Solvent Moisture-Controlled Self-Assembly of Fused Benzoimidazopyrrolopyrazines with Different Ring’s Interposition

This article shows that two extremely important families of fused heterocyclic assemblies, namely 6-methylbenzo[4,5]imidazo[1,2-a]pyrrolo[2,1-c]pyrazine and 5a-methyl-5a,6-dihydro-5H,12H-benzo[4,5]imidazo[1,2-a]pyrrolo[1,2-d]pyrazine, can be synthesized from only two available building blocks (N-allenylpyrrole-2-carbaldehyde and o-phenylenediamine) by controlling only one reaction parameter (water content of the medium). It should be emphasized that the latter class of compounds (with an a/d arrangement) is previously unknown. If the allene group is introduced not into the starting compound, but during the reaction (in superbase media), a heterocyclic ensemble, 5-methylbenzo[4,5]imidazo[1,2-a]pyrrolo[2,1-c]pyrazines, with a different position of the methyl group is formed.     

Copper oxide nanoparticle catalysed synthesis of imidazo[1,2-a]pyrimidine derivatives,their optical properties and selective fluorescent sensor towards zinc ion

Synthesis of biologically active fused imidazo[1,2-a]pyrimidines were achieved via A³ coupling involving 2-aminobenzimidazole, aldehyde and terminal alkyne, followed by 6-endo-dig cyclization using copper oxide nanoparticles under solvent free condition. Further optical properties of imidazo[1,2-a]pyrimidines were studied which showed the effect of electron-donating and electron-withdrawing substitution on the fluorescence intensities of these compounds. Out of 20 compounds, 2,4-bis(4-methoxyphenyl)benzo[4,5]imidazo[1,2-a]pyrimidine can act as a fluorescent sensor for zinc ion with detection limit 4.74?μM, which is much lower than the maximum allowable zinc concentration in drinking water by WHO.     

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.     

Convenient Way to the Synthesis of Polycyclic Fused Benzimidazole Derivatives with a Bridgehead Nitrogen Atom

Effective synthesis was developed for 1,2,3,4-tetrahydropyrido- and pyrido[1,2-a]benzimidazole-7,8-diamines that underlie the preparation of new polyazaheterocycles: pyrido[1,2-а]imidazo[4,5-f]-benzimidazole, 7Н-pyrido[1,2-а]imidazo[4,5-f]benzotriazole, pyrido[1,2-а]imidazo[4,5-g]quinoxaline.     

Synthesis of nitrogen heterocycle-fused 1,2,4-benzothiadiazine-1,1-dioxide, quinazolinone, and pyrrolidinone derivatives with a guanidine joint via sequential aza-Wittig reaction/intramolecular NH-addition cyclization/nucleophilic substitution ring closure methodology, using functionalyzed carbodiimides as key intermediates

We achieved efficient synthesis of imidazo- and pyrimido[1,2-b]benzo-1,2,4-thiadiazine-1,1-dioxides by the tandem aza-Wittig reaction/intramolecular NH-nucleophilic addition/NH-nucleophilic substitution cyclization methodology, involving sulfonamide ester-containing carbodiimides as the key intermediates. Similarly, imidazo[2,1-b]quinazolinones, imidazo[1,2-a]pyrimidinediones, and imidazo[1,2-a]imidazolidinediones were also synthesized through the aza-Wittig reaction-tandem cyclization strategy. When homochiral (l)-alanine methyl ester was incorporated as a building block into the corresponding iminophosphorane starting materials, we obtained optically active imidazo[1,2-b]benzo-1,2,4-thiadiazine and imidazo[2,1-b]quinazolinone derivatives without any racemization through the one-pot tandem methodology.     

Recent synthetic scenario on imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridines chemical intermediate

Of the biologically important benzene fused heterocycles, the most important are those containing a ring-junction nitrogen. The majority of ring junction systems do not occur naturally, but they have been important from a theoretical viewpoint, for preparation of potentially active analogues. The imidazo[1,2-a] pyridines are an important class of nitrogen ring junction heterocyclic compounds. They have huge applications in medicinal chemistry and drug molecule production. Thus, the initial discussion focuses on synthetic strategies of imidazo[1,2-a] pyridines, and later we disclose the reactivity of the imidazo[1,2-a]pyridines. This review is intended to summarize and discuss the most recent developments of synthesis and reactivity of imidazo[1,2-a]pyridines, mainly the contributions after 2007.     

One-pot,three-component synthesis of 1-amidomethyl-imidazo[1,2-a]pyridines catalyzed by ytterbium triflate

A straightforward method has been developed for the synthesis of 1-amidomethyl-imidazo[1,2-a]pyridines by Yb(OTf)₃ catalyzed three-component reaction of aldehydes, acetamide, and imidazo[1,2-a]pyridines. A series of substituted 3-substituted imidazo[1,2-a]pyridines were synthesized in moderate to good yield (21–74%) under mild reaction condition and the catalyst was recycled for four cycles.     

Efficient synthesis and antioxidant activity of coelenterazine analogues

A convenient and highly convergent method for the synthesis of new imidazo[1,2-a]pyridine-based coelenterazine analogues is reported. The imidazo[1,2-a]pyridine core was constructed through a condensation between 2-aminopyridine analogues and arylglyoxals. Additionally, a new approach to the synthesis of benzylglyoxals was introduced. The imidazo[1,2-a]pyridines display moderate antioxidant activities at a low micromolar level in 2,2-diphenyl-1-picrylhydrazyl (DPPH).     

A simple approach for the regioselective synthesis of imidazo[1,2-a]pyrimidiones and pyrimido[1,2-a]pyrimidinones

Several imidazo and pyrimido[1,2-a]pyrimidinones of type 1 and 2 were synthesized through intramolecular cyclization of pyrimidines 9 or pyrimidinones 10 bearing a variety of β and γ-aminoalcohols at the 2-position. Ring closure of the pyrimidinones of type 10 under Mitsunobu conditions lead to mixtures of both bicyclic regioisomers 1 and 2. Treatment of pyrimidines of type 9 with H₂SO₄ provided an efficient and operationally simple one-pot hydrolysis-cyclization procedure for obtaining imidazo and pyrimido[1,2-a]pyrimidinones 1 in good yields as the sole regioisomeric bicyclic product.     

Pd-catalyzed oxidative cross-coupling of imidazo[1,2-a]pyridine with arenes

A facile method for direct Pd(OAc)₂-catalyzed oxidative cross-coupling of unactivated imidazo[1,2-a]pyridine with simple arenes has been developed. The reaction shows good reaction efficiency, high regioselectivity, and good functional-group compatibility. This approach provides a useful protocol for the preparation of imidazo[1,2-a]pyridine–arene structure of interest in biological and pharmaceutical materials.     

Diverse synthesis of pyrimido[1,2-a]benzimidazoles and imidazo[2,1-b]benzothiazoles via CuI-catalyzed decarboxylic multicomponent reactions of heterocyclic azoles,aldehydes and alkynecarboxylic acids

We have developed a straightforward approach to diverse synthesis of 2,3-, 2,4-disubstituted pyrimido [1,2-a]benzimidazoles, 2,4,10-trisubstituted 2,10-dihydropyrimido [1,2-a]benzimidazoles and 2,3-disubstituted imidazo [2,1-b]benzothiazoles via multicomponent reactions (MCRs) of heterocyclic azoles, aldehydes with easily storable and handling alkynecarboxylic acids. In the presence of a catalytic amount of CuI and K₂CO₃, the pyrimido [1,2-a]benzimidazole or imidazo [2,1-b]benzothiazole scaffold could be rapidly constructed through a 6-endo-dig or 5-exo-dig cyclization, respectively. The preliminary mechanistic study suggested that the formation of 2,3- disubstituted pyrimido [1,2-a]benzimidazoles, which completes the assembly of the scaffold and its C-3 position functionalization in one pot, undergoes a novel cascade process involving a decarboxylation, A [3] coupling, 6-endo-dig cyclization, nucleophilic addition and dehydration.     

Reactions of α-ketohydrazidoyl halides with some heterocyclic amines. Facile synthesis of arylazo derivatives of fused heterocycles with a bridgehead nitrogen atom

Arylazo derivatives of imidazo[2,1-b]thiazoles, imidazo[1,2-b]pyrazoles, imidazo[1,2-b]-s-triazoles, imidazo[1,2-a]pyrimidines, and imidazo[1,2-a]pyridines were obtained in good yields from α-keto hydrazidoyl halides and 2-aminothiazole, 5-aminopyrazole, 5-aminotriazole, 2-aminopyrimidine, and 2-aminopyridine, respectively (cf. Tables I and II). The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectra, and alternate synthesis wherever possible.     

Intramolecular Ullmann-type C−N coupling for the synthesis of substituted benzo[4,5]imidazo[1,2-a]pyrrolo[3,4-c]pyridines

An efficient CuI catalyzed intramolecular Ullmann-type C−N coupling reaction is described here. Newly substituted 1H-benzo[4,5]imidazo[1,2-a]pyrrolo[3,4-c]pyridine-1,3,5(2H, 11H)-trione has been easily synthesized from ortho halogenated N-substituted pyrrolo[3,4-c]pyridine-1,3,6(5H)-triones in presence of CuI catalyst and K₂CO₃ base without any ligand. This procedure is based on intramolecular Ullmann-type reaction and provides a proficient method of making fused tetracyclic heterocycles.     

Preparation of imidazo[2,1-b]quinazolin-5(3H)-ones and related tricyclic systems using a novel,double displacement reaction

New methodology is described for the construction of tricyclic heterocycles. Thus, a double displacement reaction of l-(2-fluorobenzoyl)-2-methylthio-2-imidazoline ( 8a ) with 1,1-dialkylhydrazines gave 10-substituted 2,10-dihydroimidazo[2,1-b]quinazolin-5(3H)-ones in good yield. The corresponding 1-(2-nitrobenzoyl)-2-meth-ylthio-2-imidazolines also underwent double displacement reactions with hydrazines. Other tricyclics made using double displacement reactions were pyrimido[2,1-b]quinazolines, imidazo[1,2-a]pyrido[2,3-d]pyrimidines, and imidazo[1,2-a]pyrazolo[3,4-d]pyrimidines. Treatment of 8a with hydrazine hydrate or methylhydrazine gave products resulting from displacement, but did not afford fused benzotriazepinones.     

Oxone®-mediated direct arylselenylation of imidazo[2,1-b]thiazoles,imidazo[1,2-a]pyridines and 1H-pyrazoles

Oxone mediated reaction of imidazo[2,1-b]thiazole, imidazo[1,2-a]pyridine and 1H-pyrazole derivatives with diaryl diselenides is presented here. The methodology represents an efficient and simple protocol for carrying out the selective synthesis of 5-arylselanyl-imidazo[2,1-b]thiazoles, 3-arylselanyl-imidazo[1,2-a]pyridines and 4-arylselanyl-1H-pyrazoles in high yields using a stable, nontoxic and cheap oxidant. The reactions were conducted at 60?°C in air using acetonitrile as solvent. Alternatively, the use of ultrasound irradiation is presented as a tool for fast and efficient energy transfer that significantly reduced the reaction time.     

Convenient synthesis of fused heterocycles from α-ketohydroximoyl chlorides and heterocyclic amines

Nitroso derivatives of imidazo[1,2-a]pyridine ( 11, 13, 14 ), imidazo[1,2-a]pyrimidine ( 15 ), imidazo[1,2-a]pyrazine ( 16 ), imidazo[1,2-b]pyrazole ( 17 ), and imidazo[1,2-b]-1,2,4-triazole ( 19 ) were obtained in good yields from α-ketohydroximoyl chlorides 3 and 2-aminopyridines ( 4–6 ), 2-aminopyrimidine ( 7 ), 2-aminopyrazine ( 8 ), 5-amino-3-phenylpyrazole ( 9 ), and 3-amino-2H-1,2,4-triazole ( 10 ), respectively. Under different conditions, the reaction of 3 with 3-amino-2H-1,2,4-triazole ( 10 ) and 2-aminopyrazine ( 8 ) afforded the noncyclized substitution products 18 and 22 , respectively. The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectral data, and alternate synthesis wherever possible.     

Synthesis of nitrogen heterocycles underlain by application of 3-(4-Acetyl[phenyl)-2H-coumarin

3-(4-Acetylphenyl)-2H-chromen-2-one was obtained from 4-acetylphenyldiazonium chloride in the conditions of Meerwein reaction. Reactions of 3-[4-(2-bromoacetyl)phenyl]-2H-chromen-2-one with pyridine, 4-methylpyridine, quinoline, benzo[f]quinoline, and triphenylphosphine afforded quaternary salts, and with thioacetamide, thiourea, 2-aminopyridine, 2-aminopyrimidine, and 6-aminopurine provided the corresponding derivatives of thiazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, imidazo[2,1-i]purine. In the reaction of the same bromo derivative with thiosemicarbazide and aromatic aldehydes a thiazole ring is built and the corresponding hydrazones are formed.     

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

Access to N-protected or N-free imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives as potential antiviral compounds was achieved in good yields from N-protected 7-amino-8-halo-2-methylimidazo[1,2-a]pyridines by catalytic coupling of terminal acetylenes under mild conditions using [PdCl₂(PPh₃)₂] or [Cu(Phen)(PPh₃)₂]NO₃.     

Copper-catalyzed four-component synthesis of imidazo[1,2-a]pyridines via sequential reductive amination,condensation, and cyclization

A novel and efficient four-component approach for the synthesis of 2,3-disubstituted imidazo[1,2-a]pyridines is described. The copper-catalyzed reductive amination of 2-bromopyridine by sodium azide followed by sequential condensation and cyclization with aldehydes and isocyanides afforded the corresponding imidazo[1,2-a]pyridines in good yields.     

One-pot synthesis of imidazo[1,2-a]pyridines from benzyl halides or benzyl tosylates, 2-aminopyridines and isocyanides

A one-pot synthesis of imidazo[1,2-a]pyridines is described. Benzyl halides or benzyl tosylates are oxidized to aldehydes under mild Kornblum conditions which then undergo a three-component reaction with various 2-aminopyridines and isocyanides to afford the imidazo[1,2-a]pyridines in excellent yields.