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A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents., Grants Fondecyt 1180565, 1201880, 11200677, and 3210559. ANID/FONDAP/15110019.

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied., M.B. and E.M. are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019-917S) and Generalitat de Catalunya (2017SGR1687). A.F. thanks the MICIU/AEI from Spain for financial support (Projects CTQ2017-85821-R and PID2020-115637GB-I00, Feder funds).

Two novel organic-inorganic decavanadate materials with protonated amines were prepared from acidified aqueous solution and characterized by single crystal X-Ray diffraction, thermogravimetric analysis and IR spectroscopy. (C6N2H9)4[H2V10O28]·4H2O (I) and (C7H9NF)4[H2V10O28]·2H2O (II), were isolated in single-crystal form. For both compounds, the crystal packing is governed by the formation of various non-covalent intermolecular forces between decavanadate anions, organic cations and water molecules. For both compounds, Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to in the crystal packing for both compounds are from O⋅⋅⋅H/H⋅⋅⋅O and H⋅⋅⋅H bonds. Furthermore, topological study of weak non-covalent interactions properties was theoretically carried out using DFT. The determined HOMO and LUMO levels were to estimate the charge transfer within the structure. The photoluminescence properties and UV–Vis absorption spectra have also been investigated. Both (I) and (II) possess photoluminescence properties and produce blue and green emissions, respectively, upon irradiation with violet light., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

The high yield synthesis, characterization and biological trials of a family of compounds containing the pyrazole core (E)-3,5-dimethyl-1-(4-R-phenyl)-4-(phenyldiazenyl)-1H-pyrazoles (with R = 4-CH3O (1), 4-CH3 (2), 4-H (3), 4-F (4), 4-Cl (5), 4-CF3 (6), 4-CN (7), 4-NO2 (8), 3-Cl (9), 3-NO2 (10), 2-Cl (11) and C6F5 (12)) are reported. Hammett correlations were found for the experimental and theoretical computed data, showing the dependence of all the obtained results on the donor or acceptor nature of the R substituent. In this sense, the absorption wavelength does decrease as the electron-withdrawing character of the substituent increases. Furthermore, the wavelength intensity does follow a Hammett correlation with the sigma donor character of the substituents. The compounds were characterized using MP, EA, UV–vis, FT-IR, 1H NMR, 13C NMR including bidimensional NMR experiments (HMBC and HMQC). The structures of 4, 5 and 8 were successfully elucidated by means of X-Ray diffraction. Pyrazole based dyes are known in pharmacological areas. Therefore, biological activity of all these structures were tested against cancer cell lines over a wide library of cell lines (60), including leukemia, colon and brain cancer, showing that the compounds have anticancer activity, which expands the knowledge of this kind of dyes as targets for this critical application. Finally, quantum calculations were carried out in order to give a rational explanation to the observed UV–vis absorption bands and FT-IR signals. As shown, it is possible to tune the molecular/electronic structure of the synthesized dyes by means of changing the R substituent in the structure.

This contribution describes an updated synthetic route to 3,6-dihydro-as-indacene along with full characterization of all inter­mediates. The title compound is prepared by Mannich condensation of 2-methylfuran with formaldehyde and dimethylamine hydrochloride, quaternization of the resulting amine with methyl iodide, and conversion into the ammonium hydroxide salt by treatment with silver oxide in water. Subsequent Hoffmann elimination and [6,6]-cycloaddition through pyrolysis produces a furanocyclophane, which after photooxidation, intramolecular cycloaddition, and dehydration with sodium carbonate affords 2,3,6,7-tetrahydro-1,8-dione-as-indacene. Reduction of this diketone gives a mixture of alcohols, which after dehydration under slightly basic or acidic conditions produces 3,6-dihydro-as-indacene. The structure is confirmed by X-ray diffraction, and all intermediates are characterized by means of 1H and 13C NMR spectroscopy., The authors are grateful for the financial support from Fondo Nacional de Desarrollo Cientifico y Tecnologico, Chile (FONDECYT) (Grants 1161297, EQM120021, EQM130032, EQM150102), the Pontificia Universidad Catolica de Chile (PUC) (Grant 3913-541-81), the Scheduled Tribes Welfare Department, Government of Karnataka, India for a student fellowship (Y.D.) to pursue a research stay at the Pontificia Uni-versidad Catolica de Chile. E.M. (ICMAB) acknowledges the Severo Ochoa Program, Ministerio de Economia y Competitividad (MINECO) (SEV-2015-0496).

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared., This research was funded by MICIU/FEDER, Spain (RTI2018-093974-B-I00).

Lactose intolerance is a pathology caused by lactase enzyme deficiency, usually produced in the intestinal cells provoking symptoms as abdominal pain, bloating, diarrhea, gas and nausea. Gaxilose, 4-O-β-D galactopyranosyl-d-xylose, is used as a diagnostic drug for a non-invasive method for hypolactasia diagnosis. To date, no definitive guide for identifying gaxilose and distinguishing between crystalline forms is available. Data have been collected from a number of different analytical techniques in order to provide a full characterization of the compound and a simple method to discriminate between two solid forms., E. Molins and M. Benito thank to Severo Ochoa FunFuture project (MICINN, CEX2019-917S) and Generalitat de Catalunya (2017SGR1687).

N-Methyl-D-aspartate receptors (NMDARs) are crucial for the normal function of the central nervous system (CNS), and fundamental in memory and learning-related processes. The overactivation of these receptors is associated with numerous neurodegenerative and psychiatric disorders. Therefore, NMDAR is considered a relevant therapeutic target for many CNS disorders. Herein, we report the synthesis and pharmacological evaluation of a new scaffold with antagonistic activity for NMDAR. Specifically, a chemical library of eighteen 1-aminoindan-2-ol tetracyclic lactams was synthesized and screened as NMDAR antagonists. The compounds were obtained by chiral pool synthesis using enantiomerically pure 1-aminoindan-2-ols as chiral inductors, and their stereochemistry was proven by X-ray crystallographic analysis of two target compounds. Most compounds reveal NMDAR antagonism, and eleven compounds display IC values in a Ca entry-sensitive fluo-4 assay in the same order of magnitude of memantine, a clinically approved NMDAR antagonist. Docking studies suggest that the novel compounds can act as NMDAR channel blockers since there is a compatible conformation with MK-801 co-crystallized with NMDAR channel. In addition, we show that the tetracyclic 1-aminoindan-2-ol derivatives are brain permeable and non-toxic, and we identify promising hits for further optimization as modulators of the NMDAR function., This work was supported by FCT (Fundaç~ao para a Ci^encia e a Tecnologia, I.P.) through iMed.ULisboa (UID/DTP/04138/2019), Principal Researcher grant CEECIND/01772/2017 (M. M. M. Santos), and PhD fellowships SFRH/BD/117931/2016 (M. Espadinha) and SFRH/BD/121664/2016 (R. Lopes). Financial support from FCT and Portugal 2020 to the Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa e RNEM; LISBOA-01-0145- FEDER-402-022125) is also acknowledged. M.I.R.-F. thanks funding from the Spanish Ministry of Science, Innovation and Universities (grant RTI2018-093955-B-C21) and the technical assistance of Ms. Cristina Tortosa (European contract for young professionals). C.d.l.R. thanks funding from Instituto de Salud Carlos III, Madrid, Spain (grant PI16/01041 and PhD fellowship FI17/00079 for L. Viejo).

A short synthesis of an enantiopure pyrrolobenzodiazepine (PBD) dilactam featuring early installation of the C2-C3 unsaturation is reported. An enantioselective cooperative catalytic cascade followed by self-disproportionation of enantiomers via sublimation afforded the enantiopure 2,3-dihydro-1H-pyrrole key intermediate, 1. N-Acylation followed by reduction and lactam formation furnished the PBD dilactam.

Nitrogen compounds are widely investigated due to their pharmacological properties such as antihypertensive, antinociceptive, antibacterial, antifungal, analgesic, anticancer and inhibition activities and lately even as pesticide. In this context, we present the synthesis of new compounds: (E)-6-(3,4-dimethoxyphenyl)-3-(3-(3,4-dimethoxyphenyl)acryloyl)-1-(4-R-phenyl)- 5,6-dihydropyridazin-4(1H)-one (with R = H(1), -Cl(2), -Br(3), I(4) and COOH(5)) that was carried out by reaction of (1E, 6E)-1,7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione with a substituted phenylamine with general formula p-R-C6H4 NH2 (R = H (1), Cl (2), -Br(3), I(4) and COOH(5)). This is the first synthesis report of a pyridazinone using as precursors a curcuminoid derivative and a diazonium salt formed in situ. All compounds were characterized by EA, FT-IR, UV–Vis, Emission,1H- and13C-NMR spectroscopy and the crystalline and molecular structure of 4 was solved by X-rays diffraction method. DFT and TD-DFT quantum chemical calculations were also employed to characterize the compounds and provide a rational explanation to the spectroscopic properties. To assess the biological activity of the systems, we focused on pesticide tests on compound 2, which showed an inhibitory effect in plant growth of Agrostis tenuis Higland.

Recent findings unveil the pharmacological modulation of imidazoline I2 receptors (I2-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I2-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Moreover, LSL60101 induced hypothermia in mice while decreased pro-apoptotic FADD protein in the hippocampus. In vivo studies in the familial Alzheimer's disease 5xFAD murine model with the representative compound, revealed significant decreases in the protein expression levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in hippocampus. Overall, LSL60101 plays a neuroprotective role by reducing apoptosis and modulating oxidative stress., This work was supported by Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (Spain, PID2019-107991RB-I00, PID2019-106285RB), the Basque Government (IT1211/19) and Generalitat de Catalunya (GC) (2017SGR106). The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434) under agreement CI18-00002. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation programme. C.G.-F, F.V., C.E., S.R.-A., A.B., and M.P. Financial support was provided for F.V. (University of Barcelona, APIF_2017), S.R.-A. (Generalitat de Catalunya, 2018FI_B_00227), A.B. (Institute of Biomedicine UB_2018), J.A.G.-S. is a member emeritus of the Institut d’Estudis Catalans (Barcelona, Catalonia). E.H.-H. is supported by a predoctoral scholarship (FPI/2102/2018; Consejería de Innovación, Investigación y Turismo del Gobierno de las Islas Baleares y del Fondo Social Europeo). M.R., T.D., and K.N. kindly acknowledge the project funded by the Ministry of Science and Technological Development of the Republic of Serbia, Contract No. 451-03-68/2020-14/200161, and HORISON 2020-COST-Action CA18133 ERNEST: European Research Network on Signal Transduction. E. M. acknowledges funding to Severo Ochoa: CEX2019-917S. M.I.L, A.L.M. and J.B. gratefully acknowledge support from Xunta de Galicia (ED431C 2018/21 and ED431G 2019/02) and European Regional Development Fund (ERDF)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

The methyl-substituted Nazarov reagent 4 stereoselectively reacts with Nind-Boc indoloquinolizidine lactams to give the expected H-3/H-15 cis pentacyclic yohimbine-type adducts when using DBU as the base. However, a dramatic change of the facial selectivity was observed when the reaction was performed in the presence of Cs2CO3, leading to the corresponding trans adducts. This annulation is the key step of an stereocontrolled synthesis of the 17a-carba-analog of the heteroyohimbine alkaloid akuammigine. Theoretical calculations were used to rationalize the facial selectivity of these double Michael addition reactions.

Stereoconvergent cyclocondensation reactions of (R)- or (S)-phenylglycinol with appropriately substituted cyclohexanone-based δ-keto esters are the key steps of short synthetic routes to enantiopure 5-, 7-, and 5,7-substituted cis-decahydroquinolines. The factors governing the stereoselectivity of the cyclocondensation are discussed. The potential of the methodology is illustrated by a protecting-group-free synthesis of the phlegmarine-type Lycopodium alkaloid (-)-cermizine B.

The synthesis of a metalled double-helix containing exclusively silver-mediated C*-C* base pairs is reported herein (C* = N1hexylcytosine). Remarkably, it is the first crystal structure containing infinite and consecutive C*-AgI-C* base pairs that form a double helix. The AgI ion occupies the center between two C* residues with N(3)-Ag bond distances of 2.1 A and short AgI-AgI distances (3.1 A) suggesting an interesting argentophilic attraction as a stabilization source of the helical disposition. The solid state structure is further stabilized by metal-mediated base-pairs, hydrogen bonding and π-stacking interactions. Moreover, the angle N(3)-Ag-N(3) is almost linear in the [Ag(N1hexylcytosine)2]+ motif and the bases are not coplanar thus generating a double strand helical aggregate in the solid state. The noncovalent and argentophilic interactions have been rationalized by means of DFT calculations.

Base-catalyzed annulation reactions of 5,6-dihydro-2(1H)-pyridones with Nazarov-type reagents are reported. The effect of the solvent polarity and the concentration of the reagents is studied. The process involves two successive Michael additions and stereoselectively provides functionalized cis-perhydroisoquinolin-1-ones.

A novel and convenient synthetic route towards dialkyl as-indacenes was achieved by alkylation of malonic esters with o-xylylene dibromide, to give the corresponding tetraester, and related diacid. The alkyl groups on the central benzene ring induce intramolecular, regiospecific cycloeliminations leading selectively to the diketones, the precursors of the corresponding 1,8-dihydro-as-indacenes. The structure of the 2,7-dimethyl-1,8-dihydro-as-indacene was determined by X-ray diffraction. The compound 2,7-diethyl-1,8-dihydro-as-indacene was characterized by means of 1H NMR, 13C NMR, FT-IR, UV/Vis measurements, electrochemistry, and elemental analysis. On the other hand, quantum chemical computations based on DFT methods were carried out to get insight into the molecular and electronic structures of the studied ligands. TDDFT approach was employed to calculate the vertical excitations and characterize the nature the UV/Vis absorption bands present in the experiments showing a very good agreement between experimental and calculated values. Finally, the reactivity of the compounds was assessed using the chemical potential (μ), chemical hardness (η), and electrophilicity (ω). Also, the electron-donating (ω–), electron-accepting (ω+), and the net electrophilicity powers (ω±) indexes were studied., The authors thank the financial support from the following grants: FONDECYT Grants 1161297 and 1141138.

High enantioselection is obtained in α-amination of acyclic β-keto esters in the presence of lanthanide triflates and pybox ligands. The Eu3+ complexes proved more active than those with Yb3+ and La3+ and high dependence of ee on the type and steric bulk of the ester group was observed. Excellent results were achieved using a combination of europium triflate with ligand L4 (diphenyl-pybox). Preparation of ternary complexes (8) [(L4)(β-keto ester enolate)Ln (OTf)2] was accomplished. Complexes 8 and [(L4)(β-keto ester)Ln (OTf)2]+, identified by ESI-MS, are proposed as key intermediates of the α-amination reaction.

The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between ( R)- or ( S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from ( R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline.

A three-step procedure for the enantioselective synthesis of spiro[indolizidine-1,3′-oxindoles], consisting of a stereoselective cyclocondensation reaction between (S)-tryptophanol and a prochiral or racemic δ-oxoester, bromination of the resulting oxazolopiperidone lactam, and a final stereoselective spirocyclization, is reported.

Cyclocondensation of (R)-phenylglycinol with stereoisomeric mixtures (racemates, cis/trans) of 3-substituted 2-oxocyclohexaneacetates stereoselectively afforded tricyclic oxazoloindolone lactams, from which straightforward procedures for the stereocontrolled formation of enantiopure 7-substituted octahydroindoles with a variety of stereochemical patterns have been developed. The methodology has been successfully applied to the synthesis of (+)-α-lycorane.

We report the synthesis and X-ray characterization of N1-hexylcytosine (1) and N1-hexylcytosinium nitrate (2). N1-hexylcytosine (1) does not follow the same behaviour previously described for N1-hexylthymine and N1-hexyluracil in the solid state. This different behavior has been analyzed by means of density functional theory (DFT) calculations including the latest available correction for dispersion (D3). In addition hydrophobic and anion–π noncovalent interactions play a key role in stabilizing the 3D architectures of the compounds, which have been energetically studied using theoretical calculations and compared with similar structures retrieved from the Cambridge Structural Database (CSD). The anion–π–anion binding mode observed for nitrate in compound 2 is also observed in several crystal structures involving cytosine ring coordinated to transition metals.

Cyclization of the lactam carbonyl on the indole ring in tryptophanol-derived oxazolopiperidone lactams 2 and 6, under the classical POCl3-promoted Bischler–Napieralski conditions and under neutral conditions via the corresponding thiolactam, has been studied. Whereas tricyclic lactam 2 only leads to products coming from an α-amidoalkylation process, bicyclic lactam 6 undergoes cyclization on the lactam carbonyl, leading to the expected indolo[2,3-a]quinolizidine derivatives.

A convergent synthesis of fluvirucinin B1 from acid ent-6a and nitrile ent-9, involving an organocopper coupling, a stereoselective allylation, a ring-closing metathesis reaction, and a stereoselective hydrogenation as the key steps, is reported. The starting building blocks have been prepared in a straightforward manner from a common phenylglycinol-derived lactam 1. An unprecedented regioselective oxidation of phenylglycinol-derived secondary amines 5 to carboxylic acids 6 has been developed., Financial support from the Spanish Ministry of Economy and Competitiveness/FEDER (Projects CTQ2012-35250 and CTQ2015-65384-R) and the Generalitat de Catalunya (Grant No. 2014-SGR-155) is gratefully acknowledged. We also acknowledge the networking contribution from the COST Action CM1407.

Ethanol steam reforming has been carried out at low temperature in a catalytic membrane reactor consisting of cobalt talc (Co 3 [Si 2 O 5 ] 2 (OH) 2 ) supported over cordierite and a Pd–Ag membrane. No sweep gas has been used, therefore, pure hydrogen has been obtained in the permeate stream, which has been maintained at atmospheric pressure. The configuration with the catalyst bed packed around the membrane has shown superior performance than the staged configuration, where the honeycomb catalyst has been placed in-series with the membrane. The influence of the temperature (598–673 K) and the pressure inside the reactor (5–15 bar) on different parameters such as the hydrogen production and the pure hydrogen recovery has been evaluated. The catalytic membrane reactor device has a rapid response to changes in the ethanol–water liquid mixture load; a constant hydrogen flow has been obtained after 2 s following variations of ±10%.

A synthetic route to enantiopure cis-1,3-dimethyltetrahydroisoquinolines, synthetic precursors of naphthylisoquinoline alkaloids, has been developed. The synthesis relies on the use of a phenylglycinol-derived lactam as the starting enantiopure scaffold. After stereoselective opening of the oxazolidine ring, the C-3 methyl substituent was installed, taking advantage of the lactam carbonyl group by stereoselective hydrogenation of an α-methylenamide generated via a vinyl triflate.

In this manuscript we report the synthesis and X-ray characterization of neutral 2-(1H-imidazol-1-yl)-pyrimidine (1), 2-(1H-pyrazol-1-yl)-pyrimidine (2) and 1-(2-pyrimidinyl)-1H-benzimidazole (3). We have also obtained crystals of the corresponding hydrochlorides of compounds 1 and 3. Finally, the outer sphere complex of protonated 2-(1H-imidazol-1-yl)-pyrimidine with [CoCl4]2− as counterion is described. In several charged structures interesting anion–π interactions determine the crystal packing. Moreover, in neutral systems some stacking interactions are governed by double lone pair–π interactions. High level ab initio calculations (RI-MP2/def2-TZVP) have been used to evaluate the noncovalent interactions observed in the solid state and the interplay between them.

Cyclocondensation reactions between a variety of 2‐acyl‐3‐indoleacetic acid derivatives and (R )‐phenylglycinol were studied. Successful results were obtained from N ‐alkyl keto acid derivatives. The resulting tetracyclic lactams provide straightforward access to enantiopure 1‐substituted tetrahydro‐β‐carboline alkaloids.

Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of an unsaturated δ-keto ester derivative with (R)-phenylglycinol and the stereoselective hydrogenation of the resulting tricyclic oxazoloquinolone lactams.

We report the synthesis and X-ray characterization of N 9 -and N 6 -decyladenine hydrochloride salts. The latter exhibits interesting anion-π interactions, which are responsible for crystal packing. In contrast, the former does not present any anion-π interactions; the anion is stabilized by hydrogen-bonding interactions. Finally, a theoretical study of the different binding modes observed in the solid state is useful to explain the experimental findings.

Topological analyses of the theoretically calculated electron densities for a large set of 163 hydrogen-bonded complexes show that H···X interactions can be classified in families according to X (X = atom or π orbital). Each family is characterised by a set of intrinsic dependencies between the topological and energetic properties of the electron density at the hydrogen-bond critical point, as well as between each of them and the bonding distance. Comparing different atom-acceptor families, these dependencies are classified as a function of the van der Waals radius r X or the electronegativity χ X , which can be explained in terms of the molecular orbitals involved in the interaction. According to this ordering, the increase of χ X leads to a larger range of H···X distances for which the interaction is of pure closed-shell type. Same dependencies observed for H···O interactions experimentally characterised by means of high-resolution X-ray diffraction data show a good agreement with those obtained from theoretical calculations, in spite of a larger dispersion of values around the expected fitting functions in the experimental case. Theoretical dependencies can thus be applied to the analysis of the experimental electron density for detecting either unconventional hydrogen bonds or problems in the modelling of the experimental electron density.

The carbonylative addition between allyl halides and alkenes is described. The [2+2+1] reaction is catalyzed by Ni(I), and takes place with different strained alkenes under very mild conditions. Changes in solvent and use of different amounts of water in the reaction produce changes on the final products obtained.

Cobalt–silica (Co–SiO2) aerogel coatings were successfully grown on the walls of ceramic monolith channels, thus resulting in structured catalytic wall materials useful for gas–solid reactions. The preparation involved the synthesis in situ of SiO2 gels by the sol–gel hydrolysis and condensation of tetraethylorthosilicate (TEOS), quenching at the gelation point, incorporation of Co by impregnation, and extraction of the solvent by supercritical drying. Characterization of the aerogel-coated monoliths revealed an excellent dispersion and homogeneity of the aerogel and good adherence properties. The catalytic performance of these materials in the ethanol steam reforming reaction addressed to obtain hydrogen was studied at atmospheric pressure by carrying out consecutive cycles at 473–773–473 K with a C2H5OH:H2O ∼ 1:3 (molar) mixture and stability tests, and the results were compared with those obtained over monoliths prepared by conventional washcoating methods from Co–SiO2 xerogel. Co–SiO2 aerogel catalytic walls were about four times more active for hydrogen generation at 623 K than conventional monoliths. An unusual rapid activation of aerogel-coated monoliths was attained at 580–590 K, even after several cycles and oxidation treatments at 563–613 K, which was attributed to highly dispersed cobalt particles and higher effective diffusivity of reaction species due to high porosity and larger average pore size. The reproducible low-temperature activation of Co–SiO2 aerogels supported on ceramic monoliths may be useful for the practical application of fuel reformers to the on-site generation of hydrogen from ethanol.

The synthesis, X-ray crystal structures, and the study of the solution behavior of the palladium(II) allyl complexes [Pd(eta(3)-1R(1)-C3H4){FcCH=N-CH2-(CH2)(n)-NMe2}][PF6] {with Fc = (eta(5)-C5H5)Fe(eta(5)-C5H4), R-1 = H, and n = 2 (4) or 1 (5) or R-1 = Ph and n = 2 (6) or 1 (7)} are described. The structural studies of 4, 5, 6, and 7 showed that the allyl ligands were bound to palladium(II) in an eta(3)-fashion and the ferrocenyl-Schiff bases behaved as neutral (N,N') bidentate ligands. As observed for other Pd complexes of ligands 1 and 2, the imine conformation of the ligand in the complex strongly depends on the length of the hydrocarbon chain between the two nitrogen donors: compounds 4 and 6 exhibited an anti-(E) conformation, whereas the syn-(Z) form is observed in 5 and 7 Fe-57-Mossbauer spectra (in the solid state) and electrochemical studies based on cyclic voltammetry of 4, 5, 6, and 7 are reported. These studies reveal that the proclivity of the iron(II) toward oxidation is affected by the nature of the substituent R-1 of the allyl group {H (in 4 and 5) or Ph (in 6 and 7)}. Compounds 4 and 5 have been tested in the palladium(II) allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate using sodium diethyl 2-methylmalonate as the nucleophile. In all cases the formation of the trans-(E) isomer of the linear product (9) was strongly favored versus that of the branched derivative (10). The stoichiometric reactions of the palladium(II) allyl intermediates [Pd(eta(3)-1-Ph-C3H4){FcCH=N-CH2-(CH2)(n)-NMe2}] [PF6] {with n = 2 (6) or 1 (7)} with the nucleophile have been studied. Density functional theory (DFT) calculations of these systems have allowed us to rationalize. the structural differences as well as the regioselectivity of the catalytic and stoichiometric reactions.

The synthesis and characterization of pyrazole derivatives of general formula [C6H4-4-R-1-{(3,5-Me2–C3N2)–CH2–(η5-C5H4)Fe(η5-C5H5)}] [R = OMe (1a) or H (1b)] with a ferrocenylmethyl substituent are described.The study of the reactivity of compounds 1 with palladium(II) acetate has allowed the isolation of complexes (μ-AcO)2[Pd{κ2-C,N-C6H3-4-R-1-[(3,5-Me2–C3N2)–CH2–(η5-C5H4)Fe(η5-C5H5)]}]2 (2) [R = OMe (2a) or H (2b)] that contain a bidentate [C(sp2, phenyl), N]− ligand and a central “Pd(μ-AcO)2Pd” unit.Furthermore, treatment of 2 with LiCl produced complexes (μ-Cl)2[Pd{κ2-C,N-C6H3-4-R-1-[(3,5-Me2–C3N2)–CH2–(η5-C5H4)Fe(η5-C5H5)]}]2 (3) [R = OMe (3a) or H (3b)] that arise from the replacement of the acetato ligands by the Cl−.Compounds 2 and 3 also react with PPh3 giving the monomeric complexes [Pd{κ2-C,N-C6H3-4-R-1-[(3,5-Me2–C3N2)–CH2–(η5-C5H4)Fe(η5-C5H5)]}X(PPh3)] {X− = AcO− and R = OMe (5a) or H (5b) or X− = Cl− and R = OMe (6a) or H (6b)}, where the phosphine is in a cis-arrangement to the metallated carbon atom. Treatment of 3 with thallium(I) acetylacetonate produced [Pd{κ2-C,N-C6H3-4-R-1-[(3,5-Me2–C3N2)–CH2–(η5-C5H4)Fe(η5-C5H5)]}(acac)] (7) [R = OMe (7a) or H (7b)]. Electrochemical studies of the free ligands and the cyclopalladated complexes are also reported. The dimeric complexes 3 also react with MeO2C–C C–CO2Me (in a 1:4 molar ratio) giving [Pd{(MeO2C–C C–CO2Me)2C6H3-4-R-1-[(3,5-Me2–C3N2)–CH2–(η5-C5H4)Fe(η5-C5H5)]}Cl] (8) [R = OMe (8a) or H (8b)], which arise from the bis(insertion) of the alkyne into the σ{Pd–C(sp2, phenyl)} bond of 3.

We report the synthesis and X-ray characterization of an N,N′-tetramethylenebis(2-aminopyrimidinium) tetrafluoroborate salt that exhibits anion–π interactions that are responsible for the crystal packing. The anion forms a sandwich complex with two pyrimidine rings. When the anion is nitrate, the crystal packing is governed by anion–π interactions and hydrogen bonds, and the sandwich complex is not formed. Finally, a theoretical study of the anion–π interactions in charged pyrimidine rings is in good agreement with the experimental findings. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The Sonogashira cross coupling of aryl iodides with ter- minal alkynes has been carried out in the presence of carbon aero- gels doped with metallic palladium nanoparticles. Coupling products have been isolated in excellent yields and the catalyst sys- tem can be easily recovered in the presence of air without any par- ticular precautions and reused several times.

A straightforward synthetic route to enantiopure spiro[indole-3,3'-indolizidines] is reported. The key step is a Lewis acid promoted cyclization of a Na-tosyltryptophanol-derived oxazolopiperidone lactam in the presence of Et3SiH.

The study of the reactivity of the ferrocenyliminoalcohol [(η5-C5H5)Fe{(η5-C5H4)–CH N–(C6H4-2OH)}] (1b) with Na2[PdCl4] or Pd(OAc)2 has allowed the isolation and characterization of the heterotrimetallic complexes: trans-[Pd{(η5-C5H5)Fe[(η5-C5H4)–CH N–(C6H4-2OH)]}2Cl2] (2b), [Pd{[(η5-C5H3)–CH N–(C6H4-2O)]Fe(η5-C5H5)}{(η5-C5H5)Fe[(η5-C5H4)–CH N–(C6H4-2OH)]}] (3b) and trans-[Pd{(η5-C5H5)Fe[(η5-C5H4)–CH N–(C6H4-2O)]}2] (4b). Ligand 1b acts as a (N) (in 2b) or a (N,O)− (in 4b) ligand; while in 3b the two units of the iminoalcohol exhibit simultaneously different modes of binding {(N) and [C(sp2, ferrocene),N,O]2−}. The crystal structures of 2b · 3H2O and 3b · 1/2CHCl3 are also reported and confirm the mode of binding of the ligand in these compounds. The relative importance of the factors affecting the preferential formation of products (2b–4b) is also discussed. The study of the reactivity of 3b with PPh3 has enabled the obtention of the cyclopalladated complexes [Pd{[(η5-C5H3)–CH N–(C6H4-2O)]Fe(η5- C5H5)}(PPh3)] (6b) and [Pd{[(η5-C5H3)–CH N–(C6H4-2OH)]Fe(η5-C5H5)}Cl(PPh3)] (7b), in which 1b behaves as a [C(sp2, ferrocene),N,O]2− (in 6b) or [C(sp2, ferrocene),N]− (in 7b) ligand. Treatment of 3b with MeO2C–C C–CO2Me produces [Pd{[(MeO2C–C C–CO2Me)2(η5-C5H3)–CH N–(C6H4-2O)]Fe(η5-C5H5)}] (8b), that arises from the bis(insertion) of the alkyne into the σ[Pd–C(sp2, ferrocene)] bond. The comparison of the results obtained for 1b and [C6H5–CH N–(C6H4-2OH)] (1a) has allowed to establish the influence of the substituents on the imine carbon on their reactivity in front of palladium(II) as well as on the lability of the Pd-ligands bond. 57Fe Mossbauer studies of 2b–4b and 6b provide conclusive evidence of the effect induced by the mode of binding of 1b on the environment of the iron(II).

The synthesis and characterization of [Pd(η3-1-R1-C3H4){FcCHN−(C6H4−2SMe)}][PF6] {R1 = H (2a) or Ph (3a)} are described. A comparative study of the catalytic activity of (a) the mixtures containing [Pd(η3-C3H5)(μ-Cl)]2 and its parent ligand (1a) or H2N−C6H4−2SMe (4) and (b) the palladacycles [Pd{[(η5-C5H3)−CHN−(C6H4−2SMe)]Fe(η5-C5H5)}Cl] (5a), [Pd{(2-CH2-4,6-Me2C6H2)−CHN−(C6H4−2SMe)}Cl] (5b) in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate is also reported.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, Malaria continues to be a major cause of morbidity and mortality to this day, and resistance to drugs like chloroquine has led to an urgent need to discover novel chemical entities aimed at new targets. Here, we report the discovery of a novel class of potential antimalarial compounds containing an indolizinoindolone scaffold. These novel enantiopure indolizinoindolones were synthesized, in good-to-excellent yields and excellent diastereoselectivities, by cyclocondensation reaction of (S)- or (R)-tryptophanol and 2-acyl benzoic acids, followed by intramolecular α-amidoalkylation. Interestingly, we were able to synthesize for the first time 7,13b-cis indolizinoindolones in a two-step route. The novel compounds showed promising activity against erythrocytic stages of the human malaria parasite, Plasmodium falciparum, and liver stages of the rodent parasite Plasmodium berghei. In particular, an (S)-tryptophanol-derived isoindolinone was identified as a promising starting scaffold to search for novel antimalarials, combining excellent activity against both stages of the parasite's life cycle with low cytotoxicity and excellent metabolic and chemical stability in vitro., This work was supported by Fundação para a Ciência e a Tecnologia (FCT) through iMed.ULisboa (UID/DTP/04138/2013) and research projects PTDC/QUI-QUI/111664/2009 and PTDC/SAU-MIC/117060/2010. M. M. M. Santos would like to acknowledge FCT, “Programa Operacional Potencial Humano” and the European Social Fund for the IF Program (IF/00732/2013).

Di-2,2,2-trifluoro-1-(9-anthryl)ethyl fumarate has been synthesized from fumaric acid and enantiopure Pirkle alcohol. The Diels–Alder reaction with different dienes employing different reaction conditions was assayed, with high diastereomeric excesses obtained. The structure and geometry of the cycloadducts was analyzed by NMR, molecular mechanics and X-ray diffraction. Hydrolysis made it possible to obtain the enantioenriched trans-cyclohexene-4,5-dicarboxylate derivatives and allow us to recover chiral auxiliary.

The synthesis, characterization, and study of the reactivity of the novel cyclopalladated complexes [Pd{[(η5-C5H3)CHN(C6H4-2-CH2OH)]Fe(η5-C5H5)}Cl] (2) and [Pd{[(η5-C5H3)CHN(C6H4-2-CH2O)]Fe(η5-C5H5...

A comparative study of the electrochemical properties, 57Fe NMR and Mossbauer spectroscopic data of compounds [(η5-C5H5)Fe{(η5-C5H4)–C(R1) N–R2}] {R1 = H, R2 = CH2–CH2OH (1a), CH(Me)–CH2OH (1b), CH2C6H5 (1c), C6H4–2Me (1d), C6H4–2SMe (1e) or C6H4–2OH (1f) and R1 = C6H5, R2 = C6H4–2Me (2d)} is reported. The X-ray crystal structure of [(η5-C5H5)Fe{(η5-C5H4)–CH N–C6H4–2OH}] (1f) is also described. Density functional theoretical (DFT) studies of these systems have allowed us to examine the effects induced by the substituents of the “–C(R1) N–R2” moiety or the aryl rings (in 1d–1f) upon the electronic environment of the iron(II) centre.

The easy cycloaddition of ureas with alkynyl alkoxy biscarbene complexes afforded, in fairly good yields, new biscarbene uracil analogs. X-ray structural data is reported for the dimethyluracil biscarbene complex. By changing the reaction conditions, a new non symmetric complex was obtained whose reaction with ethylenediamine afforded a new tetrakis amino carbene complex.

A new fused ring compound 2,9-dimethyl-1,10-dihydro-dicyclopenta[a,h]naphthalene (VI), (H2L), has been synthesized from naphthalic anhydride. Two organometallic binuclear complexes, [Cp*Fe-L-FeCp*] (1) and the mixed valence compound, [ Cp ∗ Fe - L - FeCp ∗ ] + BF 4 - (2) have been characterized by spectroscopic and electrochemical techniques. The structure resolution of (1) by single crystal X-ray diffraction shows that the two organometallic fragments Cp*Fe are in an anti position. Cyclic voltammetry exhibits a potential difference of 348 mV between both redox peaks. The Mossbauer investigation at different temperatures shows a uniform environment for the neutral compound (1) and two sites, assigned to Fe2+ and Fe3+ for the compound (2). The information gathered by all the previously mentioned techniques indicates that the studied binuclear complex belongs to the mixed valence class II complexes according to the classification of Robin and Day.

The synthesis, structure and behaviour as chiral solvating agents of the enantiomers of 9-anthrylpentafluorophenylmethanol is reported.