Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/20678 |
Resumo: | Knoevenagel condensation is of great importance in organic synthesis. With the growing concern with clean methodologies, new protocols for its execution have been sought. This study looks at the applicability of the binary ethanol: water mixture in the synthesis of Knoevenagel adducts with ketones, in sequential reactions in the synthesis of coumarins and associated with Lewis acid type catalysts. When the binary ethanol: water (3: 7) system was applied to the synthesis of isatin-derived Knoevenagel adducts, the effectiveness of the methodology was confirmed, corroborated by the good times (1.5 to 7.5 hours) and yields (79 to 96%). When the same system was applied in the synthesis of coumarins from salicylaldehydes, it was noticeable that the elimination step, after cyclization, is influential in the reaction speed; with methyl cyanoacetate being the best compound with active methylene. Altogether 9 coumarins were synthesized, between 1.16 to 3.50 hours, with yields of 72 to 99%. The adducts derived from isatin and coumarins synthesized were submitted to the Swiss ADME. As pharmacokinetic data, all showed passivity of absorption by the gastrointestinal tract, in addition to not being substrates of P-Gp. However, among them, only four adducts and four coumarins, exhibited potential passive permeation through the blood-brain barrier. In the optimization of the reaction aiming at the synthesis of adducts at room temperature, the NaCl salt was the most effective of the catalysts tested in the synthesis of Knoevenagel adducts synthesized from aromatic aldehydes and malononitrile, requiring 2 to 75 minutes, obtaining yields between 83 % and 97%. This new methodology is an ecologically correct synthesis protocol due to the low toxicity of the solvents and catalyst used; operation at room temperature and ease of isolation of products as they precipitate in the reaction medium. Tests were carried out in multicomponent reactions of the Biginelli type and synthesis of 4H-pyranes, however we concluded that only the solvent systems and catalysis with a Lewis acid with low coordination number, such as the Na+ ion, are not sufficient to promote these multicomponent reactions, being the subject of future studies. |
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Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinasCondensação de KnoevenagelMistura bináriaCatáliseQuímica verdeIsatinaCumarinaKnoevenagel condensationBinary mixtureCatalysisGreen chemistryIsatinCoumarinCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAKnoevenagel condensation is of great importance in organic synthesis. With the growing concern with clean methodologies, new protocols for its execution have been sought. This study looks at the applicability of the binary ethanol: water mixture in the synthesis of Knoevenagel adducts with ketones, in sequential reactions in the synthesis of coumarins and associated with Lewis acid type catalysts. When the binary ethanol: water (3: 7) system was applied to the synthesis of isatin-derived Knoevenagel adducts, the effectiveness of the methodology was confirmed, corroborated by the good times (1.5 to 7.5 hours) and yields (79 to 96%). When the same system was applied in the synthesis of coumarins from salicylaldehydes, it was noticeable that the elimination step, after cyclization, is influential in the reaction speed; with methyl cyanoacetate being the best compound with active methylene. Altogether 9 coumarins were synthesized, between 1.16 to 3.50 hours, with yields of 72 to 99%. The adducts derived from isatin and coumarins synthesized were submitted to the Swiss ADME. As pharmacokinetic data, all showed passivity of absorption by the gastrointestinal tract, in addition to not being substrates of P-Gp. However, among them, only four adducts and four coumarins, exhibited potential passive permeation through the blood-brain barrier. In the optimization of the reaction aiming at the synthesis of adducts at room temperature, the NaCl salt was the most effective of the catalysts tested in the synthesis of Knoevenagel adducts synthesized from aromatic aldehydes and malononitrile, requiring 2 to 75 minutes, obtaining yields between 83 % and 97%. This new methodology is an ecologically correct synthesis protocol due to the low toxicity of the solvents and catalyst used; operation at room temperature and ease of isolation of products as they precipitate in the reaction medium. Tests were carried out in multicomponent reactions of the Biginelli type and synthesis of 4H-pyranes, however we concluded that only the solvent systems and catalysis with a Lewis acid with low coordination number, such as the Na+ ion, are not sufficient to promote these multicomponent reactions, being the subject of future studies.NenhumaA Condensação de Knoevenagel é de grande importância na síntese orgânica. Com a crescente preocupação com metodologias limpas, tem se buscado novos protocolos para sua execução. Este estudo vislumbra a aplicabilidade da mistura binária etanol:água na síntese de adutos de Knoevenagel com cetonas, em reações sequenciais na síntese de cumarinas e associada à catalisadores do tipo ácidos de Lewis. Aplicado o sistema binário etanol:água (3:7) na síntese de adutos de Knoevenagel derivados de isatina, percebeu-se a eficácia da metodologia, corroborada pelos bons tempos (1,5 a 7,5 horas) e rendimentos (79 a 96%). Quando aplicado o mesmo sistema na síntese de cumarinas a partir de salicilaldeídos, foi perceptível que a etapa de eliminação, posterior a ciclização, é influente na velocidade da reação; sendo o cianoacetato de metila o melhor composto com metileno ativo. Ao todo foram 9 cumarinas sintetizadas, entre 1,16 a 3,50 horas, com rendimentos de 72 a 99%. Os adutos derivados de isatina e cumarinas sintetizados foram submetidos ao Swiss ADME. Como dados farmacocinéticos, todos apresentaram passividade de absorção pelo trato gastrointestinal, além de não serem substratos da P-Gp. Porém, dentre eles, apenas quatro adutos e quatro cumarinas, exibiram potencial permeação passiva através da barreira hematoencefálica. Na otimização da reação visando a síntese dos adutos à temperatura ambiente, o sal NaCl foi o mais eficaz dos catalisadores testados na síntese de adutos de Knoevenagel sintetizados a partir de aldeídos aromáticos e a malononitrila, demandando de 2 a 75 minutos, obtendo rendimentos entre 83% e 97%. Esta nova metodologia é um protocolo de síntese ecologicamente correto devido à baixa toxicidade dos solventes e catalisador utilizados; operação à temperatura ambiente e facilidade de isolamento dos produtos à medida que precipitam no meio reacional. Testes foram realizados em reações multicomponentes do tipo Biginelli e síntese de 4H-piranos, porém concluímos que apenas os sistemas de solvente e catálise com um ácido de Lewis com baixo número de coordenação, como é o íon Na+, não são suficientes para promover estas reações multicomponentes, sendo objeto de estudos futuros.Universidade Federal da ParaíbaBrasilQuímicaPrograma de Pós-Graduação em QuímicaUFPBVale, Juliana Alveshttp://lattes.cnpq.br/5336623781494423Ferreira, João Marcos Gomes de Oliveira2021-08-11T18:40:17Z2021-02-222021-08-11T18:40:17Z2021-02-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/20678porhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2022-08-10T10:57:05Zoai:repositorio.ufpb.br:123456789/20678Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2022-08-10T10:57:05Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
title |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
spellingShingle |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas Ferreira, João Marcos Gomes de Oliveira Condensação de Knoevenagel Mistura binária Catálise Química verde Isatina Cumarina Knoevenagel condensation Binary mixture Catalysis Green chemistry Isatin Coumarin CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
title_full |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
title_fullStr |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
title_full_unstemmed |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
title_sort |
Estudo da reação de Knoevenagel em condições eco-amigáveis visando às sínteses de compostos carbonílicos α,β- insaturados e cumarinas |
author |
Ferreira, João Marcos Gomes de Oliveira |
author_facet |
Ferreira, João Marcos Gomes de Oliveira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Vale, Juliana Alves http://lattes.cnpq.br/5336623781494423 |
dc.contributor.author.fl_str_mv |
Ferreira, João Marcos Gomes de Oliveira |
dc.subject.por.fl_str_mv |
Condensação de Knoevenagel Mistura binária Catálise Química verde Isatina Cumarina Knoevenagel condensation Binary mixture Catalysis Green chemistry Isatin Coumarin CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
topic |
Condensação de Knoevenagel Mistura binária Catálise Química verde Isatina Cumarina Knoevenagel condensation Binary mixture Catalysis Green chemistry Isatin Coumarin CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Knoevenagel condensation is of great importance in organic synthesis. With the growing concern with clean methodologies, new protocols for its execution have been sought. This study looks at the applicability of the binary ethanol: water mixture in the synthesis of Knoevenagel adducts with ketones, in sequential reactions in the synthesis of coumarins and associated with Lewis acid type catalysts. When the binary ethanol: water (3: 7) system was applied to the synthesis of isatin-derived Knoevenagel adducts, the effectiveness of the methodology was confirmed, corroborated by the good times (1.5 to 7.5 hours) and yields (79 to 96%). When the same system was applied in the synthesis of coumarins from salicylaldehydes, it was noticeable that the elimination step, after cyclization, is influential in the reaction speed; with methyl cyanoacetate being the best compound with active methylene. Altogether 9 coumarins were synthesized, between 1.16 to 3.50 hours, with yields of 72 to 99%. The adducts derived from isatin and coumarins synthesized were submitted to the Swiss ADME. As pharmacokinetic data, all showed passivity of absorption by the gastrointestinal tract, in addition to not being substrates of P-Gp. However, among them, only four adducts and four coumarins, exhibited potential passive permeation through the blood-brain barrier. In the optimization of the reaction aiming at the synthesis of adducts at room temperature, the NaCl salt was the most effective of the catalysts tested in the synthesis of Knoevenagel adducts synthesized from aromatic aldehydes and malononitrile, requiring 2 to 75 minutes, obtaining yields between 83 % and 97%. This new methodology is an ecologically correct synthesis protocol due to the low toxicity of the solvents and catalyst used; operation at room temperature and ease of isolation of products as they precipitate in the reaction medium. Tests were carried out in multicomponent reactions of the Biginelli type and synthesis of 4H-pyranes, however we concluded that only the solvent systems and catalysis with a Lewis acid with low coordination number, such as the Na+ ion, are not sufficient to promote these multicomponent reactions, being the subject of future studies. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-11T18:40:17Z 2021-02-22 2021-08-11T18:40:17Z 2021-02-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/20678 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/20678 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Química Programa de Pós-Graduação em Química UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Química Programa de Pós-Graduação em Química UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801842977970061312 |