Regiospecific synthesis of 3-substituted imidazo[1,2-a]pyridines,imidazo[1,2-a]pyrimidines,and imidazo[1,2-c]pyrimidine

3-Substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[1,2-c]pyrimidine were obtained regiospecifically in yields of 35-92% in one pot by reaction of 2-aminopyridines or 2-(or 4-)aminopyrimidines, respectively, with 1,2-bis(benzotriazolyl)-1,2-(dialkylamino)ethanes.     

One-pot synthesis of imidazo[1,2-b]pyrazole,imidazo[1,2-b]-1,2,4-triazole,imidazo[1,2-a]pyridine,imidazo[1,2-a]pyrimidine,imidazo[1,2-a]benzimidazole,and 1,2,4-triazolo[4,3-a]benzimidazole derivatives

Hydrazonoyl bromides 1a-c react with 5-amino-3-phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2-aminopyridine, and 2-aminobenzimidazole to afford the corresponding imidazol[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2-a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21. © 1997 John Wiley & Sons, Inc.     

Formation of bromo-substituted imidazo[1,2-a]pyridines and their aza and thia analogs when the chichibabin reaction is carried out in dimethyl sulfoxide

The reactions of bromomethyl ketones with 2-aminopyridine, 2-aminopyrimidine, 2-aminothiazole, and 2-aminobenzothiazole in dimethyl sulfoxide lead to bromo-substituted (with respect to the position of the imadozole ring) imidazo[1,2-a] pyridines, imidazo[1,2-a]pyrimidines, imidazo[2,1-b]thiazoles, and imidazo[2,1-b]-benzothiazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 258–262, February, 1978.     

Efficient Pd(0)-mediated microwave-assisted arylation of 2-substituted imidazo[1,2-a]pyrimidines

A short and practical synthesis of 2,3-substituted imidazo[1,2-a]pyrimidines, based on microwave-assisted Heck-type arylation of 2-substituted imidazo[1,2-a]pyrimidines, was developed. A 45-membered library of 2,3-substituted imidazo[1,2-a]pyrimidines was obtained with good yields and purities using this optimized protocol.     

Preparation of 2-aryl and 2-aryloxymethyl imidazo[1,2-a]pyridines and related compounds

A series of substituted 2-aryl imidazo[1,2-a]pyridines has been prepared in which a variety of substituents are introduced on the 4′-position of the phenyl ring and on the 3, 5 , 6 or 7 position of the heterocyclic ring. Most examples have acetamido, bromo, cyano, or formyl substituents at the 4′-position. Analogous imidazo-[2,1-b]fhiazoles and imidazo[1,2-a]pyrimidines have also been prepared. Another series of compounds consisting of 4′-formylphenoxymethyl derivatives of imidazole, the three positional isomers of pyridine, thiazole, benzimidazole and ring-substituted imidazo[1,2-a]pyridines has been prepared. 2-(4′-Formylphenylethenyl) derivatives of imidazole and imidazo[1,2-a]pyridine were also prepared.     

Cu(I)-catalyzed synthesis of imidazo[1,2-a]pyridines from aminopyridines and nitroolefins using air as the oxidant

A copper-catalyzed method for the synthesis of imidazo[1,2-a]pyridines with aminopyridines and nitroolefins using air as oxidation agent in a one-pot procedure has been developed. In this process, the reaction appears to be very general and suitable for construction of a variety of imidazo[1,2-a]pyridines.     

Regiochemistry of the microwave-assisted reaction between aromatic amines and alpha-bromoketones to yield substituted 1H-indoles

The scope and regioselectivity of the Bischler (or Bischler-M?hlau) reaction between aromatic amines and alpha-bromoketones has been studied by computational and experimental techniques. It has been found that in many cases the reaction yields are improved under microwave irradiation and working in the absence of solvent. When di- and trisubstituted amines are used as substrates the regioselectivity of the reaction is different to that obtained with the corresponding primary anilines. The reaction between benzene-1,2-diamine and alpha-bromoacetophenones under the same conditions yields 2-substituted quinoxalines instead of indoles. Finally, when pyridin-2-amines and pyrimidine-2-amines are allowed to react with the corresponding alpha-bromoacetophenones, the corresponding imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines are obtained, respectively.     

An Improved Synthesis of 2-Chlorinated Imidazo[1,2-α]-pyridines and the Application of this Procedure for the Synthesis of Several New Polychlorinated Imidazo[1,2-α]Pyridnes.

Polychlorinated imidazo[1,2-α]pyridines were synthesized as analogs of certain chlorinated benzimidazoles. The imidazo[1,2-α]pyridines were obtained by a condensation of ethyl bromoacetate and chlorinated 2-aminopyridines. These condensation products were treated with an ion exchange resin to effect an exchange of hydrobromide salts with hydrochloride salts. These compounds were subsequently treated with POCl₃ to convert the imidazo[1,2-α]pyridin-2-ones into 2-chloroimidazo[1,2-a]pyridines.     

Imidazo[1,2-a]pyridines susceptible to excited state intramolecular proton transfer: one-pot synthesis via an Ortoleva-King reaction

A short and efficient route to a broad range of imidazo[1,2-a]pyridines from 2-aminopyridines and acetophenones is achieved by a tandem, one-pot process starting with an Ortoleva-King reaction. Optimal conditions for the first step were established after examining various reaction parameters (solvent, reagent ratios, and temperature). The conditions identified (1st step, neat, 2.3 equiv of 2-aminopyridine, 1.20 equiv of I(2), 4 h, 110 °C; 2nd step, NaOH(aq), 1 h, 100 °C) resulted in the formation of imidazo[1,2-a]pyridines in 40-60% yields. The synthesis is compatible with various functionalities (OH, NMe(2), Br, OMe). Products containing a 2-(2'-hydroxyphenyl) substituent undergo excited state intramolecular proton transfer (ESIPT) in nonpolar and polar-aprotic solvents. Although ESIPT-type emission in nonpolar solvents is weak, the Stokes shifts are very high (11000 cm(-1)). The comparison of the properties of six ESIPT-capable imidazo[1,2-a]pyridines shows the influence of various substituents on emission characteristics. All of them also display strong, solid-state emission in blue-green-yellow region. 2-Aryl-imidazo[1,2-a]pyridines not capable of ESIPT emit in the blue region, displaying high fluorescence quantum yield.     

One-pot Copper Nanoparticle-catalyzed Synthesis of Imidazo[1,2-α]pyridines Under Solvent-free Conditions

A direct and efficient approach to synthesize imidazo[1,2-α]pyridines through three-component one-pot reaction of 2-aminopyridine,aldehyde and terminal alkyne catalyzed by Cu-nanoparticles under solvent-free conditions has been developed.This method provides a rapid access to substituted imidazo[1,2-α]pyridines with good yields（up to 85％）.     

Solid-phase synthesis of imidazo[1,2-a]pyridine using sodium benzenesulfinate as a traceless linker

[formula: see text] The preparation of the first library of imidazo[1,2-a]pyridine derivatives on a solid support is described. A sulfone linker strategy was applied in the synthesis. Key steps involved in the solid-phase synthetic procedure include (i) alpha-haloketone resin formation by sulfinate-->sulfone alkylation, (ii) imidazo[1,2-a]pyridine ring formation by treatment with 2-aminopyridine, (iii) sulfone anion alkylation, and (iv) traceless product release by oxidation-elimination. A library of 12 imidazo[1,2-a]pyridines was synthesized.     

Efficient solid-phase synthesis of a library of imidazo[1,2-a]pyridine-8-carboxamides

A versatile method for the solid-phase synthesis of imidazo[1,2-a]pyridine-based derivatives, imidazo[1,2-a]pyridine-8-carboxamides, has been developed. They were obtained by treatment of the amino group of the polymer-bound 2-aminonicotinate with different alpha-haloketones, followed by halogenation at the 3-position of the polymer-bound imidazo[1,2-a]pyridine. The derived polymer-bound imidazo[1,2-a]pyridines 5, 6, and 7 were finally cleaved from the solid-support with an excess of primary or secondary amines. The final crude products were purified from excess amines by solid-supported liquid-liquid extraction (SLE).     

Phosphorylated imidazo[1,2-a]pyridines

The reaction of phosphorus(III) halides with imidazo[1,2-a]pyridines in the presence of bases leads to the formation of 3-phosphorylated imidazo[1,2-a]pyridines. The reaction proceeds in high yield and requires no catalysts. In the compounds obtained, in contrast to phosphorylated indolizines, the phosphorus–heterocycle bond is stable and not cleaved by dry hydrogen chloride, alcohols, or water. Imidazo[1,2-a]pyridines with the phosphinic and phosphinous groups can be alkylated both at the phosphorus and at the nitrogen atom of the heterocycle, the alkylation direction being dependent on the strength of the alkylation reagent used. © 1995 John Wiley & Sons, Inc.     

Reaction of β-lactam carbenes with 2-pyridyl isonitriles: a one-pot synthesis of 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines useful as fluorescent probes for mercury ion

The one-pot reaction of β-lactam carbenes with 2-pyridyl isonitriles followed by an acidic hydrolysis was reported, which produced 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines in moderate to good yields. Among the resulting novel imidazo[1,2-a]pyridine derivatives, 1-(6-chloro-3-(5-chloropyridin-2-ylamino)imidazo[1,2-a]pyridin-2-yl)-2-ethylbutan-1-one was demonstrated to be an efficient fluorescent probe for mercury ion both in acetonitrile and in buffered aqueous solution.     

Heterocyclizations with tosylmethyl isocyanide derivatives. A new approach to substituted azolopyrimidines

An efficient synthesis of substituted azolopyrimidines such as pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidines, pyrimido[1,6-a]indoles, benzo[4,5]imidazo-[1,2-c]pyrimidines, an imidazo[1,2-c]pyrimidine, and pyrazolo[1,5-c]pyrimidines is described. The method involves the reaction of N-protected bromomethylazoles and tosylmethyl isocyanide (TosMIC) derivatives in nonanhydrous media. The study of the reaction conditions shows that the method is only successful under phase-transfer conditions (CH2Cl2/30% aq NaOH) using benzyltriethylammonium chloride as a catalyst.     

1-Alkynyl- and 1-alkenyl-3-arylimidazo[1,5-a]pyridines: synthesis, photophysical properties, and observation of a linear correlation between the fluorescent wavelength and Hammett substituent constants

1-Alkynyl- and 1-alkenyl-3-arylimidazo[1,5-a]pyridines were synthesized. The Sonogashira coupling of 3-aryl-1-iodoimidazo[1,5-a]pyridines and various terminal alkynes with Pd(PPh(3))(2)Cl(2) (10 mol %) and CuI (10 mol %) in triethylamine at 80 °C for 12 h afforded the corresponding 1-alkenyl-3-arylimidazo[1,5-a]pyridines in good to excellent yields. The Mizoroki-Heck reaction of 3-aryl-1-iodoimidazo[1,5-a]pyridines and various styrene derivatives proceeded smoothly with Pd(OAc)(2) (5 mol %), IMes·HCl (10 mol %), and Cs(2)CO(3) (2 equiv) in DMA at 130 °C for 20 h to give the alkenylated imidazo[1,5-a]pyridines in moderate to high yields. The fluorescence maxima and fluorescence quantum yields of the alkynylated products were 458-560 nm and Φ(F) = 0.08-0.26 in chloroform solution, and those of the alkenylated imidazopyridines were 479-537 nm and Φ(F) = 0.03-0.13. The absorption behaviors of the obtained alkynylated and alkenylated imidazo[1,5-a]pyridines showed a good fit to the values predicted by TDDFT calculations at the B3LYP/6-311++G(d,p) level. In addition, the alkynylated imidazo[1,5-a]pyridines obtained showed linear correlations between the Hammett substituent constants of the substituents on the arylalkynyl group and their fluorescence wavelengths.     

Heterocyclic amino acids as synthons. Reactions with dicarbonyl compounds

From some alkyl heteroarylglycinates and dicarbonyl compounds various heterocyclic systems are easily accessible. Transformations are described which lead to imidazo[1,5-α]pyridines, heteroaryl-substituted pyrroles, pyrido[1,2-α]pyrazines, pyrido[1,2-α]pyrimidines or quinolizin-4-ones.     

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.     

Solvent and catalyst-free synthesis of imidazo[1,2-a]pyridines by grindstone chemistry

The present work describes the solvent and catalyst-free synthesis of imidazo[1,2-a]pyridines in excellent to nearly quantitative yields from 2-aminopyridines and a wide variety of ω-bromomethylketones using a grindstone procedure at 25°C to 30°C for 3 to 5 minutes. The absolute structure of the compound, 2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridine is determined by X-ray crystallography. This green strategy has several noteworthy advantages such as wide spread substrate scope, short reaction times, water work up and the products do not require any chromatographic purification. Moreover, the method does not require any specialized equipment and is highly economical, environmentally benign and easy to carry out in any laboratory. Hence, the developed method meets the concept of “benign by design” and is greener alternative to the reported procedures for the synthesis of imidazo[1,2-a]pyridines.     

A new three-carbon synthon for efficient synthesis of benzannelated and 1-(2-arylethenyl) heterocycles

The novel three-carbon synthon 1-(1H-1,2, 3-benzotriazol-1-yl)-3-chloroacetone for the synthesis of benzothiazoles, pyrido[1,2-a]indoles, and styryl-substituted indolizines and imidazo[1,2-a]pyridines is reported. The proposed routes are a general and efficient approach for heterocyclizations followed by benzannelations or attachment of arylethenyl pharmacophores.