Green synthesis approach for Fe (III), Cu (II), Zn (II) and Ni (II)-Schiff base complexes,spectral, conformational,MOE-docking and biological studies

Green synthesis of Fe (III), Cu (II), Zn (II) and Ni (II)-Schiff's-base complexes from 2-oxo-N-(pyridine-2-yl)-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)acetamide(H₂L)ligand. All new complexes were characterized via several spectroscopic and analytical techniques, to establish their molecular and structural formulae. All complexes appeared have 1:1 molar ratio (M:L). The ligand contributed as a neutral poly-dentate towards the metal ions. Moreover, material-studio program was used to predict the most fitted atomic-skeletons for investigated compounds by applying DFT method. MOE docking module (vs. 2015) was used to examine the degree of inhibition for new compounds versus three infected-cell proteins (1bqb, 2gt1 and 4esw). Also, antimicrobial and colorimetric assess for compounds that bind DNA were performed     

Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-one Derivatives

Treatment of 2-aminopyridine ( 1 ) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide ( 3 ), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one ( 4 ) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of ( 4 ) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a–j . ¹ H and ¹³C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.     

Spectroscopic characterization of halogen- and cyano-substituted pyridinevinylenes synthesized without catalyst or solvent

An efficient Knoevenagel route using green chemistry conditions was applied for the synthesis of halogen- and cyano- substituted pyridinevinylene compounds. Absorption and fluorescence emission spectra of these conjugated compounds were recorded and compared in order to evaluate the effect of substituents on the electronic properties of pyridinevinylene compounds. The substituents studied were terminal Cl and F, two or three aromatic rings, as well as a cyano group attached to a C=C double bond. The compounds synthesized are: (E)-2-(4-fluorostyryl)pyridine, (E)-2-(4-chlorostyryl)pyridine, (E)-4-(4-chlorostyryl)pyridine, 2,3-diphenylacrylonitrile, 3-phenyl-2-(pyridin-2-yl)acrylonitrile, 3-phenyl-2-(pyridin-3-yl)acrylonitrile, 2-phenyl-3-(pyridin-2-yl)acrylonitrile, 3,3′-(1,4-phenylene)bis(2-phenylacrylonitrile), 3,3′-(1,4-phenylene)bis(2-(pyridin-2-yl)acrylonitrile), and 3,3′-(1,4-phenylene)bis(2-(pyridin-3-yl)acrylonitrile). The solvent-free method used in this work allows obtaining each compound by controlling the reaction temperature. The compounds were characterized by infrared spectroscopy and 1H-NMR spectroscopy.     

Synthesis and characterization of new thiazolidinones containing coumarin moieties and their antibacterial and antioxidant activities

New coumarin derivatives, namely (2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, N-(2-(3-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide, 2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo-2-(2,3,4trimethoxyphenyl)thiazolidin-3-yl)acetamide and N-(2-(4-bromophenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide) were synthesized starting from 4-methyl-7-hydroxycoumarin. The structures of the obtained compounds were confirmed by analytical IR and NMR spectra to elucidate the different positions of protons and carbons and as well as theoretical studies (DFT/B3LYP). The new compounds were screened for antibacterial activity. Most of them are more active against E. coli S. aureus and B. subtilis than standard references.     

Unique CuI-pyridine based ligands catalytic systems for N-arylation of indoles and other heterocycles

Two pyridine-based ligands (N-((pyridin-2-yl) methyl) pyridin-2-amine) L1 and (N-((pyridin-2-yl) methylene) pyridin-2-amine) L2 are explored in present work which are inexpensive, effective and environmentally benign in their properties. These have been utilized for C-N cross coupling reaction resulting in N-arylation. The N-arylation of indole, imidazole and triazole have been successfully carried out with different aryl and heteroaryl halides using these ligands.     

Palladium complex of 6-(2-hydroxy-5-methylphenyl)-3-(pyridin-2-yl)-1,2,4-triazin-5(2<Emphasis Type="Italic">H</Emphasis>)-one: Synthesis,structure, and catalytic activity

Palladium(II) complex with 6-(2-hydroxy-5-methylphenyl)-3-(pyridin-2-yl)-1,2,4-triazin-5(2H)-one was synthesized for the first time. The ligand was prepared from 3-(pyridin-2-yl)-1,2,4-triazin-5(2H)-one and 4-methylphenol via nucleophilic substitution of hydrogen (S_N^H reaction). The complex was readily soluble in basic medium, and it effectively catalyzed Mizoroki-Heck reaction.     

Synthesis of maleopimaric and citraconopimaric acids N-[3-(pyrimidin-2-yl)aryl]amides

Acylation of 6-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine, 4-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine, and N-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine with maleopimaric and citraconopimaric acid chlorides, with benzotriazolyl maleopimarate afforded N-[3-(pyrimidin-2-yl)aryl]amides of maleopimaric and citraconopimaric acids. By the reaction of substituted N-arylamides of maleopimaric acid with methanesulfonic acid biologically active methanesulfonates were obtained.     

Synthesis of Derivatives of (1R*,10aR*)-1-Azido-10-benzylidene-4-(diethylphosphono)-1,2,10,10a-tetrahydro-2-oxo-4H-azeto[1,2-a]pyrido[1,2-d]pyrazin-9-ylium Bromide

The synthesis of some derivatives of the title compound VI is described. Bromination of diethyl (cis-3-azido-2-oxo-4-styrylazetidin-1-yl)(pyridin-2-yl)methylphosphonate ( 6 ) in MeOH gave tricyclic β-lactam 7 , while similar bromination of diethyl (cis-3-azido-2-oxo-4-vinylazetidin-1-yl)(pyridin-2-yl)methylphosphonate ( 9 ) afforded tri-cyclic β-lactam 10 . Mechanisms for these transformations are proposed (Schemes 1 and 2).     

Reduction of Aldehydes and Ketones by Transition Metal Hydrides. Part 2. Reaction of trans,trans-[WH(CO)2(NO)(PMe3)2] with pyridine,functionalized aldehydes,and ketones

The reaction of trans,trans-[WH(CO)₂(NO)(PMe₃)₂] ( 1 ) with (pyridin-2-yl)-substituted aldehydes and ketones, (pyridin-2-yl)C(O)R where R = H, Me, Ph, pyridin-2-yl, and with 6-methylpyridine-2-carbaldehyde was studied. In all cases, facile insertion of the C?O bond into the W? H bond was observed, with rapid subsequent extrusionof a coordinated CO ligand affording O,N-bidentate coordinated tungsten alkoxides. Only in case of pyridine-2-carbaldehyde and di(pyridin-2-yl) ketone, the initial n¹ O-bonded insertion product could be observed as unstable intemediates by low-temperature NMR.     

Synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a class of potent nicotinic acetylcholine receptor-ligands

In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series.     

Synthesis,structure, ADME and biological activity of three 2,6-disubstituted thiosemicarbazone derivatives

Three new 2,6-disubstituted thiosemicarbazone derivatives of pyridine, namely, 2-{amino[6-(pyrrolidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C₁₃H₂₀N₆S, 2-{amino[6-(piperidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C₁₄H₂₂N₆S, and 2-[amino(6-phenoxypyridin-2-yl)methylidene]-N,N-dimethylhydrazine-1-carbothioamide monohydrate, C₁₅H₁₇N₅OS·H₂O, have been synthesized and characterized by NMR spectroscopy and low-temperature single-crystal X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The ability of the tested compounds to inhibit bacterial growth was comparable to vancomycin as a reference drug. Compared to isoniazid (MIC 0.125 and 8 µg ml⁻¹), the compounds showed the ability to inhibit the growth of Mycobacterium tuberculosis to a moderate degree for the standard strain and at the same level or higher (MIC 4–8 µg ml⁻¹) for the resistant strain. All three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules.     

Facile microwave-assisted synthesis of bis-pyrazol pyrimidine derivatives via an <Emphasis Type="Italic">N</Emphasis>-alkylation reaction

Abstract  

We present herein a new and efficient method for synthesis of bis-pyrazol pyrimidine derivatives by N-alkylation using a microwave-assisted synthetic process. Two new compounds, N-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl nicotinonitrile and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-4-methyl nicotinonitrile, were synthesized by the N-alkylation reaction. The novel compounds were characterized by Fourier transform infrared spectrometry, ultraviolet spectroscopy, elemental analysis, and nuclear magnetic resonance spectroscopy, etc. The microwave-assisted procedures have noteworthy advantages in terms of thermal efficiency over those carried out by conventional heating methods.     

Effective asymmetric synthesis of the key chiral building blocks of 20(S)- and 20(R)-camptothecins

Abstract  

An effective diastereoselective synthesis of (S)-N,N-diethyl-2-formyl-2-(methoxymethoxy)butanamide and (S)-2-formyl-2-(methoxymethoxy)butanoic acid ethyl ester, which are two key chiral building blocks for the synthesis of 20(S)-camptothecins, has been developed by employing an asymmetric bromolactonization using (R)-proline. The (R) compounds were also synthesized to obtain 20(R)-camptothecin.     

Syntheses, characterization, X-ray crystal structures and emission properties of five oxovanadium(V) complexes with pyridyl/pyrimidyl-pyrazole derived ditopic ligands

Four oxovanadium(V) complexes of heterocycle based ditopic ligands PyPzOAP (N-[amino(pyridin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PyPzOAPz (N-[amino(pyrazin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PymPzOAP (N-[amino(pyridin-2-yl)methylidene]-1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-1H-pyrazole-3-carbohydrazonic acid) and PyPzCAP (5-methyl-1-(pyridin-2-yl)-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) and a binuclear (di-μ-oxo) oxovanadium(V) complex of the ligand PymPzCAP (1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) have been investigated. The ligands act as uninegative NNO tridentates donors for the VO₂⁺ ion exhibiting their monotopicity. The ligands show varying emission properties due to the presence of fluophoric groups like 1-(2-pyridyl)pyrazole or 1-(2-pyrimidyl)pyrazole. The vanadium(V) complexes show fluorescence quenching with respect to the used ligands to a varying extent. The complexes were characterized by UV-Vis, IR, cyclic voltammetry and X-ray crystallography.     

The formation of 'classical' and 'half unit' Schiff-base ligands from their components on a molybdenum(IV) centre

The in situ synthesis of the complex, (PPh₄)[Mo(CN)₃O(aceen)] (aceen = N-[1-(pyridin-2-yl)ethylidene]ethane-1,2-diamine), with a 'half unit' Schiff base ligand (with a free amino group) is described and compared with that of [Mo(CN)₂O(diaceen)]·H₂O (diaceen = N,N-bis[1-(pyridin-2-yl)ethylidene]ethane-1,2-diamine) in which a 'classical', tetradentate Schiff base ligand is formed. The mechanism of the 'half unit' and 'classical' template Schiff bases ligand formation is discussed.     

Zeolite-catalyzed synthesis of nicotinyl-fused indolo-pyrazoles and evaluation of their activities against Anopheles arabiensis and Lipoxygenase

A series of nicotyl-fused indolo-pyrazoles (NFIPs) were synthesized by a one-pot multicomponent reaction of aryl aldehydes, isoniazid, and indole in the presence of zeolite as a catalyst. Structures of all the synthesized compounds were established by IR, ¹H-NMR, ¹³C-NMR, 2D-NMR, TOF-MS, and elemental analysis. The products were obtained in excellent yields and high purity. All 10 compounds were screened for larvicidal and insecticidal properties against Anopheles arabiensis and tested for their lipoxygenase inhibitory activity. Compounds (3-(3-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4i ) and (3-(3-bromo-5-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4j) displayed highest larvae mortality at a 4 μg/ml dose in 24 h. Compounds (3-(4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4h ) and (3-(3-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4i ) showed a significant knockdown activity after 24 h with 70% mortality. Furthermore, (3-(4-chlorophenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4c ) and (3-(3-bromo-5-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4j ) displayed promising lipoxygenase inhibitory activity with a mortality of 70% and 60%, respectively.     

X-ray studies of three 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine cocrystals: an unexpected molecular conformation stabilized by hydrogen bonds

The results of the X-ray structure analysis of three novel 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine cocrystals are presented. These are 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine–2,4,6-tribromophenol (1/2), C₁₂H₈N₆·2C₆H₃Br₃O, 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine–isonicotinic acid N-oxide (1/2), C₁₂H₈N₆·2C₆H₅NO₃, and 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine–4-nitrobenzenesulfonamide (1/1), C₁₂H₈N₆·C₆H₆N₂O₄S. Special attention is paid to a conformational analysis of the title tetrazine molecule in known crystal structures. Quantum chemistry methods are used to compare the energetic parameters of the investigated conformations. A structural analysis of the hydrogen and halogen bonds with acceptor aromatic tetrazine and pyrazine rings is conducted in order to elucidate factors responsible for conformational stability.     

Pd-catalyzed reactions on pyridinium N-heteroarylaminides. Step-by-step synthesis of 3,5-unsymmetrically disubstituted 2-aminopyridines

Suzuki-Miyaura cross-coupling processes on N-pyridinium bromoazinyl aminides allow access to 3,5-disubstituted N-alkyl-2-aminopyridines. The synthetic pathway involves a regioselective bromination of pyridinium N-(pyridin-2-yl)aminide and a subsequent reaction with boronic acids to afford monosubstituted aminides in good yields. An additional bromination in the 5-position of the pyridine ring followed by a coupling reaction gives pyridinium N-(3,5-diarylpyridin-2-yl)aminides. Finally, a regioselective alkylation on the exo-nitrogen and reduction of the N-N bond yields highly substituted 2-aminopyridines.     

Single-crystal X-ray diffraction analysis of arylamine-containing 2,2′-bipyridine derivatives

The structures of six 2,2′-bipyridine derivatives containing aromatic amine moieties, namely N-aryl-4-aryl-1-(pyridin-2-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-3-amines, were studied by single-crystal X-ray diffraction. The molecular structures and the effect of the substituents of these compounds on the crystal packing are discussed.

     

Modification of biologically active amides and amines by fluoro-containing heterocycles 10. γ-Carbolines modified by 2-trifluoromethylimidazo-[1,2-a]pyridin-3-ylpropionamide fragments

An approach to the modification of biologically active γ-carbolines by the 2-trifluoromethylimidazo[1,2-a]pyridin-3-ylpropionamide fragments was suggested, which consisted of the reaction of N-methyl-N-(2-trifluoromethylimidazo[1,2-a]pyridin-3-yl)prop-2-enamides with γ-carbolines in the presence of catalytic amounts of cesium fluoride. Method of radioligand binding was used to study effects of the synthesized 3-(1,2,3,4-tetrahydro-5H-pyrido[4,3-b]-indol-5-yl)-N-methyl-N-[2-(trifluoromethyl)imidazo-[1,2-a]pyridin-3-yl]propanamides on the neuronal NMDA-receptors.