thiophene and benzo[b]phenanthro[3,2-d]thiophene

The syntheses of the K-oxides and K-imine derivatives of benzo[b]phenanthro[2,3-d]thiophene and benzo-[b]phenanthro[3,2-d]thiophene are described. The parent hydrocarbons 1 and 2 were oxidized with osmium tetroxide and sodium metaperiodate, and the dialdehydes 12 and 18 so formed, cyclized to the corresponding epoxides 1a,12b-dihydrobenz[b]oxireno[9,10]phenanthro[2,3-d]thiophene ( 7 ) and 1a,12b-dihydrobenz-[b]oxireno[9,10]phenanthro[3,2-d]thiophene ( 13 ). Reaction of the oxiranes with sodium azide gave mixtures of azido-alcohols that, in turn, were transformed to the thiaarene imines 1a,12b-dihydro-1H-benz[b]azirino-[9,10]phenanthro[2,3-d]thiophene ( 8 ) and 1a,12b-dihydro-1H-benz[b]azirino[9,10]phenanthro[3,2-d]thiophene ( 14 ), respectively, with the aid of tri-n-butylphosphine.     

A new approach to the synthesis of pyrido[4,3-<Emphasis Type="Italic">b</Emphasis>]indole derivatives (γ-carbolines) <Emphasis Type="Italic">via</Emphasis> cyclization of enamino dinitriles

Reactions of 2-dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole with various amines afforded enamino dinitriles and the corresponding pyrido[4,3-b]indoles (γ-carbolines). 3-Amino-4-cyano-5H-pyrido[4,3-b]indole reacted with cyclohexanone to give pentacyclic 13-amino-2,3,4,12-tetrahydro-1H-benzo[b]indolo[2,3-f]-1,8-naphthyridine. Alkylation of pyrido[4,3-b]indoles with various alkylating agents was studied.     

The synthesis of 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles,11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles and 1,2,4-triazolo[3,4-f]-1,2,4-triazino[4,5-a]indoles

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1) , as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4) . Compounds 2 were obtained by acylation of compounds 1 , followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6) . Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9) . Acylation of this last compound, followed of cyclization gave compounds 10 . All the compounds were characterized by elemental analysis and ir and ¹H-nmr spectra.