Divergent synthesis of isoindolo[2,1-a]indole and indolo[1,2-a]indole through copper-catalysed C- and N-arylations

A simple and efficient synthetic route to both isoindolo[2,1-a]indole and its structural isomer indolo[1,2-a]indole skeletons is presented. The key steps of the strategy are based on copper-catalysed C_aryl-C and C_aryl-N bond formation reactions, respectively. Moreover, we report the first copper-mediated intramolecular C-H functionalisation of an indole.     

Catalyst Deactivation during α-Pinene Isomerization. Fe-Mn-Promoted Sulfated Zirconium Oxide

This works studies the deactivation of zirconium oxide, promoted by iron and manganese catalysts (SZFM), during the -pinene isomerization. Experiments were done in liquid phase by using a batch reactor, and the solid crystalline structure was studied by XRD while the acidity by FTIR. The deactivated catalyst exhibited coke deposits and lost its Brönsted acidity, though it still kept its crystalline structure. The nature of the coke deposit formed was analyzed by infrared spectroscopy (FTIR) as well as by Temperature Programmed Oxidation (TPO). Regeneration was done in air flow, where the temperature required to restore Brönsted acidity and to totally eliminate the coke deposits was of about 873 K.     

Determination of D-fagomine in buckwheat and mulberry by cation exchange HPLC/ESI-Q-MS

d-Fagomine is an iminosugar first found in buckwheat (Fagopyrum esculentum Moench) which if used as a dietary supplement or functional food component may reduce the risks of developing insulin resistance, becoming overweight and suffering from an excess of potentially pathogenic bacteria. As d-fagomine may become increasingly important to the food industry, a reliable analytical method for its determination in natural plant sources and foodstuffs is desirable. We have devised a method to separate d-fagomine from its diastereomers 3-epi-fagomine and 3,4-di-epi-fagomine in a single run by cation exchange high-performance liquid chromatography (HPLC) with detection and quantification by mass spectrometry using electrospray ionisation and a simple quadrupole analyser (ESI–Q-MS). The method is validated and applied to the determination of d-fagomine in buckwheat groats (6.7–44 mg kg⁻¹), leaves, bran and flour. We show that buckwheat contains 3,4-di-epi-fagomine (1.0–43 mg kg⁻¹), which has not previously been reported in this source. The procedure is also applied to mulberry (Morus alba) leaves, which contain d-fagomine and 3-epi-fagomine as minor components. The new method provides a means for convenient and accurate determination of d-fagomine in plant samples and foodstuffs.     

Metallorganische Verbindungen der Lanthanoide. 88. Monomere Lanthanoid(III)-amide: Synthese und Röntgenstrukturanalyse von [Nd{N(C6H5)(SiMe3)}3(THF)], [Li(THF)2(μ-Cl)2Nd{N(C6H3Me2-2,6)(SiMe3)}2(THF)] und [ClNd{N(C6H3-iso-Pr2-2,6)(SiMe3)}2(THF)]

Organometallic Compounds of the Lanthanides. 88. Monomeric Lanthanide(III) Amides: Synthesis and X-Ray Crystal Structure of [Nd{N(C₆H₅)(SiMe₃)}₃(THF)], [Li(THF)₂(μ-Cl)₂Nd{N(C₆H₃Me₂-2,6)(SiMe₃)}₂(THF)], and [ClNd{N(C₆H₃-iso-Pr₂-2,6)(SiMe₃)} ₂(THF)] A series of lanthanide(III) amides [Ln{N(C₆H₅) · (SiMe₃)}₃(THF)_x] [Ln = Y ( 1 ), La ( 2 ), Nd ( 3 ), Sm ( 4 ), Eu ( 5 ), Tb ( 6 ), Er ( 8 ), Yb ( 9 ), Lu ( 10 )] could be prepared by the reaction of lanthanide trichlorides, LnCl₃, with LiN(C₆H₅)(SiMe₃). Treatment of NdCl₃(THF)₂ and LuCl₃(THF)₃ with the lithium salts of the bulky amides [N(C₆H₃R₂-2,6)(SiMe₃)]^? (R = Me, iso-Pr) results in the formation of the lanthanide diamides [Li(THF)₂(μ-Cl)₂Nd{N(C₆H₃Me₂-2, 6)(SiMe₃)}₂(THF)] ( 11 ) and [ClLn{N(C₆H₃-iso-Pr₂-2,6)(SiMe₃)} ₂(THF)] [Ln = Nd ( 12 ), Lu ( 13 )], respectively. The ¹H- and ¹³C-NMR and mass spectra of the new compounds as well as the X-ray crystal structures of the neodymium derivatives 3 , 11 and 12 are discussed.     

Activation of H-H and H-O bonds at phosphorus with diiron complexes bearing pyramidal phosphinidene ligands

The complex [Fe(2)Cp(2)(μ-PMes*)(μ-CO)(CO)(2)] (Mes* = 2,4,6-C(6)H(2)(t)Bu(3)), which in the solid state displays a pyramidal phosphinidene bridge, reacted at room temperature with H(2) (ca. 4 atm) to give the known phosphine complex [Fe(2)Cp(2)(μ-CO)(2)(CO)(PH(2)Mes*)] as the major product, along with small amounts of other byproducts arising from the thermal degradation of the starting material, such as the phosphindole complex [Fe(2)Cp(2)(μ-CO)(2)(CO){PH(CH(2)CMe(2))C(6)H(2)(t)Bu(2)}], the dimer [Fe(2)Cp(2)(CO)(4)], and free phosphine PH(2)Mes*. During the course of the reaction, trace amounts of the mononuclear phosphide complex [FeCp(CO)(2)(PHMes*)] were also detected, a compound later found to be the major product in the carbonylation of the parent phosphinidene complex, with this reaction also yielding the dimer [Fe(2)Cp(2)(CO)(4)] and the known diphosphene Mes*P═PMes*. The outcome of the carbonylation reactions of the title complex could be rationalized by assuming the formation of an unstable tetracarbonyl intermediate [Fe(2)Cp(2)(μ-PMes*)(CO)(4)] (undetected) that would undergo a fast homolytic cleavage of a Fe-P bond, this being followed by subsequent evolution of the radical species so generated through either dimerization or reaction with trace amounts of water present in the reaction media. A more rational synthetic procedure for the phosphide complex was accomplished through deprotonation of the phosphine compound [FeCp(CO)(2)(PH(2)Mes*)](BF(4)) with Na(OH), the latter in turn being prepared via oxidation of [Fe(2)Cp(2)(CO)(4)] with [FeCp(2)](BF(4)) in the presence of PH(2)Mes*. To account for the hydrogenation of the parent phosphinidene complex it was assumed that, in solution, small amounts of an isomer displaying a terminal phosphinidene ligand would coexist with the more stable bridged form, a proposal supported by density functional theory (DFT) calculations of both isomers, with the latter also revealing that the frontier orbitals of the terminal isomer (only 5.7 kJ mol(-1) above of the bridged isomer, in toluene solution) have the right shapes to interact with the H(2) molecule. In contrast to the above behavior, the cyclohexylphosphinidene complex [Fe(2)Cp(2)(μ-PCy)(μ-CO)(CO)(2)] failed to react with H(2) under conditions comparable to those of its PMes* analogue. Instead, it slowly reacted with HOR (R = H, Et) to give the corresponding phosphinous acid (or ethyl phosphinite) complexes [Fe(2)Cp(2)(μ-CO)(2)(CO){PH(OR)Mes*}], a behavior not observed for the PMes* complex. The presence of BEt(3) increased significantly the rate of the above reaction, thus pointing to a pathway initiated with deprotonation of an O-H bond of the reagent by the basic P center of the phosphinidene complex, this being followed by the nucleophilic attack of the OR(-) anion at the P site of the transient cationic phosphide thus formed. The solid-state structure of the cis isomer of the ethanol derivative was determined through a single crystal X-ray diffraction study (Fe-Fe = 2.5112(8) ?, Fe-P = 2.149(1) ?).     

Detection and characterization of prednisolone metabolites in human urine by LC‐MS/MS

Glucocorticosteroids are prohibited in sports when used by systemic administrations (e.g. oral), whereas they are allowed using other administration ways. Strategies to discriminate between administrations routes have to be developed by doping control laboratories. For this reason, the metabolism of prednisolone (PRED) was studied using liquid chromatography coupled to tandem mass spectrometry. A single oral (10 mg) dose of PRED was administered to two healthy male volunteers. Urine samples were collected up to 6 days after administration. Samples were hydrolyzed with β‐glucuronidase and subjected to liquid–liquid extraction with ethyl acetate in alkaline conditions. The extracts were analyzed by liquid chromatography coupled to tandem mass spectrometry. Precursor ion scan methods (m/z 77, 91, 105, 121, 147 and 171) in positive ionization and neutral loss scan methods (76 and 94 Da) in negative ionization modes were applied for the open detection of PRED metabolites. Using these methods, PRED parent compound plus 20 metabolites were detected. PRED and 11 metabolites were characterized by comparison with standards of the compounds (PRED, prednisone, 20β‐dihydro‐PRED and 20α‐dihydro‐PRED, 20β‐dihydro‐prednisone and 20α‐dihydro‐prednisone, 6β‐hydroxy‐PRED and 6α‐hydroxy‐PRED, 20β isomers and 20α isomers of 6β,11β,17α,20,21‐pentahydroxypregnan‐1,4‐diene‐3‐one, 6α,11β,17α,20β,21‐pentahydroxypregnan‐1,4‐diene‐3‐one and Δ⁶‐PRED). Using mass spectrometric data, feasible structures were proposed for seven of the remaining nine detected metabolites, including several 6‐hydroxy‐metabolites. Eleven of the characterized metabolites have not been previously described. Maximum excretion rates for PRED metabolites were achieved in first 24 h; however, most of the metabolites were still detectable in the last collected samples (day 6). Copyright © 2015 John Wiley & Sons, Ltd.     

A high-throughput method for GMO multi-detection using a microfluidic dynamic array

The ever-increasing production of genetically modified crops generates a demand for high-throughput DNA-based methods for the enforcement of genetically modified organisms (GMO) labelling requirements. The application of standard real-time PCR will become increasingly costly with the growth of the number of GMOs that is potentially present in an individual sample. The present work presents the results of an innovative approach in genetically modified crops analysis by DNA based methods, which is the use of a microfluidic dynamic array as a high throughput multi-detection system. In order to evaluate the system, six test samples with an increasing degree of complexity were prepared, preamplified and subsequently analysed in the Fluidigm system. Twenty-eight assays targeting different DNA elements, GM events and species-specific reference genes were used in the experiment. The large majority of the assays tested presented expected results. The power of low level detection was assessed and elements present at concentrations as low as 0.06 % were successfully detected. The approach proposed in this work presents the Fluidigm system as a suitable and promising platform for GMO multi-detection.     

Palladacycle Catalyzed Asymmetric PH Addition of Diarylphosphines to N‐Enoyl Phthalimides

The first asymmetric phospha‐Michael addition of diarylphosphines to N‐enoyl phthalimides has been developed in the presence of a chiral palladacycle catalyst. A library of free chiral tertiary phosphine adducts were directly obtained with excellent yields and enantioselectivities. Products can be subsequently functionalized to afford β‐phosphinoamides, the direct preparation of which from cinnamides has been notoriously challenging.     

Development of an environmentally friendly methodological approach to determine chlorinated hydrocarbons and chlorobenzenes in soils

A modified version of the quick, easy, cheap, efficient, rugged, and safe method is proposed for the determination of chlorinated pollutants in soil samples. Measurements were collected using a programmed temperature vaporizer coupled to a gas chromatograph and a µ-electron capture detector. The optimization and validation of this extraction technique for these compounds in soils have been performed in order to provide an alternative tool for determining these kinds of pollutants in soils. Advantages over conventional extraction techniques include the applicability to compounds of very different volatilities and polarities, the low cost of the reagents employed, and the possibility of being used by nonspecialist operators, with standard analytical tools. This method can be considered more environmentally friendly, due to the reduction of solvent and energy consumption and to the elimination of harmful organic solvents, reducing the negative impact of chemical analyses on the environment (principles of green analytical chemistry).