Four-step Reaction Research Articles

An Efficient and Concise Synthesis of N-3-Substituted 9-Methoxy-4H-[1]-benzopyrano[2,3-d]pyrimidine-4(5H)-imines and Form­amidine Derivatives from Methyl N-(3-Cyano-8-methoxy-4H-[1]-benzopyran-2-yl)methanimidate

A four-step microwave-assisted reaction of N-3-susbstituted 4H-[1]-benzopyrano[2,3-d]pyrimidine-4(5H)-imines and formamidine derivatives was successfully developed from primary amines, cyclic secondary amines, and methyl N-(3-cyano-8-methoxy-4H-[1]-benzopyran-2-yl)methanimidate as key intermediate. The simplicity of the microwave protocols gave facile possibilities of isolation of the desired products by simple filtration. The synthesized compounds were obtained in good yields and purity, and characterized by 1H, 13C NMR, IR, and HRMS analyses.

Synthesis and Properties of Aza-ullazines.

A range of aza-ullazines, which represent a new heterocyclic core structure, were synthesized through a scalable four-step reaction, including a Sonogashira reaction and metal-free cyclization promoted by p-toluenesulfonic acid. The optical and electrochemical properties of selected derivatives were investigated, they were found to have similar absorption and emission spectra but a higher oxidation potential than the parent ullazine core.

No Strain, No Gain? Enzymatic Ring‐Opening Polymerization of Strainless Aliphatic Macrolactones

Starting from readily available oleic and erucic acid, macrocyclic nonadecalactone (C19 ) and tricosalactone (C23 ) can be synthesized in polymerization grade purity in a four-step reaction sequence. Ring-opening polymerization (ROP) of these strainless macrolactones can be performed utilizing an enzyme as a catalyst. Despite the missing ring-strain as key driving force for smaller (strained) lactones, high molar masses (Mn ≈ 105 g mol-1 ) can be accessed in an entropically driven ROP. Polyester-19 and polyester-23 prepared feature melting temperatures well above 100 °C. Further analysis of the mechanical properties of these materials displays the resemblance to polyethylene. For example, Young's moduli on the order of 600 MPa are observed as a result of the high crystallinity of the polymer.

Insights on hydride formation over cerium-gallium mixed oxides: A mechanistic study for efficient H2 dissociation

A four-step reaction mechanism is proposed for the H2 dissociation over pure ceria and gallium-promoted mixed oxide materials, in a combined experimental and computational investigation. Two samples of cerium-gallium mixed oxides with Ce/Ga atomic ratios equal to 90/10 and 80/20 were studied by time-resolved diffuse reflectance infrared spectroscopy under H2 (D2) flow at isothermal condition in the range of 523–623K. X-ray photoelectron spectrometry allowed to conclude that only Ce4+ is reduced to Ce3+ (Ga3+ is not reduced), in agreement with density functional theory (DFT) results. The time evolution profiles of gallium hydride (GaH) species, hydroxyl groups (OH) and Ce3+ infrared signals were analyzed and kinetic rate parameters for each step were obtained by mathematical modeling. The values for activation energies were in agreement with those calculated by DFT, for the different elementary pathways. A small activation energy (∼4kcal/mol) was found for H2 dissociation found on Ga⋯OCe sites assuming that the heterolytic cleavage of the HH bond is the rate determining step. On pure ceria, the experimental activation energy is ∼23kcal/mol, showing that the addition of Ga3+ cations boosts the splitting of H2. Interestingly, the reduction step of pure CeO2 surface domains seems to proceed via a CeH/OH pair intermediate, according to DFT calculations. Moreover, 71Ga NMR experiments indicate the possible presence of gallia nanodomains. It is proposed that the generation of Ga⋯OCe sites in the perimeter of such surface gallia nanodomains is responsible for the enhanced reactivity of the mixed materials. The key role of this new type of sites to improve the efficiency of relevant catalytic reactions such as selective alkyne hydrogenation and light alkane dehydrogenation is then analyzed.

Enantioselective Organocatalytic Synthesis of 2-Oxopiperazines from Aldehydes: Identification of the Elusive Epoxy Lactone Intermediate.

An organocatalytic linchpin catalysis approach was envisaged to convert simple aldehydes into enantioenriched 2-oxopiperazines. A four-step reaction sequence (chlorination, oxidation, substitution, and cyclization) was developed and led to different substitution patterns in high yields and selectivities. The reaction mechanism was studied, and the previously elusive epoxy lactone intermediate was identified by HRMS.

Preparation, evaluation, and application of a novel reversed-phase/zwitterionic/hydrophilic interaction liquid chromatographic mixed-mode stationary phase

ABSTRACTThe present study described the preparation and application of a reversed-phase/zwitterionic/hydrophilic interaction liquid chromatography stationary phase, named as SIL-PS. The SIL-PS was prepared through a four-step reaction, chemical bonding, nucleophilic addition, SN1 substitution, and sulfonation on the silica matrix. It was featured with C12 alkyl chain, quaternary ammonium, tertiary amine, and sulfonate groups. After SIL-PS was packed into the stainless steel column (150 × 2.1 mm i.d.), chromatographic parameters, including acetonitrile content, pH, and ionic strength of the mobile phase, and the column temperature, were systematically investigated to study the retention mechanism. Electrostatic adsorptive/repulsive, partition, and hydrogen-bonding interactions were demonstrated to contribute to the retention. The stability of the SIL-PS was satisfactory, with relative standard deviations of retention factors of 1.93, 2.08, and 1.90% for loxoprofen, adenosine, and liquiritin, respectively. Additionally, to investigate the separation selectivity, the non-steroidal anti-inflammatory drugs, nucleobases/nucleotides, and alkaloids/glycosides were separated; the HPLC fingerprinting of the Cortex phellodendri extract was also conducted, and the separation performance was superior to that of the C18 column in terms of peak shape, resolution, and analytical time. The results revealed that the prepared SIL-PS possessed multifunctionalities for multiretention and could be promising for complicated samples.

Ochratoxin A Detection on Antibody- Immobilized on BSA-Functionalized Gold Electrodes.

Ochratoxin A (OTA)—a toxin produced by Aspergillus carbonarius, Aspergillus ochraceus, and Penicillium verrucosum—is one of the most-abundant food-contaminating mycotoxins. To avoid the risk of OTA consumption for humans and animals, the rapid detection and quantitation of OTA level in different commodities are of great importance. In this work, an impedimetric immunosensor for ochratoxin A (OTA) detection, a common toxic botanical contaminant, was developed via the immobilization of anti-OTA antibody on bovine serum albumin modified gold electrodes. A four-step reaction protocol was tested to modify the gold electrode and obtain the sensing substrate. All the steps of the immunosensor elaboration and also the immunochemical reaction between surface-bound antibody and ochratoxin A were analyzed using cyclic voltammetry and electrochemical impedance spectroscopy. Modification of the impedance due to the specific antigen-antibody reaction at immunosensor surface, was used in order to detect ochratoxin A. Linear proportionality of the charge transfer resistance to the concentration of OTA allows ochratoxin A detection in the range of 2.5–100 ng/mL.

Graphdiyne-supported single-atom Sc and Ti catalysts for high-efficient CO oxidation

Single-layer graphdiyne was proposed as substrate for single-atom Sc and Ti catalysts with much larger binding energy and higher thermal migration barrier than graphene. By density functional theory calculations, the electronic properties, thermal stabilities and catalytic abilities of Sc and Ti adatoms on single-layer graphdiyne were theoretically investigated. The results indicate that the C sites on graphdiyne surface are the most stable binding sites for Sc and Ti adatoms. The high migration barrier prevents the aggregation of Sc and Ti adatoms on graphdiyne surface. On graphdiyne-Sc or graphdiyne-Ti, CO could be catalytically oxidated by a four-step reaction. The reaction is both energetically and kinetically favorable with low potential barriers. Overall, Sc and Ti adatoms on single-layer graphdiyne would be excellent catalysts for CO oxidation.

Molybdenum oxide reduction using syngas and heat from an inert porous media reactor

A method of molybdenum oxide (MoO3) reduction using both the heat released and gaseous products from hydrocarbon fuels partial oxidation (H2 and CO) in a novel inert porous media reactor is studied. The numerical approach considered a two-temperature model for filtration combustion of methane with a four-step reaction mechanism to solve temperature, H2 and CO production, and MoO3 reduction through shrinking core model. A maximum for molybdenum oxide reduction was found with an increasing equivalence ratio (ϕ). Use of propane resulted in a low reduction degree and a maximum temperature of 641 K for the molybdenum oxide powder. SEM and XRD analysis were conducted on the tested powders. Empirical data predicts a favorable reduction degree for the new reactor proposed.

Structure of NDP-forming Acetyl-CoA synthetase ACD1 reveals a large rearrangement for phosphoryl transfer

The NDP-forming acyl-CoA synthetases (ACDs) catalyze the conversion of various CoA thioesters to the corresponding acids, conserving their chemical energy in form of ATP. The ACDs are the major energy-conserving enzymes in sugar and peptide fermentation of hyperthermophilic archaea. They are considered to be primordial enzymes of ATP synthesis in the early evolution of life. We present the first crystal structures, to our knowledge, of an ACD from the hyperthermophilic archaeon Candidatus Korachaeum cryptofilum. These structures reveal a unique arrangement of the ACD subunits alpha and beta within an α2β2-heterotetrameric complex. This arrangement significantly differs from other members of the superfamily. To transmit an activated phosphoryl moiety from the Ac-CoA binding site (within the alpha subunit) to the NDP-binding site (within the beta subunit), a distance of 51 Å has to be bridged. This transmission requires a larger rearrangement within the protein complex involving a 21-aa-long phosphohistidine-containing segment of the alpha subunit. Spatial restraints of the interaction of this segment with the beta subunit explain the necessity for a second highly conserved His residue within the beta subunit. The data support the proposed four-step reaction mechanism of ACDs, coupling acyl-CoA thioesters with ATP synthesis. Furthermore, the determined crystal structure of the complex with bound Ac-CoA allows first insight, to our knowledge, into the determinants for acyl-CoA substrate specificity. The composition and size of loops protruding into the binding pocket of acyl-CoA are determined by the individual arrangement of the characteristic subdomains.

X-ray Molecular Structure of ({[(1E)-3-(1<i>H</i>-Imidazol-1-yl)-1- phenylpropylidene]amino} oxy)(3,4,5-trimethoxyphenyl)- methanone: A Potential Anti-<i>Candida</i> Agent

Purpose: To elucidate the solid-state conformation as well as the imine double bond configuration of a potential anti-Candida agent ({[(1E)-3-(1H-imidazol-1-yl)-1-phenylpropylidene]amino}oxy)(3,4,5trimethoxyphenyl)methanone. Methods: Acetophenone was used as a starting material to prepare the target oximino ester in a fourstep reaction sequence. Nuclear magnetic resonance ( 1 H-NMR and 13 C-NMR) and mass spectrometry were used to confirm the chemical structure of the synthesized compounds. Thereafter, x-ray crystallography was performed on single crystals of the target compound. The solid-state conformation of the target molecule and the (E)-configuration of its imine double bond were determined via the investigation of its single crystal x-ray molecular structure. Results: The titled compound crystallized in the triclinic space group P-1 with a = 11.0719 (7) A, b = 14.6602 (9) A, c = 14.8530 (9) A, α = 67.205 (4)°, β = 80.388 (5)o, γ = 70.100 (5)°, V = 2088.2 (2) A 3 , and Z = 4. Individual molecules were packed in the crystal by three weak non-classical intermolecular hydrogen interactions, including C9A—H9AA•••O3A, C9B—H9BA•••O3B, C18B—H18C•••O2A and C20B—H20B•••O4B. Conclusion: The results of the single crystal x-ray molecular structure of the titled anti-Candida agent unequivocally confirmed its (E)-configuration.

Core-shell composite of hierarchical MoS2 nanosheets supported on graphitized hollow carbon microspheres for high performance lithium-ion batteries

In this work, a core-shell composite composed of MoS2 nanosheets grown on hollow carbon microspheres is synthesized by a hydrothermal and a subsequent annealing route. The result shows that well-graphitized hollow-carbon@highlycrystallineMoS2(HC@MoS2) was obtained after the four-step reaction. And it is found that the synthesized MoS2 is consist of 2H and 1T phases. The lithium storage property of the composite is investigated as an anode material for lithium-ion batteries. Benefited from the special morphology and structure, a stable capacity of 970mAhg−1 for over 100 cycles at a current density of 0.25Ag−1 is realized on the material. Even at a high current density of 4Ag−1, a reversible capacity as high as 560mAhg−1 is delivered. Moreover, the reasons for the excellent electrochemical performance of the material are explored and discussed in detail.

Single-Crystal X-ray Structure of Anti-<i>Candida</i> Agent, (E)-3- (1H-Imidazol-1-yl)-1-Phenylpropan-1-one O-3- Chlorobenzoyl Oxime

Purpose: To determine the conformation as well as imine double bond configuration of the anti- Candida oximino ester, 3-(1H-imidazol-1-yl)-1-phenyl- propan-1-one O-3-chlorobenzoyl oxime.Methods: The titled compound was synthesized in a four-step reaction sequence using acetophenone as a starting material. Spectral analysis, viz, nuclear magnetic resonance (1H NMR and 13C NMR spectroscopy) and mass spectrometry (MS) confirmed the chemical structure of the synthesized compounds. Subsequently, single crystals of the titled compound were subjected to x-ray crystallographic analysis.Results: The single crystal x-ray crystallography of the investigated anti-Candida agent revealed its conformation and the (E)-configuration of its imine double bond. The titled compound crystallizes in the monoclinic space group P21/c with a = 11.1894 (2)Å, b = 19.5577 (4)Å, c = 8.2201 (2)Å, β = 104.919 (2)º, V = 1738.24 (6)Å3, Z = 4. The molecules are packed in crystal structure by weak non-classical intermolecular hydrogen C2—H2A•••O2 interactions.Conclusion: X-ray crystallography analysis confirms the (E)-configuration of the titled compound.Keywords: X-ray crystallography, Synthesis, Anti-Candida, Configuration, Conformation, Single crystal

Maleimide Glycidyl Ether: A Bifunctional Monomer for Orthogonal Cationic and Radical Polymerizations.

A novel bifunctional monomer, namely maleimide glycidyl ether (MalGE), prepared in a four-step reaction sequence is introduced. This monomer allows for selective (co)polymerization of the epoxide group via cationic ring-opening polymerization, preserving the maleimide functionality. On the other hand, the maleimide functionality can be copolymerized via radical techniques, preserving the epoxide moiety. Cationic ring-opening multibranching copolymerization of MalGE with glycidol was performed, and a MalGE content of up to 24 mol% could be incorporated into the hyperbranched polymer backbone (Mn = 1000-3000 g mol(-1)). Preservation of the maleimide functionality during cationic copolymerization was verified via NMR spectroscopy. Subsequently, the maleimide moiety was radically crosslinked to generate hydrogels and additionally employed to perform Diels-Alder (DA) "click" reactions with (functional) dienes after the polymerization process. Radical copolymerization of MalGE with styrene (Mn = 5000-9000 g mol(-1)) enabled the synthesis of a styrene copolymer with epoxide functionalities that are useful for versatile crosslinking and grafting reactions.

Excited-State Dynamics of a D-π-A Type Sulfonium-Based Alkoxystilbene Photoacid Generator

The excited-state relaxation dynamics of a D-π-A sulfonium-based alkoxystilbene photoacid generator has been investigated in acetonitrile solution by using femtosecond transient absorption and nanosecond laser flash photolysis experiments. For the first time, the successive reaction steps involved in the photoinduced proton generation of a sulfonium acid generator have been kinetically and spectrally resolved from the early stages (femtosecond time scale) to the final chemical processes (microsecond domain). An overall four-step reaction scheme is established, and two main deactivation pathways limiting the proton generation efficiency are identified and quantified.

Synthesis, Docking, In Vitro and In Vivo Antimalarial Activity of Hybrid 4-aminoquinoline-1,3,5-triazine Derivatives Against Wild and Mutant Malaria Parasites.

A new series of hybrid 4-aminoquinoline-1,3,5-triazine derivatives was synthesized by a four-step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (3D-7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P.falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108N, I164L, 3QG2.pdb) type pf-DHFR-TS to highlight the structural features of hybrid molecules.

Preparation, Characterization and Growth Mechanism of Dandelion-like TiO2 Nanostructures and their Application in Photocatalysis towards Reduction of Cr(VI)

Three-dimensional (3D) dandelion-like TiO2 nanostructures were successfully synthesized from TiCl4 and water via simple hydrothermal method. The samples were characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET). The photocatalytic activity of the dandelion-like TiO2 nanostructures was evaluated by photoreduction of Cr(VI) under UV light irradiation. The results indicated that the dandelion-like rutile TiO2 nanostructures were composed of ordered nanorods with an average diameter of 17nm. Furthermore the results indicated that the dandelion-like TiO2 can be easily scaled-up and reproducible. The growth mechanism of the dandelion-like TiO2 nanostructures has been proposed to occur in a four-step reaction, i.e., (i) nucleation and nanoparticle formation; (ii) formation of spheres through self-assembly growth; (iii) further growth and (iv) agglomeration of the dandelions to form flower-like rutile TiO2. The dandelion-like TiO2 structures exhibited higher photocatalytic efficiency compared to P25 TiO2 for the photoreduction of Cr(VI). The highest photocatalytic reduction rate was with 2g of the catalyst in a 10mg/L Cr(VI) solution with pH 2. The high photocatalytic activity of the dandelion-like TiO2 nanostructures was attributed to the flower-like morphology, highest light-harvesting efficiency resulted from multiple reflections of light, hierarchical mesoporous structure and large specific surface area (81 m2/g).

Synthesis andIn VitroCytotoxic Activity of Novel Triazole-Isoxazole Derivatives

New derivatives of triazole-isoxazole were synthesized through a four-step reaction starting from various ethyl 4-aryl-2,4-dioxobutanoate derivatives. Finally, all compounds were examined by MTT assays for cytotoxic activity in two human breast cancer cell lines (MCF-7 and T-47D).

Synthesis of 4,5-fused tricyclic quinolines via an acid-promoted intramolecular Friedel–Crafts allenylation of aniline derivatives

A novel method for synthesizing 4,5-fused tricyclic quinoline derivatives based on an acid-promoted intramolecular Friedel–Crafts allenylation of anilines. Using aryl group-substituted propargyl alcohol derivatives with a meta-substituted N-Boc aniline unit as substrates, a four-step reaction sequence involving an acid-promoted intramolecular Friedel–Crafts allenylation of anilines, an acid-promoted intramolecular C–N bond formation, deprotection of the Boc group, and air oxidation proceeded in a single pot, producing the corresponding 4,5-fused tricyclic quinoline derivatives in 31–84% yield.

Synthesis and Pharmacological Activities of Some New 2-[1-Heptyl-3-(4- methoxybenzyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]acetohydrazide Derivatives

Abstract In the present investigation, the key intermediate acetohydrazide derivative 5 was synthesized starting from 3-(4-methoxybenzyl)-4-amino-4,5-dihydro-1,2,4-triazol-5-one (1) by a four-step reaction. Thiosemicarbazides 6a-f and arylidenehydrazide derivatives 8a-d were obtained from compound 5. The cyclization of compounds 6a-f in the presence of NaOH resulted in the formation of compounds 7a-f. The compounds were characterized by IR, 1H NMR, 13C NMR spectroscopy, elemental analysis and mass spectral studies. The compounds were tested for their anti-lipase, anti-α-glucosidase and anti-mycobacterial activities. Compounds 6b and 8c exhibited excellent anti-lipase activity, and compound 8d showed excellent anti-a-glucosidase activity. Compounds 3 and 4 exhibited good antituberculosis activity