Search

International audience; The following chapter surveys the functionalization of diazines and their benzo derivatives via transition metal-catalyzed C-H bond activations. Carbon-carbon and carbon-heteroatom (N, O, B, Si, halogen) bond-forming processes have been achieved in a selective manner for this type of organic molecules relevant for fields as diverse as materials sciences and biology. In addition, a particular focus is devoted to the mechanistic discussions that provide fundamental understanding for the regio-selectivity observed in these transformations. The unique role of the metal catalyst is also highlighted.

A gold(I)-catalyzed 6-endo-dig cyclization of aromatic 1,5-enyne was developed to synthesize 2-(naphthalen-2-yl)aniline. The functional group tolerance of this cyclization was examined systematically and a possible mechanism was proposed. The derivatization of 2-(naphthalen-2-yl)aniline was carried out to facile access to benzo[α]carbazole, benzo[c,h]cinnoline and dibenzo[i]phenanthridine derivatives in a divergent way.

V magistrskem delu smo preučevali, kako raznolik nabor cinolinov lahko pripravimo z novo reakcijo, katalizirano s p-toluensulfonsko kislino. Reakcija ciklizacije iz o-vinilanilinov in terc-butil nitrita poteka pri sobni temperaturi v topilu etil acetatu in s katalitsko količino p-toluensulfonske kisline. Vse nastale spojine smo okarakterizirali s pomočjo tehnik jedrske magnetne resonance, masne spektrometrije visoke ločljivosti, visokotlačne tekočinske kromatografije in infrardeče spektroskopije. Trdnim spojinam smo izmerili še tališče. o-Vinilaniline smo pripravili iz fenilacetilena in različno substituiranih anilinov s heterogenim katalizatorjem montmorilonitom K-10. Reakcijske pogoje smo optimizirali na modelni reakciji. Izolirali in okarakterizirali smo stranski produkt, derivat kinolin, ki je nastal pri reakciji. Na modelni reakciji smo optimizirali tudi reakcijo sinteze cinolinov. Osredotočili smo se na ekstrakcijo in čiščenje produkta. In this work, we have investigated the wide range of cinnolines that we can produce using the new reaction catalyzed by p-toluenesulfonic acid. The cyclization reaction takes place at room temperature in ethyl acetate. In this process, o-vinylanilines and tert-butyl nitrite are used as starting compounds and a catalytic amount of p-toluenesulfonic acid. All synthesized compounds were characterized by nuclear magnetic resonance, mass spectrometry, high- pressure liquid chromatography and infrared spectroscopy. The melting points of the solid compounds were measured. o-Vinylanilines were synthesized from phenylacetylene and various anilines. The heterogeneous catalyst montmorillonite K-10 was used for the reaction. A model reaction was carried out to optimize the reaction conditions. The product of a side reaction was isolated and characterized as a quinoline derivative. A model reaction for cinnoline synthesis was used to optimize the reaction conditions. We mainly focused on extraction and purification.

Polar Aromatic Compounds (PAC) adsorbed on soot produced in laboratory premixed flames of fossil kerosene (Jet A-1), Synthetic Paraffinic Kerosene (SPK), and Jet A-1 - synthetic biofuels (2,5-dimethylfuran, methyloctanoate, diethylcarbonate and 1-butanol) were characterized for the first time in the aim of shedding light on the combustion mechanisms and evaluating the environmental impact of these synthetic biofuels. The following families of compounds were fractioned from the soot extracts and further their relative abundances estimated: (a) oxa-AHs (xanthenes, benzoxanthene, alcoxy-AHs, furan…); (b) aldehydes-AHs, (c) ketones-AHs; (d) quinones-AHs; (e) aromatic monocarboxylic acids; (f) aromatic hydroxy-acids; (g) aromatic dicarboxylic acids; (h) nitrated-AHs (including amines, acridines, cinnoline derivatives, carbazoles…); (i) nitro-AHs. The results obtained point out that overall, soot from Jet A-1 - biofuels premixed flames are richer in PAC than soot from pure Jet A-1 and SPK. Out of the fuels studied, Jet A-1 - 1-butanol produces the highest concentrations of nitro-AHs (namely nitro-benzaldehydes), of aldehydes-AH and hydroxy-AHs (including two isomers of hydroxy-benzaldehyde); whereas Jet A-1 - diethylcarbonate produces the highest concentrations of quinone-AHs (especially phenanthrene-quinones) and large concentrations of nitrated-AHs. On the other hand, soot from Jet A-1 - methyloctanoate is the richest one in mono aromatic and dicarboxylic acids, aromatic hydroxyacids, nitrated-AHs, and esters. Combustion of the Jet A-1 - 2,5-dimethylfuran mixture emits the highest concentrations of ketone-AHs, and oxa-AHs (namely, furan derivatives). We should remark that although the soot samples were obtained from pre-mixed flames, the lab conditions being far from the industrial conditions, particularly in terms of pressure; the chemistry going on should not be so different that our findings could not be extrapolated to industrial conditions.

A highly efficient palladium-catalyzed cascade annulation of pyrazolones and aryl iodides to access various benzo[c]cinnoline derivatives has been achieved at 80 °C. A pyridine-type ligand could im...

International audience; Six-membered-diaza ring of Cinnoline has been fused on Naphthalimide dye to give a donor-acceptor system called CinNapht. This red shifted fluorophore, that can be synthetised in gram scale, exhibits a large Stoke Shift and a fluorescence quantum yield up to 0.33. It is also characterized by a strong solvatochromic effect from green to red emission as well and can be used for bioimaging.

The first Ru(II)-catalyzed cascade C–H activation/annulation reactions of N-aryl-pyrazolidinones with sulfoxonium ylides for the synthesis of cinnoline-fused pyrazolidinones are reported. This transformation proceeds smoothly under operationally simple conditions in 10 min using a simple and cheap catalytic system consisting of Ru(II) and Zn(OTf)2. A wide range of substrates were assessed in this transformation, and the products were isolated in good to excellent yields (51% to 99%).

New cinnoline derivatives have been synthesized by reductive cyclization of hydrazones obtained by condensation of various 2-nitrophenylhydrazine derivatives with methyl pyruvate and dimethyl acetylenedicarboxylate. Microbiological tests of these new derivatives were carried out against four bacterial strains, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis, as well as two fungal strains, Saccharomyces cerevisiae and Candida albicans. The synthesized compounds showed good to moderate activity.

Fourteen Novel cinnoline library compounds were designed, synthesized through a facile approach, and allowed for screening for anti-bacterial activity and anti-tubercular activity. The titled compounds were entirely synthesized by replacing alkyl groups, sulphonyl, halo groups in the 6th & 7th position of cinnoline moiety. The enlightenment of structure was done by FTIR HNMR along with elemental analysis and further docked for Structural activity. The newly synthesized Cinnoline Compounds were examined for their in vitro drug-sensitive M tuberculosis H37Hv strain. All the compounds have shown MIC between >100-12.5 μg /ml. In this investigation, we Evaluated all the compounds for Anti-bacterial activity. The main compounds were initially tested in vitro for Anti-bacterial activity against gram-positive and gram-negative bacteria by using the Disk plate method. The most active Compound 10 exhibited 12.5 μg /ml inhibitions against drug-sensitive M Tuberculosis H37Rv strain. Among all synthesized compounds CN-7 was found to be a Hit compound with MIC value 12.5 ug/ml Against E Coli.

Data on the spectroscopy of photoexcitation of trans-to-cis isomerization and fragmentation of protonated trans-azobenzene (ABH+) in an inert gas atmosphere are analyzed. Results from gas-phase isomerization are compared to ones from a liquid-phase reaction in aqueous sulfuric acid that results in the formation of cyclic benzo[c]cinnoline. There is no cyclization upon gas-phase trans-to-cis isomerization in a rarefied nitrogen medium at T = 300 K, due to the high rate of inverse cis-to-trans isomerization. It is shown that transformations in both phases proceed with the participation of phenylaminyl type cations trans- and cis-ABH+, which are chromogens. Photofragmentation of trans-ABH+ in an atmosphere of cryogenically cooled helium (T = 40 K) proceeds with the formation of fragment phenyl and phenyl diazonium cations and the participation of phenyl amine cations. Mechanisms of photofragmentation are proposed, including intermediate acts with the participation of H atoms formed by dissociation of the NH group. A fast attack of H atoms along the phenyl ring bonded to the NH group results in the breaking of the C–N bond, eliminating the possibility of trans-to-cis isomerization in a cryogenic helium atmosphere.

Straightforward method for the synthesis of pyrrolo[1,2-b]cinnolines starting from 2-nitrobenzaldehydes and 2-methylfurans has been elaborated. The key steps of the process are oxidative furan ring opening with diazonium cation and intramolecular alkylation of azo group of the resulted cinnoline with secondary allyl alcohol.

The chemistry of trinuclear silver(I) pyrazolates with aromatic, bidentate N-heterocycles, 1,10-phenanthroline, 4,6-dimethylpyrimidine, 4,7-phenanthroline, benzo[c]cinnoline, and 4-(2-pyridyl)pyrimidine are presented. Results presented here show the effects of the donor nitrogen lone-pair orientations of the N-heterocycles on the product structures. The chelating ligand, 1,10-phenanthroline with {[3,5-(CF3)2Pz]Ag}3, {[4-Cl-3,5-(CF3)2Pz]Ag}3 and {[4-Br-3,5-(CF3)2Pz]Ag}3 produced tetranuclear species, that exhibited blue luminescence under UV light. 4,6-dimethylpyrimidine and 4,7-phenanthroline that have nitrogen lone pairs in a non-chelating arrangement produced polymeric, mixed ligand silver pyrazolate complexes when treated with {[3,5-(CF3)2Pz]Ag}3. The reaction of {[3,5-(CF3)2Pz]Ag}3 with benzo[c]cinnoline did not lead to the breakup of the precursor Ag3N6 core, but resulted in a trinuclear silver complex with two- and three-coordinate silver centers. The reaction between 4-(2-pyridyl)pyrimidine and {[3,5-(CF3)2Pz]Ag}3 generated a coordination polymer featuring saddle-shaped {[3,5-(CF3)2Pz]Ag}4 units. Most of these complexes show intermolecular π-stacking and argentophilic contacts. The fluorinated pyrazolate serves as a bridging ligand in all the silver complexes.

Fluorescent probes for nitric oxide (NO), or more frequently for its oxidized surrogate dinitrogen trioxide (N2O3), have enabled scientists to study the contributions of this signaling molecule to many physiological processes. Seeking to improve upon limitations of other probes, we have developed a family of fluorescent probes based on a 2-amino-3′-dialkylaminobiphenyl core. This core condenses with N2O3 to form benzo[c]cinnoline structures, incorporating the analyte into the newly formed fluorophore, which results in product fluorescence with virtually no background contribution from the initial probe. We varied the substituents in the core in order to optimize both the reactivity of the probes with N2O3 and their cinnoline products' fluorescence wavelengths and brightness. The top candidates were then applied to cultured cells to verify that they could respond to NO within cellular milieus, and the top performer, NO530, was compared with a “gold standard” commercial probe, DAF-FM, in a macrophage-derived cell line, RAW 264.7, stimulated to produce NO. NO530 demonstrated similar or better sensitivity and higher selectivity for NO than DAF, making it an attractive potential alternative for NO tracking in various applications., A thorough structure-property relationship study has produced much-improved fluorescence probes for nitric oxide surrogate, e.g. N2O3, compared to the original NO550.

Dihydrocinnolines have significant pharmacological properties. Herein, we investigate a Cu-catalyzed tandem N-arylation reaction of phthalhydrazides with cyclic iodonium salts to construct dihydrobenzo[c]cinnoline derivatives. Various iodonium salts, such as symmetrical, unsymmetrical, aryl-aryl, and aryl-heteroaryl ones, could react with phthalhydrazides smoothly and give the title products in moderate to high yields. Moreover, the -NH2 group, which has been diarylated by cyclic iodonium salts to form carbazoles in previous reports, is also well tolerated in this work.

A gold(I)-catalyzed 6-endo-dig cyclization of aromatic 1,5-enyne was developed to synthesize 2-(naphthalen-2-yl)aniline. The functional group tolerance of this cyclization was examined systematically and a possible mechanism was proposed. The derivatization of 2-(naphthalen-2-yl)aniline was carried out to facile access to benzo[α]carbazole, benzo[c,h]cinnoline and dibenzo[i]phenanthridine derivatives in a divergent way.

The inter-fragment interactions at various binding sites and the overall cluster stability of quinolone (QNOL), cinnoline (CNOL), quinazoline (QNAZ), and quinoxaline (QNOX) complexes with H2O were studied using the density functional theory (DFT) approach. The adsorption and H-bond binding energies, and the energy decomposition mechanism was considered to determine the relative stabilization status of the studied clusters. Scanning tunneling microscopy (STM), natural bonding orbitals (NBO) and charge decomposition were studied to expose the electronic distribution and interaction between fragments. The feasibility of formations of the various complexes were also studied by considering their thermodynamic properties. Results from adsorption studies confirmed the actual adsorption of H2O molecules on the various binding sites studied, with QNOX clusters exhibiting the best adsorptions. Charge decomposition analysis (CDA) revealed significant charge transfer from substrate to H2O fragment in most complexes, except in QNOL, CNOL and QNAZ clusters with H2O at binding position 4, where much charges are back-donated to substrate. The O---H inter-fragment bonds was discovered to be stronger than counterpart N---H bonds in the complexes, whilst polarity indices confirmed N---H as more polar covalent than O---H bonds. Thermodynamic considerations revealed that the formation process of all studied complexes are endothermic (+ve ΔHf) and non-spontaneous (+ve ΔGf)., Diazanaphthalenes; Quinolone; Aqueous; DFT; Adsorption.

Starting from phenylhydrazine and glucose, a versatile cinnoline scaffold was obtained on a multigram scale and further derivatized. A simple continuous-flow hydrogenation process permits the conversion of selected cinnolines into their 1,4-dihydrocinnoline counterparts. These products are generated in high yields and high purities with residence times of less than one minute and, along with their cinnoline precursors, are expected to serve as valuable heterocyclic building blocks for future medicinal chemistry programs. University College Dublin 2020-10-05 JG: PDF replaced with correct version

Synthesis of a new series of pyrimidinothienocinnoline derivatives involves the reaction of 9-aminodibenzo[f, h]pyrimido[4′,5′:4,5]thieno[2,3-c]cinnoline-8-carbonitrile with formamide that gives 8-amino-dibenzo[f, h]-pyrimido[4′,5′:4,5]thieno[2,3-c]cinnoline. Reactions of the latter with morpholine, piperidine, malononitrile, phenylbromide, aromatic aldehydes, and ethyl cyanoacetate have been studied. Some synthesized compounds have been subjected to further transformations. The synthesized pyrimidinothienocinnoline derivatives are tested for their anti-inflammatory activity.

Crinnolines can serve as unique and versatile class of heterocycles especially in fields related to synthetic and pharmaceutical chemistry owing to their potent biological activities. They possess diversity of pharmaceutical activities as anticancer, antibacterial, anti-inflammatory, anti-allergic as well as anti-hypertensive activities. Since the first synthesis of cinnoline by Richter (1883) numerous protocols for their synthesis have been developed utilizing arenediazonium salts, aryl hydrazines and arylhydhydrazones precursors. Recently metal catalyzed C-C and C-N bond formation reactions have emerged as efficient tools for synthesis of cinnoline derivatives. This review aims to focus on the recent synthetic routes used for the synthesis of cinnoline derivatives. An effort has been carried out to provide an overview of practical methods for preparing cinnolines. Furthermore the reaction mechanisms have been described in brief.

Heterocyclic conjugated polymers BZCTVT and TAPTVT containing benzo[c]cinnoline (BZC) and tetraazapyrene (TAP), respectively, were prepared by using Stille coupling polymerization in microwave reactor. BZC and TAP act as acceptors and thiophene-vinylene-thiophene (TVT) acts as donors. Alkylated thiophene is the linker between acceptor and donor. This is the first time that tetraazapyrene was incorporated into conjugated polymers. The films of BZCTVT and TAPTVT showed maximum absorption wavelength at 522 and 534 nm, respectively. From cyclic voltammertry measurement, TAPTVT and BZCTVT exhibited low LUMO (−3.61 and −3.47 eV) and HOMO (−5.64 and −5.63 eV) energy levels. Even though BZC and TAP were planar structures, BZCTVT and TAPTVT showed large dihedral angles between alkylated thiophene and TVT (10.8–22.6°), and between alkylated thiophene and BZC and TAP (22.2–30.3°) based on their simulated energy-minimized geometry. The bottom-gate, top-contact OFETs based on TAPTVT and BZCTVT exhibited only p-channel behavior with hole mobility of 4.63 × 10−4 and 1.04 × 10−4 cm2 V−1 s−1 and current on/off ratios greater than 104 after thermal annealing. Grazing incidence X-ray diffraction (GIXRD) patterns suggested that thin films of TAPTVT and BZCTVT preferred edge-on orientation.

Modified polycyanostyrene and polynitrostyrene microspheres were designed and synthesized, which proved to be an effective carrier to prepare gold nanoparticles with pentazole gold as a catalyst precursor. The developed gold nanoparticles were characterized using scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray, X-ray power diffraction and X-ray photoelectron spectrometry. In addition, it was observed that this catalytic system successfully achieved application in the synthesis of cinnoline derivatives and hydration reactions in high yields. Mechanism investigation was conducted to better understand these transformations and catalyst systems. To the best of our knowledge, this is the first example of utilizing pentazole gold as the catalyst precursor and achieving catalytic applications.

Highly efficient rhodium(III) catalysis was developed for obtaining structurally divergent pyrazolone analogues from pyrazolones and non-activated free allyl alcohols. Notably, this new C–H activation reaction generated unexpected pyrazolo[1,2-α]cinnoline derivatives besides γ-ketone substituted edaravone derivatives, and the selectivity of this coupling reaction could be controlled by changing the conditions.

V magistrskem delu smo se ukvarjali z razvojem metode za sintezo substituiranih cinolinov katalizirano s p-toluensulfonsko kislino. Optimizirano metodo smo uporabili za sintezo različno substituiranih cinolinov, ki smo jih karakterizirali s pomočjo tehnik jedrske magnetne resonance, masne spektrometrije visoke ločljivosti ter visokotlačne tekočinske kromatografije. Začeli smo z ravojem metode za diazotiranje anilinov, z elektronprivlačnimi substituenti na aromatskem obroču, s terc-butil nitritom kot virom dušika ter p-toluensulfonsko kislino, ki je služila kot vir protonov, njena deprotonirana oblika pa je obenem kasneje služila kot stabilizirajoči anion diazonijeve soli. Izolirani diazonijevi tozilati so stabilni dlje časa brez izgub reaktivnosti. Slednje smo potrdili z reakcijo azo spajanja z elektronsko bogatima aromatskima sistemoma do usteznih azo barvil. Optimizirane pogoje diazotiranja smo nato uporabili na elektronsko bogatih anilinov, natančneje 1,2-benzodiaminu in 2-izopropenil anilinu, ki sta po pričakovanjih reagirala do cikličnih produktov. V nadaljevanju smo raziskali ciklizacijo o-vinilanilinov do ustreznih cinolinov. Za to smo najprej iz ustreznih anilinov pripravili serijo o-vinilanilinov z različnimi substituenti in fenilacetilenov. Reakcijo smo izvajali v prisotnosti heterogenega katalizatorja montmorilonit K-10 v odsotnosti topila. Tako dobljene o-vinilaniline smo nadalje ciklizirali v želene cinolinske produkte. Optimizacijo postopka smo naredili na modelni reakciji s spremljanjem vplivov narave in količine kisline, topila ter reakcijskega časa na konverzijo izhodnega anilina v produkt. Diazotiranje takšnih vinilnih sistemov v prisotnosti terc-butil nitrita in katalitskih količin p-toluensulfonske kisline vodi do nastanka substituiranih cinolinov. Poleg tega nas je zanimal mehanizem reakcije, s pomočjo katerega bi pojasnili katalitsko delovanje kisline. S pomočjo teoretičnih izračunov na osnovi gostotnega funkcionala ter preliminarnarnih kinetičnih meritev smo predlagali mehanizem reakcije, ki v ključni stopnji poteka preko tvorbe diazonijeve soli. Prav tako smo ugotovili, da p-toluensulfonska kislina v katalitski količini služi kot prenašalec protona med dvema tavtomernima oblikama intermediatov. Izračunan mehanizem nam je dal tudi vpogled v postopek diazotiranja anilinov z organskim nitritom, ki je precej drugačen od do sedaj uveljavljenih. The aim of this work was the development of an efficient method for the synthesis of substituted cinnolines using catalytic amounts of p-toluenesulfonic acid. The optimized method was used for the synthesis of a series of substituted cinnolines, which were characterized by means of nuclear magnetic resonance, mass spectrometry and high-pressure liquid chromatography. We have developed a simple method for diazotization of weakly basic anilines in the presence of p-toluensulfonic acid, which acts as proton donor and stabilizing anion, and tert-butyl nitrite as nitrogen source. The isolated diazonium tosylates show great stability over a longer period of time without loss of reactivity. The latter was confirmed by azo coupling reaction with activated arenes yielding azo dyes. The optimized diazotization reaction conditions were further used on electron rich anilines, i.e. 1,2-benzodiamine and 2-isopropenylaniline. As expected, the two reactive anilines yielded cyclic products. Furthermore, we investigated the cyclization of different o-vinylanilines to cinnolines. For that purpose, a series of substituted o-vinylanilines was synthesised from the corresponding anilines and phenylacetilenes. The reaction takes place in the presence of heterogeneous catalyst montmorillonite K-10 in the absence of solvent. The synthesized o-vinylanilines were additionally converted into the cyclic cinnolines. A model reaction was used to optimize acid loadings, solvent nature and reaction times. Applying the optimized conditions to o-vinylanilines in the presence of tert-butyl nitrite and catalytic amounts of p-toluensulfonic acid leads to the formation of substituted cinnolines. Moreover, the reaction mechanism of the described transformation was studied. Employing a solution state density functional theory simulations as well as preliminary kinetic studies gave strong support towards a reaction mechanism that proceeds via the diazonium salt formation. Additionally, it was suggested that p-toluensulfonic acid acts as a catalytic proton shuttle between two tautomeric intermediates. This mechanistic study has also offered insight into diazotization of anilines by using organic nitrite, which is fundamentaly different from previously described reactions.

A convergent strategy is reported for the construction of nitrogen-containing heterocycles from common substrates: 1,4-diketones and primary amines. Indeed, by just varying the substrates, the substituents, or the heating mode, it is possible to selectively synthesize indole, indolone (1,5,6,7-tetrahydroindol-4-one), or cinnoline (5,6,7,8-tetrahydrocinnoline) derivatives in moderate to excellent yields.

Five new binary co-crystals have been prepared through molecular self-assembly of π-electron-rich molecules, such as phenanthrene, benzo[c]cinnoline, and phenazine, in the presence of π-electron-de...

A highly efficient iridium-catalyzed cascade annulation of pyrazolones and sulfoxonium ylides to access various pyrazolo[1,2-α]cinnoline derivatives has been achieved. This novel approach expanded the application scope of coupling partners to ylides. The control experiments were performed to give insight into the mechanism of this reaction.

Efficient access to 8H-isoquinolino[1,2-b]quinazolin-8-ones and phthalazino[2,3-a]cinnoline-8,13-diones through cyclic amide-directed Ru(II)/Ir(III)-catalyzed C-H bond activation, has been developed. Consecutive C-H bond activation, carbene insertion, and condensation annulation processes were realized, affording 8H-isoquinolino[1,2-b]quinazolin-8-one and phthalazino[2,3-a]cinnoline-8,13-dione derivatives in good-to-excellent yields under mild conditions, with H2O and N2 being generated as the only byproducts.

Based on the designed conjugated ligand of N,N'-dioxide 3,3'-benzo(c)cinnoline dicarboxylic acid (H2DBCD) with the aid of d10-metal cations and two ancillary bis(imidazole) bridges, two 3D coordination polymers， namely, {[Cd(DBCD)(1,3-bib)]·(H2O)2}n (1), {[Zn(DBCD)(1,4-bib)]·(H2O)2}n (2), were constructed here. Structural analyses show compounds 1 and 2 are 3-fold and 6-fold interpenetrating dia nets, respectively. Further luminscence studies suggested that the two CPs can selectively and sensitively detect Fe3+ cation in aqueous solution and nitrobenzene derivatives nitrobenzene (NB), p-nitrotoluene (PNT), p-nitroaniline (PNA) and p-nitrophenol (PNP) in DMF.

Functionalized benzo[c]cinnoline derivatives were synthesized from easily accessible 2,2-diamino-1,1′-biaryls using a nitrite source. In this simple process, various functional groups were tolerated under mild reaction conditions, and the practicality of the process was demonstrated through the gram-scale production of the benzo[c]cinnolines.