No description available.

No description available.

Morphine and its derivatives continue to challenge the creativity of synthetic chemists. The aim of this research is to execute a short chiral synthesis of the morphinan system. Chirality is introduced via asymmetric reduction; the key step is the formation of four rings- the tetracyclic phenanthrofuran by an intramolecular Diels-Alder cycloaddition. The fifth ring was completed by three different methods, and three different pentahydrophenanthrofuran systems were obtained.

Morphine and its derivatives continue to challenge the creativity of synthetic chemists. The aim of this research is to execute a short chiral synthesis of the morphinan system. Chirality is introduced via asymmetric reduction; the key step is the formation of four rings- the tetracyclic phenanthrofuran by an intramolecular Diels-Alder cycloaddition. The fifth ring was completed by three different methods, and three different pentahydrophenanthrofuran systems were obtained.

Cette étude concerne l'optimisation, la conception et la caractérisation de microréacteurs, de type multicanaux, appliqués à l'électrosynthèse organique de composés fluorés à intérêt médical tels que le 2-Fluoro- 2-Deoxy-D-Glucose (18FDG). Les microsystèmes ont connu un développement important ces dernières années dans le domaine de la chimie fine où la volonté est de développer des outils toujours plus compétitifs. Les microréacteurs appliqués à la synthèse offrent l’avantage d’un rapport surface sur volume de la zone réactionnelle élevé (> 100 cm-1), ce qui améliore nettement les transferts de masse et d’énergie et permet de traiter de très faibles quantités dans des conditions plus sûres et plus respectueuses de l’environnement. L’élément de base du microréacteur est souvent constitué d’un simple microcanal qu’il est nécessaire de dupliquer pour fournir le débit de production adapté à une application donnée. Ainsi, un microréacteur sera souvent composé d’une série de microcanaux disposés en parallèle et connectant un canal distributeur et un canal collecteur. Cette configuration peut entraîner une faible uniformité de la distribution de l’écoulement dans les différents microcanaux de réaction et il est particulièrement important d’optimiser la géométrie du microréacteur complet pour tendre vers une distribution uniforme des temps de séjour (DTS). Dans le cas de la synthèse électrochimique, les microcanaux sont directement gravés dans deux électrodes placées en vis-à-vis et séparées par une membrane échangeuse d’ions. Une optimisation préliminaire de la DTS au sein d’une électrode composée de microcanaux parallèles de section rectangulaire est réalisée. L’arrivée et la sortie du fluide s’effectue par l’intermédiaire de deux canaux distributeur et collecteur de section également rectangulaire, mais non constante. L’optimisation vise à déterminer une évolution linéaire optimale de la largeur de ces canaux distributeur et collecteur. Un modèle analytique basé sur des hypothèses simplificatrices permet de calculer les différentes pertes de charge ainsi que les débits dans chaque microcanal, dans le cas d’un écoulement laminaire de liquide. Les résultats obtenus sont ensuite confirmés par des simulations numériques 3-D, plus précises. Un modèle hybride combinant les simulations numériques pour les canaux distributeur et collecteur et le modèle analytique pour les microcanaux parallèles est également développé. Il permet d’augmenter la finesse du maillage dans les zones sensibles de l’écoulement, sans nécessité d’accroître les ressources informatiques (mémoire et temps de simulation). Les résultats obtenus montrent un très bon accord entre les simulations numériques 3-D, le modèle hybride et le modèle analytique. Sur un exemple de 10 microcanaux parallèles, il est montré que dans le cas de la géométrie initiale, pour laquelle les canaux collecteur et distributeur sont de section constante, des écarts de l’ordre de 50 % existent entre les débits traversant les microcanaux latéraux et centraux. Après optimisation, cet écart est réduit à moins de 0,1 %. Le modèle analytique est ensuite étendu au cas d’écoulements gazeux en prenant en compte les effets non linéaires et antagonistes de la raréfaction et de la compressibilité de l’écoulement. La raréfaction est ici caractérisée par un nombre de Knudsen compris entre 0 et 0,1 et se traduit pas des sauts de vitesse à la paroi ; les écoulements dans ce régime modérément raréfié sont alors correctement modélisés par les équations compressibles de Navier Stokes associées à des conditions de glissement du second ordre en Knudsen, en prenant en compte la géométrie tridimensionnelle des microcanaux de réaction et des canaux collecteur et distributeur. / This study focuses on the optimisation, design and characterization of microreactors, of multichannel type, applied to the organic electrosyntheses of fluorinated compounds of medical interest such as the 2-Fluoro-2-Deoxy-D-Glucose (18FDG). Microsystems have known an important development these last years in the field of fine chemicals where the aim is to develop increasingly competitive tools. The microreactors applied to synthesis offer a reaction zone with high surface to volume ratio (> 100 cm-1), which significantly improves mass and energy transfers and allows treating small quantities in safer conditions and a better respect of environment. The basic element of the microreactor is often composed of a single microchannel, which is necessary to duplicate in order to provide the suitable production rate for a given application. Thus, a microreactor is often composed of a series of microchannels arranged in parallel and connecting a distributing channel to a collecting one. This configuration can result in poor uniformity of flow distribution among the reaction microchannels and it is particularly important to optimize the geometry of the microreactor in order to obtain a uniform residence time distribution (RTD). In the case of electrochemical synthesis, microchannels are directly etched into two electrodes facing each other and separated by an ion exchange membrane. A preliminary optimisation of the RTD in an electrode composed of parallel microchannels with rectangular cross-section is performed. The fluid inlet and outlet are connected to a distributing and a collecting channel with non constant rectangular cross-section. The aim of the optimisation is to determine an optimal linear evolution of the width of the distributing and collecting channels. An analytical model based on simplifying assumptions allows calculating the various pressure drops and the flowrate in each microchannel, in the case of a laminar liquid flow. The obtained results are then confirmed by more accurate 3-D numerical simulations. A hybrid model combining numerical simulations for the distributing and collecting channels and the analytical model for the parallel microchannels is also developed. This model allows a more refined mesh in the sensitive areas of the flow, without requiring additional numerical effort (memory and simulation time). The results show a good agreement between the 3-D numerical simulations, the hybrid model and the analytical model. On an example of 10 parallel microchannels, it is shown that in the case of the initial geometry (with a constant cross-section of collecting and distributing channels), the flowrate difference through the lateral and the central microchannels is in the order of 50%. After optimization, this difference is reduced to less than 0.1%. The analytical model is then extended to the case of gas flows, taking into account nonlinear and antagonist effects of rarefaction and compressibility. Rarefaction is characterized by the value of the Knudsen number which remains lower than 0.1; the flow in this moderately rarefied regime is accurately modelled by the compressible Navier-Stokes equations associated with second-order slip boundary conditions, taking into account the three-dimensional geometry of the reaction microchannels and of the collecting and distributing channels.

No description available.

<p>  </p> <p>Aromatic C-N bond formation is critical for synthetic chemistry in pharmaceutical, agrochemical, and natural product synthesis. Due to the prevalence of this bond class, many synthetic routes have been developed over time to meet the demand. The most recent and robust C-N bond formation reaction is the palladium catalyzed Buchwald-Hartwig amination. Considering the importance of the Buchwald-Hartwig amination, a high-throughput experimentation (HTE) campaign was devised to create a library in which chemists can refer to optimal reaction conditions and ligand/catalyst choice based on the nature of their substrates to be coupled. This study showed trends for the appropriate choice of ligand and catalyst, along with what bases, temperatures, stoichiometries, and solvents are appropriate for the selected substrate combination at hand. </p>

Nosso objetivo principal é aproveitar a bem conhecida diastereosseletividade &#960;-facial das (SS)-2-tolilsulfinil-1,4-benzoquinonas, em reações de Diels-Alder, para obter, via metátese olefínica fototérmica, precursores enantiopuros do capneleno e da icarugamicina. Devido à formação de uma inseparável mistura de produtos na reação da (SS)-2-tolilsulfinil-1,4-benzoquinona com 1-metilciclopentadieno comercial, esta rota se tornou inviável para obtenção do capneleno. Visando-se a síntese do precursor da icarugamicina, foram preparadas as 5 e 6-metil-2-tolilsulfinil-1,4-benzoquinonas mas, apesar dos bons resultados de seletividade &#960;-facial que estas apresentaram com o 1,3-cicloexadieno, a eliminação espontânea de ácido sulfênico nos adutos de Diels-Alder formados impediu o uso destes últimos. Numa tentativa de sobrepujar este inconveniente, uma nova quinona clorada foi preparada mas esta se mostrou um oxidante frente ao 1,3-cicloexadieno. / Our main objective is to take advantage of the well known &#960;-facial diastereoselectivity of (SS)-2-tolylsulfinyl-1,4-benzoquinones, in the Diels-Alder reactions, to obtain, via photo-thermal olefin metathesis, enantiopure precursors of capnellene and ikarugamycin. The formation of an inseparable mixture of products in the reaction of commercially available methylcyclopentadiene and (SS)-2-tolylsulfinyl-1,4-benzoquinone made this route unsuitable for obtaining capnellene. For the synthesis of ikarugamycin, the 5 and 6-methyl-2-(SS)-tolylsulfinyl-1,4-benzoquinones were prepared but, in spite of the good &#960;-diastereoselectivity they exhibited, in the reaction with 1,3-cyclohexadiene, spontaneous elimination of sulfenic acid from the formed adducts precluded their use. In an attempt to overcome this very easy elimination, a chlorinated quinone was synthesized but it showed oxidizing properties in the presence of 1,3-cyclohexadiene.

Gegenstand dieser Arbeit ist die Synthese und Charakterisierung von Bis-1,3-azol-Derivaten insbesondere im Hinblick auf ihre potentielle Einsatzfähigkeit als chemisches Sensormaterial. Nach bereits bekannten Methoden gelang es, zehn neue Bisoxazol-Derivate sowie zehn neue Dicarbonsäurediester herzustellen. Weiterhin wurden 13 neue Bisimidazol- und vier neue Lophin-Derivate synthetisiert. Die erhaltenen Röntgeneinkristallstrukturanalysen zeigen, dass vor allem lineare Bisimidazol- und Bisoxazol-Derivate gute Eigenschaften als Clathratbildner aufweisen. Die Bisoxazol-Derivate mit Pyridin als Spacerelement eignen sich vorwiegend zur Komplexierung von Nickel(II)-, Kupfer(II)- und Kobalt(II)-ionen. Aus den fluoreszenzspektroskopischen Untersuchungen geht hervor, dass verschiedene Analytdämpfe unterschiedliche Auswirkungen auf die Festkörperfluoreszenz ausüben. Somit erscheint der Einsatz von Derivaten dieser Verbindungsklasse in chemischen Fluoreszenzsensoren erfolgversprechend.

Nosso objetivo principal é aproveitar a bem conhecida diastereosseletividade &#960;-facial das (SS)-2-tolilsulfinil-1,4-benzoquinonas, em reações de Diels-Alder, para obter, via metátese olefínica fototérmica, precursores enantiopuros do capneleno e da icarugamicina. Devido à formação de uma inseparável mistura de produtos na reação da (SS)-2-tolilsulfinil-1,4-benzoquinona com 1-metilciclopentadieno comercial, esta rota se tornou inviável para obtenção do capneleno. Visando-se a síntese do precursor da icarugamicina, foram preparadas as 5 e 6-metil-2-tolilsulfinil-1,4-benzoquinonas mas, apesar dos bons resultados de seletividade &#960;-facial que estas apresentaram com o 1,3-cicloexadieno, a eliminação espontânea de ácido sulfênico nos adutos de Diels-Alder formados impediu o uso destes últimos. Numa tentativa de sobrepujar este inconveniente, uma nova quinona clorada foi preparada mas esta se mostrou um oxidante frente ao 1,3-cicloexadieno. / Our main objective is to take advantage of the well known &#960;-facial diastereoselectivity of (SS)-2-tolylsulfinyl-1,4-benzoquinones, in the Diels-Alder reactions, to obtain, via photo-thermal olefin metathesis, enantiopure precursors of capnellene and ikarugamycin. The formation of an inseparable mixture of products in the reaction of commercially available methylcyclopentadiene and (SS)-2-tolylsulfinyl-1,4-benzoquinone made this route unsuitable for obtaining capnellene. For the synthesis of ikarugamycin, the 5 and 6-methyl-2-(SS)-tolylsulfinyl-1,4-benzoquinones were prepared but, in spite of the good &#960;-diastereoselectivity they exhibited, in the reaction with 1,3-cyclohexadiene, spontaneous elimination of sulfenic acid from the formed adducts precluded their use. In an attempt to overcome this very easy elimination, a chlorinated quinone was synthesized but it showed oxidizing properties in the presence of 1,3-cyclohexadiene.