Synthesis of 5(6H)-phenanthridones using Diels-Alder reaction of 3-nitro-2(1H)-quinolones acting as dienophiles

Diels-Alder reactions of 3-nitro-2(1H)-quinolones with 1,3-butadiene derivatives were carried out to give the phenanthridone derivatives under both atmospheric and high pressure conditions. Furthermore, the reactivity of 3-substituted 2(1H)-quinolones acting as a dienophile with 2,3-dimethyl-1,3-butadiene was examined using molecular orbital (MO) calculation.     

Cycloadditions of 1-substituted 1,3-butadienes with 4- or 3-substituted 2(1H)-quinolones acting as dienophiles

Cycloadditions of 1,3-butadiene derivatives having an electron-rich group at the 1-position with 4- or 3-substituted 2(1H)-quinolones were carried out to give the richly functionalized phenanthridines under both atmospheric and high pressure conditions. Furthermore, the reactivity of 4- or 3-substituted 2(1H)-quinolones acting as a dienophile with 1-substituted dienes was examined using MO calculation.     

1-甲基-2-喹诺酮类衍生物的合成及其抗肿瘤活性

以喹啉类化合物为原料,经甲基化反应和氧化反应制得中间产物2-喹诺酮类化合物(2a~2c); 2a~2c经硝化反应制得7个硝化-2-喹诺酮类化合物{3a~3g); 3a, 3e~3g经移位取代反应合成了4个1-甲基化-4-氰化-2-喹诺酮类衍生物(4a, 4e~4g),其结构经¹H NMR, ¹³C NMR和HR-MS(EI)确证。采用MTT法评价了化合物对MCF-7, H1299, A549, PC-12, CT-26及HepG-2肿瘤细胞的抗增殖作用。研究结果表明：部分化合物对肿瘤细胞的抑制活性明显高于喹啉系列物,其中1,8-二甲基-3,5,7-三硝基-2-喹诺酮(3e)显著抑制六种肿瘤细胞的增殖,对A549的抑制活性最高,IC₅₀为2.05 μmol·L^-1; 1-甲基-6,8-二硝基-4-氰基-2-喹诺酮(4a)可选择性抑制A549和CT-26肿瘤细胞,IC₅₀分别为9.34 μmol·L^-1和18.43 μmol·L^-1。     

Synthesis of phenanthridones using Diels-Alder reactions of 4-substituted 2(1H)-quinolones acting as dienophiles

Diels-Alder reactions of 2(1H)-quinolones having an electron-withdrawing group at the 4-position with 1,3-butadiene derivatives were carried out to give the phenanthridones richly functionalized under the conditions of atmospheric and high pressure. Furthermore, the reactivities of 4-substituted 2(1H)-quinolones acting as a dienophile were examined using MO calculation.     

Divergent route to access structurally diverse 4-quinolones via mono or sequential cross-couplings

A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)-quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-catalyzed cyanations were used to functionalize the 4-quinolone core further.     

Methanetricarboxylates as key reagents for the simple preparation of heteroarylcarboxamides with potential biological activity. Part 1 reaction of methanetricarboxylates with indoline and 1,2,3,4-tetrahydroquinoline

The reaction of methanetricarboxylates 2a,b with indoline as well as 1,2,3,4-tetrahydroquinoline yields tricyclic 4-hydroxy-2(1H)-quinolones with an ester group in position 3 ( 3, 8a,b) . These heterocyclic esters condense with primary aliphatic, aromatic, and heteroaromatic amines to give the corresponding amides 5a-e and 10a-t.     

A general copper powder-catalyzed Ullmann-type reaction of 3-halo-4(1H)-quinolones with various nitrogen-containing nucleophiles

3-(N-Substituted) 4(1H)-quinolinones were synthesized using the copper-catalyzed Ullmann C-N bond forming strategy in moderate to quantitative yields. Starting from 3-halo-4(1H)-quinolones, various nucleophiles including amides, lactams, sulfonamides and NH-containing azoles have been used successfully. In all cases, the reactions take place rapidly in toluene and proceed by using copper powder as a catalyst, DMEDA as a ligand and K(2)CO(3) as a base. In addition, other related heterocycles such as 3-bromoquinolin-2(1H)-ones, 3-bromocoumarin, and 3,5-dibromo-2-pyridone show good to very high reactivity with various nucleophiles under our Cu/DMEDA catalyst system.     

Synthesis and structure of new 3-pyrazolinylcoumarins and 3-pyrazolinyl-2-quinolones

The reactions of substituted 3-cinnamoyl-4-hydroxycoumarins and 3-cinnamoyl-4-hydroxy-2-quinolones with different phenylhydrazines gave 3-hetaryl-1H-4,5-dihydropyrazoles. The product structures were studied by ¹H NMR spectroscopy and mass spectrometry. 4-Hydroxy-3-pyrazo-linylcoumarins exist in DMSO as two tautomers (4-enol and chromane-2,4-dione), while 4-hydroxy-3-pyrazolinyl-2-quinolones exist only in the enol form. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1479–1486, July, 2008.     

Investigation of 2,3'-Biquinolyl. 11. Regioselectivity in the Hydroxylation of 1-Alkyl-3-(2-quinolyl)quinolinium Halides

The hydroxylation of 1-alkyl-3-(2-quinolyl)quinolinium halides by an alkaline solution of K₃[Fe(CN)₆] in aqueous 1,4-dioxane leads to a mixture of 1-alkyl-3-(2-quinolyl)-1,2-dihydro-2-quinolones and 1-alkyl-3-(2-quinolyl)-1,4-dihydro-4-quinolones with predominance of the former. The use of the system of K₃[Fe(CN)₆]/Mg(OH)₂ in aqueous 1,4-dioxane leads to the regiospecific formation of 1-alkyl-3-(2-quinolyl)-1,4-dihydro-4-quinolones.     

UNPRECEDENTED OUTCOME OF BASE-PROMOTED NEBER REARRANGEMENT OF O-MESYLOXIME OF 2-ARYL-1,2,3,4-TETRAHYDRO-1-METHYLSUL FONYL-4-QUINOLONE- SYNTHESIS OF 4-AMINO-2-ARYLQUINOLINES

Abstract

O-Mesyloximes derived from 2-aryl-1,2,3,4-tetrahydro-1-methylsulfonyl-4-quinolones react with sodium ethoxide in ethanol to afford the 4-amino-2-arylquinolines in high yield. No traces of the 3-amino-2-aryl-4-quinolones expected from the Neber rearrangement of the substrates were detected or isolated from the reaction mixture. The structures of the products were determined using a combination of ¹H NMR, ¹³C NMR, IR and mass spectroscopic techniques.     

Synthesis of quinolines, 2-quinolones, phenanthridines, and 6(5h)-phenanthridinones via palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitroarenes with beta-halo-enals, -enones, or -esters

Palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitrobenzene (1 R = H) and its derivatives with a range of beta-halo-enals, -enones, or -esters readily affords the corresponding beta-aryl derivatives, which are converted into the corresponding quinolines, 2-quinolones, phenanthridines, or 6(5H)-phenanthridinones on reaction with dihydrogen in the presence of Pd on C or with TiCl(3) in aqueous acetone. [reaction: see text]     

Dipole moments of stereoisomers of octahydro-2-methyl-4(1h)-quinolone

Summary The dipole moments of three isomeric octahydro-2-methyl-4(1H)-quinolones were measured. The identity of the moments for all the isomers indicates that the polar groups have the same configuration in the three isomers.     

Diels-Alder reaction of 1,3-butadiene derivatives with 1-methyl-2(1H)-quinolones having an electron-withdrawing group at the 4-position.

Diels-Alder reactions of 1-methyl-2(1H)-quinolones having an electron-withdrawing group at the 4-position with isoprene, butadiene sulfone, and cyclohexadiene were performed to yield functionalized phenanthridones stereoselectively at atmospheric and at high pressure. Regioselectivity and stereochemistry of a methoxycarbonyl group were studied using the semi-empirical and ab initio MO methods, respectively.     

Synthesis of 1-(2-polyfluoroacylaminophenyl)-3-polyfluoroalkylpropane-1,3-diones and 2-polyfluoroalkyl-4-quinolones

The condensation of 2-aminoacetophenone with R^FCO₂Et (R^F = CF₃, CF₂H, CF₂CF₂H) in the presence of LiH in THF or Bu^tOK in Bu^tOH affords either 2-polyfluoroalkyl-4-quinolones or 1-(2-polyfluoroacylaminophenyl)-3-polyfluoroalkylpropane-1,3-diones, depending on the ratio of the initial reactants. The latter are hydrolyzed in an acidic medium to produce 2-polyfluoroalkyl-4-quinolones. N-Methyl-2-trifluoromethyl-4-quinolone was synthesized from 2-aminoacetophenone, CF₃CO₂Et, and MeI in the presence of Bu^tOK.     

Cyclization of 1-benzyl-1,2-dihydro-2-(substituted methylene)quinolines to pyrrolo[1,2-a]quinoline derivatives

1-Alkyl-2-alkylthioquinolinium salts were prepared from 1-alkyl-2(1H)-quinolones via 1-alkyl-2(1H)-thioquinolones in two steps. Under mild conditions, the reaction of 1-alkyl-2-alkylthioquinolinium iodides with active methylene compounds in the presence of sodium hydride afforded 1-alkyl-1,2-dihydro-2-(substituted methylene)quinolines in good yields. The cyclization of 1-benzylquinolines using acetic anhydride produced the corresponding pyrrolo[1,2-a]quinoline derivatives.     

Palladium-Catalyzed [3+2] and [2+2+2] Annulations of 4-Iodo-2-quinolones with Activated Alkynes through Selective C−H Activation

The palladium-catalyzed reaction of 4-iodo-2-quinolones with activated alkynes was investigated. Cyclopenta[de]quinoline-2(1 H)-ones and/or phenanthridine-6(5 H)-ones were obtained through [3+2] annulation involving aromatic C−H activation or [2+2+2] annulation involving vinylic C−H activation, respectively. Reasonable mechanisms for the formation of these annulation products have been proposed based on density functional theory calculations.     

Synthesis of benzo-halogenated 4-hydroxy-2(1H)-quinolones

Malondianilides 3 derived from dichloro substituted anilines 2 undergo cyclization to afford 4-hydroxy-2(1H)-quinolones 4 in very good yields using methane sulfonic acid-phosphorus pentoxide as catalyst. 3,4-Dichloro anilines 5 can be shown to yield two isomers, 7 and 8 , whereas 3-substituted anilines 9 afford merely 7-substituted 4-hydroxy-2(1H)-quinolones 11.     

4-Hydroxy-2-quinolones 7. Synthesis and biological properties of 1-R-3-(2-benzimidazolyl)-4-hydroxy-2-quinolones

Condensation of 1-R-3-carbethoxy-4-hydroxy-2-quinolones with o-phenylene diamine gives the corresponding 1-R-3-(2-benzimidazolyl)-4-hydroxy-2-quinolones. Data on a study of the antithyroid activity of the synthesized compounds is presented.For Communication 6, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 105–108, January, 1993.We express our sincere thanks to A. A. Kirichenko and T. S. Bozhko for the study of the antithyroid activity.     

Synthese von chinolin-kondensierten 2-Chinolonen und Cumarinen via Azidoverbindungen

Coumarins and 2-quinolones (1), having a 4-azido-3-benzyl-moiety, can easily by cyclized by thermo- or photolysis to 3,4-fused quino-coumarins and quino-2-quinolones (2,3).

     

Superacid-catalyzed tandem Meyer–Schuster rearrangement/intramolecular hydroamination of o-anilinopropargyl alcohols for the synthesis of 2,3-dihydro-4(1H)-quinolones

A TfOH-catalyzed synthesis of 2,3-dihydro-4(1H)-quinolones from o-anilinopropargyl alcohols was developed. Studies of N-protecting groups and substituents in phenyl rings showed that diverse groups could be applied. By controlling the catalyst loading, o-anilinopropargyl alcohols underwent the expected transformation smoothly to produce N-protected or N-deprotected 2,3-dihydro-4 (1H)-quinolones in good yields. This transformation probably involved a tandem Meyer–Schuster rearrangement/intramolecular hydroamination reaction process.