Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/26729 |
Resumo: | This work reports the synthesis of eight series of substituted trifluoromethyl heterocycle compounds, based on the synthetic versatility and regioselectivity of 4- alkoxy(amino)-5-bromo-1,1,1-trifluorpent-3-en-2-ones in reactions of Nfunctionalization using nitrogenous nucleophiles. Many of the compounds obtained have interesting physical and chemical characteristics from a pharmacological point of view, since they are analogous to synthetic drugs well known on the market and which have varied biological activities. The series of precursors, compounds (E)-4-(amino)1,1,1-trifluor-5-(5-methyl-3- (trifluormethyl)-1H-pyrazoles-1-yl)pent-3-en-2-ones (pyrazole-enaminones), was synthesized through the N-alkylation reaction via bimolecular nucleophilic substitution (SN2), where the bromine atom at position five (Cγ) of the bromo-enaminones, was replaced by the nucleophilic nitrogen of the pyrazoline ring, promoting the formation of N-alkylated products with yields ranging from 65 and 86%. From this precursor unit, cyclocondensation reactions were carried out using different dinucleophiles, exploring their synthetic versatility as building blocks and thus obtaining the other series of polyheterocycle compounds of this work that had yields between 20 and 98%. Using bispyrazoles as a platform, a controlled and regioselective synthetic route was developed containing consecutive steps of N-alkylation and cyclocondensation for the synthesis of novel polypyrazoles composed of pyrazoline monomers along along the main chain with yields between 35 and 96%. This methodology was also adapted for the construction of the necessary molecular structure that will serve as a basis for future ring-closing reactions in the synthesis of macrocycles. The products obtained were characterized by 1H and 13C NMR, mass spectrometry, high resolution mass spectrometry, elemental analysis and by x-ray diffraction. |
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2022-11-01T14:55:58Z2022-11-01T14:55:58Z2022-09-06http://repositorio.ufsm.br/handle/1/26729This work reports the synthesis of eight series of substituted trifluoromethyl heterocycle compounds, based on the synthetic versatility and regioselectivity of 4- alkoxy(amino)-5-bromo-1,1,1-trifluorpent-3-en-2-ones in reactions of Nfunctionalization using nitrogenous nucleophiles. Many of the compounds obtained have interesting physical and chemical characteristics from a pharmacological point of view, since they are analogous to synthetic drugs well known on the market and which have varied biological activities. The series of precursors, compounds (E)-4-(amino)1,1,1-trifluor-5-(5-methyl-3- (trifluormethyl)-1H-pyrazoles-1-yl)pent-3-en-2-ones (pyrazole-enaminones), was synthesized through the N-alkylation reaction via bimolecular nucleophilic substitution (SN2), where the bromine atom at position five (Cγ) of the bromo-enaminones, was replaced by the nucleophilic nitrogen of the pyrazoline ring, promoting the formation of N-alkylated products with yields ranging from 65 and 86%. From this precursor unit, cyclocondensation reactions were carried out using different dinucleophiles, exploring their synthetic versatility as building blocks and thus obtaining the other series of polyheterocycle compounds of this work that had yields between 20 and 98%. Using bispyrazoles as a platform, a controlled and regioselective synthetic route was developed containing consecutive steps of N-alkylation and cyclocondensation for the synthesis of novel polypyrazoles composed of pyrazoline monomers along along the main chain with yields between 35 and 96%. This methodology was also adapted for the construction of the necessary molecular structure that will serve as a basis for future ring-closing reactions in the synthesis of macrocycles. The products obtained were characterized by 1H and 13C NMR, mass spectrometry, high resolution mass spectrometry, elemental analysis and by x-ray diffraction.Este trabalho relata a síntese de oito séries de compostos heterociclos trifluormetil substituídos, a partir da versatilidade sintética e regiosseletividade das 4- alcoxi(amino)-5-bromo-1,1,1-trifluorpent-3-en-2-onas em reações de Nfuncionalização frente a nucleófilos nitrogenados. Muitos dos compostos obtidos possuem características físicas e químicas interessantes do ponto de vista farmacológico, visto que são análogos a fármacos sintéticos bem conhecidos no mercado e que possuem variadas atividades biológicas. A série de precursores, compostos (E)-4-(amino)1,1,1-trifluor-5-(5-metil-3- (trifluormetil)-1H-pirazóis-1-il)pent-3-en-2-onas (pirazóis-enaminonas), foi sintetizada através da reação de N-alquilacão via substituição nucleofílica bimolecular (SN2), onde o átomo de bromo na posição cinco (Cγ) das bromo-enaminonas, foi substituído pelo nitrogênio nucleofílico do anel pirazolínico, promovendo a formação dos produtos Nalquilados com rendimentos que variam entre 65 e 86%. A partir desta unidade precursora, reações de ciclocondensação foram realizadas utilizando diversos dinucleófilos, explorando sua versatilidade sintética como blocos de construção e assim, obtendo as demais séries de compostos poli-heterociclos do trabalho que tiveram rendimentos entre 20 e 98%. Utilizando os bi-pirazóis como plataforma, foi elaborada uma rota sintética controlada e regiosseletiva contendo etapas consecutivas de N-alquilação e ciclocondensação para a síntese de poli-pirazóis inéditos compostos por monômeros pirazolínicos ao longo da cadeia principal com rendimentos entre 35 e 96%. Esta metodologia também foi adaptada para construção da estrutura molecular necessária que servirá de base para reações futuras de fechamento de anel na síntese de macrociclos. Os produtos obtidos foram caracterizados por ressonância magnética nuclear de 1H e 13C, espectrometria de massas de baixa e alta resolução, análise elementar e difratometria de raios X.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em QuímicaUFSMBrasilQuímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPoli-heterociclosBromo-enonasBromo-enaminonasN-alquilacãoCiclocondensaçãoMacrociclosPolypyrazolesBromo-enonesBromo-enaminonesN-alkylationCyclocondensationMacrocyclesCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICASíntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividadeSynthesis and application of pyrazoles for the construction of polyheterocycles with potential bioactivityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisZanatta, Nilohttp://lattes.cnpq.br/0719465062354576Frizzo, ClarissaWastowski, Arci DirceuGodoi, Benhur deMostardeiro, Marco AurélioSchumacher, Ricardo Fredericohttp://lattes.cnpq.br/4065737391248739Moraes, Paulo Alexandre de100600000000600600600600600600600600233dc1de-ab03-4f57-9b85-e40dc01a2d4f2dba95c4-e357-4e3f-83e0-fafb12ebf23234c6d2e6-1cc5-4638-a14a-6ba61387c7d85804dc08-8177-4a85-ac2b-b7dafa12bbabc30fcd74-7708-48d5-ba10-655685fff8062de9199a-3fcd-44b3-8ace-06c98bdc91176c8d4d2c-6e7a-4fa7-8f85-f8e27a24863breponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGQUÍMICA_2022_MORAES_PAULO.pdfTES_PPGQUÍMICA_2022_MORAES_PAULO.pdfTese de doutoradoapplication/pdf18390292http://repositorio.ufsm.br/bitstream/1/26729/1/TES_PPGQU%c3%8dMICA_2022_MORAES_PAULO.pdfb5c668b7b745f04e1ebfe7e52c47ed8dMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
dc.title.alternative.eng.fl_str_mv |
Synthesis and application of pyrazoles for the construction of polyheterocycles with potential bioactivity |
title |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
spellingShingle |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade Moraes, Paulo Alexandre de Poli-heterociclos Bromo-enonas Bromo-enaminonas N-alquilacão Ciclocondensação Macrociclos Polypyrazoles Bromo-enones Bromo-enaminones N-alkylation Cyclocondensation Macrocycles CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
title_full |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
title_fullStr |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
title_full_unstemmed |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
title_sort |
Síntese e aplicação de pirazóis na construção de poliheterociclos com potencial bioatividade |
author |
Moraes, Paulo Alexandre de |
author_facet |
Moraes, Paulo Alexandre de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Zanatta, Nilo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0719465062354576 |
dc.contributor.advisor-co1.fl_str_mv |
Frizzo, Clarissa |
dc.contributor.referee1.fl_str_mv |
Wastowski, Arci Dirceu |
dc.contributor.referee2.fl_str_mv |
Godoi, Benhur de |
dc.contributor.referee3.fl_str_mv |
Mostardeiro, Marco Aurélio |
dc.contributor.referee4.fl_str_mv |
Schumacher, Ricardo Frederico |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4065737391248739 |
dc.contributor.author.fl_str_mv |
Moraes, Paulo Alexandre de |
contributor_str_mv |
Zanatta, Nilo Frizzo, Clarissa Wastowski, Arci Dirceu Godoi, Benhur de Mostardeiro, Marco Aurélio Schumacher, Ricardo Frederico |
dc.subject.por.fl_str_mv |
Poli-heterociclos Bromo-enonas Bromo-enaminonas N-alquilacão Ciclocondensação Macrociclos |
topic |
Poli-heterociclos Bromo-enonas Bromo-enaminonas N-alquilacão Ciclocondensação Macrociclos Polypyrazoles Bromo-enones Bromo-enaminones N-alkylation Cyclocondensation Macrocycles CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Polypyrazoles Bromo-enones Bromo-enaminones N-alkylation Cyclocondensation Macrocycles |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
This work reports the synthesis of eight series of substituted trifluoromethyl heterocycle compounds, based on the synthetic versatility and regioselectivity of 4- alkoxy(amino)-5-bromo-1,1,1-trifluorpent-3-en-2-ones in reactions of Nfunctionalization using nitrogenous nucleophiles. Many of the compounds obtained have interesting physical and chemical characteristics from a pharmacological point of view, since they are analogous to synthetic drugs well known on the market and which have varied biological activities. The series of precursors, compounds (E)-4-(amino)1,1,1-trifluor-5-(5-methyl-3- (trifluormethyl)-1H-pyrazoles-1-yl)pent-3-en-2-ones (pyrazole-enaminones), was synthesized through the N-alkylation reaction via bimolecular nucleophilic substitution (SN2), where the bromine atom at position five (Cγ) of the bromo-enaminones, was replaced by the nucleophilic nitrogen of the pyrazoline ring, promoting the formation of N-alkylated products with yields ranging from 65 and 86%. From this precursor unit, cyclocondensation reactions were carried out using different dinucleophiles, exploring their synthetic versatility as building blocks and thus obtaining the other series of polyheterocycle compounds of this work that had yields between 20 and 98%. Using bispyrazoles as a platform, a controlled and regioselective synthetic route was developed containing consecutive steps of N-alkylation and cyclocondensation for the synthesis of novel polypyrazoles composed of pyrazoline monomers along along the main chain with yields between 35 and 96%. This methodology was also adapted for the construction of the necessary molecular structure that will serve as a basis for future ring-closing reactions in the synthesis of macrocycles. The products obtained were characterized by 1H and 13C NMR, mass spectrometry, high resolution mass spectrometry, elemental analysis and by x-ray diffraction. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-11-01T14:55:58Z |
dc.date.available.fl_str_mv |
2022-11-01T14:55:58Z |
dc.date.issued.fl_str_mv |
2022-09-06 |
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 |
http://repositorio.ufsm.br/handle/1/26729 |
url |
http://repositorio.ufsm.br/handle/1/26729 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
100600000000 |
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600 600 600 600 600 600 600 600 |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Química |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Química |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
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