Application of copper(i) iodide/diorganoyl dichalcogenides to the synthesis of 4-organochalcogen isoquinolines by regioselective cn and cchalcogen bond formation

A copper-catalyzed cyclization of (ortho-alkynyl)benzaldimines with diorganoyl dichalcogenides allowed the synthesis of 4-organochalcogen isoquinolines, whereas the presence of base in the reaction medium inhibited the product formation producing the undesirable isoquinoline without the organochalcogen atom at the 4-position. The cyclization reaction was carried out by using CuI (20?%) as a catalyst with diorganoyl dichalcogenides (1.5?equiv) in the presence of DMF at 100?°C. Furthermore, the reaction did not require an argon atmosphere and was carried out in an open flask. The cyclization reaction tolerated a variety of functional groups both in ortho-alkynylbenzaldimines and diorganoyl dichalcogenides, such as trifluoromethyl, chloro, fluorine, and methoxyl, to give the six-membered heterocyclic ring exclusively through a 6-endo-dig cyclization process. The organochalcogen group present at the 4-position of the isoquinoline ring was further subjected to a selective chalcogen-lithium exchange reaction followed by the addition of aldehydes to afford the desired secondary alcohols in good yields. The obtained isoquinolines also proved to be suitable substrates for the Suzuki and Sonogashira coupling conditions affording the corresponding products through C?C bond formation.     

Packing interactions in hydrated and anhydrous forms of the antibiotic Ciprofloxacin: a solid-state NMR, X-ray diffraction, and computer simulation study

We present an experimental NMR, X-ray diffraction (XRD), and computational study of the supramolecular assemblies of two crystalline forms of Ciprofloxacin: one anhydrate and one hydrate forming water wormholes. The resonance assignment of up to 51 and 54 distinct (13)C and (1)H resonances for the hydrate is reported. The effect of crystal packing, identified by XRD, on the (1)H and (13)C chemical shifts including weak interionic H-bonds, is quantified; (1)H chemical shift changes up to ～-3.5 ppm for CH···π contacts and ～+2 ppm (CH···O((-))); ～+4.7 ppm (((+))NH···O((-))) for H-bonds. Water intake induces chemical shift changes up to 2 and 5 ppm for (1)H and (13)C nuclei, respectively. Such chemical shifts are found to be sensitive detectors of hydration/dehydration in highly insoluble hydrates.     

Synthesis and antidepressant-like activity of selenophenes obtained via iron(III)-PhSeSePh-mediated cyclization of Z-selenoenynes

We present here the synthesis and antidepressant-like action of a series of 2,5-disubstituted-3-(organoseleno)-selenophenes prepared by a novel synthetic route, the FeCl(3)-diorganyl dichalcogenide-mediated intramolecular cyclization of (Z)-chalcogenoenynes. The cyclized products were obtained in good yields. The results showed that 2c, 2d, 2e and 2o, evaluated in the mouse forced-swimming test, elicited an antidepressant-like activity. The studies clearly show that the phenyl group at the 2-position and an organoselenium group at the 3-position of the selenophene ring are essential for the antidepressant-like activity of selenophenes. A close inspection of the results also revealed that the fluorophenyl portion in the organoselenium group is fundamental for the antidepressant-like action of this class of organochalcogens.     

The block sphericity test—exact and near‐exact distributions for the likelihood ratio statistic

Using a suitable decomposition of the null hypothesis of the sphericity test for several blocks of variables, into a sequence of conditionally independent null hypotheses, we show that it is possible to obtain the expressions for the likelihood ratio test statistic, for its hth null moment, and for the characteristic function of its logarithm. The exact distribution of the logarithm of the likelihood ratio test statistic is obtained in the form of a sum of a generalized integer gamma distribution with the sum of a given number of independent logbeta distributions, taking the form of a single generalized integer gamma distribution when each set of variables has two variables. The development of near‐exact distributions arises, from the previous decomposition of the null hypothesis and from the consequent‐induced factorization of the characteristic function, as a natural and practical way to approximate the exact distribution of the test statistic. A measure based on the exact and approximating characteristic functions, which gives an upper bound on the distance between the corresponding distribution functions, is used to assess the quality of the near‐exact distributions proposed and to compare them with an asymptotic approximation on the basis of Box's method. Copyright © 2011 John Wiley & Sons, Ltd.     

A branch-and-price approach for harvest scheduling subject to maximum area restrictions

Recently, research on exact methods has been undertaken to solve forest management problems subject to constraints on the maximum clearcut area by using the area restriction model approach. Three main basic integer programming models for these problems have been discussed in the literature: the so-called cluster, path and bucket formulations. Solving these models via branch-and-bound, where all variables and constraints are used a priori, is adequately suited for real problems of a small to medium size, but is not appropriate for larger problems. In this paper, we describe a branch-and-price approach for the cluster model, and we show that this formulation dominates the bucket model, by completing the results of the dominance relationships between the bounds of the three models. Branch-and-price was tested on real and hypothetical forests ranging from 45 to 2945 stands and temporal horizons ranging from three to twelve periods were employed. Results show that the solutions obtained by the proposed approach stood within 1% of the optimal solution and were achieved in a short computation time. It was found that branch-and-bound was unable to produce solutions for most forests from 850 stands with either eleven or an average number of stands per clearcut greater or equal than eight.     

Peculiar field-dependent magnetic behavior of cyano-bridged coordination polymer Er(H2O)4[W(CN)8

The two-dimensional cyano-bridged coordination polymer Er(H(2)O)(4)[W(CN)(8)] exhibits a magnetic transition at 12 K and an unusual field-dependent transition from short-range to ferromagnetic ordering.     

An octanuclear molybdenum(VI) complex containing coordinatively bound 4,4'-di-tert-butyl-2,2'-bipyridine, [Mo8O22(OH)4(di-tBu-bipy)4]: synthesis, structure, and catalytic epoxidation of bio-derived olefins

The reaction of [MoO(2)Cl(2)(di-tBu-bipy)] (1) (di-tBu-bipy = 4,4'-di-tert-butyl-2,2'-bipyridine) with water at 100-120 °C in a Teflon-lined stainless steel autoclave, in an open reflux system, or in a microwave synthesis system gave the octanuclear complex [Mo(8)O(22)(OH)(4)(di-tBu-bipy)(4)] (2) as a microcrystalline powder in good yields. Single crystals of 2 suitable for X-ray diffraction were obtained by the reaction of MoO(3) and di-tBu-bipy in water at 160 °C for 3 days. The molecular structure of 2 comprises a purely inorganic core, Mo(4)O(8)(μ(3)-OH)(2)(μ(2)-O)(2), attached to two peripheral oxo-bridged binuclear units, Mo(2)O(4)(μ(2)-O)(2)(OH)(di-tBu-bipy)(2). The inorganic core is composed of a unique assembly of four {MoO(5)} distorted square pyramids connected to each other via edge-sharing. Overall, the octanuclear complex adopts a highly distorted form strongly resembling an "S"-shaped molecular unit. Complex 2 was applied in the catalytic epoxidation of the biorenewable olefins DL-limonene (Lim) and methyl oleate (Ole), using tert-butylhydroperoxide (TBHP) as an oxygen donor, under mild reaction conditions (55 °C, air). The reactions of Lim and Ole gave the respective epoxide monomers in fairly high selectivities at high conversions (89% 1,2-epoxy-p-menth-8-ene selectivity at 96% Lim conversion; 99% methyl 9,10-epoxystearate selectivity at 94% Ole conversion, reached within 24 h reaction). Iodometric titrations revealed no measurable "non-productive" decomposition of TBHP.     

Multiphasic Individual Growth Models in Random Environments

The evolution of the growth of an individual in a random environment can be described through stochastic differential equations of the form dY _t  = β(α − Y _t )dt + σdW _t , where Y _t  = h(X _t ), X _t is the size of the individual at age t, h is a strictly increasing continuously differentiable function, α = h(A), where A is the average asymptotic size, and β represents the rate of approach to maturity. The parameter σ measures the intensity of the effect of random fluctuations on growth and W _t is the standard Wiener process. We have previously applied this monophasic model, in which there is only one functional form describing the average dynamics of the complete growth curve, and studied the estimation issues. Here, we present the generalization of the above stochastic model to the multiphasic case, in which we consider that the growth coefficient β assumes different values for different phases of the animal’s life. For simplicity, we consider two phases with growth coefficients β ₁ and β ₂. Results and methods are illustrated using bovine growth data.     

Discrete Ti−O−Ti Complexes: Visible-Light-Activated,Homogeneous Alternative to TiO2 Photosensitisers

A series of novel bimetallic Ti^IV amine bis(phenolate) complexes was synthesised and fully characterised. X-ray crystallography studies revealed distorted octahedral geometries around the Ti centres with single or double oxo-bridges connecting the two metals. These robust, air- and moisture-stable complexes were employed as photosensitisers generating singlet oxygen following irradiation with visible light (420 nm) LED module in a commercial flow reactor. All five complexes showed high activity in the photo-oxygenation of α-terpinene and achieved complete conversion to ascaridole in four hours at ambient temperature. The excellent selectivity of these photosensitisers towards ascaridole (vs. transformation to p-cymene) was demonstrated with control experiments using a traditional TiO₂ catalyst. Further comparative studies employing the free pro-ligands as well as a monometallic analogue highlighted the importance of the ‘TiO₂-like’ moiety in the polymetallic catalysts. Computational studies were used to determine the nature of the ligand to metal charge transfer (LMCT) states and singlet–triplet gaps for each complex, the calculated trends in the UV-vis absorption spectra across the series agreed well with the experimental results.     

Batch Versus Flow Lithiation–Substitution of 1,3,4-Oxadiazoles: Exploitation of Unstable Intermediates Using Flow Chemistry

1,3,4-Oxadiazoles are a common motif in pharmaceutical chemistry, but few convenient methods for their modification exist. A fast, convenient, high yielding and general α-substitution of 1,3,4-oxadiazoles has been developed using a metalation-electrophilic trapping protocol both in batch and under continuous flow conditions in contradiction to previous reports which suggest that α-metalation of this ring system results in ring fragmentation. In batch, lithiation is accomplished at an industrially convenient temperature, −30 °C, with subsequent trapping giving isolated yields of up to 91 %. Under continuous flow conditions, metalation is carried out at room temperature, and subsequent in flow electrophilic trapping gave up to quantitative isolated yields. Notably, lithiation in batch at room temperature results only in ring fragmentation and we propose that the superior mixing in flow allows interception and exploitation of an unstable intermediate before decomposition can occur.