Triphenylene-based polymers for organic electronics

An efficient synthesis has been developed toward a novel series of conjugated blue emitting polymers containing triphenylene as repeating unit for polymer light emitting diodes (PLEDs). Soluble triphenylene-based co- and homo-polymers have been synthesized by the palladium-catalyzed Suzuki-Miyaura and the nickel-catalysed Yamamoto polycondensation reactions, respectively. The photophysical properties as well as the application of the polymers in PLED devices are presented here.rnIn addition a simple GNR fabrication method that allows for the production of atomically precise GNRs of different topologies and widths is introduced. This bottom-up approach consists in the surface-assisted coupling of suitably designed molecular triphenylene precursors into linear polyphenylenes and their subsequent cyclodehydrogenation and results in GNRs whose topology, width and edge periphery are defined by the precursor monomers. Various types of atomically precise GNRs thus eventually become available for experimental investigation and exploitation of their many predicted and technologically highly interesting properties. Furthermore, it is anticipated that this bottom-up approach of GNR fabrication will allow the engineering of chemical and electronic properties and the yet elusive realization of theoretically predicted structures such as intraribbon quantum dots, superlattice structures, or magnetic devices based on specific GNR edge states.rn

Synthese von Carbolinen durch übergangsmetall-katalysierte [2+2+2]-Cycloaddition von Alkinen und Nitrilen: Ein neuer Weg zur Totalsynthese von Lavendamycin

Carboline sind eine große Gruppe von natürlich vorkommenden Alkaloiden, die eine tricyclische Pyrido[b]indol-Ringstruktur gemeinsam habe. Das breite Spektrum biologischer Eigenschaften dieser Verbindungsklasse macht sie zu einem interessanten Syntheseziel. Die größte Herausforderung in der Darstellung von Carbolinen ist die regioselektive Funktionalisierung an den aromatischen Positionen. Im Rahmen dieser Arbeit konnte ein A ABC-Zugang zu beta- und gamma-Carbolinen entwickelt werden, dessen Schlüsselschritt der Aufbau des Carbolin-Gerüsts durch eine übergangsmetall-katalysierte [2+2+2]-Cycloaddition von 1,6-Diin-Einheiten und Nitrilen ist. Die benötigten Diin-Einheiten wurden in wenigen Schritten ausgehend von 2-Iodanilin durch eine Reaktionssequenz aus Sonogashira-Reaktion mit terminalen Alkinen, N-Tosylierung und N-Ethinylierung mit Alkinyliodonium-Salzen synthetisiert. Eine flexible Funktionalisierung dieser Diine wurde durch palladium-katalysierte sp2-sp-Kreuzkupplungsreaktionen der terminalen Alkine mit Aryl- und Alkenylhalogeniden erreicht. Cp*RuCl- und [Rh(cod)2]BF4/BINAP-katalysierte [2+2+2]-Cycloadditionen der 1,6-Diine mit elektronenarmen Nitrilen lieferte in hoher Regioselektivität beta- oder gamma-Carboline. In Übereinstimmung mit literaturbekannten übergangsmetall-katalysierten [2+2+2]-Cycloadditionen konnte dabei eine starke Abhängigkeit von sterischen und elektronischen Faktoren beobachtet werden. Um das Potential dieser Methode zu demonstrieren, wurde der Einsatz der [2+2+2]-Cycloaddition in Totalsynthese von Lavendamycin untersucht. Lavendamycin, ein aus Bakterien stammendes Chinochinolin-substituiertes beta-Carbolin mit antimikrobieller und signifikanter Antitumor-Aktivität, wurde ausgehend von Hydrochinon und 2-Iodanilin in 14 Schritten und in einer Gesamtausbeute von 29% dargestellt.

Kontinuierliche Kreuzkupplungsreaktionen in mikrostrukturierten Systemen

Im Rahmen dieser Arbeit wurden unterschiedliche Palladium-katalysierte Kreuzkupplungsreaktionen untersucht. Ein besonderes Augenmerk wurde dabei auf die Suzuki-Miyaura-Reaktion gelegt. Unter anderem aufgrund der langen Reaktionszeiten und der zweiphasigen Bedingungen ist diese Reaktionsklasse nur sehr schwer als kontinuierlicher Prozess zu etablieren. Vielen dieser Ansätze ist jedoch zu eigen, dass der große Vorteil der Mikroprozesstechnik, eine überlegene Kontrolle von Temperatur und Stofftransport, kaum ausgeschöpft wird. An diesem Punkt setzt diese Arbeit von technischer aus Seite an. Der zweite Schwerpunkt der Arbeit sind die prinzipiellen Untersuchungen an kontinuierlichen Flüssig-Flüssig-Zwei-Phasen-Reaktionen. Im Zuge des DBU-finanzierten Transkat-Projektes wurden hierbei anhand einfacher Veresterungsreaktionen grundlegende Kenntnisse zu Stofftransport, Grenzflächen und Phasentrennung innerhalb mikrostrukturierter Systeme gesammelt. Dank speziell angefertigter Glasmikroreaktoren von der Firma mikroglas chemtech GmbH war eine genaue optische und digitale Charakterisierung der Phasengrenzflächen möglich. Ein wichtiges Ergebnis war darüber hinaus, dass ionische Flüssigkeiten, als eigenständige Phasen verwendet, enorm zum Massentransfer und somit zur Reaktionsgeschwindigkeit beitragen können.

Synthetic studies towards a new fulvestrant analogue

A study towards the synthesis of a new fulvestrant analogue with improved bioavailability was carried out. In this work a twelve-step synthetic route starting from β-estradiol was optimized and a palladium (Pd)-catalyzed endo-selective Heck reaction for the functionalization of an advanced intermediate was investigated.

Developing of Germyldesulonylation and Thiodesulfonylation Reactions for the Synthesis of Novel Nucleoside Analogues. Efficient Synthesis of Novel (α-Fluoro)vinyl Sulfides

S-adenosyl-L-homocysteine (AdoHcy) hydrolase effects hydrolytic cleavage of AdoHcy to produce both adenosine and L-homocysteine and is a feedback inhibitor of S-adenosyl- L-methionine (SAM). Nucleoside analogues bearing an alkenyl or fluoroalkenyl chain between sulfur and C5' utilizing Negishi coupling reactions were synthesized. Palladium-catalyzed cross-coupling between the 5'-deoxy-5'-(iodomethylene) nucleosides and alkylzinc bromides gives analogues with the alkenyl unit. Palladium-catalyzed selective monoalkylation of 5'-(bromofluoromethylene)-5'-deoxy-adenosine with alkylzinc bromide afford adenosylhomocysteine analogues with a 6'-(fluoro)vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-L-homocysteine hydrolases. Stannydesulfonylation reaction is a critical step in the synthesis of E-fluorovinyl cytidine (Tezacitabine) a ribonucleoside reductase inhibitor with a potent anticancer activity. The synthesis involves the removal of the sulfonyl group by a radical-mediated stannyldesulfonylation reaction using tributyltin hydride. In order to eliminate the toxicity of tin, I developed a radical-mediated germyldesulonylation utilizing less toxic germane hydrides. Treatment of the protected (E)-5'-deoxy-5'-[(p-toluenesulfonyl)-methylene]uridine and adenosine derivatives with tributyl- or triphenylgermane hydride effected radical-mediated germyldesulfonylations to give 5'-(tributyl- or triphenylgermyl)methylene-5'-deoxynucleoside derivatives as single (E)-isomers. Analogous treatment of 2'-deoxy-2'-[(phenylsulfonyl)methylene]uridine with Ph3GeH afforded the corresponding vinyl triphenylgermane product. Stereoselective halodegermylation of the (E)-5'-(tributylgermyl)-methylene-5'-deoxy nucleosides with NIS or NBS provided the Wittig-type (E)-5'-deoxy-5'-(halomethylene) nucleosides quantitatively. Radical-mediated thiodesulfonylation of the readily available vinyl and (α-fluoro) vinyl sulfones with aryl thiols in organic or aqueous medium to provide a bench and environmentally friendly protocol to access (α-fluoro)vinyl sulfides were developed. Methylation of the vinyl or (α-fluoro)vinyl phenyl sulfide gave access to the corresponding vinyl or (α-fluoro)vinyl sulfonium salts. These sulfonium ions were tested as possible methyl group donors during reactions with thiols, phenols or amino groups which are commonly present in natural amino acids.

Síntese estereosseletiva da naftotectona

Tese (doutorado)—Universidade de Brasília, Instituto de Química, 2016.

Synthesis and stereochemistry of some bicyclic gamma-lactones from parasitic wasps (Hymenoptera : Braconidae). Utility of hydrolytic kinetic resolution of epoxides and palladium(II)-catalyzed hydroxycyclization-carbonylation-lactonization of ene-diols

A palladium(II)-catalyzed hydroxycyclization-carbonylation-lactonization sequence with appropriate pent-4-ene-1,3-diols provides efficient access to the bicyclic gamma -lactones, 5-n-butyl- and 5-n-hexyltetrahydrofuro-[3,2-b]furan-2(3H)-ones (3) and (4), respectively, in both racemic and enantiomeric forms. Some of the substrate pent-4-ene-1,3-diols of high enantiomeric excess (ee) have been derived from racemic terminal epoxides by hydrolytic kinetic resolution (HKR) using cobalt (III)-salen complexes. (9Z,12R)-(+)-Ricinoleic acid also serves as a chiral pool source of other pent-4-ene-1,3-diols. These syntheses and enantioselective gas chromatography confirm the structures and absolute stereochemistry of the lactones in some species of parasitic wasps (Hymenoptera: Braconidae). The highly abundant 5-n-hexyltetrahydrofuro-[3,2-b]furan-2(3H)-one (4) in Diachasmimorpha kraussii and D. longicaudata is of high ee (> 99%) with (3aR,5R,6aR) stereochemistry.

Thermodynamic non-ideality as an alternative source of the effect of sucrose on the thrombin-catalyzed hydrolysis of peptide p-nitroanalide substrates

The inhibitory effect of sucrose on the kinetics of thrombin-catalyzed hydrolysis of the chromogenic substrate S-2238 (D-phenylalanyl-pipecolyl-arginoyl-p-nitroanilide) is re-examined as a possible consequence of thermodynamic non-ideality-an inhibition originally attributed to the increased viscosity of reaction mixtures. However, those published results may also be rationalized in terms of the suppression of a substrate-induced isomerization of thrombin to a slightly more expanded (or more asymmetric) transition state prior to the irreversible kinetic steps that lead to substrate hydrolysis. This reinterpretation of the kinetic results solely in terms of molecular crowding does not signify the lack of an effect of viscosity on any reaction step(s) subject to diffusion control. Instead, it highlights the need for development of analytical procedures that can accommodate the concomitant operation of thermodynamic non-ideality and viscosity effects.

Catalyzed and non-catalyzed synthesis of bioactive monastrol

The bioactive 3,4-dihydropyrimidin-2(1H)-thione derivative known as Monastrol was synthesized under catalyzed and non-catalyzed conditions through the Biginelli multicomponent reaction under solvent-free conditions. The use of two Lewis acids (FeCl3 and CuCl2) and two Brønsted acids (HCl and CF3COOH) as catalysts improved the reaction yields of the transformation compared with the non-catalyzed reaction. The experiments investigated catalysis and its role, the importance of multicomponent reactions and their green features, and the application of these concepts to the synthesis of a biologically important structure.

First dynamic kinetic resolution of selenium-containing chiral amines catalyzed by palladium (Pd/BaSO(4)) and Candida antartica lipase (CAL-B)

An efficient method for chemoenzymatic dynamic kinetic resolution of selenium-containing chiral amines (organoselenium-1-phenylethanamines) has been developed, leading to the corresponding amides in excellent enantioselectivities and high isolated yields. This one-pot procedure employs two different types of catalysts: Pd on barium sulphate (Pd/BaSO(4)) as racemization catalyst and lipase (CAL-B) as the resolution catalyst. (C) 2009 Elsevier Ltd. All rights reserved.

Dynamic modeling of active regeneration in catalyzed and non-catalyzed diesel particulate filters

Particulate matter (PM) emissions standards set by the US Environmental Protection Agency (EPA) have become increasingly stringent over the years. The EPA regulation for PM in heavy duty diesel engines has been reduced to 0.01 g/bhp-hr for the year 2010. Heavy duty diesel engines make use of an aftertreatment filtration device, the Diesel Particulate Filter (DPF). DPFs are highly efficient in filtering PM (known as soot) and are an integral part of 2010 heavy duty diesel aftertreatment system. PM is accumulated in the DPF as the exhaust gas flows through it. This PM needs to be removed by oxidation periodically for the efficient functioning of the filter. This oxidation process is also known as regeneration. There are 2 types of regeneration processes, namely active regeneration (oxidation of PM by external means) and passive oxidation (oxidation of PM by internal means). Active regeneration occurs typically in high temperature regions, about 500 - 600 °C, which is much higher than normal diesel exhaust temperatures. Thus, the exhaust temperature has to be raised with the help of external devices like a Diesel Oxidation Catalyst (DOC) or a fuel burner. The O2 oxidizes PM producing CO2 as oxidation product. In passive oxidation, one way of regeneration is by the use of NO2. NO2 oxidizes the PM producing NO and CO2 as oxidation products. The passive oxidation process occurs at lower temperatures (200 - 400 °C) in comparison to the active regeneration temperatures. Generally, DPF substrate walls are washcoated with catalyst material to speed up the rate of PM oxidation. The catalyst washcoat is observed to increase the rate of PM oxidation. The goal of this research is to develop a simple mathematical model to simulate the PM depletion during the active regeneration process in a DPF (catalyzed and non-catalyzed). A simple, zero-dimensional kinetic model was developed in MATLAB. Experimental data required for calibration was obtained by active regeneration experiments performed on PM loaded mini DPFs in an automated flow reactor. The DPFs were loaded with PM from the exhaust of a commercial heavy duty diesel engine. The model was calibrated to the data obtained from active regeneration experiments. Numerical gradient based optimization techniques were used to estimate the kinetic parameters of the model.

Curtin-Hammett versus non-Curtin-Hammett frameworks is optimizing the enantioselective binolam/titanium(IV)-catalyzed cyanobenzoylation of aldehydes: Part 2

Extensive experimental and computational studies have been carried out on the enantioselective titanium(IV)-catalyzed cyanobenzoylation of aldehydes using 1:n Binolam:Ti(OiPr)4 mixtures as precatalysts, with the purpose of identifying the key mechanistic aspects governing enantioselectivity. HCN and isopropyl benzoate were detected in the reacting mixtures. This, as well as the reaction’s response to the presence of an exogenous base, and the failure to react in the presence of Binol:Ti(OiPr)4 mixtures, led us to propose not a direct cyanobenzoylation but an indirect process involving enantioselective hydrocyanation followed by O-benzoylation. Computational work provided positive evidence for the intervention of both indirect and direct cyanobenzoylation routes, the former being faster. However, the standard Curtin–Hammett-based optimization search ended with unsatisfactory results. Experimental and computational DFT studies (B3LYP/6-31G*) led us to conclude that: (1) the overall cyanobenzoylation of aldehydes catalyzed by 1:n Binolam:Ti(OiPr)4 mixtures involves an enantioselective hydrocyanation followed by an stereochemically inert O-benzoylation; (2) the initial complexes prevailing in a 1:1 Binolam:Ti(OiPr)4 mixture are the solvated mononuclear monomer 5·2(iPrOH) and solvated dinuclear dimer 9·2(iPrOH), whereas 9·2(iPrOH) is the major component in a 1:2 or higher 1:n mixture; (3) since the slowest step is that of benzoylation of ligated iPrOH which yields the actual catalysts 5–9, the catalytic system fits into a non-Curtin–Hammett framework, the final products deriving from a kinetic quench of the competing routes; and (4) accordingly, catalysis by 1:1 Binolam:Ti(OiPr)4 mixtures should involve cyanobenzoylations promoted by mononuclear 5, contaminated with those promoted by some dinuclear open dimer 9, whereas cyanobenzoylations catalyzed by a 1:2 and higher 1:n mixtures should be the result of catalysis promoted by the large amounts of dinuclear open dimer 9.

A potential role for isothermal calorimetry in studies of the effects of thermodynamic non-ideality in enzyme-catalyzed reactions

Attention is drawn to the feasibility of using isothermal calorimetry for the characterization of enzyme reactions under conditions bearing greater relevance to the crowded biological environment, where kinetic parameters are likely to differ significantly from those obtained by classical enzyme kinetic studies in dilute solution. An outline of the application of isothermal calorimetry to the determination of enzyme kinetic parameters is followed by considerations of the nature and consequences of crowding effects in enzyme catalysis. Some of those effects of thermodynamic non-ideality are then illustrated by means of experimental results from calorimetric studies of the effect of molecular crowding on the kinetics of catalysis by rabbit muscle pyruvate kinase. This review concludes with a discussion of the potential of isothermal calorimetry for the experimental determination of kinetic parameters for enzymes either in biological environments or at least in media that should provide reasonable approximations of the crowded conditions encountered in vivo. Copyright (C) 2004 John Wiley Sons, Ltd.