Synthesis of [1,2,4,5]tetrazino[6′,1′:2,3]imidazo[4,5-c]isoquinolin-5-ones by microwave-assisted three-component reaction

An efficient and original Ugi multicomponent reaction of aminopyridines and aminopyrimidines is reported. Starting from aminotetrazine 6 or 7, an isocyanide and an ortho-carboxybenzaldehyde, tetrazinoimidazoisoquinolinones were isolated, after few minutes of microwave irradiation, in good to excellent yields. The scope of this method was extended by using different isocyanides.     

Synthesis of pyrido[2′,1′:2,3]imidazo[4,5-b]quinoline and pyrido[1′,2′:1,2]imidazo[4,5-b]quinoline and their benzo and aza analogs via tandem catalysis

In this paper we report regioselective tandem metal-catalyzed aminations on dihaloquinolines (2-chloro-3-iodoquinoline and 2,3-dibromoquinoline) with amino(benzo)(di)azines. Eight new heterocyclic scaffolds of the dipyridoimidazole type could be synthesized. By controlling the reaction temperature selective C-2 intermolecular Pd-catalyzed amination on 2,3-dibromoquinoline with amino(benzo)(di)azines can be achieved.     

A convenient synthesis of benzofuro[3,2-c]isoquinolines and naphtho[1′,2′:4,5]furo[3,2-c]isoquinolines

A convenient method for the preparation of benzofuro[3,2-c]isoquinoline derivatives is described. The condensation reaction of methyl 2-(chloromethyl)-benzoate with substituted salicylonitriles 7a-c and intramolecular cyclization of the resulting substituted methyl 2-[(2-cyanobenzyl)oxy]benzoates 10a-c using potassium tert-butoxide results in the substituted benzofuro[3,2-c]isoquinolin-5(6H)-ones 1a-c. The same sequence of reactions starting from 2-(chloromethyl)benzonitrile and compounds 7a-c gave substituted 5-aminobenzofuro[3,2-c]isoquinolines 13a-c. In addition, this method is useful for the synthesis of other heterocycles. For example, using 1-cyano-2-naphthol 16, instead of the salicylonitriles 7a-c, gives naphtho[1′,2′:4,5]furo[3,2-c]isoquinolines.     

Synthesis of tetrahydropyrido- and pyrido-[1′,2′:1,2]imidazo[4,5-b]pyrazine derivatives

Reactions of tetrafluoropyridazine with iminopiperidine and 2-aminopiccoline gave novel tetrahydropyrido- and pyrido-[1′,2′:1,2]imidazo[4,5-b]pyrazine heterocyclic frameworks respectively in high yields.     

A novel and efficient one-pot synthesis of furo[3′,4′:5,6]pyrido[2,3-c]pyrazole derivatives using organocatalysts

A novel approach to one-pot synthesis of dihydrofuro[3′,4′:5,6]pyrido[2,3-c]pyrazole and indeno[2′,1′:5,6]pyrido[2,3-c]pyrazole derivatives have been investigated using organocatalysts that are recyclable. This new protocol has the advantages of environmental friendliness, higher yield, low cost, as well as convenient operation. The catalytic efficiency of various small organocatalysts such as l-proline, trans-4-hydroxy-l-proline, l-thiaproline, cinchonidine, (+)-cinchonine, and dl-2-phenylglycine has also been studied.     

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Novel dipyrido[1,2-a;3′,4′-d]imidazoles 7a-d, dipyrido[1,2-a;4′,3′-d]imidazoles 8a,c and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives 9a-d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2-a]pyridines 11.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Synthesis of some tetrazole fused pyrido[2,3-c]coumarin derivatives from a one-pot three-component reaction via intramolecular 1,3-dipolar cycloaddition reaction of azide to nitriles

Some novel tetrazole fused pyrido[2,3-c]coumarin derivatives 5/7/9 were synthesized from a one-pot three-component reaction of 4-chloro-3-formylcoumarins 2, sodium azide 3, and alkyl/aryl acetonitriles 4/6/8.     

Regio and diastereoselective synthesis of functionalized 2,3-dihydrofuro[3,2-c]coumarins via a one-pot three-component reaction

An efficient and straightforward synthesis of furo[3,2-c]coumarins via the one-pot three-component condensation of aromatic aldehydes, 4-hydroxycoumarin and α-chloroketones in refluxing n-propanol is described. Pyridine or a mixture of AcOH and AcONH₄ was used as a basic catalyst.     

Synthesis of substituted dipyrido[3,2-a:2′,3′-c]phenazines and a new heterocyclic dipyrido[3,2-f:2′,3′-h]quinoxalino[2,3-b]quinoxaline

Three new α,α′-diimine ligands were synthesized based on condensation of 1,10-phenanthroline-5,6-dione with 1,2-phenylenediamine derivatives using different approaches. All compounds were fully characterized by IR, ¹H and ¹³C NMR, UV-visible, and MS spectroscopies. We report the first example of a dipyrido[3,2-f:2′,3′-h]quinoxalino[2,3-b]quinoxaline, which exhibits a strong absorption at 430 nm and an interesting electrochemical behavior. These new molecules may have biological potential and are of synthetic and technological importance.     

Synthesis of pyrimido[6,1-a]isoquinolines via a one-pot, four-component reaction

An efficient one-pot synthesis of pyrimido[6,1-a]isoquinoline-1-carboxylate derivatives is described. This involves the four-component reaction between primary amines, alkyl acetoacetates, isoquinoline and trichloromethylchloroformate (diphosgene) under mild conditions at ambient temperature.     

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxalines

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxalines by the facile cyclizations of 2,3-dichloroquinoxalines with 2-aminopyridines and of 2-amino-3-chloroquinoxalines with various substituted pyridines is described.     

Synthesis and conformational analysis of naphth[1′,2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine and naphth[1′,2′:5,6][1,3]oxazino[3,4-c][1,3]benzoxazine derivatives

A new functional group, the hydroxy group, was inserted into a Betti base by reaction with salicylaldehyde, and the naphthoxazine derivatives thus obtained were converted by ring-closure reactions with formaldehyde, acetaldehyde, propionaldehyde or phosgene to the corresponding naphth[1′2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine derivatives. Further, the conformational analysis of these polycyclic compounds by NMR spectroscopy and an accompanying molecular modelling are reported; especially, both quantitative anisotropic ring current effects of the aromatic moieties in these compounds and steric substituent effects were employed to determine the stereochemistry of the naphthoxazinobenzoxazine derivatives.     

Fused isoquinolines: 3-aryl-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione-2-spiro-4′-(1′-alkyl-1′,4′-dihydropyridine)s

Previously unknown 3-arylamino-1,2-dihydro-1-isoquinolones were obtained by condensation of 2-cyanomethylbenzoic acid with arylamines. Isonicotinoylation of the compounds was shown to proceed at the carbon atom in the 4-position to give 3-arylamino-4-isonicotinoyl-1,2-dihydro-1-isoquinolones which were quaternized with alkylating agents and formed the corresponding pyridinium salts. Deprotonation of the latter induced intramolecular conjugated addition with the pyrrole ring closure and formation of spiro compounds. The structure of the products was confirmed by NMR, IR and UV spectroscopy and by synthesis of the model compound, 3-(4-tolyl)-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione.     

Electrochemical properties of pyrido[1′,2′:1,2]imidazo[4,5-b]pyrazine and pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxaline derivatives

The peak potentials (Ep) of 3-substituted pyrido[1′,2′:1,2]imidazo[4,5-b]pyrazine and pyrido[1′,2′:1,2]-imidazo[4,5-b]quinoxaline derivatives are sufficiently correlated with Hammett substituent constant ～_m and with the PM3 calculated LUMO energy levels, and the linear relationship between electron potentials of 9-substituted pyridoimidazoquinoxalines and the LUMO energy levels is also found out.     

Synthesis of pyridino[3′,2′:4,5]pyrrolo[3,2-g]pyrrolo[3,4-e]indolizin-1,3-dione and pyrrolo[3,2-c]pyrazole skeletons

A three step synthesis of an isogranulatimide analogue, in which the imidazole moiety is replaced by a pyrrole unit and the indole heterocycle is replaced by a 7-azaindole moiety is described. Moreover, a novel synthetic pathway to the pyrrolo[3,2-c]pyrazole skeleton is reported.     

Cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines): synthesis, structure and mechanism of their formation

Reactions of 3-alkylamino-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones with cyclohexyl- and cycloheptylamines in the presence of AgPy₂MnO₄ produce novel cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines). Detailed information concerning the scope and mechanism of these transformations is discussed.     

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]pyrazines from 2,3-dichloro-5,6-dicyanopyrazine with 2-aminopyridines

Novel synthesis of the title compounds by the facile cyclization between 2,3-dichloro-5,6-dicyanopyrazine and various 2-aminopyridines under relatively mild conditions is described. The reactivity depended on the basicity of 2-aminopyridines.     

Pyrido[2′1′:2,3]imidazo[4,5-c]isoquinoline and the alkylation of pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one

The reaction of 2-aminopyridine, o-phthaldehydic acid and potassium cyanide gave pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one, which upon treatment with propargylbromide, yielded both O and N alkylated products. 2-Aminopyridine, o-phthaldehyde and potassium cyanide gave 1-cyano-2-(2-pyridyl)isoindole which rearranged in acid to give the previously unreported parent pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinole. Structures were confirmed using uv, ir, nmr and x-ray spectroscopy.     

Synthesis of imidazo[1,2a]pyridines via three-component reaction of 2-aminopyridines, aldehydes and alkynes

A novel three-component reaction towards the synthesis of imidazo[1,2a]pyridines was independently developed based on 2-aminopyridines, aldehydes and alkynes, and thereby imidazo[1,2a]pyridines were obtained in acceptable yields by the CuSO4/TsOH catalyzed three-component reaction.