Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

Methyl 2-benzoylamino-3-dimethylamonopropenoate in the synthesis of heterocyclic systems. A simple synthesis of amino derivatives of isomeric naphthopyranones and naphthodipyranones

A simple synthesis of the amino derivatives of 3H-naphtho[2,1-b]pyran-3-one 5b-d, 8,11 , and 20 , 2H-naphtho[1,2-b]pyran-2-one 14 and 19 , 2H,6H-naphtho[1,2-b:3,4-b']dipyran-2,6-dione 9 , 2H,11H-naphtho[2,1-b:3,4-b']dipyran-2,11-dione 12 , and 3H,9H-naphtho[1,2-b:5,6-b']dipyran-3,9-dione 15 from the corresponding monohydroxynaphthalenes 2c,d , dihydroxynaphthalenes 2b, 7, 10 , and 13 , and tetralones 16 and 17 with methyl 2-benzoylamino-3-dimethylaminopropenoate (3) in acetic acid is described.     

基于3,5-二((4'-羧基苄基)氧)苯甲酸和4'-(4-吡啶基)-2,2':6',2"-三联吡啶为混合配体的两个配合物的水热合成与晶体结构

在水热条件下,以3,5-二（（4''-羧基苄基）氧）苯甲酸（H3bcb）和4''-（4-吡啶基）-2,2''：6'',2"-三联吡啶（PYTPY）为混合配体构筑了2个过渡金属配合物[Co（H₂bcb）₂（PYTPY）]_n （1）和[Mn（H₂bcb）₂（PYTPY）]_n （2）,利用元素分析、红外光谱以及单晶X射线衍射表征其结构。分析表明配合物1和2为一维链状结构。此外,2个配合物展示了优良的热稳定性。磁化率的测试结果表明,配合物1和2在2 K和8 K以下时展示了反铁磁相互作用。     

基于3,5-二((4'-羧基苄基)氧)苯甲酸和4'-(4-吡啶基)-2,2':6',2"-三联吡啶为混合配体的两个配合物的水热合成与晶体结构

在水热条件下,以3,5-二((4''-羧基苄基)氧)苯甲酸(H₃bcb)和4''-(4-吡啶基)-2,2'':6'',2"-三联吡啶(PYTPY)为混合配体构筑了2个过渡金属配合物[Co(H₂bcb)₂(PYTPY)]_n(1)和[Mn(H₂bcb)₂(PYTPY)]_n(2),利用元素分析、红外光谱以及单晶X射线衍射表征其结构。分析表明配合物1和2为一维链状结构。此外,2个配合物展示了优良的热稳定性。磁化率的测试结果表明,配合物1和2在2 K和8 K以下时展示了反铁磁相互作用。     

Model Complexes for Ureases: A Dinickel(II) Complex with a Novel Asymmetric Ligand and Comparative Kinetic Studies on Catalytically Active Zinc,Cobalt, and Nickel Complexes

The dinuclear nickel(II) complex of the asymmetric ligand 1‐[N,N‐bis(2‐pyridylmethyl)amino]‐3‐[2‐(3,5dimethyl‐1H‐pyrazol‐1‐yl)ethoxy]‐2‐hydroxypropane (HL1) was prepared as a model for the active site of urease. The novel complex [Ni₂(L1)(MeCOO)(ClO₄)(EtOH)₂](ClO₄) · 0.5 Et₂O ( 1 ) crystallizes in the triclinic space group P 1 with a = 11.639(2) Å, b = 12.571(3) Å, c = 16.341(3) Å, α = 92.29°, β = 106.54°, and γ = 113.73°. The nickel ions (c.n. 6) are bridged by the alkoxy donor substituent of the ligand and an acetate anion. The dinuclear nickel(II), cobalt(II), and zinc(II) complexes of the ligands 1‐[N,N‐bis(2‐benzimidazolylmethyl)amino]‐3‐[2‐(3,5‐dimethyl‐1 H‐pyrazol‐1‐yl)ethoxy]‐2‐hydroxypropane (HL2), N‐methyl‐N,N',N'‐tris(2‐benzimidazolylmethyl)‐2‐hydroxy‐1,3‐diaminopropane (HL3), and N,N,N',N'‐tetrakis(2‐benzimidazolylmethyl)‐2‐hydroxy‐1,3‐diaminopropane (HL4) were investigated for their activity towards the hydrolysis of the test substrate p‐nitrophenyl acetate (npa) in ethanol‐water (1 : 1). The second‐order rate constants for the cleavage of npa were determined for all complexes. The profile of the pH dependence indicates that a hydroxide initially binds to the metal ion. The bound nucleophile subsequently attacks the test substrate. The results are discussed in terms of a refined model for the structure activity relationships of the dinuclear active site of urease.     

Domino reactions in the synthesis of benzothieno[2,3-c]pyridines. New one-pot method of preparing 2-([1]benzothieno-[2,3-c]pyridin-1-yl)benzoic acids and 8,13b-dihydro[1]benzothieno[2',3':3,4]pyrido-[2,1-a]isoindol-5(7?H)-ones

A series of previously unknown 2-([1]benzothieno[2,3-c]pyridin-1-yl)benzoic acids and 8,13b-dihydro-[1]benzothieno[2',3':3,4]pyrido[2,1-a]isoindol-5(7 H)-ones has been synthesized using domino reactions, taking place at the cyclization of 2-[3-oxo-4-(phenylsulfanyl)butyl]-1,3-isoindolinediones in polyphosphoric acid.     

Synthesis of novel 5H‐Pyrimido[5,4‐b]mdole‐(1H,3H)2,4‐diones as potential ligands for the cloned α1‐adrenoceptor subtypes

A new series of 3‐[ω‐[4‐(4‐substituted phenyl)piperazin‐1‐yl]alkyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)‐2,4‐diones ( 3–10 and 12–13 ) were synthesized from the N‐(2‐chloroethyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 1 ) or the N‐(3‐chloropropyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 2 ) and a number of 1‐(4‐substi‐tuted‐phenyl)piperazines. 3‐[2‐[4‐(4‐Aminophenyl)piperazin‐1‐yl]ethyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione ( 14 ) was obtained by reduction of the parent nitro compound 8 . The obtained 5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione derivatives were tested towards cloned α_1A, α_1B and α_1D adrenergic receptors subtypes in binding assays. Some compounds showed good affinity and selectivity for the α_1D‐adrenoceptor subtype.     

Synthesis of Cyclopenta[4',5']pyrido[3',2':4,5]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidine Derivatives. Dimroth Rearrangement of Triazolopyrimidines

Methods of the preparation of 9- (methylsulfanyl)cyclopenta[4',5']pyrido[3',2':4,5]thieno[3,2-d]- pyrimidines and pentacyclic triazolopyrimidines derivatives were developed. The Dimroth rearrangement of these compounds was studied.     

Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones and their sulfinyl and sulfonyl derivatives

A method for the synthesis of previously unknown pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones was suggested, which includes a condensation reaction of substituted 3-cyanopyridine-2(1H)-thiones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation products with potassium tert-butoxide. The oxidation of the condensation products to sulfoxides or sulfones and subsequent treatment of these compounds with potassium tert-butoxide led to substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11-oxides or substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11,11-dioxides.

     

Low-energy fragmentations of five isomeric [H3, C,N, O2] +· ions

The low-energy fragmentation characteristics of the [H₃,C,N,O₂]^+· isomers [H₃CNO₂]^+· (a), [H₂C?N(O)OH]^+· (b), [H₃CONO]^+· (c), [HC(O)NHOH]^+· (d) and [HC(OH)?NOH]^+· (e) were studied in detail by metastable ion mass spectrometry. In agreement with most earlier observations, appearance energy measurements established the potential energy surface of the isomers a, b and c, showing the intricate interrelations between them. It was concluded that a isomerizes into b prior to fragmentation by loss of ^·OH and H₂O and into c before loss of ^·H and H₃CO^· moreover, the reverse reactions do not take place on the metastable time-frame. The dominant metastable process for isomers d and e (obtained via HCN loss from glyoxime) was generation of [H₂NOH]^+·. For isomer e this process was proposed to involved a rate-determining isomerization into d. It was concluded that isomers d and e do not intercommunicate with ions a, b and c prior to fragmentation. Neutralization-reionization mass spectrometry indicated that the enol form of formohydroxamic acid as well as the keto counterpart are stable in the gas phase.     

TiO2 Nanoparticles Immobilized on Carbon Nanotubes: An Efficient Heterogeneous Catalyst in Cyclocondensation Reaction of Isatins with Malononitrile and 4-Hydroxycoumarin or 3,4-Methylenedioxyphenol under Mild Reaction Conditions

TiO₂ nanoparticles supported on carbon nanotubes (TiO₂-CNTs) as an efficient heterogeneous catalyst was used for the synthesis of spiro[3,4′]1,3-dihydro-2H-indol-2-one-2′-amino-5′-oxo-4'H,5'H-pyrano[3′,2′-c]chromen-3′-yl cyanides and spiro[3,8′]1,3-dihydro-2H-indol-2-one-6′-amino-8'H-[1′,3′]dioxolo[4′,5′-g]chromen-7′-yl cyanides via the cyclocondensation reaction of isatins with malononitrile and 4-hydroxycoumarin or 3,4-methylenedioxyphenol in aqueous media at room temperature. This reaction offers several sustainable and economic benefits such as high yields of products, convenient operation, and use of non-toxic catalyst in water media.     

Synthesis,Crystal Structure,and Luminescence of a Three-Dimensional Supramolecular Compound Based on a Dinuclear Tin Cluster

A three-dimensional (3D) supramolecular compound, [(phen)LSnS]₂·(H₂O)₂ (phen = 1,10-phenanthroline, L = mercaptoacetic acid), has been synthesized and the crystal structure was determined by a single crystal X-ray diffraction study. 1 is triclinic, space group P-1 with a = 6.695(1) Å, b = 10.929(2) Å, c = 12.117(2) Å, α = 114.55(3)°, β = 93.53(2)°, γ = 104.06(3)°, and Z = 1. The dinuclear cluster of [(phen)LSnS]₂ and H₂O are linked into a 3D supramolecular framework by a combination of O[sbnd]H…O, C[sbnd]H…O hydrogen bonds and π–π stacking interactions. Its luminescence property is discussed.     

Synthesis,spectral, DFT calculations and antibacterial studies of Fe(III) complexes of new fluorescent Schiff bases derived from imidazo[4',5':3,4]benzo[1,2‐c]isoxazole

New fluorescent heterocyclic ligands were synthesized by the reaction of 8‐(4‐chlorophenyl)‐3‐alkyl‐3H‐imidazo[4',5':3,4]benzo [1,2‐c]isoxazol‐5‐amine with p‐hydroxybenzaldehyde and p‐chlorobenzaldehyde in good yields. The coordination ability of the ligands with Fe³⁺ ion was examined in an aqueous metanolic solution. Schiff base ligands and their metal complexes were characterized by elemental analyses, IR, UV–vis, mass, and NMR spectra. The optical properties of the compounds were investigated and the results showed that the fluorescence of all compounds is intense and their obtained emission quantum yields are around 0.15 – 0.53. Optimized geometries and assignment of the IR bands and NMR chemical shifts of the new complexes were also computed by using density functional theory (DFT) methods. The DFT‐calculated vibrational wavenumbers and NMR chemical shifts are in good agreement with the experimental values, confirming suitability of the optimized geometries for Fe(III) complexes. Also, the 3D‐distribution map for HOMO and LUMO of the compounds were obtained. The new compounds showed potent antibacterial activity and their antibacterial activity (MIC) against Gram‐positive and Gram‐negative bacterial species were also determined. Results of antibacterial test revealed that coordination of ligands to Fe(III) leads to improvement in the antibacterial activity.     

Two New Tetranuclear Cluster-based Coordination Polymers based on Isomorphic Semi-rigid Tetracarboxylate Ligands: Syntheses,Structures, and Luminescent Properties

Two new tetranuclear cluster-based compounds, namely [Cd₂(L1)(H₂O)(DMA)]_n ( 1 ) and [Cd₂Ba₂(L2)(H₂O)₆(DMA)]_n ( 2 ) [H₄L1 = 3-(3',5'-dicarboxylphenoxy) phthalic acid, H₄L2 = 6-(3',4'-dicarboxyl-phenoxy) isophthalic acid, DMA = N,N'-dimethylacetamide], were successfully synthesized under solvothermal conditions and structurally characterized by single-crystal X-ray diffraction analyses. Compound 1 features a two-dimensional (2D) layered framework with tetranuclear [Cd₄(COO)₆] clusters as building subunits, and can be simplified into a binodal (3, 6)-connected kgd topological network with the schläfli symbol of {4³}₂{4⁶;6⁶;8³}, and compound 2 features a three-dimensional (3D) complicated framework based on heterometallic tetranulear [Cd₂Ba₂(COO)₈] cluster subunits, and can be simplified into a binodal (3, 6)-connected topological network. In addition, compounds 1 and 2 not only have high thermal stabilities but also show strong luminescent emissions at room temperature.     

Syntheses and properties of 4,6-dimelhyl[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7(4H,6H)dione 1-oxide

New convenient syntheses of 4,6-dimethyl[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7(4H,6H)-dione 1-oxide (I) from 1,3-dimethyl-6-hydroxylaminouracil by means of nitrosative and nitrative cyclizations are described. Compound I was converted into 4,6-dimethyl[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7(4H,6H)dione [4,6-dimethyl-5,7(4H,6H)furazano[3,4-d]pyrimidinedione] by refluxing in dimethylformamide. Transformation of I to 1,3,7,9-tetramethyl-2,4,6,8(1H,3H,7H,9H)pyrimido[5,4-g]pteridinetetrone and/or 1,3,6,8-tetramethyl-2,4,7,9(1H,3H,6H,8H)pyrimido[4,5-g]pteridinetetrone is described.     

Thermal,acid-catalyzed,and photolytic transformations of spirocyclic 3H-pyrazoles formed by reactions of methyl,phenyl, and p-tolyl phenylethynyl sulfones with 9-diazofluorene

Methyl, phenyl, and p-tolyl phenylethynyl sulfones react with 9-diazofluorene in diethyl ether at 20°C to give 1,3-dipolar cycloaddition products according to von Auwers’ rule, the corresponding spirocyclic 3H-pyrazoles. The spiro adducts undergo isomerization into 5-R-sulfonyl-3-phenylpyrazolo[1,5-f]phenanthridines on heating in boiling toluene for 2 h; heating of the same pyrazoles in boiling benzene, acetonitrile, or ethanol leads to mixtures of 5-R-sulfonyl-3-phenylpyrazolo[1,5-f]phenanthridines and 3-R-sulfonyl-3a-phenyl-3aH-dibenzo[e,g]indazoles, the latter prevailing. The indazoles are kinetically controlled thermolysis products which are quantitatively converted into phenanthridines on heating in toluene. Sulfonyl-substituted spirocyclic 3H-pyrazoles and indazoles in glacial acetic acid at 20°C in the presence of a catalytic amount of sulfuric acid are transformed into 3a-phenyl-2H-dibenzo[e,g]indazol-3(3aH)-one. Under analogous conditions, sulfonyl-substituted phenanhtridines give rise to 3-phenyl-1H-dibenzo[e,g]indazole. Photolysis of spirocyclic 3H-pyrazoles yields mixtures of sulfonylcyclopropenes and 2H-cyclopenta[j,k]fluorenes.     

A Novel 3D Framework Coordination Polymer based on Succinato bridged Helical Chains Connected by 4, 4' ‐ Bipyridine: [Cu(bpy)(H2O)2(C4H4O4)]?2H2O

Blue needle—shaped crystals of [Cu(bpy)(H₂O)₂(C₄H₄O₄)]· 2H₂O were obtained by slow evaporation of a methanolic aqueous solution containing a fresh Cu(C₄H₄O₄)· 2H₂O precipitate, 4, 4′—bipyridine, and ammonia. Within the complex, the six—coordinated Cu atoms are linked by bis—monodentate gauche succinate anions into chains propagating helically around the [001] axis. The chains are interconnected by 4, 4′—bipyridine ligands into a 3D framework with the crystal H₂O molecules located in the channels along the [100], [010] and [110] directions. The Cu²⁺ ions are in distorted octahedral coordination of two nitrogen and four oxygen atoms (equatorial bonds: Cu—N 1.986(5), 2.015(5)Å; Cu—O 1.950(6), 1.954(6)Å; axial bonds Cu—O: 2.524(9), 2.539(8)Å). Furthermore, the thermal and magnetic behavior of the compound will be discussed. Crystal data: hexagonal, P6₁ (no. 169), a = 11.066(2)Å, c = 24.965(5)Å, V = 2647.5(8)ų, Z = 6, R = 0.0528 and wR₂ = 0.1103 for 1426 observed reflections (F_o² > 2σ(F_o²)) out of 2170 unique reflections.     

Condensed benzopyrans III. 3H,4H[1] benzopyrano [3,4-b] pyrrol-4-ones

The diazotization of 3-aminocoumarin followed by its reduction gave the cournarin-3-yl-hydrazine which, without isolation, reacted with various carbonyl compounds in a Fisher's indohzation reaction to give derivatives (Ib-Ih) of the yet unreported system 3H,4H[1]benzopyrano[3,4-b]pyrrol-4-one.     

A photo-ionization study of organosulfur ring compounds: Thiirane,thietane and tetrahydrothiophene

The gas phase heats of formation of several organosulfur cations were determined from thiirane, thietane and tetrahydrothiophene precursor molecules by photoionization mass spectrometry. Heats of formation at 0 K and 298 K are reported for the following ions: [H₂CS]^+˙, [H₃CS]⁺, [C₂H₃S]⁺, [C₂H₄S]^+˙, [C₃H₅S]⁺, [C₃H₆S]^+˙, [C₄H₇S]⁺ and [C₄H₈S]^+˙. The [C₄H₇S]⁺ (m/z 87), [C₂H₄S]^+˙ (m/z 60), [C₂H₃S]⁺ (m/z 59), [C₄H₇]⁺ (m/z 55), [C₄H₆]^+˙ (m/z 54) and [CH₂S]^+˙ (m/z 46) ions are produced from metastable tetrahydrothiophene ions at photon energies between 10.2 and 10.7 eV. Decay rates of internal energy selected parent ions to the m/z 60, 59, 55 and 54 fragments were measured by threshold photoelectron-photoion coincidence, the results of which are compared to statistical theory (RRKM/QET) calculations. The [C₂H₄S]^+˙ ion from tetrahydrothiophene is found to have the thioacetaldehyde structure. From the measured [C₂H₄S]^+˙ onset a ΔH = 50±8 kJ mol^?1 was calculated for the thioacetaldehyde molecule.