Approaches for introducing high molecular diversity in scaffolds: Fast parallel synthesis of highly substituted 1H-quinolin-4-one libraries

We have developed a two steps strategy for the parallel synthesis of highly diversified quinolin-ones. In the first step we have combined and improved different synthetic methods for generating quinolin-4-ones bearing four different substitutions at specific positions using round bottomed flasks. The synthesis was assessed for a large number of substituted quinolin-4-ones. In the second step, the improved method was adapted to a parallel array synthesis using a 12 positions carrousel as demonstrated for the synthesis of 42-variable quinolin-4-ones. The first combinatorial library set 14(a-x) was obtained with a chemical purity of more than 95% without purification, the second library set 15(a-r), which included two synthetic steps, needed combinatorial purification using an innovative parallel purifier. The proposed approach contributes to a more extensive diversification of molecular scaffolds in general and provides access to highly substituted quinolinones in particular.     

Multicomponent sonochemical synthesis of podands

An efficient sonochemical methodology is described for the synthesis of new podands containing substituted dihydropyrimidines.     

Silica-supported sulfonic acid-functionalized ionic liquid coated with [bmim][PF<Subscript>6</Subscript>] as a scavenger for the synthesis of amides

The methodology of using a silica gel-supported functionalized ionic liquid as a scavenger in the purification of parallel synthesis products was demonstrated. Silica-supported sulfonic acid-functional ionic liquid was synthesized by etherification, aminate, and quaternary aminate from activated silica gel and 3-chloropropyl trimethoxysilane, imidazole, and 1,4-butanesultone, which was followed by acidification using trifluoromethanesulfonic acid and anion exchange with potassium hexafluorophosphate. A conventional ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate was then used to coat the surface of the silica gel. The silica-supported functionalized ionic liquid was used as a scavenger in the removal of excess amine in the parallel synthesis of amides. Desired products were obtained in excellent yields and purity with a sequestration time of less than 100 min at room temperature. After scavenging, the scavenger was easily filtered out and regenerated.     

Fluorous parallel synthesis of a hydantoin/thiohydantoin library

Fluorous tagging strategy is applied to solution-phase parallel synthesis of a library containing hydantoin and thiohydantoin analogs. Two perfluoroalkyl (Rf)-tagged -amino esters each react with six aromatic aldehydes under reductive amination conditions. Twelve amino esters then each react with 10 isocyanates and isothiocyanates in parallel. The resulting 120 ureas and thioureas undergo spontaneous cyclization to form the corresponding hydantoins and thiohydantoins. The intermediate and final product purifications are performed with solid-phase extraction (SPE) over FluoroFlash^TM cartridges, no chromatography is required. Using standard instruments and straightforward SPE technique, one chemist accomplished the 120-member library synthesis in less than five working days, including starting material synthesis and product analysis.     

Aminoheterocycles as synthons for combinatorial Biginelli reactions

Chlorotrimethylsilane (TMSCl) has been utilized as an efficient promoter and water scavenger in the synthesis of diverse dihydropyrimidines via Biginelli type MCR-heterocyclization using aminoheterocycles. High yields and a simple workup of target compounds enable the facile generation of combinatorial libraries comprising more than 2,000 compounds of high structural and functional diversity. A representative set of 89 compounds is described.     

Application of an almost traceless linker in the synthesis of 2-alkylthiobenzimidazole combinatorial libraries

Resin-bound triphenylphosphine was coupledto 4-fluoro-3-nitrobenzyl bromide, and2-alkylthiobenzimidazoles were synthesized onresin in 4 steps using standard chemistries. Cleavage of the compounds from the resin wasachieved with 10% NaOH in MeOH to leave amethyl group at the attachment point. A totalof 47 amines and 40 electrophiles wereevaluated, defining the scope of the reactions,culminating in the synthesis of an 80-membertest library of high purity as determined by HPLC.     

The use of high-throughput synthesis and purification in the preparation of a directed library of adrenergic agents

A library of potential agonists and antagonists for adrenergic receptors was prepared using high-throughput solution-phase parallel synthesis. Traditional solution-phase reductive amination reactions followed by rapid purification by ion exchange chromatography yielded products with near-analytical purity. An array of ketones and amines, arranged in an 8 × 12 matrix, were combined to form 96 individual compounds. This revised version was published online in August 2006 with corrections to the Cover Date.     

Efficient synthesis of 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-2-carboxylic acid derivatives from aniline

The first reported synthesis of potential kinase inhibitors, 4-oxo-4,5-dihydrothieno[3,2- $c$ ]quinoline-2-carboxylic acid derivatives starting from aniline is described. This efficient high yielding sequence was carried out in six steps without any chromatographic purification. A tandem nucleophilic aromatic substitution/cyclization reaction was used as a key step in the sequence. The versatile intermediate 2-carboxylic acid was used as a suitable precursor to access the functionalization of the C-ring, by convergent analog synthesis of several novel derivatives.     

Parallel synthesis of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids

The preparation of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids using a combination of solid– and solution-phase organic synthesis is described. The key intermediates, enantiopure five- or six-membered tri-O-benzyl cyclic nitrones, were efficiently prepared on solid support from accessible chiral furanosides and pyranosides, respectively. The substituent diversity was achieved by a diastereoselective addition of a variety of Grignard reagents to the cyclic nitrones in solution-phase synthesis. All reaction steps and work-up procedures were modified to allow the use of automated equipment. A 36-membered demonstration library with three diversity elements (core, configuration, and substituent) was prepared in good yield and purity.     

Purification of carbon single-wall nanotubes by potassium intercalation and exfoliation

A purification procedure for single-wall carbon nanotubes prepared by the arc-discharge method is described that employs a new step of potassium intercalation. Thermogravimetric analysis, Raman spectroscopy, X-ray diffraction, and transmission electron microscopy were used to characterize the results of each purification step. This potassium intercalation step is particularly useful for exfoliating the graphitic shell structure that typically surrounds the metal catalyst particles that remain from the nanotube synthesis. By exfoliating the shell structure, subsequent treatments are more efficacious for removing the metal catalyst particles. By testing full purification procedures, it is demonstrated that with potassium intercalation the number of purification steps can be reduced. PACS 81.05.Tp; 33.20.Fb; 81.07.De; 81.20.Ym; 71.20.Tx     

Polarization entanglement purification using the temporal degree of freedom

Polarization entangled photon pairs are easily perturbed in noisy channels. We propose a polarization entanglement purification method using temporal degree of freedom, followed by the conventional iterative purification. The entanglement fidelity can be improved to any degree, and the steps needed are less than those using conventional iteration method.     

Relaxation times and line widths of isotopically-substituted nitroxides in aqueous solution at X-band

Optimization of nitroxides as probes for EPR imaging requires detailed understanding of spectral properties. Spin lattice relaxation times, spin packet line widths, nuclear hyperfine splitting, and overall lineshapes were characterized for six low molecular weight nitroxides in dilute deoxygenated aqueous solution at X-band. The nitroxides included 6-member, unsaturated 5-member, or saturated 5-member rings, most of which were isotopically labeled. The spectra are near the fast tumbling limit with T₁∼T₂ in the range of 0.50–1.1 μs at ambient temperature. Both spin–lattice relaxation T₁ and spin–spin relaxation T₂ are longer for ¹⁵N- than for ¹⁴N-nitroxides. The dominant contributions to T₁ are modulation of nitrogen hyperfine anisotropy and spin rotation. Dependence of T₁ on nitrogen nuclear spin state m_I was observed for both ¹⁴N and ¹⁵N. Unresolved hydrogen/deuterium hyperfine couplings dominate overall line widths. Lineshapes were simulated by including all nuclear hyperfine couplings and spin packet line widths that agreed with values obtained by electron spin echo. Line widths and relaxation times are predicted to be about the same at 250 MHz as at X-band.     

Magnetophoresis behaviour at low gradient magnetic field and size control of nickel single core nanobeads

Magnetic separation of organic compounds, proteins, nucleic acids and other biomolecules, and cells from complex reaction mixtures is becoming the most suitable solution for large production in bioindustrial purification and extraction processes. Optimal magnetic properties can be achieved by the use of metals. However, they are extremely sensitive to oxidation and degradation under atmospheric conditions. In this work Ni nanoparticles are synthesised by conventional solution reduction process with the addition of a non-ionic surfactant as a surface agent. The nanoparticles were surfacted in citric acid and then coated with silica to form single core Ni nanobeads. A magnetophoresis study at different magnetic field gradients and at the different steps of synthesis route was performed using Horizontal Low Gradient Magnetic Field (HLGMF) systems. The reversible aggregation times are reduced to a few seconds, allowing a very fast separation process.     

Formation of Ti and TiN ultra-thin films on Si by ion beam sputter deposition

Ultra-thin titanium and titanium nitride films on silicon substrate were obtained by ion beam sputtering of titanium target in vacuum and nitrogen atmosphere, using argon ions with energy of 5 keV and 15 μA target current. Elemental composition and chemical state of obtained films were investigated by X-ray photoelectron spectroscopy with using Mg-Kα X-ray radiation (photon energy 1253.6 eV). It was shown that it is possible to form both ultra-thin titanium films (sputtering in vacuum) and ultra-thin titanium nitride films (sputtering in nitrogen atmosphere) in the same temperature conditions. Photoelectron spectra of samples surface, obtained in different steps of films synthesis, detailed spectra of photoelectron emission from Si 2p, Ti 2p, N 1s core levels and also X-ray photoelectron spectra of Auger electrons emission are presented.     

Dynamics of high-barrier surface reactions: laser-assisted associative desorption of N2 from Ru(0001)

We have determined the dynamics and energetics of associative desorption of N2 from Ru(0001) using both an experimental technique, laser-assisted associative desorption, and density functional calculations. These show that N2 is preferentially desorbed into very high vibrational states and that the barriers between gas phase N2 and adsorbed N atoms increase from 2 to >3 eV with increasing N coverage on the surface. This experimental technique is found to be quite insensitive to low barrier steps and defects which complicate interpretations from other methods of studying high-barrier surface reactions.     

SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF HIGHLY PURE PERYLENE FLUORESCENT DYES

Two new perylene dye, N, N′-bis-(aminododecyl)-3, 4, 9, 10-perylenebis (dicarboximide) (1) and N, N′-bis-(4-chlorophenyl)-3, 4, 9, 10-perylenebis (dicarboximide) have been synthesized. Because the solubility of perylene derivatives is very low, their synthesis and purification are difficult. The imides 1 and 2 are easily prepared with high yield. Dye 2 has a lower density than the density of air. They are highly fluorescent and very photostable dyes. With high fluorescent quantum yield they are suggested as new convenient standards for the fluorescence quantum yield measurements in 500–650 nm region. The report includes the electronic absorption and emission spectra, extinction coefficients and fluorescence quantum yields. Applications of the dyes are discussed.     

以MCM-22分子筛为前驱体制备MCM-36分子筛

以MCM-22分子筛为前驱体,对原料配比和合成步骤等参数进行调变,探索了MCM-36分子筛的合成规律。通过X射线衍射、扫描电镜和N2吸附-脱附等表征方法对所合成的MCM-36分子筛物理化学性质进行表征。结果表明,以MCM-22为前驱体,溶胀原料质量配比为1∶3∶1.2时,MCM-36分子筛介孔和微孔比表面积最大。     

A Soft Chemistry Route to Selective Nickel‐Based Nanocatalysts with Faceted Morphologies

A one pot synthesis of alumina supported faceted nickel nanoparticles is carried out following a simple, inexpensive, and sustainable pathway. Tailoring the different chemical steps of catalyst preparation allow the faceted morphology to be maintained while reducing the organic leftover. Moreover, this work shows the key role of the halide ions on the nanoparticles shaping that occurs during the reduction step under H₂. The predominant role of the {111} facets on the performance of the resulting supported nanocatalysts is also demonstrated. Indeed, catalytic tests in selective hydrogenation of polyunsaturated hydrocarbons performed for both faceted nanocatalysts and reference Ni show a clear selectivity enhancement for the former. The positive impact of {111} faceted Ni catalysts on hydrogenation selectivity is of particular interest to reduce the purification steps after the catalyzed reaction.     

Ultra-fast synthesis of magnetic and luminescent silica beads for versatile bioanalytical applications

A method for the synthesis of both spherically shaped micro/nano silica particles and silica hybrid particles using a novel inverse sol–gel suspension technique was developed. The technique enables the synthesis of beads within seconds and provides a simple basis for quantum dot and biosubstances encapsulation. The carriers can be used as DNA adsorbents, individually addressable optical codes for bioassays and biomolecule library screening as well as photonic crystals.     

Automatically Purification of Aqueous CdTe Nanocrystals in Water-ethanol Co-environment

Purification is a separated post-treatment step after the synthesis of nanocrystals (NCs) in order to exclude excess ligands and monomers in NC solution. The common purification process involves many manipulations, such as concentrating, addition of anti-solvents and centrifugation, which are troublesome and time consuming. In this work, we originally integrate NC synthesis and NC purification in one-pot via selecting water-ethanol co-environment for NC synthesis and NC purification. Our research shows that NCs can grow in water-ethanol mixture. When growing into critical size, NCs will automatically precipitate from the solution. Element analysis demonstrates that precipitates fraction fits well with stoichiometric of ligand-capped NCs. Excess monomers are left in supernatant, and thus achieving automatically purification of NCs in the water-ethanol co-environment. By adjusting the volume ratios of water and ethanol in bi-solvent system, different-sized purified NCs can be controlled. Besides, this water-ethanol co-environment can be used in both thermal-promoted and hydrazine-promoted growth.