2-(Benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidates: Synthesis,characterization and antimicrobial activity evaluation

A series of new 2-(benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidate derivatives (7a-j) of biological interest are synthesized in two steps via an in situ process without the isolation of the intermediate. 2-(Benzo[d]thiazol-2-yl) phenol (3) was treated with 4-nitrophenyl phosphorodichloridate(4) to obtain the monochloro intermediate, 2-(benzo[d]thiazol-2-yl)phenyl (4-nitrophenyl) phosphorochloridate(5). It was subsequently reacted with various amines, 6(a-j) to afford the desired title products. IR, NMR (¹H, ¹³C and ³¹P), mass spectral and elemental analysis are used to characterize the structures of the newly synthesized compounds. The antibacterial and antifungal activities are determined by the growth of inhibition of bacteria and fungi of the title compounds at two concentrations, 50 and 100 µg/mL, and minimum inhibitory concentrations to the active compounds. The compounds 7e, 7f and 7j exhibited promising inhibition activity against bacterial strains and 7c, 7e and 7i against A. niger and C. albicans and MIC values are in the range of 10.0–15.0 µg/mL.     

New,Convenient, One-Pot Method for the Synthesis of Thiazolyl-pyrazolones from Dehydroacetic Acid Derivative via a Multicomponent Approach

A convenient one-pot method for the synthesis of thiazolyl-pyrazolones was described in excellent yields. Reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one with thiosemicarbazide and ethyl 2-(2-arylhydrazono)-3-oxobutanoates in anhydrous ethanol under reflux conditions afforded the corresponding 4-(2-arylhydrazono)-1-(4-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)thiazol-2-yl)-3-methyl-1H-pyrazol-5(4H)-one in good yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, infrared, ¹H NMR, and mass spectroscopic studies.     

Synthesis of novel bis(chromenes) and bis(chromeno[3,4-C]pyridine) incorporating piperazine moiety

Novel bis(2-oxo-2H-chromene) as well as bis(2-imino-2H-chromene) derivatives incorporating piperazine moiety were prepared by the cyclocondensation reaction of bis(2-hydroxybenzaldehyde) with two equivalents of each of the appropriate β-ketoesters or acetonitrile derivatives. The bis(2-imino-2H-chromene-3-carbothioamide) derivative was used as a key synthon for construction of novel bis(3-(4-substituted thiazol-2-yl)-2H-chromen-2-one) derivatives via its cyclocondensation with a series of the appropriate α-halocarbonyl derivatives. Moreover, the bis(2-hydroxybenzaldehyde) reacted with four equivalents of the appropriate acetonitrile derivatives to afford the corresponding bis(3H-chromeno[3,4-c]pyridine) derivatives. Elucidation of the structure of the novel bis(chromenes) bearing piperazine nucleus was established by the spectral data and elemental analyses.     

Microwave-assisted Hantzsch thiazole synthesis of N-phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines from the reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones and thioureas

N-Phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines (6a-q) have been synthesized by the Hantzsch thiazole reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones (4a-e) with suitably substituted thioureas using microwave heating. The ethanones (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with chloroacetylchloride in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Synthesis,crystal structure and catalytic performance of bis (imino)pyridyl nickel complexes

Two new Ni(II) complexes of 2,6-bis[1-(2,6-diethylphenylimino)ethyl]pyridine (L¹), 2,6-bis[1-(4-methylphenylimino)ethyl]pyridine (L² ) have been synthesized and structurally characterized. Complex Ni(L¹)Cl₂?·?CH₃CN (1), exhibits a distorted trigonal bipyramidal geometry, whereas complex Ni(L¹)(CH₃CN)Cl₂ (2), is six-coordinate with a geometry that can best be described as distorted octahedral. The catalytic activities of complexes 1, 2, Ni{2,6-bis[1-(2,6-diisopropyl-phenylimino)ethyl]pyridine} Cl₂?·?CH₃CN (3), and Ni{2,6-bis[1-(2,6-dimethylphenylimino) ethyl]pyridine}Cl₂?·?CH₃CN (4), for ethylene polymerization were studied under activation with MAO.     

Preparation and characterization of binuclear CuII complexes derived from diamines and dialdehydes

New macrocyclic complexes were synthesized by template reaction of 1,7-bis(2-formylphenyl)-1,4,7-trioxaheptane, 1,4-bis(2-carboxyaldehydephenoxy)butane or 1,3-bis(2-carboxyaldehydephenoxy)propane with 1,4-bis(2-aminophenoxy)butane, 1,3-bis(2-aminophenoxy)butane, 1,4-bis(4-chloro-2-aminophenoxy)butane or 1,3-bis(4-chloro-2-aminophenoxy)butane and Cu(NO₃)₂ ·?3H₂O or Cu(ClO₄)₂ ·?6H₂O, respectively. The complexes have been characterized by elemental analysis, IR, ¹H and ¹³C NMR, UV–Vis spectra, magnetic susceptibility, conductivity measurements and mass spectra. All complexes are diamagnetic and binuclear.     

Novel half‐sandwich η5‐Cp *–rhodium(III) and η5‐Cp *–ruthenium(II) complexes bearing bis(phosphino)amine ligands and their use in the transfer hydrogenation of aromatic ketones

Two new half‐sandwich η⁵‐Cp*–rhodium(III) and η⁵‐Cp*–ruthenium(II) complexes have been prepared from corresponding bis(phosphino)amine ligands, thiophene‐2‐(N,N‐bis(diphenylphosphino)methylamine) or furfuryl‐2‐(N,N‐bis(diphenylphosphino)amine). Structures of the new complexes have been elucidated by multinuclear one‐ and two‐dimensional NMR spectroscopy, elemental analysis and IR spectroscopy. These Cp*–rhodium(III) and Cp*‐ruthenium(II) complexes bearing bis(phosphino)amine ligands were successfully applied to transfer hydrogenation of various ketones by 2‐propanol. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,characterisation and structural aspects of some symmetrical organotellurium halides based on Bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride

Bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride (2) has been synthesised in good yield by reacting 1-(2-chloroethyl)-3,5-dimethylpyrazole with in situ prepared sodium telluride, Na₂Te in an aqueous solution. A number of new organotellurium halides from bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride have been synthesised by using different halogenating reagents. Reaction of 2 with bromine gave bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride dibromide (5a) in addition to unexpected product bis(2-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride dibromide (5b). All compounds were characterized by different spectroscopic techniques viz., ¹H, ¹³C, ¹²⁵Te NMR, Mass spectroscopy, IR and CHN analysis. EDXRF studies have also been employed to confirm the identity of 5a and 5b. Thermal gravimetric analysis of bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride (IV) chloride (4) and bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride (IV) iodide (5c) reveals the thermal stability of these molecules above 100°C. The X-ray studies of 5c shows trigonal bipyramidal geometry around tellurium atom and intermolecular secondary interaction viz., C-H π stacking between H23A and C22 showing a supramolecular packing between two molecules.     

2-Amino-4-(aminomethyl)thiazole-based derivatives as potential antitumor agents: design,synthesis, cytotoxicity and apoptosis inducing activities

Novel 2-amino-4-(aminomethyl)thiazole derivatives were designed and synthesized by a facile method including the Hantzsch construction of thiazole core followed by amidation and nucleophilic substitution steps. Bioassay results showed that 4-(tert-butyl)-N-[4-(piperazin-1-ylmethyl)thiazol-2-yl]-benzamide and 4-(tert-butyl)-N-{4-[(4-piperidinopiperidin-1-yl)methyl]thiazol-2-yl}benzamide possessed similar activities compared with 5-fluorouracil. The 4-piperidino-piperidin-1-yl-containing derivative also suppressed proliferation of cultured tumor cells by inducing apoptosis.     

Encapsulation of Pd(II) by N4 and N2O2 macrocyclic ligands: their use in catalysis and biology

New macrocyclic Schiff base Pd(II) compounds were synthesized by treating N₄ and N₂O₂ macrocycles with palladium chloride in a 1 : 1 ratio. The resulting macrocyclic compounds were characterized by elemental, IR, ¹H-NMR, ¹³C-NMR, mass, molar conductance, magnetic susceptibility, electronic spectra, and thermal analysis. These compounds were used as catalysts in the development of an efficient catalytic method for reduction of organic substrates having nitro, olefinic, acetylenic, and aldehyde groups under mild reaction conditions. The biological activities of all the macrocycles and macrocyclic Pd(II) compounds have been tested against gram positive (Bacillus subtilis and Staphylococcus aureus) and gram negative (Escherichia coli and Klebsiella pneumonia) bacteria and found to be more active than commercially available antibacterial drugs like Streptomycin and Ampicillin.     

Structural and Spectral Study of Nickel(II) Complexes of Pyridyl bis{3‐piperidyl‐, bis{hexamethyleneiminyl‐, bis{N(4)‐diethyl‐, and bis{N(4)‐dipropylthiosemicarbazones}

Pyridyl bis(N(4)‐substituted thiosemicarbazones), in which the substituents replacing the NH₂ group on the thiosemicarbazone moieties are piperidyl, H₂Plpip; hexamethyleneiminyl, H₂Plhexim; diethylamino, H₂Pl4DE; and dipropylamino, H₂Pl4DP, have been synthesized. These bis(thiosemicarbazones) and their nickel(II) complexes have been characterized with IR, electronic, mass, and ¹H and ¹³C NMR spectra. Crystal structures have been solved for H₂Plpip and all four nickel(II) complexes. H₂Plpip does not possess hydrogen bonding between the thiosemicarbazone moieties, but is in the Z isomeric form with intramolecular hydrogen bonding from both thiosemicarbazone moieties to pyridine nitrogen atoms. The nickel(II) complexes possess square‐planar N₂S₂ (i. e., imine nitrogen and thiolato sulfur atoms) centers and the two pyridine ring nitrogen atoms are not coordinated.     

One-Pot Synthesis of Novel 2-(Thiazol-2-yl)-4,5-dihydropyridazin-3(2H)-one Derivatives Catalyzed by Activated KSF

A series of 2-(thiazol-2-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by one-pot multicomponent cyclocondensation of ketoacid, thiosemicarbazide, and phenacyl bromide using catalytical amount of KSF in EtOH under reflux. The straightforward synthesis, presence of two important class of heterocyclic rings in the individual molecule, easy workup of the products, rapid reaction, mild conditions, and good to excellent yields are notable features of this protocol.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis and characterization of macrocyclic polystyrene block-copolymers

The synthesis of macrocyclic polystyrene- block-poly(2-vinylpyridine) and macrocyclic polystyrene- block-poly(dimethylsiloxane) was carried out by initiation of 2-vinylpyridine (2VP) and hexamethyl-cyclotrisiloxane (D3) by difunctional living polystyryllithium followed by coupling with 1,4-bis(bromethyl)benzene (1,4-DBX) and dichloro-dimethylsilane (Cl₂SiMe₂), respectively. A small portion of the living ABA precursors were protonated to serve as isobaric linear precursors. The linear and macrocyclic block copolymers were characterized by size-exclusion chromatography (SEC). The ratios of apparent cyclic/linear SEC molecular-weight maxima versus degree of polymerization (DP) show increases with decreasing DP varying from 0.70 ± 0.03 at high DP ≤ 200 to 0.78 ± 0.044 at low DP (≥60) whereas that of the linear ABA block copolymers decreased. Increases in glass transition temperature (Tg) were also observed for the cyclic PS-b-PDMS copolymers with respect to the isobaric linear precursors. The macrocycles were characterized by ¹H and ¹³C NMR and in the case of macrocyclic PS-b-PDMS by ²⁹Si NMR as well. Broadening in the NMR absorptions of the macrocyclic block copolymers is general and is similar to that observed for the homopolymers. Differemtial scanning calorimetry (DSC) analysis of the PS-b-P2VP macrocycles shows increases in Tg at lower molecular weight as was observed for the PS and P2VP macrocycles.     

Synthesis of novel scaffolds based on thiazole or triazolothiadiazine linked to benzofuran or benzo[d]thiazole moieties as new hybrid molecules

Abstract

A synthesis of novel hybrid molecules containing thiazole or bis(thiazoles) each bearing benzofuran and/or benzo[d]thiazole moieties by the reaction of the appropriate thioamide derivatives with the corresponding bis-bromoacetyl derivatives is reported. Mono- and bis(triazolothiadiazine) derivatives based on benzofuran or benzo[d]thiazole moieties were also synthesized in good yields by the reaction of the appropriate bis(bromoacetyl) derivatives with each of 4-amino-5-mercapto-1,2,4-triazoles and their corresponding bis-derivatives.     

Synthesis and biological activities of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety

A series of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety were designed, synthesized and evaluated for their antibacterial, antifungal and antiviral activities. The bioassay results indicated that most of target compounds showed good antiviral activities against tobacco mosaic virus (TMV) and antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs). Especially, the anti-Xoo effect of title compounds 5k (N-(5-methoxybenzo[d]thiazol-2-yl)-2-((5-(2-tolyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) and the anti-Rs effect of title compounds 5a (N-(5-nitrobenzo[d]thiazol-2-yl)-2-((5-(4-(trifluorom ethyl)phenyl)-1,3,4-thiadiazol-2-yl)thio)acetmide) respectively reached 52.4% and 71.6% at 100?µg/mL, which are superior to that of bismerthiazol (32.0% and 52.3%). In addition, the protective and inactivation activities of title compound 5i (N-(5-methoxybenzo [d]thiazol-2-yl)-2-((5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) against TMV were 79.5% and 88.3%, respectively, which are better than that of ningnanmycin (76.4% and 86.8%). The above research showed that benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety may be used as potential molecular templates in searching for highly-efficient antiviral and antibacterial agents.     

Synthesis and characterization of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and dihydro-alkylthio-benzyloxopyrimidine (S-DABO) analogs containing a benzo[<Emphasis Type="Italic">d</Emphasis>]thiazol moiety

A series of novel dihydro-alkylthio-benzyloxopyrimidine (S-DABO) and 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT) analogs bearing a (benzo[d]thiazol-2-yl)methyl moiety at the C⁶ position of the pyrimidine core have been synthesized. 5-Allyl-6-{(benzo[d]thiazol-2-yl)methyl}-2-thiouracil and 5-allyl-6-{(benzo-[d]thiazol-2-yl)methyl}uracil were alkylated to give, respectively, S²- and N¹- ethoxymethyl and -methylthiomethyl uracil derivatives. 5-Allyl-6-[(benzo[d]thiazol-2-yl)methyl]-2-thiouracil was also alkylated by S² with methyl bromoacetate and hydrolyzed to the corresponding acid.     

Ru(II)-PBTNNXN complex bearing functional 2-(pyridin-2-yl)benzo[d]thiazole ligand catalyzed α-alkylation of nitriles with alcohols

Six tridentate NNN ligand precursors derived from 2-(pyridin-2-yl)benzo[d]thiazole(PBT) with different linkers, ^PBTNN^XN (X = NH, NMe, O, S) ( 1a – 1f ), have been successfully prepared. The electronic properties of ^PBTNN^XN ligands are well tunable by differing linkers between PBT skeleton and the pyridine ring, and/or by introducing electron-donating/withdrawing groups on the pyridine ring (R = OMe or F). The ligand precursors and representative complexes Ru (^PBTNN^NHN)Cl₂(PPh₃) ( 2a ), Ru (^PBTNN^NMeN)Cl₂(PPh₃) ( 2b ), and Ru (^PBTNN^SN)Cl₂(PPh₃) ( 2f ) have been characterized by NMR spectroscopy, high-resolution mass spectroscopy, and Fourier transform infrared (FT-IR). The molecular structures of 1f , 2a , and 2f have been determined by X-ray diffraction study. The results indicate that ^PBTNN^NHN ligand in the complex presented coplanar with two five-membered chelating rings. It should be noted that 2a featuring a NH group exhibits superior performance compared to those with other linkers (such as NMe, O, or S). A variety of heterocyclic and aromatic nitriles with aromatic and aliphatic alcohols have been explored in α-alkylation for good to excellent yields. Based on kinetic experiments and mechanistic studies, a proposed mechanism was put forward. Ru-H species and benzaldehyde, which was oxidized from benzyl alcohol, were detected in the catalytic cycle.     

Synthesis,Characterization, and Molecular Docking of Novel bis‐thiazolyl Thienothiophene Derivatives as Promising Cytotoxic Antitumor Drug

A novel, facile reaction for the synthesis of series of bis‐thiazole derivatives has been developed from the reaction of the appropriate thiosemicarbazone derivatives and bis‐2‐bromoacetylthieno[2,3‐b ]thiophene derivatives in ethanol under reflux. The structures of the newly synthesized products were established on the basis of spectral data (mass, IR, and ¹H and ¹³C NMR) and elemental analyses. Fifteen compounds of the synthesized compounds were evaluated for their anticancer activity against human liver hepatocellular carcinoma cell line (HepG2). All compounds showed anticancer activity but differs in potency comparable with the reference drug Cisplatin. Moreover, molecular docking study using MOE software predicted the best binding mode between the most active compound 5o into the active site of human heat‐shock protein 90. The computational studies are confirming the results in biological activity.     

Synthesis of four novel pendant armed macrocyclic ligands and their interaction with lanthanide(III) cations

The ability of La³⁺ ions to form stable complexes with four novel pendant-armed N_xO_y-macrocycles derived from 2,6-bis(2-formylphenoxymethyl)pyridine, L¹, L², L³, and L⁴, has been studied. The corresponding (unsubstituted) parent ligands were prepared by the reaction between 2,6-bis(2-formylphenoxymethyl)pyridine and three different amines: 1,2-bis(2-aminophenoxy)propane (L¹), diethylenetriamine (L²), and 3,6-dioxa-1,8-octanediamine (L³ and L⁴). This was followed for the parent ligands of L¹, L³, and L⁴ by in situ reduction with sodium borohydride. The pendant-armed ligands were then synthesized by the alkylation of the free-NH groups with p-(L¹ and L³) and o-nitrobenzyl bromide (L⁴), and 2-chloromethylpyridine chlorohydrate (L²). A series of Ln(III) complexes were prepared for the four ligands by the direct synthesis between the corresponding macrocycle and Ln(III) hydrated nitrates and perchlorates. The number of complexes obtained from the pendant-armed macrocycles is lower than that of the (unsubstituted) parent ones, suggesting that the introduction of pendant arms in the macrocyclic skeletons increases the selectivity of the ligands. More complexes were synthesized when using nitrate as the counterion, showing the important role of the counterion in the complexation reaction. The text was submitted by the authors in English.     

Synthesis and spectral studies of macrocyclic Cu(II) complexes by reaction of various diamines,copper(II) perchlorate and 1,4-bis(2-carboxyaldehyde phenoxy)butane

Six macrocyclic complexes, were synthesized by reaction of 1,4-bis(2-carboxyaldehyde phenoxy)butane and various amines and their copper(II) perchlorate complexes were synthesized by template effect reaction of 1,4-bis(2-carboxyaldehyde phenoxy)butane, Cu(ClO₄)₂?·?6H₂O and amines. The metal-to-ligand ratios were found to be 1?:?1. Cu(II) metal complexes are 1?:?2 electrolytes as shown by their molar conductivities (Λ_M) in DMF (dimethyl formamide) at 10^?3?M. The Cu(II) complexes are proposed to be square planar based on elemental analysis, FT–IR, UV–Vis, magnetic susceptibility measurements, molar conductivity measurements, and mass spectra.