Dissertations / Theses on the topic 'Aldol condensation reaction'

Résumé anglais uniquement
Nowadays there is an urgent need to develop green chemical processes, where the use and generation of toxic substances can be avoided. Indeed, the lignocellulose feedstock destructuration will produce aqueous solutions of ketones or aldehydes and it would be an important breakthrough to develop solid base catalysts capable to promote the aldol condensation. In this thesis, the main results are shown as follows: Magnesium and rare earth mixed oxides (MgReOx), rare earth modified MgAl-HT catalyst were prepared and were evaluated in liquid phase acetone self-aldolization. Rare earth modified MgAl catalysts show enhanced catalystic activity than MgReOx catalysts. Rehydrated MgAl-HT modified with Y and La, also present a higher water tolerance for aldol reaction. The same catalysts were also applied to acetone gas phase self-condensation reaction. At low temperature, the mesityl oxide is the main product for all the catalysts. At high temperatures, deactivation rate is lowered over MgAlCe(Y)O catalysts, and the presence of trimers (selectivity of IP over 50%) is much more noticeable for the MgAlY(Ce)O catalysts. A good balance between basicity and acidity is proposed to increase the selectivity of IP. In the cross condensation of citral and acetone, the citral conversion and pseudoionone yield were significantly enhanced over Mg3AlaY1-aOx catalysts. A general mechanism of reaction was proposed that the Y modified MgAl mixed oxides undergoes the rehydration by the water formed during the reaction, and the rehydrated catalysts with active Brønsted basic sites are responsible for the significantly improvement of catalytic activity

Atmospheric aldol self-reactions of octanal, heptanal and hexanal in a range of aqueous H2SO4 w/v% concentrations as a catalyst were studied in both bulk liquid-liquid experiments and gas-liquid experiments. Initially, a new practical methodology was developed and enhanced to monitor aldol reactions in aqueous acidic media. The evaluation of a quenching and extracting method were performed, confirming the suitability, reliability and reproducibility of the extraction method. In bulk studies, aldol products of the three aldehydes were separated and identified by preparative HPLC, GC-MS and NMR. The major aldol products observed at high acid concentrations were alpha,β-unsaturated aldehyde (dimer), trialkyl benzene (trimer) and tetraalkylcycloocta-tetraene (tetramer). The trimer of octanal was formed as trioxane in low sulfuric acid concentration and the possible mechanism accretion reaction pathways of high and low acid concentrations are proposed in this study. A systematic kinetic study of octanal, heptanal and hexanal in the bulk experiments at 65, 60 and 55 w/v% H2SO4 at 294 K were monitored using gas chromatographic equipped with a flame ionisation detector (GC-FID). The rate constants were generally estimated using second order kinetics and observed to increase as a function of sulfuric acid concentrations and also as the chain length of aliphatic aldehyde increased. The aldol self-reaction in the bulk experiment was too fast at room temperature to be easily measured using a quenching method therefore attempts were made to follow the reaction at low temperature (0 °C). The result at low temperature indicated that the rate constant of aldehyde was reduced but there was an issue of rapid rise in temperature as a result of mixing concentrated sulfuric acid with aqueous solution of the aldehyde. A gas bubbling system was developed which better simulates atmospheric reality, and which also resolves the issue of temperature rise on mixing. Two different methodologies were used: one in which the aldehyde was continually added, and one where a fixed amount was added from the gas phase and the reaction was then allowed to proceed, monitored at selected time intervals. The precision and accuracy of the fixed method was then further improved by the addition of an internal standard (IS). Using this, the concentrations of aliphatic aldehydes (C6-C8) were calibrated using an experimentally determined response factor and used to follow the loss of the reactant aldehydes. Similar methods were applied to the aldol dimers (C6-C8), which were purified and used to calibrate the chromatographic response. The rate constant for octanal, heptanal and hexanal at 76 wt% and 294 K were 0.0969 M-1 s-1, 0.1497 M-1 s-1 and 0.2622 M-1 s-1 respectively. There are some observations based upon the results presented in this thesis that may be of atmospheric significance: (i) phase separation between organic and aqueous layers in both the bulk experiment and in the bubbling system; (ii) the acid strength dependence and concentration-dependence of the various products; (iii) the faster rates than previously reported, and variation between bulk and bubbling; and (v) the time-dependent colour changes. Further work to explore these observations is proposed.

O dióxido de carbono no estado supercrítico (CO2-SC) tem despertado considerável interesse nos últimos anos como um novo solvente para reações orgânicas. Nesta tese foi investigada a influência do uso de CO2 supercrítico, associado ou não a líquidos iônicos ou cossolventes, como solvente em reações químicas visando à obtenção de precursores quirais. Foram estudadas as reações de condensação Aldólica, de Morita-Baylis-Hillman (MBH) e do tipo adição de Michael, empregando Organocatálise quando conveniente, isto é, catalisadores provenientes de aminoácidos e ácidos carboxílicos. As reações de MBH foram otimizadas através de um planejamento experimental e sua condição ótima se deu a 70°C, 110 bar, com 6 equivalentes de H2O, tempo reacional de 2h30 min e sem a presença de liquido iônico, tendo um rendimento de 84,6%. Para as condensações aldólicas os melhores resultados com acetona e p-nitrobenzaldeido como materiais de partida foram obtidos a 150 bar e 40°C, com a presença de liquido iônico, em 2 horas de tempo reacional com um rendimento de 54,0% e um excesso enantiomérico de 79,0% utilizando o catalisador (2S,4R)-4-(terc-butildimetilsililoxi)pirrolidina-2-ácido carboxílico. Com ciclohexanona como material de partida foram obtidos a 150 bar e 40°C com a presença de um doador de prótons (resina de troca iônica) em 2 horas de tempo reacional com um rendimento de 70,9% e um excesso enantiomérico de 91,2%, utilizando o catalisador (2S,4R)-4-(terc-butildimetilsililoxi)pirrolidina-2-ácido carboxílico. Outros aldeídos e cetonas utilizados como materiais de partida apresentaram rendimentos menores. Estudos de comportamento de fases foram feitos para os materiais de partida, catalisadores e produtos da reação de condensação Aldólica. Os melhores rendimentos foram obtidos em situações em que os materiais de partida e os catalisadores eram solúveis na fase supercrítica, mas os produtos não, formando uma segunda fase.
Supercritical carbon dioxide (sc-CO2) has attracted considerable interest in the last years as a new solvent for organic reactions. In this thesis, the influence of supercritical CO2 use, associated or not to ionic liquids or cosolvents, as a solvent for chemical reactions aiming at the synthesis of chiral precursors was studied. Aldol condensation, Morita-Baylis-Hillman (MBH) and Michael addition reactions were studied, employing organocatalysis when it was convenient, i.e., catalysts derived from aminoacids or carboxylic acids. MBH reactions were optimized through experimental design, resulting in a maximum yield of 84.6% for the optimal condition at 70°C, 110 bar, and 6 equivalents of H2O, reaction time of 2h30 min and the absence of ionic liquids. For the Aldol condensation reactions employing acetone and p-nitrobenzaldehyde, a maximum yield of 54.0%, with an enantiomeric excess of 79.0% was obtained at 150 bar, 40°C, 2h reaction time, in the presence of ionic liquid, using the catalyst (2S,4R)-4-(terc-butyldimethylsililoxy)pirrolidine-2-carboxylic acid. The yields were significantly lower for other aldehydes and ketones. Yields for Michael addition reactions were very low and their study was discontinued. Phase behavior studies were performed with starting materials, catalysts and products for the Aldol condensation reactions. The best yields were obtained for situations where the starting materials and catalysts were soluble in the supercritical phase and the products were not, forming a second phase.

La reaction de wittig-horner realisee dans des conditions douces (milieu aqueux peu basique) a l'aide de composes dicarbonyles permet d'acceder par bisaldolisation a des cyclenols alpha -fonctionnalises. Grace a cette technique douce, la reaction de wittig-horner est chimioselective et ne s'effectue que sur les sites carbonyles tres actifs (aldehydes)

Cette these presente la synthese et la reactivite de triflates du germanium en tant qu'agents de germylation et catalyseur acide de lewis. Le premier chapitre decrit plusieurs voies de synthese de mono- et ditriflates du germanium par action de l'acide triflique sur differents composes organomettaliques. Le deuxieme chapitre est consacre a la germylation de nombreuses fonctions organiques a partir des triflates du germanium ou de chlorogermanes. Pour ces deux voies de synthese, une etude mecanistique est menee afin d'interpreter la regiochimie et la stereochimie de la germylation. Le troisieme chapitre met en evidence l'activite catalytique des triflates germanies en tant qu'acide de lewis dans la reaction d'aldolisation croisee entre les enols o- et c- germanies et un aldehyde, un acetal ou une imine. La diastereoselectivite observee pour ces reactions a pu etre interpretee a partir d'un mecanisme d'approche a interactions steriques et electrostatiques minimales faisant intervenir des etats de transitions ouverts ou cycliques. La reaction de friedel et crafts, sous catalyse par le triflate de trimethylgermanium, fait l'objet du dernier chapitre.

Dans le cadre des substances antiappetantes pour insectes phytophages, nous presentons la premiere synthese totale de la bisabolangelone. Il s'agit d'un antiappetant sesquiterpenoide, present dans angelica silvestris. La strategie de synthese, fait appel a une reaction tres peu exploitee : l'additioon intramoleculaire d'un alcool sur une triple liaison. Cette reaction permet d'acceder au motif (methyl-3 butene-2 ylidene)-2 tetrahydrofuranne de facon stereospecifique. Dans un premier temps, l'etude d'un modele nous a permis de connaitre la versatilite et les limites d'application de cette reaction. Apres plusiurs tentatives infructueuses, nous sommes parvenus au produit cible. Au cours de cette synthese, nous avons ete confrontes aux reactions suivantes : aldolisations ; additions de lithiens acetyleniques ; cycloadditions 1-3 dipolaires ; protections et deprotection selectives de polyols

Depuis bien une dizaine d'annees, une des activites de notre laboratoire est le developpement de nouvelles methodologies de synthese en vue d'acceder efficacement a une famille de composes particuliers que sont les bakkanes. Ils sont caracterises par la presence d'un squelette hydrindanique et d'une spiro, methylene, butyrolactone qui est a l'origine des activites biologiques tres diverses des bakkanes. Notre laboratoire avait developpe une approche souple et efficace des spirolactones hydrindaniques. Elle avait permis la synthese du ()- et du (+)-bakkenolide-a, du ()-homogynolide-b, du ()- et du (-)-homogynolide-a et du ()-palmosalide-c mais s'est averee infructueuse pour la synthese du 9-acetoxyfukinanolide. Au cours de ce travail, nous avons realise les premieres syntheses du ()- et du (-)-9-acetoxyfukinanolide avec une totale stereoselectivite. Notre strategie fait intervenir 3 etapes cles dont la formation du squelette hydrindanique par expansion de cycle, la formation de la spirolactone par cyclisation radicalaire d'un -cetoester propargylique par le mn(iii) et une reaction de retroaldol-aldolisation qui permet d'acceder a la stereochimie des bakkanes naturels. A partir d'un intermediaire cle de cette synthese, nous avons pu acceder rapidement au dihydrofukinolidol, bakkane non naturel, intermediaire central des bakkenolides difonctionnalises. Ce travail nous a permis par ailleurs, de developper une nouvelle methodologie de formation d'-acyl, methylene, butyrolactones par cyclisation radicalaire de -cetoesters propargyliques obtenus par transesterification en milieu neutre de -cetoesters methyliques.

Les réactions de métathèse sont des méthodes performantes pour la création de doubles liaisons carbone-carbone et leurs popularités s'expliquent par l'accessibilité des catalyseurs nécessaires à celles-ci et par la facilité de mise en oeuvre de ces réactions. Elles ont par ailleurs trouvé de nombreuses applications dans la synthèse de molécules naturelles.Les aurisides A et B sont des molécules naturelles d'origine marine isolées du lièvre des mers Dolabella Auricularia en 1996. Ces macrolides présentent une activité cytotoxique intéressante contre des lignées de cellules cancéreuses HeLaS3 avec des valeurs d'IC50 de 0,17 et 1,2 μg/mLrespectivement.Nous avons dans un premier temps développé une voie d'accès au fragment C1-C9 des composés naturels en se basant sur la réaction de métathèse croisée des oléfines. Une étude sur le mode formation de la structure macrocylique par un processus séquentiel impliquant une réaction demétathèse cyclisante et une cétalisation transannulaire a ensuite été conduite sur des composés modèles permettant l'obtention de macrolactones analogues. Cette méthodologie a ensuite été appliquée à la synthèse stéréocontrôlée du squelette carboné des aurisides seulement dépourvu de sa chaîne latérale attaché sur l'atome de carbone C13.Enfin la réaction de métathèse croisée a également été exploitée dans un processus tandem avec celle d'hydrogénation pour la synthèse énantiosélective du 6-hydroxydodécanoate de pentadécyle,composant principal de l'huile essentiel Ylang-Ylang, et qui est également utilisé en médecine traditionnelle contre le choléra.

碩士
國立中正大學
化學暨生物化學研究所
102
Asymmetric synthesis of highly enantioselective steroid skeleton with six stereogenic centers has been achieved by a sequential organocatalyzed Michael-Michael-aldol condensation and Henry reaction with nitroalkane and α,β-unsaturated aldehyde.

碩士
國立中正大學
化學暨生物化學研究所
106
We refered to Wang’s thesis, sythesized the N-heterocyclic carbenes (NHCs) molecules, (Mesbim)(CH2)11SH (8), used gold nanoparticles anchored thiol protecting groups [Au-SR] (R = CH3(CH2)6CH2SH) (9) as the carrier, and exchanged part of protecting groups to (Mesbim)(CH2)11SH (8), finally we got gold nanoparticles supported catalyst RS-Au-Smes (10). The other side, we sythesized another NHCs molecular catalyst, [HOOCMMIM][PF6] (2), and anchored on ZnO nanoparticles to make the zinc oxide nanoparticles supported catalysts ZnO-[HOOCMMIM][PF6] (3). According to theese nanoparticles supported organic molecules could be well dispersed in organic solvents, we did the quick and accurate structure identification by solution NMR and TEM. NHCs were usually applicated on forming C-C bond between aldehydes, therefore, we utilized the NHCs molecular catalyst, [HOOCMMIM][PF6] (2), on aldol condensation reaction. In addition, the NHCs ion liquid could make aldehydes nucleophilic during the condensation catalysus, so we also attempted to catalize nucliphilic substution reaction, these catalytic consequents of two reactions were compared with zinc oxide nanoparticles supported catalysts ZnO-[HOOCMMIM][PF6] (3). We discover the catalytic consequents were very close, this result illstrated that the ZnO nanopaticles as carrier would not reduce catalytic activity of organic catalysts. Finally, we did the recycling and re-catalization test of ZnO-[HOOCMMIM][PF6] (3), we found the nanoparticle catalysts could make 85 % catalysis yield after 12 recycles. That was to say, the nanoparticle-supported molecular catalysts would cut the cost of producing the molecule, by the way, it could decrease the recycling time and the unnecessary wastes.