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1
Richmond, Craig J. "Applications for imidazophenanthridine-based heterocycles." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/1406/.
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The physical properties and reactivity of 2,3-dihydro-1H-imidazo[1,2-f]phenanthridinium cations (DIPs) and analogous heterocycles have been investigated. The adapted syntheses developed were applied to a range of aryl amines and more elaborate substrates, such as bifunctional aminoquinolinium cations and amino functionalised polyoxometalates (POMs). 1,2,3,12b-tetrahydroimidazo[1,2-f]phenanthridines (TIPs), an intermediate in the 3-step cascade synthesis of DIPs, have also been isolated. Derivatisation of the TIP structure at the imidazo-N position enables control of the reactivity of the intermediate with respect to electronic potential and pKa, allowing isolation of a selection of TIP structures. Correlations between these parameters and reaction outcome have been made and other influences such as steric and solvent effects have also been investigated. Investigation of the structure and properties of the TIP framework led to the discovery of a pH dependent cyclisation between the ring-closed TIP form and the ring-open aminoethylphenanthridinium (AEP) form. The complementary TIP and AEP forms can be further manipulated by oxidation or reduction to convert them to their “pH-inert” forms, DIP and aminoethyldihydrophenanthridine (AEDP). These four interchangeable states formed the basis of a redox “lockable” molecular switch that could be useful for molecular level information processing and data storage. The pH dependent cyclisation between the TIP and AEP forms was also investigated as a targeting mechanism for potential intercalating antitumour agents. The system looks to exploit the pH difference between cancerous tissues and normal tissue to combine high cytotoxicity with high selectivity, a desirable trait that is unfortunately absent in most chemotherapeutic agents. Preliminary in vitro assays have shown the TIP/AEP frameworks to have IC50 values in the pM range in human ovarian cancer cell lines, comparable to cisplatin and the closely related DIP intercalaters.
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Davies, Deiniol Hedd. "Synthesis and applications of Guanidine Heterocycles." Thesis, Bangor University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519556.
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Mossaraf, Hossain. "Solvent free synthesis of some heterocycles and their applications." Thesis, University of North Bengal, 2017. http://ir.nbu.ac.in/handle/123456789/2621.
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Rozgowska, Emma Jayne. "N-amino heterocycles : applications in flash vacuum pyrolysis." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5280.
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Routes to N-amino heterocycles were reviewed and findings applied to generate flash vacuum pyrolysis (FVP) precursors of two types - ketene generators and azol-1-yl radical generators. N-Amino heterocycles can be used as nitrogen radical generators, the N-N bond being homolytically cleaved at furnace temperatures of approximately 850 °C. A number of 2-substituted benzimidazoles were synthesised and subsequently Naminated. The 2-arylbenzimidazole precursors 1-amino-2-(2-methylphenyl)-1Hbenzimidazole and 1-amino-2-(2-ethylphenyl)-1H-benzimidazole were synthesised and subjected to FVP. The hydrogen transfer processes of the resulting azol-1-yl radicals were investigated. Pyrolysis of 1-amino-2-(2-methylphenyl)-1Hbenzimidazole resulted in three products; 2-(2-methylphenyl)-1H-benzimdazole, 11H-benzo[4,5]imidazo[1,2-a]isoindole and 1-(2-methylphenyl)-1Hbenzo[ d]imidazol-2-amine. Pyrolysis of 1-amino-2-(2-ethylphenyl)-1Hbenzimidazole resulted in five products, four of which have been successfully isolated and identified as 2-(2-ethylphenyl)-1H-benzimidazole, 5,6- dihydrobenzo[4,5]imidazo[2,1-a]isoquinoline, 1-(2-ethylphenyl)-1Hbenzo[ d]imidazol-2-amine and 11-methyl-11H-benzo[4,5]imidazo[2,1-a]isoindole. The mechanism of formation of most products is initiated by hydrogen atom transfer to the azol-1-yl radical position. N-Aminopyrazole was reacted with 5-methoxymethylene-2,2-dimethyl-1,3-dioxane- 4,6-dione to form the corresponding 5-(N-aminopyrazolyl)methylene derivative, which, when subjected to FVP, eliminates acetone and carbon dioxide to form a methyleneketene. This subsequently undergoes a [1,3]-hydrogen shift giving an imidoylketene which can collapse onto the neighbouring nitrogen atom forming pyrazolo[1,2-a][1,2,3]triazin-5-ium-4-olate (a novel heterocyclic mesomeric betaine system) or cyclise onto the adjacent carbon atom to yield a pyrazolopyridazinone. On variation of the furnace temperature it was apparent the former forms at relatively moderate temperatures (~500 °C) whereas the latter begins to predominate as the furnace temperature increases (~700 °C). The relationship between these kinetic and thermodynamic products was modelled using DFT calculations. By using substituted pyrazole precursors, substituents could be incorporated into all three available positions around the pyrazole ring. Using substituted acrylic esters as alternative imidoylketene generators, substituents could also be incorporated into both available positions in the pyridazinone ring. All corresponding betaine and pyrazolopyridazinone products were isolated and characterised.
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Tao, Beata 1973. "Applications of planar-chiral heterocycles in asymmetric catalysis." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/8047.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2002.Vita.
Includes bibliographical references.
The development of planar-chiral heterocycles for asymmetric catalysis and their applications to enantioselective processes were investigated. Reactions including the kinetic resolution of propargylic alcohols, the enantioselective ring opening of meso epoxides, and the asymmetric hydrosilylation of ketones were studied. ... During the past few years, our group has developed lb as one of the most effective and versatile nonenzymatic acylation catalysts for the kinetic resolution of arylalkylcarbinols. Surprisingly, however, when the optimized reaction conditions were applied to the kinetic resolution of secondary propargylic alcohols, only low to moderate selectivity factors were obtained. Detailed investigations revealed that triethylamine serves as a competitive general base catalyst in the acylation reaction of propargylic alcohols, thereby suppressing the intrinsic selectivity factor. When base is omitted, the selectivity factor for propargylic alcohol 2 (R1 = Ph, R2= Me) increases from 6 to 20. Using this new protocol, we can effect the kinetic resolution of a number of propargylic alcohols with selectivity factors of 10 or above. ... Catalysts in which oxygen is the nucleophilic site effect a number of useful transformations. In view of the utility of planar-chiral pyridine derivatives such as 1, it occurred to us that pyridine N-oxides 3 might also prove to be effective asymmetric catalysts. We synthesized complexes 3a-c and were gratified to discover that 3a efficiently catalyzes the ring opening of cis-stilbene oxide by SiC14, albeit in modest enantiomeric excess.
(cont.) By increasing the steric demand of the bottom ring, we found that the selectivity increases significantly. Thus, bulky derivative 3c affords 92% ee in the ring opening of cis-stilbene oxide at -85 C. A number of epoxides can be desymmetrized in very good yield and high stereoselectivity under these conditions (up to 98% ee). ... In addition, we have also synthesized a new family of planar-chiral N,P-ligands (4). The ligand design allows incorporation of different substituents on the phosphorus atom and on the C5R5 bottom ring, thereby providing a means for tuning catalyst enantioselectivity. We chose the asymmetric hydrosilylation of ketones to test the effectiveness of our ligand design. In general, sterically demanding silanes such as MesPhSiH2 and (o-tol)2SiH2 furnish better enantioselectivities than simple silanes like Ph2SiH2. Among the planar-chiral ligands tested, we found that ligand 4a gives the best yields and enantioselectivities for a wide array of substrates (arylalkyl ketones: up to 99% ee; dialkyl ketones: up to 96% ee). Deuterated benzaldehyde-l-d can also be reduced with excellent enantioselectivity (95% ee). Access to chiral silanes is also possible using the same ligand.
by Beata Tao.
Ph.D.
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Shrestha, Tej Bahadur. "Heterocycles for life-sciences applications and information storage." Diss., Kansas State University, 2010. http://hdl.handle.net/2097/13540.
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Doctor of PhilosophyDepartment of Chemistry
Stefan H. Bossmann
The photochromic spirodihydroindolizine/betaine (DHI/B) system has been reinvestigated applying picosecond, microsecond, stationary absorption measurements, and NMR-kinetics. The first surprise was that the electronic structure of the betaines is quite different than commonly assumed. The photochemical ring-opening of DHIs to betaines is a conrotatory 1,5 electrocyclic reaction, as picosecond absorption spectroscopy confirms. The (disrotatory) thermal ring-closing occurs from the cisoid betaine. The lifetime of the transoid betaine is 60 s at 300 K, whereas the lifetime of the cisoid isomer is of the order of 250 microseconds. According to these results, the electrocyclic back reaction of the betaines to the DHI is NOT rate determining, as previously thought, but the cisoid-transoid-isomerization of the betaine. Although the presence of a second nitrogen atom increases the photostability of the spirodihydroindolizine-pyridazine/betaine-system remarkably, the photochemical reaction mechanism appears to be exactly the same for spirodihydroindolizine-pyridazine/betaine-system. A nondestructive photoswitch or an information recording systems has been explored using styryl-quinolyldihydroindolizines. Both isomers DHI and betaine are fluorescent. When the blue betaine is stabilized in a thin polymethyl methacrylate (PMMA) matrix, it is stable for several hours even in room temperature and very stable at 77K. Although irradiation of visible light = 532 nm allows the photo-induced reaction of the Betaine back to the DHI, a nondestructive read-out can be performed at λ = 645 nm upon excitation with λ = 580 nm. Image recording (write) and read-out, as well as information storage (at 77K) have been demonstrated. Charged and maleimide-functionalized DHI/B systems have beed synthesized for use as photochemical gates of the mycobacterial channel porin MspA. Positively charged and maleimide functionalized DHI groups that were attached to the DHI/B-system permit the binding of the photoswitch to selective positions in the channel proteins due to the presence of a cysteine moiety. An inexpensive new method for the large scale synthesis of coelenterazine is developed. A modified Negishi coupling reaction is used to make pyrazine intermediates from aminopyrazine as an economical starting material. This method permits the use of up to 1g coelenterazine per kg body weight and day, which turns the renilla transfected stem cells into powerful light sources.
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Goon, Simon. "Applications of the Vilsmeier reagent in synthesis." Thesis, University of Sunderland, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245363.
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Melling, Robert Craig. "Synthesis and applications of enantiopure N-heterocycles of C2-symmetry." Thesis, Queen Mary, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393104.
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Fra, Fernández Laura. "New Applications of Iodine(III) Reactivity: Synthesis and Functionalization of Heterocycles." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/456301.
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S'han desenvolupat dues metodologies diferents per a la síntesi de indols emprant la reactivitat de iode hipervalente. En primer lloc, s'ha proposat una reacció de ciclació en la qual s'han obtingut un total de 21 exemples amb bons rendiments, a més d'estudiar el possible mecanisme d'aquesta reacció a través de diferents proves mecanístiques com ara la tècnica de marcatge de deuteri . D'altra banda, s'ha realitzat una metodologia alternativa amb substrats de partida diferents per obtenir un total de 18 exemples en bons rendiments a través tant d'una transformació estequiomètrica com catalítica. El mecanisme de la reacció s'ha estudiat en profunditat realitzant diferents estudis mecanístics, com per exemple, l'efecte dels substituents de diferent naturalesa electrònica en un dels anells aromàtics, a través de la correlació de Hammett.
A més de l'aplicació de compostos de iode hipervalente per a la síntesi d'heterocicles, els seus derivats quirals s'han fet servir per al desenvolupament d'una reacció enantioselectiva per a la 4-hidroxilació de fenols.Se han desarrollado dos metodologías diferentes para la síntesis de indoles empleando la reactividad de Yodo hipervalente. En primer lugar, se ha propuesto una reacción de ciclación en la que se han obtenido un total de 21 ejemplos con buenos rendimientos, además de estudiar el posible mecanismo de dicha reacción a través de diferentes pruebas mecanísticas como por ejemplo la técnica de marcaje de deuterio. Por otro lado, se ha realizado una metodología alternativa con sustratos de partida diferentes para obtener un total de 18 ejemplos en buenos rendimientos a través tanto de una transformación estequiométrica como catalítica. El mecanismo de la reacción se ha estudiado en profundidad realizando diferentes estudios mecanísticos, como por ejemplo, el efecto de los sustituyentes de diferente naturaleza electrónica en uno de los anillos aromáticos, a través de la correlación de Hammett. Además de la aplicación de compuestos de yodo hipervalente para la síntesis de heterociclos, sus derivados quirales se han usado para el desarrollo de una reacción enantioselectiva para la 4-hidroxilación de fenoles.
Two different methodologies have been developed for the synthesis of indoles using hypervalent iodine reactivity. First, a cyclization reaction has been proposed in which a total of 21 examples were obtained with good yields. In order to elucidate the reaction mechanism, different kinetic experimentes were performed such as the deuterium labellind technique . On the other hand, an alternative methodology has been performed with different starting materials obtaining a total of 18 examples in good yields through both a stoichiometric and catalytic transformation. The mechanism of the reaction has been studied by performing different mechanistic studies, such as the effect of the substituents of different electronic nature on one of the aromatic rings, through the Hammett correlation. In addition to the application of hypervalent iodine compounds for the synthesis of heterocycles, their chiral derivatives have been used for the development of an enantioselective reaction for the 4-hydroxylation of phenols.
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Gentili, Denis <1982>. "Synthesis of five-membered heterocycles and of nanostructured systems for nanomedicine applications." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2461/1/Gentili_Denis_tesi.pdf.
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Gentili, Denis <1982>. "Synthesis of five-membered heterocycles and of nanostructured systems for nanomedicine applications." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2461/.
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Martyn, Derek Craig. "Nitrogenous heterocycles : modulation of chemical properties, and applications to synthetic and medicinal chemistry." Thesis, University of Canterbury. Chemistry, 2003. http://hdl.handle.net/10092/5650.
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This thesis examines ways in which the chemical reactivity of benzimidazole-, pyrrole- or pyrrolizinone-based heterocycles can be modulated. The latent reactivity of these systems has been used to develop enzyme inhibitors, antitumour compounds and a novel amino acid derivatisation technique.
Chapter One introduces the concept of modulated chemical reactivity, with illustrative examples from biochemistry, synthesis and medicinal chemistry. The application of latent reactivity towards the inhibition of serine proteases, a class of proteolytic enzymes, is then reviewed. Two inhibitor classes are discussed, the first of which require an inorganic cofactor, e.g. a metal ion, for enhanced activity. Secondly, mechanism-based inhibitors, which rely on activation by the protease to covalently derivatise the enzyme, are discussed. The application of latent reactivity to effect DNA alkylation, and hence inhibit tumour cell growth, is also reviewed. This section places particular emphasis on alkylators that arc attached to an intercalator to enhance their affinity for DNA.
Chapter Two describes the inhibition of -chymotrypsin, a representative serine protease, by compounds that were proposed to exhibit enhanced activity upon the coordination of Zn2+. The attempted synthesis of the putative inhibitors 2.1a-b was hindered by the instability of the diamine precursors 2.2a-b. The model compound 2.1c was prepared, however this compound was prone to deuteration and oxidation at its methylene bridge. Benzimidazoles 2.14a-c were subsequently prepared, in addition to the dihydrochloride salt of 2.14a. These compounds were moderate to weak inhibitors of a-chymotrypsin, and no Zn2+-mediated enhancement of inhibition was observed. Benzimidazole 2.14b was shown to coordinate Zn(OAc)2 by 1H NMR spectroscopy, which illustrated that the lack of Zn2+-enhanced inhibition of a-chymotrypsin by compounds of type 2.14 did not result from an inability to complex metal ions.
Chapter Three describes the inhibition of a-chymotrypsin by a new series of C2-acyl-C5- (hydroxyalkyl)pyrroles. These compounds are postulated to be mechanism-based inhibitors. The pyrrole-based peptidomimetics 3.13a and 3.14a were prepared and assayed against a-chymotrypsin. Minimal difference in activity was observed between these compounds, despite the bulky hydrophobic moiety at C5 of 3.14a, which was proposed to bind more tightly to the S1 subsite than the 5-(hydroxymethyl) group of 3.13a. Mass spectrometry of 3.13a incubated with a-chymotrypsin suggested that inhibition was noncovalent in nature. Modifications at the C2 position of 3.13a led to the preparation of 3.13b, 3.24 and 3.25, of which the latter was the optimal inhibitor, and an IC50 value of 108 M was determined for this compound. The attempted solid phase synthcsis of 3.13a was ineffectual due to the instability of the 5-(hydroxymethyl)pyrrole moiety to TFA. Solid phase synthesis of a 5-formylpyrrole precursor to 3.13a gave the desired product 3.36 as an inseparable mixture with pyrrole acid 3.16b. Solution phase synthesis of the 5- (hydroxymethyl)pyrrole 3.35, which possessed a carboxylic acid moiety, afforded an unstable compound.
Chapter Four details a novel derivatisation method for amino acids, whereby the amine is first "capped" by pyrrole acid 3.16b. Subsequent reaction with hydrocinnamoyl chloride releases the latent spectrophotometric properties of the pyrrole-amino acid adduct. A previous study afforded pyrrolizinones 4.11a-c, and this study expanded the range of pyrrolizinones available for analysis to include 4.11d-i and 4.17a-b. Initial UV-vis spectroscopic analysis revealed that methanol degraded pyrrolizinone 4.11e. UV-vis spectroscopy of 4.11a-i/4.17a-b in acetonitrile revealed that the variable R1 and R2 groups did not affect the Amax and 8 values in a systematic manner. Analysis of the LRMS fragmentation patterns for 4.11a i/4.17a-b, and their pyrrole precursors 3.18a-i/3.29a-b, revealed that a production was generated whose mass was dependent on the R1 group. The abundance of the diagnostic product ion was dependent on the nature of R1 and R2. Fragmentation was increased by the technique of electron impact, compared to electro spray ionisation.
Chapter Five describes the application of 5-(hydroxymethyl)pyrroles towards the development of DNA alkylators with latent reactivity. Attachment of an intercalator to the pyrrole moiety via an alkyl linker was proposed to increase cytotoxicity. Model studies afforded 5.21 (naphthyl-based) and 5.31 (quinolyl-based), however the synthetic methodology was not amenable to compounds that incorporated anthryl or acridine moieties, i.e. "true intercalators". Compounds 5.21 and 5.31 displayed moderate activity against the P388 cancer cell line. The 5-(hydroxymethyl)pyrrole substructure analogue (5.41) elicited no activity in the P388 assay. Compound 5.31 did not react with aniline, which suggested that compounds of this type would not effect DNA alkylation in vivo. A DNA binding assay revealed that 5.31 had a low affinity for the genetic material, which rationalised its moderate P388 activity. Compounds 5.21 and 5.31 displayed minimal antiviral and antimicrobial activity.
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Krikorian, Markrete. "Probing the two-dimensional assembly of inorganic complexes and heterocycles for sensing applications." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/112517.
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Thesis: Ph. D. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references.
Chemiresistive sensing is a facile, affordable, efficient, and translatable way to detect compounds at concentrations as low as parts per billion; however, the key mechanism of molecular sensing is still unknown. In this thesis, a fundamental approach is used to study molecular assembly and reactivity by looking at the intermolecular interactions of each system presented to determine how specific interactions impact the macroscopic properties or ability of the chemical species to detect incoming analyte gases relevant for chemical sensing. Scanning Tunneling Microscopy (STM) was used as a primary tool to better understand the changes to a sensing system at the molecular level. In a similar vein, several platinum complexes useful as luminescence-based chemical sensors were studied using various liquid crystalline characterization techniques to understand how their intermolecular properties impacted their bulk assembly behavior. The Swager lab has developed chemiresistive and luminescence-based sensors for a wide variety of applications and it is the hope that fundamental studies such as this will help elucidate the molecular basis of the sensing response and in the long term will allow for the development of more sophisticated and predictable sensors.
by Markrete Krikorian.
Ph. D. in Inorganic Chemistry
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Dwyer, P. Owen. "New applications of 5-amino-1,2,3-triazoles in the synthesis of functionalised heterocycles." Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/13752.
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The ability of 5-amino-1-arylmethyl-1H-1,2,3-triazole derivatives to undergo novel diazotative deaminative cyclisation reactions to afford 1,2,3-triazolo[5,1-a] isoindolenines was also studied. The mechanism of this novel type of deaminative cyclisation reaction was investigated and the results obtained suggest the involvement of previously undescribed 1,2,3-triazolyl cation species. Attempts to induce the acid-catalysed triazole scission of 1,2,3-triazolo[5,1-a]isoindolenine derivatives led to the formation of intractable materials presumably derived from the polymerisation of the isoindolenine cleavage products. It was found that the diazotisation of 5-amino-1-arylmethyl-1H-1,2,3-triazole derivatives with arylmethyl groups activated by powerful electron-donating substituents, such as a methoxyl, resulted in cyclisation to afford derivatives of the novel 1,2,3-triazolo[5,1-c]benzo-,2,4-triazepine ring system. It was also found that such 1,2,3-triazolo[5,1-c]benzo-1,2,4-triazepine derivatives showed a tendency to undergo base-catalysed tautomerism leading to loss of the aromaticity due to the benzene ring. In addition, the acid-catalysed triazole scission of triazolobenzo-1,2,4-triazepine derivatives was studied and shown to be disfavoured. The scope of the diazotative deaminative cyclisation reactions of various 5-amino-1-aryl-1H-1,2,3-triazole derivatives was investigated and shown to provide practical methods for the synthesis of bridgehead-fused 1,2,3-triazolobenzoisoquinoline and 1,2,3-triazolophenanthridine derivatives. The acid-catalysed triazole scission of 1,2,3-triazolophenanthridine derivatives was demonstrated to provide a viable route to usefully functionalised phenanthridine derivatives. In contrast 1,2,3-triazolobenzoisoquinoline derivatives proved to be stable to acid-catalysed triazole scission.
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Niu, Jingze. "Development and applications of rhodium-catalysed reactions to explore the synthesis of heterocycles." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:1bea588d-c54e-429a-8e12-66de38ffb3ad.
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This thesis, submitted for the degree of Doctor of Philosophy in Organic Chemistry, documents new methodologies towards the synthesis of saturated heterocycles. These methods utilise a variety of novel S- and N-chelating alkenyl aldehyde substrates, and exploit a Rh(I)-catalytic system for the coupling of these aldehydes with alkynes, alkenes and boronic acids. Chapter 1 presents a literature review surveying the development of both intramolecular and intermolecular rhodium-catalysed hydroacylation, paying particular attention to the use of chelating substrates to promote hydroacylation and suppress the decarbonylation process. The importance of N-heterocycles in pharmaceutical and natural products is also documented. Chapter 2 demonstrates the use of heterocycle-derived β-S-enals as bifunctional substrates in a rhodium-catalysed hydroacylation/Suzuki coupling sequence, resulting in the three-component assembly of heterocyclic product. An intensive study of the derivatization of the substituted heterocyclic products is also described. Chapter 3 presents a kinetic resolution study on tropane derivatives using the rhodium-catalysed alkyne hydroacylation reaction. A wide range of chiral phosphine ligands and a variation of reaction conditions and chelating groups have been explored. Chapter 4 documents an investigation of the rhodium-catalysed hydroacylation reaction using N-chelating alkenyl aldehyde substrates. A variety of β-aminoenal precursors were obtained using the Buchwald-Hartwig amination. The optimisation of the reaction conditions using various bis-phosphine ligands with different chelating groups has been documented. A brief alkyne and alkene component scope is also included. Chapter 5 documents the experimental data. Appendix presents 1H, 13C and 19F NMR spectra of novel compounds and chiral HPLC data.
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CINQUIN, CHRISTOPHE. "Nouvelles voies d'acces aux heterocycles azotes a cinq chainons enantiomeriquement purs. Applications en synthese." Paris 11, 1996. http://www.theses.fr/1996PA112081.
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Le travail presente dans ce memoire concerne la synthese de composes azotes chiraux par transfert de chiralite controle par un groupe thermolabile. Dans un premier temps, a ete mise au point la synthese d'hemiaminals (equivalents d'aldehydes-gamma-amines) bicyclique rigides optiquement actifs via une transesterification enantioselective catalysee par la lipase de pseudomonas cepacia. Au cours de cette etude un nouveau rearrangement du systeme bicyclique 7-oxabicyclo2. 2. 1hept-5-ene a ete mis en evidence. La premiere partie decrit une reaction de wittig-horner sur la fonction aldehydique de ces hemiaminals, suivie d'une addition 1,4 de michael intramoleculaire hautement diastereoselective. Une reaction de retro diels-alder, elimine la copule chirale et donne acces a des 2,5-dihydropyrroles homochiraux fonctionnalises en position 2. Ces dihydropyrroles ont ete utilises pour la synthese de composes naturels ou non, antiviraux potentiels: la lactone de geissman-waiss, precurseur de pyrrolizidines hydroxylees, d'une pyrrolidine polyhydroxylee, ainsi que de la ruspolinone. Dans une deuxieme partie ont ete abordees, les reactions d'addition de reactifs organometalliques sur des imines et des ions iminiums bicycliques rigides. La reactivite de ces substrats azotes s'est revelee bonne et la diastereoselectivite excellente. Une reaction de retro diels-alder conduit a des (z)-gamma-aminoalcools-alpha, beta-ethyleniques, composes possedant un grand potentiel synthetique
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Dalai, Suryakanta. "New applications of methyl 2-chloro-2-cyclopropylideneacetate towards the synthesis of biologically important heterocycles." [S.l.] : [s.n.], 2005. http://webdoc.sub.gwdg.de/diss/2005/dalai.
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Qiao, Shuang 1971. "Design, synthesis and mechanistic studies of boron and phosphorus heterocycles and their applications in asymmetric catalysis." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85295.
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Vidal, Albalat Andreu. "Asymmetric epoxidation of electron-deficient olefins and synthetic applications." Doctoral thesis, Universitat Jaume I, 2016. http://hdl.handle.net/10803/396342.
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Aquest treball expandeix l'utilitat sintètica dels nitroepòxids, fent d'ells excel·lents precursors de 1,4-diazaheterocicles; com per exemple, quinoxalines, tetrahidroquinoxalines, piperazines i pirazines. Mitjançant una metodologia simple i efectiva, es poden sintetitzar fàcilment compostos saturats (piperazines, tetrahidroquinoxalines) o insaturats (quinoxalines, pirazines), controlant que les condicions siguen reductives o oxidants respectivament. També s'ha reportat la síntesi d'altres heterocicles com tiomorfolines i morfolinols.
D'altra banda, s'ha exposat l'epoxidació asimètrica de nitroalquens via catàlisi per transferència de fase. S'ha elucidat i proposat un mecanisme d'acció sobre el paper del catalitazador en l'enantioselectivitat, després d'un intensiu estudi sobre les condicions de reacció. Els resultats experimentals s'han recolzat amb estudis computacionals.The present work expands the synthetic versatility of nitroepoxides and the synthesis of diverse 1,4-diazaheterocycles, including quinoxalines, piperazines, tetrahydroquinoxalines and pyrazines, has been reported. In a simple methodology, adding reductive or oxidative agents to the reaction mixture allows the formation of saturated (piperazines, tetrahydroquinoxalines) or unsaturated (quinoxalines, pyrazines) heterocycles, respectively. The synthesis of other heterocycles, such as morpholinols and thiomorpholines, is also described. The first effective asymmetric epoxidation of nitroalkenes via phase transfer catalysis is also reported. Several efforts were made to elucidate the role of the catalyst and other conditions on the enantioselectivity. Experimental observations were supported by DFT studies.
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Chong, Eugene. "Early transition metal complexes of pyridine derivatives : applications in the catalytic synthesis of amines and N-heterocycles." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50998.
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The work described in this thesis focuses on the development of pyridine-derived group 4 and 5 complexes for application in the catalytic synthesis of selectively substituted amines. Two different catalytic alkene hydrofunctionalization reactions were targeted: hydroamination and hydroaminoalkylation. Respectively, these transformations provide atom-economical strategies for the formation of new C–N and C–C bonds on amines, using simple alkenes as the alkylating agents. A series of bulky mono(2-aminopyridinate)tris(dimethylamido)titanium complexes with varying steric parameters were synthesized and explored for intramolecular hydroamination reactivity using aminoalkene substrates. A titanium catalyst capable of room-temperature hydroamination reactivity was identified for the synthesis of gem-disubstituted 5- and 6-membered-ring products. This catalyst has good breadth of reactivity, including the challenging 7-membered-azepane ring formation and hydroamination with internal alkenes. A catalytically active 2-aminopyridnate-supported imido titanium complex was prepared, and reactivity investigations of this complex suggest that this reaction proceeds via an intermediate imido [2+2] cycloaddition pathway. Various 3-substituted-2-pyridonate ligands were synthesized and examined as ancillary ligands for targeting chemoselectivity for intramolecular hydroaminoalkylation over hydroamination. Systematic ligand screening studies showed that bis(3-phenyl-2-pyridonate)bis(dimethylamido)titanium complex is selective for hydroaminoalkylation over hydroamination. This is the first catalyst that can selectively α-alkylate primary aminoalkenes to access both 5- and 6-membered-cycloalkylamines with good substrate-dependent diastereoselectivity. Mechanistic and stoichiometric experiments using this complex support the involvement of a bimetallic imido species in the reaction. Notably, a titanium(III) species was isolated during these investigations. Reliable synthesis of this titanium(III) complex and examination of its reactivity showed that it is not active for hydroaminoalkylation. Varying combinations of mixed 2-pyridonate/alkyl/amido/chloro tantalum complexes were targeted to expand the substrate scope for intermolecular hydroaminoalkylation. The synthesis of mono(2-pyridonate)/alkyl/chloro tantalum complex was unsuccessful. Instead, bis(2-pyridonate)tantalum alkyl complexes were formed. While these complexes showed hydroaminoalkylation reactivity for terminal alkenes, their thermal and light sensitivity presents difficulty for synthetic application. The design and synthesis of a mixed 2-pyridonate-Ta(NMe₂)₃Cl provided a sterically accessible metal center for the hydroaminoalkylation of sterically demanding disubstituted alkenes. This complex is the first effective precatalyst for the alpha-alkylation of unprotected secondary amines using unactivated (E)- and (Z)-internal alkenes without C=C bond isomerization.Science, Faculty of
Chemistry, Department of
Graduate
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Hagar, M. E. F. A. K. "Nitrogen Ligands in Homogeneous Catalysis: Applications to The Synthesis of Nitrogen Heterocycles and Development of New Chiral Ligands." Doctoral thesis, Università degli Studi di Milano, 2009. http://hdl.handle.net/2434/148633.
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1)Synthesis of Indoles by intermolecular Cyclization of Unfunctionalized Nitroarenes and Alkynes: One-step Synthesis of the Skeleton of Fluvastatin. 2)Chiral Cyclopropylamines in the Synthesis of New Ligands; First Asymmetric Alkyl-BIAN Compounds. 3) Use of formates as an alternative to carbon monoxide for the reductive cyclization of orto-nitrostyrenes to indoles. 4) A new strategy for the synthesis of indoles by metal catalyzed reduction by CO of beta-nitrostyrenes
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Szücs, Rózsa. "Phosphorus modified PAHs : tunable π-systems for optoelectronic applications." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S022/document.
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Les Hydrocarbures Polycycliques Aromatiques (abréviés PAHs en anglais) sont des synthons importants du point de vue expérimental et théorique en raison de leurs potentielles applications dans des dispositifs optoélectroniques tels que les diodes électroluminescentes organiques, les cellules solaires ou les transistors à effet de champs. Les propriétés des PAHs peuvent être modifiées par l'insertion d'hétéroatomes dans le squelette carboné sp2. Cependant, les exemples de PAHs modifiés par un atome de P sont très rares. Nous avons démontré expérimentalement et théoriquement que l'insertion d'un atome de P en périphérie du PAH a un impact important sur la structure électronique de l'ensemble du système π-étendu, comme le montre l'étude des orbitales frontières HO (Haute Occupée) et BV (Basse Vacante). Ces deux orbitales moléculaires gardent les caractéristiques spatiales du phosphole parent. Cependant l'écart HO-BV est fortement diminué en raison de l'interaction du phosphole et du système π-conjugué bidimensionnel. En effet, la densité électronique est délocalisée sur l'ensemble de la structure carbonée. L'effet de la modification chimique de l'atome de P (dont la complexation par des métaux de transition) sur les propriétés électroniques a été étudié et il a été démontré qu'elle permet de modifier finement les propriétés optiques. L'aromaticité est également un paramètre fondamental des systèmes π-conjugués (poly)cycliques. L'aromaticité locale de chaque cycle des PAHs a été étudiée grâce au calcul du paramètre NICS(1). La modification de l'aromaticité locale de l'hétérocycle à 5 chainons (par variation de l'hétéroatome) a un fort impact sur l'aromaticité locale des cycles adjacents. Il a également été montré que la cyclo-addition sur les PAHs phosphorés a lieu sur l'hétérocycle de plus faible aromaticité et permet de préparer des PAHs inéditsPolycyclic aromatic hydrocarbons (PAHs) are important targets of experimental and theoretical studies, because of their potential use in optical and electronic devices, such as light-emitting diodes, field-effect transistors or photovoltaics. The properties of PAH systems can be modified by embedding heteroatoms into the sp2 backbone, however for P-modified PAHs, only a few examples exist. During my PhD research, I studied the properties of P-containing extended π-systems. It has been revealed by density functional calculations that the incorporation of phosphorus at the edge position of a PAH has a significant effect on the electronic structure of the entire π-system, as can be seen through the HOMO and LUMO. On the one hand, both orbitals keep the spatial characteristics of the parent heterocycle, on the other hand, the reduced HOMO-LUMO gap compared to the parent heterocycle is a consequence of the interaction between the phosphole unit and the extended aromatic system, as the molecular orbitals are delocalized through the sp2 carbon skeleton. We investigated the effect of chemical modification (including complexation) at the phosphorus atom, and found that due to the variation of the hyperconjugative interaction it can be used to fine-tune the optical properties. Aromaticity is one of the key characteristics of π-systems. During its investigation we have established that the local aromaticities in the investigated ring system could be best described by the NICS(1) values. The modification of the local aromaticity of the five-membered ring (by the variation of the heteroatom) has a significant impact on the local aromaticities of some of the other rings as well. It has been shown that the Diels-Alder cycloaddition of the P-embedded PAHs proceeds at those rings which exhibit the lowest aromaticity
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Liu, Shih-Yuan 1975. "Applications of novel boron-nitrogen containing heterocycles : design and synthesis o planar-chiral Lewis acids for stereoselective organic synthesis." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/30063.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2004.Vita.
Includes bibliographical references.
Because Lewis acids are very versatile mediators of a variety of stereoselective organic transformations, a great deal of effort has been devoted toward the development of chiral Lewis acids. This thesis describes the design, synthesis, and applications of 1,2-azaborolyl complexes as a novel family of planar-chiral Lewis acids that can perform a wide range of stereoselective transformations. The 1,2-azaborolyl ligand is a five-membered B-N bearing heterocycle that is isoelectronic and isostructural with the ubiquitous cyclopentadienyl ligand. In Part I of this dissertation, the feasibility of using boron-substituted 1,2-azaborolyls as tunable cyclopentadienyl surrogates is established. Thus, X-ray structural and spectroscopic studies demonstrate that 1,2-azaborolyls can serve as six-electron [pi]-ligands to a variety of transition metals and that the electronic nature of the boron substituent can modulate the properties of the resulting complexes. Building on the foundations of 1,2-azaborolyl ligand chemistry described in Part I, we establish in Part II that 1,2-azaborolyl complexes bearing good leaving groups on boron can serve indeed as planar-chiral Lewis acids. As a result, we have successfully synthesized a number of enantiomerically pure planar-chiral Lewis acids, and we show through structural and stereochemical correlation studies that these Lewis acids can activate substrates such as aldehydes and imines toward stereoselective nucleophilic attack in a predictable fashion. Specifically, we have investigated planar-chiral Lewis acid mediated nucleophilic attack of Grignard reagents to imines and Lewis acid mediated Mukaiyama aldol reaction of aldehydes with silyl ketene acetals.
(cont.) Our studies indicate that unfavorable peri-interactions between the imine substrate and the Lewis acid may be the conformation-controlling element for nucleophilic additions to imines. On the other hand, detailed mechanistic studies of the Mukaiyama aldol reaction suggest a reaction pathway involving an intermediate with a coplanar aldehyde-Lewis acid conformation. These studies demonstrate the broad scope and the high efficiency with which the chiral information is transferred from the planar-chiral Lewis acid to its substrates. Consequently, the turnover step (regeneration of the active Lewis acid) represents the last hurdle to be addressed for achieving asymmetric Lewis acid catalysis. Part III of this thesis describes miscellaneous applications that have been discovered during the course of the development of 1,2-azaborolyl-based planar-chiral Lewis acids. In Chapter 7, we present a surprisingly mild and versatile method for palladium-catalyzed Suzuki cross-couplings of aryl chlorides in the presence of a triarylphosphine. With this catalytic system, both sterically demanding and electronically deactivated aryl chlorides can be efficiently coupled with a range of boronic acids in good yields, and coupling of activated aryl chlorides can be accomplished at room temperature. In Chapter 8, we report the synthesis and characterization of novel 1,2-azaborines and their potential as benzene surrogates.
by Shih-Yuan Liu.
Ph.D.
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Nafe, Julia Christine Ruth [Verfasser], and Paul [Akademischer Betreuer] Knochel. "Preparation and functionalization of new N- and S-heterocycles for material science applications / Julia Christine Ruth Nafe ; Betreuer: Paul Knochel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1122019432/34.
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Mosrin, Marc [Verfasser], and Paul [Akademischer Betreuer] Knochel. "Regio- and chemoselective metalations of N-heterocycles : applications to the synthesis of biologically active compounds / Marc Mosrin ; Betreuer: Paul Knochel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/118479412X/34.
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ANSELMO, MANUEL. "Exploitation of Photochemistry and Visible Light Photoredox Catalysis towards novel transformations in Organic Synthesis: Multicomponent Reactions, synthesis of heterocycles and other applications." Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/941702.
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Kulkarni, G. M. "Transition metal nitrenes-synthetic applications in aziridination and bicyclic N-heterocycles and use of nitrogen ligands in heck suzuki coupling and amination reactions." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2006. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2486.
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Ren, Hongjun. "Preparation of Condensed N-Heterocycles via Chemoselective Benzylic C-H Activations and Preparation of Alkenylmagnesium Reagents, Allylic Zinc Reagents and their Applications in Organic Synthesis." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-62454.
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Sanchez, Duque Maria del Mar. "Nouvelles applications de l'addition de Michael organo catalysée dans des réactions domino multicomposés énantiosélectives." Thesis, Aix-Marseille 3, 2011. http://www.theses.fr/2011AIX30047.
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Au cours de ce travail, nous nous sommes intéressés à explorer le potentiel d’une réaction multicomposés initiée par une addition de Michael conduisant à des dérivés de 2,6-DABCO. Dans ce contexte, nous avons tout d’abord étudié l’étendue de la réaction en modifiant les différents partenaires et paramètres réactionnels. Dans le but de rendre ce procédé plus éco-compatible, l’utilisation de liquides ioniques recyclables a aussi été étudié. Dans certains cas, les liquides ioniques ont permis de s’affranchir du solvant organique toxique et du catalyseur hétérogène de la réaction. Enfin, afin de mettre en œuvre une synthèse multicomposés énantiosélective de 2,6-DABCO, nous avons été amenés à développer une nouvelle méthodologie d’addition de Michael énantiosélective organocatalysée de béta-cétoamides sur des dérivés carbonylés alpha,béta-insaturés. Ainsi, des adduits comportant un centre stéréogène quaternaire entièrement carboné ont pu être obtenus avec de bons rendements et des excès énantiomériques qui atteignent 99%. Une étude sur la réactivité de ces adduits nous a permis d’accéder à différentes familles de composés poly(hétéro)cycliques optiquement actifs d’un grand intérêt synthétiqueIn this work, we explored the potential of a Michael addition-initiated multicomponent reaction leading to 2,6-DABCO derivatives. In this context, we first studied the scope of the reaction by changing the partners and the parameters of the reaction. In view of making the process more eco-friendly, the use of ionic liquids was also investigated and found that in some cases, the ionic liquids could replace the toxic organic solvent and the heterogeneous catalyst of the reaction. Finally, the implementation of an enantioselective multicomponent synthesis of 2,6-DABCO led us to develop a new methodology of an organocatalytic enantioselective Michael addition of beta-ketoamides to alpha, beta-unsaturated carbonyls. In this way, adducts containing an all-carbon quaternary stereocenter were obtained in good yields and high to excellent enantiomeric excesses (up to 99%). The study of the reactivity of these adducts allowed the access to different families of optically active poly(hetero)cyclic compounds of high synthetic interest
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Gholap, A. R. "Application of ionic liquids/ultrasound towards the study of cross coupling reactions, multi- component reactions; synthesis of enaminones/pd enaminone complexes and their applications; studies towards the synthesis of novel biologically active nitrogen heterocycles." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2008. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2642.
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Benaissa, Idir. "Ligands imidazo[1,5-a]pyridin-3-ylidènes fonctionnalisés : synthèse, chimie de coordination et applications en catalyse à l'or(I)." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30194.
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Ce travail s'inscrit dans le cadre de la chimie des carbènes N-hétérocycliques (NHCs) et a pour objectif principal le développement de nouveaux ligands NHCs basés sur la plateforme imidazo[1,5-a]pyridin-3-ylidène (IPy) dont la position 5 est fonctionnalisée par un hétérocycle barbiturique anionique ou neutre, et potentiellement chiral. L'intérêt majeur de cette structure bicyclique rigide réside dans la géométrie "en L" des ligands générés, qui est particulièrement bien adaptée à la catalyse à l'or(I). Dans un premier temps, notre attention s'est portée sur une version achirale de cette famille. Après avoir décrit la voie de synthèse vers les précurseurs zwitterioniques, les complexes anioniques et neutres d'or(I) supportés respectivement par un NHC anionique et par des ligands NHCs neutres obtenus par C- et O-fonctionnalisation de la partie malonate de l'hétérocycle barbiturique ont été synthétisés et caractérisés. L'étude comparée de ces complexes en tant que pré-catalyseurs dans des réactions d'hydroélémentation des alcynes et de réactions domino, impliquant une cycloisomérisation des énynes-1,6 suivie d'une addition nucléophile, a montré que le complexe à ligand O-méthylé est le meilleur de la série, ainsi que supérieur aux NHCs classiques tant en termes d'activité que de sélectivité (TON et TOF). L'efficacité remarquable de ces complexes d'Au(I) a été rationalisé par la stabilisation électronique et stérique de l'espèce active d'or(I) cationique par le ligand NHC. Dans un deuxième temps, le processus d'oxydation des complexes d'Au(I) en Au(III) en utilisant un oxydant externe a été étudié en détails, et a montré que le ligand anionique se réarrangeait pour passer de monodente dans les complexes d'Au(I) à bidente de type LX dans les complexes d'Au(III), par déformation de l'hétérocycle barbiturique et réhybridation du carbone malonique central. Ce comportement s'est révélé général dès que la géométrie de coordination du centre métallique laisse un site de coordination en cis du centre carbénique. Les complexes de Pd(II), Rh(I), Ir(I) et Mn(I) ont ainsi été synthétisés et caractérisés. L'analyse structurale des complexes montre que le degré d'hybridation du carbone malonique est fonction de l'électrophilie du métal, avec un caractère sp3 plus marqué lorsque le centre métallique est plus pauvre en électrons. Une bibliothèque de trois ligands chiraux a été synthétisée à partir de la (S)-(-)-1-phényléthylamine comme source de l'information chirale à travers une stratégie de synthèse convergente et analogue à celle des dérivés achiraux. Les complexes d'Au(I) correspondant ont été synthétisés et utilisés comme des pré-catalyseurs dans des réactions domino d'énynes-1,6 et permettent d'accéder à de bons rendements et des excès énantiomériques allant jusqu'à 70%. En parallèle, la réactivité de la plateforme 5-bromoimidazo[1,5 a]pyridinium avec les esters maloniques et les esters de 2-arylacétates a été développée. Cette étude a mis le point sur l'utilisation des NHCs libre comme des intermédiaires réactionnels dans la synthèse des composés mésoioniques hétérotricycliques fusionnésThis PhD work concerns the chemistry of N-heterocyclic carbenes (NHCs) and its main objective consists in the development of new NHC ligands based on the imidazo[1,5-a]pyridin-3-ylidene (IPy) platform whose position 5 is functionalized by an anionic or neutral, and potentially chiral barbituric heterocycle. The major advantage of this rigid bicyclic structure lies in the "L-shaped" geometry of the generated ligands, which is particularly well adapted to gold (I) catalysis. In a first time, the chemistry of an achiral version of this family is reported. After describing the synthetic pathway to the zwitterionic precursors, the anionic and neutral gold(I) complexes supported respectively by an anionic NHC and neutral NHC ligands obtained by C- and O-functionalization of the malonate part of the barbiturate heterocycle were synthesized and characterized. The comparative study of these complexes as pre-catalysts in alkyne hydroelementation and domino reaction reactions, involving cycloisomerization of 1,6-enyne followed by nucleophilic addition, showed that the O-methylated ligand complex is the best in the series, as well as superior to conventional NHCs in both activity and selectivity (TON and TOF). The remarkable efficacy of these Au(I) complexes has been rationalized by the electronic and steric stabilization of the active species of cationic gold(I) by the NHC ligand. In a second step, the oxidation process of Au(I) to Au(III) complexes using an external oxidant was studied in detail, and showed that the anionic ligand rearranged from monodentate in Au(I) complex to LX-type bidentate ligand in Au(III) complexes, resulting from a deformation of the barbituric heterocycle and rehybridization of the central malonic carbon atom. This behavior is general as soon as the coordination geometry of the metal center leaves a cis coordination site next to the carbenic center. The complexes of Pd(II), Rh(I), Ir(I) and Mn(I) are thus synthesized and characterized. Structural analysis of the complexes shows that the degree of malonic carbon hybridization is a function of the electrophilicity of the metal, with a more pronounced sp3 character when the electron-density on the metal is lower. A library of three chiral ligands has been synthesized from (S)-(-)-1-phenylethylamine as the source of chiral information through a convergent synthesis strategy similar to that of achiral derivatives. The corresponding Au(I) complexes have been synthesized and used as pre-catalysts in 1,6-enyne domino reactions and provide access to good yields and enantiomeric excesses of up to 70%. In parallel, the reactivity of the 5-bromoimidazo[1,5-a]pyridinium platform with malonate esters and 2-arylacetate esters has been developed. This study proves the intermediacy of free NHCs as reaction intermediates in the synthesis of fused heterotricyclic mesoionic compounds
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Monticelli, Marco. "Novel di(N-heterocyclic carbene) ligands and related transition metal complexes." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAE051.
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Le travail de thèse, en co-tutelle entre l'Université de Padoue et l'Université de Strasbourg, se concentre sur la chimie des carbènes bis-(N-hétérocycliques) et peut être divisé en quatre familles de ligands qui constituent les quatre chapitres du manuscript : i) complexes métalliques de Cu(I), Ag(I), Au(I), Ir(III) et Ru(II) avec des ligands di(carbène N-hétérocyclique) portant un pont phénylène rigide entre les unités carbèniques; ii) complexes métalliques de Cu(I), Ag(I), Au(I) et Ru(II) combinant un ligand NHC fonctionnalisé avec un triazole dans la position 5 du squelette; iii) complexes métalliques d’Ag(I), Au(I) et Pd(II) avec des ligands hétéroditopiques à base d'un imidazol-2-ylidène et d’un 1,2,3-triazol-5-ylidène reliés par un pont propylène; iv) proligands bis (benzoxazoles) et les tentatives de complexation sur des métaux de transitionThe PhD, a collaboration between the University of Padova and the University of Strasbourg, is focused on the chemistry of di(N-heterocyclic carbene) ligands and can be divided in four families of ligands that constitute the four chapters: i) metal complexes (Cu(I), Ag(I), Au(I), Ir(III), Ru(II)) with di(N-heterocyclic carbene) ligands bearing a rigid phenylene bridge between the carbene units; ii) metal complexes (Cu(I), Ag(I), Au(I), Ru(II)) combining an imidazole-based NHC ligand functionalized with a triazole in the 5 position of the backbone; iii) metal complexes (Ag(I), Au(I), Pd(II)) with heteroditopic ligands based on imidazol-2-ylidene and 1,2,3-triazol-5-ylidene moieties connected with a propylene bridge; iv) bis(benzoxazolium) proligands and attempted synthesis of related transition metal complex
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Brachet, Etienne. "Nouvelles réactions métallocatalyées pour la création de liaisons C-N et C-S : applications à la synthèse d'inhibiteurs de la Hsp90." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114836/document.
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Les travaux rapportés dans ce mémoire concernent le développement de nouvelles réactions métallo-catalysées pour la création de liaison carbone-hétéroatomes ainsi que leurs applications à la synthèse d’inhibiteurs de la protéine de choc thermique 90.Au cours de ce travail, l’étude de la réactivité d’hétérocycles de type quinoxalinones et N-aminoazoles vis-à-vis du couplage de Buchwald-Hartwig a été réalisée. Des conditions ont ainsi pu être développées pour créer la liaison carbone-azote entre des 3-chloroquinoxalinones et des partenaires nucléophiles azotés (amides, azoles…) afin de construire une bibliothèque d’analogues du 6BrCaQ en série quinoxalinone. Par ailleurs, la création de la liaison carbone-azote de motifs N-aminoazoles avec des partenaires hétérocycliques halogénés (coumarines, quinoléines…) ou aromatiques halogénés a été étudiée. Celle-ci a permis l’accès à une chimiothèque d’analogues du 6BrCaQ ainsi que le développement du couplage permettant la mono- ou di-substitutions des motifs N-aminoazoles.Dans le dernier chapitre de ce manuscrit, la création de la liaison carbone-soufre en série glycosidique métallo-catalysés (Pd et Ni) entre des thioglycosides et divers aglycones électrophiles (halogénures (hétéro)aromatiques, vinyliques et acétyleniques) a été examiné. Tous les composés obtenus lors de ce travail sont en cours d’évaluation biologiqueThe development of new metal-catalyzed reactions to form carbon-heteroatom bonds have been studied in order to access to hsp90 inhibitors. For this purpose, reactivity of various 3-chloroquinoxalinone have been explored towards Pd-catalyzed Buchwald-Hartwig reaction with nitrogen nucleophiles (amides, azoles…) which allow access to a serie of 6BrCaQ analogues. In the same objective, the reactivity of N-aminoazole moieties in a Buchwald-Hartwig cross-coupling reaction has been also performed. This methodology led to the synthesis of new 6BrCaQ analogues. Moreover, conditions have been defined to access mono- or di-arylated N-aminoazoles structures starting from aryl chlorides. Finally, reactivity studies on metal-catalyzed carbon-sulfur bond forming reaction between thioglycosides as new nucleophiles partners with various aglycon halides ((hetero)aromatics, alkenyls and alkynyls halides) have been performed. Thanks to a nickel- or a palladium-catalysis, we have been able to introduce these thiosugars on various electrophiles partners and complex molecules. Thioglycosylated 6BrCaQ has been thus obtained.Biological evaluations of new synthesized compounds are currently in progress
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Caruthers, Heather Anne. "Applications of heterocyclic synthesis." [Ames, Iowa : Iowa State University], 2009.
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Shirtcliff, Laura Donnell. "'Coarctate' cyclizations : applications to heterocycle synthesis /." view abstract or download file of text, 2006. http://proquest.umi.com/pqdweb?did=1188876631&sid=1&Fmt=2&clientId=11238&RQT=309&VName=PQD.
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Thesis (Ph. D.)--University of Oregon, 2006.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 336-357). Also available for download via the World Wide Web; free to University of Oregon users.
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Majhail, Manjeet K. "Applications of rhodium-catalysed hydroacylation in heterocycle synthesis." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:0ac3e86d-e031-408b-b861-20740853bb0b.
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The work compiled in this thesis documents the development of new methodologies towards the synthesis of a range of N-containing heterocycles. These methods utilise intermolecular Rh(I)-catalysed hydroacylation of chelating aldehydes with alkynes and alkenes to install carbonyl groups, which are exploited in subsequent heterocycle forming cascades. Chapter 1 presents a literature review of the development of both intramolecular and intermolecular rhodium-catalysed hydroacylation, with the focus of different methods to suppress decarbonylation and promote constructive catalysis. A brief description of some precedented examples of hydroacylation in heterocycle synthesis is also included. Chapter 2 describes the optimisation studies for the hydroacylation of S-/N-chelating aldehydes with terminal and internal propargylic amines. The studies are largely focussed on achieving high regioselectivity for the linear gamma-amino enone product. The cyclisation of these gamma-amino enone adducts to form pyrrole rings is also described. Chapter 3 presents the de novo one-pot cascade synthesis of mono-, di- and tri- substituted pyrroles via a highly regioselective hydroacylation pathway. The pyrroles are exploited in further modifications to access fully substituted heteroaromatic systems or in a three-component coupling of aldehydes, propargylic amines and boronic acids or alkynes to access 'traceless' pyrrole rings. The one-pot cascade methodology is extended to the synthesis of dihydropyrroles, through the hydroacylation of allylic amines, which grants access to pyrrolidine rings via diastereoselective reductions. Chapter 4 details the initial investigations towards the development of rhodium- catalysed hydroacylation of ynamides with chelating aldehydes. This provides access to beta-amino enones in a regioselective manner. These hydroacylation products, which are known to be versatile building blocks, are subsequently exploited in the synthesis of five- and six-membered heterocycles via bi-nucleophilic additions. Chapter 5 discusses the conclusions of the research and the potential for further work. Chapter 6 compiles the experimental procedures and data.
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Nocanda, Xolani Wittleton. "Applications of Baylis-Idllman methodology in the synthesis of chromene derivatives." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1018257.
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The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives,. including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration. Evidence supporting this sequence has been obtained from the isolation ofBaylis-Hillman products from reactions involving the use of tertbutylclimethylsilyl-protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the ''Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of climeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis of sulfurcontaining heterocyclic systems, and a range of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiocbromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiocbromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. Thiochromene and chromene derivatives were converted to the corresponding 3 -carboxylic acids and coupled with a specially prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing cbromene and thiochromene termini in ca. 60% yield.
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Dengiz, Cagatay. "Acyl Azides: Application To The Synthesis Of Various Heterocycles." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613892/index.pdf.
Full textAbstract:
Pyrazoles, isoindolinones, benzodizepinones and dihydroquinolinones are very important heterocycles for their biological properties. Many pharmaceutical agents include these units as core structures. Reactive molecules such as acyl azides, free radicals and formyl groups are used as key step reactants in these studies. Regiospesific hydrolysis and esterifications are used to reach target starting materials. Two different methodology are used for critical ring closure steps. Benzodiazepinones, and isoindolinones are obtained by base mediated ring closure reactions whereas thionyl chloride mediated procedure is used for dihydroquinolinones. Moreover, chloroacetonylation of the double bonds is also examined. Addition of acetylacetone to various alkenes was performed with in the presence of Mn(OAc)3 and HCl. Removal of one of the acetyl groups with ammonia under very mild conditions provided compounds derived from chloroacetonylation of the double bonds.
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Elliott, Mark Christopher. "Transition metal catalysis : application to the synthesis of novel heterocycles." Thesis, Loughborough University, 1994. https://dspace.lboro.ac.uk/2134/13422.
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Ganto, Mlungiseleli MacDonald. "Application of Baylis-Hillman methodology in the construction of complex heterocyclic targets." Thesis, Rhodes University, 2009. http://hdl.handle.net/10962/d1006703.
Full textAbstract:
Baylis-Hillman reactions using various aromatic aldehydes, activated alkenes and catalysts have been used to: - access an extensive range of poly-heterocyclic products;explore chemoselectivity; and optimise reaction efficiency. Chromone-3-carbaldehydes and chromone-2-carbaldehydes, prepared via Vielsmeier-Haack and Kostanecki-Robinson methodology, respectively, have been used as Baylis-Hillman substrates with four different catalysts, viz., 1,4-diazabicyclo[2.2.2]octane (DABCO), 3-hydroxyquinuclidine (3-HQ), imidazole and N’,N’,N’,N’- tetramethylpropanediamine (TMPDA), and with methyl vinyl ketone (MVK), methyl acrylate, cyclic enones (2-cyclohexen-1-one, 2-cyclopenten-1-one and chromones) as activated alkenes. Reactions of the chromone- -carbaldehydes with MVK afforded dimeric Baylis-Hillman adducts when catalyzed by DABCO but when the same reactions were repeated using 3-HQ as catalyst, the dimeric products were accompanied by tricyclic Baylis-Hillman adducts. Use of excess MVK, however, led to mixtures of the normal Baylis-Hillman adducts and the tricyclic adducts – interestingly, with the apparent absence of the dimeric products. While reactions of chromone-3-carbaldehydes with methyl acrylate afforded the normal Baylis-Hillman adducts, the chromone-2- carbaldehydes produced, instead, rearrangement products, consistent with an earlier, single observation. Reactions of 2-nitrobenzaldehydes with cyclic enones using imidazole as catalyst afforded the normal Baylis-Hillman adducts, reductive cyclisation of the 2-cyclohexen-1- one and 2-cyclopenten-1-one adducts, using acetic acid and iron powder, afforded the corresponding quinoline erivatives. Treatment of cyclic enones with pyridine-2-carbaldehydes and quinoline-2-carbaldehydes using TMPDA as catalyst generally gave the expected Baylis-Hillman adducts. However, indolizine derivatives were isolated directly from Baylis-Hillman reactions involving pyridine-2-carbaldehydes and 2-cyclohexen-1-one. The remaining Baylis-Hillman adducts were cyclized to the corresponding indolizines by treatment with acetic anhydride both under reflux and under microwave-assisted conditions, the latter approach providing remarkably rapid and efficient access to the polycyclic products. Computer modelling studies have been conducted on selected polycyclic products at the Molecular Mechanics (MM), Quantum Mechanical (QM) and Density Functional (DFT) levels. The theoretical results have been used to calculate UV, IR and NMR absorption data, which have been compared, in turn, with the experimental spectroscopic data. Use has also been made of the estreNova NMR prediction programme and, generally, good agreement has been observed between the predicted and experimental spectroscopic data.
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Deegan, Jonathan E. "Aryl and Alkyl Migration Strategies for the Functionalization and Application of 1,2-Azaborines:." Thesis, Boston College, 2019. http://hdl.handle.net/2345/bc-ir:108582.
Full textAbstract:
Thesis advisor: Shih-Yuan LiuAs BN-CC isosterism becomes an increasingly valuable strategy to expand chemical space and increase molecular diversity, methods for functionalizing and utilizing BN-heteroarenes remain limited in comparison to those for all-carbon arenes. Described herein are initial studies aimed at developing methods for the late-stage functionalization of substituted 1,2-azaborines through controlled aryl and alkyl migrations. Furthermore, investigations into the application of B-aryl and B-alkyl 1,2-azaborines as transmetalation reagents in Suzuki-Miyaura cross-coupling reactions are presented
Thesis (MS) — Boston College, 2019
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Nyoni, Dubekile. "Application of the Baylis-Hillman methodology in the construction of novel heterocyclic derivatives." Thesis, Rhodes University, 2008. http://eprints.ru.ac.za/1134/.
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Campbell, Patrick, and Patrick Campbell. "Hydrogen Storage Applications of 1,2-Azaborines." Thesis, University of Oregon, 2012. http://hdl.handle.net/1794/12555.
Full textAbstract:
The development of safe and efficient hydrogen storage materials will aid in the transition away from fossil fuels toward a renewable, hydrogen-based energy infrastructure. Boron-nitrogen (BN) containing materials have attracted much attention due to their high hydrogen storage capacity and fast kinetics of hydrogen release. Furthermore, computational studies predict that hydrogen storage materials based on the BN-heterocycle 1,2-azaborine may enable reversible H2 uptake and release, with little additional energy input. This thesis develops the basic science needed for a hydrogen storage platform based on BN-heterocycles such as 1,2-azaborine. Chapter I is a review of recent developments in azaborine chemistry. Chapter II describes a regeneration scheme from a "spent" 1,2-azaborine hydrogen storage material to "fully charged" fuel using molecular H2 and H-/H+ equivalents. Chapter III describes the experimental determination of the resonance stabilization energy of 1,2-azaborines using reaction calorimetry. Chapter IV explores the effect of boron-substitution on the rate and extent of hydrogen release from BN materials. Chapter V describes work on a project unrelated to hydrogen storage, the synthesis and electronic parameter determination of the first 1,2- azaborine-containing phosphine ligand analog.
This dissertation includes previously published and unpublished co-authored
material.
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Walji, Dhiran. "A radical approach towards the synthesis of novel pyridine and pyrimidine based heterocycles." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=62164.
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Brownsort, Peter Alexander. "Applications of 1,3,4-oxathiazol-2-ones in heterocyclic synthesis." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/13091.
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Brensing, Tess. "Reduction of heterocyclic amine formation in beef by surface application of spices." Thesis, Kansas State University, 2011. http://hdl.handle.net/2097/13120.
Full textAbstract:
Master of ScienceFood Science Institute
J. Scott Smith
Heterocyclic amines (HCAs) are cancer causing compounds formed during the cooking of meat. Previous studies show that incorporating antioxidant spices into meat as well as marinating meat with antioxidant spices reduces formation of HCAs. The purpose of this study was to determine if commercially available spices applied to the surface of meat could effectively reduce HCA formation. Two commercially available spice blends and one blend of spices with known quantities of antioxidant spices were sprinkled onto the surface of beef just prior to pan-frying. The quantities of spices used were based on the amounts customarily consumed in typical Western cooking. The results of direct application were then compared to marinating with the same types and amounts of spices. The antioxidant potential of the spices was analyzed using DPPH and total phenolics methods. Results indicated that the spices would be effective antioxidants. Low recovery rates and problems during the extraction process made results inconclusive, but suggest that further research may find that applying spices directly to the surface of meat in consumer acceptable quantities may be as effective as marinating at reducing the formation of HCAs.
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Monticelli, Marco. "Novel di(n-heterocyclic carbene) ligands and related transition metal complexes." Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3422292.
Full textAbstract:
In the last decades, N-heterocyclic carbenes (NHC) ligands have been studied by many
groups due to their peculiarity in terms of major stability and versatility with respect to
other type of ligands based on nitrogen (amines, imines, etc.) or phosphorous
(phosphines, phosphites, etc.) donor atoms.
Nowadays, the role of these ligands in the chemistry of transition metal complexes is
pivotal, and the applications of the resulting compounds span from catalysis to
luminescence to bioinorganic chemistry.
This PhD, a collaboration between the University of Padova and the University of
Strasbourg, is focused on the chemistry of di(N-heterocyclic carbene) ligands and can
be divided in four families of ligands that constitute the four chapters:
i) metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid
phenylene bridge between the carbene units;
ii) metal complexes combining an imidazole-based NHC ligand functionalized with
a triazole in the 5 position of the backbone;
iii) metal complexes with heteroditopic ligands based on imidazol-2-ylidene and 1,2,3-triazol-5-ylidene moieties connected with a propylene bridge;
iv) bis(benzoxazolium) proligands and attempted synthesis of related transition metal
complexes.
i) Metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid phenylene bridge between the carbene units.
Ortho- meta- and para-phenylene bis(imidazolium) salts have been used as proligands for the syntheses of various silver(I) complexes. These compounds, with general formula [Ag2L2](PF6)2 (L=di(N-heterocyclic carbene) ligand), have been used as transmetalating agents for the formation of the corresponding gold(I) and copper(I) complexes. These compounds maintain the same dinuclear dicationic molecular structure as for the silver(I) precursors, as confirmed by the resolved solid state crystal structures.
The photoluminescence properties of the synthesized complexes have been studied and are strongly influenced by the structure of the di(NHC) ligand employed. In particular, the gold(I) complexes show interesting quantum yields of emission modulated by the
geometry of the complex (distance between the two metal centers) and also by the packing of the complexes in solid state.
With the ortho-phenylene silver(I) diNHC complex, the transmetalation was also successful for the access to mononuclear ruthenium(II) and iridium(III) complexes that show a chelate coordination of the ligand on the metal center.
ii) metal complexes combining an imidazole-based NHC ligand functionalized with a triazole in the 5 position of the backbone.
The copper catalyzed azide alkyne cycloaddiction reaction (CuAAC) also called “click reaction” has been used for the functionalization of the [5-(trimethylsilyl)ethynyl]-1-methylimidazole with a 1,2,3-triazole ring. As function of the methylating agents, it was possible to alkylate only the nitrogen on the imidazole ring (proligand i) or both on imidazole and triazole rings (proligands l and m).
Starting from the proligands l and m, silver(I) complexes of stoichiometry Ag:L 1:1 (L=di(N-heterocyclic carbene) ligand) have been obtained, albeit with poor purity due to the oily nature of the products.
Using the proligand i it has been possible to isolate a silver(I) complex of formula AgCl(NHC), which has been successively employed for the synthesis of gold(I), copper(I) and ruthenium(II) complexes.
The in vitro cytotoxic activities of these compounds have been evaluated and in these preliminary results the silver(I) complex appears the most active and selective.
iii) metal complexes with heteroditopic ligands based on imidazol-2-ylidene and 1,2,3-triazol-5-ylidene moieties connected with a propylene bridge.
Heteroditopic proligands have been successfully synthesized using the CuAAC click reaction followed by methylation and anion exchange.
A series of novel di-NHC gold(I) complexes, having general formula [Au2L2](PF6)2, have been synthesized and fully characterized through the transmetalation of the di-NHC moiety from pre-formed silver(I) complexes. The same pathway has been adopted for the synthesis of palladium(II) complexes that show the chelation of two ligands on the same metal center (i.e. homoleptic complexes).
Due to the presence of two different carbene units (imidazole-2-ylidene and triazol-5-ylidene), it is possible to obtain a mixture of isomers which has been investigated by NMR and mass analyses.
iv) bis(benzoxazolium) proligands and attempted synthesis of related transition metal complexes.
Finally the chemistry of benzoxazole has been investigated. Different proligands containing benzoxazole rings have been synthesized starting from the corresponding diamine.
These organic scaffolds have been used as proligands for the synthesis of metal complexes. Unfortunately, despite the various reaction conditions adopted (deprotonating agent, solvent, temperature, time...), the results obtained in this regard
are not satisfactory, probably for the intrinsic instability of the ligand precursors and/or of the corresponding free carbenes.Nelle ultime decadi, i leganti carbenici N-eterociclici sono stati studiati da numerosi gruppi in virtù delle loro peculiarità, quali maggiore stabilità e versatilità rispetto a leganti con atomi donatori all’azoto (ammine, immine etc.) o al fosforo (come per esempio fosfine, fosfiti ed altri). Attualmente, il ruolo di questi leganti nella sintesi di complessi con metalli di transizione è essenziale e le applicazioni dei corrispondenti complessi spaziano dalla catalisi alla luminescenza fino alla chimica bioinorganica. Questo dottorato, effettuato in collaborazione tra l’Università degli Studi di Padova e l’Università di Strasburgo, è focalizzato sulla chimica dei carbeni N-eterociclici e può essere diviso in quattro differenti capitoli: i) complessi metallici con leganti dicarbenici N-eterociclici legati da ponte fenilene rigido; ii) complessi metallici con legante carbenico N-eterociclico funzionalizzato con un triazolo in posizione 5 del backbone; iii) complessi metallici con leganti eteroditopici basati su unità imidazol-2-ilideniche e triazol-5-ilideniche legate tra loro mediante ponte propilenico; iv) leganti bis(benzossazolici) e tentativi di sintesi dei corrispondenti complessi con metalli di transizione. i) complessi metallici con leganti dicarbenici N-eterociclici legati da ponte fenilene rigido. Complessi di argento(I) sono stati sintetizzati partendo dai sali precursori dei leganti bisimidazolici con ponte orto- meta- e para-fenilenico. Tali complessi, con formula generale [Ag2L2](PF6)2 (L = legante dicarbenico N-eterociclico), sono stati usati come agenti di transmetallazione per l’ottenimento dei complessi di oro(I) e rame(I) corrispondenti; questi composti mantengono la medesima natura dinucleare dicationica dei precursori di argento, confermata dalla risoluzione delle strutture mediante diffrazione ai raggi X. Le proprietà di luminescenza dei complessi sintetizzati sono state studiate e sono fortemente influenzate dalla struttura del legante dicarbenico N-eterociclico utilizzato. In particolare i complessi di oro(I) presentano interessanti rese quantiche di emissione che variano a seconda della geometria del complesso (in termini di distanza tra i centri metallici) e soprattutto per il packing dei complessi allo stato solido. A partire dal complesso di argento con legante dicarbenico a ponte orto-fenilene, la reazione di transmetallazione è stata utilizzata per la sintesi di complessi mononucleari di rutenio(II) e iridio(III) che mostrano la chelazione dell’unità dicarbenica al centro metallico. ii) complessi metallici con legante carbenico N-eterociclico funzionalizzato con un triazolo in posizione 5 del backbone. La reazione di cicloaddizione azide alchino rame catalizzata (CuAAC) comunemente chiamata “reazione di click” è stata utilizzata per la funzionalizzazione del composto [5-(trimetilsilil)etinil]-1-metilimidazolo con un anello 1,2,3-triazolo. Utilizzando differenti agenti metilanti è possibile metilare solamente l’azoto dell’anello imidazolico (precursore del legante, i) o entrambi gli anelli imidazolico e triazolico (precursori dei leganti, l e m). Partendo dai precursori dei leganti, l e m, sono stati ottenuti complessi di argento(I) con rapporto Ag:L 1:1 (L = dicarbene N-eterociclico), anche se con bassa purezza a causa della natura oleosa dei prodotti. Utilizzando il precursore i è stato possibile isolare il complesso di argento(I) con formula AgCl(NHC), che è stato successivamente impiegato per la sintesi dei complessi di oro(I), rame(I) e rutenio(II). L’attività citotossica in vitro di tali composti è stata valutata e risultati preliminari mostrano un’attività e selettività maggiore per il complesso di argento(I) rispetto agli altri complessi metallici studiati. iii) complessi metallici con leganti eteroditopici basati su unità imidazol-2-ilideniche e triazol-5-ilideniche legate tra loro mediante ponte propilenico. Precursori dei leganti eteroditopici sono stati sintetizzati mediante reazione di click CuAAC, seguita da metilazione e scambio di anione. Una nuova serie di complessi di oro(I), con formula generale [Au2L2](PF6)2, è stata ottenuta mediante reazione di transmetallazione dell’unità dicarbenica N-eterociclica a partire dal complesso di argento(I) preformato. La medesima via sintetica è stata utilizzata per la sintesi di un complesso di palladio(II) che mostra la chelazione di due unità dicarbeniche allo stesso centro metallico. A causa della presenza di due diverse unità carbeniche (imidazol-2-ilidene e triazol-5- ilidene) è possibile ottenere una miscela di isomeri la cui composizione è stata analizzata mediante spettri NMR e tecniche di massa. iv) leganti bis(benzossazolici) e tentativi di sintesi dei corrispondenti complessi con metalli di transizione. Precursori dei leganti con anello benzossazolico sono stati sintetizzati a partire dalla relativa diammina. Queste molecole organiche sono state utilizzate come precursori dei leganti per la sintesi di diversi complessi con metalli di transizione. Sfortunatamente, nonostante le differenti condizioni di reazione utilizzate (agente deprotonante, solvente, temperatura, tempo…), i risultati ottenuti non sono soddisfacenti, probabilmente a causa dell’instabilità intrinseca dei precursori e/o dei relativi carbeni.
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Ball, Jennifer Claire. "Asymmetric synthesis of polycyclic heterocycles & application to the synthesis of comosidine." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555717.
Full textAbstract:
This work demonstrates the use of a Diels-Alder/retro Diels-Alder approach using a chiral anthracene auxiliary to control the stereochemistry of subsequent reactions. A range of N-substituted maleimide cycloadducts have been prepared and asymmetric transformations undertaken to give N-acyliminium ion precursors. N-Acyliminium ions have been formed under standard conditions and a range of nucleophiles used to form tertiary and quaternary stereocentres. For the synthesis of polycyclic heterocycles, a N-[2-(6-methoxypyridin-2-yl)ethyl] cycloadduct was prepared in 3 steps from commercially available starting materials. Asymmetric transformations were carried out; reduction and Grignard addition to form hydroxy-lactams both in high yield with high selectivity. The N-acyliminium ion was then formed for both systems but unfortunately, due to the inherent electron poor nature of the pyridine ring, even with an activating methoxy group, no ring formation occurred and side products predominated. For the synthesis of natural product comosidine, a N-(3,4-dimethoxyphenylpropyl)maleimide cycloadduct was prepared in high yield and a range of nucleophiles added to prepare hydroxy-lactam analogues. When subjected to Friedel-Crafts conditions in an attempt to form a 7 membered ring, no cyclisation took place. In fact, intramolecular Friedel-Crafts additions were shown to be highly dependent on the ring size that is being formed when using a dimethoxyphenyl group as nucleophile. Indeed the 6 membered ring is the only size that will form. Attempts to make 5, 7 and 8 membered rings by this method are not viable, and computational studies show the desired FriedelCrafts products are relatively less stable than the alkenes that are indeed formed experimentally for the 7 and 8 ring analogues. Intermolecular Friedel-Crafts reactions have also been undertaken using nucleophiles such as furan, thiophene and indole, accessing tertiary stereocentres (seven examples in 54 - 100% yield) and quaternary stereo centres (five examples in 50 - 100% yield). Retro Diels-Alder reaction of furan addition cycloadduct containing a quaternary stereocentre yielded a substituted maleimide derivative in 100% yield and 97% enantiomeric excess. This demonstrates the use of this strategy to construct quaternary stereo genic centres. A further attempt to prepare comosidine used a Parham cyclisation; using an aryl iodide to form the desired 7 membered ring. This proved to be very successful and gave the corresponding hydroxy-lactam in high yield. Addition of carbon nucleophiles such as silyl enol ethers, were then tested on a range of substituted N-acyliminium ions to prove the overall methodology before application to the natural product. Three examples with tertiary stereocentres were prepared in 97 - 98% yield and four examples with quaternary stereocentres formed in 78 - 95% yield, exclusively. The nature of the Nacyliminium ion itself has found to be very important. If the iminium ion is unstabilised, nucleophilic addition is relatively facile. However, if a stabilising group is attached such as a phenyl ring, attack is much more difficult and harsher reaction conditions are needed. The N-acyliminium ion formed for comosidine was found to be very stable and therefore would not react with any nucleophile tested. Several ideas to overcome the stability and unreactivity of very electron rich N-acyliminium ions have been investigated. Finally, the formal synthesis of (+)-hygrine has been completed by use of the methodology; using addition of acetone to the N-acyliminium ion formed from Nmethylmaleimide hydroxy-lactam in 100% yield. Other steps including cycloreversion, hydrogenation and amide reduction gave the enantioenriched protected natural product in 7 steps from 9-(1-methoxyethyl) anthracene auxiliary and N-methyl maleimide.
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Towler, Joannah M. R. "The application of intramolecular N-acyliminium cyclisation strategies towards biologically active heterocycles." Thesis, Loughborough University, 2011. https://dspace.lboro.ac.uk/2134/9113.
Full textAbstract:
We describe the application of N-acyliminium cyclisation strategies to access a range of heterocycles with potential for biological activity. We have described an asymmetric approach towards the anti-tumour pyrroloisoquinoline alkaloid (R)-(+)-crispine A. We have achieved a synthesis of the pyrrolo[2,1-a]benzazepine template which is a sub-unit of the Homoerythrina alkaloids, and the functionalised dodecahydrobenz[a]indolo[3,2-h]quinolizine template, which is a sub-unit of the manadomanzamine alkaloids. In addition, we have described an asymmetric synthesis of the α-hydrazino pyrroloisoquinoline ring system, towards the synthesis of conformationally restricted peptidomimetics.
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Wagland, A. M. "The application of the Diels-Alder reaction in the synthesis of some nitrogen heterocycles." Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377952.
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