Green Synthesis of 6‐Aryl‐5,6‐dihydrobenzo[4,5]imidazo[1,2‐c]quinazoline Derivatives in Ionic Liquid under Catalyst‐free Conditions

Using ionic liquids as green media, a series of 6‐arylbenzo[4,5]imidazo[1,2‐c]quinazoline derivatives is synthesized via a reaction of 2‐(1H‐benzo[d]imidazol‐2‐yl)aniline and benzaldehydes in the air. While the intermediate products of 6‐aryl‐5,6‐dihydrobenzo[4,5]imidazo[1,2‐c]quinazolines were obtained in high yields at the same conditions under nitrogen protection.     

Catalyst‐free Synthesis of 5‐Arylimidazo[1,2‐c]quinazoline Derivatives in Ionic Liquids

The reaction of 2‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)aniline and aromatic aldehyde was treated in ionic liquids under catalyst‐free condition and gave dehydrogenated 5‐aryl‐2,3‐diphenylimidazo[1,2‐c ]quinazolines. The same reaction gave un‐aromatized 5‐aryl‐2,3‐diphenyl‐5,6‐dihydroimidazo[1,2‐c ]quinazoline derivatives while it was controlled in an inert gas. This procedure approach to imidazo[1,2‐c ]quinazolines has the advantages of milder reaction conditions, one‐pot, catalyst free, high yields, and environmentally benign.     

One‐pot Combinatorial Synthesis of Benzo[4,5]imidazo‐[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one Derivatives

A series of novel fused tetracyclic benzo[4,5]imidazo[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one derivatives were synthesized via the reaction of aryl aldehyde, 2H‐thiopyran‐3,5(4H,6H)‐dione, and 1H‐benzo[d]imidazol‐2‐amine in glacial acetic acid. This protocol features mild reaction conditions, high yields and short reaction time.     

One‐pot Synthesis of Benzo[4,5]imidazo[1,2‐a]pyridine Derivatives in Aqueous Conditions

One‐pot reaction of cyclic 1,3‐diketones, dimethylformamide dimethylacetal (DMFDMA) and 2‐(1H‐benzo[d ]imidaz‐2‐yl)acetonitrile was found to be a highly selective process leading to 4‐oxo‐1,2,3,4‐tetrahydrobenzo[4,5]imidazo[1,2‐a ]quinolin‐6‐yl cyanides. Optimized reaction conditions using water as solvent at room temperature or under microwave heating allowed high yields of the target products required no additional purification.     

Synthesis of Imidazo[1,2‐a]pyridines and Imidazo[2,1‐b]thiazoles Attached to a Cycloalkyl or Saturated Heterocycle Containing a Tertiary Hydroxy Substitution

A new method has been developed for the synthesis of imidazo[1,2‐a]pyridines, imidazo[2,1‐b]thiazoles, and benzo[d]imidazo[2,1‐b]thiazoles attached to a cycloalkyl or saturated heterocycle containing a tertiary hydroxy substitution. Readily available substituted 2‐aminopyridines, 2‐aminothiazoles, and 2‐aminobenzothiazoles were treated with bromohydroxycycloalkyl ethanones to afford the desired products in good yields.     

A new approach for the synthesis of some pyrazolo[5,1‐c]triazines and pyrazolo[1,5‐a]pyrimidines containing naphtofuran moiety

Naphtho[2,1‐b]furan‐2‐yl)(8‐phenylpyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)methanone, ([1,2,4]triazolo[3,4‐c][1,2,4]triazin‐6‐yl)(naphtho[2,1‐b]furan‐2‐yl)methanone, benzo[4,5]imidazo[2,1‐c][1,2,4]triazin‐3‐yl‐naphtho[2,1‐b]furan‐2‐yl‐methanone, 5‐(naphtho[2,1‐b]furan‐2‐yl)pyrazolo[1,5‐a]pyrimidine, 7‐(naphtho[2,1‐b]furan‐2‐yl)‐[1,2,4]triazolo[4,3‐a]pyrimidine, 2‐naphtho[2,1‐b]furan‐2‐yl‐benzo[4,5]imidazo[1,2‐a]pyrimidine, pyridine, and pyrazole derivatives are synthesized from sodium salt of 5‐hydroxy‐1‐naphtho[2,1‐b]furan‐2‐ylpropenone and various reagents. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation, and alternative synthetic route whenever possible. J. Heterocyclic Chem., (2012).     

Structural Transformation of Methoxy‐Substituted Benzo[de]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐ones

Structural transformation of two methoxy derivatives of benzo[de]benzo[4,5]imidazo[2,1‐a]‐isoquinolin‐7‐one were determined via spectroscopic analysis. The transformation mechanism was proposed as the breakage and reformation of the lactam bond.     

Synthesis of pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]pyrimidines related to zaleplon,a new drug for the treatment of insomnia

This paper describes the preparation of some pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]‐pyrimidines substituted on the pyrimidine moiety by a 4‐[(N‐acetyl‐N‐ethyl)amino]phenyl group. A new synthesis of related benzo[h]pyrazolo[1,5‐a]‐, benzo[h]pyrazolo[5,1‐b]‐ and benzo[h]1,2,4‐triazolo[1,5‐a]‐quinazolines is also reported.     

Solvent‐Driven Iodine‐Mediated Oxidative Strategies for the Synthesis of Bis(imidazo[1,2‐a]pyridin‐3‐yl)sulfanes and Disulfanes

Two efficient iodine‐mediated strategies, which are economical and one‐pot, are described to access bis(imidazo[1,2‐a ]pyridin‐3‐yl)sulfanes and bis(imidazo[1,2‐a ]pyridin‐3‐yl)disulfanes in chloroform and acetic acid, respectively, by a direct oxidative homocoupling of imidazo‐heterocycles using inexpensive sodium sulfide as a sulfur source. These strategies are scalable, and an array of substrates delivered their corresponding stable sulfur‐bridged imidazo‐heterocycles in excellent yields.     

Polycyclic N‐Heterocyclic Compounds. Part 81: Synthesis and Evaluation of Pentacyclic 1,2,4,5‐Tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine and Related Compounds as Potential Antiplatelet Aggregators

Dehydrative ring closure reactions were carried out on fused 4‐(2‐hydroxyethylamino) (or 2‐hydroxyethoxy or 2‐hydroxyethylthio)pyrimidines ( 2a , 2b , 2c ) to give fused 2,3‐dihydroimidazo[1,2‐c] (or 2,3‐dihydrooxazolo[3,2‐c] or 2,3‐dihydrothiazolo[3,2‐c])pyrimidines. This reaction produced the pentacyclic 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine ( 3a ) and 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]thiazolo[3,2‐c]pyrimidinium chloride ( 3c ) from the 2‐hydroxyethylamino‐derivative and 2‐hydroxyethylthio‐derivative, respectively. In contrast, 2‐hydroxyethoxy‐derivative ( 2b ) gave the rearrangement product, 3‐(2‐chloroethyl)‐5,6‐dihydro[1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidin‐4(3H)‐one ( 4 ). Effects of the synthesized compounds on collagen‐induced platelet aggregation were also evaluated.     

Imidazo[2,1‐b]thiazoles,imidazo[2,1‐b]imidazoles and Pyrrolo[1,2‐c]imidazoles. synthesis,structure and evaluation of benzodiazepine receptor binding

As a continuation of our studies on bicyclic heterocycles with benzodiazepine receptor affinity, derivatives with a 5:5 bicyclic skeleton, namely imidazo[2,1‐b]thiazoles, imidazo[2,1‐b]imidazoles and pyrrolo[1,2‐c]imidazoles were prepared. The compounds possessed an aromatic substituent with different spatial arrangement and distance to the bicyclic skeleton. X‐ray structure analysis was performed for Z‐2‐(4‐chlorobenzylidene)‐5,5‐diphenyl‐2,3,5,6‐tetrahydroimidazo[2,1‐b]imidazoline‐3,6‐dione ( 6a ) and 5‐amino‐6‐cyano‐7‐phenyl‐1‐oxo‐3‐thioxo‐2,3‐dihydro‐1H‐pyrrolo[1,2‐c]imidazole ( 20a ). In contrast to the previously described arylideneimidazo[2,1‐b]thiazepinones the smaller heterocyclic ring systems investigated in this study were devoid of meaningful benzodiazepine receptor affinity as well as anti‐convulsant activity.     

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.     

Synthesis of Novel 7‐methylene‐6,7‐dihyrobenzo[f]Benzo[4,5]Imidazo[1,2‐d][1,4]Oxazepines via Base‐mediated Regioselective Intramolecular Hydroamination

A versatile and transition metal‐free approach for the synthesis of new 7‐methylene‐6,7‐dihyrobenzo[f]benzo[4,5]imidazo[1,2‐d][1,4]oxazepines were developed by an efficient 7‐exo‐dig regioselective hydroamination of 2‐(2‐(prop‐2‐yn‐1‐yloxy)phenyl)‐1H‐benzo[d]imidazole in the presence of potassium carbonate in DMF at 90°C.     

Polycyclic N‐Heterocyclic Compounds. Part 75: Synthesis of 2,4‐Disubstituted 5,6‐dihydro[1]benzoxepino[5,4‐d]pyrimidines and 12‐Substituted 1,2,4,5‐Tetrahydro[1]benzoxepino[4,5‐e]imidazo[1,2‐c]pyrimidines as Potential Antiplatelet Aggregators

Libraries of tricyclic 2‐substituted 4‐alkylamino‐5,6‐dihydro[1]benzoxepino[5,4‐d]pyrimidines and tetracyclic 12‐substituted 1,2,4,5‐tetrahydro[1]benzoxepino[4,5‐e]imidazo[1,2‐c]pyrimidines were synthesized as part of our research to develop new effective antiplatelet drugs. Several alkyl and aryl groups were used as substituents at the 2‐position. Evaluation of the effects of the newly synthesized compounds on collagen‐induced platelet aggregation revealed several promising antiplatelet candidates with potencies superior to aspirin.     

One‐pot Sequential Reactions Featuring a Copper‐catalyzed Amination Leading to Pyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines and Dihydropyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines

Tetracyclic skeletons combining an imidazo[1,2‐a]pyridine moiety with a quinoline framework such as pyrido[2′,1′:2,3]imidazo[4,5‐b]quinoline are stimulating increasing interests since they are close isosteres of a series of powerful antiproliferative compounds. In this paper, we report a novel methodology for the synthesis of pyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines through one‐pot sequential reactions of commercially available or readily obtainable 2‐aminopyridines, 2‐bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover, dihydropyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines could also be obtained in a similar manner by using various ketones as the substrates in place of aldehydes. Notably, the whole procedure combines condensation/amination/cyclization reactions in one pot to give complex compounds in a simple and practical manner. Compared with literature methods, the synthetic strategy reported herein has the advantages of readily available starting materials, structural diversity of products, good functional group tolerance, and obviation of step‐by‐step operations.     

Nanomagnetically modified thioglycolic acid (γ‐Fe2O3@SiO2‐SCH2CO2H): Efficient and reusable green catalyst for the one‐pot domino synthesis of spiro[benzo[a]benzo[6,7]chromeno[2,3‐c]phenazine] and benzo[a]benzo[6,7]chromeno[2,3‐c]phenazines

Superparamagnetic nanoparticles of modified thioglycolic acid (γ‐Fe₂O₃@SiO₂‐SCH₂CO₂H) represent a new, efficient and green catalyst for the one‐pot synthesis of novel spiro[benzo[a ]benzo[6,7]chromeno[2,3‐c ]phenazine] derivatives via domino Knoevenagel–Michael–cyclization reaction of 2‐hydroxynaphthalene‐1,4‐dione, benzene‐1,2‐diamines, ninhydrin and isatin. This novel magnetic organocatalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least six times without significant loss in its activity. The catalyst was fully characterized using various techniques. This procedure was also applied successfully for the synthesis of benzo[a ]benzo[6,7]chromeno[2,3‐c ]phenazines.     

A convenient synthesis of novel pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazinones from imidazo[1,2‐a]pyridines

The imidazo[1,2‐a]pyridine system was investigated as a synthon for the building of very attractive fused triazines, a planar, angular tri‐heterocycle with potential biological activity. Thus ethyl 3‐nitroimidazo[1,2‐a]pyridine‐2‐carboxylate was treated with ammonia or with an excess of primary amines to generate the corresponding substituted nitro carboxamidoimidazopyridines. The nitro substituent in the latter products, was reduced to yield 3‐amino‐2‐carboxamidoimidazo[1,2‐a]pyridine derivatives, which in turn were treated with nitrous acid to furnish 1‐oxo‐2‐substituted pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazines.     

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.     

Synthesis of Novel Disubstituted Pyrazolo[1,5‐a]pyrimidines,Imidazo[1,2‐a]pyrimidines,and Pyrimido[1,2‐a]benzimidazoles Containing Thioether and Aryl Moieties

A series of novel 6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐7‐phenylpyrazolo[1,5‐a]pyrimidines, 5‐phenyl‐6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]imidazo[1,2‐a]pyrimidines, and 2‐phenyl‐3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]pyrimido[1,2‐a]benzimidazoles have been synthesized in four steps starting with 2‐hydroxyacetophenone. The intermediate 3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐4H‐1‐benzopyran‐4‐ones reacted with pyrazol‐3‐amines, 5‐methylpyrazol‐3‐amine, and 1H‐imidazol‐2‐amine, 1H‐benzimidazol‐2‐amine via a cyclocondensation to give the title compounds in the presence of MeONa as base, respectively. The approach affords the target compounds in acceptable‐to‐good yields. The new compounds were characterized by their IR, NMR, and HR mass spectra.     

Comparative Study on the Reactivity of 6‐Haloimidazo[1,2‐a]pyridine Derivatives towards Negishi‐ and Stille‐Coupling Reactions

The scope of the Suzuki‐cross‐coupling reaction of 6‐haloimidazo[1,2‐a]pyridines is dependent on the availability of the (hetero)arylboronic acids. Thus, with the aim to develop expanded applications of (hetero)arylations of imidazo[1,2‐a]pyridines, we investigated the Negishi‐ and Stille‐cross‐coupling reactions at the 6‐position. Remarkably, attempts to apply the Negishi‐cross‐coupling conditions to the organozinc derivative prepared from 6‐haloimidazo[1,2‐a]pyridine via a lithium? zinc exchange led to the 5‐phenyl compound 3 in 54% yield instead of the desired 6‐phenyl isomer (Scheme 1). In contrast, various commercially available halogenated five‐ or six‐membered‐ring heterocycles were efficiently coupled to the 6‐(trialkylstannyl)imidazo[1,2‐a]pyridine under Stille conditions (Table 2).