Showing papers on "Hydrazone published in 2017"

Photochromic Hydrazone Switches with Extremely Long Thermal Half-Lives.

Abstract: A family of easily accessible light-activated hydrazone switches has been developed having thermal half-lives of up to 2700 years! Structure–property analysis shows that replacing the rotor pyridyl group of our typical hydrazone switch with a phenyl one leads to the long-lived negative photochromic compounds. The switching properties of the hydrazones in both toluene and DMSO were assessed offering insights into the kinetics and thermodynamics of the switching process.

Redox Control over Acyl Hydrazone Photoswitches.

Abstract: Photoisomerization provides a clean and efficient way of reversibly altering physical properties of chemical systems and injecting energy into them. These effects have been applied in development of systems such as photoresponsive materials, molecular motors, and photoactivated drugs. Typically, switching from more to less stable isomer(s) is performed by irradiation with UV or visible light, while the reverse process proceeds thermally or by irradiation using another wavelength. In this work we developed a method of rapid and tunable Z→E isomerization of C═N bond in acyl hydrazones, using aromatic thiols as nucleophilic catalysts. As thiols can be oxidized into catalytically inactive disulfides, the isomerization rates can be controlled via the oxidation state of the catalyst, which, together with the UV irradiation, provides orthogonal means to control the E/Z state of the system. As a proof of this concept, we have applied this method to control the diversity of acyl hydrazone based dynamic combinatori...

Pyridyl-Acyl Hydrazone Rotaxanes and Molecular Shuttles.

Abstract: We report on rotaxanes featuring a pyridyl-acyl hydrazone moiety on the axle as a photo/thermal-switchable macrocycle binding site. The pyridyl-acyl E-hydrazone acts as a hydrogen bonding template that directs the assembly of a benzylic amide macrocycle around the axle to form [2]rotaxanes in up to 85% yield; the corresponding Z-hydrazone thread affords no rotaxane under similar conditions. However, the E-rotaxane can be smoothly converted into the Z-rotaxane in 98% yield under UV irradiation. The X-ray crystal structures of the E- and Z-rotaxanes show different intercomponent hydrogen bonding patterns. In molecular shuttles containing pyridyl-acyl hydrazone and succinic amide ester binding sites, the change of position of the macrocycle on the thread can be achieved through a series of light irradiation and heating cycles with excellent positional integrity (>95%) and switching fidelity (98%) in each state.

Computational Study on γ-C–H Functionalization of α,β-Unsaturated Ester Catalyzed by N-Heterocyclic Carbene: Mechanisms, Origin of Stereoselectivity, and Role of Catalyst

Abstract: The N-heterocyclic carbene (NHC)-catalyzed γ-C–H deprotonation/functionalization of α,β-unsaturated esters with hydrazones leading to the δ-lactams has been theoretically investigated by using density functional theory. Three possible reaction mechanisms including Mechanism A, for which the NHC catalyst serves as a nucleophilic catalyst to attack on the carbonyl carbon atom to initiate the reaction, Mechanism B, in which NHC triggers the reaction through the hydrogen bond, and Mechanism C, which is the direct deprotonation/functionalization process without the presence of NHC, have been suggested and studied in detail. The most favorable Mechanism A was identified to proceed through the following processes: nucleophilic attack on the carbonyl carbon of the ester by NHC, γ-deprotonation, formal [4 + 2] cycloaddition of dienolate with hydrazone, and regeneration of NHC. Multiple possible deprotonation pathways were explored, and the additive base such as K2CO3 would significantly lower the energy barrier. T...

A novel colorimetric and ratiometric fluorescent Cu2+ sensor based on hydrazone bearing 1,8-naphthalimide and pyrrole moieties

Abstract: A 1,8-naphthalimide hydrazone derivative bearing a pyrrole unit is a highly selective ratiometric fluorescent Cu 2+ probe used to monitor intracellular Cu 2+ in HeLa cells. This probe functions via a unique hydrolysis mechanism through Cu 2+ -promoted electrophilic substitution. Binding is confirmed through UV–vis absorption, fluorescence measurements, mass spectroscopy, IR, X-ray single crystal diffraction, and DFT calculation.

Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes

Abstract: Two chromone hydrazone ligands HL1 and HL2 were synthesized and characterized by elemental analyses, IR, 1H NMR & 13C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV–Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose.

Electronic Effects of Aromatic Rings on the Catalytic Activity of Dioxidomolybdenum(VI)–Hydrazone Complexes

Abstract: Nine dioxidomolybdenum(VI) complexes were synthesized by the ‎reaction of MoO3 with tridentate hydrazone Schiff base ligands ‎obtained from the reaction of aromatic acid hydrazides (3-hydroxy-2-‎naphthoic acid hydrazide, 4-pyridine carboxylic acid hydrazide or 2-‎furane carboxylic acid hydrazide) and ortho-hydroxy aldehyde ‎derivatives (5-iodo-2-hydroxybenzaldehyde, 2-hydroxy-1-‎naphthaldehyde or 2-hydroxy-3-methoxybenzaldehyde). All ligands ‎and complexes were characterized by elemental analysis and ‎spectroscopic methods. The structures of seven complexes were ‎further elucidated by single-crystal X-ray diffraction analysis which ‎indicated a distorted octahedral geometry at the metal centre. ‎Spectroscopic and X-ray analyses indicated that the ligands are ‎coordinated to the molybdenum(VI) ion as dinegative ligands due to ‎deprotonation of phenolic OH and amidic NH groups upon ‎complexation. These complexes were used as catalyst in ‎the oxidation of cyclooctene and thioanisol in the presence of ‎hydrogen peroxide as environmental friendly oxidant. In order to ‎achieve the highest catalytic activity, the effects of important ‎parameters such as solvent, temperature and the molar ratio of ‎oxidant to substrate were optimized. The results indicate that ‎electron-withdrawing substituents on the ligands increase the ‎catalytic activity of dioxidomolybdenum(VI)-hydrazone complexes.‎

New Pyrazole-Hydrazone Derivatives: X-ray Analysis, Molecular Structure Investigation via Density Functional Theory (DFT) and Their High In-Situ Catecholase Activity.

Abstract: The development of low-cost catalytic systems that mimic the activity of tyrosinase enzymes (Catechol oxidase) is of great promise for future biochemistry technologic demands. Herein, we report the synthesis of new biomolecules systems based on hydrazone derivatives containing a pyrazole moiety (L1–L6) with superior catecholase activity. Crystal structures of L1 and L2 biomolecules were determined by X-ray single crystal diffraction (XRD). Optimized geometrical parameters were calculated by density functional theory (DFT) at B3LYP/6–31G (d, p) level and were found to be in good agreement with single crystal XRD data. Copper (II) complexes of the compounds (L1–L6), generated in-situ, were investigated for their catalytic activities towards the oxidation reaction of catechol to ortho-quinone with the atmospheric dioxygen, in an attempt to model the activity of the copper containing enzyme tyrosinase. The studies showed that the activities depend on four parameters: the nature of the ligand, the nature of counter anion, the nature of solvent and the concentration of ligand. The Cu(II)-ligands, given here, present the highest catalytic activity (72.920 μmol·L−1·min−1) among the catalysts recently reported in the existing literature.

Kinetic Selectivity and Thermodynamic Features of Competitive Imine Formation in Dynamic Covalent Chemistry

Abstract: The kinetic and thermodynamic selectivities of imine formation have been investigated for several dynamic covalent libraries of aldehydes and amines. Two systems were examined, involving the reaction of different types of primary amino groups (aliphatic amines, alkoxy-amines, hydrazides and hydrazines) with two types of aldehydes, sulfobenzaldehyde and pyridoxal phosphate in aqueous solution at different pD (5.0, 8.5, 11.4) on one hand, 2-pyridinecarboxaldehyde and salicylaldehyde in organic solvents on the other hand. The reactions were performed separately for given amine/aldehyde pairs as well as in competitive conditions between an aldehyde and a mixture of amines. In the latter case, the time evolution of the dynamic covalent libraries generated was followed, taking into consideration the operation of both kinetic and thermodynamic selectivities. The results showed that, in aqueous solution, the imine of the aliphatic amine was not stable, but oxime and hydrazone formed well in a pH dependent way. On the other hand, in organic solvents, the kinetic product was the imine derived from an aliphatic amine and the thermodynamic products were oxime and hydrazone. The insights gained from these experiments provide a basis for the implementation of imine formation in selective derivatization of mono-amines in mixtures as well as of polyfunctional compounds presenting different types of amino groups. They may in principle be extended to other dynamic covalent chemistry systems.

Copper-Catalyzed Transformation of Hydrazones into Halogenated Azabutadienes, Versatile Building Blocks for Organic Synthesis

Abstract: A one-step copper-catalyzed reaction of aldehyde-derived N-substituted hydrazones with CCl4 resulted in efficient synthesis of 4,4-dichloro-1,2-diazabuta-1,3-dienes. It was proven that this C–C bond-forming cascade reaction operates via an addition of trichloromethyl radical to the C═N bond of hydrazone followed by a base-induced elimination of HCl. The reaction was found to be very general, as diverse hydrazones possessing various aromatic groups at N-site, as well as aromatic, aliphatic, and heterocyclic substituents at C-site, are capable partners for coupling with a wide range of polyhalogenated compounds (CCl3Br, CBr4, CCl3CN, CCl3COOEt, CCl3CF3, CBr3CF3) to produce a family of functionalized 1,2-diazabuta-1,3-dienes. It was demonstrated that the prepared heterodienes are highly versatile building blocks for straightforward assembly of various valuable acyclic and heterocyclic molecules.

Addition of N -nucleophiles to gold( iii )-bound isocyanides leading to short-lived gold( iii ) acyclic diaminocarbene complexes

Abstract: Reaction of [AuCl3(CNR1)] (R1 = Xyl, Cy, (S)-CHMePh) with amines unexpectedly proceeds via the redox pathway giving gold(I)–isocyanides and imines, while the addition of benzophenone hydrazone to the isocyanide ligand in [AuCl3(CNR1)] at RT leads to short-lived gold(III) acyclic diaminocarbene complexes [AuCl3{C(NHNCPh2)NHR1}].

Synthesis of 4-Acylpyrazoles from Saturated Ketones and Hydrazones Featured with Multiple C(sp3)-H Bond Functionalization and C-C Bond Cleavage and Reorganization.

Abstract: In this paper, an efficient and convenient one-pot synthesis of diversely substituted 4-acylpyrazole derivatives via copper-catalyzed one-pot cascade reactions of saturated ketones with hydrazones is reported. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through the dehydrogenation of a saturated ketone and the [2 + 3] cyclization of the enone with hydrazone followed by an aromatization-driven C–C bond cleavage and reorganization. To our knowledge, this is the first example in which the biologically and pharmaceutically important yet otherwise difficult-to-obtain 4-acylpyrazole derivatives are directly prepared from saturated ketones and hydrazones featured with multiple aliphatic C–H bond functionalization and C–C bond cleavage and reorganization. Compared with literature methods, this novel process has advantages such as simple and economical starting materials, a sustainable oxidant, excellent regioselectivity, and good efficiency.

Facile synthesis of 1-aminoindoles via Rh(III)-catalysed intramolecular three-component annulation

Abstract: The facile synthesis of various 1-aminoindoles from readily available aryl hydrazines, diazo compounds and ketones via rhodium catalysed C–H activation has been developed. The reaction was carried out under mild reaction conditions using hydrazone as a directing group, which was formed by the in situ condensation of hydrazines and ketones. This protocol exhibits a broad substrate scope and step economy, releasing N2 and H2O as the byproducts, obviating the need for external oxidants and pre-functionalized substrates.

Divergent Synthesis of 1H-Indazoles and 1H-Pyrazoles from Hydrazones via Iodine-Mediated Intramolecular Aryl and sp3 C–H Amination

Abstract: A divergent intramolecular C−H amination of hydrazones has been developed employing molecular iodine (I2) as the sole oxidant. The required hydrazone substrates were readily obtained by condensation of hydrazines with the corresponding ketones. In the presence of potassium iodide, I2-mediated oxidative cyclization of diaryl and tert-butyl aryl ketone hydrazones produced 1H-indazoles via direct aryl C−H amination. Under similar reaction conditions, primary and secondary alkyl ketone hydrazones were transformed into 1H-pyrazole products in a reaction involving sp3 C−H amination. This synthetic methodology does not involve transition metals, and is operationally simple, providing facile access to indazole and pyrazole derivatives in an efficient and scalable fashion.

Co(iii) complexes of (1,3-selenazol-2-yl)hydrazones and their sulphur analogues.

Abstract: The first Co(III) complexes with (1,3-selenazol-2-yl)hydrazones as an unexplored class of ligands were prepared and characterized by NMR spectroscopy and X-ray diffraction analysis. The novel ligands act as NNN tridentate chelators forming octahedral Co(III) complexes. The impact of structural changes on ligands’ periphery as well as that of isosteric replacement of sulphur with selenium on the electrochemical and electronic absorption features of complexes are explored. To support the experimental data, density functional theory (DFT) calculations were also conducted. Theoretical NMR chemical shifts, the relative energies and natural bond orbital (NBO) analysis are calculated within the DFT approach, while the singlet excited state energies and HOMO–LUMO energy gap were calculated with time-dependent density functional theory (TD-DFT). The electrophilic f− and nucleophilic f+ Fukui functions are well adapted to find the electrophile and nucleophile centres in the molecules. Both (1,3-selenazol-2-yl)- and (1,3-thiazol-2-yl)hydrazone Co(III) complexes showed potent antimicrobial and antioxidant activity. A significant difference among them was a smaller cytotoxicity of selenium compounds.

Chromium(III), manganese(II) and iron(III) complexes based on hydrazone Schiff-base and azide ligands: synthesis, crystal structure and antimicrobial activity

Abstract: A tridentate NNO donor hydrazine Schiff base, HL, was obtained from condensation of pyridine 2-carbaldehyde and 4-hydroxy benzohydrazide. HL and azide ligands with Cr(III), Mn(II) and Fe(III) have been used to synthesize [Cr(L)(N3)(OCH3)]2 (1), [Mn(HL)2(N3)2] (2), and [Fe(L)(N3)(OCH3)]2·H2O (3). HL is quite diverse in its chelating ability and can be a neutral or monoanionic ligand as a tridentate unit. In this paper, we report structures showing different denticities of the ligand having different charges. The ligand 1–3 was characterized by elemental analysis, FT-IR, and UV–vis spectral studies and solid-state structures were determined by single-crystal X-ray diffraction analysis, revealing that 1 and 3 are binuclear, while 2 is mononuclear. The efficiencies of the ligand and the three complexes were evaluated for antimicrobial activity; MIC data revealed that HL 1–3 are not strongly active in comparison to standard drugs.

Fluoran salicylaldehyde hydrazone Zn(II) complexes: reversible photochromic systems both in solution and in a solid matrix

Abstract: Fluoran dyes have been widely used as chromogenic reagents in piezochromic and thermochromic materials due to their intrinsic halochromic properties. However, reports on fluoran-based photochromic materials are still rare. In this work, a series of fluoran salicylaldehyde hydrazone Zn(II) complexes (1-Zn, 2-Zn and 3-Zn) were facilely prepared. The complexes exhibited excellent reversible photochromism with remarkable fatigue resistance both in solution and in a solid matrix. Due to the multiple colors of the fluoran parts, these complexes exhibited different colors after UV light irradiation. Particularly, a black color was obtained for 3-Zn, which is relatively infrequent because black photochromism systems are still very uncommon. The photochromic mechanism was proposed, where the tautomerism from the enol form to the keto form in the salicylaldehyde hydrazone moiety was induced by UV light irradiation, accompanied by a spirolactam ring-opening reaction and yielding colored products. A smaller group adjacent to the spirolactam ring was favorable for the stability of the colored products. The influences of different metal ions and solvents on the photochromism of these complexes were also studied. Moreover, patterns were successfully visualized in thin layer silica gel that was impregnated with the complexes after UV light irradiation, which suggested that they can be promising candidates for photo-patterning.

Visible-light mediated directed perfluoroalkylation of hydrazones

Abstract: Perfluoroalkylation of N-alkylhydrazones has been achieved via visible light mediated photoredox reactions between the hydrazone and perfluoroalkyl iodide (RfI). This protocol provides a convenient and efficient access to a series of perfluoroalkylated aromatic aldehyde hydrazones which tolerates a wide range of functional groups on the aromatic ring, and allows the use different types of primary and secondary perfluoroalkyl iodides with up to eight carbon atoms. Furthermore, aliphatic aldehyde hydrazones and N-monosubstituted hydrazones which are unreactive in previously reported hydrazone perfluoroalkylation reactions now take part in the reaction under our reaction conditions to give a satisfactory yield of products. Stern–Volmer quenching studies and spin-trapping experiments indicated that these reactions proceed by free radical addition of the Rf radical to the azomethine atom followed by one electron oxidation of the hydrazyl radical and deprotonation of the diazenium cation.

Hydrazone Linker as a Useful Tool for Preparing Chimeric Peptide/Nonpeptide Bifunctional Compounds.

Abstract: The area of multitarget compounds, joining two pharmacophores within one molecule, is a vivid field of research in medicinal chemistry. Not only pharmacophoric elements are essential for the design and activity of such compounds, but the type and length of linkers used to connect them are also crucial. In the present contribution, we describe compound 1 in which a typical opioid peptide sequence is combined with a fragment characteristic for neurokinin-1 receptor (NK1R) antagonists through a hydrazone bridge. The compound has a high affinity for μ- and δ-opioid receptors (IC50= 12.7 and 74.0 nM, respectively) and a weak affinity for the NK1R. Molecular modeling and structural considerations explain the observed activities. In in vivo test, intrathecal and intravenous administrations of 1 exhibited a strong analgesic effect, which indicates potential BBB penetration. This letter brings an exemplary application of the hydrazone linker for fast, facile, and successful preparation of chimeric compounds.

Photochemical and Electrochemical Triggered Bis(hydrazone) Switch

Abstract: Herein, we report the synthesis of a double hydrazone capable of undergoing photochemical E/Z isomerization through the imine double bonds. The bis(hydrazone) 1-E,E can be considered as a "two-arm" system in which the controlled movement of each arm is obtained by photo-modulation, making possible the appearance of two isolable metastable isomeric states 1-E,Z and 1-Z,Z. Such states are characterized by very specific structural, optical, and electrochemical properties. The latter allows the reversible return from either 1-E,Z or 1-Z,Z to the 1-E,E state. Our results are of great importance in the further development of molecular machines and photochemically controlled reactions by introducing for the first time double hydrazones as tunable photochemical switches.

Multicomponent Synthesis of Some Molecular Hybrid Containing Thiazole Pyrazole as Apoptosis Inducer.

Abstract: The present study describes a multicomponent synthesis of molecular hybrid containing pyrazole, thiazole moiety using hydrazone as a linker, which have been synthesized by condensation of 1-phenyl-3-(aryl)-1H-pyrazole-4-carbaldehydes 1A-B: , thiosemicarbazide and α-bromoketones 2A-C: .The target hybrid compounds, 1-((1-phenyl-3-aryl-1H-pyrazole-4-yl)methylene)-2-(4-arylthiazole-2-yl)hydrazine 3A-F: are characterized by 1H-NMR, 13C NMR, FT-IR and mass. Apoptosis inducing ability and cytotoxic nature of all the hybrid compounds having thiazole, pyrazole and hydrazone were assessed by using biological assays viz morphological, fluorescence and tunel assays on granulosa cells of ovarian antral follicles of goat (Capra hircus) in vitro. Apoptosis was recognized and quantified using differential staining of ethidium bromide and acridine orange where apoptotic cells exhibited red fluorescence and live normal cells with intact cell membrane and normal nucleus displayed bright green fluorescence. Among the tested compounds, compound 3E: and 3B: showed the maximum potency to induce apoptosis with percentage of apoptosis 25.61±2.95and 23.45±1.46 respectively followed by 3F: (20.95±0.40) and 3D: (20.44±1.60) in comparison with control (5.14±0.44).

Fluorescence chemosensor properties of two coumarin-based compounds for environmentally and biologically important Al3+ ion

Abstract: In this study, two novel coumarin-based compounds called 2-Acetylpyrazine (coumarin-3'-formyl) hydrazone (1) and 2-Acetylpyrazine (7'-diethylaminocoumarin-3'-formyl) hydrazone (2) have been designed, synthesized and characterized. Compound I showed higher selectivity and sensitivity for Al3+ over other environmentally and biologically important metal ions than compound 2, and a remarkable enhancement of compound 1 in fluorescence emission intensity at 486 nm with a large red-shift was observed in the presence of Al3+. This phenomenon was attributed to the inhibition of the photoinduced electron-transfer (PET) process upon complexation of 1 with Al3+. Thus, compound 1 could be used as a fluorescent sensor for Al3+. (C) 2016 Elsevier B.V. All rights reserved.