A new synthetic approach to functionalize pyrimido[4,5-<Emphasis Type="Italic">b</Emphasis>]quinoline-2,4(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>)-diones via a three-component one-pot reaction

Functionalized pyrimido[4,5-b]quinoline-2,4 (1H,3H)-diones were synthesized by a three-component one-pot reaction involving barbituric acid, aldehydes, and anilines. The use of commercially available anilines allowed the facile syntheses of pyrimido[4,5-b]quinolinediones substituted in all the positions on the benzene ring with electron donor or electron withdrawing groups. This straightforward method circumvents the preparation of unstable substituted 2-aminobenzaldehydes that limits the scope of previously described syntheses. Furthermore, access to the 5-substituted derivatives is now also possible starting from aliphatic or aromatic aldehydes. Our strategy and methodology offer significant and practical improvements over other methodologies.     

An efficient and facile synthesis of new tetracyclic fused pyrazolo[4,3-<Emphasis Type="Italic">c</Emphasis>][1,2,4]triazino[4,5-<Emphasis Type="Italic">a</Emphasis>]quinolin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

Reaction of amidrazones 1a–1i with (1,5-dihydro-3-methyl-5-oxo-1-phenyl-4H-pyrazol-4-ylidene)propanedinitrile (2) in ethyl acetate solution in one-step reaction led to the formation of unprecedented pyrazolo[4,3-c][1,2,4]triazino[4,5-a]quinolin-4(5H)-ones 3a–3g along with pyrazolo[4,3-c][1,2,4]triazino[4,5-a]quinolin-12b-oles 3h–3m in moderate to excellent yields. These novel heterocycles were formed via a Michael addition reaction followed by intramolecular cyclization via a dearomatization process.     

A new one-pot three-component synthesis of 2,4-diamino-5<Emphasis Type="Italic">H</Emphasis>-chromeno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine-3-carbonitrile derivatives

In this study, a three-component one-pot synthesis of new 2,4-diamino-5H-chromeno[2,3-b]pyridine-3-carbonitriles derived from 2-amino-1,1,3-tricyanopropene, salicylic aldehydes and secondary cyclic amines is reported. The reaction is conducted in ethanol at ambient temperature in good-to-excellent yields.     

Sulfamic acid catalyzed solvent-free synthesis of 10-aryl-7,7-dimethyl-6,7,8,10-tetrahydro-9H-[1,3]-dioxolo [4,5- <Emphasis Type="Italic">b</Emphasis>]xanthen-9-ones and 12-aryl-9,9-dimethyl-8,9,10,12-tetrahydro-11H-benzo[<Emphasis Type="Italic">a</Emphasis>]xanthen-11-ones

Three-component one-pot synthesis of some novel 10-aryl-7,7-dimethyl-6,7,8,10-tetrahydro-9H-[1,3]-dioxolo[4,5-b]xanthen-9-ones, which have not been published before, and 12-aryl-9,9-dimethyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-ones from condensation of 3,4-methylenedioxyphenol or β-naphthol, aldehydes and dimedone under solvent-free conditions at 120 °C is reported.     

Substituted <Emphasis Type="Italic">N</Emphasis>-aminothioglycolurils containing thiosemicarbazone moiety and their cytotoxic activity in vitro

A library of hybrid molecules bearing thioglycoluril and (hetero)aromatic aldehyde thiosemicarbazone moieties was synthesized via a tandem hydrazone formation—ring contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with (hetero)aromatic aldehydes. All synthesized compounds were tested for their cytotoxic activity against rhabdomyosarcoma, A549, and MS human cancer cell lines by MTT-assay. Among the derivatives, (E)-4-benzylideneamino-1,3-dimethyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one 1f was found to have the most marked antiproliferative activity toward the tested cell lines (1f: IC\(_{50}= 20.6,\) 23.7, and 6.4 \(\upmu \)M, respectively). The IC\(_{50}\) value of thioglycoluril 1f against normal human embryonic kidney cells HEK293 was 72.5 \(\upmu \)M, which appeared to be 3–11-fold higher than IC\(_{50}\) values of 1f against human cancer cells.     

Ionic liquid-promoted multi-component reaction: novel and efficient preparation of pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridinone,pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]-quinolinone and their hybrids with pyrimidine nucleoside

The utilization of an ionic liquid, [bmim][BF₄] as both reaction medium and promoter for a multi-component reaction of aldehyde (1) and 5-amino-3-methyl-1-phenylpyrazole (2) with Meldrum acid (3) or dimedone (5) is studied. From this reaction, pyrazolo[3,4-b]pyridinone (4) and pyrazolo[3,4-b]quinolinone (6) derivatives were prepared in high yields. This novel procedure showed such advantages as environmentally benign nature, enhanced efficiency, simple operation process, and mild reaction conditions. As an application, the procedure was successfully used in the preparation of a set of pyrimidine nucleoside–pyrazolo[3,4-b]pyridine and pyrazolo[3,4-b]quinolinone hybrids with potential biological activities.     

Diversity oriented heterocyclizations of pyruvic acids,aldehydes and 5-amino-<Emphasis Type="Italic">N</Emphasis>-aryl-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides: catalytic and temperature control of chemoselectivity

Heterocyclization reactions of pyruvic acids, aromatic aldehydes and 5-amino-N-aryl-1H-pyrazole-4-carboxamides yielding four different types of final compounds are described. The reactions involving arylidenpyruvic acids lead with high degree of selectivity to either 4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids or 5-[(2-oxo-2,5-dihydrofuran-3-yl)amino]-1H-pyrazoles, depending on the catalyst type or temperature regime. The interactions based on arylpyruvic acids can take place under kinetic or thermodynamic control producing 7-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-7-carboxylic acids or 3-hydroxy-1-(1H-pyrazol-5-yl)-1,5-dihydro-2H-pyrrol-2-ones, respectively.     

Parallel and automated library synthesis of 2-long alkyl chain benzoazoles and azole[4,5-<Emphasis Type="BoldItalic">b</Emphasis>]pyridines under microwave irradiation

Summary A versatile route to 40-membered library of 2-long alkyl chain substituted benzoazoles (1 and 2) and azole[4,5-b]pyridines (3 and 4) via microwave-assisted combinatorial synthesis was developed. The reactions were carried out in both monomode and multimode microwave oven. With the latter, all reactions were performed in high-throughput experimental settings consisting of an 8×5 combinatorial library designed to synthesize 40 compounds. Each step, from the addition of reagents to the recovery of final products, was automated. The microwave-assisted N-long chain alkylation reactions of 2-alkyl-1H-benzimidazole (1) and 2-alkyl-1H-benzimidazole[4,5-b] pyridines (3) were also studied.     

One-pot microwave-assisted protocol for the synthesis of substituted 2-amino-1<Emphasis Type="Italic">H</Emphasis>-imidazoles

Abstract  

An efficient microwave-assisted one-pot two-step protocol was developed for the construction of disubstituted 2-amino-1H-imidazoles. This process involves the sequential formation of 2,3-dihydro-2-hydroxyimidazo[1,2-a]pyrimidinium salts from readily available 2-aminopyrimidines and α-bromoketones, followed by cleavage of the pyrimidine ring with hydrazine.     

Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines

A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from ??,??-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an ??,??-unsaturated ester, malononitrile, and an aryl substituted guanidine.     

Synthesis of cyano-2,3-dihydropyrrolo[1,2-<Emphasis Type="Italic">f</Emphasis>]phenanthridine derivatives via a domino-Knoevenagel-cyclization

Abstract  

In a new multicomponent reaction phenanthridine reacts with isocyanides and malonitrile in the presence of benzaldehyde derivatives to produce 2-aryl-3-(alkyl- or arylimino)-2,3-dihydropyrrolo[1,2-f]phenanthridine-1,1(12b H)-dicarbonitrile in a simple, mild, and efficient protocol in excellent yields.     

A diversity-oriented synthesis of pyrazolo[4,3-<Emphasis Type="Italic">f</Emphasis>]quinoline derivatives with potential bioactivities via microwave-assisted multi-component reactions

Six new series of pyrazolo[4,3-f]quinoline derivatives with potential bioactivities were synthesized by the three-component reactions of aromatic aldehydes, 5-aminoindazole, and various cyclic 1,3-dicarbonyl compounds under microwave irradiation. This protocol has the valuable features of structural diversity of products, broader substrate scope, operational simplicity, high yields, and short reaction time. Moreover, the structure of compound 88a was confirmed by an X-ray crystallographic analysis and attested to the chemoselectivity of reaction where 1-methyl barbituric acid participated.     

Self-trapping of the <Emphasis Type="Italic">d</Emphasis>-<Emphasis Type="Italic">d</Emphasis> charge transfer exciton in bulk NiO evidenced by X-ray excited luminescence

Soft X-ray (XUV) excitation did make it possible to avoid the predominant role of the surface effects in luminescence of NiO and revealed a bulk luminescence with a puzzling well isolated doublet of very narrow lines with close energies near 3.3 eV which is assigned to recombination transitions in self-trapped d-d charge transfer (CT) excitons formed by coupled Jahn-Teller Ni⁺ and Ni³⁺ centers. The conclusion is supported both by a comparative analysis of the CT luminescence spectra for NiO and solid solutions Ni _x Zn_{1 − x} O, and by a comprehensive cluster model assignment of different p-d and d-d CT transitions, their relaxation channels. To the best of our knowledge, it is the first observation of the luminescence due to self-trapped d-d CT excitons.     

A diversity oriented, microwave assisted synthesis of N-substituted 2-hydro-4-amino-pyrido[2,3-d]pyrimidin-7(8H)-ones

A protocol for the synthesis of N-substituted 2-hydro-4-amino-pyrido[2,3-d]pyrimidin-7(8H)-ones (11) is described. Thus, the formylation of a 2-aminopyridone 12 in 85% formic acid/Ac₂O, proceeding via in situ cyclization to the intermediate formamide 13, affords the corresponding 2-hydro-4-oxo-pyridopyrimidine 14, which is converted to a 4-chloro-pyridopyrimidine 15 upon treatment with POCl₃. The subsequent transformation to the title compounds is carried by treatment with the corresponding amine in MeOH under microwave irradiation conditions.     

Unexpected deviation from diene behaviour of uracil amidine: towards synthesis of some pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine derivatives

Condensation products obtained from the treatment of uracil amidine with preformed or in situ generated suitably substituted olefins unexpectedly undergo intramolecular cyclisation during silica gel chromatography to generate pyrido[2,3-d]pyrimidines. Various reaction conditions are studied and the altered nature of the uracil amidine molecule is further explored by reacting it with different suitably substituted alkenes.     

New Fluorescent Sensors Based on 1<Emphasis Type="Italic">H</Emphasis>-pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]quinoline Skeleton

Novel fluorescing dyes 1,3,4-triphenyl-6-(1,4,7,10-tetraoxa-13-aza-cyclopentadec-13-ylmethyl)-1H-pyrazolo[3,4-b]quinoline (K1) and 2-[(2-hydroxyethyl)-(1,3,4-triphenyl-1H-pyrazolo[3,4-b]quinolin-6-ylmethyl)-amino]ethanol (L1) have been synthesized and investigated by the means of steady state and time-resolved fluorescence techniques. These compounds act as sensors for the fluorescence detection of small inorganic cations (lithium, sodium, barium, magnesium and calcium) in solvents of different polarities (THF and acetonitrile). The mechanism, which allows application of these compounds as sensors, is an electron transfer from the electro-donative part of molecule to the acceptor part (fluorophore), which is retarded upon complexation of the electro-donative part by inorganic cations. We found that crown ether-containing compound is very sensitive to the addition of any investigated ions but amino alcohol-containing one exhibits better selectivity to the addition of two-valued cations. Two kinds of the complexes (LM⁺ and L₂M⁺) were found in the investigated systems. In addition, the dyes may be used as fluorescence indicators in solvents of lower polarity like tetrahydrofuran.     

Structural relationships in the solid state of the anti-chagas agent (<Emphasis Type="Italic">E</Emphasis>)-phenylethenylbenzofuroxan

The crystal structure and the vibrational spectrum of a potential drug for Chagas‘s disease treatment, the (E)-isomer of phenylethenylbenzofuroxan 1 (5(6)(E)-[(2-phenylethenyl)]benzo[1,2-c]1,2,5-oxadiazole N-oxide), are reported. In order to provide insights into structural relationships, quantum mechanical calculations were employed starting from crystal structure. These results have given theoretical support to state interesting structural features, such as the effect of some intermolecular contacts on the molecule conformation and the electronic delocalization decreasing through atoms of the benzofuroxan moiety. Furthermore, the MOGUL comparative analysis in the Cambridge Structural Database provided additional evidences on these structural behaviors of compound 1. Intermolecular contacts interfere on the intramolecular geometry, as, for instance, on the phenyl group orientation, which is twisted by 12.32(6)° from the ethenylbenzofuroxan plane. The experimental Raman spectrum of compound 1 presents unexpected frequency shift and also anomalous Raman activities. At last, the molecule skeleton deformation and the characteristic vibrational modes were correlated by matching the experimental Raman spectrum to the calculated one.     

A <Emphasis Type="Italic">q</Emphasis>-deformed particle algebra with a unique <Emphasis Type="Italic">d</Emphasis>-dimensional representation

We present an algebra generated by a single pair of creation and annihilation operators b and b*. We prove that the algebra has a unique d-dimensional representation. Physically this algebra corresponds to a system where there are at most d − 1 particles in a state with otherwise same quantum numbers.     

Analysis of the spectrum of the Zn-like Kr VII ion: Highly excited 4<Emphasis Type="Italic">p</Emphasis>4<Emphasis Type="Italic">d</Emphasis> and 4<Emphasis Type="Italic">p</Emphasis>5<Emphasis Type="Italic">s</Emphasis> configurations

The spectrum of the Zn-like Kr VII ion, excited in a capillary discharge and recorded with a high resolution in the wavelength range of 300–1000 Å, was studied. Previously performed identification of the transitions from the levels of the 4s4f, 4s5s, 4s5p, and 4s5d configurations is confirmed and extended, and the energies of these levels are specified. The (4p ²+4s4d)?4p4d and (4p ²+4s5s)?4p5s transitions are identified for the first time, and the energies of all the levels of the 4p4d and 4p5s configurations are determined. The results of the analysis performed are confirmed by semiempirical calculations in terms of the Hartree-Fock method. These results are also shown to conform to the experimental data obtained for lighter ions of the Zn I isoelectronic sequence.     

<Emphasis Type="Italic">Ab initio</Emphasis> theory of the electronic structure and spectra of impurity <Emphasis Type="Italic">nl</Emphasis> ions

The fundamentals of the theory of the electronic structure of impurity clusters and the results of numerical calculations for the iron-, lanthanum-, and actinium-group ions in Me⁺ⁿ: [L]_k clusters are presented. The effects of the interionic distance and ligands in the Me⁺ⁿ: [L]_k clusters on the electronic structure of the nl ^N and nl^N?1n′l′ configurations of the 3d, 4f, and 5f ions are considered. The correspondence between the optical and x-ray spectra of different impurity crystals is also analyzed.