Bis-heterocyclic Compounds Research Articles

Vicinal Bisheterocyclizations of Alkynes via Nucleophilic Interception of a Catalytic Platinum Carbene

A novel platinum-catalyzed double heterocyclization of propargylic ethers is described. The transformation exploits the intermediacy of a key α,β-unsaturated carbene. The reactivity of this carbene is such that systems can be developed which avoid a complicating 1,2-hydrogen migration, allowing remarkable versatility in the selective syntheses of oxygen- and nitrogen-containing vicinal bis-heterocyclic compounds.

ChemInform Abstract: Synthesis of Triazole and Isoxazole Based Novel Unsymmetrical Bis‐heterocycles.

Novel unsymmetrical bis-heterocyclic compounds encompassing triazole and isoxazole moieties were synthesized by employing 1,3-dipolar cycloaddition/click chemistry approach using 5-butynyl-1,2,3-triazoles and 5-butynyl isoxazoles.

Synthesis of bis-heterocyclic compounds with a phenylene bridge from 1,4- and 1,3-bis(2-chloro-2-cyanovinyl)benzenes

Reaction of binucleophiles with 1,4- and 1,3-bis(2-chloro-2-cyanovinyl)benzenes, synthesized using a catalytic olefination of terephthalic and isophthalic aldehydes, gave high yields of aminopyrazoles, 3-amino-5-arylthiophene-2-carboxylic acid esters, and 2,4-diamino-6-arylpyrimidines.

Synthesis of Various S-S Linked Symmetric Bisazaheterocycles: A Review

There has been an increasing interest in discovering and developing small molecules that are of pharmaceutical importance. Heterocyclic compounds are known to be the most versatile class of these types of molecules, either prepared synthetically or occurring in nature. However, in some cases, it has been reported that the activity is enhanced to a larger extent when these heterocycles are repeated in the molecule separated by a suitable spacer, i.e., a bis-heterocycle. Thus, the synthesis of new bis-heterocyclic compounds has become an eye-catchy field to explore in the recent past owing to their pharmacological, biological and industrial importance. The synthesis of bis-heterocycles is mainly achieved by join- ing heterocyclic nuclei together using a variety of linkers and points of linkages. These structural permutations and com- binations have given an unlimited number of available bis-heterocycles. Use of S-S linkage is one such facile method of getting bis-heterocycles as they are easily obtained from the oxidation of thiols and protected thiols by using broad range of reagents and reaction conditions. Disulphide linkage being an integral part of the biological system, as disulphide bonds are found in peptides and proteins, also adds to the efficacy of these bis-heterocycles.

Synthesis of Thieno[2,3-b]thiophene Containing Bis-Heterocycles-Novel Pharmacophores

Thioenethiophene derivatives represent an important class of compounds with diverse biological activities. We describe here the synthesis of a new series of thieno[2,3-b]thiophene containing bis-heterocyclic compounds 3–7. All the compounds were evaluated for their in vitro antioxidant potential, α-glucosidase and β-glucuronidase inhibiton and anticancer activity against PC-3 cell lines. Compounds 2b (IC50 = 1.3 ± 0.2 μM), 5a (IC50 = 2.3 ± 0.4 μM) and 5b (IC50 = 8.7 ± 0.1 μM) showed a potent inhibition of β-glucuronidase enzyme, more active than the standard d-saccharic acid 1,4-lactone (IC50 = 45.8 ± 2.5 μM). Compounds 5a (IC50 = 22.0 ± 0.3 μM) and 5b (IC50 = 58.4 ± 1.2 μM) were also found to be potent α-glucosidase inhibitors as compared to standard drug (acarbose, IC50 = 841 ± 1.7 μM).

Three Novel Sequential Reactions for the Facile Synthesis of a Library of Bisheterocycles Possessing the 3-Aminoimidazo[1,2-a]pyridine Core Cata­lyzed by Bismuth(III) Chloride

Novel, one-pot, two-step, sequential protocols for the synthesis of 1,4-phenylene bisheterocyclic compounds have been developed. Successive sequencing of the Groebke–Blackburn–­Bienaymé reaction with Ugi-azide, Hantzsch and Biginelli reactions results in rapid and efficient formation of bisheterocyclic compounds. A simple, fast and high yielding method for the synthesis of 3-aminoimidazo[1,2-<i>a</i>]pyridines catalyzed by bismuth(III) chloride under solvent-free conditions is reported. Bismuth(III) chloride is also an efficient catalyst for the Ugi-azide reaction under solvent free conditions.

New bispyrazoline derivatives built around aliphatic chains: Synthesis, characterization and antimicrobial studies

The bispyrazolines 3a–3h built around the alkyl chains of varying lengths have been synthesized from the cyclization reactions of bischalcones with phenyl hydrazine. The bischalcones 2a–2h were obtained from the Claisen–Schmidt reactions of acetophenone with various bisaldehydes 1a–1h. The intermediate bischalcones and final bisheterocyclic compounds have been characterized by means of IR, 1H-NMR, 13C-NMR, Mass (ESI) and elemental analysis. The antibacterial and antifungal activities of the synthesized compounds were also evaluated against the Klubsellia pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillius subtilis and Aspergillius janus, Aspergillus niger and Pencillium glabrum, respectively. The antimicrobial behaviour of the bispyrazolines 3a–3h is found to be dependent on the length of internal spacer unit.

Sulfonated rice husk ash (RHA-SO3H) as a highly efficient and reusable catalyst for the synthesis of some bis-heterocyclic compounds

Sulfonated rice husk ash (RHA-SO3H), a newly reported solid acid catalyst, was efficiently used for the synthesis of 4,4′-(arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols), 3,3′-(arylmethylene)-bis-(4-hydroxycoumarins) and bis(indolyl)methanes. The procedure gave the products in excellent yields within very short reaction times under mild and green conditions. Also this catalyst can be reused several times without appreciable loss of its catalytic activity.

Intramolecular hydrogen bonds C-H⋯N in bisheterocyclic compounds according to 1H and 13C NMR data

Data of 1H and 13C NMR spectra show that in 2,2′-bipyridyl, 1-vinyl-2(2′-pyridyl)benzimidazole, 1-vinyl-3-vinylsulfanyl-5-(2-furyl)-1,2,4-triazole, and 1-vinyl-5-vinylsulfanyl-3-(2-furyl)-5-vinylthio-1,2,4-triazole exists a weak intramolecular hydrogen bond between the heterocyclic fragments. It causes a downfield shift of the bridging proton signal in the 1H NMR spectrum by 0.6–0.7 ppm and an increase in the corresponding direct coupling constant 13C-1H by 1.5–2.0 Hz. These variations in the spectral parameters can be efficiently used in the conformational analysis for establishing with the use of NMR method which conformers are predominantly populated in the heterocyclic compounds.

A Novel and Expedient Approach to New Thiazoles, Thiazolo[3,2-a]pyridines, Dihydrothiophenes, and Hydrazones Incorporating Thieno[2,3-b]thiophene Moiety

This paper reports details about the synthesis of a series of novel functionalized symmetrical bis-heterocyclic compounds containing a thieno[2,3-b]thiophene motif. Bis-thiazole derivatives 2, 3a-c and thiazolo[3,2-a]pyridine derivatives 4a-c are achieved. The hitherto unknown dihydrothiophene derivatives 6a-d via bis-pyridimium salt 5 are obtained. Additionally, the novel hydrazonothieno[2,3-b]thiophene derivatives 10a-c are obtained via bis-tosylacetylthieno[2,3-b]thiophene derivative 9. All compounds are characterized by 1H-, 13C-NMR, GCMS, IR, and UV-vis spectrometry. These compounds represent a new class of sulfur and nitrogen containing heterocycles that should also be of interest as new materials.

Comprehensive and Facile Synthesis of Some Functionalized Bis-Heterocyclic Compounds Containing a Thieno[2,3-b]thiophene Motif

A comprehensive and facile method for the synthesis of new functionalized bis-heterocyclic compounds containing a thieno[2,3-b]thiophene motif is described. The hitherto unknown bis-pyrazolothieno[2,3-b]thiophene derivatives 2a–c, bis-pyridazin othieno[2,3-b]thiophene derivatives 4, bis-pyridinothieno[2,3-b]thiophene derivatives 6a,b, and to an analogous bis-pyridinothieno[2,3-b]thiophene nitrile derivatives 7 are obtained. Additionally, the novel bis-pyradazinonothieno[2,3-b]thiophene derivatives 9, and nicotinic acid derivatives 10, 11 are obtained via bis-dienamide 8. The structures of all newly synthesized compounds have been elucidated by 1H, 13C NMR, GCMS, and IR spectrometry. These compounds represent a new class of sulfur and Nitrogen containing heterocycles that should also be of interest as new materials.

ChemInform Abstract: Synthesis of 1,4‐Phenylene‐bridged Bis‐Heterocyclic Compounds

AbstractReview: 103 refs.

Theoretical study on the mechanism of cycloaddition reaction between dichlorogermylene silylene (Cl2Ge=Si:) and acetaldehyde

The mechanism of the cycloaddition reaction between singlet state dichlorogermylene silylene (Cl2Ge=Si:) and acetaldehyde has been investigated with the MP2/cc-pvtz//MP2/6-31G* method. According to the potential energy profile, it can be predicted that the reaction has four competitive dominant reaction pathways. The presented rule of this reaction is that the 3p unoccupied orbital of Si: atom in dimethylgermylene silylene(Cl2Ge=Si:) inserts the π orbital of acetaldehyde from the oxygen side, resulting in the formation of intermediate. In the intermediate and two reactants, two four-membered ring silylenes, with Si and O in the syn-position and opposite orientation, respectively, are generated, as the [2+2] cycloaddition reaction has occurred between the two bonding π orbital in dichlorogermylene silylene and acetaldehyde. Because of the unsaturated property of Si: atom in the two four-membered ring silylenes, they can further react with acetaldehyde to form two silicic bis-heterocyclic compounds. Simultaneity, the drive of ringlet tensility and unsaturated property of Si: atom in the four-membered ring silylene makes it isomerize into a distorted four-membered ring product and a Cl-transfer product and a H-transfer product, respectively.

Synthesis of 1,4-phenylene bridged bis-heterocyclic compounds

Synthesis of 1,4-phenylene bridged bis-heterocyclic compounds

Purine Scaffold Effect on Fluorescence Properties of Purine-Hydroxyquinolinone Bisheterocycles

The fluorescence properties of bisheterocyclic compounds that contain purine and the 3-hydroxyquinolin-4(1H)-one skeleton connected with an aliphatic spacer of a different length/structure (3HQP) were examined. It was found that the introducing of the spacer-purine scaffold led in the comparison to 3HQs themselves to (1) the possibility of the effectual excitation in the wider range of excitation wavelengths, moreover, some derivatives can be excited at relatively high wavelengths around 400 nm, (2) the lowering of the quantum yield and (3) the slight longer wavelength shift of the dual emission spectra. Tested organic solvents did not affect significantly the 3HQP fluorescence properties. The characters of emission spectra as well as the quantum yields of 3HQPs were notably influenced by the ratio of water and DMSO in their composed mixture applied as a solvent. With increasing water content in the mixture both I(1)/I(2) and the quantum yield decreased.

Synthesis and Bioactivity of Novel Bis‐heterocyclic Compounds Containing Pyrazole and Oxadiazoline

AbstractNucleophilic addition of the starting material 3‐aryl‐1‐phenyl‐4‐formylpyrazoles (1∼3) and 4‐substituted aryloxyacetyl hydrazine (4a∼4e) afford hydrazone compounds containg pyrazolyl (5a∼5e, 6a∼6e, 7a∼7e) in the ethanol. These adducts were refluxed in Ac2O and furnished a series of novel bis‐hetero‐cyclic compounds. (8a∼8e, 9a∼9e, 10a∼10e) via cyclic reaction. The structures of all newly synthesized compounds were established by IR, 1H NMR, MS and elemental analysis. New compounds conducted preliminary tests of antibacterial activities about Fusarium oxyaporium, Verticillium dahliae, Rhizoctonia solani, Pychium aphanidermatum, Alternaria solani, Sclerotinia sclerotiorum. The results showed that the inhibiting rate of the bis‐heterocyclic compounds (8a∼8e, 9a∼9e, 10a∼10e) was higher than the pyrazolyl hydrazones (5a∼5e, 6a∼6e, 7a∼7e) obviously.

Ab initio study on the mechanism of cycloaddition reaction between H2Si=Si: and formaldehyde

The mechanism of the cycloaddition reaction between singlet H2Si=Si: and formaldehyde has been investigated with the CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has three competitive dominant reaction pathways. The reaction rules presented is that the 3p unoccupied orbital of the Si: atom in H2Si=Si: inserts the π orbital of formaldehyde from the oxygen side, resulting in the formation of an intermediate. Isomerization of the intermediate further generates a four-membered ring silylene (the H2Si–O in the opposite position). In addition, the [2+2] cycloaddition reaction of the two π-bonds in H2Si=Si: and formaldehyde also generates another four-membered ring silylene (the H2Si–O in the syn-position). Because of the unsaturated property of the Si: atom in the two four-membered ring silylenes, the two four-membered ring silylenes could further react with formaldehyde, generating two silicic bis-heterocyclic compounds. Simultaneously, the ring strain of the four-membered ring silylene (the H2Si–O in the syn-position) makes it isomerize to a twisted four-membered ring product.

Solid-Phase Synthesis of Highly Diverse Purine-Hydroxyquinolinone Bisheterocycles

Solid-phase synthesis of bisheterocyclic compounds that contain purine and the 3-hydroxyquinolin-4(1H)-one skeleton connected with an aliphatic spacer of a different length/structure is described. The reaction sequence started from the primary amines immobilized on aminomethylated polystyrene resin equipped with an acid-labile linker (4-(4-formyl-3-methoxyphenoxy)butyric acid). After the arylation of amines with 2,6-dichloropurine via its C(6), purine N(9) was alkylated and subsequently the chlorine at purine C(2) was substituted with aliphatic diamines. The resulting terminal amino group was used as the starting point for the synthesis of 3-hydroxyquinolin-4(1H)-one precursors based on the acylation with 3-amino-4-(methoxycarbonyl)benzoic acid followed by the saponification of the methyl ester and esterification of the resulting carboxylic acid with various haloketones. The intermediates were cleaved from the resin, and their cyclization to the target purine-hydroxyquinolinone bisheterocycles was accomplished by heating in acetic or trifluoroacetic acid.

Synthesis of some alkoxy based bisthiadiazolines

The bisthiadiazolines 3a–3h built around the alkyl chains of varying lengths have been synthesized in good yields by refluxing bisthiosemicarbazones 2a–2h in acetic anhydride. The reactions of bisaldehydes 1a–1h with thiosemicarbazide in alcoholic medium provided 2a–2h and the former were obtained by using the reported methods. The formation and stereochemical features of the bisthiadiazolines 3a–3h are found to be independent of the internal spacer length. The intermediates 2a–2h and bisheterocyclic compounds 3a–3h have been characterized by means of IR, 1H NMR, 13C NMR, Mass (ESI) and elemental analysis.

Ab initioStudy of Mechanism of Forming Germanic Bis-Heterocyclic Compound Between Dichloro-Germylene Carbene (Cl2Ge = C:) and Formaldehyde

The mechanism of the cycloaddition reaction of forming germanic bis-heterocyclic compound between singlet dichloro-germylene carbene and formaldehyde has been investigated with CCSD(T)//MP2/6–31G* method, from the potential energy profile, we predict that the reaction has two competitive dominant reaction pathways. The presented rule of this reaction: the 2p unoccupied orbital of the C atom in dichloro-germylene carbene insert the π orbital of formaldehyde from oxygen side, resulting in the formation of intermediate. In the intermediate and between two reactants, because of the two bonding π orbital in dichloro-germylene carbene and formaldehyde have occurred [2+2] cycloaddition reaction, forming two four-membered ring compounds in which Ge and O are in the opposite orientation and in the syn-position, respectively. Because of the unsaturated property of C atom from carbene in the two four-membered ring compounds, they further reacts with formaldehyde, resulting in the generation of two germanic bis-heterocyclic compounds.