Regioselective synthesis and antimicrobial evaluation of some thioether–amide linked 1,4-disubstituted 1,2,3-triazoles

A series of 1,4-disubstituted 1,2,3-triazoles having thioether as well as amide linkage were synthesized from aryl(prop-2-yn-1-yl)sulfanes and 2-azido-N-substituted acetamides through Cu(I) catalyzed click reaction. Structures of newly synthesized compounds (3a–3x) were confirmed by spectral techniques like FTIR, ¹H NMR, ¹³C NMR, and HRMS. The synthesized triazoles were evaluated for in vitro antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Compounds 3m and 3q displayed appreciable broad spectrum antimicrobial activity against tested microbial strains. The nanoformulations of compounds 3m and 3q were also prepared and examined against one bacterial strain and one fungal strain.     

Trichloroisocyanuric acid-mediated synthesis of 1,5-fused 1,2,4-triazoles from N-heteroaryl benzamidines via intramolecular oxidative N–N bond formation

A convenient synthesis of 1,5-fused 1,2,4-triazoles from readily available N-heteroaryl benzamidines is reported. The reaction is efficiently promoted by trichloroisocyanuric acid to afford the desired products, mostly in high yields and in relatively short time, through direct metal-free oxidative N–N bond formation. The mild nature of the synthesis and short reaction time are notable advantages of the developed protocol. This protocol is effective toward various substrates having different functionalities.     

Experimental and theoretical study of the dissociation enthalpy of the N–O bond on 2-hydroxypyridine N-oxide: theoretical analysis of the energetics of the N–O bond for hydroxypyrydine N-oxide isomers

The standard (p^∘=0.1 MPa) molar enthalpy of formation of crystalline 2-hydroxypyridine N-oxide was measured, at T=298.15 K, by static bomb calorimetry and the standard molar enthalpy of sublimation, at T=298.15 K, was obtained using Calvet microcalorimetry. These values were used to derive the standard molar enthalpy of formation of 2-hydroxypyridine N-oxide in gaseous phase, and to evaluate the dissociation enthalpy of the N–O bond. Additionally, high-level density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional have been performed for the three isomers of hydroxypyridine N-oxide in order to confirm the experimental trend for the dissociation enthalpy of the (N–O) bond.     

‘Green’ synthesis of 1,4-disubstituted 5-iodo-1,2,3-triazoles under neat conditions,and an efficient approach of construction of 1,4,5-trisubstituted 1,2,3-triazoles in one pot

An environmentally friendly and efficient method for synthesis of 1,4-disubstituted 5-iodo-1,2,3-triazoles through [Cu(phen)(PPh₃)₂]NO₃-catalyzed cycloaddition of organic azides and iodoalkynes under solvent-free conditions was developed. Based on this, a one-pot method for the synthesis of fully substituted 1,2,3-triazoles via cycloaddition/Suzuki reactions was also demonstrated in this report.     

Variationally determined electronic states for the theoretical analysis of intramolecular interaction: I. Resonance energy and rotational barrier of the C–N bond in formamide and its analogs

We present a new method that produces a variationally determined zeroth-order wave function for the analysis of intramolecular interactions between the fragments of a molecule. In our method, called the space-restricted wave function (SRW) method, this wave function is defined with nonorthogonal orbitals, which are obtained using the appropriately restricted variational spaces. The wave function thus obtained represents the electronic state with the target interactions deactivated, and it is constructed without unnecessarily breaking bonds, in contrast to some of the existing methods. Furthermore, we can perform energy decomposition analysis of intramolecular interactions using the zeroth-order functions that the SRW method yields. The validity of the SRW method is demonstrated in the analysis of the resonance energy and the rotational barrier of the C–N bond in formamide and its analogs. This method gives energy components that are different from those given by existing methods. With these components, we elucidate the origin of the rotational barrier from another point of view. Our SRW method gives meaningful results for the investigation of electron behavior and the nature of the molecular system.     

Rhodium(III)-catalyzed synthesis of indoles from 1-alkylidene-2-arylhydrazines and alkynes via C–H and N–N bond cleavages

1-Alkylidene-2-arylhydrazines undergo annulative coupling with internal alkynes in the presence of a rhodium(III) catalyst and a copper(II) salt. The reaction proceeds through cleavage of the C–H and N–N bonds of hydrazines to afford 1,2,3-trisubstituted indole derivatives.     

Design and applications of new phosphine-free tetradentate Pd-catalyst: Regioselective C–H activation on 1-substituted 1,2,3-triazoles and indoles(NH-Free)

This article describes the synthesis of a new phosphine free tetradentate Pd catalyst using dl-2,3-diaminopropionic acid. The complex was characterized by Mass, IR, and ¹H NMR. The catalyst is air stable at room temperature and non-hygroscopic. Application of this new catalyst to regioselective C–H activation on 1-substituted 1,2,3-triazole and indoles with aryl iodides to get corresponding C-5 and C-2 arylated products with satisfactory yields. All the products were characterized by spectroscopic studies.     

Design,synthesis, activity evaluation and QSAR studies of novel antimalarial 1,2,3-triazolo-β-lactam derivatives

This paper describes the synthesis of some new β-lactam derivatives containing the 1,2,3-triazole moiety. All the compounds were evaluated for their in vitro antimicrobial and antimalarial activities. Moderate to excellent antimalarial activities were encountered. The results showed that compounds 5a, 5c, 5f, 5i exhibited the most potent antimalarial activity with IC₅₀ values of 0.85, < 0.97, < 0.97, 1.81 µM against chloroquine-resistant P. falciparum K1 strain. A QSAR study highlights the structure–activity relationships that correlate the observed antimalarial activities with changes in the compounds’ structural features.     

Ferrocenyl substituted triphenylamine based donor–acceptor molecular systems; synthesis,photophysical, electrochemical,and theoretical studies

A series of push–pull molecular systems 5–14 were designed, and synthesized by the Sonogashira cross-coupling, Knoevenagel condensation, and cycloaddition reactions. The donor ‘ferrocenyl substituted triphenylamine’ was kept constant, whereas the acceptors were varied (malononitrile, indanone, and tetralone). The electronic absorption spectra of the ferrocenyl substituted triphenylamine based donor–acceptor (D–A) compounds 5–9 exhibit intense intramolecular charge transfer (ICT) band in the visible region (415–502 nm). The incorporation of the tetracyanoethylene (TCNE) group in compounds 5–9 results in new D–A system 10–14, which exhibits the ICT band in the region 630–700 nm. The electrochemical studies suggest considerable donor–acceptor interaction. The computational studies reveal strong D–A interaction, and show good agreement with the experimental results.     

One-pot synthesis of 1,2,3-triazoles from boronic acids in water using Cu(II)-β-cyclodextrin complex as a nanocatalyst

We report here the one-pot synthesis of 1,2,3-triazoles of arylboronic acids in water. An efficient method has been developed for the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with sodium azide in the presence of Cu(2)-β-CD (CD = Cyclodextrin) as a nanocatalyst in water followed by a click cyclization reaction with an alkyne at room temperature in air without any additives. This method is simple, rapid, and high yielding.     

One-pot sonochemical synthesis of superhydrophobic organic–inorganic hybrid coatings on cotton cellulose

Inspired by the surface structure of lotus leaves, different types of superhydrophobic cellulosic materials with contact angle (CA) of higher than 150° are currently provided. However, fabrication of these surfaces in a facile one-step coating process is one of the challenging issues. This paper describes a facile method to sonochemically synthesize superhydrophobic organic–inorganic hybrid coatings on cotton fabric by an alkaline-catalyzed co-hydrolysis and co-condensation of tetraethylorthosilicate and alkyltrialkoxysilanes. The influence of alkyl chain length (methyl, octyl, hexadecyl) of silane and reaction time was investigated. Surface structure of the fabrics was investigated by SEM, EDS, FTIR spectroscopies, and reflectance spectrophotometry. Wettability properties were studied by measuring water CA, shedding angle (SHA) and resistance to wetting by a series of ethanol–water mixtures of different surface tensions. The results showed that the treated fabrics were coated with a homogeneous thin nano-scaled coating of hybrid silica nano-particles. The fabrics demonstrated CA of higher than 150°, SHA in the range of 6–24° and different stickiness to water droplets. The fabrics treated by silanes with longer alkyl chain length and at higher reaction time revealed better water repellency. The coatings were nearly transparent, could not affect the color of the fabrics and had high stability against repeated washing. In addition, mechanical properties of the fabrics were not substantially affected.     

One-pot synthesis of ortho-acylphenols by palladium-catalyzed phenol C–H addition to nitriles

The regioselective one-pot synthesis of ortho-acylphenols via the palladium-catalyzed addition of phenols to nitriles and subsequent hydrolysis is reported. The acylation reaction proceeded smoothly using the Pd(OAc)₂/DMSO system and TFA as the additive. This method also provides a direct strategy for the synthesis of a salicylketoxime scaffold.     

How delocalized is N,N,N',N'-tetraphenylphenylenediamine radical cation? An experimental and theoretical study on the electronic and molecular structure

The electronic and molecular structure of N,N,N',N'-tetraphenylphenylenediamine radical cation 1(+) is in focus of this study. Resonance Raman experiments showed that at least eight vibrational modes are strongly coupled to the optical charge resonance band which is seen in the NIR. With the help of a DFT-based vibrational analysis, these eight modes were assigned to symmetric vibrations. The contribution of these symmetric modes to the total vibrational reorganization energy is dominant. These findings are in agreement with the conclusions from a simple two-state two-mode Marcus-Hush analysis which yields a tiny electron-transfer barrier. The excellent agreement of the X-ray crystal structure analysis and the DFT computed molecular structure of 1(+) on one hand as well as the solvent and solid-state IR spectra and the DFT-calculated IR active vibrations on the other hand prove 1(+) adopts a symmetrical delocalized Robin-Day class III structure both in the solid state and in solution.     

Ultrasonic and ir investigations of N–H bond complexes

Complex formation of 1?:?1 mixtures of naphthols, viz. (α-naphthol and β-naphthol) with triethylamine in benzene have been studied at a frequency of 2?MHz in the concentration range of 0.010–0.090 and at varying temperatures of 30, 40 and 50°C. Using the measured ultrasonic velocity, the thermoacoustical parameters such as adiabatic compressibility, intermolecular free length, molar sound velocity, molar compressibility and acoustic impedance have been calculated. The ultrasonic velocity shows a maxima and adiabatic compressibility shows a corresponding minima as a function of concentration for these mixtures. These, in turn, are used to study the solute–solute interaction and the possibility of complex formation between unlike molecules of naphthols and triethylamine through intermolecular hydrogen bonding. The hydrogen bond is formed between hydrogen atom of naphthols and nitrogen atom of triethylamine molecule. The result obtained using infrared spectroscopy for both the systems also supports the existence of complex formation through intermolecular hydrogen bonding.     

Microwave-assisted solid-phase synthesis,cellular uptake,and cytotoxicity studies of cymantrene–peptide bioconjugates

Five cymantrene (CpMn(CO)₃) bioconjugates of enkephalin (ENK), neurotensin (NT), pseudoneurotensin (pNT), NLS, and TAT were prepared by automated solid phase peptide synthesis (SPPS) under microwave irradiation in all steps, including peptide chain elongation, incorporation of the cymantrene moiety, final deprotection, and cleavage from the resin. The compounds were obtained in pure form with minimal work-up procedures and characterized by RP-HPLC, ESI-MS, and IR spectroscopy. They are efficiently internalized in HT-29 human colon cancer cells (0.22 to 0.48 nmol Mn/mg cell protein) and non-cytotoxic at up to 100 μM. With the carbonyl CO bands clearly detectable even in the presence of an octapeptide chain as in the cymantrene–NLS conjugate, these compounds will be useful as IR spectroscopic probes in peptide biodistribution studies.     

Improved and expanded one-pot,two-component Boulton-Katritzky syntheses of N–N bond containing bicyclic heterocycles

Improved and expanded one-pot, two-component syntheses of bicyclic heterocycles containing a 3-N-acyl-3-amino-1,2-pyrazole motif from N′-hydroxy-carboxyamidines and acylbenzotriazoles have been developed. Importantly, this sequence obviates the need for hydrazine or N-aminating reagents to synthesize the key nitrogen–nitrogen (N–N) bond of these heterocycles, which is formed via Boulton-Katritzky rearrangement. A diverse array of pharmaceutically relevant N–N containing heterocycles has been prepared with this methodology using readily available reagents without the need for special equipment or conditions.     

Directionality of intermolecular C–F···F–C interactions in crystals: experimental and theoretical charge density study

Bonding intermolecular F···F interactions were analyzed in crystal of a fluorinated benzene derivative using topological analysis of experimental charge density distribution. It was found that the values of electron density and potential energy density in bond critical points of the F···F interactions in crystal depended on the distance between the fluorine atoms, rather than on the corresponding C–F···F angles. The directionality of these F···F interactions was demonstrated by DFT-D and MP2 calculations for model hexafluorobenzene dimers. Possible discrepancies between dimerization energies computed by ab initio methods and via empirical correlations are discussed.     

Pd-catalyzed ligand-free C(5)–H arylation of 1,4-disubstituted 1,2,3-triazoles promoted by microwaves

Pd(OAc)₂-catalyzed regioselective C(5)–H arylation of 1,4-disubstituted 1,2,3-triazoles was achieved without ligand under microwave conditions in 1?h, generating 1,4,5-trisubstituted 1,2,3-triazoles with good to excellent yields. The obtained molecules can be easily converted into 4,5-disubstituted 1,2,3-triazoles through the debenzylation process with one-pot manipulation.     

Aryloxy and benzyloxy compounds of zirconium: Synthesis, structural characterization and studies on solvent-free ring-opening polymerization of ?-caprolactone and δ-valerolactone

A series of aryloxy compounds and benzyloxy derivatives of Zr(IV) were synthesized in good yields and purity, employing the alcoholysis route. They were completely characterized with different spectroscopic techniques and single crystal X-ray diffraction. A high degree of fluxional behavior of these compounds was understood through variable-temperature NMR studies. X-ray diffraction studies prove that these compounds exist as dimers in the solid state. They are potent catalysts for the ring-opening polymerization of ?-caprolactone (CL) and δ-valerolactone (VL) resulting in high polymers with good number average molecular weights (M_n) and molecular weight distributions (MWDs). The degree of control in these polymerizations was found to be superior with the zirconium compounds when compared with the titanium analogues. The rate of polymerization was found to be slower for the zirconium compounds, as realized from kinetic studies. Analysis of the MALDI-TOF and ¹H NMR spectra of low molecular weight oligomers of CL synthesized using these compounds reflect that these polymerizations proceed by the activated monomer mechanism.