Dissertations / Theses on the topic 'Organic green chemistry'

Thesis (Ph. D.)--University of Oregon, 2007.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 158-183). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.

Chlorofluorocarbons were once commonly used as propellants and refrigerants due to their stability, low toxicity and excellent physical properties. They were phased out, however, after being identified as ozone-depleters, and have been replaced by hydrofluorocarbons (HFCs) and other fluorocarbon derivatives (FCDs). The high temperature-resistant characteristic of these materials is beneficial for many applications; however, the robust nature of the C-F bonds leads to their persistence in the environment. Frequently, the synthesis of HFCs and FCDs involves energy-intensive processes and toxic precursors, such as chlorocarbons and heavy metals. In accordance with the shift to greener, more sustainable chemistry, more energy efficient methods employing less hazardous and non-toxic materials for the generation of HFCs and FCDs need to be developed. Organometallic catalysis offers potential new routes to the synthesis of fluorinated compounds. We sought to study the reactivity of tetrafluoroethylene and 1,1-difluoroethylene with a variety of iron complexes to increase our understanding of the bonding and chemistry of coordinated fluoro-olefins. Crystal structures were obtained for the parent and dppe substituted metallaycles: Fe(CF2) 4(CO)4 and Fe(CF2)4(K2-dppe)(CO) 2. Sterics were found to be responsible for the preferential formation of three- versus five-membered metallacycles through investigating the reactivity of TFE with iron phosphine- and phosphite-carbonyl complexes, as well as with the homoleptic complex pentakis(2,6-dimethylphenylisocyanide)iron and the anionic complex K[FeCp(CO)2]. The five-membered metallacycle was selectively formed with the mono-substituted phosphine and phosphite complexes, whereas, the di-substituted complexes yield the olefin (three-membered metallacycle) complexes. With the goal of developing methods for iron-mediated fluoride abstraction, the reactivity of these iron fluoro-metallacycles with a variety of Lewis acids was probed. Extremely electrophillic fluoro-carbenes were generated. A more electron rich metal centre, as in the thermally synthesized K[FeCp(CF 2)4(CO)2], is required to facilitate fluoride abstraction and stabilize the fluor-ocarbene. The results that were obtained in this investigation set the stage well for further development of iron-based organofluorometallic chemistry and our desire to functionalize the alpha-carbon of the metallacycle enroute to the generation of novel FCs.

Owing to the importance of gold nanoparticles in catalysis, designing of them has become a major focus of the researchers. Most of the current methods available for the synthesis of gold nanoaprticles (GNPs) suffer from the challenges of polydispersity, stability and use of toxic and harmful chemicals. To overcome these limitations of conventional methods, in our present study, we made an attempt to design a method for the green synthesis of monodispersed and stable gold nanoparticles by sugars which act as reducing and stabilizing agent. Characterization of synthesized nanoparticles was done by using various analytical techniques such as transmission electron microscope (TEM), dynamic light scattering spectroscopy (DLS), UV-Vis spectroscopy, scanning electron microscopy and electron dispersion spectroscopy. The synthesized sugar GNPs (S-GNPs) were spherical in shape and in the size range of 10 ± 5 nm. p-Nitrophenol reduction assay was used as a model system to determine the catalytic reduction activity of various sugar capped GNPs, monosaccharides (fructose), disaccharide (sucrose) and trisaccharide (raffinose) GNPs. The effect of temperature and the size of ligand on catalytic activity was also evaluated at different temperature using UV-Vis spectrometer. Using the spectroscopic data, rate constant (k) for three sugar capped GNPs was determined followed by its activation energy (Ea) and exponential (A) factor.

Organic aerosol (OA) is a ubiquitous component of atmospheric particulate that influences both human health and global climate. A large fraction of OA is secondary in nature (SOA), being produced by oxidation of volatile organic compounds (VOCs) emitted by biogenic and anthropogenic sources. Despite the integral role of SOA in atmospheric processes, there remains a limited scientific understanding of the chemical and physical changes induced in SOA as it ages in the atmosphere. This thesis describes work done to increase the knowledge of processes and properties of atmospherically relevant SOA. In the work presented in this thesis, I have worked on improving an existing innovative, soft ionization aerosol mass spectrometer and utilized it to establish chemical mechanisms for oxidation of atmospherically relevant organic precursors (i.e., Green Leaf Volatiles). I discovered that SOA formation from cis-3-hexen-1-ol is dominated by oligomer and higher molecular weight products, whereas the acetate functionality in cis-3-hexenylacetate inhibited oligomer formation, resulting in SOA that is dominated by low molecular weight products. One of the most important factors contributing to uncertainties in our estimations of SOA mass in the atmosphere, remains our basic assumption that atmospheric SOA is liquid-like, which we have found to be untrue. Hence, I developed a methodology to estimate the phase state of SOA and identified new parameters that can have significant influence on the phase state of atmospheric aerosol. This simplified method eliminates the need for a Scanning Mobility Particle Sizer (SMPS) and directly measures Bounce Factor (BF) of polydisperse SOA using only one multi-stage cascade Electrostatic Low Pressure Impactor (ELPI). The novel method allows for the real time determination of SOA phase state, permitting studies of the relationship between SOA phase, oxidative formation and chemical aging in the atmosphere. I demonstrated that SOA mass loading (CSOA) influences the phase state significantly. Results show that under nominally identical conditions, the maximum BF decreases by approximately 30% at higher CSOA and suggests that extrapolation of experiments not conducted at atmospherically relevant SOA levels to simulate the chemical properties may not yield results that are relevant to our natural environment. My work has provided a better understanding of the mechanisms of aerosol formation at atmospheric concentrations, which is necessary to understand its physical properties. This improved understanding is fundamental to accurately model aerosol formation in the atmosphere, and subsequently evaluate their large-scale effect on human health and environment.

The thesis subject is mainly involved in Green Chemistry approach. Thiophene, furan and pyridine carboxaldehydes were chosen as starting compounds and vinylation and allylation with Grignard reaction afforded the corresponding racemic heteroaryl substituted allylic and homoallylic alcohols. Subsequent resolution with enzymes (PS-Amano II, Lipozym and Novazym 435) gave enantiomerically enriched alcohols with the e.e. values varied between 65 and 99%. The absolute configurations of all substrates are known. As a result of O-allylation with the common procedure formed the feasible carbon backbone for the ring closing metathesis reaction. All ring closing metathesis reactions were performed by Grubbs&rsquo
catalyst with just 5% catalyst loading. The absolute configurations of dihydrofuran and dihydropyran derivatives are known, since the chiral center configurations of all substrates are preserved throughout all the applied processes.

Aerosols play important roles in atmospheric and environmental processes. Not only do they impact human health, they also affect visibility and climate. Despite recent advances made to under their sources and fate, there remains a limited understanding of the mechanisms that lead to the formation of aerosols and their ultimate fate in the atmosphere. These knowledge gaps provide the crux of the research reported herein, which has focused on identifying novel sources of atmospheric aerosol, characterizing its physical and optical properties, and rationalizing these properties using an in-depth knowledge of the molecular level mechanisms that led to its formation. Upon mowing, turfgrasses emit large amounts of green leaf volatiles which can then be oxidized by ozone to form SOA. Overall, the mowing of lawns has the potential to contribute nearly 50 µg SOA per square meter of lawn mowed. This SOA contribution is on the same order of magnitude as other predominant SOA sources (isoprene, monoterpenes, sesquiterpenes). Turfgrasses represent an interesting and potentially meaningful SOA source because they contribute to SOA and also because they cover large land areas in close proximity to oxidant sources. Another related SOA precursor is sugarcane, which is in the same family as turfgrass and is among the largest agricultural crops worldwide. Globally, the ozonolysis of sugarcane has the potential to contribute 16 Mg SOA to the atmosphere, compared to global estimates of SOA loading that range from 12-70 Tg SOA. In order to fully understand the role of atmospheric SOA on the radiative budget (and therefore climate), it is also important to understand its optical properties; its ability to absorb vs scatter light. Turfgrass and sugarcane produced SOA that was weakly absorbing while its scatter efficiency was wavelength and size-dependent. Interestingly, SOA formed under both dry (10% RH) and wet (70% RH) conditions had the same bulk chemical properties (O:C), yet significantly different optical properties, which was attributed to differences in molecular-level composition. The work presented herein represents a unique, inclusive study of SOA precursors. A complete understanding of the chemistry leading to SOA formation is used to understand its physical and optical properties and evaluate these large-scale effects of SOA from these precursors.

Nowadays, the modern chemical industry has to deal with increasing environmental concerns, including the disposal of waste and its economic impact, or the diminution of important worldwide resources such as transition metals. In this Ph.D. thesis, we aimed to bring improvement in this area by the development of green processes, based on the use of recyclable heterogeneous catalysts. By combining the catalytic properties of several metal cations with the properties of solid catalysts such as polyoxometalates or zeolites, we were able to set up new tools for organic synthesis. Silver-doped polyoxometalates proved to be very efficient catalysts in the rearrangement of alkynyloxiranes to furans. Acetals and spiroketals were synthetized by dihydroalkoxylation of alkynediols under catalysis with silver-zeolites. As a perspective, we highlighted the potential applications of such green procedures in the total synthesis of more complex molecules. The first results suggested that these environmental friendly processes should gain increasing interest in the future.

On the verge of entering the post-antibiotic era, numerous efforts are in place to regain the waning charm of antibiotics which are proving ineffective against most “Superbugs”. Engineered nanomaterials, especially gold nanoparticles (GNPs) capped with antibacterial agents, are proving to be an effective and novel strategy against multidrug resistant (MDR) bacteria. In this study, we report a one-step synthesis of antibioticcapped GNPs (25 ± 5 nm) utilizing the combined reducing and capping ability of a cephalosporin antibiotic, ceftazidime. No signs of aggregation or leaching of ceftazidime from GNP surface was observed upon its storage. Antibacterial testing showed dosedependent broad spectrum activity of Cef-GNPs against both Gram-positive (S. bovis and E. durans) and Gram-negative (P. aeruginosa and E. aerogenes) bacteria. A significant reduction in the minimum inhibition concentration (MIC) of Cef-GNPs was observed as compared to the ceftazidime by itself against Gram-negative bacteria. The MIC of Cef- GNPs were 0.1 mg mL-1 (P. aeruginosa and E. aerogenes) and 1.2 mg mL-1 (E. durans and S. bovis). Cef-GNPs exerted bactericidal action on both P. aeruginosa and E. durans by disrupting the cellular membrane resulting in leakage of cytoplasmic content and death of bacterial cell. Our investigation and results provides an additional step in the development of antibiotic capped GNP as potent next generation antibacterial agents.

De nos jours, l’industrie chimique est de plus en plus confrontée à la question de son impact environnemental. Dans le même temps, elle doit faire face à la diminution des ressources de matières premières importantes tels que les métaux de transition, tout en respectant des contraintes économiques. Ces travaux de thèse avaient pour but de tenter de répondre à ces exigences, par le développement de méthodologies de synthèse basées sur l’utilisation de catalyseurs hétérogènes recyclables. En combinant les propriétés catalytiques de certains ions métalliques avec les propriétés de catalyseurs solides tels que les polyoxométallates ou les zéolithes, nous avons pu mettre au point de nouveaux outils pour la synthèse organique. Les polyoxométallates dopés à l’argent ont démontré leur efficacité dans le réarrangement d’alcynyloxiranes en furanes. La synthèse de spiroacétals et d’acétals par dihydroalkoxylation d’alcyne diols a été effectuée pour la première fois en catalyse à l’argent, via l’utilisation de zéolithes. En perspective, nous avons mis en évidence les applications potentielles de ces procédés verts dans la synthèse totale de molécules plus complexes. Les premiers résultats suggèrent que de telles synthèses plus respectueuses de l’environnement ont tout intérêt à être davantage utilisées à l’avenir
Nowadays, the modern chemical industry has to deal with increasing environmental concerns, including the disposal of waste and its economic impact, or the diminution of important worldwide resources such as transition metals. In this Ph.D. thesis, we aimed to bring improvement in this area by the development of green processes, based on the use of recyclable heterogeneous catalysts. By combining the catalytic properties of several metal cations with the properties of solid catalysts such as polyoxometalates or zeolites, we were able to set up new tools for organic synthesis. Silver-doped polyoxometalates proved to be very efficient catalysts in the rearrangement of alkynyloxiranes to furans. Acetals and spiroketals were synthetized by dihydroalkoxylation of alkynediols under catalysis with silver-zeolites. As a perspective, we highlighted the potential applications of such green procedures in the total synthesis of more complex molecules. The first results suggested that these environmental friendly processes should gain increasing interest in the future

In this research project, reduction or complete elimination of organic solvents is explored in the synthesis of cyclic imides using a technique that brings reagents into favorable position to react. Cocrystal Controlled Solid-State Synthesis (C3Sy3), takes advantage of supramolecular interactions such as hydrogen bonding and π-π stacking to form a cocrystal which can sequential be heated to complete the condensation reaction and produce a desirable product. Twenty-five successful condensation reactions result in high and clean yield. C3Sy3 of cyclic imides with auxiliary hydrogen bonding moieties like carboxylic acid, carboxylate or pyridyl groups are amenable to form additional solid-state materials. These moieties are useful in forming coordinate covalent bonds with metal cations. Using these C3Sy3 synthesized molecules as ligands, various Metal-Organic Materials (MOMs) are self-assembled. These MOMs offer unique qualities owing to the properties of the cyclic imides. With the addition of accessible carbonyl groups, they may participate as hydrogen bond acceptors or hydrophilic groups. Various degrees of rotation of N-phenyl substituents around the imide plane allow for structural flexibility as a route to supramolecular isomers in MOMs. The ease in imide synthesis may allow the fast scale-up of these ligands for industrial application. Similar ligands are generally synthesized by cross-coupling or substitution reactions that require expensive catalyst and various organic solvents. Metal-organic materials are a class of compounds amenable to crystal engineering owing to the directional coordinate covalent bonds between metal or metal clusters and organic ligands. They are characterized by X-ray diffraction, spectroscopy, volumetric and gravimetric analysis. The C3Sy3 imides were used to construct various MOMs, from discrete nanostructures to extended 3-periodic frameworks that possess viable internal space for applications pertaining to porous materials. Structural characterization by single crystal X-ray diffraction and structure-function relations are addressed. Gas sorption experiments show that many of these materials are structurally robust and retain crystallinity after evacuation. Ion exchange and guest uptake experiments using the synthesized materials demonstrate their potential as agents for sequestration. The bottom-up synthesis of metal-organics materials is leading the field of crystal engineering with built-in properties, showing promise by combining attributes from both inorganic and organic components.

The decreasing availability of fossil fuels and their negative environmental impacts requires urgent need of developing renewable energy. The main objective of this research was to develop low-dimensional nanomaterials for harvesting solar and mechanical energy with high conversion efficiency. In particular, photoelectrochemical water splitting and photovoltaic cell applications driven by sunlight were investigated in this project. A highly efficient triboelectric nanogenerator was investigated for harvesting mechanical energy. The device was further integrated with an organic solar cell for harvesting both mechanical energy and solar energy. My research work started with the synthesis of nanostructured materials. Electrospinning, as well as electrospray, was developed to synthesise nanofibres and hollow hemispheres. The influences of processing parameters to the morphologies and structures of the nanomaterials were systematically investigated. An electrophoretic deposition method was also developed to form good-quality nanostructured metal oxide thin films, which were applied in photoelectrochemical water splitting. The metal oxide hollow hemisphere thin films were also applied in dye-sensitised solar cells. A transparent and flexible triboelectric nanogenerator was developed in order to harvest mechanical energy. The contact electrodes were created using metal nanowire percolation networks embedded in a polymer matrix. The correlation between the energy conversion performances and optical property of the triboelectric electrodes were comprehensively studied as a function of the areal fraction of the metal nanowires. A flexible hybrid cell, integrating the solar cell with the triboelectric device, was designed by constructing an organic solar cell under a single-electrode triboelectric nanogenerator. The hybrid cell could convert both solar and mechanical energies into electricity independently and simultaneously. Such devices are potentially able to supply electricity day and night. Nanomaterials offer novel approaches for enhancing the efficiency of harvesting solar and mechanical energy in a hybrid device.

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009.
Committee Chair: Ragauskas, Arthur; Committee Member: Bunz, Uwe; Committee Member: Cairney, John; Committee Member: Collard, David; Committee Member: Singh, Preet. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Heterogeneous catalysts are key materials in research and industry. Herein we study two materials in different stages of development toward being applied as heterogeneous catalysts. First, MoO3SnO2 was synthesized and studied as a catalytic system similar to Sn-beta zeolites. While the Mo-based catalyst did not show similar activity to Sn-beta, it did show interesting reactivity in activating carbonyls and oxidizing organic substrates. Second, a method was developed for grafting amines onto carboxylic acid functionalized carbon nanotubes for CO2 capture. The method was successful for grafting monomer ethylamine groups onto CNT and can be further developed to allow for polymeric amine groups to be grafted.

Metal organic frameworks (MOFs) is a quite recently discovered porous material group which shows potential in many different areas. One of these areas is carbon capture; the framework structure of the porous materials allows gas molecules to adsorb to the surface of the pores. MOFs are conventionally synthesised at high temperatures and with hazardous solvents. The goal of this projectwas to synthesise highly porous MOFs at room temperature with water as the main solvent, using environmentally friendly and non-hazardous precursors. As well as the room temperature synthesis, conventional synthesis methods were used with the same precursors as comparison. The materials were characterised with X-ray diffraction, thermogravimetrical methods and IR-spectroscopy. To assess the porosity of the materials, gas adsorption evaluation was performed with CO2, N2, SF6, and CH4 at 20⁰C. In the end, three novel porous magnesium-based materials and one zirconium-based material were successfully synthesised. One of the magnesium-based materials showed a moderately high CO2 adsorption (2.38mmol/g), and could be synthesised at room temperature. The zirconium-based material showed a remarkably high selectivity (17.7) for SF6 over N2 and a high surface area (550m2/g)

The racemic homoallylic and homopropargylic alcohol derivatives were resolved by applying chemoenzymatic method using various lipase type enzymes i.e., PS-C II, Lipozyme, CAL-B. The enantiomeric excess values of the resultant alcohols were determined by HPLC. These enantiomerically enriched homoallylic and homopropargylic alcohols were subjected to N-propargylation and N-allylation, respectively, by SN2 and modified Mitsunobu reactions. During the course of all reactions, stereochemistry of the chiral centers were under controlling according to the known reaction mechanisms. The resultant chiral N-tosylated enyne derivatives afforded the corresponding chiral fused cyclopenta[c]pyridinone derivatives (69, 73, 75 and 77) with acceptable chemical yields and excellent diastereoslectivity depending upon the conformational effect on the complete remote stereochemical control for the newly generated chiral centers. The chemoenzymatic applications done with biocatalysis (lipases) and the Pauson-Khand reaction are involved in &ldquo
Green Chemistry&rdquo
approach.

Kyoto University (京都大学)
0048
新制・課程博士
博士(人間・環境学)
甲第21178号
人博第850号
新制||人||203(附属図書館)
29||人博||850(吉田南総合図書館)
京都大学大学院人間・環境学研究科相関環境学専攻
(主査)教授 吉田 寿雄, 教授 内本 喜晴, 教授 田部 勢津久
学位規則第4条第1項該当

Les fortes tensions liées à l'approvisionnement en ressources minérales ont motivé de nombreuses recherches sur les substitutions innovantes et le recyclage. La biomasse riche en métaux produite par les techniques de phytoextraction s'est récemment avérée être une ressource pour la Chimie Verte. Cette biomasse permet de produire de nouveaux catalyseurs appelés « écocatalyseurs ». Ceux-ci permettent la production de nouvelles molécules, des meilleurs rendements en synthèse, une régio- et une chimio-sélectivité accrues… Ceci donne une valeur ajoutée potentielle et donc le possible développement d'une filière économique. Cette nouvelle approche pourrait motiver le développement de la phytoextraction, une technique considérée comme prometteuse, mais qui après 20 années de recherches n'a toujours pas trouvé de débouché crédible. Dans ce cadre, les haut lieux de la biodiversité « métallophyte », tels que la Nouvelle-Calédonie, ont leur importance pour évaluer l'approvisionnement en biomasse. En Nouvelle-Calédonie, l'ambitieuse et coûteuse restauration écologique de ces écosystèmes miniers très dégradés est mise en doute. Dans ce cas, le développement de la phytoextraction sur les carrières et verses à stériles pourrait apporter des revenus, tout en assurant une forme de réhabilitation. Cette thèse s'intéresse à la possibilité d'une filière en Nouvelle-Calédonie, de la plante au produit chimique en passant par le catalyseur
Increasing pressure on mineral resources has drawn research efforts into innovative supply and recycling. Metal-rich biomass produced in phytoextraction proved an interesting starting-material for Green Chemistry. It allows the production of new catalysts, referred to as ‘ecocatalysts'. They provide the following benefits: access to new molecules, increased yields in chemicals production, increased regio- and chemo-selectivity… This results in potentially high added-value and possible development of a new economic outlet. This new approach to using metal-rich biomass could spur the development of phytoextraction, a technique considered promising for long, yet without credible economic applications. In this regard metallophyte biodiversity hotspots, such as New Caledonia are of particular interest to assess biomass supply. Ambitious and costly ecological restoration of the mining environment in New Caledonia is increasingly questioned. The development of phytoextraction on most degraded areas, e.g. quarries and wastes piles, to produce biomass for Ecocatalysis could provide revenues, while ensuring reclamation. This thesis looks into a possible outlet in New Caledonia, from plants to catalysts and final chemical products

Coal is a very prominent energy source in the world, but it is environmentally unattractive due to its high sulfur and ash content as well as its alleged contribution towards climate change, but it is affordable, abundant, and has high energy content. Thus, utilizing coal in a cleaner and more efficient way has become necessary. One promising clean coal technology involves fully gasifying coal into synthesis gas, cleaning it, and feeding it into a high-efficiency combined cycle, such as an Integrated Gasification Combined Cycle (IGCC). Inspired by the recent success of warn gas cleanup (WGCU), mild and partial gasification are proposed as less energy intensive options. This Integrated Mild/Partial Gasification Combined Cycle (IMPGC) could significantly save energy and improve efficiency. The objective of this study is to investigate the capabilities of IMPGC as both a new plant and a retrofit option for traditional coal power plants with and without carbon capture. I MPGC relies on the principles of mild and partial gasification and the recently available WGGU technology with the following benefits: a.) completely negate the need for syngas cooling; b.) significantly reduce the energy needed to fully thermally crack the volatiles and completely gasify the char as in the IGCC system; c.) preserve the high chemical energy hydro-carbon bonds within the feedstock to allow more efficient combustion in the gas turbine; d.) reduce the size of gasifier and piping to reduce the costs; and e.) enable retrofitting of an old coal power plant by preserving the existing equipment. The software used (Thermoflex®) was first validated with established cases from the U.S. Department of Energy. For new plants, the results show that IMPGC’s efficiency is 8 percentage points (20%) higher than IGCC, 8 points higher than a modern subcritical Rankine cycle, and 3-4 points higher than an ultra-supercritical (USC) cycle. When retrofitting older plants, a minimum improvement of over 4 points is predicted. When carbon capture is involved, IMPGC’s efficiency becomes 10 points better than a subcritical plant and 8 points better than a USC plant. Emissions wise, IMPGC is better than IGCC and much better than Rankine cycle plants.

Succinic acid is a compound used for manufacturing lacquers, resins, and other coating chemicals. It is also used in the food and beverage industry as a flavor additive. It is predominantly manufactured from petrochemicals, but it can also be produced more sustainably by fermentation of sugars from renewable feedstocks (biomass). Bio-based succinic acid has excellent potential for becoming a platform chemical (building block) for commodity and high-value chemicals. In this study, we focused on the production of bio-based succinic acid from the fiber of sweet sorghum (SS), which has a high fermentable sugar content and can be cultivated in a variety of climates and locations around the world. To avoid competition with food feedstocks, we targeted the non-edible ‘bagasse’, which is the fiber part after extracting the juice. Initially, we studied various conditions of pretreating SS bagasse to remove most of the non-fermentable portions and expose the cellulose fibers containing the fermentable sugars (glucose). Concentrated (83%) phosphoric acid was utilized at mild temperatures of 50-80 °C for 30-60 minutes at various bagasse loadings (10-15%) using a partial factorial experimental design. After pretreatment, the biomass was subjected to enzymatic hydrolysis with commercial cellulase enzyme (Cellic® Ctec2) to identify the pretreatment conditions that lead to the highest glucose yield that is critical for the production of succinic acid via fermentation with the bacterium Actinobacillus succinogenes. As the pretreatment temperature and duration increased, the bagasse color changed from light brown to dark brown-black, indicating decomposition, which ranged from 15% to 72%. The pretreatment results were fitted with an empirical model that identified 50 °C for 43 min at 13% solids loading as optimal pretreatment conditions that lead to the highest glucose release from sweet sorghum bagasse. Biomass pretreated at those conditions and subjected to separate enzymatic hydrolysis and fermentation with A. succinogenes yielded almost 18 g/L succinic acid, which represented 90% of the theoretical yield, a very promising performance that warranties further investigation of bio-based succinic acid production from sweet sorghum bagasse, as a more sustainable alternative to succinic acid produced from fossil sources, such as oil.

The Systemic Arterial Hypertension (SAH) has a high prevalence and low rates of control and its major complication infarction. In the center of the genesis of these diseases are found the Advanced Glycation Endproducts (AGEs), whose first inhibitor described was the aminoguanidine. Amongst the therapeutic arsenal available for treating hypertension are the guanidines agonists of α2-adrenergic receptors of central action. Given the high prevalence of hypertension and high mortality rates associated with complications of the disease, this work proposes the synthesis of aminoguanidinehydrazones (AGH) with potential application for the treatment of hypertension and at another time, the creation of rigid molecular frameworks for these flexible AGHs that allow the obtention of prototypes that, retaining the anti-hypertensive activity, are useful for prevention of damage caused by ischemic heart disease. It was synthesized 20 AGHs with different aromatic substituents, which yields ranged from about 70 to 90%, using classical methods of condensation between aminoguanidine and different aromatic aldehydes, being described here for the first time the antihypertensive activity for one of them, the compound 234, also known as LQM01. Among the synthesized AGHs, four were selected to serve as the basis for the synthesis of rigid analogs, and 25 different substances were obtained with yields ranging around 40 to 90% using a variety of synthetic strategies. Of these 25 substances, 13 are new, there are no reports in the literature of its synthesis and / or pharmacological activities. In a second step, this paper also proposes a new methodology development study for the reaction of carbon-nitrogen bond formation in aqueous medium catalyzed by copper in order to contribute to the arsenal of currently available reactions for arylation of primary amines and amides, with a reaction that is easy to perform, inexpensive and environmentally friendly. Two new methods were developed, one allowing the arylation of primary amines and other the arylation of primary and secondary amides and certain heterocyclic amines, both supplemented with TPGS using water as solvent and glucose as a reducing agent. In the arylation of primary amines model we bring here 34 examples of reactions, including different aliphatic and aromatic amines and aromatic and heteroaromatic halides with yields ranging around 50 to 90%. We also bring 34 examples of reactions with the catalyst system to arylation of amides, including reactions with aromatic and aliphatic amides, a lactam, aryl and heteroaryl halides, and also some heterocyclic amines with yields ranging around 60 to 90%. This work allowed two important contributions, one in the field of Medicinal Chemistry, with the synthesis of novel derivatives rigid molecular frameworks of AGHs with potential application in cardiovascular disease and other contribution in the field of Synthetic Organic Chemistry, with the development of new methodologies for C-N bond formation in an aqueous medium and with the use of sustainable additives.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A Hipertensão Arterial Sistêmica (HAS) é uma doença com alta prevalência e baixas taxas de controle, que traz como uma das principais complicações o infarto. No centro da gênese destas doenças encontramos os chamados Produtos Finais de Glicação Avançada (AGEs), cujo primeiro inibidor descrito foi a aminoguanidina. Dentre o arsenal terapêutico disponível para o tratamento da hipertensão estão as guanidinas agonistas de receptores α2‐adrenérgicos de ação central. Tendo em vista a alta prevalência de HAS e taxas de mortalidade associadas às complicações decorrentes da doença, este trabalho propõe a síntese de aminoguanidinoidrazonas (AGHs) com aplicação potencial para o tratamento da HAS e em outro momento, a criação de arcabouços moleculares rígidos para estas AGHs flexíveis que permitam a obtenção de protótipos que, retendo a atividade anti‐hipertensiva, sejam úteis para prevenção dos danos provocados pelas doenças isquêmicas do coração. Foram sintetizadas 20 AGHs carregando diferentes substituintes aromáticos, cujos rendimentos variaram da ordem de 70 a 90%, utilizando metodologia clássica de condensação entre a aminoguanidina e diferentes aldeídos aromáticos, sendo aqui descrita pela primeira vez a atividade anti‐hipertensiva para uma delas, o composto 234, também conhecido por LQM01. Dentre as AGHs sintetizadas, quatro foram selecionadas para servirem como base para a síntese de análogos rígidos, sendo obtidas 25 substâncias diferentes, das classes dos diidroimidazois, tetraidropirimidinas, aminotriazinas, aminopirimidinas e benzotriazepinaminas, com rendimentos variando da ordem de 40 a 90%. Destas 25 substâncias, 13 são inéditas, não havendo relatos na literatura de sua obtenção e/ou atividades farmacológicas Em um segundo momento, o presente trabalho propõe também um estudo de desenvolvimento de metodologia inédita de formação de ligação carbononitrogênio em meio aquoso, catalisada por cobre com o intuito de contribuir para o arsenal de reações disponível atualmente para a arilação de aminas primárias e amidas com uma reação que seja de fácil execução, barata e ambientalmente correta. Foram desenvolvidas duas metodologias inéditas, uma permitindo a arilação de aminas primárias e outra, a arilação de amidas primárias, secundárias e algumas aminas heterocíclicas, ambas utilizando água suplementada com TPGS como solvente e glicose como agente redutor. No modelo de arilação de aminas primárias trazemos aqui 34 exemplos de reações, incluindo diferentes aminas alifáticas e aromáticas e haletos aromáticos e heteroaromáticos, cujos rendimentos variaram da ordem de 50 a 90%. Trazemos também 34 exemplos de reações com o sistema catalítico de arilação de amidas, incluindo reações com amidas aromáticas, alifáticas, uma lactama, haletos de arila e heteroarila e também algumas aminas heterocíclicas, cujos rendimentos variaram da ordem de 60 a 90%. O presente trabalho permitiu duas contribuições importantes, uma no campo da Química Medicinal, com a síntese de inovadores arcabouços moleculares rígidos derivados das AGHs com potencial aplicação em doenças cardiovasculares e outra contribuição no campo da Química Orgânica Sintética, com o desenvolvimento de novas metodologias de formação de ligação C‐N em meio aquoso e com a utilização de aditivos sustentáveis.

Le but de cette étude est d’évaluer l’utilisation de la chromatographie préparative dans le cadre de la conception d’un procédé de purification d’acides organiques. Les acides principalement étudiés sont les acides lactique et succinique. Ils sont produits par fermentation et utilisés depuis longtemps dans l’industrie comme additifs. Ils sont aussi identifiés comme des molécules plateformes très intéressantes pour le développement de la chimie verte, à partir de carbone renouvelable. En particulier, ils constituent des monomères pour l’industrie des bioplastiques. A la différence des utilisations historiques, ce type d’application requière des niveaux de pureté beaucoup plus importants. Ces puretés sont atteintes via des étapes supplémentaires d’extraction liquide-liquide, de distillation et/ou de cristallisation. Nous avons cherché à évaluer si la mise en œuvre de la chromatographie préparative pouvait permettre d’atteindre les spécifications requises. Pour cela, la chromatographie a été étudiée en détails en tant qu’opération unitaire, afin de mieux comprendre les mécanismes de séparation des composés étudiés et les paramètres de mise en œuvre. Deux types de résine ont été principalement utilisés, une cationique forte et une anionique forte. Dans un premier temps, l’étude thermodynamique de l’adsorption de trois acides organiques en solution pure a été réalisée. Elle a révélé un comportement très différent pour les deux résines : l’adsorption sur la résine cationique forte est assez linéaire alors que sur l’anionique forte, elle est fortement non linéaire et suit un modèle de Langmuir. L’influence de la vitesse sur la forme des pics et donc la dispersion pendant la séparation a ensuite été étudiée. Il a été montré que l’efficacité de la colonne diminue linéairement avec la vitesse d’élution, conformément au modèle de Van Deemter. Il a aussi été mis en évidence que la pente de cette droite est la même à l’échelle laboratoire et sur le pilote à une échelle dix fois plus grande. Elle peut ainsi permettre de prévoir l’évolution de l’efficacité de la colonne au changement d’échelle. Des solutions en mélange synthétiques et réels ont été étudiées, afin d’évaluer l’influence sur la séparation des paramètres opératoires, tels que la charge, la concentration de l’alimentation, le pH… 2 Sur la résine anionique, une première modélisation a été effectuée à partir de ces résultats expérimentaux. Elle a permis de mettre en évidence, qu’un mécanisme d’adsorption de type Langmuir ne suffit pas à expliquer la forme et la position des pics. Nous avons supposé qu’un mécanisme d’échange d’ions de la forme dissociée des acides organiques pourrait aussi entrer en jeu. Cet échange aurait un impact important sur la forme et la position des pics, bien que les acides organiques soient très majoritairement sous leur forme neutre. Les séparations mises en évidence à l’échelle laboratoire ont été validées à l’échelle pilote en chromatographie continue ISMB. Il a été montré que la résine anionique permet d’atteindre une plus grande pureté que la résine cationique avec une productivité similaire. Un procédé complet de purification a pu être testé avec de l’acide succinique, mettant en jeu une acidification par électrodialyse bipolaire, une concentration par osmose inverse, une séparation par chromatographie préparative sur résine anionique forte et une décoloration par nanofiltration. Le produit a ensuite été cristallisé afin de se comparer à un produit industriel. Le produit obtenu est proche des spécifications attendues et est plutôt meilleur que le produit industriel. Une étape supplémentaire d’échange d’ions aurait vraisemblablement permis d’obtenir des cristaux de grade polymère. Nous avons donc montré que la chromatographie a sa place dans un procédé de purification d’acides organiques, dans le but d’obtenir une très haute pureté
The objective of this study is to evaluate the use of preparative chromatography in the context of the elaboration and optimization of an innovative purification process of organic acids from biotechnology. Lactic and succinic acids were mainly studied. They are produced by fermentation and used in industry as additive, for a long time. They are identified as promising building blocks for green chemistry development, from renewable carbon. In particular, they are monomers for bioplastic industry. Unlike historical utilizations, this new type of application requires much higher purity levels. Those purities are currently obtained by additional purification steps, like liquid-liquid extraction, distillation and/or crystallization. We tried to evaluate if the required specifications may be reached by the implementation of preparative chromatography. For this chromatography was studied in details as unitary operation, in order to better understand separation mechanisms of studied compounds and implementation parameters. Two resin types were mainly used, a strong cationic one and a strong anionic one. Firstly, thermodynamic study of the adsorption of three organic acids in pure solution was performed. It revealed very different performances for both resins: adsorption on strong cationic resin is quite linear, whereas on strong anionic one adsorption is strongly nonlinear and fits with Langmuir model. Elution velocity influence on peak shape and so on dispersion was then studied. Column efficiency decreases linearly with elution velocity, accordingly to Van Deemter model. It was shown that the line slope was identical at lab scale and on a pilot ten times bigger. Then it may be used to predict column efficiency evolution during scale-up. Mixing solutions from synthetic or real origin were studied, to evaluate operational parameter influence on the separation, as load, feed concentration, pH… On the strong anionic resin, a first modeling was developed for experimental results. It highlighted that Langmuir type adsorption mechanism is not able to explain peak shape and position. We supposed that an ion exchange mechanism with the organic acid dissociated part may happen. This exchange may have a significant impact on peak shape and position, even if organic acids are mainly in molecular form, because of a low work pH. 4 Separations established at lab scale were validated at pilot scale in continuous chromatography ISMB. It was demonstrated that the anionic resin allows to reach a higher productivity than the cationic one, with a similar productivity. A complete purification process was tested with succinic acid, using bipolar electrodialysis acidification, reverse osmosis concentration, preparative chromatography separation with a strong anionic resin and nanofiltration discoloration. Product was then crystallized, to be compared to an industrial product. Our crystals were close to waited specifications and relatively better than the industrial ones. An additional ion exchange step could have allows to reach polymer grade. We show that chromatography is useful in an organic acid purification process, in order to reach a very high purity

Green chemistry principles have been applied to the enhancement of two industrial chemistry problems. An industrially used reaction to form alcohols from aldehydes and ketones, the Meerwein-Ponndorf-Verley reduction, was improved by introducing a new catalyst Al(OtBu)₃. Due to the lower state of aggregation of this catalyst versus the conventional Al(OiPr)₃ catalyst, reduction rates were found to be faster in both pure iPrOH and mixed solvent systems for three model compounds: benzaldehyde, acetophenone, and a complex, chiral ketone, (S)-CMK. This allowed for the successful implementation of two important milestones; lowering the amount of catalyst needed necessary to complete the reactions (an economic benefit and lower waste) and the conversion from traditional batch reactions to continuous flow (a processing benefit) whereby reactions can be scaled-out rather than scaled-up. Another industrially important field of research that was focused on was CO₂ capture. High energy demands from current CO₂ capture methods such as aqueous amine solvents, specifically from coal-fired power plant flue gas, led to the development of non-aqueous reversible ionic liquids based on silylated amines. Structural modifications of the substitution around the silicon atom, the length of the alkyl chain bonding the silicon and amine, branching along the alkyl backbone, and investigating secondary and primary amines within this class of silylated amines were completed. These amines were reacted with CO₂ and the CO₂ capacity, the ionic liquid viscosity, reversal temperature and reaction enthalpy were all considered as a function of structure. In all cases the capacity was found to be not only greater than that of monethanolamine, an industrial standard, but higher than theoretical predictions through the formation of carbamic acid. Viscosity, reversal temperature, and reaction enthalpy were all found to be tunable through structure. These modifications gave significant insight into the necessary direction for optimization of these solvents as energy-efficient replacements of current CO₂ capture technology.

Pine weevils cause major damage to newly planted conifer seedlings in reforestation areas. However, recent findings indicate that small (“mini”) seedlings, planted at the age of 7-10 weeks, are gnawed less by pine weevils than the larger, conventionally planted seedlings. Thus, it has been proposed that planting young conifer seedlings in clear-cut areas may reduce the damage caused by pine weevils. In attempts to determine why mini seedlings appear to be less damaged by pine weevils than “conventional” seedlings, the volatiles released by Norway spruce and Scots pine mini seedlings were investigated, since such chemicals are of great importance in herbivore-plant communication, inter alia acting as repellents, attractants or antifeedants. Volatiles from the seedlings were collected, separated and identified by solid phase microextraction (SPME) followed by gas chromatography-mass spectrometry. The results show that there are high levels of chemodiversity among both spruce and pine seedlings. Between-tissue and age-related variations in their emissions were also found. Norway spruce clones infested by mites were also examined to assess genotype- and pest-specific stress reactions of Norway spruce. Finally, the effects of certain spruce defense compounds on the behavior of the large pine weevil Hylobius abietis were examined.
QC 20100818

This thesis is about sustainability within chemistry, the so-called, green chemistry. With this work  I seek to combine green chemistry with sustainable  development  and find methods for teaching green chemistry in a laboratory environement.  I have designed  and tested two labs with ingredients of green  chemistry and sustainable development in my study. I wanted to determine if my design model  leads to conception for the students. The students have through forms and interviews declared their perspective on the education and their conception. In a laboratory environment the pros of a laboratory way of work should be recognized. Pre- and post-work puts the lab in a context. The students understand the concepts better if they are allowed to test their knowledge in a discussion. The teachers role in the discussion should be to lift the level of the discussion by controlling the conversation and in a constructiveway contribute to making the discussion move forward whenever necessary.
Denna uppsats behandar hållbarhet inom kemi, den så kallade gröna kemin. Med arbetet söker jag förena grön kemi med hållbar utveckling och hitta metoder för att undervisa grön kemi i en laborativ miljö. I undersökningen har jag designat och testat två laborationer med inslag av grön kemi och hållbar utveckling. Jag ville undersöka om undervisningsmodellen leder till en begreppsutveckling hos studenter och elever. Studenterna/eleverna har genom enkäter och intervjuer uttalat sig om dels sina egna kunskaper och dels om undervisningens inslag och dess bidrag till deras begreppsutveckling. I ett laborativt sammanhang bör fördelarna med ett laborativt arbetssätt utnyttjas. Förarbete och efterarbete ger laborationen ett sammanhang. Studenten/eleven förstår begreppen bättre om de får testa sina kunskaper i en diskussion. Lärarens roll i diskussionen bör vara att lyfta diskussionsnivån genom att styra samtalet och på ett konstruktivt sätt bidra till att föra diskussionen framåt när det är nödvändigt.

Le développement d'une chimie soucieuse de l'environnement doit passer par la recherche de solutions concernant l'utilisation de solvants organiques. Ces solvants sont souvent toxiques et volatiles et créent, surtout dans le cas des solvants halogénés, des dégâts environnementaux. L'objectif premier de ce projet est de développer des alternatives à l'utilisation en chimie de solvants organiques toxiques et volatiles. Plus précisément, le but est de mettre au point des méthodes de transformations chimiques qui permettent de diminuer fortement l'utilisation de solvant ou de les remplacer par des solvants alternatifs. Le développement de ces méthodes par mécanochimie a permis d'atteindre cet objectif. Plusieurs méthodologies ont été développées et appliquées à la protection des acides aminés ainsi qu'à la synthèse de molécules bioactives que sont les hydantoïnes, avec notamment la préparation de composés pharmaceutiques tels que la phénytoïne et l'éthotoïne, deux médicaments prescrits contre l'épilepsie
The development of environmentally-friendly chemistry has to go through the search for solutions concerning the use of organic solvents. Such solvents are often toxic and volatile, and create, especially in the case of halogenated solvents, environmental damage. The primary objective of this project is to develop alternatives to the use in synthetic chemistry of toxic and volatile organic solvents. Specifically, the goal is to develop methods of chemical transformations that can greatly reduce the use of solvent or replace them with alternative solvents. The development of these methods by mechanochemistry enabled to achieve this goal. Several methodologies have been developed and applied to the protection of amino acids and the synthesis of bioactive molecules such as hydantoins, including the preparation of pharmaceutical compounds such as phenytoin and ethotoin, two drugs prescribed against epilepsy

L’utilisation de semi-conducteurs organiques dans les dispositifs électroniques offre d’intéressantes perspectives. En effet, ils permettent d’alléger le poids de ces dispositifs en plus de diminuer grandement le coût de leur fabrication. Cependant, une des principales problématiques associées à ces semi-conducteurs organiques est leur procédé de fabrication qui requiert des solvants organiques toxiques et de multiples étapes de synthèse. Dans ce travail, un nouveau procédé de synthèse respectueux de l’environnement a été mis au point. Une seule étape était nécessaire à la préparation des semi-conducteurs, en utilisant la réaction de polycondensation entre une diamine et un dialdéhyde. Cette réaction a été réalisée à température ambiante, dans un solvant vert, l’éthanol, et sans utilisation de catalyseurs, minimisant ainsi la consommation énergétique et utilisant un milieu réactionnel de source renouvelable et peu toxique. Après leur dopage, ces polymères ont présentés des propriétés de conduction comparables à celles des principaux semi-conducteurs organiques. La deuxième partie de cette thèse a été consacrée à l’étude de l’utilisation du papier comme support pour les dispositifs d’électronique organique; s’affranchissant ainsi de l’utilisation de substrats généralement non biodégradables et/ou de sources non renouvelables (plastique ou verre). Deux stratégies ont été utilisées à cette fin. La première consistait en un dépôt direct des polymères semi-conducteurs à la surface de filaments de cellulose. La deuxième est basée sur la création d’un lien covalent entre les semi-conducteurs et la pâte Kraft, en utilisant la réaction de cycloaddition 1,3-dipolaire de Huisgen catalysée par le cuivre (CuAAc)
The use of organic semiconductors in electronic devices offers interesting prospects. Indeed, they make it possible to lighten the weight of these devices in addition to greatly reducing the cost of their manufacture. However, one of the main problems associated with these organic semiconductors is their manufacturing process, which requires toxic organic solvents and multiple synthesis steps. In this work, a new environmentally friendly synthesis process has been developed. A single step was necessary for the preparation of the semiconductors, using the polycondensation reaction between a diamine and a dialdehyde.This reaction was carried out at room temperature in ethanol, a green solvent and without the use of catalysts, thus minimizing energy consumption and using a reaction medium from a renewable and low-toxicity source. After their doping, these polymers exhibited conduction properties comparable to those observed for conventional organic semiconductors.The second part of this thesis was devoted to the study of the use of paper as a support for organic electronics devices; hus avoiding the use of generally non-biodegradable and/or non-renewable substrates (plastic or glass). Two strategies have been used to this end. The first consisted of a direct deposit of the semiconducting polymers to the surface of cellulose filaments.The second is based on the creation of a covalent bond between the semiconductors and the Kraft pulp, using the copper-catalyzed Huisgen 1,3-dipolar cycloaddition reaction (CuAAc)

L'objectif central de notre thèse de doctorat visait l'utilisation d'halogénures d'aryles en tant qu'électrophiles dans des réactions de substitution nucléophile aromatique (SNAr). D'abord, nous avons cherché à former des liaisons C(aryl) hétéroatome par réaction entre des nucléophiles hétéroatomiques et des halogénures d'aryles substitués par des groupements électro-attracteurs. Les résultats de cette étude ont été comparés à des incohérences relevées dans la littérature et montrent que l'ordre de réactivité d'halogénures d'aryles communément accepté n'est pas toujours respecté. Un effet positif a été observé par l'ajout de 2,2,6,6-tétraméthyl-3,5-heptanedione pour l'arylation de phénols avec des halogénures d'aryles substitués par des groupements électro-donneurs, ce qui en fait la première méthode capable de générer des diaryléthers par cette voie réactionnelle sans ajout de catalyseurs métalliques. Ensuite, nous avons mis au point une réaction générale d'± arylation de cétones aromatiques avec des halogénures d'aryles dans des conditions réactionnelles douces. L'utilisation du t-BuOK, une base inorganique capable de transferts mono-électroniques, et de DMF comme additif permet la synthèse d'±-arylcétones avec d'excellents rendements. Cette méthode a été appliquée à la synthèse d'hétérocycles fusionnés et de (Z)-tamoxifène, des molécules montrant une activité biologique. Une étude mécanistique a montré que l'anion carbamoyle du DMF est impliqué dans une étape clé de transfert mono-électronique avec des halogénures d'aryles. Nous avons également appliqué cette méthode à la substitution nucléophile vinylique de ″-halostyrènes. Bien que des précédents de la littérature font état de mécanismes ioniques pour les réactions de ces substrats, nos résultats expérimentaux supportent un mécanisme radicalaire. Enfin, nous avons tenté de mettre au point le premier protocole permettant la synthèse de biaryles dissymétriques au départ d'halogénures d'aryles et de triarylbismuths(III) via une catalyse par des sels de cuivre. Malgré le fait que de nombreux ligands bidentates et tétradentates ont été testés, les faibles rendements obtenus font que les conditions réactionnelles demeurent à optimiser. Globalement, nous avons donc apporté une contribution en ce qui concerne la détermination de la frontière expérimentale entre la SNAr et la catalyse métallique, la fonctionnalisation en ± de cétones aromatiques et la synthèse de biaryles dissymétriques par réactions de couplages croisés de triarylbismuths catalysées au cuivre
The primary objective of our doctoral research was centered on the use of aryl halides as electrophiles for nucleophilic aromatic substitution (SNAr). First, we tried to create C(aryl)−heteroatom bonds by reacting heteroatom nucleophiles with aryl halides substituted by electron-withdrawing groups. The results of this study were compared with inconsistencies found in the literature and show that the expected order of reactivity of aryl halides is not always observed. A beneficial effect was observed by adding 2,2,6,6-tetramethylheptane-3,5-dione to the reaction of phenols and aryl halides substituted by electron-donating groups in what is the first method allowing the synthesis of diarylethers without added metal catalysts by this pathway. Second, we developed a general α-arylation reaction of aryl ketones with aryl halides under mild reaction conditions. Use of KOt-Bu, an inorganic base capable of single-electron transfer, and DMF as additive enables the synthesis of α-arylketones in excellent yields. This method was applied to the synthesis of fused heterocycles and (Z) tamoxifen, molecules possessing biological activity. A mechanistic study showed that the carbamoyl anion of DMF is involved in a single-electron transfer reaction with aryl halides as the key step of the mechanism. We next applied this method to the nucleophilic vinylic substitution of β-halogenostyrenes. While literature precedents suggest ionic mechanisms for reactions involving these substrates, we obtained experimental evidence suggesting a radical mechanism. Third, we tried to develop the first protocol enabling the copper-catalyzed synthesis of unsymmetrical biaryls starting from aryl halides and triarylbismuthanes(III). Although many bidentate and tetradentated ligands were tested, further optimization is required in order to develop a general method, as only low yields are obtained. Globally, we have contributed to the determination of the experimental frontier between SNAr and metallic catalysis, to the α-functionnalization of aryl ketones and to the synthesis of biaryls through copper-catalyzed cross-coupling reactions of triarylbismuths

The present Thesis studies three alternative solvent groups as sustainable replacement of traditional organic solvents. Some aspects of fluorinated solvents, supercritical fluids and ionic liquids, have been analysed with a critical approach and their effective “greenness” has been evaluated from the points of view of the synthesis, the properties and the applications. In particular, the attention has been put on the environmental and human health issues, evaluating the eco-toxicity, the toxicity and the persistence, to underline that applicability and sustainability are subjects with equal importance. The “green” features of fluorous solvents and supercritical fluids are almost well-established; in particular supercritical carbon dioxide (scCO2) is probably the “greenest” solvent among the alternative solvent systems developed in the last years, enabling to combine numerous advantages both from the point of view of industrial/technological applications and eco-compatibility. In the Thesis the analysis of these two classes of alternative solvents has been mainly focused on their applicability, rather than the evaluation of their environmental impact. Specifically they have been evaluated as alternative media for non-aqueous biocatalysis. For this purpose, the hydrophobic ion pairing (HIP), which allows solubilising enzymes in apolar solvents by an ion pairing between the protein and a surfactant, has been investigated as effective enzymatic derivatisation technique to improve the catalytic activity under homogeneous conditions in non conventional media. The results showed that the complex enzyme-surfactant was much more active both in fluorous solvents and in supercritical carbon dioxide than the native form of the enzyme. Ionic liquids, especially imidazolium salts, have been proposed some years ago as “fully green” alternative solvents; however this epithet does not take into account several “brown” aspects such as their synthesis from petro-chemical starting materials, their considerable eco-toxicity, toxicity and resistance to biodegradation, and the difficulty of clearly outline applications in which ionic liquids are really more advantageous than traditional solvents. For all of these reasons in this Thesis a critical analysis of ionic liquids has been focused on three main topics: i) alternative synthesis by introducing structural moieties which could reduce the toxicity of the most known liquid salts, and by using starting materials from renewable resources; ii) on the evaluation of their environmental impact through eco-toxicological tests (Daphnia magna and Vibrio fischeri acute toxicity tests, and algal growth inhibition), toxicity tests (MTT test, AChE inhibition and LDH release tests) and fate and rate of aerobic biodegradation in soil and water; iii) and on the demonstration of their effectiveness as reaction media in organo-catalysis and as extractive solvents in the recovery of vegetable oil from terrestrial and aquatic biomass. The results about eco-toxicity tests with Daphnia magna, Vibrio fischeri and algae, and toxicity assay using cultured cell lines, clearly indicate that the difference in toxicity between alkyl and oxygenated cations relies in differences of polarity, according to the general trend of decreasing toxicity by decreasing the lipophilicity. Independently by the biological approach in fact, all the results are in agreement, showing a lower toxicity for compounds with oxygenated lateral chains than for those having purely alkyl lateral chains. These findings indicate that an appropriate choice of cation and anion structures is important not only to design the IL with improved and suitable chemico-physical properties but also to obtain safer and eco-friendly ILs. Moreover there is a clear indication that the composition of the abiotic environment has to be taken into account when the toxicity of ILs in various biological test systems is analysed, because, for example, the data reported in the Thesis indicate a significant influence of salinity variations on algal toxicity. Aerobic biodegradation of four imidazolium ionic liquids, two alkylated and two oxygenated, in soil was evaluated for the first time. Alkyl ionic liquids were shown to be biodegradable over the 6 months test period, and in contrast no significant mineralisation was observed with oxygenated derivatives. A different result was observed in the aerobic biodegradation of alkylated and oxygenated pyridinium ionic liquids in water because all the ionic liquids were almost completely degraded after 10 days, independently by the number of oxygen in the lateral chain of the cation. The synthesis of new ionic liquids by using renewable feedstock as starting materials, has been developed through the synthesis of furan-based ion pairs from furfural. The new ammonium salts were synthesised in very good yields, good purity of the products and wide versatility, combining low melting points with high decomposition temperatures and reduced viscosities. Regarding the possible applications as surfactants and biocides, furan-based salts could be a valuable alternative to benzyltributylammonium salts and benzalkonium chloride that are produced from non-renewable resources. A new procedure for the allylation of ketones and aldehydes with tetraallyltin in ionic liquids was developed. The reaction afforded high yields both in sulfonate-containing ILs and in ILs without sulfonate upon addition of a small amount of sulfonic acid. The checked reaction resulted in peculiar chemoselectivity favouring aliphatic substrates towards aromatic ketones and good stereoselectivity in the allylation of levoglucosenone. Finally ILs-based systems could be easily and successfully recycled, making the described procedure environmentally benign. The potential role of switchable polarity solvents as a green technology for the extraction of vegetable oil from terrestrial and aquatic biomass has been investigated. The extraction efficiency of terrestrial biomass rich in triacylglycerols, as soy bean flakes and sunflower seeds, was comparable to those of traditional organic solvents, being the yield of vegetable oils recovery very similar. Switchable polarity solvents as been also exploited for the first time in the extraction of hydrocarbons from the microalga Botryococcus braunii, demonstrating the efficiency of the process for the extraction of both dried microalgal biomass and directly of the aqueous growth medium. The switchable polarity solvents exhibited better extraction efficiency than conventional solvents, both with dried and liquid samples. This is an important issue considering that the harvest and the dewatering of algal biomass have a large impact on overall costs and energy balance.

In the last decade considerable attention has been devoted to the rewarding use of Green Chemistry in various synthetic processes and applications. Green Chemistry is of special interest in the synthesis of expensive pharmaceutical products, where suitable adoption of “green” reagents and conditions is highly desirable. Our project especially focused in a search for new green radical processes which might also find useful applications in the industry. In particular, we have explored the possible adoption of green solvents in radical Thiol-Ene and Thiol-Yne coupling reactions, which to date have been normally performed in “ordinary” organic solvents such as benzene and toluene, with the primary aim of applying those coupling reactions to the construction of biological substrates. We have additionally tuned adequate reaction conditions which might enable achievement of highly functionalised materials and/or complex bioconjugation via homo/heterosequence. Furthermore, we have performed suitable theoretical studies to gain useful chemical information concerning mechanistic implications of the use of green solvents in the radical Thiol-Yne coupling reactions.

Les amines aromatiques sont largement considérées comme des intermédiaires réactionnels prometteurs pour la production de colorants, d'antioxydants, de produits pharmaceutiques et de produits chimiques agricoles. La méthode la plus utilisée pour la préparation des amines aromatiques est l’hydrogénation catalytique en général. Les procédés d'hydrogénation catalytique des composés nitroaromatiques utilisent des métaux de transition, tels que (Pt, Ni, Pd,..), de solvants organiques et source d’hydrogène comme H2. Cependant, l'utilisation de catalyseurs métalliques présente certains inconvénients tels que le coût élevé, le recyclage du système, ainsi que certaines préoccupations environnementales. Les solvants organiques ont également été utilisés au cours de ces processus, ce qui a nécessité une consommation d'énergie élevée pour la récupération des amines aromatiques. Enfin, l’utilisation de H2 peut entraîner également des risques liés à la sécurité. Dans le présent travail, des procédés « verts » et sûrs pour la réduction des composés nitroaromatiques en amines aromatiques en présence de matériaux carbonés ou de biomasse lignocellulosique dans des conditions subcritiques ont été développés. Dans un premier temps notre intérêt dans ce travail s'est porté sur l'utilisation directe du carbone qui présente comme avantages, son faible coût et sa disponibilité, cela a donné lieux à un nouveau procédé plus « vert » et plus sécuritaire. Le mécanisme réactionnel de ce dernier a été étudié en utilisant le logiciel CIRCE qui est un logiciel de thermodynamique basé sur la méthode de Monte Carlo. Ce procédé a été ensuite appliqué à différents composés nitrés aromatiques substitués par une fonction organique en particulier pour la préparation du 3-aminobenzoique à partir du 3-nitrobenzaldehyde. Par la suite les matériaux carbonés ont été remplacés par de la biomasse lignocellulosique qui est la sciure de bois imprégné par une base dans l’eau à l’état subcritique. En effet l'eau connue comme solvant vert pourraient impliquer de nouveaux procédés « verts » en conditions critiques et engendrer H2 permet d’apporter le dihydrogène nécessaire pour la faisabilité de la réaction
Aromatic amines are widely regarded as promising reaction intermediates for the production of dyes, antioxidants, pharmaceuticals and agricultural chemicals. The most widely used method for the preparation of aromatic amines is catalytic hydrogenation in general. The catalytic hydrogenation processes of nitroaromatic compounds use transition metals, such as (Pt, Ni, Pd, ..), organic solvents and hydrogen source like H2. However, the use of metal catalysts has certain disadvantages such as the high cost, recycling of the system, as well as certain environmental concerns. Organic solvents were also used during these processes, which required high energy consumption for the recovery of aromatic amines. Finally, the use of H2 can also lead to safety risks. In the present work, “green” and safe processes for the reduction of nitroaromatic compounds into aromatic amines in the presence of carbonaceous materials or lignocellulosic biomass under subcritical conditions have been developed. Initially, our interest in this work focused on the direct use of carbon which has the advantages, its low cost and its availability, this gave rise to a new process that is "greener" and safer. The reaction mechanism of the latter was studied using CIRCE software which is thermodynamic software based on the Monte Carlo method. This process was then applied to various aromatic nitro compounds substituted by an organic function in particular for the preparation of 3-aminobenzoic starting from 3-nitrobenzaldehyde. Subsequently carbonaceous materials were replaced by lignocellulosic biomass which is sawdust impregnated with a base in water in the subcritical state. Indeed, water known as a green solvent could involve new "green" processes in critical conditions and generate H2 makes it possible to supply the dihydrogen necessary for the feasibility of the reaction

[ES] En este trabajo de tesis doctoral, la investigación se ha centrado en el desarrollo de diferentes procesos catalíticos heterogéneos empleando materiales híbridos orgánico-inorgánicos porosos (MOFs y sílices funcionalizadas) y materiales orgánicos aromáti-cos (PAFs), que se han estudiado en diversas reacciones orgánicas. Tras la preparación de los MOFs en estudio, se han caracterizado sus propiedades estructurales y se han determinado sus centros activos en los clústeres metálicos (circonio, hafnio o cerio). La reactividad de estos MOFs y de los materiales híbridos sílice-aminas se ha estudia-do teniendo en cuenta sus centros catalíticos; estas reacciones se han optimizado lle-vando a cabo un estudio de los mecanismos de reacción. Finalmente, se han preparado sólidos homoquirales de tipo PAF que presentan el sistema binaftilo, cuya reactividad también ha sido probada. Más específicamente, en el capítulo 3 se ha estudiado la esterificación de amidas, que permite convertirlas en ésteres, grupos funcionales más versátiles. Esta transfor-mación se ha abordado desde la catálisis heterogénea via MOFs basados en circonio, hafnio y cerio de las series MOF-808, UiO-66 y MOF-801. El catalizador más eficien-te para la esterificación de amidas ha sido el MOF-808-Zr. Mediante análisis TGA y la adsorción de una molécula sonda básica (CO) estudiada utilizando espectroscopia FT-IR, se han determinado los centros ácidos de Lewis y Brönsted presentes en ellos. De los MOFs preparados en este trabajo, el MOF 808-Zr posee una menor conectividad de los clústeres metálicos y un mayor tamaño de poro mayor que el UiO-66 y el MOF-801; además, tiene el balance adecuado de centros ácidos y básicos de Brönsted y Lewis para activar los sustratos de la reacción. El alcance de la alcoholisis con n-butanol se ha extendido a un gran número de sustratos (amidas primarias, secundarias y terciarias; aromáticas y alifáticas). La reacción también se ha estudiado en condicio-nes no solvolíticas con alcoholes más complejos. El catalizador es estable durante la reacción y puede ser reutilizado fácilmente. El mecanismo de reacción en la esterifica-ción de benzamida con n butanol catalizada por MOF-808-Zr se ha investigado me-diante el análisis cinético empleando el modelo de LHHW y el estudio in situ de las interacciones moleculares por FT-IR. En el capítulo 4, se ha investigado la deuteración por intercambio isotópico deute-rio/hidrógeno catalizada por aminas soportadas en sílice comerciales empleando D2O como fuente de deuterio. Este procedimiento es aplicable a una gran gama de sustra-tos, como compuestos carbonílicos, sales de organofosfonio, nitrocompuestos e, inclu-so, hormonas esteroideas. La estabilidad del catalizador, SiO2-(CH2)3-NH2, se mantie-ne hasta en 10 usos de reacción sin pérdidas significativas de la actividad. Por último, en el capítulo 5, se afronta la síntesis y aplicación de PAFs homoquira-les donde se ha integrado el esqueleto del BINOL (1,1′-binaftil-2,2′-diol) y del BIN-BAM (1,1' binaftil-2,2'-disulfonimida) generando tres nuevos PAFs activos en catáli-sis asimétrica: PAF-3,3'-(S)-BINOL, PAF-6,6'-(R)-BINOL y PAF 3,3'-(S)-BINBAM. En concreto, el PAF-6,6'-(R)-BINOL ha demostrado su actividad catalítica en la reacción de alquilación de aldehídos aromáticos con dietil-zinc y el catalizador PAF-3,3'-(S)-BINBAM es activo en la reacción aldólica de Mukaiyama y la reducción del doble enlace de compuestos carbonílicos a,b-insaturados.
[CA] En aquesta tesi doctoral, la investigació s'ha centrat en el desenvolupament de dife-rents processos catalítics heterogenis emprant materials híbrids orgànic-inorgànics porosos (MOFs i sílices funcionalitzades) i materials orgànics aromàtics (PAFs), que s'han estudiat en diverses reaccions orgàniques. Després de la preparació dels MOFs en estudi, s'han caracteritzat les seues propietats estructurals i s'han determinat els seus centres actius en els clústers metàl·lics (zirconi, hafni o ceri). La reactivitat d'aquests MOFs i dels materials híbrids sílice-amines s'ha estudiat tenint en compte els seus cen-tres catalítics; aquestes reaccions s'han optimitzat duent a termini un estudi dels meca-nismes de reacció. Finalment, s'han preparat sòlids homoquirals de tipus PAF que presenten el sistema binaftilo, la reactivitat del qual també ha sigut provada. Més específicament, en el capítol 3 s'ha estudiat l'esterificació d' amides, que per-met convertir-les en èsters, grups funcionals més versàtils. Aquesta transformació s'ha abordat des de la catàlisi heterogènia via *MOFs basats en zirconi, hafni i ceri de les sèries MOF-808, UiO-66 i MOF-801. El catalitzador més eficient per a l'esterificació d'amides ha sigut el MOF-808-Zr. Mitjançant anàlisi TGA i l'adsorció d'una molècula sonda bàsica (CO) estudiada utilitzant espectroscopia FT-IR, s'han determinat els cen-tres àcids de Lewis i Brönsted presents en ells. Dels MOFs preparats en aquest treball, el MOF 808-Zr posseeix una menor connectivitat dels clústers metàl·lics i una major grandària de porus que el UiO-66 i el MOF-801; a més, té el balanç adequat de centres àcids i bàsics de Brönsted i Lewis per a activar els substrats de la reacció. L'abast de l'alcoholisi amb n-butanol s'ha estés a un gran nombre de substrats (amides primàries, secundàries i terciàries; aromàtiques i alifàtiques). La reacció també s'ha estudiat en condicions no solvolítiques amb alcohols més complexos. El catalitzador és estable durant la reacció i pot ser reutilitzat fàcilment. El mecanisme de reacció en l'esterifica-ció de benzamida amb n-butanol catalitzada per MOF-808-Zr s'ha investigat mitja-nçant l'anàlisi cinètica emprant el model de LHHW i l'estudi in situ de les interaccions moleculars per FT-IR. En el capítol 4, s'ha investigat la deuteració per intercanvi isotòpic deuteri/hidrògen catalitzada per amines suportades en sílices comercials emprant D2O com a font de deuteri. Aquest procediment és aplicable a una gran gamma de substrats, com a com-postos carbonílics, sals d'organofosfoni, nitrocompostos i, inclosa, hormones esteroi-dals. L'estabilitat del catalitzador, SiO2-(CH2)3-NH2, es manté fins a 10 usos de reac-ció sense pèrdues significatives de l'activitat. Finalment, en el capítol 5, s'afronta la síntesi i aplicació de PAFs homoquirals on s'ha integrat l'esquelet del BINOL (1,1′-binaftil-2,2′-diol) i del BINBAM (1,1'-binaftil-2,2'-disulfonimida) generant tres nous PAFs actius en catàlisi asimètrica: PAF-3,3'-(S)-BINOL, PAF-6,6'-(R)-BINOL i PAF 3,3'-(S)-BINBAM. En concret, el PAF-6,6'-(R)-BINOL ha demostrat la seua activitat catalítica en la reacció d'alquilació d'aldehids aromàtics amb dietil-zinc i el catalitzador PAF-3,3'-(S)-BINBAM és actiu en la reacció aldólica de Mukaiyama i la reducció del doble enllaç de compostos carbonílics a,b-insaturats.
[EN] In this Doctoral Thesis, the research has been focused on the development of different heterogeneous catalytic processes using hybrid porous organic-inorganic materials (MOFs and functionalized silicas) and organic aromatic materials (PAFs), which have been studied in various organic reactions. After the preparation of the MOFs under study, their structural properties have been characterised and their active centres in the metal clusters (zirconium, hafnium or cerium) have been determined. The reactivity of these MOFs and the hybrid silica-mine materials has been studied considering their catalytic centres; these reactions have been optimised by carrying out a study of the reaction mechanisms. Finally, homochiral PAF-type solids have been prepared with the binafil system, whose reactivity has also been tested. More specifically, the esterification of amides has been studied in Chapter 3. This reaction allows to convert the amides into esters, which are more versatile functional groups. This transformation has been approached from the heterogeneous catalysis via MOFs based on zirconium, hafnium and cerium of the MOF-808, UiO-66 and MOF-801 series. The most efficient catalyst for amide esterification has been MOF-808-Zr. Using TGA analysis and the adsorption of a basic probe molecule (CO) studied using FT-IR spectroscopy, the acid centres of Lewis and Brönsted present in them have been determined. Among the MOFs prepared in this work, MOF 808-Zr has a lower metal cluster connectivity and a larger pore size than UiO-66 and MOF-801; it also has the appropriate balance of acid and basic Brönsted and Lewis centres to activate the reaction substrates. The scope of n-butanol alcoholysis has been extended to a large number of substrates (primary, secondary and tertiary amides; aromatic and aliphatic). The reaction has also been studied in non-solvolitic conditions with more complex alco-hols. The catalyst is stable during the reaction and can be easily reused. The reaction mechanism in the esterification of benzamide with n-butanol catalysed by MOF-808-Zr has been investigated through kinetic analysis using the LHHW model and the in situ study of molecular interactions by FT-IR. In Chapter 4, the deuteration by isotopic deuterium/hydrogen exchange catalysed by commercial silica-supported amines using D2O as a source of deuterium has been investigated. This procedure is applicable to a wide range of substrates, such as carbonylic compounds, organophosphonium salts, nitro compounds and, even, steroid hormones. The stability of the catalyst, SiO2-(CH2)3-NH2, is maintained for up to 10 reaction uses without significant loss of activity. Finally, in Chapter 5, the synthesis and application of homochiral PAFs, in which the structure of BINOL (1,1′-binaftil-2,2′-diol) and BIN-BAM (1,1' binaftil-2,2'-disulfonimide) has been integrated, is discussed. Three new PAFs active in asymmetric catalysis has been generated: PAF-3,3'-(S)-BINOL, PAF-6,6'-(R)-BINOL and PAF 3,3'-(S)-BINBAM. In particular, PAF-6,6'-(R)-BINOL has demonstrated its catalytic activity in the alkylation reaction of aromatic aldehydes with diethyl zinc and the catalyst PAF-3,3'-(S)-BINBAM is active in the Mukaiyama aldolic reaction and the reduction of the double bond of carbonylic a,b-unsaturated compounds.
Villoria Del Álamo, B. (2021). Síntesis de catalizadores sólidos orgánicos e híbridos orgánicos-inorgánicos y su aplicación [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/163789
TESIS

In questo progetto si è studiata la sintesi del dimetiladipato (DMA) utilizzando come reagenti il ciclopentanone ed il dimetilcarbonato. Nello specifico ci si è prefissati di studiare l’effetto di alcuni parametri di reazione prestando grande attenzione al sistema catalitico e al meccanismo di reazione. Tutte le prove sono state eseguite in fase liquida in un sistema batch. Inizialmente è stato valutato l’effetto di alcuni parametri (tempo e temperatura) utilizzando ossido di zinco commerciale come catalizzatore, il quale, confermando studi precedenti, si è dimostrato essere potenzialmente un buon catalizzatore per la sintesi di interesse. In seguito, attraverso l’analisi dei dati ottenuti, si è deciso di proseguire lo studio testando diverse tipologie di catalizzatori, a partire da ossidi di zinco di sintesi a più alta area superficiale ed altri catalizzatori a base di ossidi metallici, come MgO e ZrO2, sistemi supportati, come ZnO/CeO2 e ZnO/SiO2 e, infine, un ossido misto di zinco e magnesio (Zn/Mg/O). In conclusione, attraverso le nuove tipologie di catalizzatori testati, il sistema catalitico è stato reso più attivo, sia a livello di conversione dei reagenti che di resa in dimetiladipato, ma persistono delle problematiche legate alla selettività e alla resa del prodotto di interesse.

Afin de développer une chimie plus respectueuse de l'environnement, l'accès à de nouveaux procédés est nécessaire. Plus spécifiquement, dans le domaine de l'oxydation, l'utilisation d'oxydants toxiques doit être bannie, l'utilisation de solvants limitée et l'utilisation de catalyseurs recyclables développée. Dans ce contexte, deux approches " vertes " ont été explorées. La première d'entre elle consiste à éliminer ou remplacer l'acide acétique, additif qui, en présence de H2O2 et de complexes de Mn ou de Fe, favorise la formation exclusive d'époxydes lors d'oxydation d'alcènes. Pour cela, deux stratégies ont été testées. La première consiste à introduire dans la seconde sphère de coordination de complexes de Fe(III) et de Mn(II) des fonctions fluoroalcools devant faciliter l'activation d'H2O2. Comparés aux complexes analogues non modifiés, aucune amélioration de l'activité catalytique pour l'oxydation de cyclooctène n'est observée. Cependant, des complexes de Ni(II) et de Co(II) à ligands non modifiés ont démontré une activité catalytique élevée pour la photoproduction d'hydrogène. La seconde stratégie est basée sur le remplacement de l'acide acétique. Pour cela, en utilisant des billes de silice fonctionnalisées par des fonctions COOH (SiO2@COOH) comme co-réactif, une sélectivité significative en faveur de l'époxyde est observée lors de l'oxydation d'alcènes en présence de complexes de Mn(II) et de Fe(III) à ligand BPMEN. La seconde approche concerne des réactions d'(ép)oxydation sans solvant et utilisant des catalyseurs recyclables à base de polyoxométallates (POMs). Les catalyseurs SiO2@PMo et SiO2@PW, respectivement obtenus par greffage ionique de H3PMo12O40 ou H3PW12O40 sur des billes de silices fonctionnalisées par des fonctions pendantes NH2 (SiO2@NH2). Avec une faible charge catalytique, les deux catalyseurs sont efficaces lors de réactions d'oxydation avec une meilleure sélectivité que les POM libres. De plus, les deux catalyseurs réutilisés ont donné des conversions et des sélectivités similaires après deux recyclages
In order to develop a chemistry more respectful of the environment, access to sustainable processes is mandatory. More specifically, in the field of oxidation chemistry, use of toxic oxidants has to be banished, use of solvents limited and reusable catalysts developed. In this context, two types of greener approaches have been explored. The first approach concerns removal or replacement of acetic acid, an additive - in association with H2O2, favoring exclusive formation of epoxides with Mn and Fe metal complexes as catalysts. For this objective, two strategies have been explored. The first one consists in introducing fluoroalcohol functions in the second coordination sphere of metal complexes with pyridinophane-based ligand to easily activate H2O2. Those complexes did not enhance the catalytic activity for cyclooctene oxidation reactions in comparison to analogous Mn(II) and Fe(III) complexes with unmodified ligands. However, Ni(II) and Co(II) metal complexes with unmodified ligands display interesting catalytic activity for H2 photoproduction. The second strategy aimed to replace acetic acid. Using silica beads functionalized with COOH pendant arms (SiO2@COOH) as additive and H2O2 as oxidant, catalytic epoxidation reactions catalyzed by Mn(II) and Fe(III) metal complexes with BPMEN ligand displayed significant selectivity towards epoxide. The second approach concerns organic-solvent free (ep)oxidation processes with catalysts based on polyoxometalates (POMs). Catalysts SiO2@PMo and SiO2@PW, respectively obtained by ionic grafting of H3PMo12O40 or H3PW12O40 on silica beads functionalized with NH2 pending functions (SiO2@NH2), have been fully characterized. With low catalyst loading, both catalysts displayed efficient oxidation activity and better selectivity than the free POMs. Moreover, recovered beads gave similar conversion and selectivity after two recycling processes

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
It is notable that with technological advances and scientific research, organic synthesis has provided the synthesis of several compounds that are essential to meet the needs of mankind. 3-Indolyl-glycine derivatives have been the subject of several studies, since they are precursors of non-proteinogenic amino acids that act as synthetic intermediates of compounds with important biological activity. However, the synthetic routes described in the literature for these compounds present disadvantages, since they use organic solvents, extreme temperatures, non-recoverable catalysts and long reaction periods. Thus, the search for the development of alternative methodologies has attracted great attention in Organic Synthesis in order to reduce environmental impact, reduce process costs and minimize waste formation. In view of this scenario, the proposal of a new methodology for the synthesis of 3-indolyl glycine derivatives, via a multi-component reaction (Aza-Friedel-Crafts) between indoles, ethylglyoxalate and anilines, which follow the principles established by Green Chemistry, are somewhat of great interest to be studied. After a systematic study of the reaction conditions, two synthetic methodologies were established. In the first methodology a catalyst and surfactant was used in the reaction, under ambient temperature, however this condition led to the formation of by-product from the rearrangement of the desired product. In addition, the catalytic system of this synthetic methodology presented potential to be recycled, but its (re) use showed a decrease in yields, and it is not feasible to use this methodology. Thus, another synthetic methodology was proposed, in which only surfactant was used without the use of the catalyst, with heating of 50 ºC. The second methodology was more feasible, since the yields of the products obtained with the variation of the indole substrate were excellent. The synthesized compounds were evaluated for their biological activity. Bioassays of phytotoxic activity on lettuce seeds (Lactuca sativa) were carried out, in which it was verified that these compounds interfere in seed germination and root growth. Compounds 4b, 4j and 4n showed remarkable germination inhibitory activity at the concentration of 25 ppm. In inhibition of growth, compounds 4a, 4l and 4n showed inhibitory activity already at concentrations of 10 ppm. Such compounds were as active as the glyphosate and atrazine herbicides tested. It is emphasized that compound 4n had inhibitory activity both for germination and for growth of the species studied. Thus, the compounds presented in this paper provide an experimental basis for future studies on pesticides based on 3-Indolyl-glycine derivatives, since it has potential applications for herbicidal activity.
É notório que com os avanços tecnológicos e com as pesquisas científicas, a síntese orgânica proporcionou a síntese de diversos compostos que são essenciais para suprir as necessidades da humanidade. Os compostos derivados de 3-Indolil-glicina tem sido alvo de diversos estudos, visto que são precursores de aminoácidos não proteinogênicos que atuam como intermediários sintéticos de compostos com importante atividade biológica. Entretanto, as rotas sintéticas descritas na literatura para estes compostos apresentam desvantagens, visto que as mesmas utilizam solventes orgânicos, temperaturas extremas, catalisadores não recuperáveis e longos períodos de reação. Desse modo, a busca pelo desenvolvimento de metodologias alternativas tem atraído grande atenção na Síntese Orgânica de modo a proporcionar a redução do impacto ambiental, reduzir custos do processo e minimizar a formação de resíduos. Diante desse cenário, a proposta de uma nova metodologia para a síntese de derivados de 3-indolil-glicina, via reação multicomponente (Aza-Friedel-Crafts) entre indóis, etilglioxalato e anilinas, que contemplam os princípios estabelecidos pela Química Verde, são algo de grande interesse a ser estudado. Após um estudo sistemático das condições de reacão, estabeleceram-se duas metodologias sintéticas. Na primeira metodologia foi utilizado um catalisador e surfactante na reação, sob temperatura ambiente, entretanto essa condição levou a formação de subproduto oriundo do rearranjo do produto desejado. Além disso, o sistema catalítico dessa metodologia sintética apresentou potencial de ser reciclado, porém sua (re)utilização demonstrou um decréscimo nos rendimentos, não sendo viável o uso dessa metodologia. Desse modo foi proposta outra metodologia sintética, na qual só foi utilizado surfactante sem o uso do catalisador, com aquecimento de 50 ºC. A segunda metodologia se mostrou mais viável, visto que os rendimentos dos produtos obtidos com a variação do substrato indólico foram excelentes. Os compostos sintetizados foram avaliados quanto à sua atividade biológica. Bioensaios de atividade fitotóxica em sementes de alface (Lactuca sativa) foram realizados, nos quais se verificou que estes compostos interferem na germinação das sementes e no crescimento das radículas. Os compostos 4b, 4j e 4n mostraram notável atividade inibitória de germinação na concentração de 25 ppm. Na inibição do crescimento, os compostos 4a, 4l e 4n apresentaram atividade inibitória já nas concentrações de 10 ppm. Tais compostos foram tão ativos quanto os herbicidas glifosato e atrazina testados. Salienta-se que o composto 4n teve atividade inibitória tanto para a germinação quanto para o crescimento da espécie estudada. Desse modo, os compostos apresentados neste trabalho fornecem uma base experimental para futuros estudos sobre pesticidas à base dos derivados de 3-Indolil-glicina, visto que tem aplicações potenciais para atividade herbicida.

abstract: Organic compounds are influenced by hydrothermal conditions in both marine and terrestrial environments. Sedimentary organic reservoirs make up the largest share of organic carbon in the carbon cycle, leading to petroleum generation and to chemoautotrophic microbial communities. There have been numerous studies on the reactivity of organic compounds in water at elevated temperatures, but these studies rarely explore the consequences of inorganic solutes in hydrothermal fluids. The experiments in this thesis explore new reaction pathways of organic compounds mediated by aqueous and solid phase metals, mainly Earth-abundant copper. These experiments show that copper species have the potential to oxidize benzene and toluene, which are typically viewed as unreactive. These pathways add to the growing list of known organic transformations that are possible in natural hydrothermal systems. In addition to the characterization of reactions in natural systems, there has been recent interest in using hydrothermal conditions to facilitate organic transformations that would be useful in an applied, industrial or synthetic setting. This thesis identifies two sets of conditions that may serve as alternatives to commonplace industrial processes. The first process is the oxidation of benzene with copper to form phenol and chlorobenzene. The second is the copper mediated dehalogenation of aryl halides. Both of these processes apply the concepts of geomimicry by carrying out organic reactions under Earth-like conditions. Only water and copper are needed to implement these processes and there is no need for exotic catalysts or toxic reagents.
Dissertation/Thesis
Masters Thesis Geological Sciences 2020

This thesis entitled “Organic Transformations in Water: Synthetic and Mechanistic Studies towards Green Methodologies” is in two parts. Part-I describes various synthetic studies aimed at developing improved methodologies; Part-II describes certain mechanistic studies directed towards an improved understanding of phase transfer catalysis and the hydrophobic effect. Water is uniquely advantageous as a solvent. It is environmentally benign, non-flammable, liquid over a wide temperature range and possesses a high heat capacity that makes it inherently safe. Water also catalyses chemical transformations between insoluble organic reactants. Water thus serves as a reaction medium, a product partitioner and a reaction catalyst.1 Part-I:- Reactions in Water under both Microwave and Ambient Conditions Part-I is further divided into three chapters. Chapter II deals with reactions of 2-nitroalcohols (2NAs), and is divided into three sections. Section A describes the synthesis of nitroalkanes via the microwave-assisted, water-mediated chemoselective reduction of 2NAs using tributyltin hydride (Bu Scheme 1 ). The 2NAs, synthesized from nitromethane and aldehydes (aliphatic, alicyclic, heterocyclic or m- & p-substituted aromatic aldehydes), were converted into corresponding nitroalkanes in excellent yields. The 2NAs derived either from substituted nitromethane [nitroethane, (nitromethyl)benzene, etc.] or bulky aldehydes (o-substituted aromatic aldehydes), however, failed to furnish nitroalkanes under these conditions. Also a major solvent effect was observed: the extent of conversion was greater in water than in water-polar 3SnH) as reducing agent. The chemoselective reduction of 2NAs to nitroalkanes was observed accidentally while trying to remove the nitro group of 2NAs in a Bu3SnH-AIBN-water system under microwave conditions. When equimolar quantities of 2NA and Bu3SnH were added to water, microwave irradiation led to nitroalkanes (protic solvent mixtures and the reaction did not occur either in aprotic polar or non-polar solvents. Scheme 1. Microwave assisted chemoselective reduction of 2NAs to nitroalkanes in Bu3SnH-water In Section B, the microwave assisted synthesis of nitroalkanes from nitroalkenes has been described. Equimolar quantities of nitroalkene and Bu Scheme 2 ). The nitroalkenes substituted even by bulky groups at C-1 & C-2 were converted into corresponding nitroalkanes. Hence the drawback of the method described in Section A was overcome by employing nitroalkenes as starting materials. 3SnH in water under microwave irradiation, led to excellent yields of corresponding nitroalkanes (Scheme 2). The nitroalkenes substituted even by bulky groups at C-1 & C-2 were converted into corresponding nitroalkanes. Hence the drawback of the method described in Section A was overcome by employing nitroalkenes as starting materials. Scheme 2. Microwave assisted reduction of nitroalkenes to nitroalkanes in Bu3SnH-water In Section C, the synthesis of nitroalkenes via dehydration of 2NAs in a K Scheme 3 ). Thus, the dehydration of 2NAs has been accomplished under relatively mild conditions. (It was observed that the 2NAs bearing bulky groups underwent the retro-Henry reaction rather than dehydration.) 2CO3-water system has been described. This conversion was accomplished at 0-5 °C in 5-30 minutes, the nitroalkenes being isolated in good yields (Scheme 3). Thus, the dehydration of 2NAs has been accomplished under relatively mild conditions. (It was observed that the 2NAs bearing bulky groups underwent the retro-Henry reaction rather than dehydration.) Scheme 3. Dehydration of 2-NAs in aqueous K2CO3 solution Chapter III describes the chemoselective reduction of ketoaldehydes. This was serendipitously discovered during attempted enantioselective reduction of prochiral ketones using amino acid-NaBH Scheme 4 ). The method provides a mild and efficient route for the chemoselective reduction of aldehydes under aqueous basic conditions. 4-Na2CO3 in water. When equimolar quantities of aldehyde and ketone were added to a solution NaBH4 in aqueous Na2CO3 at ambient temperature, the aldehydes were selectively reduced. Good yields of primary alcohols were generally observed with excellent chemoselectivities. Extension of this study to the selective reduction of ketoaldehydes under the above reaction conditions furnished ketoalcohols in > 70% yields with > 80% chemoselectivities (Scheme 4). The method provides a mild and efficient route for the chemoselective reduction of aldehydes under aqueous basic conditions. Scheme 4. Chemoselective reduction of ketoaldehydes with NaBH4-Na2CO3 in water Chapter IV deals with deprotection of various acetals, thioacetals and tetrahydropyranyl (THP) ethers in hexane under ambient conditions, by employing chloral hydrate as reagent. Chloral hydrate is a crystalline solid with pK2 When a a 9.66.stirred suspension of excess chloral hydrate in hexane was treated with the acetal, thioacetal or THP ether, the corresponding aldehyde, ketone and alcohol were obtained in good to excellent yields (stirred suspension of excess chloral hydrate in hexane was treated with the acetal, thioacetal or THP ether, the corresponding aldehyde, ketone and alcohol were obtained in good to excellent yields (stirred suspension of excess chloral hydrate in hexane was treated with the acetal, thioacetal or THP ether, the corresponding aldehyde, ketone and alcohol were obtained in good to excellent yields ( Scheme 5. Chloral hydrate catalyzed hydrolysis of acetals, thioacetals including THP ethers Part-II:- Mechanistic Studies on Phase Transfer Catalysis and The Hydrophobic Effect Part-II is in two chapters. Chapter V describes a study of the mechanism of the phase transfer catalyzed (PTC) nucleophilic reaction of cyanide ion with alkyl halides in decane ( Scheme 7 ). In the extraction mechanism proposed earlier,3 the PTC forms the mixed species, tributylhexadecylphosphonium cyanide (THPB), which is believed to be more soluble in decane than is the starting cyanide. A problem with this explanation is that the positive free energy of transfer of the cyanide ion from the aqueous to the organic phase, which is unlikely to be offset by solvation energy of the hexadecyl and butyl groups. Scheme 6. Cyanide displacement reaction of 1-chloro octane3 The present studies explore the possibility that the reaction occurs via the formation of aggregates resembling reverse micelles ( Figure 1 ). In these, the hydrocarbon residues point outwards, with the ionic species ensconced in a deeply embedded interior along with a certain number of water molecules. Thus, the ionic species are not only shielded from the organic medium, but also stabilized in a relatively polar micro-environment (largely via dipolar interactions and hydrogen bonding). It is assumed that this stabilization energy surpasses the positive free energy of transfer of cyanide ion from aqueous to the organic phase. Figure 1. Typical representation of cyanide displacement reaction in THPB-decane-water micellar pool In fact, NMR studies on the structural dynamics of THPB in solution offered evidence of aggregation. Also, a correlation between the structures of catalyst and reactant was observed in studies with various other PTC’s. Chapter VI deals with the mechanism of the Diels-Alder reaction (DAR) in water. The concept of the hydrophobic effect (HE)4 and preferential hydrogen bonding of water with the polarized transition state5 have been invoked to explain the apparent acceleration of Diels-Alder reactions in water. The present studies explore the possibility that the highly polar water microenvironment stabilizes the transition state. Semi-quantitative rate studies of DAR involving water soluble reactants indicate that the possible role of solvation and hydrogen bonding on the polarized transition state as the key factor in the rate enhancement of water mediated DAR. The DAR in the presence of a catalytic amount of water along with the organic solvent catalyzed the reaction more efficiently, as compared to the reaction in pure organic solvent. It was also observed that there was a prominent effect of traces of water on the rate in solvent-free conditions. .

Le 21e siècle est le berceau d’une conscientisation grandissante sur les impacts environnementaux des processus utilisés pour synthétiser des molécules cibles. Parmi les avancées qui ont marqué ces dernières décennies, il est également question de réduction de déchets, de conservation de l’énergie et de durabilité des innovations. Ces aspects constituent les lignes directrices de la chimie verte. De ce fait, il est impératif de développer des stratégies de synthèse dont les impacts environnementaux sont bénins. Dans ce mémoire nous présentons la synthèse, la caractérisation et l’étude des propriétés catalytiques en milieu aqueux d’un ligand composé d’une unité -cyclodextrine native, d’une unité imidazolium et d’une chaine alkyle à 12 carbones. Ce ligand hybride s’auto-assemble dans l’eau sous forme de micelles, permettant ainsi d’effectuer en sa présence des couplages de Suzuki-Miyaura dans l’eau, avec de bons rendements. La fonctionnalisation de la face primaire de la -cyclodextrine par un noyau alkyl-imidazolium, précurseur de ligand de type carbène N-hétérocyclique, a permis le développement d’un système catalytique vert et hautement recyclable. Dans un deuxième temps, nous présentons l’utilisation du même ligand hybride dans des couplages de Heck dans l’eau, démontrant ainsi la versatilité du ligand.
Chemistry keeps evolving in new directions. Research has provided improved methodologies for the design and synthesis of targeted molecules. At the same time, the 21st century is witnessing increasing concern about the environmental impacts of chemical wastes. A new philosophy of chemical research and engineering has emerged, known as «Green chemistry». This concept encourages the design of products, processes and technologies that minimize the use and generation of hazardous substances. Therefore, there is an urge to develop environmentally friendly process to convert molecules into product of interest. In the present thesis, we describe the synthesis, characterization and catalytic properties of a novel alkylimidazolium-modified β-cyclodextrin (-CD). Our strategy was to construct a single amphiphilic bimodal ligand by the combination of a mass transfer unit (-CD), covalently bound to a ligand moiety (alkylimidazolium, an N-heterocyclic carbene (NHC) precursor) for aqueous catalysis. First, we demonstrated that the introduction of a dodecyl chain on the imidazolium moiety attached to the primary face of a native β-CD allows the formation of a highly active micellar self-assembled catalytic system in neat water with remarkable recyclable properties for the Suzuki–Miyaura coupling. In addition, we studied the versatility of this self-assembled bimodal system by performing Heck coupling in neat water.