Orientador: Carlos Roque Duarte Correia / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-25T12:41:45Z (GMT). No. of bitstreams: 1 Silva_AllanRibeiroda_M.pdf: 5660730 bytes, checksum: 71d03bc58e1f2eb29f270eee660d5e18 (MD5) Previous issue date: 2013 / Resumo: Nos últimos anos, o emprego da reação de Heck-Matsuda tem atraído nteresse de diversos grupos de pesquisa como alternativa conveniente aos protocolos tradicionais da reação de Heck. Com o objetivo de obter os compostos bioativos fempiprano (12), tolpropamina (14), fendilina (15), prenilamina (17) e droprenilamina (18) neste trabalho avaliamos a arilação de Heck-Matsuda de aminas alílicas N-protegidas. Entretanto, esta metodologiamostrou-se problemática devido a baixa regiosseletividade e dificuldades na purificação dos produtos. Como alternativa, a arilação de Heck com sais de diazônio do acrilato de metila foi utilizada para a obtenção da unidade diarilmetano na forma do éster 3,3-difenil-propanoato de metila (67), intermediário comum na síntese dos compostos 12, 15, 17, 18. Conversão do éster 67 no ácido carboxílico 71, seguido da reação com diferentes aminas, contendo a substituição desejada, permitiu a síntese das amidas correspondentes, que foram reduzidas com AlH3, levando aos produtos alvos deste estudo, com rendimentos globais entre 38 e 61% em 5 etapas a partir do acrilato. Para a síntese da tolpropamina (14) foi estudada a arilação de cinamatos de metila com sais de diazônio. O melhor resultado foi observado quando foi utilizado o 4-bromo-cinamato de metila e o sal de tetrafluorborato 3-cloro-4-metil-benzenodiazônio, resultando no cinamato -arilado (97) em rendimento de 83% em uma relação diasteroméricas em favor do produto de configuração E (E/Z = 11/1). Em seguida, o éster obtido foi hidrolisado, transformado em uma amida e reduzido com AlH3, resultando na amina 14 com rendimento global de 47% em 5 etapas a partir do cinamato. De uma maneira geral, a reação de Heck-Matsuda mostrou-se eficiente para obter os compostos desejados, com rendimentos globais entre 38 e 61% em 5 etapas de reação / Abstract: In the last few years applications of the Heck-Matsuda reaction have been attracting the interest of many research groups as a convenient alternative to the conventional Heck reactions. Aiming at the preparation of the bioactive compounds fempiprano (12), tolpropamine (14), feniline (15), prenylamine (17) and droprenylamine (18), we have initially evaluated the Heck-Matsuda arylation of protected N-allylamines. However, this strategy proved to be problematic due to its low regioselectivity and some difficulties in the purification of the compounds. As an alternative, the Heck arylation of methyl acrylate with aryldiazonium tetrafluoroborates was employed for the construction of the diarylmethane unit as the methyl 3,3-diphenylpropanoate (67), a common intermediate for the synthesis of compounds 12, 15, 17, and 18. Transformation of ester 67 into the carboxylic acid 71, followed by the reaction with several different amines containing the appropriate substitution pattern, has allowed the synthesis of the corresponding amides. These were reduced with AlH3 leading to the desired targets of this study in overall yields of 38% to 61% over 5 steps from the starting acrylate. For the synthesis of tolpropamine (14), we evaluated the Heck arylation of methyl cinnamates with aryldiazonium salts. The best result was obtained when we used 4-bromomethylcinnamate and 3-chloro-4-methylbenzenediazonium tetrafluoroborate, thus providing the beta-arylated cinnamate 97 in 83% yield in a diastereomeric ratio in favor of the Ediastereomer of 11:1. Next, the ester obtained was hydrolyzed, converted into an amide and reduced with AlH3 providing amine 14 in an overall yield of 47% over 5 steps from the methyl cinnamate. Overall, the Heck-Matsuda reaction proved to be an efficient method to prepare the desired targets in yields varying from 38-61% yield over 5 steps / Mestrado / Quimica Organica / Mestre em Química

Orientador: Carlos Roque Duarte Correia / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-22T19:40:59Z (GMT). No. of bitstreams: 1 Biajoli_AndreFranciscoPivato_D.pdf: 15667381 bytes, checksum: c96d7fd628b3e5359cce9f6bbe7c724c (MD5) Previous issue date: 2013 / Resumo: Tetrafluoroboratos de arenodiazônio são compostos estáveis e de fácil preparo que têm sido largamente empregados na reação de Heck-Matsuda, permitindo o desenvolvimento de métodos rápidos, brandos e livres de fosfinas. No tocante à arilação direta de compostos (hetero)aromáticos, uma metodologia que emergiu na década de 2000 e que dispensa a necessidade de pré-funcionalização de ambos os parceiros de acoplamento, sais de arenodiazônio foram empregados com sucesso como fontes de radicais arílicos. Por outro lado, a arilação direta de (hetero)aromáticos com sais de arenodiazônio através da catálise por metais de transição havia sido relatada, até há pouco, em apenas um trabalho na literatura (de 1999), com os rendimentos obtidos sendo, na melhor das hipóteses, modestos. Isto posto, resta claro que o desenvolvimento de uma metodologia que explore sais de arenodiazônio em arilações diretas catalisadas por metais de transição seria um avanço importante na química destes sais. Com isso, no presente trabalho foi desenvolvida uma metodologia rápida e em condições brandas para a arilação de indóis, benzofurano e benzotiofeno empregando-se paládio como catalisador. A alta nucleofilicidade dos indóis, que tendem a reagir com sais de arenodiazônio formando compostos azo (corantes), pôde ser contornada, com os produtos monoarilados desejados sendo obtidos com altas regiosseletividades e bons rendimentos. Também foi estudado o comportamento de outros heteroaromáticos, como furanos e o tiofeno, em arilações diretas com sais de arenodiazônio via paládio. Estudos mecanísticos forneceram evidências de que as reações apresentadas operam a partir de uma espécie altamente eletrofílica de arilpaládio catiônico que vem a ser atacada pelos compostos heteroaromáticos eletronicamente ricos / Abstract: Aryldiazonium tetrafluoroborates are stable, easy-to-prepare compounds that have been largely employed in Heck-Matsuda reactions, allowing the development of fast, mild and phosphine-free methods. Regarding direct arylations of (hetero)aromatic compounds, an area of research that emerged at the beginning of the current century, arildiazonium salts have been employed mainly as radical sources; on the other side, only one example in the literature (dating from 1999) presented arylations of heteroaromatic compounds with aryldiazonium salts in a non-radicalar, transition metal-catalyzed process, with poor yields being observed. With that in mind, it is clear that a methodology exploiting the full potential of aryldiazonium salts in a non-radicalar fashion is highly desirable. Therefore, in the present work a methodology for the direct arylation of indoles, benzofuran and benzothiophene employing palladium as catalyst is presented. The high nucleophilicity of indoles, that are prone to react with these salts to furnish azocompounds (dyes), could be surpassed, with the desired monoarylated products being obtained with both high yields and regioselectivity. The behaviour of 2-methylfuran and thiophene was also investigated. Mechanistically, evidences pointing to the formation of a highly electrophilic cationic arylpalladium species that is attacked by the electronrich heterocycles are presented / Doutorado / Quimica Organica / Doutor em Ciências

Orientador: Carlos Roque Duarte Correira / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-20T23:15:33Z (GMT). No. of bitstreams: 1 Prediger_Patricia_D.pdf: 29103926 bytes, checksum: bd694717759d7b58fda99bfb77a7fa06 (MD5) Previous issue date: 2012 / Resumo: O presente trabalho foi centrado na arilacao de Heck-Matuda de diferentes olefinas com sais de arenodiazonio e a aplicacao dos produtos arilados na sintese de compostos bioativos. O trabalho esta dividido em dois capitulos: 1) Reacoes de acoplamento de Heck-Matsuda entre aminas alilicas e sais de arenodiazonio e suas aplicacoes nas sinteses de compostos bioativos. 2) Estudos da reacao de Heck-Matsuda em liquidos ionicos e suas aplicacoes na sintese de derivados C-azanucleosideos, potenciais compostos antituberculose. Com relacao a primeira parte do trabalho, foi desenvolvida uma metodologia abrangente para a reacao de Heck-Matsuda entre alilaminas e sais de arenodiazonio. Foram empregados diversos derivados de aminas alilicas e diferentes sais de arenodiazonio contendo grupamentos doadores, retiradores de eletrons e grupos volumosos. Para todos os casos foram obtidos rendimentos de bons a excelentes, em alta regio- e estereosseletividades em favor do produto ¿×- arilado de configuracao trans. Adicionalmente, a aplicacao deste protocolo forneceu os compostos bioativos naftifina, abamina, abamina SG, alverina e cloridrato de cinacalcet, tendo como etapa-chave a reacao de Heck altamente seletiva. A segunda parte do trabalho envolveu as reacoes de Heck-Matsuda entre a ftalimida alilica e sais de diazonio liquidos ionicos. Nestas reacoes, foram obtidos rendimentos e seletividades semelhantes aos observados com o solvente convencional benzonitrila. Alem disso, foram estudadas reacoes com geracao in situ de sal de hexafluorfosfato de arenodiazonio em [bmim] [PF6], seguida pela reacao de Heck-Matsuda em procedimento ¡§one pot¡¨. Por fim, foram realizadas as sinteses de dois derivados de C-azanucleosideos, tendo como etapa-chave a reacao de Heck-Matsuda entre um enecarbamato endociclico e sal de arenodiazonio. Estes compostos terao suas atividades antituberculose avaliadas pelo grupo de pesquisa do professor Mourey em Toulouse, na França / Abstract: The present work was focused in the Heck-Matsuda arylation of several olefins with arenediazonium salts and in the application of the arylated products as intermediates in the syntheses of bioactive compounds. The work is divided in two chapters: 1) Heck-Matsuda reactions between allyl amines and arenediazonium salts and their applications in the synthesis of bioactive compounds, 2) Studies of the Heck-Matsuda reaction in ionic liquids and its application to the synthesis of Cazanucleosides, which are potential antituberculosis compounds. Regarding the first part of this work, a comprehensive methodology for the Heck-Matsuda reaction between allylamines and arenediazonium salts was developed. Several allyl amines derivatives and differents arenediazonium salts were sucessfully employed. Both electron donating and withdrawing groups, as well as bulky substituents, were well tolerated in the diazonium salt. In all cases good to excellent yields and high regio- and stereoselectivities in favor of the ¿×-trans arylated products were obtained. Additionally, some of the adducts prepared by this highly selective Heck reaction were employed as intermediates in the total synthesis of the bioactive compounds naftifine, abamine, abamine SG, alverine and cinacalcet hydrochloride. The second part of this work adressed the Heck-Matsuda reaction between allylic phthalimide and arenediazonium salts in ionic liquids. Under the investigated conditions, the yields and selectivities were similar to those previous achieved with the conventional solvent benzonitrile. In addition, we evaluated the in situ generation of the 4-fluorbenzenediazonium hexafluorophosphate salt in [bmim][PF6], followed by the Heck-Matsuda reaction in a one pot procedure. Finally, we carried out the synthesis of two C-azanucleosides using the Heck-Matsuda reaction with an endocyclic enecarbamate as the key step. As a further development of this work, these compounds will be evaluated regarding their potential antituberculosis activity by Professor Mourey's research group in Toulouse, France / Doutorado / Quimica Organica / Doutora em Ciências

Ce travail de thèse réalisé à l’Institut de Chimie Moléculaire de l’Université de Bourgogne et en collaboration avec le PET Research Centre, porte sur la synthèse d’une nouvelle classe de pinces à fluorures dérivés d’aminoacides dans le but de piéger les ions [18F]-fluorures par formation d’une liaison B-F et d’évaluer leur potentiel en tant qu’agent d’imagerie TEP. Les travaux ont tout d’abord concerné la conception, la synthèse et la caractérisation des nouveaux sels de phosphoniums boronatés et trifluoroborates dérivés d’aminoacides. Ainsi, par quaternisation de l’o-boronate phényl phosphine avec des β-iodo amino esters ou des γ-iodo amino esters, les sels correspondants sont obtenus sans racémisation et avec des rendements atteignant 88%. La saponification des phosphoniums boronatés aminoesters donne les dérivés avec la fonction acide libre, tandis que l’acidolyse par HCl mène à l’amine correspondante offrant ainsi, l’opportunité d’un couplage ultérieur à une biomolécule. Ensuite, les dérivés trifluoroboratés sont facilement préparés par réaction de KHF2 en solution dans un mélange hydroalcoolique. Les études de stabilités en milieux aqueux des phosphoniums o-trifluoroborates aminoacides ont permis d’établir que ces dérivés sont extrêmement stables à l’hydrolyse. Enfin, la [18F]-radiosynthèse des sels de phosphonium boronatés a été étudiée selon deux méthodes: par échange isotopique 18F-19F direct à partir d’un trifluoroborate et par marquage direct d’un sel de phosphonium boronaté en présence d’un mélange de fluorures [18F] et KHF2. Intéressement, après une synthèse totale de 50 minutes comprenant le séchage azéotropique, la synthèse et la purification, [18F]-203c a été obtenu avec un rendement radiochimique de 10% corrigé de la décroissance, une pureté radiochimique ≥97% et une activité spécifique de 0.13 GBq/µmol. / This thesis project, which is part of a collaboration between the Institut de Chimie Moléculaire de l’Université de Bourgogne and the Positron Emission Tomography Research Centre, is about the synthesis of fluoride pincers derived from amino acids based on 18F-B bond construction to get a new class of PET imaging agents. First, this project concerned the design, synthesis and characterisation of new boronato and trifluoroborato phosphonium amino acid salts. Quaternisation of o-boronate phenyl phosphine with β-iodo amino esters or γ-iodo amino ester leads to the corresponding salts without racemisation and in yields up to 88%. Saponification of boronato phosphonium amino esters afford the free carboxylic acid derivatives, whereas HCl acidolysis leads to the corresponding amino compounds which offers the opportunity of further biomolecule coupling. Then, o-trifluoroborate phosphonium salts are efficiently prepared by reaction with KHF2 in solution on hydroalcoholic mixture. The kinetic stabilities of these o-trifluoroborate phosphoniums have shown extremely stable compounds to hydrolysis. Finally, [18F]-radiosyntheses of phosphonium salts was studied according to two methods : by 18F-19F isotopic exchange from trifluoroborate or by carrier added preparation of [18F]-fluoride ions from boronate phosphonium salts. Satisfactingly, after a total synthesis of 50 minutes (including azeotropic drying, synthesis and purification), [18F]-203c was obtained with a RCY on 10% decay corrected, a RCP ≥ 97% and a specific activity of 0.13 GBq/µmol.

Dans le cadre du développement des réacteurs de génération IV, une des voies de recherche concerne le développement des réacteurs à neutron rapide à caloporteur sodium. Le CEA a pour projet la construction d'un prototype de réacteur de ce type appelé " ASTRID ". En réponse aux besoins de développement de ce prototype, des recherches sont menées sur la disponibilité et, en particulier, sur la réduction des temps de lavage du sodium résiduel des assemblages de combustible, lors de leur déchargement. En effet, le lavage étant réalisé avec de l'eau, qui est très réactive avec le sodium, celle-ci est amenée de façon très progressive pour le traitement. Une solution alternative, actuellement à l'étude au CEA, et qui fait l'objet de ce mémoire de thèse, consiste en l'utilisation de solutions aqueuses salines permettant de ralentir la cinétique de la réaction du sodium avec l'eau. Ce travail de thèse présente les différents sels évalués et tente d'expliquer leur mécanisme d'action. / Within the framework of the development of generation IV reactors one of the research tracks is related to the development of fast neutron reactors using fluid sodium heat transfer...

Please read the abstract in the section 00front of this document. / Thesis (DPhil)--University of Pretoria, 2010. / Chemistry / unrestricted

No description available.

La récupération et le recyclage des systèmes catalytiques dans la formation de liaisons carbone-carbone reste un défi scientifique important pour des raisons économiques et environnementales. Leur immobilisation sur des polymères insolubles permet une séparation simple par filtration et une purification facile des composés finaux. Les organosilices sont des gels de silice modifiés par des fragments organiques. Elles ont été appliquées comme supports pour une grande variété de catalyseurs. Dans ce travail, différentes organosilices ont été préparées par le procédé sol-gel ou par des méthodes de post-fonctionnalisation. Les matériaux contenant des alkylidènes de ruthénium ont été testés pour des réactions de métathèse d'oléfines, tandis que ceux qui sont dérivés de prolinamides sont des organocatalyseurs chiraux efficaces pour les aldolisations asymétriques (recyclage possible jusqu'à 5 fois). Enfin, on a contrôlé les propriétés morphologiques et texturales des silsesquioxanes pontées en ajustant les conditions de synthèse lors de l'hydrolyse-polycondensation de sels d'imidazolium silylés contenant des fonctions urée. / The recovery and recycling of catalytic systems in carbon – carbon bond forming reactions remains a scientific challenge of economical and environmental relevance. Their immobilization onto insoluble polymers allows a simple separation of the final compounds by filtration and an easy purification. Organosilicas are silica gels modified with organic moieties, which have been applied as versatile supports for a great variety of catalysts. In the present work, several organosilicas have been prepared by sol-gel procedures and post-functionalization methods. Some materials containing ruthenium alkylidenes were successfully tested in olefin metathesis reactions, whereas silica-supported prolinamides resulted in efficient chiral organocatalysts in asymmetric aldolizations (recycling up to 5 runs possible). Finally, the control of the morphologic and textural properties of self-assembled bridged silsesquioxanes was possible by adjusting the synthetic conditions in the hydrolytic polycondensation of silylated imidazolium salts containing urea functions.

Quaternary ammonium salts are surface active bactericides. A mechanism of their biological activity has been well studied experimentally, and it encompasses two stages. The first stage involves electrostatic interactions of polar functional groups of the salts with oppositely charged functional groups on a bacterial cell surface, and the second stage includes incorporation of their lipophilic groups into a bacterial cell membrane. However, despite numerous experimental studies, computational modelling of this mechanism with the aim to support experimental observations with theoretical conclusions, to the author's knowledge, has not yet been reported. In the current study, linear regression models correlating theoretical descriptors of lipophilicity and electronic properties of mono- and disubstituted imidazolium carboxylates with their biological activity towards Escherichia coli have been developed. These models established that biological activity of these salts is governed by the chemical structures of imidazolium cations, and that the centre of this biological activity is located in the long alkyl side chains of the cations. It was also found that these side chains have an intrinsic electronic potential to form internal C-H- -H-C electrostatic interactions when their lengths reach seven carbon atoms. Additionally, the nature of the C-H- -O-C inter-ionic electrostatic interactions in imidazolium carboxylates has been explored via a topological analysis of these interactions in 1-ethyl-3-methylimidazolium acetate. Thus, it was established that these electrostatic interactions are hydrogen bonds.

Orientador: Carlos Roque Duarte Correia / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-14T14:22:36Z (GMT). No. of bitstreams: 1 Pastre_JulioCezar_D.pdf: 10159507 bytes, checksum: 4f4f32c2c414df354e1d53179d9ebe18 (MD5) Previous issue date: 2009 / Resumo: Neste trabalho, efetuou-se um estudo da reação de Heck de acrilatos substituídos com sais de arenodiazônio. Um protocolo estereosseletivo para a preparação de acrilatos b,b-diarilssubstituidos foi desenvolvido, baseando-se na arilação Heck do cinamato de metila com sais de arenodiazônio, catalisada por Pd(OAc)2, em metanol. A diastereosseletivade da reação de Heck apresentou uma acentuada dependência com a natureza eletrônica do sal de arenodiazônio empregado. A metodologia ainda forneceu uma rota conveniente para 3-arilindanonas e 4-ariltetralonas, permitindo as sínteses formais totais da (±)-indatralina (4 etapas, 54 % de rendimento global) e da (±)-sertralina (7 etapas, 49 % de rendimento global). A extensão da metodologia para acrilatos mais substituídos (inclusive para acrilatos cíclicos) foi feita com sucesso para a maioria dos casos e os adutos de Heck foram obtidos em bons rendimentos e seletividades, independente do padrão de substituição do sal de arenodiazônio empregado. Esta metodologia foi aplicada à síntese total da (±)-paroxetina (8 etapas, 15 % de rendimento global) e da (±)-nocaína (6 etapas, 20 % de rendimento global). Verificou-se ainda que a reação de arilação de Heck empregando sais de arenodiazônio ocorre de maneira eficiente em meios reacionais alternativos, como PEG e líquidos iônicos. Uma série de líquidos iônicos quirais inéditos do tipo piridínio, imidazolínio e imidazólio foi preparada e testada, não revelando nenhuma incidência no curso estereoquímico da reação. Os resultados obtidos demonstram o enorme potencial sintético do emprego de sais de arenodiazônio em reações de Heck, constituindo uma metodologia bastante versatil em Síntese Orgânica. / Abstract: In this work, we present a study of the Heck reaction of substituted acrilates with arenediazonium salts. A stereoselective protocol for the preparation of b,b-disubstituted acrylates in good yields by means of a Heck-Matsuda reaction was accomplished. The method employs a base- and ligand-free Heck reaction of methyl cinnamate using arenediazonium salts as electrophiles. The Heck reaction displays a remarkable electronic dependence regarding the diastereoselectivity of the arylation process, which correlates with the electronic nature of the arenediazonium salts employed. The overall methodology provides a convenient route to 3-arylindanones and 4-aryltetralones allowing the concise formal total syntheses of the therapeutically important psychoactive compounds (±)-indatraline (4 steps, 54 % global yield) and (±)-sertraline (7 steps, 49 % global yield). The methodology was also successfully extended to more substituted acrylates and the Heck adducts were obtained in good to excellent yields, regardless of the substitution pattern of the arenediazonium salt employed. This methodology was applied to the total synthesis of (±)-paroxetine (8 steps, 15 % global yield) and (±)nocaine (6 steps, 20 % global yield). We also verified that the Heck reaction using arenediazonium salts occurs in an efficient way in alternative reaction media, like PEG and ionic liquids. A series of new chiral ionic liquids was prepared and evaluated in the Heck reaction. In spite the overall performance of the Heck reaction, in all the cases studied no asymmetric induction was detected. Our results demonstrate the enormous synthetic potential of the Heck reaction using arenediazonium salts, constituting a versatile methodology in Organic Synthesis. / Doutorado / Quimica Organica / Doutor em Ciências