The kinetic study of thermal decomposition of compounds (A)-(E) had been examined. The thermal decomposition product of 1,1-dimethyl-5-(1-isobutenyl)-1-pyrazoline is 1,1-dimethyl5-(1-isobutenyl)cyclopropane, no hydrogen transfer or rearrangement was occured. The only isolated thermal decomposition product of 3-methyl-3,4-dicarboxylic anhydride-l-pyrazoline was dirnethylmaleic anhydride. Since carbon dioxide was found in the decomposition process and the amount of nitrogen gas and carbon dioxide was not the same, it indicated that the decarboxylation product was not come from the nitrogen freed anhydride product.Ball State UniversityMuncie, IN 47306

Thèse de doctorat : Chimie organique : Strasbourg 1 : 2006. / Titre provenant de l'écran-titre. Bibliogr. p. 179-184.

No description available.

Thèse (M.Sc.)--Université Laval, 2008 . / Bibliogr.: f. 102-132. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 75-79).

Some compounds, analogous to those found in naturally occurring systems, are found to possess chemotherapeutic activity. Some, in the form of their nucleoside or nucleotide derivatives, are valuable antimetabolites in that they may block normal RNA or DNA polymerisation, or may be incorporated into nucleic acids to form fraudulent, but not necessarily defective, polymers. Modification of natural ring systems, with a view to promoting chemotherapeutic activity is therefore of considerable interest; variation in the position and nature of the modification or ring substituent having a marked effect on chemotherapeutic activity. It is the purpose of this thesis to suggest methods for the facile synthesis of various uracils, pyrazoles and pyrazolo [3,4-d] - pyrimidines with alkyl, aryl and glycosyl substituents such that the nature of the ring substituents is easily varied. To this end a number of ethoxymethylene reagents were prepared which, by reaction with primary amines and hydrazines, would give acyclic intermediates capable of easy cyclisation into the uracil, pyrazole and pyrazolo [3,4-d] pyrimidine ring systems. Variation in the nature of specific substituents being determined by the choice of amine or hydrazine, other substituents being varied by modification of the original reagent. / S.R.G.

Les différentes techniques d'extraction et d'analyse existant pour étudier les insecticides contenus dans le miel ne permettent pas toujours d'atteindre de faibles limites de détection. Or, pour évaluer la toxicité des pesticides, des valeurs de limites de détection de l'ordre du ng/g doivent être obtenues. L'objectif de ce travail a été de développer des méthodes d'extraction et d'analyse compatibles avec différents types de miels (miels de nectars et de miellats, monofloraux et multifloraux) et permettant de rechercher 25 insecticides d'intérêt appartenant à 3 familles (nicotinoïdes, pyréthrinoïdes et pyrazoles,), avec des limites de détection les plus faibles possibles et en éliminant au maximum les interférences liées à la matrice. Après comparaison de différentes méthodes d'extraction, la technique retenue est basée sur la méthode QuEChERS EN 15662, qui consiste en une extraction et une purification à l'aide de sels adaptés à la matrice et aux composés à extraire. Les analyses ont ensuite été effectuées en chromatographie en phase gazeuse couplée à la spectrométrie de masse en tandem (GC-MS²), pour les pyrazoles et les pyréthrinoïdes, et en chromatographie liquide haute performance couplée à la spectrométrie de masse en tandem (LC-MS²) pour les nicotinoïdes et un pyrazole, les réglages des appareils devant être optimisés pour permettre d'obtenir une limite de détection très basse. Les rendements d'extraction obtenus sont majoritairement compris entre 60 et 140%. Les méthodes développées sont spécifiques pour les miels testés. / Several extraction and analytical techniques existing to study insecticides in honey do not always allow reaching low limits of detection. However, to evaluate the toxicity of pesticides, values of limits of detection have to be close to 1 ng/g. The aim of this work was to develop extraction and analytical methods compatible with various types of honey (nectars and honeydews, monofloral and multifloral) and allowing to look for 25 insecticides belonging to 3 families (nicotinoids, pyrethroids and pyrazoles), with the lowest possible limits of detection and eliminating the maximum interference due to the matrix. After comparison of different extraction methods, the reserved technique is based on the QuEChERS EN 15662 method, which consists of an extraction and a purification with mixtures of salts adapted to the matrix and to the compounds to be extracted. Analysis were then performed using gas chromatography coupled with tandem mass spectrometry (GC-MS²) for the pyrazoles and the pyrethroids, and using high performance liquid chromatography coupled with tandem mass spectrometry (LC-MS²) for the nicotinoids and one pyrazole. Device settings have to be optimized to obtain a very low limit of detection. The mean extraction yields were typically between 60 and 140%. The methods are specific for tested honeys. These methods are applicable to analyze commercial honeys and allow reaching limits of detection between 0.2 and 0.7 ng/g. In practice, the dosage of these 3 families in different types of honeys, at low concentrations can be made in routine in an analysis laboratory.

La recherche de nouvelles réactions est un des enjeux fondamentaux de la chimie organique. En dehors de l’approche classique basée sur la conception d’une réaction en s’appuyant sur les propriétés chimiques des substrats, une nouvelle approche utilisant le criblage systématique de combinaisons aléatoires de fonctions réactives a été récemment adoptée par plusieurs groupes. Cette stratégie nécessite un outil analytique permettant de cribler un très grand nombre de réactions par jour et d’identifier les meilleures combinaisons conduisant à la formation de produits intéressants. Les travaux de thèse présentés dans ce mémoire s’inscrivent dans le contexte de l’utilisation des techniques de dosages immuno-enzymatiques (ELISA) comme outil de criblage pour la recherche de nouvelles réactions de couplage. Dans un premier temps le criblage de 2688 combinaisons de fonctions réactives et de catalyseurs choisies au hasard a été effectué. Ce criblage a permit de mettre en évidence deux nouveaux couplages en présence de sels de cuivre : une réaction entre les thiourées et les phénols conduisant à la formation des isourées et une réaction entre les N-hydroxythiourées et les alcynes conduisant à la formation des thiazole-2-imines. Dans un second temps le criblage de 2816 combinaisons de fonctions sélectionnées, cette fois-ci, de façon rationnelle a été effectué. Ce criblage a visé la découverte de nouvelles cycloadditions [3+2] répondant aux critères de la chimie « click ». Ainsi l’utilisation de dosage immuno-enzymatique a été étendue à l’optimisation des nouvelles réactions découvertes ainsi qu’à l’évaluation de leurs cinétique, chimiosélectivité et biocompatibilité. Près de 3000 tests complémentaires effectuées sur les « hits » issus du criblage primaire ont ainsi permit de mettre en évidence 4 nouvelles réactions de couplage dont une nouvelle réaction « click » : la cycloaddition sydnone-alcyne catalysée au cuivre (CuSAC). Dans la dernière partie de ce manuscrit les études plus détaillées sur la réaction CuSAC ont été effectuées, notamment l’identification de la structure du produit de couplage et l’étendue du champ d’application de cette réaction. Enfin, l’aspect « click » de la réaction CuSAC a été illustré par l’application de cette réaction au marquage d’une protéine. / Discovery of new reactions is one of the fundamental goals in organic chemistry. In addition to the traditional approach to reaction discovery, consisting in designing a reaction on the basis of known chemical properties of reagents, new approaches based on the screening of random combinations of reactive functions and catalysts have been recently developed. The main prerequisite of this strategy is an analytical tool allowing screening of a big number of reactions per day and identifying combinations leading to the formation of unanticipated products. In the work presented herein a high-throughput immunoassay screening has been used for the discovery of new coupling reactions. In the first part of this work a screening of 2688 combinations of randomly chosen reactive functions and catalysts was carried out. This screening led to the discovery of two copper-promoted coupling reactions: a reaction between thioureas and phenols leading to the formation of isoureas through desulfurization; and a reaction between N-hydroxythioureas and alkynes leading to the formation of thiazole-2-imines. In the second part of the work a screening of 2816 combinations of rationally designed chemical functions and catalysts was carried out. This screening was focused on the discovery of catalytic [3+2] cycloadditions that comply with the standards of “click” chemistry. In this study, the use of immunoassay screening was extended to optimize new reactions and to evaluate their kinetics, chemoselectivity and biocompatibility. Therefore, around 3000 complementary tests were carried out on the hits, identified in the primary screening. This allowed the discovery of 3 new coupling reactions and one new “click” reaction: a copper-catalyzed sydnone-alkyne cycloaddition (CuSAC). The last part of the work was focused on detailed studies of the CuSAC reaction. Identification of the structure of the coupling product and substrate scope of this reaction was carried out. Finally, the applicability of the CuSAC reaction for bioconjugation was demonstrated by an example of protein labeling.

M.Sc. / 2-(Pyrazol-1-ylmethyl)pyridine ligands were synthesised by phase transfer alkylation of 2-picolyl hydrochloride with the appropriate pyrazole. These ligands were subsequently reacted with NiCl2, NiBr2, FeCl2 or CoCl2 to form the respective complexes. The substituents on the pyrazole included phenyl and tert-butyl groups as well as electron withdrawing CF3 groups. The substituents played an important role in the steric and electrophilic nature of the metals. A second ligand design is 2,6-bis(pyrazol-1-ylmethyl)pyridine and were prepared by phase transfer alkylation of 2,6-bis(chloromethyl)pyridine with two mole equivalents of the appropriate pyrazole. These ligands were reacted with NiCl2, NiBr2, FeCl2 or CoCl2 to form the respective complexes. A third ligand design is 2-(chloromethyl)- or 2-(bromomethyl)-6-(pyrazol-1-ylmethyl)pyridine and were prepared by the selective alkylation of 2,6-bis(chloromethyl)pyridine with one mole equivalent of the appropriate pyrazole. These ligands were also reacted with NiCl2, NiBr2, FeCl2 or CoCl2 to form the respective complexes. Characterisation of all compounds was done by a range of spectroscopic techniques as well as X-ray crystallography and elemental analysis. The data showed good fit to the proposed structures and in a few cases were confirmed by X-Ray crystallography. All complexes were tested as catalysts for ethylene and higher olefin oligomerisation and showed good activity. The production of alkenes were confirmed in toluene and hexane, however, due to the use of EtAlCl2 and toluene the oligomers were alkylated to form the Friedel-Crafts alkylation products. Similar alkylation was observed for the higher olefin reactions. In comparison, the same reactions in hexane resulted in only C4, C6 and C8 oligomers. When higher olefin reactions were also conducted in hexane, polymeric solids were observed.

Os radicais livres são espécies químicas que reagem rapidamente com diversos compostos e alvos celulares, por possuírem tempo de meia vida muito curto e serem espécies altamente instáveis. A formação destes compostos constitui uma ação contínua e fisiológica, cumprindo funções biológicas essenciais as quais ocorrem pela perda ou adição de um único elétron a um composto não radicalar. Estas reações podem ocorrer em processos bioquímicos do sistema imune ou químicos, causando prejuízo às células através da destruição de componentes, como proteínas, lipídios, açúcares e nucleotídeos. Sabe-se que existem compostos que são efetivos contra tais espécies, prevenindo os danos provocados pelo estresse oxidativo. O objetivo deste trabalho foi estudar compostos heterocíclicos que possuam nitrogênio em sua estrutura (azóis), que figuram na literatura como moléculas exemplares de compostos de aplicação farmacológica de amplo espectro. Dentre estes compostos foram analisados os derivados de pirazóis (26 compostos), tiazóis (7 compostos) e 1 isoxazol (3,5-dimetilisoxazol). Estes 34 compostos foram avaliados pela metodologia ORAC (Capacidade de Absorção de Radicais Oxigênio) a fim de determinar e/ou de avaliar seu potencial antioxidante. A escolha do método ORAC se deu pelo fato das moléculas estudadas apresentarem características hidrofílicas e lipofílicas, além de ser um método validado pela literatura, disponível e de ampla aplicação. O método ORAC avalia a capacidade antioxidante da amostra, medindo sua habilidade de proteger a fluoresceína (FL) da oxidação pelo AAPH no meio reacional. O AAPH é um gerador de radicais livres que a 37°C retira hidrogênio do meio, promovendo a redução da fluorescência da fluoresceína em λ medido pelo tempo. Seis compostos apresentaram atividade antioxidante de boa à moderada: 3,5-dimetil-1H-pirazol (2.382 µmol eq.Trolox/g); 3-fenil-5-(4-fluorfenil)-1-tiocarbamoil-4,5-diidro-1H-pirazol (6.354 µmol eq.Trolox/g); 3-fenil-5-(2-metoxifenil)-1-tiocarbamoil-4,5-diidro-1H-pirazol (8.739 µmol eq.Trolox/g); 5-(2,4-diclorofenil)-3-fenil-1-tiocarbamoil-4,5-diidro-1H-pirazol (6.022,226 µmol eq.Trolox/g); 2-[5-(4-metoxifenil)-3-fenil-4,5-diidro-1H-pirazol-1-il]-4-feniltiazol (3.135 µmol eq.Trolox/g); e finalmente 2-[5-(3-nitrofenil)-3-fenil-4,5-diidro-1H-pirazol-1-il]-4-feniltiazol (2.700 µmol eq.Trolox/g). Os experimentos com o método ORAC para os azóis estudados apresentaram reprodutibilidade na execução experimental e demonstraram ser uma alternativa viável para estudos de moléculas sintéticas de potencial antioxidante. / Free radicals are chemical species that react rapidly with various compounds and target cells, as they have a very short half life and are highly unstable. The formation of these compounds consists of a continuous, physiological action, which includes essential biological functions and occurs through the loss or addition of a single electron to a non-radical compound. These reactions may occur in biochemical processes of the immune system, or by chemical reactions, causing damage to the cells through the destruction of components such as proteins, lipids, sugars and nucleotides. It is known that compounds exist which are effective against these species, preventing damage caused by oxidative stress. The object of this work was to study heterocyclic compounds that have nitrogen in their structure (azoles), which appear in the literature as exemplary molecules of compounds with a wide spectrum of pharmacological applications. Of these compounds, derivatives of pyrazoles (26 compounds), thiazoles (7 compounds) and 1 isoxazole (3,5-dimethylisoxazole) were analyzed. These 34 compounds were evaluated by the ORAC (Oxygen Radicals Absorption Capacity) in order to determine and/or evaluate its antioxidant potential. The choice of ORAC method is based on the fact that the molecules studied have hydrophilic and lipophilic characteristics, as well as a method validated by the literature, which is available and widely used. The ORAC method evaluates the antioxidant capacity of the sample, measuring its ability to protect the fluorescence (FL) of the oxidation by the AAPH in the reaction medium. AAPH is a generator of free radicals which, at 37°C, removes hydrogen from the medium, promoting the reduction of fluorescence from fluorescein in λ measured by time. Six compounds present good to moderate antioxidant activity: 3,5-dimethyl-1H-pyrazole (2.382 µmol eq.Trolox/g); 3-phenyl-5-(4-fluorphenyl)-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole (6.354 µmol eq.Trolox/g); 3-phenyl-5-(2-methoxyphenyl)-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole (8.739 µmol eq.Trolox/g); 5-(2,4-diclorophenyl)-3-phenyl-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole (6.022,226 µmol eq.Trolox/g); 2-[5-(4-methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-il]-4-phenylthiazole (3.135 µmol eq.Trolox/g); and finally, 2-[5-(3-nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-il]- 4-phenylthiazole (2.700 µmol eq.Trolox/g). Experiments with the ORAC method for the azoles studied present reproducibility in the experimental execution, and have proven to be a viable alternative for studies of synthetic molecules with antioxidant potential.