Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)benzaldehydes with aryl amines

Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles, via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles, which were successfully hydrolyzed with hydrochloric acid to give pyrrolo[1,2-a]indol-9-ones.     

Synthesis of fluoroquinoxalin-2(1<Emphasis Type="Italic">H</Emphasis>)-one derivatives containing substituents in the pyrazine and benzene fragments

6,7-Difluoroquinoxalin-2-one reacted with indoles, 5,5-dimethylcyclohexane-1,3-dione, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, resorcinol, and pyrogallol on heating in acetic acid to give products of hydrogen substitution in the heterocyclic fragment. Heating of 6,7-difluoro-3-(1H-indol-3-yl)quinoxalin-2(1H)-ones with N-methylpiperazine gave the corresponding 7-(4-methylpiperazin-1-yl) derivatives.     

Site-selective Suzuki-Miyaura reactions of 2,3-dibromo-1H-inden-1-one

The first transition metal-catalyzed cross-coupling reactions of 2,3-dibromo-1H-inden-1-one are reported. The Suzuki-Miyaura reaction of 2,3-dibromo-1H-inden-1-one with 2 equiv of arylboronic acid gave 2,3-diaryl-1H-inden-1-ones. The reaction with 1 equiv of arylboronic acid gave 2-bromo-3-aryl-1H-inden-1-ones with very good site-selectivity. The one-pot reaction of 2,3-dibromo-1H-inden-1-one with two different arylboronic acids afforded 2,3-diaryl-1H-inden-1-ones containing two different terminal aryl groups.     

Reductive coupling of hydantoins with benzophenones by low-valent titanium: Synthesis of 4-substituted 1H-imidazol-2(3H)-ones and unusual two-to-two coupled products

The reductive coupling of 1,3-dimethyhydantoin with benzophenones by TiCl₄-Zn in THF gave 4-diarylmethyl-1H-imidazol-2(3H)-ones as four-electron reduced one-to-one coupled products and their dimers as two-to-two coupled products predominantly by controlling the reaction conditions. The reductive coupling of 5-alkyl-1,3-dimethyhydantoins with benzophenones produced 5-alkyl-4-diarylmethyl-1H-imidazol-2(3H)-ones as the sole products irrespective to the reaction conditions. On the other hand, the reductive coupling of 1,3-dimethyhydantoin with cyclic benzophenones selectively 4-arylhydroxymethyl-1H-imidazol-2(3H)-ones as two-electron reduced one-to-one coupled products and they were further reduced to 4-diarylmethyl-1H-imidazol-2(3H)-ones.     

Novel syntheses of 3-anilino-pyrazin-2(1H)-ones and 3-anilino-quinoxalin-2-(1H)-ones via microwave-mediated Smiles rearrangement

In this Letter, we report a novel approach to the preparation of 3-anilino-pyrazin-2(1H)-ones and 3-anilino-quinoxalin-2(1H)-ones from the corresponding 3-halo pyrazin-2-amines and 3-haloquinoxalin-2-amines, using a microwave-mediated Smiles rearrangement.     

A rapid and versatile synthesis of novel pyrimido[5,4-b]carbazoles

A one-pot synthesis of 2-dialkylamino-5,11-dimethyl-6H-pyrimido[5,4-b]carbazol-4(3H)-ones, as new ellipticine analogs, starting from aminocarbazole derivatives is reported. This method allowed us to prepare a library of potentially useful compounds in the pharmaceutical field.     

Visible-light-induced chemoselective reactions of quinoxalin-2(1H)-ones with alkylboronic acids under air/N2 atmosphere

A visible-light-induced chemoselective reactions of quinoxalin-2(1H)-ones with alkylboronic acids in the presence of air (O₂) and N₂ atmosphere was developed under transition-metal free conditions, providing 3-alkylquinoxalin-2(1H)-ones and 3,4-dihydroquinoxalin-2(1H)-ones, respectively. The overall strategy accommodates a broad scope of substituted quinoxalin-2(1H)-ones and alkylboronic acids with good to excellent product yields.     

Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones

The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones 5, 6a-d from 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d is reported. The 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d were obtained from regiospecific bromination of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 1, 2a-d with molecular bromine. The NMR and X-ray diffraction data showed that 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones were brominated at 4-position in the pyrrolidin-2-one ring.     

The synthesis of phthalazin-1(2H)-ones and 3-hydroxyisobenzofuran-1(3H)-ones via the ring contraction of tropones

Phthalazin-1(2H)-ones and 3-hydroxyisobenzofuran-1(3H)-ones were synthesized by the reactions of tropones with hydrazines and alcohols, respectively, via the ring contraction.     

2,3-Dihydro-1H-1,3-diazepin-2-ones: synthesis and novel rearrangements into pyrrole derivatives

A novel synthesis of 2,3-dihydro-1H-1,3-diazepin-2-ones based on thermal elimination of methanol from 4-methoxy-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones has been developed. The prepared dihydrodiazepinones underwent two new rearrangements under basic or acidic conditions to give the pyrrole derivatives, 3-(aminomethylene)-2,3-dihydro-1H-pyrrol-2-ones and 1-carbamoyl-1H-pyrroles, respectively. Plausible mechanisms for the rearrangements are proposed.     

Direct introduction of heterocyclic residues into 1,2,4-triazin-5(2H)ones

3-Aryl-1,2,4-triazin-5(2H)-ones 1a-c react with indoles 2a-c in trifluoroacetic acid/chloroform or in boiling butanol or acetic acid to give 3-aryl-6-(indolyl-3)-1,6-dihydro-1,2,4-triazin-5(2H)-ones 3a-g . Oxidation of the dihydro-1,2,4-triazin-5(2H)-ones 3a-e afforded 6-(indolyl-3)-1,2,4-triazin-5(2H)-ones 4a-e , products of nucleophilic substitution of hydrogen in 1a-c . Refluxing 1b with N-methylpyrrote 5b in butanol for an extended time resulted in the formation of 3-(4-chlorophenyl)-6-(1-meuiylpyrrolyl-2)-1,2,4-triazin-5(2H)-one 4h. The reaction of 1a-c with indoles 2a-c , pyrroles 5a,b , 1,3-dimethyl-2-phenylpyrazol-4-one (8) and aminothiazoles 9a,b in acetic anhydride affords the 1-acetyl-3-aryl-6-hetaryl-1,6-dihydro-1,2,4-triazin-5(2H)-ones 6a-s . Reaction of 1a-c with N-methyl-pyrrole 5b in acetic anhydride gives beside the 1:1 addition products 6h-k also the 2:1 addition products 7a-c .     

Synthesis and reactions of 1-hydroxy-9,9a-dihydro-1H-imidazo[1,2-a]indol-2-(3H)-ones

1-Hydroxy-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-ones, as a new type of azaheterocyclic hydroxamic acids, have been synthesized regioselectively from 1-carbamoylmethyl- or 1-(methoxycarbonyl)methyl-2,3,3-trimethyl-3H-indolium salts by reaction with hydroxylamine in the presence of a strong base. The alkylation and reduction with sodium borohydride of these novel heterocycles have been investigated. When treated with protic acids 1-hydroxy- or 1-alkoxy-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-ones underwent ring opening of the imidazolidine to afford 1-[2-(hydroxyamino)-2-oxoethyl]-2,3,3-trimethyl-3H-indolium salts. The structural assignments are based on extensive ¹H, ¹³C and ¹⁵N NMR spectroscopic studies and single crystal X-ray analyses.     

Superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids: synthesis of quinolin-2(1H)-one derivatives

The superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids by Bronsted superacids (CF₃SO₃H, HSO₃F) or strong Lewis acids AlX₃ (X=Cl, Br) results in the formation of 4-aryl quinolin-2(1H)-ones in quantitative yields. The vinyl triflates or vinyl chlorides may be formed as additional reaction products. The investigated amides in reactions with benzene give 4,4-diaryl 3,4-dihydroquinolin-2-(1H)-ones under the superelectrophilic activation. 4-Aryl quinolin-2(1H)-ones in POCl₃ are converted into 4-aryl 2-chloroquinolines. 4-Fluorophenyl-4-phenyl 3,4-dihydroquinolin-2-(1H)-one give N-formylation products in a yield of 79% under the Vilsmeier–Haack reaction conditions.     

Uncatalyzed addition of indoles and N-methylpyrrole to 3-formylchromones: synthesis of (chromon-3-yl)bis(indol-3-yl)methanes and E-2-hydroxy-3-(1-methylpyrrol-2-ylmethylene)chroman-4-ones under solvent-free conditions

(Chromon-3-yl)bis(indol-3-yl)methanes and E-2-hydroxy-3-(1-methylpyrrol-2-ylmethylene)chroman-4-ones have been obtained in good yields from 3-formylchromones on reaction with indoles and N-methylpyrrole under solvent-free conditions.     

A tandem multi-component synthesis of 5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones

The five-component reaction of ethyl 2-[(2-oxopropyl)sulfanyl]acetate, aromatic aldehydes, and ammonium acetate affords two diastereomers of 5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones via a novel tandem Mannich-enamine-substitution sequence. Presumably, they are generated from ethyl 2-[(4-oxo-2,6-diaryl-3-piperidinyl)sulfanyl]acetates. During the formation of the trans-5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]-thiazin-2(3H)-ones from ethyl 2-[(4-oxo-2,6-diaryl-3-piperidinyl)sulfanyl]acetates, the configuration at the carbon bearing an aryl group adjacent to the enamide CC double bond is inverted via ring opening and closure. When o-substituted benzaldehydes were employed in this reaction, 5,7-diaryl-5,6-dihydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones were obtained via air oxidation, along with trans-5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]-thiazin-2(3H)-ones.     

Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.     

Reactivity of 3-formyl- and 3-cyanothiochromones toward some N- and C-nucleophiles. Novel synthesis of 3-substituted 2-aminothiochromones

The reactions of 3-formylthiochromone with o-phenylenediamines, o-aminobenzenethiol, and indoles proceeded at the aldehyde group to give 3-(benzimidazol-2-yl)thiochromone, 3-(benzothiazol-2-yl)thiochromone, and 3-di(indol-3-yl)methylthiochromones, respectively. 3-Formyl- and 3-cyanothiochromones react with primary aromatic amines and phenylhydrazine to give the corresponding anils and phenylhydrazones of 3-formyl- and 2-amino-3-formylthiochromones. The reaction of 3-cyanochromones with o-phenylenediamines gave 2-amino-3-[(2-aminophenyl)iminomethyl]-4H-chromen-4-ones.     

Synthesis of different isoindolone embedded heterocycles with phenolic subunits from a common intermediate, 3-(2′-hydroxyaroyl)-2,3-dihydroisoindol-1-ones

A series of biologically important isoindolone embedded heterocycles such as tetracyclic 2,4-diamino-5-aryl-10-oxo-10H-1,10a-diazaindeno[2,1-a]indene-3-carbonitriles and tricyclic 1-aryl-3,5-dioxo-1H-imidazo-[3,4-b]isoindoles have been synthesized from an easily derived common intermediate, 3-(2′-hydroxyaroyl)-2,3-dihydroisoindol-1-ones. The significant advantages of the present methodologies are the use of simple and easily available starting materials and reagents, operational simplicity, and good yields of the products with high atom-economy.     

Regioselective synthesis of 1H,3H,6H[2]benzopyrano[4,3-d]pyrimidine-2,4-diones and 12H-benzopyrano[3,2-c][1]benzopyran-5-ones by radical cyclization

5-Hydroxy uracils or 4-hydroxy[1]benzopyran-2-ones were refluxed with 2-bromobenzyl bromides in acetone in the presence of anhydrous potassium carbonate to afford a number of 5-(2′-bromobenzyloxy) pyrimidine-2,4-dione (80-92%) or 4-(2′-bromobenzyloxy) benzopyran-7-ones (70-82%) respectively. These were then refluxed with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of azobisisobutyronitrile (AIBN) for 3-4 h to give 1H,3H,6H [2]benzopyrano[4,3-d]pyrimidine-2,4-diones (75-85%) or 12H-benzopyrano[3,2-c][1]benzopyran-5-ones (70-85%) respectively.     

A one-pot synthesis and 1,3-dipolar cycloaddition of [1,2]dithiolo[4,3-b]indole-3(4H)-thiones

Treatment of N-substituted 2-methyl-1H-indoles 1 with S₂Cl₂ and DABCO in chloroform gave the corresponding [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5 by the addition of triethylamine in high yield. 1,2-Dithiole-3-thiones 5 underwent cycloaddition with one or two DMAD equivalents to afford either 2-(3-thioxo-1,3-dihydro-2H-indol-2-ylidene)-1,3-dithioles 10 or fused 4,5-dihydrothiopyrano[3,2-b]indoles 9.