Benzofurans. Improved syntheses of bufuralol, 7-ethyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran,and 1″-oxobufuralol, 7-acetyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran

An improved laboratory scale synthesis of bufuralol ( 1 ) and 1″-oxobufuralol ( 4 ) was accomplished. The intermediate benzofurans were prepared via aromatization of 2,3-dihydrobenzofurans or by a one-step acidcatalyzed cyclization from 2,2-diethoxyethyl 4-bromo-6-ethyl-2-formylphenyl ether ( 23 ). Base-catalyzed cyclization of 3-(5-bromo-3-ethyl-2-hydroxyphenyl)-1.2-epoxypropane ( 16 ) provided the key intermediate, 5-bromo-7-ethyl-2-hydroxymethyl-2,3-dihydrobenzofuran ( 17 ). Selective functionalization of the C-2 and C-7 positions of the benzofuran ring system was accomplished to afford both 1 and 4 .     

Fused 1,2,4-triazole heterocycles. IV. Synthesis of four new heterocyclic ring systems of [1,2,4]triazolo[1,3]thiazinoquinolines

Syntheses of 5H-[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,4-c]quinolines 8, 5H-[1,2,4]triazolo[3′,4′:2)3][1,3]thiazino[5,4-c]quinolines 9, 5H-[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,6-c]quinolines 14 and 5H-[1,2,4]triazolo[3′,4′:2,3][1,3]thiazino[5,6-c]quinolines 15 are described starting from 4-chloro-3-chloromethylquinaldine (4) and 1,2,4-triazole-5-thiols 5 taking advantage of different reactivity of the chlorine atoms of 4 under different reaction conditions. The structures of products 8, 9, 14 and 15 and the intermediates leading to them were confirmed by desulfurization, unequivocal syntheses and nmr spectroscopy as well.     

Synthesis of 9-azolyl-3-(4-phenyl-4h-1,2,4-triazol-3-yl)-4h,8h-pyrano-[2,3-<Emphasis Type="Italic">f</Emphasis>]chromene-4,8-diones

The reaction of 6-ethyl-8-formyl-7-hydroxy-3-(4-phenyl-4H-1,2,4-triazol-3-yl)chromone with 2-azolyl-acetonitriles gave 8-iminopyrano[2,3-f]chromen-4-ones, whose acid hydrolysis led to pyrano-[2,3-f]chromene-4,8-diones containing azaheterocyclic substituents at C-3 and C-9.     

Acetylene chemistry. Part 28. New C-2 substituted furo[2,3-b]quinolines via Pd-catalyzed reaction

Four new C-2 substituted furo[2,3-b]quinolines have been synthesized via Pd-catalyzed reaction. The present study was to provide furo[2,3-b]quinolines for biological studies on the influence of the side chain length and its polarity of the biological activity particularly against phytopathogenic bacteria and fungi.     

Condensation of ethyl cydopentanone-2-carboxylate withN-arylmethylene-2-naphthylamines

The condensation of ethyl cyclopentanone-2-carboxylate withN-arylmethylene-2-naphthylamines depending on the conditions of reaction affords 4-aryl-l-ethoxycarbonyl-lH-2,3,4,5-tetrahydrocyclopenta-[c]benzo[f]quinolines, 4-aryl-l-ethoxycarbonyl-lH-2,3-dihydrocyclopenta[c]benzo[f]quinolines, and 4-aryllH-2,3-dihydrocyclopenta[c]benzo[f]quinolines.     

2‐Aryl‐4‐azido‐3‐(bromo/iodo)quinolines as substrates for the synthesis of primary 4‐amino‐2,3‐disubstituted quinoline derivatives

Staudinger reaction of the 2‐aryl‐4‐azido‐3‐bromoquinolines and 2‐aryl‐4‐azido‐3‐iodoquinolines with triphenyl phosphine in refluxing tetrahydrofuran afforded series of 2‐aryl‐3‐halogeno‐4‐(triphenylphosphoranylideneamino)quinolines. The latter were, in turn, hydrolyzed to the corresponding primary 4‐amino‐2‐aryl‐3‐(bromo/iodo)quinolines using 80% acetic acid under reflux. Tetrakis(triphenylphosphine)‐palladium(O)‐catalyzed Suzuki reaction of the 2‐aryl‐3‐iodo‐4‐(triphenylphosphoranylideneamino)‐quinolines with phenylboronic acid in dimethyl formamide in the presence of 2 M K₂CO₃ followed by hydrolysis of the incipient 2,3‐diaryl‐4‐(triphenylphosphoranylideneamino)quinolines with 80% acetic acid afforded the 4‐amino‐2,3‐diarylquinolines.     

The investigations in 2,3′-biquinoline series. 25*. Synthesis of 4-(2-quinolinyl)-pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinolines and 4-(2-quinolyl)-imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinolines

A method has been developed for the synthesis of 4-(2-quinolinyl)-1,2,3,3a-tetrahydropyrrolo-[1,2-a]quinolines based on the 1,3-dipolar cycloaddition reaction of α,β-unsaturated carbonyl compounds to 2,3′-biquinolinium salts. Oxidation in benzene using MnO₂ gave 4-(2-quinolinyl)-pyrrolo[1,2-a]quinolines. It was found that a side product of the 1,3-dipolar cycloaddition is 7,14-di-benzoyl-6,13-di(2-quinolyl)-6a,7,13a,14-tetrahydro-7a,14a-diazadibenzo[a,h]anthracene. Reaction of 1′-phenacyl-2,3′-biquinolinium salts with hydroxylamine in acetic acid gave 4-(2-quinolyl)imidazo-[1,2-a]quinolines. *For Communication 24 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 433–439, March, 2009.     

The synthesis of benzofuroquinolines. IV. Some halobenzofuro[2,3-B]- and [3,2-C]quinoline derivatives

Some 8- or 9-halobenzofuro[2,3-b]quinolines ( 1a , 8-F, 8-C1, 9-F, 9-Cl) and 9-halobenzofuro[2,3-b]quinoline-11-carboxylic acid ( 1b , F, Cl) were synthesized from 6- or 7-halo-3-(2-methoxyphenyl)-2-oxo-1,2-dihydroquino-line-4-carboxylic acids ( 3 ). And, some 9-halo-11(6H)-benzofuro[2,3-b]quinolinone ( 8 , F, Cl, Br) and 2-halo-6(5H)-benzofuro[3,2-c]quinolinone ( 9 , F, Cl, Br) were synthesized from 6-halo-4-hydroxy-3-(2-methoxyphenyl)-2(1H)-quinolinone ( 7 ), and they were converted to the corresponding chlorohalobenzofuroquinolines ( 1c , 9-F, 9-C1, 9-Br, and 2 , F, Cl, Br).     

Reactions of 4-Methoxy-3-quinolinyl and 1,4-Dihydro-4-oxo-3-quino-linyl Sulfides Aiming at the Synthesis of 4-Chloro-3-Quinolinyl Sulfides

The preparation of 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 or 1,4-dihydro-4-oxo-3-(alkylthio)quinolines 4 by acid catalysed hydrolysis of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 4-methoxy-3-(alkylthio)-quinolines 2 is described. The reactions of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 with phosphoryl chloride in DMF afforded 4-chloro-3′-alkylthio-3,4′-diquinolinyl sulfides 5 . Treatment of the title compounds 1 or 3 with boiling phosphoryl chloride systems:leads to 4-chloro-3-(alkylthio)quinolines 6 and thioquinanthrene but those of alkoxy- or oxo-quinolines 2 or 4 lead to 4-chloro-3-(alkylthio)quinolines 6 . The reactions of N-methyl-4(1H)-quinolinones 3n and 4n with phosphoryl chloride directed to 4-chloro-3-(alkylthio)quinolines 6 were studied as well.     

The synthesis of monomethoxy[1]benzothieno[2,3-c]quinolines

A series of monomethoxy[1]benzothieno[2,3-c]quinolines 24-28 were prepared by photocylization of the appropriate 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamides 9–13 to [1]benzothieno[2,3-c]quinolin-6(5H)-ones 14-18 followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 19-23 then dechlorination resulting in the title compounds except for 25 which was achieved by direct reduction of 15 . Reaction of 24-28 with methyl iodide provided the corresponding N-methyl quaternary salts 29-33 . Also, conversion of 4-meth-oxy[1]benzothieno[2,3-c]quinolin-6(5H)-one 16 to 4-methoxy-6-methylthio[1]benzothieno[2,3-c]quinoline 35 and 4,6-dimethoxy[1]benzothieno[2,3-c]quinoline 36 is described.     

Cycloaddition reactions of ketoimines. Part II. Synthesis of substituted phenanthridines and cyclopenta[c]quinolines

Substituted 4-benzoyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines 3 and 6-benzoyl-5,6,6a,7,8,10a-hexahydrophenanthridines 10 are obtained through Lewis acid catalyzed addition of 1-phenyl-2-arylamino-2-methoxyethanones 2 to cyclopentadienes and 1,3-cyclohexadiene respectively. Compounds 3 can be converted to the aromatized analogues by reaction with 2,3-dichloro-5,6-dicyanobenzoquinone in refluxing benzene. Compounds 10 are oxidized by sulfur either in decalin or in quinoline to substituted 6-benzoylphenanthridines.     

2-Dichloromethyl-4-methyl-2,3-dihydrofuro[3,2-c]-quinoline derivatives

Substituted 2-dichloromethyl-4-methyl-2,3-dihydrofuro[3,2-c]quinolines were obtained by cyclization of substituted 2-methyl-3-(3,3-dichloroallyl)-4-hydroxquinolines, and 2-dichloromethyl-2,4-dimethyl-2,3-dihydrofuro[3,2-c]quinolines were isolated from 2-methyl-3-(2-methyl-3,3,dichloroallyl)-4-hydroxyquinolines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 84–86, January, 1973.     

Programmed Multiple C-H Bond Functionalization of the Privileged 4-hydroxyquinoline Template

The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C−H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C−H functionalization of a “programmed” 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalization, of which four were targeted. The C-2 and C-8 decorations were directed by an N-oxide, before taking benefit of an O-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalize position 5. Our study highlights the power of multiple C−H functionalization to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.     

Synthetic studies on pyrroloquinolines. II. Studies on the syntheses and chemical properties of 1H-pyrrolo[2,3-b] quinolmes

This paper describes the syntheses and the properties of 1H-pyrrolo[2,3-6]quinolines derived from 2,3-dihydrofuro[3,2-c]quinolines or 3-(β-chloroethyl)-2,4-dichloroquinolines. The discrepancy on the physical data of 1H-pyrrolo[2,3-b]quinoline between our product and Perkin's previously reported product is also discussed.     

A novel synthesis for quinoline derivatives

Condensation of ethyl 2-(2-oxo-2,3-dihydro-1H-indolid-3-ene)cyanoacetate and/or 2-(2-oxo-2,3-dihydro-1H-indolid-2-ene)malononitrile with 3-methylpyrazolin-5-one, 1-phenyl-3-methyl-pyrazolin-5-one, benzoyl acetonitrile or ethyl acetoacetate affords different substituted quinolines. The reaction is suggested to proceed through a nucleophilic addition followed by ring opening and recyclization steps.     

Synthesis of some pyrimido[4′,5′:4,5]thieno[2,3-b]quinolines and related heterocycles

Several thieno[2,3-b]quinolines 6a-i have been synthesized. These compounds were used as key intermediates in the synthesis of oxazino[4′,5′:4,5]thieno[2,3-b]quinoline 8 , pyrimido[4′,5′:4,5]-thieno[2,3-b]quinolines 9–12 , triazino[4′,5′:4,5]thieno[2,3-b] quinolines 14 and imidazo[4′,5′:4,5]-thieno[2,3-b]quinolines 17 .     

Synthesis of 2H-pyrano[2,3-b]quinolines. Part I

3,4-Dihydro-2H-pyrano[2,3-b]quinolines 5a-e and 2H-pyrano[2,3- b ]quinolines 10a-c were synthesised starting from the appropriate ω-chloro-n-valeroylanilides 2a-e . Compounds 10a-c were transformed to analogs of the novel antihypertensive agent Cromakalim ( 1 ).     

One-pot palladium-catalyzed C-I and C-H bond activation and subsequent Suzuki-Miyaura cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with arylboronic acids

The 2-aryl-3-iodo-4-(phenylamino)quinolines undergo one-pot palladium-mediated C-I and C-H bond activation and subsequent Suzuki-Miyaura cross-coupling with arylboronic acids under anhydrous conditions to afford mixture of 2,3-diaryl-4-(phenylamino)quinolines (minor) and 2-aryl-4-([(1,1′-biaryl)-2-yl]amino)quinoline derivatives (major). The 2,3-diaryl-4-(phenylamino)quinolines were isolated as major products when 2 M K₂CO₃ was used as a base. A plausible mechanism, which implicates a six-membered palladacycle intermediate is proposed for the formation of the observed mixture of products. The prepared compounds were characterized using a combination of spectroscopic and X-ray crystallographic techniques.     

Stereoselective synthesis of highly enantioenriched 3-methyl-2-cyclohexen-1-ones possessing an asymmetric quaternary carbon as C-4 or C-6: a sugar template approach

The 1,4-addition of the enolate generated from α-methylated acetoacetate incorporated at C-4 of methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-α-d-glucopyranoside to methyl vinyl ketone, followed by aldol condensation of the resulting 1,4-addition product under two base-mediated conditions, provided 4-O-functionalized d-glucose derivatives with high diastereoselectivity. These products install a 3-methyl-2-cyclohexen-1-one-4- (or -6-) carboxylic acid as the O-4 ester, in which C-4 or C-6 is an asymmetric quaternary carbon. Removal of the sugar template from those aldol condensation products provided synthetically useful 3,6-dimethyl-2-cyclohexen-1-one-6-carboxylic acid and 3,4-dimethyl-2-cyclohexen-1-one-4-carboxylic acid derivatives both in high enantioenriched forms.     

Synthesis and Characterization of New Heterocyclic Compounds Containing Thienylbenzo[h]Quinoline Moiety

In this paper the reaction of 2‐(2′‐thienylmethylene)‐3,4‐dihydronaphthalen‐2(1H)‐one ( 1 ) with cyanothioacetamide gave a mixture of 3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2(1H)‐thione ( 2 ) and the related disulfide 3 . Compound 2 was reacted with some halo compounds namely; ethyl chloroacetate, chloroacetamide, chloro(N‐(p‐chlorophenyl))acetamide, N¹‐chloroacetylsulfanilamide, and 2‐chloromethyl‐1H‐benzimidazole to produce a series of 2‐(substituted)methylthio‐3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)benzo[h]quinolines 4a , 4b , 4c , 4d , 4e and 11 . Upon heating the latter compounds with sodium ethoxide, they underwent intramolecular Thorpe–Zeigler cyclization to furnish the corresponding 2‐(substituted)‐3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]thieno[2,3‐b]quinolines 5a , 5b , 5c , 5d , 5e and 12 . (3‐Cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2‐ylthio)acethydrazide ( 8 ) and the related isomer, 3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)thieno[2,3‐b]benzo[h]quinoline‐2‐carbohydrazide ( 9 ), were also synthesized. Most of the aforementioned compounds were used as key intermediates for synthesizing other benzo[h]quinolines, benzo[h]thieno[2,3‐b]quinolines as well as benzo[h]pyrimido[4′,5′:4,5] thieno[2,3‐b]quinolines. The structure of all synthesized compounds was confirmed by spectroscopic measurements and analytical analyses.