The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 9. Synthesis of 2-arylquinoline alkaloids

A one-step synthesis of N-methyl-2-aryl-4-quinolone alkaloids is described. These compounds are readily prepared from the reaction of an N-methylisatoic anhydride with the lithium enolate of an acetophenone. By this method, the reaction of N-methylisatoic anhydride ( 5 ) or 5-methoxy-N-methylisatoic anhydride ( 7 ) with acetophenone produces the alkaloids N-methyl-2-phenyl-4-quinolone ( 1 ) and eduline ( 2 ) in 81% and 70% yield, respectively. An analogous reaction of 5 with 3,4-methylenedioxyacetophenone gives graveoline ( 3 ) in 63% yield whereas 7 and α-methoxyacetophenone affords japonine ( 4 ) in 61% yield.     

Synthesis and condensation reactions of the boron difluoride complex with 3-acetyl-4-hydroxy-1-methyl-2-quinolone

A reaction of 3-acetyl-4-hydroxy-1-methyl-2-quinolone with boron trifluoride etherate gave its boron difluoride complex. Condensation of this complex with various carbonyl compounds afforded new 2-quinolone derivatives (polymethine and styryl dyes) that intensely absorb in the visible region of the spectrum and show effective fluorescence. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1701–1706, August, 2008.     

The nitroalkene showing dual behaviors in the same reaction system

The nitroalkene moiety of 1-methyl-3,6,8-trinitro-2-quinolone showed dual behaviors in the same reaction system, namely electron-poor heterodiene and dienophile, and affording polycyclic products.     

Novel azo dyes derived from 8-methyl-4-hydroxyl-2-quinolone：Synthesis, UV-vis studies and biological activity

In this study, N,N'-di-(2-methylphenyl)malonamide was synthesized and reacted with polyphosphoric acid to afford 8-methyl-4-hydroxyl-2-quinolone. Eight novel azo disperse dyes were then synthesized by linking diazotized p-substituted aniline derivatives with 8-methyl-4-hydroxyl-2-quinolone. The solvatochromism of these azo dyes in various solvents was evaluated. All the compounds were then evaluated for their antibacterial activity against four bacteria, namely, Bacillus subtilis, Micrococcus luteus, Salmonella enterica, and Pseudomonas aeruginosa. The results showed that some of these compounds have high levels of antibacterial activity.     

The chemistry of 2h-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 17 Synthesis of 2-alkyl-4-quinolone alkaloids via a one-step reaction of N-methylisatoic anhydride with methyl ketone enolates

Lithium enolates derived from aliphatic methyl ketones react with N-methylisatoic anhydride (5) at ?78° to give 2-alkyl-4-quinolone alkaloids 7 in a single step. The method was used to synthesize both double bond isomers of 1-methyl-2-(8-tridecenyl-4(1H)-quinolinone (8) thereby showing that the alkaloid evocarpine possesses the Z-olefin stereochemistry 8a. Reduction of 8a provided the alkaloid dihydroevocarpine (16). Compound 16 was also directly prepared from the reaction of 5 with the lithium enolate of 2-pentadecanone.     

Studies on ketene and its derivatives. CXI . Photoreaction of diketene with 2(1H)-quinolone derivatives

Photoreaction of diketene with 4-methyl-2(1H)-quinolone and 1,4-dimethyl-2(1H)-quinolone gave 2R*,2aR*,SbR*- and 2R*,2aS*8bS*-8b-methyl-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline-2-spiro-2′-(oxetan)-4′-one ( 6a and 6b ), and their 4-methyl derivatives 7a and 7b , respectively. Thermolysis of compounds 6 and 7 afforded 2aR*,8bS*-8b-methyl-2-methylene-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline ( 8 ) and its 4-methyl derivatives 9 , respectively. Similarly, photolysis of diketene and 4-acetoxy-2(1H)-quinolone gave 1R*,2aS*,8bS*- and 1R*,2aR*,8bR*-8b-acetoxy-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]-quinoline ( 11a and 11b ). Alcoholysis of compounds 11a and 11b with hydrogen chloride in methanol gave 1-hydroxy-1-(methoxycarbonyl)methylcyclobuta[c]quinoline derivative 12 and 13 which were transformed to 4-acetyl-3-methyl-2(1H)-quinolone ( 15 ) by further alcoholysis. Photoreaction of diketene with 2(1H)-quinolone derivatives gave the corresponding cyclobuta[c]quinoline spirooxetanone derivatives 18 and 23 , which, by thermolysis, were transformed to 2-methylenecyclobuta[c]quinoline 23 and 25 , respectively.     

4-Hydroxy-2-quinolones. 2. Simple synthesis of arboricine

Acylation of methyl N-methylanthranilate with phenylacetyl chloride with subsequent intramolecular cyclization of the resulting anilide was used to synthesize 1-methyl-3-phenyl-4-hydroxy-2-quinolone (arboricine).See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 522–524, April, 1992.     

The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment

Pseudomonas aeruginosa produces 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), a quorum-sensing (QS) signal that regulates numerous virulence genes including those involved in iron scavenging. Biophysical analysis revealed that 2-alkyl-3-hydroxy-4-quinolones form complexes with iron(III) at physiological pH. The overall stability constant of 2-methyl-3-hydroxy-4-quinolone iron(III) complex was log beta(3) = 36.2 with a pFe(3+) value of 16.6 at pH 7.4. PQS was found to operate via at least three distinct signaling pathways, and its precursor, 2-heptyl-4-quinolone (HHQ), which does not form an iron complex, was discovered to function as an autoinducer molecule per se. When PQS was supplied to a P. aeruginosa mutant unable to make pyoverdine or pyochelin, PQS associated with the cell envelope and inhibited bacterial growth, a finding that reveals a secondary function for PQS in iron entrapment to facilitate siderophore-mediated iron delivery.     

Acetals of lactams and acid amides. 46. Unusual reactions of α-cyano-β-dimethylaminocrotonamide with anthranilic acid derivatives

It has been shown that the reaction of the enaminoamide -cyano--dimethylaminocrotonamide with anthranilic acid and its ethyl ester unexpectedly gives quinazoline-2,4-dione and 2-methyl-3-cyano-4-quinolone, respectively. The structures of the products were confirmed by their spectra and by direct synthesis.For communication 45, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 84–87, January, 1986.     

Preparative isolation and purification of alkaloids from the Chinese medicinal herb Evodia rutaecarpa (Juss.) Benth by high-speed counter-current chromatography

High-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water system (5:5:7:5, v/v) was applied to the isolation and purification of alkaloids from the Chinese medicinal plant Evodia rutaecarpa (Juss.) Benth. Five kinds of alkaloids were obtained and yielded 28 mg of evodiamine (I), 19 mg of rutaecarpine (II), 21 mg of evocarpine (III), 16mg of 1-methy-2-[(6Z,9Z)]-6,9-pentadecadienyl-4-(1H)-quinolone (IV), 12 mg of 1-methyl-2-dodecyl-4-(1H)-quinolone (V) from 180 mg of crude extract in a one-step separation, with the purity of 98.7%, 98.4%, 96.9%, 98.0%, 97.2%, respectively, as determined by high performance liquid chromatography (HPLC). The structures of these compounds were identified by 1H NMR and 13CNMR.     

Quantum-Chemical Study of Proton Transfer and Photoreactions of Quinolone Derivatives

The possible routes of deactivation of electronically excited states of 4-methyl-7-hydroxy-2-quinolone and its protolytic forms were analyzed. The relative contribution of radiative and nonradiative deactivation channels of electronic excitation energy was determined, and the rate constants of photophysical processes (internal conversion and intersystem crossing) occurring upon light absorption by these forms were estimated.     

Schmidt Reaction on 2-Aryl-1,2,3,4-tetrahydro-4-quinolone

Synthesis and stereochemistry of 2-aryl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 2-aryl-2,3-dihydro-4H-tetrazolo [1,5-d]-1H-1,4-benzodiazepine is reported by the Schmidt reaction on 2-aryl-1,2,3,4-tetrahydro-4-quinolone.     

Preparation and proton spectra of 1-aryl-1,2-dihydro-2-quinolones

1-Phenyl-, 1-m-tolyl- and 1-p-tolyl-1,2-dihydro-2-quinolone have been prepared by treating the potassium derivative of 1,2-dihydro-2-quinolone with the corresponding aryl bromide in the presence of finely divided copper. The use of o-bromotoluene in this reaction gave trace amounts of a crystalline material which upon the basis of mass spectrum analysis was assigned 2-o-tolyloxyquinoline as a structure. The 1-aryl groups caused an unusual chemical shift of the 8-proton to the Δ 6.64–6.70 region. This behavior paralleled that observed for the 7-proton of 6-phenyl-6H-indeno[1,2-c]isoquinoline-5,11-dione in earlier studies.     

Reactions of 2′-NHR-Chalcone Dibromides with Ammonia

Synthesis of 2′-NHR-chalcone dibromides and their reaction with methanolic ammonia are discussed. Depending on the character of the R group, ethylenimine, -bromochalcone, 2,3-dimethoxypropan-1-one and 1,2,3,4-tetrahydro-4-quinolone derivatives were obtained.     

Synthesis of isocoumarin, 1-isoquinolone and 4(1H)-quinolone derivatives via seleno-intermediates

The reaction of 2-styrylbenzoic acids 2 with N-phenylselenosuccinimide (N-PSS) affords 3-phenyl-iso-coumarin derivatives 3 and 3,4-dihydro-3-phenyl-4-(phenylseleno)isocoumarins 4 via selenolactonization. The reaction of 2-styrylbenzamides 5 and 1-(2-aminophenyl)-3-phenyl-2-peropen-1-one derivatives 11 with N-PSS also resulted in the formation of 1-isoquinolone 6 and 4(1H)-quinolone derivatives 12 , respectively.     

Differences in the mass spectra of isomeric benzolactams

It is shown that 3- and 4-substituted dihydro-2-quinolones can be distinguished from the isomeric dihydro-1-isoquinolones by mass spectrometry. The [M - CO]⁺ ion is characteristic for the mass spectra of dihydroquinolone derivatives, whereas retrodiene fragmentation of the molecular ion is characteristic for dihydroisoquinolone derivatives. The intense [M - R]⁺ and [M - R, - H₂O]⁺ ion constitute evidence that the substituent is located in the 3 (for dihydroisoquinolones) or 4 (for dihydroquinolones) position. The processes that occur in the fragmentation were confirmed by data from the high-resolution mass spectra, an analysis of the observed metastable ions, and an analysis of the mass spectra of 3-methyl-3,4-dihydro-1-isoquinolone and 4-methyl-3,4-dihydro-2-quinolone containing deuterium attached to the nitrogen atoms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 246–249, February, 1979.     

Raney nickel reductions—VIII A synthesis of 1:2-benzanthracene and its 3′-methyl and 4-methyl derivatives

1:2-Benzanthracene and the 3′-methyl derivative have been prepared by Raney nickel reduction of the sulphuric esters of the leuco derivatives of 1:2-benzanthraquinone and 4′-chloro-3′-methyl-1:2-benzanthraquinone, followed by dehydrogenation. 3-Hydroxy-1:2-benzanthraquinone was methylated in the 4-position by formaldehyde, sodium hydrosulphite and sodium hydroxide solution (the Marschalk reaction). Simultaneous reduction of the nuclear hydroxyl and quinone groups was effected by Raney nickel reduction of the trisulphuric ester of 3:9:10-trihydroxy-4-methyl-1:2-benzanthracene, and the resultant hexahydro-4-methyl-1:2-benzanthracene was dehydrogenated to 4-methyl-1:2-benzanthracene. The preparation of 3:4:9:10-dibenzopyrene from Mayvat brilliant red AF by Raney nickel reduction of the sulphuric ester of the leuco derivative and subsequent dehydrogenation is described.     

Computational assessment of the electronic structure of 1-azacyclohexa-2,3,5-triene (3 delta 2-1H-pyridine) and its benzo derivative (3 delta 2-1H-quinoline) as well as generation and interception of 1-methyl-3 delta 2-1H-quinoline

Treatment of a solution of 3-bromo-1-methyl-1,2-dihydroquinoline (9) and [18]crown-6 in furan or styrene with KOtBu followed by hydrolysis afforded a mixture of 1-methyl-1,2-dihydroquinoline (10) and 1-methyl-2-quinolone (11). If the reaction was performed in [D(8)]THF and the mixture was immediately analysed by NMR spectroscopy, 2-tert-butoxy-1-methyl-1,2-dihydroquinoline (17) was shown to be the precursor of 10 and 11. The structure of 17 is evidence for the title cycloallene 7, which arises from 9 by beta elimination of hydrogen bromide and is trapped by KOtBu to give 17 so fast that cycloadditions of 7 with furan or styrene cannot compete. Since this reactivity is unusual compared to the large majority of the known six-membered cyclic allenes, we performed quantum-chemical calculations on 8, which is the parent compound of 7, and the corresponding isopyridine 6 to assess the electronic nature of these species. The ground state of 6 was no longer an allene (6 a) but the zwitterion 6 b. In the case of 8, the allene structure 8 a is more stable than the zwitterionic form 8 b by only approximately 1 kcal mol(-1). These results suggest a high reactivity of 6 and 8 towards nucleophiles and explains the behaviour of 7. In addition to the ground states, the low-lying excited states of 6 and 8 were considered, which are represented by the diradicals 6 c and 8 c and, as singlets, lie above 6 b and 8 a by 19.1-24.8 and 14.4-17.7 kcal mol(-1), respectively.     

1-methyl-2-undecyl-4(1H)-quinolone as an irreversible and selective inhibitor of type B monoamine oxidase

The inhibitory compound of monoamine oxidase (MAO) activity was isolated from the CH(2)Cl(2) fraction of the fructus of Evodia rutaecarpa and identified as 1-methyl-2-undecyl-4(1H)-quinolone (1). Compound 1 showed a selective inhibition of type B MAO (MAO-B) activity with the IC(50) value of 15.3 microM using a substrate kynuramine, but did not inhibit type A MAO (MAO-A) activity. The kinetic analysis using Lineweaver-Burk plots indicated that compound 1 competitively inhibited MAO-B activity with the K(i) value of 9.91 microM. The inhibition of MAO-B by compound 1 was found to be irreversible by dialysis of the incubation mixture. These results suggest that compound 1 is a potent irreversible inhibitor of MAO-B, and may regulate catecholamine content in the neurons.     

Conversion of 2-amino-3-phenyl-4-quinolone to 1H-2,3-dihydro-2,9-dioxo-10-phenylimidazo[1,2-a]quinoline

1H-2,3-Dihydro-2,9-dioxo-10-phenylimidazo[1,2-a]quinoline has been obtained from 2-amino-3-phenyl-4-quinolone by acylation with chloroacetyl chloride and cyclization of the intermediate 2-di(chloroacetyl)amino-3-phenyl-4-chloroacetoxyquinoline. The reaction of the latter with morpholine was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 388–390, March, 1990.