Dissertations / Theses on the topic 'Furkan'

This thesis describes the use of silver nitrate and iodine to promote 5-endo-dig cyclisations in the synthesis of furans. The oxidation of furylethanols will be discussed as will methods to synthesise furylacetic acids. The total synthesis of a natural product, Plakorsin B will be described along with the total synthesis of the furan fatty acids F5 and F6 as well as giving an overview of their proposed role in Nature. Finally, a new methodology for methylation of halogenated heterocycles will be discussed.

La recherche scientifique concernant les polymères biosourcés augmente rapidement pendant les dernières années, poussée par des croissantes préoccupations écologiques et économiques, ainsi que par l'incertitude sur la disponibilité future de ressources pétrochimiques limitées. Durabilité est un mot-clé de ce processus. Dans ce cadre, des produits respectueux de l'environnement, y compris des molécules et des additifs eco-compatibles, sont maintenant recherchés pour remplacer les polymères à base de pétrole par ceux dérivés de matières premières naturelles.Les résines époxydes sont des polymères thermodurcissables très polyvalents, extrêmement résistants à la corrosion, à l'humidité et aux produits chimiques, avec une bonne force d'adhérence à la plupart des matériaux et un faible retrait lors du durcissement. En raison de leurs températures de transition vitreuse élevées et de leur excellente résistance mécanique, les résines époxydes sont largement utilisées dans une large gamme d'applications, telles que l'électronique, les adhésifs structuraux, les composites pour l'aérospatiale et les revêtements protecteurs.Actuellement, plus des deux tiers des résines époxydes sont à base de diglycidyl éther de Bisphénol A. Dans cette industrie, la tendance à remplacer les matériaux dérivés du pétrole par des matériaux biosourcés est également liée à la nécessité de remplacer le bisphénol A (BPA), une molécule controversée, reconnu comme un perturbateur endocrinien et une substance reprotoxique. En particulier en application comme revêtement, l'utilisation de BPA présente un risque pour les utilisateurs d'aliments et de boissons conditionnés dans des récipients traités avec des résines époxydes. Les effets de la contamination du corps humain causée par le BPA sont le diabète, maladies cardiovasculaires, modification des enzymes hépatiques et les lésions de l'appareil reproducteur. Pour ces raisons, cette molécule a été interdite dans de nombreux pays pour la fabrication de produits pour enfants, ainsi qu'en France et au Canada de tous les matériaux en contact direct avec les aliments. La nécessité de développer de nouvelles résines époxy est donc urgente.Les molécules bio-dérivées développées depuis maintenant présentent des structures chimiques les plus diverses, chacune d’elles produisant des propriétés différentes des polymères finaux. Les caractéristiques particulières des résines époxydes sont liées à la structure aromatique de ses composants. Les molécules aromatiques présentes dans les matières premières naturelles proviennent principalement de la lignine, un des principaux constituants des parois cellulaires naturelles. Cependant, pour extraire des fragments aromatiques de la lignine, des procédés difficiles et consommateurs d’énergie sont nécessaires. Un substitut précieux des molécules aromatiques, facilement récupérables du glucose, sont les molécules furaniques ; leur validité a été étayée par plusieurs études.À la lumière de ce qui précède, les travaux présentés ici sont focalisés sur la production de résines époxyde à base de furane comme substitut potentiel de DGEBA dans l’industrie du revêtement de boîtes de conserve. Le cycle complet du matériau a été étudié : des synthèses de monomères époxydes furaniques ont été proposées, puis des thermodurcis époxydes ont été obtenus et caractérisés à la fois dans leurs propriétés chimiques et physiques (étude de la cinétique de durcissement, des propriétés mécaniques et thermiques). En outre, l’application des matériaux thermodurcissables époxydes proposés comme revêtement interne des boîtes de conserve a été testée<br>Research on bio-based polymers is rapidly increasing in last years, pushed by growing environmental and economic concerns, as well as by the uncertainty about future availability of finite petrochemical resources. Sustainability is a keyword in this process. In this frame, products that are respectful towards the environment, including eco-compatible building blocks and additives, are now researched to replace petroleum-based polymers with those derived from naturally occurring feedstocks. Epoxy resins are very versatile thermosetting polymers, extremely resistant to corrosion, moisture and chemicals, with good adhesive strength toward most materials (wettability) and low shrinkage upon curing. Due to their high glass transition temperatures and excellent mechanical strength, epoxy resins are widely employed in a broad range of applications, such as electronics, structural adhesives, aerospace composites and protective coatings. More than two-thirds of epoxy resins nowadays are based on diglycidyl ether of bisphenol A. In this industry the trend to replace petrol-derived materials with bio-based ones is related also to the necessity to substitute the Bisphenol A (BPA), a controversial building block recognized as an endocrine disrupter and reprotoxic substance. In particular in application as coating, the use of BPA results in hazard for customers of food and beverage products packed into containers treated with epoxy resins. The effects of human body contamination caused by BPA are diabetes, cardiovascular diseases, altered liver enzymes and reproductive apparatus damages. For these reasons, this molecule has been banned in many countries for the manufacturing of child products, and in France and Canada from all the materials in direct contact with food. The necessity to develop new epoxy resins results therefore urgent.Bio-derived molecules since now developed show the most various chemical structure, each of them producing different properties of final polymers. Peculiar characteristic shown by epoxy resins are related to the aromatic structure of its components. Aromatic molecules present in natural feedstock are mainly derived from lignin, one of the principal constituents of natural cell walls. However, to extract aromatic moieties from lignin, difficult and energy consuming processes are required. A valuable replacement of aromatic molecules, easily recoverable from glucose, are furanic molecules; their validity has been supported by several studies. In the light of the above, the work here presented is focused on production of furanic bio-based epoxy resins as potential substitute of DGEBA in can coating industry. The complete cycle of the material has been studied: the synthesis of furanic epoxy monomers and epoxy thermosets, the characterization of their chemical and physical properties (study of curing kinetics, mechanical and thermal properties). Furthermore, the application of bio-based epoxy thermosets as cans internal lining has been evaluated. Experimental results demonstrated that the obtained resins have good potential to be proposed as good alternatives to the traditional BPA-containing epoxy resins

O objetivo deste trabalho foi iniciar o estudo de uma nova metodologia sintética para a obtenção do sistema 11-oxabiciclo[6.2.1]undecano, o esqueleto estrutural básico de uma classe de produtos naturais conhecidos como furanoeliangolidos. A abordagem sintética proposta envolveria a formação de um composto bicíclico através da reação de Diels-Alder com derivados de furano, seguida pela formação de um hexanel e, finalmente, ruptura de uma ligação central para formação do sistema macrocíclico. Além disso, a reação de Diels-Alder entre derivados de furano e acetileno dará origem a compostos que apresentam como esqueleto estrutural o sistema 7-oxabiciclo[2.2.1]heptano, que podem ser utilizados como material de partida para a síntese de diversos produtos naturais. Iniciamos este estudo com a reação de Diels-Alder entre o 3,4-dimetoxi-2-metil furano e o bromopropiolato de metila, onde foi obtido o produto 85, que após algumas modificações deu origem ao composto 92. Entretanto, após inúmeras tentativas não conseguimos transformar o composto 92 no triciclo desejado. Para evitar essas transformações que se mostraram problemáticas, resolvemos estudar a reação de Diels-Alder entre derivados de furano e benzoquinonas 2,5-dissubstituídas, que dará origem aos adutos devidamente funcionalizados para serem transformados no derivado do sistema 11-oxabiciclo [6.2.1]undecano. No entanto, após o estudo dessas reações de cicloadição, observamos que elas têm o equilíbrio fortemente deslocado no sentido dos materiais de partida. Por esse motivo, a continuidade desta metodologia sintética mostrou ser inviável. Iniciamos então, um estudo da reação de Diels-Alder entre os diverso derivados de furanos e acetilenos. Após o estudo dessas reações de Diels-Alder foi possível verificar que a maioria dos adutos derivados dos furanos é instável no meio reacional. Os melhores resultados obtidos nessas reações de Diels-Alder foram usando o acetilenodicarboxilato de dimetila como dienófilo. Os adutos obtidos são intermediários importantes e bem funcionalizados, que podem ser utilizados na continuidade do estudo de desenvolvimento de nova metodologia sintética para a obtenção do sistema 11-oxabiciclo[6.2.1]undecano<br>The aim of this work was to start the study of a new methodology to synthesize the 11-oxabicycle[6.2.1]undecane system, the main carbon skeleton of the furanoheliangolides. The proposed synthetic approach involves the preparation of a bicyclic compound through a Diels-Alder reaction with furan derivatives, followed by formation of a six membered ring and, finally, cleavage of the central bond to obtain of the macrocyclic system. The Diels-Alder reaction between furan and acetylene derivatives gives a compound with the 7-oxabicyclico[2.2.1]heptane system, that is a potential starting material for the synthesis of several natural products. We started this study with the Diels-Alder reaction between the 3,4-dimethoxy-2-methylfuran and methyl bromopropiolate, and obtained the product 85 that after some modifications furnished the compound 92. However, after various attempts we were unable to convert the compound 92 into the desired tricycle. We have then decided to study the Diels-Alder reaction between furan and 2,5-disubstituted benzoquinone derivatives, that could furnish the adducts properly functionalized to be transformed in the 11-oxabicyclico[6.2.1]undecane system. However, we observed that the equilibrium is strongly shifted towards the starting materials in these cycloaddition reactions. This methodology has thus showed to be impracticable. As a third alternative, we affected the study the Diels-Alder reaction between the furans derivatives and the acetylenes. The adducts obtained present 7-oxabicyclico[2.2.1]heptane system that could be used to synthesizes of structural skeleton of furanoheliangolide.

Dietary fish oil supplementation has long been shown to have significant health benefits, largely stemming from the anti-inflammatory activity of the ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) present in fish oils. The anti-inflammatory properties of these fatty acids has been linked to beneficial health effects, such as protecting the heart, in individuals consuming diets rich in fish, or supplemented with fish oils. These effects are highly notable in the Māori people native to coastal regions of New Zealand; the significantly lower rates of heart problems compared to the inland populous has been attributed to the consumption of the green lipped mussel Perna Canaliculus. Commercially available health supplements based on the New Zealand green lipped mussel include a freeze-dried powder and a lipid extract (Lyprinol®), the latter of which has shown anti-inflammatory properties comparable to classical non-steroidal anti-inflammatory drugs (NSAIDs) such as Naproxen. GCMS analysis of Lyprinol by Murphy et al. showed the presence of a class of ω-4 and ω-6 PUFAs bearing a highly electron rich tri- or tetra-alkyl furan ring, which were designated furan fatty acids (F-acids). Due to their instability, isolation of F-acids from natural sources cannot be carried out and a general synthetic route toward this class of natural products was required. To accomplish this, the biosynthesis of F-acids was mimicked by utilising an oxidation of 1,3-dienes, followed by a dehydration/aromatisation to generate the heterocyclic furan ring. Singlet oxygen was chosen as the means of oxidising the conjugated dienes giving endoperoxides. To mimic the biological aromatisation of the peroxide intermediates the Appel reagent was chosen and, in a novel application of the reagent, was exploited as a mild, metal free method of dehydrating the cyclic peroxides to their corresponding furans. The biomimetic furan synthesis was applied toward a selection of 1,3-diene substrates bearing a range of pre-installed functionalities and substitution patterns including alkyl, aryl, alkenes, cyclopropyl rings, silyl ethers, and esters, alongside being applied to the total synthesis of the furan fatty acid F5. A brief exploration of the possibility of performing the aromatisation reaction under catalytic conditions was carried out, to determine whether endoperoxides could be converted to furans without needing a stoichiometric quantity of Appel reagent, by harnessing a catalytic quantity of triphenylphosphine oxide and regenerating the active P(V) species via reaction with oxalyl chloride. Furthermore, an optimisation study was carried out using a simple design of experiments procedure to ascertain the ideal conditions for carrying out the Appel-type dehydration of endoperoxides. Finally, the scope of the reaction sequence was expanded to be performed in a continuous flow reactor, with telescoping of the singlet oxygen diene oxidation and Appel-type aromatisation to increase oxidation yields and to omit the requirement for isolation of peroxide intermediates, and was applied to the synthesis of a selection of 2,5-diaryl furan motifs.

Dissertação de Mestrado em Segurança Alimentar<br>O furano tem sido detectado em diversos alimentos em particular nos que são sujeitos a tratamento térmico durante o processo de preparação industrial. É considerado um composto potencialmente cancerígeno para seres humanos, pelo que a sua presença nos alimentos se tornou uma questão de segurança alimentar. Desde 2007 que a Autoridade Europeia para a Segurança Alimentar tem procurado recolher o maior número de informação possível, relativa à presença de furano nos alimentos. Neste trabalho utilizou-se a técnica de Cromatografia Gasosa de Espaço de Cabeça acoplada a um espectrómetro de massa (HS-GC/MS) para avaliar os teores de furano em feijões enlatados. Foram analisadas 10 amostras (latas) independentes, seleccionadas aleatoriamente no mercado, de três marcas comercializadas em Portugal. A concentração média obtida foi de 3,27 ng/g, numa gama que variou entre 2,61 e 4,45 ng/g. Os limites de detecção calculados foram de 0,80 ng/g para as amostras PD, 1,26 ng/g para as amostras C e de 0,58 ng/g para as amostras F. Os limites de quantificação foram, respectivamente, de 2,44, 3,82 e 1,77 ng/g. Os coeficientes de variação do método foram inferiores a 10% e a percentagem de recuperação foi de 95%. Para estudar o efeito do tratamento térmico doméstico, foram também, analisadas amostras aquecidas à temperatura de 80°C, tendo-se verificado um aumento significativo na concentração do furano detectada. Comparou-se ainda a concentração média do furano obtido nos feijões em lata com a concentração média para o mesmo tipo de feijão conservado em frascos de vidro, tendose constatado não existirem diferenças significativas.<br>ABSTRACT - Furan has been detected in various foods in particular in those that suffer heat-treatment during industrial preparation. It is considered a potentially carcinogenic compound to humans, so its presence in foods has become a matter of food security. Since 2007, the European Food Safety Authority has thought to collect as much information as possible on the presence of furan in food. In this work we used the technique of head space gas chromatography coupled with mass spectrometry HS-GC/MS to assess the levels of furan in canned beans. We analyzed 10 independent samples (cans), randomly selected on the market, and from three brands sold in Portugal. The average concentration obtained was 3.27 ng/g, with a range that varied between 2.61 and 4.45 ng/g. The detection limits calculated were 0.80 ng/g for samples PD, 1.26 ng/g for samples C and 0,58 ng/g for samples F. The limits of quantification were, respectively, 2.44, 3.82 and 1,77 ng/g. The coefficients of variation of the method were less than 10% and the recovery was 95%. To study the effect of house heat treatment, samples heated at 80°C were also analyzed, and there have been a significant increase in the concentration of detected furan. It is also compared the average concentrations of furan obtained from canned beans with the average concentrations for the same type of beans stored in glass bottles. No significant differences were found.

Furan and its derivatives are commonly found in numerous compounds such as natural products, polymers and medicines. The furan ring system is not only the core component to many natural products, but also serves as a key synthetic intermediate to access other more complex molecules. Among furan derivatives, furan fatty acids (F-acids) are an important class of natural products which are widely distributed in nature, and occupy a unique place in the field of medicinal chemistry because of their potent biological and pharmacological activity. This thesis examines the development of novel approaches towards highly substituted furans, with the ultimate goal of applying novel and high efficiency methods to the synthesis of F-acids and their derivatives. The first total synthesis of a natural product, an F-acids metabolite originally isolated from shark (Lamna ditropis) bile, was accomplished by the utilisation of an iodocyclisation of the corresponding 3-alkyne-1,2-diol to construct the furan nucleus; the synthetic route will be discussed in this thesis. Through the study of palladium-catalysis of a formal cyclisation to construct the furan ring system, a general route to access different F-acids has been developed. Splitting the F-acids into relatively simple fragments allows for easy preparation and modification of two fragments to produce a range of F-acids. The synthetic route was then applied to the formal synthesis of a natural product, F-acid F6. After optimisation of the synthetic route, total synthesis of F-acids F4, F6 and their analogues was accomplished.

The intramolecular Diels-Alder reaction of furan (IMDAF) provides a high degree of structural complexity in one step. However, reaction reversibility issues and the lower reactivity of furan in comparison to non-aromatic dienes prevent more widespread use of furan as a diene component in such reactions. Initial efforts to develop a new mode of organocatalysis which we hoped would facilitate IMDAF reaction was unfortunately unsuccessful, thus alternative means of IMDAF facilitation were investigated. For the first time, a comprehensive synthetic and computational study of the effect of halogen substitution on the IMDAF reaction has been undertaken. We have successfully demonstrated that halogenation of the furan moiety facilitates the IMDAF reaction (displaying increased reactivity to the non-halogenated analogue, regardless of halogen position), whereas dienophile halogenation hinders it. Additionally, careful selection of the position of the halogen on the furan can somewhat overcome the detrimental effect of having a halogen on the dienophile leading to highly functionalised cycloadducts with potential for further modification. Computational data produced by Martin Paterson and Justyna McKinlay support the idea that frontier molecular orbital effects cannot explain the experimental observations and we thus believe that the reactions are controlled by the interplay of three factors: positive charge stabilisation in the transition state and product, steric effects and a dipolar interaction term identified by the high level calculations. Finally, we have briefly demonstrated that nitro groups on the furan moiety also facilitate the IMDAF reaction whereas acyl groups appear to hinder the reaction. STEREOCHEMICAL ABSTRACT Any chiral compounds included in this thesis are racemic in nature. However, for clarity, such mixtures are schematically represented by drawings of only one of the enantiomers.

Norovirus causes roughly 23 million cases of foodborne illnesses in the United States each year. While this virus was characterized over 30 years ago, it remains non-cultivatable in human cells, resulting in an incomplete understanding of the host cell's response to infection. However, in 2004 murine norovirus (MNV) was found to be cultivatable in mice and has since been successfully cultured in RAW 264.7 cells. MNV has become an important model system for studying norovirus, as it is structurally and genetically similar to human norovirus. A global proteomics approach using fluorescently tagged, activity-based probes and 2D differential gel electrophoresis analysis was used to study MNV infection. Specifically, the process of cell death was investigated to determine if apoptosis, or programmed cell death, occurred in response to infection. Through the 2D differential gel analysis, 27 differentially regulated proteins were identified at 4 hours post infection, and 22 differentially regulated proteins were identified at 12 hours post infection; a strong majority of these proteins have been related to apoptosis in the literature. Using fluorescently-labeled activity-based probes and fluorimetric assays, we have monitored the activation of several caspases induced by viral infection. Infected samples show a significant increase in caspase activity over control samples within the first few hours post infection, indicating a virally induced activation of caspases. Cells were also infected in the presence of a pan-caspase inhibitor, Boc-D(OMe)-fmk, which led to caspase-independent cell death. Using propidium iodide and Hoechst staining, it was concluded that infected cells undergo necrosis in the presence of the caspase-inhibitor, while those infected in the absence of the inhibitor undergo apoptosis. From these studies it can be concluded that cells infected with MNV undergo a caspase-mediated, apoptotic cell death, while the caspase-independent cell death can be classified as necrosis. This study provides significant insight to norovirus-induced cell death.

Die elektrochemische Copolymerisation von Furan und Thiophen oder 3-Chlorothiophen wurde erfolgreich realisiert in einer Elektrolytlösung von Bortrifluorid-Diethylether + Ethylether (Verhältnis 1:2) bei konstantem Elektrodenpotenzial. Die Zugabe von Trifluoroessigsäure (TFA) (10 Vol-%) zu Bortrifluorid-Diethylether + Ethylether (Verhältnis 1:2) erniedrigte das Oxidationspotenzial der Monomere; die Polymerisationsgeschwindigkeit erhöhte sich, da TFA die Ionenleitfähigkeit des Elektrolyts vergrößert. Die Homopolymere zeigen nur einen Redoxpeak, verursacht durch Polymeroxidation und - reduktion. Die elektrochemische Copolymerisation wird bei verschiedenen Potenzialen und mit unterschiedlichen Thiophen- oder 3-Chlorothiophenkonzentrationen untersucht. Die Copolymere zeigen ein Redoxpeakpaar, dessen Position sich wesentlich von der der Homopolymere unterscheidet. Mit zunehmendem Polymerisationspotenzial und/oder zunehmender Konzentration an Thiophen- oder 3-Chlorothiophen werden auch mehr Thiophen- oder 3-Chlorothiopheneinheiten in den Copolymerfilm eingebaut. Ein Elektropolymerisationmechanismus wird für die Copolymere vermutet und die Copolymere weisen eine recht gute Langzeitstabilität der Redoxaktivität nach Zyklen in Acetonitril auf. In situ UV-Vis-Spektren der Homo- und Copolymerfilme wurden gemessen und λ1max, welches dem π → π*- Übergang entspricht, wurde bestimmt. Der optische Übergang bei λ2max vom Valenzband in das höhere Bipolaronband wurde ebenfalls bestimmt. Die Bandlücke für die Homo- und Copolymerfilme beim direkten Übergang wurde von der Kante im Absorptionsspektrum abgeschätzt. Die elektrochemische Thermodynamik für die Homo- und Copolymerfilme deutet darauf hin, dass jeweils ein Elektron von den Polymersegmenten, bestehend aus 4 Monomereinheiten, entfernt wird. Die untersuchten leitfähigen Filme zeigen einen Leitfähigkeitssprung mit einer stabilen Leitfähigkeit bis EAg/AgCl= 2 V. Diese Leitfähigkeitsänderung ist reversibel. Polyfuran hat verglichen mit Polythiophen eine geringere Leitfähigkeit und die Leitfähigkeit von Poly(3-chlorothiophen) ist rund eine Zehnerpotenz niedriger als die von Polythiophen. Da das in situ Leitfähigkeitsverhalten der Copolymere nicht die Summe der einzelnen Homopolymere bildet, kann man ausschließen, dass es sich bei den abgeschiedenen Copolymeren um Blockcopolymere handelt. Mit Hilfe der FTIR-Spektroskopie wurden Schwingungsspektren der Homo- und Copolymerfilme aufgenommen. Die Ergebnisse zeigen, dass es zur α-α'-Verknüpfung zwischen den Radikalkationen während der Copolymerisation kommt, was charakteristisch ist für α-substituierte fünfgliedrige heterozyklische Verbindungen. Der Mechanismus der elektrochemischen Degradation von Furan-Thiophen-Copolymeren wird ebenfalls mit Hilfe der gemessenen Spektren beschrieben. Die in situ Resonanz-Raman-Spektroskopie ergab, dass die spektroskopischen Eigenschaften der Copolymere zwischen denen der Homopolymere lagen. Bei höheren Polymerisationspotenzialen und höheren Konzentrationen an Thiophen oder 3-Chlorothiophen werden mehr Thiophen- oder 3- Chlorothiopheneinheiten in die Copolymerketten eingebaut. Es ist offensichtlich, dass die Ramanspektren der Copolymere wesentlich komplexer sind als die der Homopolymere, wodurch die Auswertung erschwert wird. Dennoch erinnern die Ramanspektren der Copolymere an die der Homopolymere. Die spektroelektrochemischen Eigenschaften der Copolymere haben bestätigt, dass deren Charakteristika zwischen denen der Homopolymere liegen, was deutlich macht, dass die Oxidation von Monomeren möglich ist und dass die Copolymerketten demnach aus Furan- und Thiophen- bzw. 3- Chlorothiopheneinheiten bestehen können<br>Electrochemical copolymerization of furan and thiophene or 3-chlorothiophene was successfully realized in a solvent system consisting of boron trifluoride ethyl ether (BFEE) + ethyl ether (EE) (ratio 1:2) at constant electrode potential. The addition of trifluoroacetic acid (TFA) (10 % by volume) to BFEE + EE (ratio 1:2) decreased the oxidation potential of the monomers; the polymerization rate was also accelerated because TFA increases the ionic conductivity of the electrolyte. The homopolymers have only one redox peak caused by polymer oxidation and reduction. Electrochemical copolymerization both at different potentials and with different thiophene or 3-chlorothiophene concentrations is investigated. The copolymers show one anodic/cathodic peak couple that appears at a position quite different from the positions observed with homopolymers. More thiophene or 3-chlorothiophene units are incorporated into the copolymer film with an increasing polymerization potential of the copolymer and/or with an increasing concentration of thiophene or 3- chlorothiophene in the feed. An electropolymerization mechanism of copolymers has been proposed, and the copolymers show a fairly good long-term stability of the redox activity after cycling in acetonitrile. In situ UV-Vis spectra of the homo- and copolymer films were measured and λ1max which corresponds to the π → π* transition is determined. The optical transition with λ2max from the valence band into the higher bipolaron band is also assigned. The band gap (Eg) for homo- and copolymer films from a direct interband transition is estimated from the absorption edge of the spectrum. The redox thermodynamics of the homo- and copolymer films suggest that one electron is removed from polymer segments containing four monomer units. The studied conducting films show a single conductivity change with a stable conductivity up to EAg/AgCl= 2 V. The conductivity of these films is almost restored when the potential shift direction is reversed. Polyfuran compared to polythiophene, has a lower conductivity and the conductivity of poly(3-chlorothiophene) is around one order of magnitude lower than that of polythiophene. The in situ conductivity properties of the copolymers are not the sum of those of the individual homopolymers. This result may eliminate the possibility that the copolymers can be considered as block copolymers. Vibrational spectra of homo- and copolymer films investigated in this study have been obtained using FTIR spectroscopy. The results indicate that α-α' coupling of radical cations has taken place in the copolymerization. This is a characteristic of α-substituted five-membered heterocyclic compounds. The electrochemical degradation mechanism of furan-thiophene copolymers is also described using the obtained spectra. The in situ resonance Raman spectroscopy of the copolymers shows spectroscopic properties intermediate between those of homopolymers. At higher polymerization potentials and at higher concentrations of thiophene or 3-chlorothiophene in the feed more thiophene or 3-chlorothiophene units are incorporated into the copolymer chains. It is obvious that the Raman spectra of the copolymers are more complex than those of homopolymers, which makes the assignment difficult. However, the in situ Raman spectra of the copolymers are reminiscent of those of the homopolymers. The spectroelectrochemical properties of the copolymers confirmed that the copolymers show intermediate characteristics between the homopolymers, implying that oxidation of monomers is possible and the copolymer chains may accordingly be composed of furan and thiophene or 3-chlorothiophene units

O objetivo do presente trabalho foi o de avaliar a capacidade seladora de diferentes materiais, associados ou não à irradiação laser, na região de furca de molares humanos, utilizando como microrganismo traçador o Enterococcus faecalis (ATCC 29212). Para tal, quarenta e oito molares inferiores humanos extraídos foram utilizados. As raízes foram seccionadas 4 mm abaixo da região da furca e a luz dos canais vedadas apicalmente com resina composta fotopolimerizável. A seguir, a cirurgia de acesso foi realizada e a câmara coronária preparada quimicamente com solução de hipoclorito de sódio a 1% reagindo com creme de Endo-PTC® durante 45 minutos. A irrigação final foi realizada com 5 mL de solução de EDTA-T 17%, durante 3 minutos, seguindo-se lavagem com 10 mL de solução de hipoclorito de sódio 1%. Após o preparo químico, os dentes foram divididos aleatoriamente em 5 grupos experimentais, de acordo com o agente impermeabilizante da furca: GI AHPlus ®; GII cianoacrilato de etila; GIII aplicação do laser Nd:YAG; GI associado aplicação do laser Nd:YAG + AH-Plus e GII associado aplicação do laser Nd:YAG + cianoacrilato de etila. Grupos controles positivo e negativo da esterilidade, da viabilidade bacteriana, foram desenvolvidos. Os dentes foram individualmente montados em seringas plásticas de 5 mL preparadas previamente e este aparato foi acoplado a uma câmara inferior, que continha meio de cultura TSB, sendo vedado com silicone. Esse conjunto foi esterilizado com radiação ionizante Co60 e os espécimes receberam 500 L do inóculo ajustado na escala Mc Farland 3 na câmara superior. A cada dois dias o meio de cultura foi renovado, estabelecendo-se um período de observação de 30 dias. Os resultados indicaram que a permeabilidade dentinária foi melhor controlada pela aplicação de cianoacrilato de etila na região da furca, não tendo o uso da irradiação laser contribuído para melhora do nível de impermeabilização da dentina.<br>The sealer capacity of differents materials, associated or not to the irradiation laser, in the furcal region of human molars, utilizing Enteroccocus faecalis ATCC 29212 whit micro-organism to inoculate this region, was the objective of the present research. For such forty-eight mandible human molars extracted were utilized. These roots were cute 4mm down the region of the furcal and the light of the canal roots sealed with resin composed. The surgery of access was carried out and the coronary camara prepared chemically with 1,0 % sodium hypochlorite reacting with Endo- PTC® cream during 45 minutes. The final irrigation by 17 % EDTA-T was performed, during 3 minutes, following the washing with 10 mL 1,0 % sodium hypochlorite. After the chemical preparation the teeth were divided randomly in 5 experimental groups, according to the material that turn the furcal region impermeability: GI AH-Plus®; GII cianoacrilato of etila; GIII Nd: YAG irradiation; GI associated Nd: YAG irradiation + AH-Plus® and GII associated Nd: YAG irradiation + cianoacrilato of etila. Groups controls of the sterility, positive and negative, were evaluated. The teeth individually were putted into the plastic syringes of 5 mL prepared previously, sterilized with Co60 radiation, and this apparatus was coupled to the lower chamber, that count TSB bacterial culture, being sealed with silicona of addition, Araldite® and Super Bonder®. The specimens were inoculated whit 500 L of the Enteroccocus faecalis adjusted in the Mc Farland 3 scale in the upper chamber. To each two days the environment of culture were renewed. The specimens of all of the groups presented microleakage in 11 days of observation. The results showed that the group whit cianoacrilato of etila gave better impermeability furcal region, followed by the AH Plus®, association of the laser Nd: YAG irradiation + cianoacrilato of etila, laser Nd: YAG irradiation and, finally, association of the laser Nd: YAG + AH Plus®.

The starting material for this project was the highly functionalized compound 3,3,4,4- tetraethoxybut-1-yne (TEB) and it can be prepared from ethyl vinyl ether by a 4-steps synthesis. The third and the fourth step in TEB synthesis were sensitive to reaction conditions, so it was developed a strategy to try to optimize the third step and obtain TEB with higher yields. An approach, which tries to optimize also the fourth step, will be developed in further works. Several γ-hydroxy-α,β-unsaturated acetylenic ketones can be prepared from 3,3,4,4- tetraethoxybut-1-yne. TEB and γ-hydroxy-α,β-unsaturated acetylenic ketones have been previously synthesized in good yields using various reaction routes. In this work will be shown the synthesis of 1,1-diethoxy-5-hydroxyhex-3-yn-2-one, 1,1-diethoxy-5-hydroxyundec-3-yn-2-one and 1,1-diethoxy-5-hydroxydodec-3-yn-2-one, which will react with ethyl acetoacetate to give, respectively, ethyl 4-(3,3-diethoxy-2-oxopropyl)-2,5-dimethylfuran-3-carboxylate, ethyl 4-(3,3-diethoxy-2-oxopropyl)-5-hexyl-2-methylfuran-3-carboxylate and ethyl 4-(3,3-diethoxy-2-oxopropyl)- 5-heptyl-2-methylfuran-3-carboxylate furan derivatives. This thesis project was carried out during the year 2011, at the Department of Chemistry of the University of Bergen.

This thesis describes the use of both silver nitrate, and iodine, to promote 5-endo-dig cyclisations for the formation of furans. The synthesis of kahweofuran and other furan-containing fragrance compounds is described, along with an investigation into the selectivity of the 5-endo-dig cyclisation process. Chapter 2 describes the synthesis of furan-containing analogues of known fragrance compounds using a silver-catalysed cyclisation methodology. The analysis of some of these compounds by an "expert nose" is discussed. Chapter 3 describes the synthesis of kahweofuran, a furan-containing compound reported to be one of the major odour constituents of roasted coffee. Chapter 4 describes an investigation into the cyclisation of triols upon exposure to silver nitrate or iodine when more than one cyclisation pathway is possible.

L'ouverture de cycle aromatique catalysée par le palladium a été récemment observée par une équipe de l'ENSTA. Ce type de réactivité du palladium n'a jamais été observé auparavant et entre en compétition avec l'activation C-H classique. Ce travail de thèse a consisté à étudier ces réactions d'un point de vue théorique pour mieux en comprendre les mécanismes.Nous avons tout d'abord cherché la fonctionnelle permettant la meilleure description de la compétition entre la complexation azote/alcène en comparant plus de soixante fonctionnelles à des calculs CCSD(T)/CBS. Nous avons retenu la fonctionnelle GGA BP86.Nous avons ensuite étudié la réaction de Heck intramoléculaire à partir de la N-allyl-2-iodo-aniline. Nous avons justifié que l'indole soit le produit majoritairement obtenu, et montré que l'azote ne joue pas de rôle sur la régiosélectivité. Cependant, dans certains cas, l'azote inhibe la réaction en piégeant le complexe de palladium. Une étude théorique a montré que le facteur prépondérant de cette inhibition est la population électronique de l'azote et non l'hybridation du carbone benzylique.L'ouverture du furane a été ensuite considérée. Parmi tous les mécanismes proposés, notre étude théorique a montré que la voie principale est celle de la β-alkoxyelimination, potentiellement assistée par la trialkylamine présente dans le milieu.Enfin, nous avons étudié l'ouverture du benzylfurfurylaniline. Le mécanisme est similaire à celui observé pour l'ouverture du furane jusqu'à la régénération du complexe de palladium catalytique. En effet, dans le ce cas, la base azotée joue le rôle d'un donneur de proton.

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.

Thesis presented in partial fulfillment of the requirements for the degree of Master of Technology (MTech) at Department of Chemistry, Faculty of Applied Science, Cape Peninsula University of Technology 2011<br>Aromatic polyamides (PAs) are widely used as high-performance polymers in technical applications due to their unique combination of outstanding thermal, optical, mechanical and chemical properties. Although PAs are mostly utilized where strength or heat resistance is of primary concern, they also find use in other important applications such as in NOMEX membranes for desalination of brackish water or seawater. PAs do however have some disadvantages such as high melting points, high glass transition temperatures (T 9) and a limited solubility in most organic solvents, wh.ich makes their processing difficult. Polyureas (PUs) are generally known for their excellent thermal stability and high chemical resistance due to the presence of thermally stable bonds of aromatic or heterocyclic ring systems along their backbone. Both polymer systems are poorly researched when it comes*' the introduction of furan units into the chains. The same is valid for cases where two or more different diacids or diamines are incorporated. The aim of this study was therefore to investigate the influence of furan units in the polymer chains and the change in properties if the composition of starting materials is varied further. Nineteen PAs were prepared via the interfacial polymerization method and the homogeneous phase polymerization method. These polymers were prepared either with furan- or isophthalic acids in their chains and then compared with the copolymers, containing both diacids in different ratios. Products were characterized by various analytical techniques. Furanoyl-2,5-dichloride (FDC) and different amounts of isophthaloyl chloride (IPDC) - 0, 10, 30 and 50% - as the basic starting monomers were reacted individually with four diamines: m-phenylen diamine (MPD), 4,4'-diamino diphenylsulfone (DDS), 4,4'-diamino diphenylether (ODE) and 2,4-bis(4-aminophenyl)-6-phenyl-1,3,5-triazine-2,4,6-triamine (BAT) by interfacial or homogeneous polycondensation reactions. Two polyureas, starting with furanoyl-2,5-diazide (FDZ) and transformed into the diisocyanate were prepared by reaction with two diamines, namely MPD and DDS in homogeneous solution. The PAs and PUs were characterized by Fourier-Transform Infrared Spectroscopy (FTIR), Proton NMR CH), Carbon NMR C3C), Gel Permeation Chromatography (GPC), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). The water up-take per polymer unit (mol water I repeat unit of the polymer) was measured. The values for 70% Relative Humidity (RH) were between 0.87 and 1 ~80 moles of water per repeat unit and for 43% RH between 0.40 and 1.35 mols.

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-01-10T11:20:37Z No. of bitstreams: 1 mairadoprado.pdf: 27438645 bytes, checksum: 23706315731d08c2400d4c554bf8ee9b (MD5)<br>Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-01-23T11:39:49Z (GMT) No. of bitstreams: 1 mairadoprado.pdf: 27438645 bytes, checksum: 23706315731d08c2400d4c554bf8ee9b (MD5)<br>Made available in DSpace on 2018-01-23T11:39:49Z (GMT). No. of bitstreams: 1 mairadoprado.pdf: 27438645 bytes, checksum: 23706315731d08c2400d4c554bf8ee9b (MD5) Previous issue date: 2017-10-27<br>Devido ao seu curto período de presa, o Biodentine permite aos endodontistas realizar o tratamento do canal radicular na mesma visita que o reparo da perfuraçãp de furca. O objetivo deste estudo foi avaliar o emprego do Biodentine no reparo de perfurações de furcas, através de análises de superfície e interface, avaliando o efeito de diferentes protocolos de irrigação, associados ao uso de NaOCl e diferentes agentes ácidos / quelante na resistência de união e morfologia do Biodentine. Perfurações na região de furca com diamentro de 1,5 mm foram produzidas em 60 molares inferiores permanentes. As paredes da área perfurada foram contaminadas com sangue. Para o selamento das perfurações empregou-se o Biodentine, que foi manipulado de acordo com as recomendações do fabricante. As perfurações foram seladas e após 10 minutos, tempo de presa do material, as amostras foram avaliadas em relação a topografia por microscopia eletrônica de varredura (MEV). Em seguida as amostras foram divididas em 6 grupos de acordo com o regime de irrigação. No grupo de controle, todo procedimento de irrigação foi realizado com água destilada. Nos outros 5 grupos, utilizou-se NaOCl 5,25% como irrigante inicial, seguido de água destilada no grupo DW; EDTA 17% no grupo EDTA; ácido fosfórico 37% no grupo PA; ácido cítrico 10% no grupo CA; e ácido maleico 7% no grupo MA. Após os regimes de irrigação, os dentes foram novamente avaliados por MEV. As fotomicrografias foram avaliadas comparativamente, em relação a presença de alterações antes e após os regimes de irrigação, utilizando um sistema de escore. O teste de resistência de união por push-out foi realizado 7 dias após o preparo das amostra e os dados foram analisados estatisticamente usando os testes de Kruskal-Wallis e Dunn (p < 0,05). Todos os regimes de irrigação modificaram a topografia do Biodentine. Os efeitos do protocolos de irrigação na superfície do Biodentine levaram a alterações na interface desse material com a dentina. Os regimes que utilizaram água destilada e EDTA como irrigante final mostraram valores de resistência de união estatisticamente inferiores aos demais grupos. Os grupos controle, PA, CA e MA não diferiram estatisticamente. Conclui-se que todos os regimes de irrigação modificaram a topografia do Biodentine. Protocolos de irrigação utilizando NaOCl e NaOCl associado ao EDTA levaram a uma redução nos valores de resistência de união do Biodentine à dentina.<br>Due to its short setting time, Biodentine permits endodontists to perform the root canal treatment in the same visit of the furcal repair. The aim of this study was to evaluate the use of Biodentine in furcal repair through surface and interface analyzes, evaluating the effect of different irrigation protocols, associated to the use of NaOCl and different acids / chelating agents on the push-out bond strength and morphology of Biodentine. Furcal perforations with diameter of 1.5 mm were produced in 60 permanent mandibular molars. The walls of the perforated area were contaminated with blood. Biodentine was used for the perforations sealing, which was manipulated according to the manufacturer's recommendations. The perforations were sealed. After 10 minutes, the setting time, the samples were topographically evaluated by scanning electron microscopy (SEM). The samples were then divided into 6 groups according to the irrigation regime. In control group, all irrigation procedure was performed using distilled water. In the others 5 groups, 5.25% NaOCl was used as initial irrigant followed by distilled water in DW group; 17% EDTA in EDTA group; 37% phosphoric acid in PA group; 10% citric acid in CA group; and 7% maleic acid in MA group. Once more, after the irrigation regimens, the teeth were evaluated by SEM. The photomicrographs were evaluated comparatively, in relation to the presence of alterations before and after the irrigation regimes using a score system. Push-out bond strength (POBS) test was performed 7 days after sample preparation and data were statistically analyzed using Kruskal-Wallis and Dunn tests (p < 0.05). All irrigation regimens modified the topography of Biodentine. The effects of irrigation protocols on Biodentine surface led to changes in the interface of this material with dentin. The regimens that used DW and EDTA as final irrigant showed bond strength values statistically lower than the other groups. Control PA, CA, and MA groups did not differ statistically. In conclusion, all irrigation regimens modified the topography of Biodentine. Irrigation protocols, using NaOCl and NaOCl associated with EDTA, led to a reduction in bond strength values from Biodentine to dentin.

2-Alkyltetrahydroftirans have been prepared from C10-C18 primary alcohols. Complete characterisation of these compounds by mass spectral and NMR studies has been achieved. Ring-opening reactions of the 2-alkyltetrahydrofurans have been studied and have provided an insight into the chemistry of these compounds, highlighting differences in reactivities and reaction products compared with the parent molecule, tetrahydrofuran. The C10-C18 2-alkyltetrahydrofurans have been subjected to a variety of ring cleavage reactions involving reaction with Lewis acids and/or acyl halides to produce compounds of the type; RCH(X)CH2CH2CH2-Y and RCH(Y)CH2CH2CH2-X R = C6H29 - C14H29, X = halogen atom, Y = acyl group This work has demonstrated the ease with which these compounds may be ring opened. In some cases the reaction with the 2-alkyltetrahydrofiirans was observed to be more rapid and vigorous than with tetrahydrofuran itself. This was not always the case: The acid catalysed reaction of tetrahydrofiaran with dodecanol resulted in formation of the diether shown below, and a diester was similarly formed by the acid catalysed reaction of tetrahydrofliran with lauric acid. R0(CH2)4OR diether (R = C12H25) RCOO(CH2)4OCOR diester (R= C1H23) The analogous reactions with substituted tetrahydrofurans were slow and diether/diester yield was extremely low. Introduction of the alkyl group at position two of the tetrahydrofuran ring severely impeded the reaction. Instead the hydroxy ethers shown below were the major cyclic ether derived products. C12H25-O-CH(R)(CH2)3-OH and C12H25-O-(CH2)3CH(R)-0H. (R = C6H13) Oxidation of the 2-alkyltetrahydrofurans was readily achieved by treatment with ruthenium tetroxide and resulted in formation of the corresponding alpha-alkyl-gamma-lactones and gamma-keto acids in almost quantitative yields and RCO(CH2)2COOH (R=C6H13-C14H29).

Il est d'usage de parler d’un « Pasolini frioulan », jouant, à notre avis, sur l'ambiguïté de cette expression selon le sens que l’on veut attribuer au terme «frioulan» : substantif, entendu comme langue, ou bien adjectif. Ou encore, les deux à la fois, puisque l'opération recherchée par Pasolini était justement de fusionner en quelque sorte ces deux valeurs en une seule réalité culturelle.En essayant de se plonger avec prudence dans l’intimité de l’auteur nous avons organisé notre travail autour de trois axes qui correspondent respectivement au frioulan, à la poétique et au théâtre. Nous avons suivi un chemin qui trace une ligne directrice de l'expérience frioulane qui commence avec Poesie a Casarsa, en passant par ledit « journal inédit » et s’achève avec le drame théâtral « I turcs tal Friul ».L'approche analytique des trois phénomènes explique comment le timp furlan de Pasolini n’est pas une exclusivité biographique ou poétique (La meglio gioventù), mais une réalité riche et complexe dans laquelle les concepts de langue, d'identité et d'autonomie sont liés au Frioul. En ce qui concerne Pasolini et son séjour au Frioul nous ne pouvons parler d’une immersion totale dans l’ « Eden » frioulan, mais plutôt d’un jeu culturel très intéressant entre italianité et « frioulanité », qui nous permet de placer où bon nous semble les frontières pasoliniennes dans l'identité frioulane<br>When approaching the so called “Pasolini friulano” [Friulian Pasolini], the specialists usually play on the ambiguity of the italian term “friulano”: Friulian as a noun, i.e. the language, or as an adjective, i.e. relating to the region? In our opinion the term covers both of them, because the intended purpose of Pasolini was precisely to merge somehow these two values into an unique cultural reality.Exploring carefully the author’s personal word more through the analysis of his literary works than his biographical data, this research focuses mainly on the Friulian language, the poetry, and the theatre. Having Poesie a Casarsa as starting point, it discusses also the so called Diario Inedito and the drama I Turcs tal Friul, with the aim to establish useful guidelines for a better understanding of the Friulian experience of Pasolini. The analytical approach of these three literary works proves that the timp furlan [friulian time] is not just a poetic or biographical fact (La meglio gioventù): it covers actually a very rich and complex reality, in which the idea of Friuli is strictly connected to the concepts of language, identity and political autonomy. During his stay in Friuli, Pasolini has not experienced a full-immersion in a Friulian Eden. Rather, he played a very interesting cultural game with the ideas of being Italian and/or Friulian. In this context, it is not possible to mark out clearly the Friulian identity of Pasolini and for this reason its boundaries can be shifted at leisure

Made available in DSpace on 2009-11-18T18:56:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2000<br>As mudanças que se processam no mercado de energia elétrica, bem como a iminência de sua privatização, levaram Furnas Centrais Elétricas ao desenvolvimento de programas de educação continuada que dotassem seu corpo gerencial de competências adequadas a esse novo cenário. Esse estudo de caso buscou avaliar, à luz dos postulados teóricos e do novo desenho do setor elétrico ,a efetividade desses programas que buscaram por um lado, capacitar as gerências no domínio de competências alinhadas com a estratégias de negócios da empresa e, por outro lado, subsidiar o processo de sucessão gerencial, uma vez que encontra-se em curso um programa de desligamento voluntário a que aderiu um número significativo de ocupantes de cargos gerencias. Os programas tiveram o mérito de suscitar reflexões sobre aspectos relevantes para o futuro da organização, o que foi expresso nos projetos elaborados como parte do processo de avaliação, que propuseram mudanças ou aprimoramento de setores específicos da empresa.

Polymeric materials are strongly entrenched in our society, where PVC is one of the most versatile one. The replacement of traditional phthalates plasticizers, used in the production of soft PVC, has been object of intense research in the last decades, due to their toxicological effects on humans and environmental and the increasing awareness regarding the use of fossil fuels. Bio-based platform chemicals, 5-hydroxymethylfuran (HMF) and 2,5-furandicarboxylic acid (FDCA), accessible from lignocellulosic biomass, have been used in this research as starting materials for the production of alternative furan-based plasticizers. By reduction reaction of HMF, 2,5-bishydroxymethylfuran (BHMF) was obtained and involved in a esterification reaction, which led successfully to the first desired furan-based plasticizer. An esterification acid-catalyzed by Amberlyst-15 on tetrahydrofuran- 2,5-dicarboxylic acid (THFDCA), obtained from FDCA by hydrogenation reaction, gave access to the second promising plasticizer. First investigations of BHMF and 2,5-bis(hydroxymethyl)tetrahydrofuran (BHMTHF) etherification reactions were carried out, in order to obtain further substrates that could be used as potential plasticizers.

Tetrahydrobenzofurans and tetrahydroindoles are two very valuable classes of substances which have wide usage area<br>either as starting materials for drug substances or many other compounds which have fused heterocyclic rings in their structures and pharmacophore for many complex natural products<br>syntheses of derivatives of these compounds with different substitution patterns, is an exciting challenge for many scientists. Benzofuran and tetrahydroindole derivatives, which are potent bioactive substances, are synthesized from various cyclohexanone derivatives that are allylated by Stork-enamine or Mn(OAc)3 mediated allylation methods. Allylated ketones are later transformed to benzofuran derivatives upon treatment with base or tetrahydroindole derivatives upon treatment with primary amines.

Diels-Alder reactions, inter- and intramolecular, are of paramount importance in synthetic organic chemistry. Few reactions can compete with the Diels-Alder cycloaddition with respect to the degree of structural complexity that can be achieved in a single synthetic step. The high regio- and stereoselectivity typically displayed by this pericyclic process and the ease of execution have contributed toward its popularity. In the present report, we describe work towards and the study of heteronuclear intramolecular Diels-Alder re~ctions involving substrates containing a furan ring (the diene) tethered to a diazene moiety (the dienophile). A model study on the synthesis of chiral racemic intramolecular Diels-Alder substrates is presented, followed by work towards chiral non-racemic substrates. The tricyclic Diels-Alder adducts obtained herein are potential precursors to a wide variety of novel, functionalised spiro-amide systems, which are anticipated to find use as building blocks in the synthesis of natural products, or their synthetic bioactive structural analogues.

Oxidation of furan rings in the presence of hydroxy groups can lead to spirobutenolides. This methodology has been applied in synthetic studies towards three natural products: Pyrenolide 0 - An antileukaemic fungal metabolite. AL-(1) - An antitumor plant natural product. Sawaranospirolides - Four highly oxygenated spiroacetals isolated from the heartwood of the Sawara tree.

Doutoramento em Química<br>A futura e inevitável escassez dos recursos fósseis, juntamente com o aumento imprevisível dos seus preços, levou, nas últimas décadas, a um aumento impressionante de iniciativas dedicadas não só à procura de fontes alternativas de fornecedores de energia, mas também de produtos químicos e polímeros a partir de fontes renováveis, em particular da biomassa vegetal. Entre estes, os polímeros derivados de monómeros furânicos constituem uma classe única de materiais cujas estruturas podem, em princípio, simular virtualmente os seus homólogos actualmente derivados de recursos fósseis. O anel furânico é uma estrutura heterocíclica com um carácter diénico pronunciado, o que torna-o um dieno particularmente apropriado para a reacção de Diels-Alder (DA) com dienófilos como a maleimida. Um dos aspectos mais relevantes da reacção de DA é a sua reversibilidade em função da temperatura, a qual permite que os aductos sejam facilmente revertidos nos seus precursores por aumento da temperatura (reacção de retro-DA). No caso específico da combinação furano-maleimida, a formação do aducto predomina até cerca de 60ºC, enquanto a reacção inversa é dominante acima de 100ºC. A combinação desta característica da reacção de DA com a química de compostos furânicos pode abrir um novo caminho para a preparação de materiais macromoleculares funcionais com base em fontes renováveis e com aplicações promissoras como auto-reparação e reciclabilidade. O principal objectivo desta Tese, é a síntese e caracterização de novos materiais poliméricos termo-reversíveis, aplicando a reacção de DA a monómeros complementares com estruturas dos tipos furânico (o dieno, designado por A) e de maleimida (o dienófilo, designado por B). A primeira etapa neste trabalho envolveu a síntese, purificação e caracterização de novos monómeros furânicos e de maleimida do tipo AA, A3, BB, B3, AB, AB2, cada um com diferentes grupos separadores das funções reactivas. Posteriormente, estes monómeros foram polimerizados e despolimerizados por ciclos de DA/retro-DA utilizando diferentes combinações. A formação e dissociação de todos os aductos de DA foram seguidas por ambas espectroscopias de UV e RMN de 1H. O primeiro sistema de DA estudado foi uma combinação modelo entre reagentes mono-funcionais (-A+-B), nomeadamente o acetato furfurílico (FA) e a N-metilmaleimida (MM), ambos comercialmente disponíveis. O objectivo desta abordagem foi estudar a cinética e o equilíbrio da formação/dissociação dos aductos de DA e obter indicações sobre as condições mais adequadas a serem usadas na preparação dos correspondentes novos materiais macromoleculares. Além disso, pretendia-se verificar a presença ou ausência de reacções secundárias que poderiam intervir em ambas as vias directa e inversa das reacções, mesmo após vários ciclos. A espectroscopia de UV forneceu informação quantitativa sobre a cinética de formação do aducto através da diminuição progressiva da absorvência máxima a 293 nm correspondente ao grupo maleimida, a diferentes temperaturas (35, 50, 65 ºC) Reciprocamente, a correspondente reacção de retro-DA foi seguida a 90 ºC através do aumento do mesmo pico. A reversibilidade destes sistemas foi verificada com sucesso após uma sequência de ciclos de DA/retro-DA. Adicionalmente, verificou-se que os espectros originaram um ponto isosbéstico, provando que estes sistemas não envolvem quaisquer reacções secundárias. Uma vez que foi usado um excesso de FA, as reacções de DA modelo apresentaram um comportamento cinético de pseudo-primeira ordem, com a constante de velocidade k mais alta (2.1x10-5 dm3mol-1s-1) para T=65 ºC. A correspondente energia de activação foi de 39.0 kJ.mol-1. A reacção de retro-DA seguiu um comportamento de primeira ordem, com constante de velocidade de 1.6x10-6 s-1. A evolução deste sistema por RMN de 1H a 65ºC deu-nos informações mais detalhadas sobre a sua evolução estrutural, ou seja, à medida que a intensidade dos picos atribuídos à formação do aducto aumentaram progressivamente ao longo do tempo, os pertencentes aos reagentes iniciais diminuiram proporcionalmente. O “rendimento final”, calculado após 20 dias à temperatura ambiente, foi de aproximadamente 70%. A reacção de retro-DA foi depois seguida a 90ºC, observando-se tal como na espectroscopia de UV, o deslocamento da reacção no sentido da regeneração dos reagentes de partida. A viabilidade de múltiplos ciclos de DA/retro-DA estabelecidos pela espectroscopia de UV foi igualmente confirmada por RMN de 1H. O passo seguinte envolveu o estudo de um sistema de policondensação linear baseado no crescimento gradual por reacção de DA entre um monómero bisfurânico A-A e um do tipo bismaleimida B-B, seguindo a mesma abordagem que no sistema modelo. O poliaducto linear foi obtido a partir de soluções equimolares dos monómeros, por reacção de DA a 65ºC. O progresso desta polimerização foi seguido por espectroscopia de UV e RMN de 1H e, mais qualitativamente, pelo aumento da viscosidade do meio. A reacção seguiu um comportamento de segunda ordem, com uma constante de velocidade de 9.4x10-6 dm3mol-1s-1, e observou-se novamente um ponto isosbéstico nos dados de UV. Os espectros de RMN apresentaram o padrão esperado, nomeadamente o aumento progressivo dos sinais associados ao aducto e a correspondente diminuição dos grupos furano e maleimida livres. A despolimerização do poliaducto através da reacção de retro-DA foi seguida a 110ºC usando as mesmas técnicas. Os dados de UV mostraram o retorno progressivo da absorção dos grupos de maleimida, seguindo um comportamento cinético de primeira ordem, com constante de velocidade de 2.5x10-6 s-1, até à completa regeneração de ambos os monómeros. Os espectros de RMN providenciaram mais uma vez informação estrutural sobre o progresso da despolimerização, a qual foi acompanhada por uma diminuição progressiva da viscosidade. Adicionalmente, para seguir a retro- DA, adicionou-se um excesso de composto furânico monofuncional, nomeadamente o 2,5-dimetilfurano (DMFu), ao sistema de modo a bloquear as funções maleimida complementares, evitando assim a repolimerização após arrefecimento. Os productos isolados foram então o monómero bisfurânico AA, DMFu que não reagiu e o bisaducto não-polimerizável de BB com DMFu. Este resultado indicou claramente que o polímero foi de facto revertido nos seus monómeros durante a reacção de retro-DA. O terceiro sistema estudado foi outra polimerização linear, seguindo as mesmas condições experimentais que os anteriores, mas com uma estratégia diferente de modo a contornar o problema clássico de assegurar a estequiometria exacta dos monómeros. As estruturas dos monómeros utilizados incorporam ambos os grupos reactivos, i.e, moléculas do tipo A-B. A polimerização prematura destes monómeros intrinsecamente reactivos foi evitada com a protecção do grupo maleimida na forma de um aducto de DA com furano, até a incorporação do substituinte furânico na outra extremidade. Portanto, a policondensação destes monómeros foi iniciada após a desprotecção in situ deste composto mediante aquecimento, seguido de arrefecimento até à temperatura adequada para polimerizar. Os resultados obtidos por UV e RMN sugerem que de facto o uso de monómeros do tipo A-B oferece um melhor sistema linear. Em seguida, foram estudados sistemas de policondensação não-linear por reacção de DA, entre monómeros (um ou ambos) com funcionalidade superior a dois, nomeadamente sistemas do tipo A3+B-B ou A-A+B3, seguindo mais uma vez as mesmas condições experimentais. Uma vez que utilizam monómeros complementares contendo, em média, mais de duas funcionalidades, estes sistemas conduzem a materiais reticulados. Nestes estudos, foram usadas três razões molares de [maleimida]/[furano], nomeadamente 1.0, 0.75 e 0.5, de modo a estudar ambas as situações de não-gelificação e reticulação. Ambos sistemas apresentaram um comportamento regular e boa reciclabilidade quer para gerar situações que possam conduzir à formação de redes a diferentes graus de conversão, ou que possam parar antes da sua obtenção, conforme previsto pela equação de Flory-Stockmayer. Como esperado, a utilização de grupos complementares em quantidades estequiométricas produziu o espessamento mais rápido e a reticulação quase completa; à medida que a quantidade relativa de monómero trifuncional decresceu, as reacções pararam antes da reticulação, ou seja, originaram meios altamente viscosos contendo polímeros solúveis altamente ramificados. As reacções de retro-DA a 110 ºC conduziram à gradual dissolução das partículas de gel (quando presentes), tendo sido comprovado pelos espectros de UV e de RMN de 1H, evidenciado a regeneração dos monómeros. Tal como no sistema do tipo A-A+B-B, a reacção de retro-DA foi seguida adicionando um excesso de DMFu ao sistema reaccional. Como esperado, os produtos finais foram os monómeros furânicos, o DMFu em excesso e o trisaducto ou o bisaducto maleimida-DMFu, o que confirma a eficiência da despolimerização com regeneração dos monómeros iniciais. O último sistema de policondensação por reacção de DA envolveu um monómero assimetricamente substituído do tipo AB2, capaz de originar estruturas macromoleculares hiper-ramificadas que não reticulam. Este estudo preliminar deste sistema foi seguido nas mesmas condições experimentais que os anteriores, apresentando um comportamento com as características esperadas.<br>The inevitable future scarcity of fossil resources, together with their skyrocketting prices, has led in the last decades to a dramatic increase of initiatives devoted not only to the search for alternative sources of energy providers, but also to the search for chemical commodities and polymers from renewable resources, namely the vegetable biomass. Among these, polymers from furan monomers constitute a unique class of materials whose structures can in principle simulate virtually all their current fossil-derived counterparts. The furan heterocycle displays a pronounced dienic character, which makes it highly suitable as diene in the Diels-Alder (DA) reaction, with dienophiles like maleimide. One of the most relevant aspects of the DA reaction is its thermal reversibility, which allows the adducts to be readily reverted to their precursors as the temperature is raised (retro-DA reaction). In the specific case of the furan-maleimide combination, the adduct formation dominates up to ca. 60ºC, whereas the reverse reaction is overwhelming above ca. 100ºC. The coupling of this DA feature with the furan chemistry can open a new way to prepare functional macromolecular materials based on renewable resources with novel properties and promising applications like mendability and recyclability. In this Thesis, the main goal is the synthesis and characterisation of novel thermoreversible polymer materials by means of the DA reaction, using complementary monomers bearing furan (the diene, assigned as A) and maleimide (the dienophile, assigned as B) moieties. The first step in this study was the synthesis, purification and characterization of new furan and maleimide monomers, viz. AA, A3, BB, B3, AB, AB2, each bearing different spacing moieties separating the reactive functions. They were then polymerized and depolymerised using different modes of DA/retro-DA cycles. The formation and decoupling of all the DA adducts were followed by both UV and 1H NMR spectroscopy. The first DA system investigated was on a model combination of monofunctional reagents (-A+-B), namely the commercially available furfuryl acetate (FA) and N-methylmaleimide (MM). The purpose of this approach was to study the kinetics and the equilibrium of the formation/decoupling of the DA adducts and to provide clear indications about the most appropriate conditions to be applied in the preparation of the corresponding novel macromolecular materials. Additionally, it aimed at verifying that no detectable side reactions intervened in both forward and backward pathways, even after several cycles. The UV spectroscopy provided quantitative information on the kinetics of the DA adduct formation by monitoring the progressive decrease in the maximum absorbance at 293 nm related to the maleimide moiety, at different temperatures (35, 50, 65ºC). Conversely, the corresponding retro-DA reaction was followed at 90ºC through the increase of the same peak. The reversibility of these systems was successfully checked over a couple of cycles. Additionally, all set of spectra gave rise to an isosbestic point, which proved that these systems did not involve any side reactions.Since an excess of FA was used here, these model DA reactions displayed a pseudo-first order behaviour, with the highest rate constant k (2.1x10-5 M-1.s-1) for T= 65ºC. The corresponding activation energy was found to be 39.0 kJ.mol-1. The retro-DA reaction followed a first order behaviour, with a rate constant of 1.6x10-6s-1.The evolution of the same system followed by 1H NMR spectroscopy at 65ºC gave a detailed insight into its structural evolution, viz. as the intensity of the peaks assigned to the adduct formation progressively increased with time, those belonging to the initial reagents decreased correspondingly. The “final yield” taken after 20 days at room temperature, was approximately 70%. The retro- DA reaction was then carried out at 90ºC, and showed the same features as its UV counterparts, namely the displacement of the reaction towards the regeneration of the initial reagents. The feasibility of multiple DA/retro-DA cycles established by UV spectroscopy was confirmed here. The subsequent stage involved the study of a linear polycondensation system based on the stepwise DA growth between a difuran monomer A-A and a complementary bismaleimide B-B, following the same approach as the model system. The formation of the linear DA polyadduct was achieved by letting equimolar solutions evolve at 65 ºC. The progress of this polymerization was followed by UV and 1H NMR spectroscopy and, more qualitatively, by the increase in the viscosity of the medium. The reaction followed a second order behaviour, with a rate constant of 9.4x10-6 M-1.s-1, and again, a characteristic isosbestic point was observed in the UV data. The NMR spectra gave the expected pattern, namely the progressive increase in the signals associated with the adduct and the corresponding decrease of those attributed to the unreacted furan and maleimide cycles. The depolymerization of the polyadduct through the retro-DA reaction was followed at 110ºC by the same techniques. The UV time scans showed the progressive return of the absorption due to maleimide moieties following a first-order kinetic pattern, with a rate constant of 2.5x10-6 s-1, until both monomers were fully regenerated. The 1H NMR spectra provided once more structural information about the course of this depolymerization, which was accompanied by a progressive decrease in viscosity. Additionally to follow the retro-DA, an excess of a monofunctional furan compound, namely 2,5-dimethylfurfural (DMFu), was added to the system in order to block the complementary maleimide functions, thus avoiding the repolymerisation after cooling. The isolated products were then the difuran monomer AA, the unreacted DMFu and the non-polymerizable bisadduct of BB with DMFu. This result clearly indicated that the polymer had indeed reverted to its monomers during the retro-DA. The third system studied was another linear polymerization, following the same experimental conditions as the previous, but with a different strategy, in order to avoid the classical problem of ensuring the exact monomer stoichiometry. Here, the monomers incorporated both reactive moieties in their structures, i.e. A-B molecules. Here, the premature polymerization of these intrinsically reactive monomers was avoided by protecting the maleimide group in the form of a furan-DA adduct, until the incorporation of the furan moiety. Therefore, the polycondensation of these monomers was initiated after the in situ deprotection of this compound through heating, followed by the cooling to appropriate temperature for polymerization. The results obtained by both UV and NMR spectroscopy suggested that indeed the use of an A-B monomer provides a better linear system. Non-linear DA polycondensations between monomers (one or both) with functionality higher than two, viz. A-A+B3 or A3+B-B systems, were then studied, following once more the same experimental conditions. The use of complementary monomers bearing on average more than two functionalities lead to crosslinked materials. In these systems, three [maleimide]/[furan] molar ratios, viz. 1.0, 0.75 and 0.50, were applied in order to examine both nongelling and crosslinking situations. Both types of systems displayed a clean-cut behaviour and good recyclability to generate situations either leading to the formation of a network at different degrees of conversions, or ending before its attainment, as predicted by the Flory-Stockmayer equation. As expected, the use of complementary moiety stoichiometry produced the most rapid thickening and near-complete crosslinking, whereas as the relative amount of trifunctional monomer was decreased, the reactions stopped short of crosslinking, i.e. gave highly viscous media containing soluble highly branched polymers. The retro-DA reactions at 110ºC revealed the gradual dissolution of the gel particles (when present), while the UV and 1H NMR spectra gave, once more, the details of the depolymerization processes leading the systems steadily back to the monomers. As in A-A+B-B depolymerization, to follow the retro-DA, an excess of DMFu DA trap, was added to the systems under the same conditions. As expected, the final products were the furan monomers, the unreacted DMFu and the non-polymerizable trisadduct or the bisadduct of maleimide-DMFu, confirming the efficiency of the retro-DA depolymerisation in the regeneration of the starting monomers. The last DA polycondensation system involved an assymmetrically substituted monomer of the AB2 type, capable of generating hyperbranched macromolecular structures that do not crosslink. This preliminary study was followed by the experimental approach applied above and the behaviour of the system displayed the expected features.<br>POCTI; FCT; FSE - SFRH/BD/28271/2006