Strecker reaction and α-amino nitriles: Recent advances in their chemistry,synthesis, and biological properties

α-Amino nitrile compounds have a profound impact on bio-chemical sciences, as they have been prepared from inexpensive starting materials and have become valuable intermediates in the chemical synthesis of vitally important heterocyclic and carbocyclic molecules, which serve as suitable models in pharmacological and biological research. The α-amino nitrile moiety has been found in the structure of different alkaloids, while the α-amidoacetonitrile group is an essential fragment of new anti-hyperglycemic drugs and promising pharmacological and agrochemical agents. Due to their synthetic, biological and practical importance, this review highlights the recent information about the preparation of α-amino nitriles through the Strecker-type and α-cyanation reactions, their chemical and biological properties, as well as their synthetic application, paying attention on the wonderful capacity for generating novel molecular diversity for pharmacological, biological and agrochemical researches, which ends with the total synthesis of complex alkaloids, preparation of new N-heterocycles and α-aminonitrile-containing drugs. Analyzing modern synthetic protocols for the Strecker-type reactions and cyanation reactions based on cross-dehydrogenative coupling (CDD) process, the advantages and disadvantages of new catalysts and green reaction conditions are also discussed. In addition, remarkable biological properties of α-amidoacetonitrile derivatives as potent and selective protease inhibitors as well as promising pesticidal agents were briefly reviewed. The bibliography includes 461 references.     

Microgel,nanogel and hydrogel–hydrogel semi-IPN composites for biomedical applications: synthesis and characterization

Quaternary ammonium salt hydrogels from a cationic monomer, (3-acrylamidopropyl)-trimethylammonium chloride (APTMACl), in a variety sizes such as bulk, micro- and nano- has been prepared. The synthesis of micro- and nanogels were carried out in the microenvironment of water-in-oil microemulsions using two types of surfactants, namely, L-α- phosphatidylcholine (lecithin) and dioctyl sulfosuccinate sodium salt (AOT). Additionally, hydrogel–hydrogel composite semi-interpenetrating polymer networks (semi-IPN) was synthesized by dispersing previously prepared micro/nanogel into neutral monomers such as acrylamide (AAm) or 2-hydroxylethyl methcarylate (HEMA) before network formation. Hydrogel swelling and pH response behaviors have been investigated for bulk gels. Morphology, structure, and size of nano-, micro- and bulk materials were explored utilizing transmission electron microcopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was confirmed with gel electrophoresis that completely charged nanogel form a strong complex with DNA.     

Heteropolymolybdate–amino acid complexes: synthesis,characterization and biological activity

Three Keggin-type polyoxometalates functionalized by amino acids, (C₅H₁₃N₂O₂)₂(H₃O)PMo₁₂O₄₀·8H₂O 1, (C₅H₁₄N₂O₂)₂SiMo₁₂O₄₀·12H₂O 2 and (C₅H₁₄N₂O₂)₂GeMo₁₂O₄₀·12H₂O 3, were synthesized and characterized by elemental analysis, IR and ¹H?NMR spectra and single-crystal X-ray diffraction. The X-ray crystallographic study showed that the structures of the three compounds involved N–H···O and O–H···O hydrogen bonds among the protonated ornithine cations, water molecules and the heteropolyanion cluster, and thus represent a model interaction between polyoxometalates and proteins. These complexes display inhibitory actions to the human cancer cells Hela and PC-3?m in vitro.     

New saccharinate complexes with 3,3′-azobispyridine ligand: synthesis,characterization, and spectroscopic properties

The new metal complexes with saccharinate (sac) and 3,3′-azobispyridine (3,3′-abpy), [Ni(H₂O)₄(3,3′-abpy)₂](sac)₂ (1), [Cu(sac)₂(H₂O)(μ-3,3′-abpy)]_n (2), [Zn(H₂O)₄(3,3′-abpy)₂](sac)₂ (3), [Cd(sac)₂(H₂O)₂(μ-3,3′-abpy)]_n (4), and [Hg₂(μ-sac)₂(sac)₂(μ-3,3′-abpy)(3,3′-abpy)₂]_n (5), were synthesized and characterized by IR spectra, elemental analysis, and single-crystal X-ray diffraction. Spectroscopic (UV–vis and photoluminescence) and thermal properties were also investigated. Single-crystal X-ray analysis reveals that Ni(II) and Zn(II) are coordinated by four aqua ligands and two nitrogens of 3,3′-abpy, while sac is a counter-ion in 1 and 3. In 2, Cu(II) and all ligands are linked by coordination bonds and 3,3′-abpy ligands connect the Cu(II) centers forming a 1-D coordination polymer. In 4, sac N-coordinated to Cd(II) and distorted octahedral geometry of Cd(II) ion is completed by two aqua and bridging 3,3′-abpy ligands. In 5, sac bridges two Hg(II) ions to generate dinuclear [Hg₂(μ-sac)₂] units. These dinuclear units are connected by 3,3′-abpy to form a 1-D coordination polymer. The photoluminescence spectra of 3 and 5 show blue fluorescent emission bands, and these emissions can probably be assigned to intraligand fluorescent emissions. Thermal decompositions of the compounds are also discussed. For all complexes, magnetic susceptibility measurements show expected magnetic behavior.     

Pigments with improved properties – microreaction technology as a new approach for synthesis of pigments –

Clariant, as an important pigment producer forces the investigation of new pigments with improved qualities and properties to fulfill the rising tomorrow's demands of customers. For these reasons, new production ways like microreaction technology are included. This paper focuses on results obtained in manufacturing pigments in a lab-scale microreactor as well as in a microreactor pilot plant. Investigations of the diazotation, azo-coupling and laking steps of pigments have shown not only the principle feasibility of these reactions in laboratory microreactors but also significant improvement of coloristic properties. The microreactor pilot plant, realized by the concept of numbering-up instead of conventional scaling-up process, allowed more detailed investigations of the complete azo-pigments synthesis under production conditions.     

Mononuclear copper(I) complexes with triphenylphosphine and N,N′-disubstituted thioureas: synthesis,characterization, and biological evaluation

Abstract

Twelve new complexes, of the general formula CuCl(TPP)₂Tu^1–12 (Tu?=?thiourea), were synthesized by the reaction of CuCl(TPP)₃ (TPP?=?triphenylphosphine) and various N,N′-disubstituted thioureas. The structures of the synthesized complexes were characterized by different techniques such as Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy (¹H, ¹³C, ³¹P, and ¹⁹F), and the representative complexes (1, 2 and 12) were analyzed via single crystal X-ray diffraction. The single crystal X-ray analysis revealed that copper(I) is coordinated with chlorine, two TPP, and the thiourea ligands through the sulfur atom in a mononuclear distorted tetrahedral mode. The compounds were tested for antibacterial, antifungal, cytotoxicity, antileishmanial, and antioxidant activities. The results showed that the synthesized complexes are significantly more active than the free ligands and the commercial reference compounds. The high biological activities of the complexes versus free ligands can be attributed to the copper(I) chloride complexation with thiourea ligands. The synthesized complexes were also evaluated, both experimentally and theoretically, for DNA binding studies. The UV-visible spectroscopic and molecular docking studies demonstrated that the complexes are conjugating with DNA through a groove binding mode.     

Synthesis,characterization, and biological studies of lanthanide complexes with 2,6-pyridine dicarboxylic acid and α-picolinic acid

Four new solid ternary complexes of lanthanide with 2,6-pyridine dicarboxylic acid and α-picolinic acid [Ln(DPA)(L^α)(H₂O)] · 2H₂O (Ln = La³⁺, Ce³⁺, Eu³⁺, or Gd³⁺; DPA = 2,6-pyridine dicarboxylic acid; HL^α = α-picolinic acid) have been synthesized and characterized by elemental analysis, molar conductance, FT-IR, UV–Vis, and TG–DTA. The antibacterial activities indicate that all the complexes exhibit antibacterial ability against Escherichia coli and Staphylococcus aureus with broad antimicrobial spectra. The anticancer activity of the La complex against K562 tumor cell in vitro is measured using methyl thiazolyl tetrazolium (MTT) colorimetry and flow cytometry. The La complex can induce K562 tumor cell apoptosis, presenting the best apoptosis effect by acting on the S period after inducing K562 tumor cell for 72 h.     

Case synthesis of a β-chloro bulky bis-pocket corrole: Crystallographic characterization and photophysical properties

A new bulky 2-chloro-5,10,15-tris(2,4,6-triphenylphenyl)-corrole was casually synthesized and the effect of mono-β-chlorination on its photophysical, electrochemical properties and light-induced singlet oxygen generation was investigated.     

Copper complexes of pyridyl–tetrazole ligands with pendant amide and hydrazide arms: synthesis,characterization, DNA-binding and antioxidant properties

Pyridyl–tetrazole ligands 2-(5-(pyridin-2-yl)-1H-tetrazol-1-yl)acetamide (L1), 2-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)acetamide (L2), 2-(5-(pyridin-2-yl)-1H-tetrazol-1-yl)acetohydrazide (L3) and 2-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)acetohydrazide (L4) have been prepared and coordinated with CuCl₂·2H₂O to furnish the corresponding complexes [Cu(L1) ₂ ]–[Cu(L4) ₂ ]. EPR spectra of the complexes are characteristic of square planar geometries, with nuclear hyperfine spin 3/2. DNA-binding studies using UV–Vis absorption spectroscopy, viscosity and thermal denature studies revealed that all of these complexes are avid binders of calf thymus DNA. The antioxidant properties of the free ligands and the Cu(II) complexes were investigated using the p-nitrosodimethyl aniline hydroxyl radical scavenging method, and [Cu(L4) ₂ ] was found to show the highest activity.     

Preparation,characterization and electrical transport properties of individual α-MnO2 and β-MnO2 nanorods

Electrical transport experiments are performed on individual α-MnO₂ and β-MnO₂ nanorods. Both of α-MnO₂ and β-MnO₂ nanorods are synthesized via hydrothermal routes. A three-region method is used to analyze their nonlinear current–voltage characteristics. Under low biases, the effective contact barrier height is roughly estimated to be 0.05 eV for α-MnO₂ and 0.15 eV for β-MnO₂, respectively. As the applied bias is high enough, the contact barriers are significantly tilted and the current is largely tunneling. The conductance of α-MnO₂ and β-MnO₂ nanorods at room temperature is roughly estimated to be 5.98 and 1.74 × 10^?3 cm^?1 Ω^?1, respectively. And the thermal-activation energy is roughly estimated to be 0.047 and 0.226 eV, respectively. Our results are probably the bases for their applications in nanosized electrical devices.     

Supramolecular engineering of a 2D Kagomé lattice: synthesis, structures, and magnetic properties

Two 2D Mn (II) complexes, [Mn3(TzDC)2(phen)3] x 2 H2O (1; H3TzDC = 1,2,3-triazole-4,5-dicarboxylic acid, phen = 1,10-phenanthroline) and [Mn3(TzDC)2(bipy)3] x 4 H2O (2; bipy = 2,2'-bipyridine), were synthesized by hydrothermal reactions and characterized magnetically, and complex 1 was the first example of the chiral complex with a Kagomé lattice connectivity obtained through spontaneous resolution.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

A synthesis of esters, amides, and sulfones bearing a 1-cyclopentenyl group at the α-position from cyclobutanones with one-carbon ring-expansion

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from cyclobutanones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters, lithium enolate of carboxylic acid N,N-dimethylamides, or lithium α-carbanion of alkyl phenyl sulfones gave adducts in high yields. The adducts were treated with isopropylmagnesium chloride or ethylmagnesium chloride in dry toluene to give esters, amides, and sulfones bearing a 1-cyclopentenyl group at the α-position in moderate to good yields with one-carbon ring-expansion via magnesium carbenoid 1,2-CC insertion reaction. The magnesium carbenoid 1,2-CC insertion reaction proved to be highly stereospecific. The reaction mechanism and origin of the specificity are described.     

Pd-catalyzed regioselective hydroarylation of α-(2-aminoaryl)-α,β-ynones with organoboron derivatives as a tool for the synthesis of quinolines: experimental evidence and quantum-chemical calculations

The Pd-catalyzed hydroarylation of β-(2-aminoaryl)-α,β-ynones with organoboron derivatives, leading to 2,4-diarylquinolines in good to excellent yields through sequential cycloamination, has been investigated. The reaction is catalyzed by both Pd(II) and Pd(0) precatalysts, and can be carried out even under neutral conditions. The regiochemical outcome is inverted with respect to the Pd-catalyzed hydroarylation of β-(2-aminoaryl)-α,β-ynones with aryl iodides. This aspect has been rationalized using quantum-chemical calculations, which show significant differences between the energy barriers of the regioisomeric transition states for the migratory insertion (hydropalladation) step, and are consistent with the charge density of the π complex that undergoes such insertion.     

The synthesis,characterization, and theoretical hydrogen gas adsorption properties of copper(II)-3,3′-thiodipropionate complexes with imidazole derivatives

Three new coordination polymers, [Cu(μ₃-tdp)(im)₂]_n (1), {[Cu(μ₃-tdp)(1-mim)₂]·0.5H₂O}_n (2) and {[Cu₂(μ₃-tdp)₂(4-mim)₄]·H₂O}_n (3) [tdpH₂ = 3,3′-thiodipropionic acid, im = imidazole, 1-mim = 1-methylimidazole and 4-mim = 4-methylimidazole], have been prepared and characterized by spectroscopic techniques (IR and UV–Vis), elemental analyzes, magnetic measurements, thermal analyzes, and single-crystal X-ray diffraction. Complexes 1–3 crystallize in the monoclinic system with space groups of C2/c and P2₁/c, respectively. In 1–3, tdp is a bridging ligand to form 1-D chains, which are extended into a 2-D layer by hydrogen bonding and π···π interactions. The 3,3′-thiodipropionate exhibits an unexpected coordination mode in 1–3. Simulations were used to assess the potential of the complexes in H₂ storage applications.     

Single-crystalline α-Fe2O3 with hierarchical structures: Controllable synthesis, formation mechanism and photocatalytic properties

A dual iron precursors system in a hydrothermal process was developed for controllable fabrication of α-Fe₂O₃ hierarchical structures with different morphologies. Micro-pines, snowflakes and bundles were successfully synthesized simply by tuning the total concentration of the two iron precursors K₄[Fe(CN)₆] and K₃[Fe(CN)₆] and their molar ratio. The obtained α-Fe₂O₃ hierarchical structures were characterized using field-emission scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy and energy-dispersive X-ray analysis. The effect of experimental conditions on the morphologies of the α-Fe₂O₃ crystals was systematically investigated. A possible formation mechanism of different α-Fe₂O₃ hierarchical structures was proposed. Good photocatalytic properties were observed for all the hierarchical structures.     

Cationic olefin Pd(II) complexes bearing α-iminoketone N,O-ligands: synthesis, intramolecular and interionic characterization and reactivity with olefins and alkynes

Complexes [Pd(η¹, η²-5-OMe-C₈H₁₂)(N,O)]BF₄ (N,O=2,6-(i-Pr)₂(C₆H₃)NC(Ph)-C(Ph)O, 1; 2,6-(i-Pr)₂(C₆H₃)NC(Me)-C(Ph)O, 2; 2-benzoylpyridine, 3) were synthesized by the reactions of [Pd(η¹,η²-5-OMe-C₈H₁₂)Cl]₂ with the suitable N,O-ligand. They were tested as catalysts for olefin or alkyne polymerizations. During such reactions 1-3 quantitatively transformed into their η¹,η²-1-OMe-C₈H₁₂ isomers (1a-3a). The same isomerization occurred in methylene chloride, even in the absence of olefins or alkynes, with a much slower rate. All complexes were fully characterized in solution by multinuclear and multidimensional low temperature NMR spectroscopy. The solid state structures of complexes 1 and 1a were investigated by X-ray single crystal studies. ¹⁹F, ¹H-HOESY NMR experiments carried out in methylene chloride-d₂ at 217 K indicated that the anion prefers to locate on the side of N,O-ligand shifted toward the O-arm in 1-1a and 2-2a while it approaches the N-arm in 3 and 3a compounds.     

Hydrothermal synthesis,characterization and properties of a d10 metal coordination polymer with a layered structure based on carboxyphosphinate ligand, 4,4′-bipyridine and four-coordinated zinc ion

Abstract

Hydrothermal reaction of Zn(NO₃)₂ · 6?H₂O with 2-carboxyethyl(phenyl)phosphinate (H₂L) and 4,4'-bipyridine (4,4′-bipy) led to a novel zinc(II) carboxyphosphinate [ZnL(4,4′-bipy)_0.5]_n (1). The zinc ion is tetrahedrally coordinated by two phosphinate oxygen atoms, one carboxylate oxygen atom, and one nitrogen atom of 4,4′-bipy ligand. The L^2- ligand and zinc ion can be seen as three- and four-connected nodes, respectively. Compound 1 shows a layered network with (3,4)-connected topology. It exhibits a broad blue fluorescent emission band at 459?nm, which can be attributed to 4,4′-bipy intraligand emission as well as to H₂L emission. It is a diamagnetic system between 300?K and 11?K.     

Cadmium(II) complexes of 5-nitro-salicylaldehyde and α-diimines: synthesis,structure and interaction with calf-thymus DNA

Five Cd(II) complexes with the anion of 5-NO₂-salicylaldehydeH (5-NO₂-saloH) in the absence or presence of the α-diimine 1,10-phenanthroline (phen), 2,2′-dipyridylamine (dpamH), 2,2′-dipyridine (bipy), or 2,9-dimethyl-1,10-phenanthroline (neoc) were synthesized and characterized as [Cd(5-NO₂-salo)₂(CH₃OH)₂] (1), [Cd(5-NO₂-salo)₂(phen)]·2CH₃OH·H₂O (2), [Cd(5-NO₂-salo)₂(dpamΗ)] (3), [Cd₃(5-NO₂-salo)₆(bipy)₂] (4), and [Cd(5-NO₂-salo)(neoc)(NO₃)]₂ (5). Based on spectroscopic results (IR, UV, NMR), elemental analysis and conductivity measurements an octahedral geometry around cadmium metal ion is suggested, with the 5-NO₂-salicylaldehyde ligand having different coordination modes. The structures determined by X-ray crystallography verified neutral mononuclear 1–3 and trinuclear 4. Simultaneous TG/DTG–DTA technique was used to analyze the thermal behavior of 1, 2, and 3. The complexes bind tightly to calf-thymus DNA mainly by intercalation, as concluded by DNA viscosity measurements and exhibit significant displacement of EB from the EB-DNA complex.