New general synthesis of benzo[4,5]imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine and benzo[4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazoline derivatives

The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under solvent-free conditions unexpectedly afforded benzo[4,5]imidazo[1,2-a]pyrimidine, benzo[4,5]imidazo[2,1-b]-quinazoline, and 2,2′-(benzene-1,2-diyldiimino)bis[pyrimidin-4(3H)-ones]. The described reaction is the first example of synthesis of these heterocyclic systems by fusion of benzimidazole to pyrimidine or quinazoline and is likely to follow ANRORC mechanism.     

Efficient route to benzo[4,5]imidazo[2,1-a]phthalazines

Benzo[4,5]imidazo[2,1-a]phthalazines have been obtained from various o-nitrophenylhydrazines through different 2-(2-nitrophenyl)-1,2-dihydro-1-phthalazinones as intermediates using an elaborated advanced procedure. An activated chlorine atom in 2-nitrophenyl moiety of the latter is able to undergo nucleophilic substitution for secondary alicyclic amines yielding novel substituted phthalazinones. Their one-pot reduction and cyclodehydration yield a series of novel substituted benzo[4,5]imidazo[2,1-a]phthalazines.     

1,3-dipolar cycloaddition of diazomethane to quinoid derivatives of pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazole

Reactions of diazomethane with quinone mono(di)imines and methylidene quinone imines of pyrido[1,2-a]benzimidazole series occurs by the route of 1,3-dipolar cycloaddition and leads to the formation of quinoid compounds, in particular, previously unknown heterocyclic structures of indazolo[7',6':4,5]imidazo-[2,1-j]quinoline, indazolo[7',6':4,5]imidazo[2,1-e]acridine, indazolo[4',5':4,5]imidazo[2,1-j]quinoline, and indazolo[4',5':4,5]imidazo[2,1-e]acridine.     

Synthesis of benzo[4,5]imidazo[2,1-a]phthalazines

5,9-Disubstituted benzo[4,5]imidazo[2,1-a]phthalazines are synthesized efficiently from acylbenzoic acids and 2-nitro-5-chlorophenylhydrazine. Nucleophilic substitution in phthalazinones gave a variety of the title compounds after reduction and cyclization.     

Synthesis of imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridones and imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridines as potential antibacterial agents

Abstract  New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug. Graphical abstract        

Synthesis of dihydrobenzoimidazo[2,1-a]isoquinolines

A one-pot protocol toward several substituted 5,6-dihydrobenzo[4,5]imidazo[2,1-a]isoquinolines 1 starting with 2-allylbenzaldehydes 2 was described. The process was carried out the one-pot condensation/hydroamination reaction of substituted 2-allylbenzaldehydes 2 with 1,2-diaminobenzenes 3 in refluxing toluene in good yields. Skeleton 2 was prepared via one-pot ortho-metalative PhBCl₂-mediated double alkylation of hydroxybenzaldehyde 4 with LDA in moderate yields.     

Synthesis of naphtho[2',3':4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]-thiazole-5,10-dione and naphtho[2',3':4,5]imidazo-[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]benzothiazole-7,12-dione

The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminothiazole in MeONa/MeOH at 60oC for 3 h gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]thiazole-5,10-dione in 64% yield. The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminobenzothiazole under the above-mentioned conditions gave 2-(benzo[d]thiazol-2-ylamino)-3-bromonaphthalene-1,4-dione in 64% yield, which on treatment with Na/THF or NaN₃/acetone under reflux conditions gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]- benzothiazole-7,12-dione in 69 and 56% yields, respectively.     

Synthesis of imidazo[4,5-a]acridones and imidazo[4,5-a]acridines as potential antibacterial agents

Abstract  

New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug.     

Synthesis of benzimidazo[2,1-b]benzothiazole derivatives through sequential Cu-catalyzed domino coupling and Pd-catalyzed Suzuki reaction

A variety of benzo[d]benzo[4,5]imidazo[2,1-b]thiazoles were efficiently and conveniently synthesized from the Cu-catalyzed domino coupling of o-dihaloarenes with 2-mercaptobenzimidazoles. The reaction is also applicable to a series of multi-functional substrates, affording the halo-containing products with excellent selectivity. The brominated products can further react with arylboronic acids under Pd catalysis to furnish the aryl-substituted benzimidazo[2,1-b]benzothiazole derivatives.     

Intramolecular amidation: synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of 2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde and 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.     

Recyclable Carbon Nitride Nanosheet-Photocatalyzed Aminomethylation of Imidazo[1,2-a]pyridines in Green Solvent

An efficient and eco-friendly carbon nitride nanosheet(NM-g-C3N4)-catalyzed decarboxylative coupling reaction of imidazo-fused heterocycles(i.e.,imidazo[1,2-a]pyridines,benzo[d]imidazo[2,1-b]thiazole)with N-phenylglycines in dimethyl carbonate(DMC)has been developed.The toxic solvents,external oxidants,and restricted reaction conditions could be effectively avoided in this powerful and sustainable protocol.Remarkably,NM-g-C3N4 could be straightforwardly recovered by simple centrifugation and recycled and reused at least 7 times without an obvious decrease in catalytic activity.     

Selective,C-3 Friedel-Crafts acylation to generate functionally diverse,acetylated Imidazo[1,2-a]pyridine derivatives

Carbon-carbon bonds are integral for pharmaceutical discovery and development. Frequently, CC bond reactions utilize expensive catalyst/ligand combinations and/or are low yielding, which can increase time and expenditures in pharmaceutical development. To enhance CC bond formation protocols, we developed a highly efficient, selective, and combinatorially applicable Friedel-Crafts acylation to acetylate the C-3 position of imidazo[1,2-a]pyridines. The reaction, catalyzed by aluminum chloride, is both cost effective and more combinatorial friendly compared to acetylation reactions requiring multiple, stoichiometric equivalents of AlCl₃. The protocol has broad application in the construction of acetylated imidazo[1,2-a]pyridines with an extensive substrate scope. All starting materials are common and the reaction requires inexpensive, conventional heating methods for adaptation in any laboratory. Further, the synthesized compounds are predicted to possess GABA activity through a validated, GABA binding model. The developed method serves as a superior route to generate C-3 acetylated imidazo[1,2-a]pyridine building-blocks for combinatorial synthetic efforts.     

Synthesis and properties of cyanomethyl derivatives of imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine,imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine,and imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazole

2-Cyanomethyl derivatives were obtained of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[2,1-b]thiazole, and their reactivity was investigated by an example of imidazo[1,2-a]pyridine: It was subjected to nitration, bromination, azo coupling and nitrosation. Acylation of the methylene group effected by amino acids esters with a subsequent addition of the amino group to the cyano group resulted in the formation of 5-amino-4-imidazo[1,2-a]-pyridin-2-yl-1-phenyl-1,2-dihydro-3H-pyrrol-3-one and 2-amino-1-ethyl-3-imidazol[1,2-a]pyridin-2-yl-4(1H)-quinolinone.     

One-Pot Synthesis of Benzo[4,5]imidazo[1,2-a]pyrimidin-2-ones Using a Hybrid Catalyst Supported on Magnetic Nanoparticles in Green Solvents

The conversion of soluble polyoxometalate into insoluble polyoxometalate is considered to be one of the major challenges in synthetic organic chemistry. Here, polyoxometalate was bonded to the salt part of an organic branch immobilized on the silica-coated Fe₃O₄ nanoparticle and characterized using various techniques. The fabricated complex was used as a heterogeneous catalyst in a novel one-pot reaction for synthesis of benzo[4,5]imidazo[1,2-a]pyrimidin-2-ones using aromatic amines, dimethyl acetylenedicarboxylate (DMAD), derivatives of benzaldehyde and 2-aminobenzimidazole in water/ethanol as a green solvent. 21 derivatives of benzo[4,5]imidazo[1,2-a]pyrimidin-2-one were synthesized by this method and fully characterized. The high stability of the catalyst showed that it can be reused for 6 times without decreasing in activity. The combination of new synthetic method, new ferromagnetic heterogeneous nano-catalyst, green solvent and simple separation method were presented in this work.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

Solvent-free reaction between acenaphthoquinone, various benzils and ammonium acetate: synthesis of 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones

A simple synthesis of benzo[d,e]imidazo[2,1-a]isoquinolines is described. Heating a mixture of acenaphthoquinone, a benzil, and ammonium acetate under solvent-free conditions afforded 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones in good to excellent yields.     

A visible-light-promoted cross-dehydrogenative-coupling reaction of N-arylglycine esters with imidazo[1,2-a]pyridines

A mild and convenient visible-light-promoted cross-dehydrogenative-coupling reaction between N-arylglycine esters and imidazo[1,2-a]pyridines for the construction of CC bond was developed. A range of N-arylglycine esters and imidazo[1,2-a]pyridines were able to undergo the CDC reaction readily to afford α-heteroaryl substituted α-amino acid derivatives in good to excellent yields. A tentative mechanism for the photoredox reaction was also proposed. Importantly, the use of copper(II) salt as the sole catalyst in this visible-light-promoted transformation makes this reaction sustainable and practical.     

Visible-Light-Driven Sulfonylation/Cyclization to Access Sulfonylated Benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-ones

Visible-light-driven sulfonylation/cyclization of N-methacryloyl-2-phenylbenzoimidazoles has been successfully developed. Using commercially available sulfonyl chloride as sulfonylation reagent, a wide range of sulfonylated benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-ones with potential antitumor activity were provided in acceptable to excellent yields. This method has the advantages of mild reaction conditions and outstanding functional group tolerance, and provides a new strategy for the development of potential antitumor lead compounds.     

Catalyst-free rapid synthesis of benzo[4,5]imidazo[1,2-a]-pyrimidine-3-carboxamides via four-component coupling in one pot

A new class of fused tricyclic benzo[4,5]imidazo[1,2-a]-pyrimidine-3-carboxamide derivatives was synthesized via an environmentally benign one pot sequential four-component condensation reaction of an amine, 2,2,6-trimethyl-4H-1,3-dioxin-4-one, an aldehyde and 1H-benzo[d]imidazol-2-amine without using catalyst in good yields.     

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.