Effects of Electron-Withdrawing Strengths of the Substituents on the Properties of 4-(Carbazolyl-R-benzoyl)-5-CF3-1H-1,2,3-triazole Derivatives as Blue Emitters for Doping-Free Electroluminescence Devices.

The synthesis of four 4-(carbazolyl-R-benzoyl)-5-CF3-1H-1,2,3-triazoles with extra groups ((3-methyl)-phenyl-, 4-fluorophenyl-, quinolinyl-, or (3-trifluoromethyl)-phenyl-) in the acceptor fragment has been reported. The effects of substituents with different electron-withdrawing strengths on the thermal, electrochemical, photophysical, and electroluminescence properties of the synthesized compounds are discussed. The results of X-ray analyses and density functional theory (DFT) calculations support unusual molecular packing and electronic properties. The compounds are capable of glass formation with glass transition temperatures ranging from 54-84 °C. Ionization potentials of the compounds are in the range of 5.98-6.22 eV and electron affinities range from 3.09 to 3.35 eV. Under ultraviolet excitation, the neat films of the compounds exhibit blue emission with photoluminescence quantum yields ranging from 18 to 27%. The films of selected compounds are used for the preparation of host-free light-emitting layers of organic light-emitting diodes with very simple device structures and an external quantum efficiency of 4.6%.

Bioisosteric replacement of 1H-1,2,3-triazole with 1H-tetrazole ring enhances anti-leukemic activity of (5-benzylthiazol-2-yl)benzamides.

Previously, we discovered that N-(5-benzyl-1,3-thiazol-2-yl)-4-(5-methyl-1H-1,2,3-triazol-1-yl)benzamide possessed a remarkable cytotoxic effect on 28 cancer cell lines with IC50 < 50 µM, including 9 cancer cell lines, where IC50 was in the range of 2.02-4.70 µM. In the present study, we designed a novel N-(5-benzylthiazol-2-yl)amide compound 3d that was synthesized using the original bioisosteric replacement of 1H-1,2,3-triazole ring by the 1H-tetrazole ring. A significantly enhanced anticancer activity in vitro with an excellent anti-leukemic potency towards chronic myeloid leukemia cells of the K-562 line was demonstrated. Two compounds - 3d and 3l - were highly cytotoxic at nanomolar concentrations towards various tumor cells of the following lines: K-562, NCI-H460, HCT-15, KM12, SW-620, LOX IMVI, M14, UACC-62, CAKI-1, and T47D. As a highlight, the compound N-(5-(4-fluorobenzyl)thiazol-2-yl)-4-(1H-tetrazol-1-yl)benzamide 3d inhibited the growth of leukemia K-562 cells and melanoma UACC-62 cells with IС50 of 56.4 and 56.9 nM (SRB test), respectively. The viability of leukemia K-562 and pseudo-normal HaCaT, NIH-3T3, and J774.2 cells was measured by the MTT assay. Together with SAR analysis, it allowed the selection of a lead compound 3d, which demonstrated the highest selectivity (SI = 101.0) towards treated leukemic cells. The compound 3d caused DNA damage (single-strand breaks detected by the alkaline comet assay) in the leukemic K-562 cells. The morphological study of the K-562 cells treated with compound 3d revealed changes consistent with apoptosis. Thus, the bioisosteric replacement in (5-benzylthiazol-2-yl)amide scaffold proved to be a perspective approach in the design of novel heterocyclic compounds with enhanced anticancer potential.

Thiocyanatoarylation of Methyl Vinyl Ketone under Meerwein Conditions for the Synthesis of 2-Aminothiazole-Based Heterocyclic Systems.

4-Aryl-3-thiocyanatobutan-2-ones were prepared by Meerwein reactions from methyl vinyl ketone and aryldiazonium salts under copper(II) catalysis in 35-75% yields. α-Thiocyanato ketones regioselectively react with 1-methyl-3-aminopyrazole forming N-(3-pyrazolyl)-substituted 2-aminothiazoles in 80-91% yields. An ester group in position 3 of the pyrazole induced a regioselective ring-closure reaction followed by an intramolecular cyclization, which gave first representatives of a new heterocyclic system, pyrazolo[4,3-e]thiazolo[3,2-a]pyrimidine, in 74-93% yields. In addition, the preparations of 5-benzyl-4-methylthiazol-2-ones in 84-93% yields are described.

Exciplex-Forming Systems of Physically Mixed and Covalently Bonded Benzoyl-1H-1,2,3-Triazole and Carbazole Moieties for Solution-Processed White OLEDs.

Using the newly designed exciplex-forming 1,2,3-triazole-based acceptors with fast and efficient singlet → triplet intersystem crossing (ISC) processes, carbazole and benzoyl-1H-1,2,3-triazole derivatives were synthesized by Dimroth-type 1,2,3-triazole ring formation and Ullmann-Goldberg C-N coupling reactions. Due to the exciplex formation between covalently bonded electron-donating (carbazole) and 1,2,3-triazole-based electron-accepting moieties with small singlet-triplet splitting (0.07-0.13 eV), the compounds exhibited ISC-assisted bluish-green thermally activated delayed fluorescence. The compounds were characterized by high triplet energy levels ranging from 2.93 to 2.98 eV. The most efficient exciplex-type thermally activated delayed fluorescence was observed for ortho-substituted carbazole-benzoyl-1H-1,2,3-triazole which was selected as a host in the structure of efficient solution-processed white light-emitting diodes. The best device exhibited a maximum power efficiency of 10.7 lm/W, current efficiency of 18.4 cd/A, and quantum efficiency of 7.1%. This device also showed the highest brightness exceeding 10 thousand cd/m2. Usage of the exciplex-forming host allowed us to achieve a low turn-on voltage of 3.6 V. High-quality white electroluminescence was obtained with the close to nature white color coordinates (0.31, 0.34) and a color rendering index of 92.

Nitrileimines as an alternative to azides in base-mediated click [3 + 2] cycloaddition with methylene active nitriles.

Nitrileimines were implemented in practical click protocols with oxopropanenitriles for the straightforward 5-amino-1H-pyrazole synthesis via 1,3-dipolar cycloaddition. The reaction proceeds at room temperature in a short time with base catalysis and no chromatographic purification. High purity products were isolated by simple filtration. The selectivity of the reaction was observed.

Thermodynamic properties of some isomeric 5-(nitrophenyl)-furyl-2 derivatives.

BACKGROUND: The aim of the current work was to determine thermodynamical properties of 5-(nitrophenyl)-2-furaldehyde oximes and 3-[5-(nitrolphenyl)-2-furyl]acrylic acids. RESULTS: The temperature dependences of saturated vapor pressures of 5-(nitrophenyl)-2-furaldehyde oximes and 3-[5-(nitrolphenyl)-2-furyl]acrylic acids were determined by the Knudsen effusion method. The results are presented by the Clapeyron-Clausius equation in linear form, and via this form, the standard enthalpies of sublimation of compounds were calculated at 298.15 K. The standard molar formation enthalpies of compounds in crystalline state at 298.15 K were determined indirectly from the corresponding standard molar combustion enthalpy, obtained using combustion bomb calorimetry. The non-nearest neighbour interactions (strain) in molecule were defined. The ideal-gas enthalpies of investigated compounds formation and the data available from the literature were used for calculation of group-additivity parameters and the correction terms useful in the application of the Benson correlation. CONCLUSION: Determining the thermodynamic properties for these compounds will contribute to solving practical problems pertaining to optimization processes of their synthesis, purification and application. It will also provide a more thorough insight regarding the theoretical knowledge of their nature and are necessary for the application of the Benson group-contribution correlation for calculation of Δ f H m ( 298.15 K ) o (g)calc.

Proapoptotic effects of novel thiazole derivative on human glioma cells.

The aim of the present study was to investigate the antiproliferative and proapoptotic actions of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide derivative (compound 5) in glioma cells in comparison with the actions of temozolomide (TMZ) and doxorubicin (Dox), used as positive controls. The antiproliferative activity of the compound 5, TMZ, and Dox on human glioblastoma U251 and human glioblastoma multiform T98G cells was measured using the MTT test. Western blot analysis, fluorescent microscopy, agarose gel retardation assay, flow cytometric analysis, and the DNA comet assay under alkaline conditions were carried out to study the effect of compound 5 on U251 cells. This compound showed ~20 times higher cytotoxicity toward U251 and T98G cells compared with the effects of TMZ and approximately two times higher activity than that of the Dox. Compound 5 induced apoptosis in U251 cells by PARP1 and caspase 3 cleavage mechanisms, also inducing an increase in the level of Bax and Bim proapoptotic proteins and a decrease in the level of phosho-ERK1/2 kinase. The cytotoxicity of compound 5 was associated with an increase in the production of the hydrogen peroxide and the formation of DNA single-strand breaks. This compound 5 did not intercalate into a DNA molecule. Thus, the novel thiazole derivative (compound 5) proved to be a potential antiglioma drug that showed much higher cytotoxic action on human glioma cells compared with the effects of TMZ and Dox. Its cytotoxicity is associated with apoptosis induction, production of the reactive oxygen species, and formation of DNA single-strand breaks without significant DNA intercalation.

Anticancer Activity Evaluation of New Thieno[2,3-d]pyrimidin-4(3H)-ones and Thieno[3,2-d]pyrimidin-4(3H)-one Derivatives.

Anticancer screening of several novel thienopyrimidines has been performed. The thienopyrimidine derivatives were synthesized from available starting materials according to the convenient synthetic procedures using a one-pot solvent-free reaction which gave a wide access to thienopyrimidine-derivative production. The synthesized compounds were preselected via molecular docking to be tested for their anticancer activity in NCI 60 cell lines. It was observed that some compounds showed remarkable anticancer activity. It was found that the most active compound among thieno[2,3-d]pyrimidine-4(3H)-ones is 2-(benzylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one, which possesses cytotoxic activity on almost all cancer cell lines with mean growth 51.01%, where the most sensitive was the melanoma cell line MDA-MB-435 with GP (Growth Percent) = -31.02%. The patterns of structure⁻activity that are important for further optimization of the structure and the creation of more selective and active anticancer agents were proposed.

Thermodynamic properties of 5(nitrophenyl) furan-2-carbaldehyde isomers.

BACKGROUND: The aim of the current work was to determine thermo dynamical properties of 5(2-nitro phenyl)-furan-2-carbaldehyde, 5(3-nitro phenyl)-furan-2-carbaldehyde and 5(4-nitro phenyl)-furan-2-carbaldehyde. RESULTS: The temperature dependence of saturated vapor pressure of 5(2-nitro phenyl)-furan-2-carbaldehyde, 5(3-nitro phenyl)-furan-2-carbaldehyde and 5(4-nitro phenyl)-furan-2-carbaldehyde was determined by Knudsen's effusion method. The results are presented by the Clapeyron-Clausius equation in linear form, and via this form, the standard enthalpies, entropies and Gibbs energies of sublimation and evaporation of compounds were calculated at 298.15 K. The standard molar formation enthalpies of compounds in crystalline state at 298.15 K were determined indirectly by the corresponding standard molar combustion enthalpy, obtained using bomb calorimetry combustion. CONCLUSIONS: Determination of the thermodynamic properties for these compounds may contribute to solving practical problems pertaining optimization processes of their synthesis, purification and application and it will also provide a more thorough insight regarding the theoretical knowledge of their nature.Graphical abstract:Generalized structural formula of investigated compounds and their formation enthalpy determination scheme in the gaseous state.

New Convenient Strategy for Annulation of Pyrimidines to Thiophenes or Furans via the One-pot Multistep Cascade Reaction of 1H-Tetrazoles with Aliphatic Amines.

A versatile, convenient, efficient and high-yield synthetic method for 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[2,3-d]pyrimidin-4(3H)-ones, 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[3,2-d]pyrimidin-4(3H)-ones, and benzofuro[3,2-d]pyrimidin-4(3H)-ones preparation has been developed. The reaction proceeded without using solvents and included several steps. A variety of thieno[2,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives with substituents of different nature were obtained in high yields from substituted alkyl 2-(1H-tetrazol-1-yl)thiophene-3-carboxylates, 3-(1H-tetrazol-1-yl)thiophene-2-carboxylates, and 3-(1H-tetrazol-1-yl)benzofuran-2-carboxylate after their treatment with aliphatic amines.

5-Iodo-3-phenyl-2,1-benzoxazole.

The title compound, C13H8INO, was prepared by a condensation reaction of 4-nitro-benzene with phenyl-acetonitrile in NaOH-ethanol solution. There are two independent mol-ecules in the asymmetric unit, in which the dihedral angles between the benzene ring and the benzoisoxazole unit are 4.2 (3) and 4.1 (3)°. The crystal packing is governed by C-H⋯N, C-I⋯π and C-I⋯O inter-actions.

(4R*,4aR*,7aS*)-5-Oxo-6-phenyl-4a,5,6,7,7a,8-hexa-hydro-4H-furo[2,3-f]isoindole-4-carb-oxy-lic acid.

The asymmetric unit of the title compound, C(17)H(15)NO(4), contains two independent mol-ecules with similar geometric parameters. In both mol-ecules, the conformation of the cyclo-hexene ring is half-chair, while the pyrrolidinone ring adopts an envelope conformation with the γ-carbon atom of the α-pyrrolidinone ring as the flap. In the crystal, O-H⋯O hydrogen bonds between the carb-oxylic and carbonyl groups link alternate independent mol-ecules into chains propagating in the b-axis direction. The crystal packing also features weak C-H⋯π inter-actions.

1-{5-[2-Chloro-5-(trifluoro-meth-yl)phen-yl]thio-phen-2-yl}ethanone.

In the title molecule, C(13)H(8)ClF(3)OS, the dihedral angle between the mean planes of 2-chloro-5-(trifluoro-meth-yl)phenyl and tiophene rings is 54.37 (5)°. The acethyl group is twisted by 8.1 (2)° with respect to the thio-phene ring. The CF(3) group is disordered over two sets of sites with occupations of 0.49 (3) and 0.51 (3). The crystal packing features C-H⋯F and C-H⋯O hydrogen bonds, forming dimers which are connected into chains along the c axis by C-H⋯O hydrogen bonds and C-Cl⋯π [Cl⋯π = 3.415 (1) Šand C-Cl⋯π = 151.56 (5)°] inter-actions. The chains are further connected into layers perpendicular to the a axis by C-H⋯O inter-actions.

(6aS*,6bS*,11R*,11aR*)-6-(2-Furyl-methyl)-5,12-dioxo-5,6,6a,6b,7,11,11a,12-octa-hydro-furo[3',2':5,6]isoindolo[2,1-a]quinazoline-11-carb-oxy-lic acid.

The title compound, C(23)H(18)N(2)O(6), is the product of an intra-molecular thermal cyclo-addition within 1-malein-2-[(E)-2-(2-fur-yl)vin-yl]-4-oxo-3,4-dihydro-quinazoline. The mol-ecule comprises a previously unknown fused penta-cyclic system containing two five-membered rings (2-pyrrolidinone and furan) and three six-membered rings (benzene, 2,3-dihydro-4-pyrimidinone and dihydro-cyclo-hexa-ne). The central five-membered pyrrolidinone ring has the usual envelope conformation. The six-membered dihydro-pyrimidinone and dihydro-cyclo-hexane rings adopt a half-boat and a half-chair conformation, respectively. The dihedral angle between the planes of the terminal benzene and furan rings is 45.99 (7)°. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. Weak C-H⋯O hydrogen bonds consolidate further the crystal packing, which exhibits π-π inter-actions, with a short distance of 3.556 (3) Šbetween the centroids of benzene rings of neighbouring mol-ecules.

8a-Methyl-5,6,8,8a,9,10-hexa-hydro-10,12a-epoxy-isoindolo[1,2-a]isoquinolinium iodide.

The title compound, C(17)H(18)NO(+)·I(-), is an adduct resulting from an intra-molecular Diels-Alder reaction of methallyl chloride with 3,4-dihydro-1-furylisoquinoline. The cation comprises a fused penta-cyclic system containing three five-membered rings (dihydro-pyrrole, dihydro-furan and tetra-hydro-furan) and two six-membered rings (tetra-hydro-pyridine and benzene). The five-membered rings have the usual envelope conformations, and the central six-membered tetra-hydro-pyridine ring adopts the unsymmetrical half-boat conformation. In the crystal, cations and iodide anions are bound by weak inter-molecular hydrogen-bonding inter-actions into a three-dimensional framework.

2-[(2Z,3E)-2-Hy-droxy-imino-5-phenyl-2,3-dihydro-3-thienyl-idene]-2-phenyl-acetonitrile.

In the crystal structure of the title compound, C(18)H(12)N(2)OS, centrosymmetric dimers are stabilized both by van der Waals inter-actions and by two types of inter-molecular O-H⋯N hydrogen bonds. In addition, an intra-molecular C-H⋯S hydrogen bond is observed. The dihedral angles between the central ring and the two pendant phenyl rings are 7.4 (1) and 45.06 (9)°.

One-pot multicomponent synthesis of 1-aryl-5-methyl-N-R2-1H-1,2,3-triazole-4-carboxamides: an easy procedure for combinatorial chemistry.

A convenient synthetic protocol was elaborated for creation of combinatorial libraries of 1-(R(1)-phenyl)-5-methyl-N-R(2)-1H-1,2,3-triazole-4-carboxamides. As starting materials, commercially available or readily prepared azides, amines, and diketene were selected for the reaction which has proceeded in a one-pot system with high yields and in short time.

3-(4-Chloro-phen-yl)-2,1-benzisoxazole-5-carbonyl chloride.

The molecule of the title compound, C(14)H(7)Cl(2)NO(2), is not planar; the dihedral angle between the mean planes of the chloro-phenyl and benzisoxazole rings is 20.32 (7)°. The carbonyl chloride group is twisted with respect to the benzisoxazole ring by 2.5 (1)°. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯Cl hydrogen bond. In the crystal packing, adjacent mol-ecules are linked into dimers by inter-molecular C-H⋯O hydrogen bonds. The dimers are further stacked into columns along the unique axis direction by π-π stacking inter-actions, with a centroid⋯centroid distance of 3.828 (5) Å. Other weak inter-molecular C-H⋯O and C-H⋯Cl inter-actions are also present.