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Synthesis of Dibenzofurans via a Palladium Catalyzed Oxidative Ring Closure ReactionAkram, Sadia 01 May 2013 (has links)
The cannabinoid partial agonist BAY 59-3704 has been identified as an attractive target to explore structure-activity relationships at cannabinoid receptors for the development of a therapeutic agent for psychostimulant addiction. This thesis will describe the studies associated with the optimization of a palladium-catalyzed oxidative ring closure reaction for the synthesisof dibenzofuran analogues from substituted diaryl ethers. These dibenzofurans are viewed as rigid analogues of BAY 59-3704 and will provide useful information about molecular interactions at cannabinoid receptors. The scope and limitations of the palladium-catalyzed oxidative ring closure reaction as it relates to the synthesis of the target dibenzofuran analogues will be presented.
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Development Of New Synthetic Methodologies For Furan Fused HeterocyclesErgun, Merve 01 January 2013 (has links) (PDF)
Furopyranones and furopyrrolones are furan-fused bicyclic heterocycles containing pyranone and pyrrolone framework respectively. Many natural products and pharmaceutical agents include these core structures. In this study, new synthetic methodologies were developed for the synthesis of furopyranone and furopyrrolone derivatives. In the first section of this thesis, methyl 2-(2-methoxy-2-oxoethyl)-3-furoate was hydrolyzed forming 2-(carboxymethyl)-3-furoic acid which underwent intramolecular cyclization reaction using two different methodologies forming furopyranone derivatives. In the second part of the study, 2-(carboxymethyl)-3-furoic acid was regioselectively converted to acyl azide, which was accomplished by utilizing the reactivity differences between the two acid functionalities within the molecule. This acyl azide was then transformed into urea derivative to perform cyclization reaction yielding a new furan-fused heterocycle, furopyrrolone. In both parts of this study, ring closure reactions were achieved benefiting from the reactivities of different carbonyl groups within the molecules.
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Development Of New Synthetic Methodologies For Indole Derivatives: Chemistry Of Homophthalic AcidKilikli, Ahmet Alper 01 February 2010 (has links) (PDF)
Synthesizing nitrogen containing heterocyclic compounds is one of the leading research areas throughout the organic chemistry due to their significant activities on biological systems. Among the various biologically active molecules, indole derivatives are of prime importance on the grounds of their proven clinical roles. Objective of this study is to synthesize new indole derivatives those may contribute treatment of several diseases like their analogues via a recently developed synthetic methodology. Besides this, another objective is to observe and discuss effects of two different substituents on the homophtalic acid system through the synthetic route. Initially starting from homophtalic and 3-methoxybenzoic acid two different homophtalic acid derivatives were synthesized as starting materials. Then the corresponding acyl azide and isocyanate derivatives were generated which might further be used as a precursor to construct a variety of indole derivatives. After synthesizing urea derivatives, ring-closure under the basic conditions generated the heterocyclic units. Whole products were conscientiously purified and characterized.
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Synthesis of Tadpole-Like PolystyrenesZhang, Fan, Mr. 17 September 2014 (has links)
No description available.
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Nouvelle approche vers la synthèse de la thapsigargine (guaianolides) par réaction de métathèse ényne cyclisante / New approach toward the synthesis of thapsigargin (guaianolides) using ring closing enyne metathesisJouanneau, Morgan 10 December 2013 (has links)
La thapsigargine, lactone sesquiterpénique de type guaïanolide d’origine naturelle, est un puissant inhibiteur des enzymes ubiquitaires SERCAs (Sarco-Endoplasmic Reticulum Ca2+-ATPases) et est actuellement en phase clinique pour le traitement du cancer de la prostate non-hormono dépendant. Au cours de cette thèse, nous avons développé une nouvelle approche pour la synthèse de cette molécule, suffisamment flexible pour permettre de préparer des analogues ayant un bon degré de diversité structurale. Cette voie met en jeu une métathèse cyclisante d’ényne pour former le squelette bicyclique [5-7] de cette molécule. La préparation du précurseur de métathèse a nécessité le développement de deux voies différentes. La première utilise le ditertbutylacétylène dicarboxylate comme matière de départ et met en jeu un procédé original Michael-Wittig en un pot. Malgré une étude approfondie de cette étape ayant permis d’optimiser les conditions opérationnelles avec un rendement de 65%, cette voie s’est finalement avérée non applicable pour la synthèse envisagée ceci en raison d’un manque de chimiosélectivité au niveau d’une étape décisive. Une deuxième voie a donc été développée. Elle utilise la 2-méthylcyclopentane-1,3-dione comme produit de départ et offre le précurseur de métathèse en série racémique en 10 étapes et un rendement de 8%. Les quatre centres stéréogènes C1, C3, C10 et C6 sont mis en place grâce à des réactions diastéréosélectives (d.r ≥ 80%). La dernière étape de cette voie est une réaction d’alkynylation d’un aldéhyde conjugué avec piégeage in-situ de l’alcool secondaire obtenu. La configuration relative du centre C-6 de ce précurseur de métathèse s’est avéré par la suite épimère de celui de la thapsigargine (nOe mesurés après RCEYM). Des essais de métathèse cyclisante ont ensuite été réalisés sur l’ényne obtenue dans différentes conditions incluant l’utilisation de catalyseurs originaux fournis par le Pr. Marc Mauduit (université de Rennes). Ces réactions se sont montrées concluantes, fournissant le squelette bicyclique [5,7] de la thapsigargine avec de bons rendements (de 61 à 89%).A la suite de cette étape, un ensemble de réactions a été réalisé afin de mettre en place les groupements fonctionnels nécessaires à la transformation de la plateforme bicyclique obtenue en thapsigargine. De nombreuses difficultés ont été rencontrées : les tentatives d’épimérisation du centre C-6, d'époxydation de l'adduit de cyclisation ou encore de formation de -lactone se sont révélées infructueuses ou ont conduit à des résultats inattendus. L’idée d’exploiter la présence du centre stéréogène C-6 de configuration non naturelle pour installer le centre C-8 crucial pour l’activité biologique de la thapsigargine, via un réarrangement sigmatropique [1,3] de type suprafacial catalysé à l’or (catalyseur de Nolan), a été également testée. De manière inattendue, le produit de réarrangement est obtenu avec inversion faciale, indiquant le passage probable par un cation allylique.Ainsi, au cours de ce travail, deux composés bicycliques [5,7] oxygénées en C8, précurseurs raisonnables de la thapsigargine et analogues, ont été synthétisés par deux voies qui diffèrent au niveau du réarrangement final des produits de cyclisation hydroxylés en C6obtenu après métathèse cyclisante. A partir de de la 2-méthylcyclopentan-1,3-dione commerciale l’un est obtenu en 13 étapes avec 3% de rendement et l’autre en 12 étapes avec 5% de rendement. L’ensemble des essais de réactions effectuées sur les adduits de métathèse permettent de mieux cerner leur réactivité. / Thapsigargin, a guaianolide sesquiterpene lactone of natural origin is a potent inhibitor of ubiquitous SERCA enzymes (Sarco-Endoplasmic Reticulum Ca2+-ATPase) and is currently in clinical trial phase 1 for the treatment of non-hormono dependent prostate cancer. In this work a new approach for the synthesis of thapsigargin has been developed, flexible enough to allow the elaboration of analogues with a high degree of structural diversity. The strategy developed involves an enyne metathesis cyclization reaction (RCEYM) to form the bicyclic [5,7] scaffold of these molecules. For the synthesis of the required precursor of RCEYM, two successive routes have been explored. The first one uses tert-butylacetylene dicarboxylate as starting material and involves a one-pot Michael-intramolecular Wittig reaction. Conditions have been found to allow an efficient synthesis of trisubstituted cyclopentenones. Unfortunately this route has proved difficult to use for the programmed synthesis because of the lack of chemoselectivity at a decisive strategic level. A second approach was developed starting from commercial 2-methyl-cyclopentane-1,3-dione, providing the required racemic precursor of the metathesis reaction in 10 steps and 8% yield. The four C1, C3, C6 and C10 stereogenic centers are set up through diastereoselective reactions (dr ≥ 80%). The final step of the synthesis of this precursor involves an alkynylation reaction of an aldehyde combined with in-situ trapping of the secondary alcohol obtained. The relative configuration of center C6 was shown to be the inverse of that of thapsigargin. Metathesis cyclization assays were then carried out on this intermediate enyne under different conditions, including the use of original catalysts provided by Prof. Marc Mauduit (University of Rennes). These reactions provided the expected [5,7] bicyclic core of thapsigargin with good yields (61 to 89%). In the third part of the thesis, a set of reactions have been attempted to put in place the necessary functional groups for the achievement of the synthesis of thapsigargin. Many difficulties were encountered: attempted epimerization of the C6 center, epoxidation of the RCEYM cyclization adduct or attempts to form a -lactone either were unsuccessful or led to unexpected results. The idea of using the presence of the stereogenic center of unnatural configuration at C6 to install the hydroxyl group at C8, crucial for the biological activity of thapsigargin, via a gold-catalyzed (Nolan catalyst) suprafacial sigmatropic [1,3] rearrangement was experimented. Unexpectedly, the rearranged acetate adduct was obtained with facial inversion, indicating a probable allyl cation intermediate. Thus, in this work, two [5,7] bicyclic oxygenated compounds at C8 have been synthesized from commercial 2-methylcyclopentane-1,3-dione through two pathways that differ in the conditions leading to the final rearrangement of the cyclic C6-hydroxylated RCEYM adducts. One of them is obtained in 13 steps with 3% yield and the second in 12 steps with 5% yield. Both compounds appear to be suitable intermediates for the syntesis of thapsigargin and its analogues. All tests performed on the adducts, obtained after RCEYM, helps us to identify their reactivity.
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Generation and Succeeding Reactions of Allenyl IsothiocyanatesJawabrah Al-Hourani, Baker Salim Yacoub 06 October 2005 (has links) (PDF)
In this work, the [3,3] sigmatropic rearrangement of different substituted propargyl
thiocyanates and double [3,3] sigmatropic rearrangement of enynyl isothiocyanates either by
flash vacuum pyrolysis or by thermolysis in solution are studied.
Additionally, the intramolecular reactions of the resulting allenyl isothiocyanates are studied,
and the reaction mechanisms for the generation of the final products, such as [1,5] sigmatropic
migrations or electrocyclic ring closures, are explained.
These highly reactive allenyl isothiocyanates are used as appropriate electrophilic precursors
for the preparation of novel examples of thiazoles substituted at C-2 position using different
types of nucleophiles. For the formation of these substituted thiazoles, the necessary
nucleophilicity as well as the regioselectivity, the stereoselectivity, and the reaction
mechanisms are investigated. / In der vorliegenden Arbeit sind die [3,3]-sigmatrope Umlagerung von verschiedenen
Propargylthiocyanaten und die doppelte [3,3]-sigmatrope Umlagerung von Eninylisothiocyanaten
entweder durch Blitzvakuumthermolyse oder Thermolyse in Lösung untersucht worden.
Zusätzlich wurden die intramolekularen Reaktionen der resultierten Allenylisothiocyanate
studiert. Außerdem sind die Reaktionsmechanismen zur Bildung der Thermolyseprodukte wie
z.B. die [1,5]-sigmatropen Umlagerungen und die elektrocyclischen Ringschlüsse erklärt.
Die hochreaktiven Allenylisothiocyanate sind als geeignet elektrophile Vorläufer zur Synthese
von neuen Thiazolen verwendbar, die an der C-2 Position substituiert sind. Dabei kommen
verschiedene Nucleophile zum Ansatz. Für die Bildung dieser substituierten Thiazole sind die
Regioselektivität, Stereoselektivität, Reaktionsmechanismen und der Bereich der einsetzbaren
Nucleophile untersucht worden.
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Fonctionnalisation de complexes de bore(III), synthèse et propriétés : application au photovoltaïque organique / Functionnalization of boron(III) complexes, synthesis and properties : application to organic photovoltaicsHuaulmé, Quentin 18 November 2016 (has links)
Ces travaux de thèse ont visé à étudier la fonctionnalisation de complexes mono et ditopique de bore(III), BODIPY et BOPHY, en vue d’une application en cellule solaire organique. Les caractérisations préliminaires des nouveaux matériaux synthétisés ont permis d’identifier les matériaux aux propriétés physico-chimiques les plus adaptées à une telle application. Ainsi, il a été possible d’utiliser pour la première fois un dérivé de BOPHY comme matériau de type p prometteur au sein d’une cellule solaire organique, et un rendement de conversion énergétique de 4,2% a été atteint. La fonctionnalisation orthogonale du 1,3,5,7-tétraméthyles BODIPY a permis de faire passer le rendement de conversion de référence de BODIPY comme matériaux de type p de 4,7 à 5,8%. Enfin, une méthodologie synthétique originale et polyvalente d’obtention de BODIPY α-fusionnés, les BOBIM, a été développée. Présentant à la fois une absorption intense dans le visible et une très forte affinité électronique, ils ont été caractérisés comme matériaux de type n. / A study of the functionalization of boron(III) complexes, BODIPY and BOPHY, was carried out in order to characterize new n and p-type materials for bulk heterojunction organic solar cells. The properties of this materials were investigated through spectroscopic, electrochemical and charges transport analysis, and the most promising candidates were characterized in photovoltaic devices. For the first time a BOPHY derivative was used as p-type materials in such organic solar cell, providing a promising PCE of 4.2%. A study of the orthogonal functionalization of the 1,3,5,7-tetramethyls BODIPY allowed the synthesis and characterization of a new BODIPY based p-type material which exhibits the highest PCE of 5.8% for such material to date. The last chapter of this thesis develops an original and versatile synthetic method to obtain α-fused BODIPY. This family of molecules exhibit both intense absorption in the near-IR and low lying LUMO, and has been hence characterized as n-type materials.
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Generation and Succeeding Reactions of Allenyl IsothiocyanatesJawabrah Al-Hourani, Baker Salim Yacoub 05 October 2005 (has links)
In this work, the [3,3] sigmatropic rearrangement of different substituted propargyl
thiocyanates and double [3,3] sigmatropic rearrangement of enynyl isothiocyanates either by
flash vacuum pyrolysis or by thermolysis in solution are studied.
Additionally, the intramolecular reactions of the resulting allenyl isothiocyanates are studied,
and the reaction mechanisms for the generation of the final products, such as [1,5] sigmatropic
migrations or electrocyclic ring closures, are explained.
These highly reactive allenyl isothiocyanates are used as appropriate electrophilic precursors
for the preparation of novel examples of thiazoles substituted at C-2 position using different
types of nucleophiles. For the formation of these substituted thiazoles, the necessary
nucleophilicity as well as the regioselectivity, the stereoselectivity, and the reaction
mechanisms are investigated. / In der vorliegenden Arbeit sind die [3,3]-sigmatrope Umlagerung von verschiedenen
Propargylthiocyanaten und die doppelte [3,3]-sigmatrope Umlagerung von Eninylisothiocyanaten
entweder durch Blitzvakuumthermolyse oder Thermolyse in Lösung untersucht worden.
Zusätzlich wurden die intramolekularen Reaktionen der resultierten Allenylisothiocyanate
studiert. Außerdem sind die Reaktionsmechanismen zur Bildung der Thermolyseprodukte wie
z.B. die [1,5]-sigmatropen Umlagerungen und die elektrocyclischen Ringschlüsse erklärt.
Die hochreaktiven Allenylisothiocyanate sind als geeignet elektrophile Vorläufer zur Synthese
von neuen Thiazolen verwendbar, die an der C-2 Position substituiert sind. Dabei kommen
verschiedene Nucleophile zum Ansatz. Für die Bildung dieser substituierten Thiazole sind die
Regioselektivität, Stereoselektivität, Reaktionsmechanismen und der Bereich der einsetzbaren
Nucleophile untersucht worden.
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Development of the Solution-Spray Flash-Vacuum-Pyrolysis Technique in the Synthesis of Allenyl Isothiocyanates and Synthesis of Complex 2-Amino-1,3-thiazole Derivatives / Entwicklung der Solution-Spray Blitzvakuumpyrolyse-Technik in der Synthese von Allenylisothiocyanaten und Synthese komplexer 2 Amino-1,3-thiazolderivateRichter, Frank 27 July 2015 (has links) (PDF)
Gas-phase thermolysis is a long-known and well established method for the preparation of reactive species. It is, however, limited to relatively volatile substances, which are easily vaporised. In the present work, the solution-spray technique for preparative scale was developed. With this technique, it is possible to subject low-volatile substances, which hardly vaporise even under high-vacuum conditions, to gas-phase thermolysis. By utilising oil nozzles used in heating and burner systems, it was possible to integrate a stable solution-spray into the existing flash-vacuum-pyrolysis system. The influence of several variables, such as flow-rate, pressure, temperature and solvent was determined. The solution-spray technique was applied in [3,3]-sigmatropic rearrangements of certain propargyl thiocyanates to the corresponding allenyl isothiocyanates.
Furthermore, the parent compound propa-1,2-dienyl isothiocyanate was reacted with various sterically demanding primary and secondary amines to form 2-amino-1,3-thiazoles in moderate to excellent yields. Based on this, a catalyst-free four-center three-component reaction was developed. 2-Amino-1,3-thiazoles with complex substituents in 5-position at the heterocyclic ring are formed. Reaction mechanisms are discussed to explain the occurance of a highly substituted 1,3-thiazine structure. The influence of reaction temperature, concentrations and solvent were determined and are also discussed.
It was shown that 2-amino-5-methyl-1,3-thiazoles are the apparently first aromatic substance class, that readily undergoes Prins-type 1,3-dioxane ring-formation. / Die Gasphasenthermolyse ist eine lang bekannte und etablierte Methodik zur Synthese reaktiver Spezies. Sie ist allerdings auf flüchtige Substanzen mit einer guten Verdampfbarkeit beschränkt. Für schwerflüchtige Verbindungen, welche sich selbst im Hochvakuum nur mäßig oder gar nicht in die Gasphase bringen lassen, wurde in der vorliegenden Arbeit die Solution-Spray-Technik für die Anwendung im präparativen Maßstab entwickelt. Unter Verwendung von Ölzerstäuberdüsen, wie sie in der Heizungs- und Brennertechnik Anwendung finden, wurde die Erzeugung eines stabilen Lösungs-Sprays in die vorhandene Blitzvakuumpyrolyse-Technik integriert. Der Einfluss verschiedener Variablen, wie Flussrate, Druck, Temperatur und Lösungsmittel wurde untersucht. Die Solution-Spray-Technik wurde für die [3,3]-sigmatrope Umlagerung bestimmter Propargylthiocyanate zu Allenyl-isothiocyanaten angewendet.
Des Weiteren wurde Propa-1,2-dienylisothiocyanat – das einfachste Allenylisothiocyanat – mit diversen sterisch anspruchsvollen primären und sekundären Aminen in mäßigen bis exzellenten Ausbeuten zu 2-Amino-1,3-thiazolen umgesetzt. Darauf aufbauend konnte eine Vier-Zentren-drei-Komponenten-Reaktion entwickelt werden. Es entstehen in hohen Ausbeuten 2-Amino-1,3-thiazole mit komplexen Substituenten an der 5-Position des Heterocyclus. Reaktionsmechanismen werden diskutiert um die alternative Bildung einer hochsubstituierten 1,3-Thiazinstruktur zu erklären. Der Einfluss von Reaktionstemperatur, Konzentration und Lösungsmittel auf das Produktverhältnis wurde ebenfalls untersucht und wird diskutiert.
Es konnte gezeigt werden, dass 2-Amino-5-methyl-1,3-thiazole als offenbar erste aromatische Substanzklasse sehr gute Substrate für die Bildung von 1,3-Dioxanen nach Prins darstellen.
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Development of the Solution-Spray Flash-Vacuum-Pyrolysis Technique in the Synthesis of Allenyl Isothiocyanates and Synthesis of Complex 2-Amino-1,3-thiazole DerivativesRichter, Frank 29 June 2015 (has links)
Gas-phase thermolysis is a long-known and well established method for the preparation of reactive species. It is, however, limited to relatively volatile substances, which are easily vaporised. In the present work, the solution-spray technique for preparative scale was developed. With this technique, it is possible to subject low-volatile substances, which hardly vaporise even under high-vacuum conditions, to gas-phase thermolysis. By utilising oil nozzles used in heating and burner systems, it was possible to integrate a stable solution-spray into the existing flash-vacuum-pyrolysis system. The influence of several variables, such as flow-rate, pressure, temperature and solvent was determined. The solution-spray technique was applied in [3,3]-sigmatropic rearrangements of certain propargyl thiocyanates to the corresponding allenyl isothiocyanates.
Furthermore, the parent compound propa-1,2-dienyl isothiocyanate was reacted with various sterically demanding primary and secondary amines to form 2-amino-1,3-thiazoles in moderate to excellent yields. Based on this, a catalyst-free four-center three-component reaction was developed. 2-Amino-1,3-thiazoles with complex substituents in 5-position at the heterocyclic ring are formed. Reaction mechanisms are discussed to explain the occurance of a highly substituted 1,3-thiazine structure. The influence of reaction temperature, concentrations and solvent were determined and are also discussed.
It was shown that 2-amino-5-methyl-1,3-thiazoles are the apparently first aromatic substance class, that readily undergoes Prins-type 1,3-dioxane ring-formation. / Die Gasphasenthermolyse ist eine lang bekannte und etablierte Methodik zur Synthese reaktiver Spezies. Sie ist allerdings auf flüchtige Substanzen mit einer guten Verdampfbarkeit beschränkt. Für schwerflüchtige Verbindungen, welche sich selbst im Hochvakuum nur mäßig oder gar nicht in die Gasphase bringen lassen, wurde in der vorliegenden Arbeit die Solution-Spray-Technik für die Anwendung im präparativen Maßstab entwickelt. Unter Verwendung von Ölzerstäuberdüsen, wie sie in der Heizungs- und Brennertechnik Anwendung finden, wurde die Erzeugung eines stabilen Lösungs-Sprays in die vorhandene Blitzvakuumpyrolyse-Technik integriert. Der Einfluss verschiedener Variablen, wie Flussrate, Druck, Temperatur und Lösungsmittel wurde untersucht. Die Solution-Spray-Technik wurde für die [3,3]-sigmatrope Umlagerung bestimmter Propargylthiocyanate zu Allenyl-isothiocyanaten angewendet.
Des Weiteren wurde Propa-1,2-dienylisothiocyanat – das einfachste Allenylisothiocyanat – mit diversen sterisch anspruchsvollen primären und sekundären Aminen in mäßigen bis exzellenten Ausbeuten zu 2-Amino-1,3-thiazolen umgesetzt. Darauf aufbauend konnte eine Vier-Zentren-drei-Komponenten-Reaktion entwickelt werden. Es entstehen in hohen Ausbeuten 2-Amino-1,3-thiazole mit komplexen Substituenten an der 5-Position des Heterocyclus. Reaktionsmechanismen werden diskutiert um die alternative Bildung einer hochsubstituierten 1,3-Thiazinstruktur zu erklären. Der Einfluss von Reaktionstemperatur, Konzentration und Lösungsmittel auf das Produktverhältnis wurde ebenfalls untersucht und wird diskutiert.
Es konnte gezeigt werden, dass 2-Amino-5-methyl-1,3-thiazole als offenbar erste aromatische Substanzklasse sehr gute Substrate für die Bildung von 1,3-Dioxanen nach Prins darstellen.
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