The Radical Ions of Indolizino [6,5,4,3-aij]quinoline and Some of its Derivatives

Indolizino [6,5,4,3-aij]quinoline (1) and its 3,9-dimethyl- (2) , di-tert-butyl- (3) and diphenyl- (4) derivatives yield persistent radical cations which have been studied by ESR and ENDOR spectroscopy. The corresponding radical anions have also been prepared, but only that of 3 was amenable to a complete characterization by hyperfine data. The π-spin populations in the radical anions are essentially localized on the 13-membered C-perimeter, and thus both the HOMO and LUMO of 1 exhibit an ‘annulenyl character’. The radical anions of 1 and 2 have gradually been converted into those of the corresponding 3,4-dihydro derivatives ( 1 -H₂ and 2 -H₂) which have been unambiguously identified by a combination of preparative and spectroscopic methods.     

The synthesis of novel polycyclic heterocyclic ring system via photocyclization. 18. Benzo[h]naphtho-[1′,2′:4,5]thieno[2,3-c]quinoline and benzo[h]naphtho-[1′,2′:4,5]thieno[2,3-c] [1,2,4]triazolo[4,3-a]quinoline

The synthesis of two previously unknown polycyclic ring systems, benzo[h]naphtho[1′2′:4,5]-thieno[2,3-c]quinoline ( 1 ) and benzo[h]naphtho[1′,2′:4,5]thieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline ( 2 ), was achieved via oxidative photocyclization of 1-chloro-N-(1-naphthyl)naphtho[2,1-b]thiophene-2-carboxamide ( 5 ). The total assignment of their ¹H and ¹³C nmr spectra was determined by the concerted use of two-dimensional nmr methods.     

The Synthesis of Novel Polycyclic Heterocyclic Ring Systems via Photocyclization. 12. Benzo[h]naphtho-[2′,1′:4,5]thieno[2,3-c]quinoline and benzo[f]-naphtho[2′,1′:4,5]thieno[2,3-c]quinoline

The synthesis of two previously unknown heterocyclic ring systems, namely benzo[h]naphtho[2′,1′:4,5]thi-eno[2,3-c]quinoline (1) and benzo[f]naphtho[2′,1:4,5]thieno[2,3-c]quinoline (2) was accomplished via photocyclization of the appropriate amides followed by chlorination and catalytic dechlorination. The total assignment of ¹H and ¹³C nmr spectra of 2 was determined utilizing two-dimensional nmr methods, providing unequivocal structural proof of the two novel polycyclic ring systems.     

Synthesis of substituted dihydrobenzo[f]pyrimido[4,5-b]-quinolines as tetracyclic 5-deaza nonclassical folates

Cyclocondensation of 2,4,6-triaminopyrimidine ( 10 ) with chlorovinyl aldehyde 7 afforded the linear regioisomer 9,1 1-diamino-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 1 ) while the cyclocondensation of 2,6-diamino-4-hydroxypyrimidine ( 11 ) or 6-amino-2,4-dihydroxypyrimidine ( 12 ) with chlorovinyl aldehyde 7 was regiospecific affording the linear regioisomers 9-amino-11-oxo-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 2 ) and 9,11-dioxo-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 3 ) respectively. The linear structures of these compounds were established by ¹H nmr and ¹³C nmr spectral data.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 5. [1]Benzothieno[2,3-c]naphtho[2,1-f]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline

Two previously unknown heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[2,1-f]quinoline ( 4 ) and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline ( 5 ) were synthesized via photocyclization of 3-chloro-N-(2-phenanthryl)benzo[b]thiophene-2-carboxamide ( 8 ) followed by chlorination and dechlorination. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing inverse-detected HMQC and HMBC two-dimensional nmr spectroscopic methods.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 4 . Benzo[f]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and Benzo[h]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and the total assignment of their 1H- and 13C-NMR spectra

The synthesis of two novel polycyclic heterocyclic ring systems via photocyclization are reported. These are benzo[f]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and benzo[A]thieno-[2′,3′:4,5]thieno[2,3-c]quinoline. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing two-dimensional nmr spectroscopic methods.     

Complete assignment of the 1h- and 13c-nmr spectra of [1]benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline. Concerted use of two-dimensional nmr techniques

The ¹H- and ¹³C-nmr spectra of [1]benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]-naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline were totally assigned using a combination of two-dimensional nmr techniques. After correlation of the proton signals by a COSY spectrum and one-bond heteronuclear correlation, complete assignment of the ¹H- and ¹³C-nmr spectra of the novel heterocyclic compounds required the application of long-range CH coupling information particularly for quarternary resonance assignments and the orientations of individual spin systems relative to one another.     

Assignments of the 1H and 13C NMR spectra of pseudo-symmetric heterocyles using the HMQC-TOCSY experiment to differentiate overlapping spin systems

The ¹H nmr spectra of phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline, benzo[f]phenanthro-[9′,10′:4,5]thieno[2,3-c]quinoline and benzo[h]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline are highly congested. For each compound, all protons abide in an aromatic environment complicated by pseudo-symmetric regions which result in multiple overlap of the different spin systems these molecules contain. We illustrate here the utility of the HMQC-TOCSY experiment to identify spin systems when the proton spectrum is highly congested. To complete the assignment of the ¹H and ¹³C nmr spectra of each compound the HMBC experiment is used to assign the quaternary carbons.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,and benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 13 ), benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 14 ), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 15 ).     

On the synthesis of thieno[3,2-c]quinoline N-oxide and thieno-[3,2-C]isoquinoline N-oxide. The nmr spectra of the six isomeric thieno-fused quinoline and isoquinoline N-oxides

The synthesis of the two remaining isomeric monothieno-analogues of phenanthridine N-oxide, thieno-[3,2-c]quinoline N-oxide and thieno[3,2-c]isoquinoline N-oxide, is described. The ¹H and ¹³C nmr spectra of all six isomeric thieno-fused quinoline and isoquinoline N-oxides are discussed.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

1,4-Cycloaddition reactions. III. Synthesis of furo[3,2-c]pyrido[2,3-g]quinolines,Furo[2,3-a] [4,7]phenanthrolines,Furo[3,2-c]pyrrolo[2,3-g]quinolines,Furo[3,2-c]pyrrolo[3,2-g]quinolines,and Furo[3,2-c]furo[2′,3′:4,5]pyrido[2,3-g]quinolines from 2,3-dihydro-5-methylfuran and schiff bases

The 1,4-cycloaddition of 2,3-dihydro-5-methylfuran (II) to 1-acetyl-1,2,3,4-te trahydro-6-[(p-hydroxybenzylidene)amino]quinoline (VIII) in the presence of boron trifluoride gave two pairs of epimers, namely dl-10-acetyl-2,3,3a,4,5,7,8,9,10,11b-decahydro-4-(p-hydroxyphenyl)-11b-methylfuro[3,2-c]pyrido[2,3-g]quinoline (IXa and b) and dl-8-acetyl-2,3,3a,4,5,8,9,10,11,-11c-decahydro-4-(p-hydroxyphenyl)-11c-methylfuro[2,3-a][4,7]phenanthroline (Xa and b). dl-9-Acetyl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-hydroxyphenyl)-10b-methyl-2H-furo[3,2-c] pyrrolo-[2,3-g]quinoline (XIIIa) was the predominant product isolated from the reaction of II with 1-acetyl-5-[p-(hydroxybenzylidene)amino]indoline (XII). When 1-acetyl-6-[(p-hydroxybenzylidene)amino]indoline (XVI) was treated with 2,3-dihydro-5-methylfuran (II), two epimers of dl-7-acetyl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-hydroxyphenyl)-10b-methyl-2H-furo[3,2-c]pyrrolo[3,2-g]quinoline (XVIIa and b) were obtained. dl-2,3,3a,4,5,6b,8,9,9a,10,11,12b-Dodecahydro-4,10-bis(p-methoxyphenyl)-6b,12b-dimethylfuro[3,2-c]furo[2′,3′:4,5]pyrido[2,3-g]quinoline (XX) was formed when 2,3-dihydro-5-methylfuran was allowed to react with N,N'-bis(p-methoxybenzylidene)-p-phenylcnediamine (XIX). Structure assignments were made from NMR spectra. None of the compounds exhibited appreciable biological activity.     

The synthesis of novel polycyclic heterocyclic ring systems. 3. Synthesis and NMR spectroscopy of 15-chloro[1]benzo-thieno[2″,3″:3′,4′]naphtho[1′,2′:4,5]thieno[2,3-c]quinoline

The polycyclic heterocyclic compound with a novel ring system, 15-chloro[1]benzothieno[2″,3″:3′,4′]-naphtho[1′,2′:4,5]thieno[2,3-c]quinoline was synthesized via photocyclization of 3-chloro-N-phenyl[1]-benzothieno[2′,3′:3,4]naphtho[2,1-b]fhiophene-2-carboxamide followed by chlorination with phosphorus oxychloride. The assignment of its ¹H and ¹³C nmr spectra was accomplished by utilizing two-dimensional nmr methods.     

Synthesis,ABTS-Radical Scavenging Activity,and Antiproliferative and Molecular Docking Studies of Novel Pyrrolo[1,2-a]quinoline Derivatives

A new 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-radical scavenging and antiproliferative agents of pyrrolo[1,2-a]quinoline derivatives have been synthesized. An efficient method for the synthesis of 14 novel diversified pyrrolo[1,2-a]quinoline derivatives has been described using 4-(1,3-dioxolan-2-yl)quinoline and different phenacyl bromides in acetone and followed by reacting with different acetylenes in dimethylformamide/K₂CO₃. The structure of the newly synthesized compounds was determined by infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The in vitro antioxidant activity revealed that among all the tested compounds 5n exhibited maximum scavenging activity with ABTS. Compound 5b has showed good antiproliferative activity as an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase.     

Synthesis of some fused triazoloquinolines

The reaction of 3 -amino-1,2,4-triazolo[4,3-a]quinoline ( II ) with diethyl ethoxymethylenemalonate and ethyl acetoacetate/ethyl trifluoroacetoacetate afforded 10-carboethoxy-9-oxo-9H-pyrimido[1′,2′:1,5][1,2,4]triazolo-[4,3-a]quinoline ( III ) and 11-methyl/trifluoromethyl-9-oxo-9H-pyrimido[1′,2′:1,5][1,2,4]triazolo[4,3-a]quinoline ( IV/V ) respectively. 2-Chloropyridine-3-carboxylic acid chloride reacted with II to yield 5-oxo-5H-pyrido-[3″,2″:5′,6′]pyrimido[1′,2′:1,5][1,2,4]triazolo[4,3-a]quinoline ( VII ), a new ring system.     

Action of HCl on 3-hydroxypyrazolo(iso)quinolines to give 1-chloropyrazoles: evidence for an addition–elimination mechanism by ab initio calculations in gas phase and water

 Addition–elimination reactions involving a nucleophile and a remote leaving group [S^H _N(AE)^tele] are well-known under basic conditions, especially amongst electron-poor six-membered heterocycles, but are less commonly encountered for five-membered heterocycles and are rare under acidic conditions. Concentrated HCl converts 1-hydroxy-1H-pyrazolo[3,4-c] isoquinoline and 1-hydroxy-1H-pyrazolo[3,4-c]quinoline into 3-chloro-1H-pyrazolo[3,4-c]isoquinoline and 3-chloro-1H-pyrazolo[3,4-c]quinoline, respectively. However, apparently neither the isomeric 1-hydroxy-1H-pyrazolo[4,3-c](iso)-quinolines nor the parent 1-hydroxypyrazole undergo this reaction. Additionally, all these systems are refractory under basic conditions. We present a plausible mechanism for the reaction, involving the 3-addition of Cl^- to the diprotonated heterocycle, followed by the elimination of water. Calculations of the initial transition states and intermediates, using optimisation at B3LYP/6-311+G(d,p), including thermochemistry [HF/6-31+G(d)], and single-point Poisson–Boltzmann self-consistent reaction field determination of the free energy of solvation (Jaguar Poisson–Boltzmann self-consistent reaction field), support this mechanism and reproduce the observed order of reactivity, the addition step being 2–4 kcal less favourable for the isomeric 1-hydroxy-1H-pyrazolo[4,3-c](iso)quinolines and provide a rationalisation for the role of strong acid. Received: 27 June 2002 / Accepted: 6 September 2002 / Published online: 14 February 2003     

Bis-aminoquinolines as potential antimalarial agents and a novel fused ring system,pyrano[3,2-c:5,6-c′]diquinoline

3,3′(1,3-Ethyliminodimethylene)bis(4-hydroxy-6-methoxy-2-methyl)quinoline ( 2c ) and related compounds were synthesized. 3,3-Methylenebis(4-hydroxy-6-methoxy-2-methyl)quinoline ( 5 ) was prepared and upon treatment with phosphorus oxychloride gave 1,13-dimethyl-5,9-dimethoxy-14H-pyrano[3,2-c:5,6-c′]diquinoIine (6), a novel ring system.     

A Facile Synthesis of Novel 9-Methyl[1, 2, 3]Selenadiazoles[4, 5-b]Quinoline and 9-Methyl[1, 2, 3]Thiadiazole[4, 5-b]Quinoline as a New Class of Antimicrobial Agents

2-chloro-4-methyl quinoline 2 on condensation with semicarbazide hydrochloride gave its semicarbazone. This on reaction with SeO ₂ and SOCl₂ yielded a new class of novel selenadiazoles 4 and thiadiazoles 5, respectively. The structure of all the compounds were elucidated on the basis of elemental analysis, IR, ¹ H NMR, and the mass spectral data. Some derivatives of 9-methyl[1, 2, 3]selenadiazole[4, 5-b] quinoline and 9-methyl[1, 2, 3]thiadiazole [4, 5-b]quinoline have been screened for antimicrobial activities.     

Quino[1,2-c]quinazolines. I. Synthesis of quino[1,2-c]quinazolinium derivatives and the related indazolo[2,3-a]quinoline derivatives as analogs of the antitumor benzo[c]phenanthridine alkaloids

9,10-Dimethoxy-1,2,3,4,12,13-hexahydro-1-oxoquino[1,2-c]quinazolinium perchlorate, 1,2,3,4,13,24-hexahydro-1-oxo[1,3]dioxolo[4,5-g]quino[1,2-c]quinazolinium perchlorate, 6-methyl-2,3,9,10-tetramethoxyquino-[1,2-c]quinazolinium perchlorate and 2,3-dimethoxy-13-methyl[1,3]dioxolo[4′,5′:6,7]quino[1,2-c]quinazolinium perchlorate were synthesized as analogs of the potent antitumor benzo[c]phenanthridine alkaloids nitidine and fagaronine. The related 2,3,8,9-tetramethoxyindazolo[2,3-a]quinoline and 2,3-dimethoxy[1,3]dioxolo-[4,5-g]indazolo[2,3-a]quinoline were also synthesized. Further, the novel formation of 6,7-dimethoxy-2-(2-ethylamino-4,5-dimethoxyphenyl)quinoline via reductive alkylation with Raney nickel in refluxing ethanol is also reported.     

1,4-Cycloaddition reactions. II. Preparation of p-dioxino[2,3-g]furo[3,2-c] quinolines,p-dioxino[2,3-f] furo[3,2-c] quinolines,and [1,3] dioxolo[4,5-g] furo[3,2-c] quinolines from 2,3-dihydro-5-methylfuran and schiff bases

The boron trifluoride catalyzed 1,4-addition of 2,3-dihydro-5-methylfuran to N-(p-methoxy-benzylidene)-1,4-benzodioxan-6-amine (II) gave 2 pairs of epimers, 2,3,3a,4,5,8,9,11b-octahydro-4-(p-methoxyphenyl)-11b-methyl-p-dioxino[2,3-g]furo[3,2-c]quinoline (IIIa and b) and 2,3,7,8,8a,9.10,1la-octahydro-8-(p-methoxyphenyl)-11a-methyl-p-dioxino[2,3-f]furo[3,2-c]quinoline (IVa and b). When N-(p-methoxybenzylidene)-3,4-methylenedioxyaniline (V) was condensed with 2,3-dihydro-5-methylfuran in an analogous manner, a mixture of 2 epimers of 2,3,3a,4,5,10b-hexahydro-4-(p-methoxyphenyl)-10b-methyl[1,3]dioxolo[4,5-g]furo[3,2-c]quinoline (VIa and b) was isolated. Treatment of this mixture with sulfur afforded 6-(p-methoxyphenyl)-8-methyl-1,3-dioxolo[4,5-g]quinoline-7-ethanol (VIII). Structural assignments for all of the products were made from NMR spectra. None of the compounds possessed appreciable biological activity.