A parallel synthesis demonstration library of tri-substituted indazoles containing new antimutagenic/antioxidant hits related to benzydamine

A solution phase strategy for the multiple parallel synthesis of a demonstration library of indazoles is described by which regio-selectivity problems inherent to previous syntheses of this nucleus are largely overcome. Synthesis of selected components proceeded satisfactorily indicating that a fully realized library of indazole analogs could readily be produced using this methodology. Simple modifications of the basic nucleophilic aromatic substitution route unambiguously produce a range of N-1 substitutions (alkyl, aryl and aralkyl) in 50-75% yields. Next a range of substituents was introduced at the C-3 position in 50-80% yields by O-alkylation. Careful choice of reagents and reaction conditions were required to prevent by-product formation due to competing alkylation at N-2 (trace to 15% yields). When present, these contaminants were readily removed by chromofiltration. A third diversity site was sketched in at C-5 in 75-90% yield by reductive alkylation or acylation. Screening of some of the demonstration library members in vitro revealed highly active antioxidants suggesting that producing a full library would be worthwhile.     

An ab initio study of ground state, electronic and thermodynamical properties of GaP and Ga2P

In the present paper, we report an ab initio calculation of the ground state, electronic and thermodynamical properties like constant volume lattice specific heat, vibrational energy, internal energy, and entropy for GaP and Ga₂P is presented. These properties are obtained after calculating the phonon spectrum over the entire Brillouin zone. The calculations were performed using the ABINIT program package, which is based on density functional theory (DFT) method and the use of pseudopotentials and plane wave expansion. Difference in the ground state properties such as electronic structure and thermodynamical properties are discussed. The thermodynamical properties follow the expected trend. There is a good agreement between present theoretical and limited available experimental data in the case of ground state such as lattice constant and bulk modulus and electronic properties. With the increase of Ga atoms in the unit cell the semiconducting nature of Ga₂P turns to metallic. There is a noticeable difference in the thermodynamical properties in the case of both gallium compounds.     

Multinuclear complexes containing [Pt2(μ-S)2(Ptolyl3)4] as a metallo-ligand

Treatment of [PtCl₂(Ptolyl₃)₂] (tolyl = 4-MeC₆H₄) with Na₂S in benzene gave [Pt₂(μ₂-S)₂(Ptolyl₃)₄] (1), which is soluble in common organic solvents. Reactions of (1) with various metal complexes have been studied and several polynuclear metal aggregates isolated. These new complexes were characterized by elemental analysis and n.m.r. spectroscopy. This revised version was published online in June 2006 with corrections to the Cover Date.     

Low‐temperature sol–gel transformation of methyl silicon precursors to silica‐based hybrid materials

Six new methyl silicon (IV) precursors of the type [MeSi{ON?C(R)Ar}₃] [when R = Me, Ar = 2‐C₅H₄N ( 1 ), 2‐C₄H₃O ( 2 ) or 2‐C₄H₃S ( 3 ); and when R = H, Ar = 2‐C₅H₄N ( 4 ), 2‐C₄H₃O ( 5 ) or 2‐C₄H₃S ( 6 )] were prepared and structurally characterized by various spectroscopic techniques. Molecular weight measurements and FAB (Fast Atomic Bombardment) mass spectral studies indicated their monomeric nature. ¹H and ¹³C{¹H} NMR spectral studies suggested the oximate ligands to be monodentate in solution, which was confirmed by ²⁹Si{¹H} NMR signals in the region expected for tetra‐coordinated methylsilicon (IV) derivatives. Thermogravimetric analysis of 1 revealed the complex to be thermally labile, decomposing to a hybrid material of definite composition. Two representative compounds ( 2 and 4 ) were studied as single source molecular precursor for low‐temperature transformation to silica‐based hybrid materials using sol–gel technique. Formation of homogenous methyl‐bonded silica materials (MeSiO_3/2) at low sintering temperature was observed. The thermogravimetric analysis of the methylsilica material indicated that silicon‐methyl bond is thermally stable up to a temperature of 400 °C. Reaction of 2 and Al(OPrⁱ)₃ in equimolar ratio in anhydrous toluene yielded a brown‐colored viscous liquid of the composition [MeSi{ON?C(CH₃)C₄H₃O}₃.Al(OPrⁱ)₃]. Spectroscopic techniques ¹H, ¹³C{¹H}, ²⁷Al{¹H} and ²⁹Si{¹H} NMR spectra of the viscous product indicated the presence of tetracoordination around both silicon and aluminum atoms. On hydrolysis it yielded methylated aluminosilicate material with high specific surface area (464 m²/g). Scanning electron micrography confirmed a regular porous structure with porosity in the nanometric range. Copyright © 2008 John Wiley & Sons, Ltd.     

Periodic orbits around the collinear libration points in the restricted three body problem when the smaller primary is a triaxial rigid body and bigger primary is a source of radiation pressure

Periodic orbits belonging to the stromgren families A, B and C around the collinear libration points in the restricted three body problem have been studied when the smaller primary is a triaxial rigid body and more massive body is a source of radiation pressure. These families are determined in three different cases: (i) classical case, (ii) when bigger primary is a source of radiation pressure, (iii) when smaller primary is a triaxial rigid body and bigger primary is a source of radiation pressure. The Liapunov stability of each periodic solution has also been examined.      

Direct amplitude detection of Zernike modes by computer-generated holographic wavefront sensor: Modeling and simulation

A fast holographic wavefront sensor is proposed using a computer-generated hologram (CGH). This CGH is a multiplexed hologram of different Zernike mode–amplitude combinations, and is designed in such a manner as to get the corresponding spots on the detector according to the presence and strength of a particular aberration. Interference between the aberrated wavefront (with a single mode–amplitude combination) and the Fourier transform of an image with single bright pixel (defined as dot image) is numerically calculated for one hologram. Different mode–amplitude combination and corresponding different positions of bright pixels (dots) are taken to compute various holograms and then all the holograms are multiplexed to get the final hologram. When the aberrated wavefront with a particular mode–amplitude combination is incident onto the multiplexed hologram, the corresponding dot is generated in the Fourier plane. A lens performs the Fourier transform in optical domain and provides the instant detection of amplitude of the respective Zernike mode. The main advantage of the scheme is to avoid the need of any computations, which makes it really fast. The simulation results are presented with the cross-talk analysis for few Zernike terms.     

Optimal batch sizing in a multi-stage production system with rework consideration

In a production system, rework process plays an important role in eliminating waste and effectively controlling the cost of manufacturing. Determining the optimal batch size in a system that allows for rework is, therefore, a worthwhile objective to minimize the inventory cost of work-in-processes and the finished goods. In this paper, models for the optimum batch quantity in a multi-stage system with rework process have been developed for two different operational policies. Policy 1 deals with the rework within the same cycle with no shortage and policy 2 deals with the rework done after N cycles, incurring shortages in each cycle. The major components that play a role in minimizing this cost of the system are manufacturing setups, work-in-processes, storage of finished goods, rework processing, waiting-time, and penalty costs to discourage the generation of defectives. The mathematical structure of this rework processing model falls under a nonlinear convex programming problems for which a closed-form solution has been proposed and results are demonstrated through numerical examples, followed by sensitivity analyses of different important parameters. It is concluded that the total cost in policy 2 tends to be smaller than that in policy 1 at lower proportion of defectives if the in-process carrying cost is low. Policy 2 may be preferred when the work-in-process carrying cost is low and the penalty cost is negligible.     

Transition metal-free Suzuki type cross-coupling reaction for the synthesis of dissymmetric ketones

A simple, efficient and metal-free route for the synthesis of dissymmetric ketones through Suzuki type cross-coupling reaction has been established. This strategy signifies an attractive, cost-effective and operationally convenient tool for the synthesis of a wide range of dissymmetric ketones. Although conventional routes for the synthesis of ketones have been widely used, the potential challenge with these methods is functional group tolerance. The reported metal-free method represents a reaction with moderate functional group tolerance. The procedure is operationally convenient and shows broad substrate scope with good to excellent product yields.     

载体对其负载的Cu-Co双金属催化剂上5-羟甲基糠醛氢解选择性生成2,5-二甲基呋喃的影响

碳-氧键氢解是生物质呋喃基化合物制备交通燃料常见的模型反应,其中5-羟甲基糠醛(HMF)转化为汽油添加剂2,5-二甲基呋喃(DMF)尤为引人关注.本文采用CeO2,ZrO2和Al2O3负载的Cu-Co双金属催化剂用于HMF选择性氢解制DMF的反应中.采用X射线衍射、N2吸附-脱附、投射电镜、H2-程序升温还原、氨-程序升温脱附和元素分析表征了新鲜的和使用过催化剂的结构,并将其与催化活性相关联.Cu-Co/CeO2催化剂通过在大的Cu颗粒上还原C=O键生成了最多的2,5双(羟甲基呋喃)(BHMF).但Cu-Co/Al2O3催化剂具有高度分散的Cu,Cu-Co复合氧化物和大量的弱酸位,因而生成DMF的选择性最高.Cu-Co/ZrO2催化剂则由于存在强酸位,DMF选择性较低,生成了各种过度氢解产物,如2,5而甲基四氢呋喃和5,5-二(亚甲基)双(2-甲基呋喃).因此,考察了Cu-Co/Al2O3催化剂上的反应路径,以及温度、氢气压力和时间等操作条件的影响,使其具有较优的HMF转化率和DMF选择性.