2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas
Ano de defesa: | 2022 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química
|
Departamento: |
Química
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/26747 |
Resumo: | This thesis presents the results on the synthesis, structural study, and evaluation of the photophysical properties of new (E)-5-(alkyl/aryl/heteroaryl)-2-amino-3-(aryldiazenyl)-7-(trifluoromethyl)pyrazolo[1,5- a]pyrimidine (5a-q), which were obtained using intramolecular cyclization reactions of the precursors (E)-3,5- diamino-4-(heteroaryldiazenyl)-1H-pyrazoles (3a-g) and 4-alkoxy-4-alkyl[aryl(heteroaryl)]-1,1,1-trifluor-3-alken2-ones (β-ATC) (4a-j) in 50-90% yields. Emission and UV-Vis properties were investigated in different solvents. All compounds were absorbed in the ultraviolet region showing low fluorescence in the solution. In sequence, initiating the derivatization reactions of the heterocyclic system 5, Sonogashira reactions were carried out, and three new series of derivative aryacetylenes were synthesized (6-8). These reactions were carried out exclusively for the 4-bromophenyl substituents at the 5-position and/or at the 3-position (3-diazenyl) in the pyrazolo[1,5- a]pyrimidine series (5). Thus, series of (E)-2-amino-5-phenyl-3-((4-(heteroarylethynyl)phenyl)diazenyl)-7- (trifluoromethyl)pyrazolo[1,5-a]pyrimidine (6a-e), (E)-2-amino-3-(phenyldiazenyl)-5-(4- (arylethynyl)phenyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (7a-e) and (E)-2-amino-5-(4- (arylethynyl)phenyl)-3-((4-(arylethynyl)phenyl)diazenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (8a-c) were isolated in 20-87% yields. Subsequently, compounds 6–8 had their photophysical properties (absorption and emission) obtained, and their interaction studies on human serum albumin (HSA) biomolecules were evaluated. Afterwards, selected pyrimidines from the series 5a-q were used as starting materials in reaction with sodium azide. These reactions unexpectedly resulted in an unprecedented series of twinned triazoles in the form of 2,8- (aryl/heteroaryl)-6-(trifluoromethyl)-1ʎ2 ,2ʎ4 -1H-[1,2,3]triazolo[4',5':3,4]pyrazolo[1,5-a]pyrimidine (9a-k), which can be obtained by two different methodologies in 25-85% yields. In the second part of this thesis, other structural variations were developed based on pyrazolo[1,5-a]pyrimidines (11). Therefore, from 5-amino-3- methyl-1H-pyrazole (10) and β-ATC (4), a series of 2-methyl-5-(alkyl/aryl/heteroaryl)-7- (trifluormethyl)pyrazolo[1,5-a]pyrimidine (11) was obtained. Compounds 11 have already been described in the literature. Additionally, the fluorescent properties and UV-Vis absorption in different solvents were investigated, and as a result, it was found that all compounds show high fluorescence in solution. Furthermore, solid-state stabilities were evaluated via thermogravimetric analysis. Compounds (11) were then used as starting materials for the synthesis of heterocycles produced in the second part of this study, which evaluated the reactivity of position 3 of the pyrazolo[1,5-a]pyrimidine system (11) with the insertion of halogens and derivatization through the study of Sonogashira reactions. Halogenation reactions using NBS and NIS as the halogenating reagent allowed for obtaining 3-bromo and 3-iodo derivatives (12, 14). In sequence, the regioselectivity of C-C bond formation was studied using Sonogashira reactions, which provided the phenylacetylene derivatives 15-16 in yields of 45-79%. Furthermore, the novel compounds 2-methyl-3-iodo-5-aryl-pyrazolo[1,5-a]pyrimidines (14), led to the formation ix of substituted bis-trifluoromethyl systems, 2-methyl-5-aryl(heteroaryl)-3,7-bis(trifluoromethyl)pyrazolo[1,5- a]pyrimidine (17), in 30-85% yields, using MFSDA as the trifluoromethylating agent. As final derivatizations, the following were applied: a classical formylation reaction (Vilsmeier-Haack) functionalizing the 3-position of compounds 11, which provided the formation of an unprecedented series of 3-formyl-2-methyl-5-(aryl/heteroaryl)- 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (18) in yields between 60-90%, and (ii) reaction of aldehydes 18 with malononitrile. This final reaction enabled the synthesis of a novel series of 2-((2-methyl-5-(aryl/heteroaryl)- 7-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl)methylene)malononitriles (19) in yield of 40-85%. All chemical compounds related to the unpublished series produced in this thesis were characterized by melting point and structurally elucidated via routine spectroscopic and spectrometric techniques, that is, ¹H, ¹³C, and 19F NMR, oneand two-dimensional (HSQC, HMBC), CHN or HRMS elemental analysis, and single-crystal X-ray diffraction (CCDC recording) when appropriate. |
id |
UFSM_9fcea3a194d69c6d6ff08b79816556da |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/26747 |
network_acronym_str |
UFSM |
network_name_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
repository_id_str |
|
spelling |
2022-11-04T12:34:09Z2022-11-04T12:34:09Z2022-08-19http://repositorio.ufsm.br/handle/1/26747This thesis presents the results on the synthesis, structural study, and evaluation of the photophysical properties of new (E)-5-(alkyl/aryl/heteroaryl)-2-amino-3-(aryldiazenyl)-7-(trifluoromethyl)pyrazolo[1,5- a]pyrimidine (5a-q), which were obtained using intramolecular cyclization reactions of the precursors (E)-3,5- diamino-4-(heteroaryldiazenyl)-1H-pyrazoles (3a-g) and 4-alkoxy-4-alkyl[aryl(heteroaryl)]-1,1,1-trifluor-3-alken2-ones (β-ATC) (4a-j) in 50-90% yields. Emission and UV-Vis properties were investigated in different solvents. All compounds were absorbed in the ultraviolet region showing low fluorescence in the solution. In sequence, initiating the derivatization reactions of the heterocyclic system 5, Sonogashira reactions were carried out, and three new series of derivative aryacetylenes were synthesized (6-8). These reactions were carried out exclusively for the 4-bromophenyl substituents at the 5-position and/or at the 3-position (3-diazenyl) in the pyrazolo[1,5- a]pyrimidine series (5). Thus, series of (E)-2-amino-5-phenyl-3-((4-(heteroarylethynyl)phenyl)diazenyl)-7- (trifluoromethyl)pyrazolo[1,5-a]pyrimidine (6a-e), (E)-2-amino-3-(phenyldiazenyl)-5-(4- (arylethynyl)phenyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (7a-e) and (E)-2-amino-5-(4- (arylethynyl)phenyl)-3-((4-(arylethynyl)phenyl)diazenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (8a-c) were isolated in 20-87% yields. Subsequently, compounds 6–8 had their photophysical properties (absorption and emission) obtained, and their interaction studies on human serum albumin (HSA) biomolecules were evaluated. Afterwards, selected pyrimidines from the series 5a-q were used as starting materials in reaction with sodium azide. These reactions unexpectedly resulted in an unprecedented series of twinned triazoles in the form of 2,8- (aryl/heteroaryl)-6-(trifluoromethyl)-1ʎ2 ,2ʎ4 -1H-[1,2,3]triazolo[4',5':3,4]pyrazolo[1,5-a]pyrimidine (9a-k), which can be obtained by two different methodologies in 25-85% yields. In the second part of this thesis, other structural variations were developed based on pyrazolo[1,5-a]pyrimidines (11). Therefore, from 5-amino-3- methyl-1H-pyrazole (10) and β-ATC (4), a series of 2-methyl-5-(alkyl/aryl/heteroaryl)-7- (trifluormethyl)pyrazolo[1,5-a]pyrimidine (11) was obtained. Compounds 11 have already been described in the literature. Additionally, the fluorescent properties and UV-Vis absorption in different solvents were investigated, and as a result, it was found that all compounds show high fluorescence in solution. Furthermore, solid-state stabilities were evaluated via thermogravimetric analysis. Compounds (11) were then used as starting materials for the synthesis of heterocycles produced in the second part of this study, which evaluated the reactivity of position 3 of the pyrazolo[1,5-a]pyrimidine system (11) with the insertion of halogens and derivatization through the study of Sonogashira reactions. Halogenation reactions using NBS and NIS as the halogenating reagent allowed for obtaining 3-bromo and 3-iodo derivatives (12, 14). In sequence, the regioselectivity of C-C bond formation was studied using Sonogashira reactions, which provided the phenylacetylene derivatives 15-16 in yields of 45-79%. Furthermore, the novel compounds 2-methyl-3-iodo-5-aryl-pyrazolo[1,5-a]pyrimidines (14), led to the formation ix of substituted bis-trifluoromethyl systems, 2-methyl-5-aryl(heteroaryl)-3,7-bis(trifluoromethyl)pyrazolo[1,5- a]pyrimidine (17), in 30-85% yields, using MFSDA as the trifluoromethylating agent. As final derivatizations, the following were applied: a classical formylation reaction (Vilsmeier-Haack) functionalizing the 3-position of compounds 11, which provided the formation of an unprecedented series of 3-formyl-2-methyl-5-(aryl/heteroaryl)- 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (18) in yields between 60-90%, and (ii) reaction of aldehydes 18 with malononitrile. This final reaction enabled the synthesis of a novel series of 2-((2-methyl-5-(aryl/heteroaryl)- 7-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl)methylene)malononitriles (19) in yield of 40-85%. All chemical compounds related to the unpublished series produced in this thesis were characterized by melting point and structurally elucidated via routine spectroscopic and spectrometric techniques, that is, ¹H, ¹³C, and 19F NMR, oneand two-dimensional (HSQC, HMBC), CHN or HRMS elemental analysis, and single-crystal X-ray diffraction (CCDC recording) when appropriate.A presente tese apresenta os resultados sobre a síntese, o estudo estrutural e a avalição das propriedades fotofísicas de novos (E)-5-(alquil/aril/heteroaril)-2-amino-3-(arildiazenil)-7-(trifluorometil)pirazolo[1,5-a]pirimidinas (5aq), as quais foram obtidas empregando reações ciclização intramolecular dos precursores (E)-3,5-diamino-4- (heteroarildiazenil)-1H-pirazóis(3a-g) e 4-alcóxi-4-(alquil/aril/heteroaril)-1,1,1-triflúor-3-alquen-2-onas (β-ATC) (4a-j) com rendimentos de 50-90%. Propriedades de emissão e UV-vis foram investigadas em diferentes solventes, tendo-se observado que todos os compostos absorvem na região do ultravioleta apresentando baixa fluorescência em solução. Em sequência, iniciando as reações de derivatização do sistema heterocíclico 5, foram realizadas reações de Sonogashira, sendo sintetizadas três séries inéditas de arilacetilenos derivados (6-8). Estas reações foram executadas exclusivamente para os substituintes 4-bromofenila na posição 5 e/ou na posição 3 (3-diazenil) na série de pirazolo[1,5-a]pirimidinas (5). Desta forma, séries de (E)-2-amino-5-fenil-3-((4- (heteroariletinil)fenil)diazenil)-7-(trifluorometil)pirazolo[1,5-a]pirimidinas (6a-e), (E)-2-amino-3-(fenildiazenil)- 5-(4-(ariletinil)fenil)fenil)-7-(trifluorometil)pirazolo[1,5-a]pirimidina (7a-e) e (E)-2-amino-5-(4-(ariletinil)fenil)- 3-((4-(ariletinil)fenil)diazenil)-7-(trifluorometil)pirazolo[1,5-a]pirimidinas (8a-c) foram isoladas com rendimentos de 20-87%. A seguir, os compostos 6–8 tiveram suas propriedades fotofísicas (absorção e emissão) obtidas e seus estudos de interação em biomoléculas de albumina de soro humana (HSA) foram avaliados. Posteriormente, pirimidinas selecionadas da série 5a-q foram usadas como materiais de partida em reação com azida de sódio. Estas reações resultaram, de forma inesperada, em uma série inédita de triazóis geminados na forma de 2,8-(aril/heteroaril)-6-(trifluorometil)-1ʎ 2 ,2ʎ 4 -1H-[1,2,3]triazolo[4',5':3,4]pirazolo[1,5-a]pirimidinas (9a-k), a qual pode ser obtida através de duas metodologias diferentes em rendimentos de 25-85%. Na segunda parte desta tese foram desenvolvidas outras variações estruturais partindo de pirazolo[1,5-a]pirimidinas (11). Assim, a partir de 5-amino-3-metil-1H-pirazol (10) e das β-ATC (4) foi obtida uma série de 2-metil-5-(alquil/aril/heteroaril)-7- (trifluormetil)pirazolo[1,5-a]pirimidinas (11). Os compostos 11 já foram descritos na literatura. Adicionalmente, foram investigadas as propriedades fluorescentes e absorção UV-Vis em diferentes solventes e, como resultado, verificou-se que todos os compostos apresentam alta fluorescência em solução. Além disso, as estabilidades no estado sólido foram avaliadas via análise termogravimétrica. Os compostos (11) foram, então, utilizados como materiais de partida para a síntese dos heterociclos produzidos na segunda parte deste estudo, na qual foi avaliada a reatividade da posição 3 do sistema pirazolo[1,5-a]pirimidina (11) com a inserção de halogênios e derivatização com o estudo de reações de Sonogashira. As reações de halogenação utilizando NBS e NIS como reagente halogenante possibilitaram a obtenção de 3-bromo e 3-iodo derivados (12, 14). Em sequência, foi estudada a regioseletividade da formação de ligação C-C por meio de reações de Sonogashira, as quais forneceram os fenilacetilenos derivados 15-16 em rendimentos de 45-79%. Além disso, os compostos inéditos 2-metil-3-iodo5-aril-pirazolo[1,5-a]pirimidinas (14), conduziram à formação de sistemas bis-trifluormetil substituídos, 2-metil5-aril(heteroaril)-3,7-bis(trifluorometil)pirazolo[1,5-a]pirimidinas (17), com rendimentos de 30-85%, utilizando MFSDA como agente trifluormetilante. Como derivatizações finais foram aplicadas: (i) uma reação clássica de formilação (Vilsmeier-Haack) funcionalizando a posição 3 dos compostos 11, a qual proporcionou a formação de uma série inédita de 3-formil-2-metil-5-(aril/heteroaril)-7-(trifluorometil)pirazolo[1,5-a]pirimidinas (18) com rendimentos entre 60-90% e (ii) reação dos aldeídos 18 com de malononitrila. Esta reação final possibilitou a síntese de uma série inédita de 2-((2-metil-5-(aril/heteroaril)-7-(trifluorometil)pirazolo[1,5-a]piridin-3- il)metileno)malononitrilas (19) em rendimentos de 40-85% Todos os compostos químicos relativos às séries inéditas produzidas nesta tese foram caracterizados por ponto de fusão e elucidados estruturalmente via técnicas espectroscópicas e espectrométricas de rotina, ou seja, RMN de ¹H, ¹³C e 19F, uni- e bidimensionais (HSQC, HMBC), HRMSe difração de raios X em monocristal (registro CCDC) quando conveniente.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGSFundação de Apoio à Tecnologia e Ciência - FATECporUniversidade 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/openAccessPirazolo[1,5-a]pirimidinaTriazóisSonogashiraTrifluormetilaçãoVilsmeier-HaackPropriedades fotofísicasPyrazolo[1,5-a]pyrimidineTriazolesTrifluoromethylationPhotophysical propertiesCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicasTrifluoromethyl-substituted 2-amino-3-aryldiazenylpyrazolo[1,5-a]pyrimidines: synthesis, derivatizations and photophysical properties evaluationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBonacorso, Helio Gauzehttp://lattes.cnpq.br/7275608974248322Merlo, Aloir AntonioIglesias, Bernardo AlmeidaBender, Caroline RaquelAndrighetto, Rosáliahttp://lattes.cnpq.br/5739053525357685Stefanello, Felipe Salvador10060000000060060060060060060060006c852ad-d805-43c3-99d6-93a6a86f507cb51e5b9a-37ea-4550-8a4c-fa623585e740fa2e7141-9b4f-43d6-a7af-6718960f91a7bef0481f-6297-4683-a6d3-ce04e5d709e3bbf4c9f1-b597-4547-81c3-a11a31ce856ee3edfd90-e2a3-4aa7-9f4f-c6afc921f98freponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/26747/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53ORIGINALTES_PPGQUÍMICA_2022_STEFANELLO_FELIPE.pdfTES_PPGQUÍMICA_2022_STEFANELLO_FELIPE.pdfTese de Doutoradoapplication/pdf42519561http://repositorio.ufsm.br/bitstream/1/26747/1/TES_PPGQU%c3%8dMICA_2022_STEFANELLO_FELIPE.pdf971d3f481a80ed184bc3b249e978ce9bMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/26747/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD521/267472022-11-04 09:34:09.849oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-11-04T12:34:09Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
dc.title.alternative.eng.fl_str_mv |
Trifluoromethyl-substituted 2-amino-3-aryldiazenylpyrazolo[1,5-a]pyrimidines: synthesis, derivatizations and photophysical properties evaluation |
title |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
spellingShingle |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas Stefanello, Felipe Salvador Pirazolo[1,5-a]pirimidina Triazóis Sonogashira Trifluormetilação Vilsmeier-Haack Propriedades fotofísicas Pyrazolo[1,5-a]pyrimidine Triazoles Trifluoromethylation Photophysical properties CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
title_full |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
title_fullStr |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
title_full_unstemmed |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
title_sort |
2-amino-3-arildiazenil-pirazolo[1,5-a]pirimidinas trifluormetilsubstituídas: síntese, derivatizações e avaliação das propriedades fotofísicas |
author |
Stefanello, Felipe Salvador |
author_facet |
Stefanello, Felipe Salvador |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bonacorso, Helio Gauze |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7275608974248322 |
dc.contributor.referee1.fl_str_mv |
Merlo, Aloir Antonio |
dc.contributor.referee2.fl_str_mv |
Iglesias, Bernardo Almeida |
dc.contributor.referee3.fl_str_mv |
Bender, Caroline Raquel |
dc.contributor.referee4.fl_str_mv |
Andrighetto, Rosália |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5739053525357685 |
dc.contributor.author.fl_str_mv |
Stefanello, Felipe Salvador |
contributor_str_mv |
Bonacorso, Helio Gauze Merlo, Aloir Antonio Iglesias, Bernardo Almeida Bender, Caroline Raquel Andrighetto, Rosália |
dc.subject.por.fl_str_mv |
Pirazolo[1,5-a]pirimidina Triazóis Sonogashira Trifluormetilação Vilsmeier-Haack Propriedades fotofísicas |
topic |
Pirazolo[1,5-a]pirimidina Triazóis Sonogashira Trifluormetilação Vilsmeier-Haack Propriedades fotofísicas Pyrazolo[1,5-a]pyrimidine Triazoles Trifluoromethylation Photophysical properties CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Pyrazolo[1,5-a]pyrimidine Triazoles Trifluoromethylation Photophysical properties |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
This thesis presents the results on the synthesis, structural study, and evaluation of the photophysical properties of new (E)-5-(alkyl/aryl/heteroaryl)-2-amino-3-(aryldiazenyl)-7-(trifluoromethyl)pyrazolo[1,5- a]pyrimidine (5a-q), which were obtained using intramolecular cyclization reactions of the precursors (E)-3,5- diamino-4-(heteroaryldiazenyl)-1H-pyrazoles (3a-g) and 4-alkoxy-4-alkyl[aryl(heteroaryl)]-1,1,1-trifluor-3-alken2-ones (β-ATC) (4a-j) in 50-90% yields. Emission and UV-Vis properties were investigated in different solvents. All compounds were absorbed in the ultraviolet region showing low fluorescence in the solution. In sequence, initiating the derivatization reactions of the heterocyclic system 5, Sonogashira reactions were carried out, and three new series of derivative aryacetylenes were synthesized (6-8). These reactions were carried out exclusively for the 4-bromophenyl substituents at the 5-position and/or at the 3-position (3-diazenyl) in the pyrazolo[1,5- a]pyrimidine series (5). Thus, series of (E)-2-amino-5-phenyl-3-((4-(heteroarylethynyl)phenyl)diazenyl)-7- (trifluoromethyl)pyrazolo[1,5-a]pyrimidine (6a-e), (E)-2-amino-3-(phenyldiazenyl)-5-(4- (arylethynyl)phenyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (7a-e) and (E)-2-amino-5-(4- (arylethynyl)phenyl)-3-((4-(arylethynyl)phenyl)diazenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (8a-c) were isolated in 20-87% yields. Subsequently, compounds 6–8 had their photophysical properties (absorption and emission) obtained, and their interaction studies on human serum albumin (HSA) biomolecules were evaluated. Afterwards, selected pyrimidines from the series 5a-q were used as starting materials in reaction with sodium azide. These reactions unexpectedly resulted in an unprecedented series of twinned triazoles in the form of 2,8- (aryl/heteroaryl)-6-(trifluoromethyl)-1ʎ2 ,2ʎ4 -1H-[1,2,3]triazolo[4',5':3,4]pyrazolo[1,5-a]pyrimidine (9a-k), which can be obtained by two different methodologies in 25-85% yields. In the second part of this thesis, other structural variations were developed based on pyrazolo[1,5-a]pyrimidines (11). Therefore, from 5-amino-3- methyl-1H-pyrazole (10) and β-ATC (4), a series of 2-methyl-5-(alkyl/aryl/heteroaryl)-7- (trifluormethyl)pyrazolo[1,5-a]pyrimidine (11) was obtained. Compounds 11 have already been described in the literature. Additionally, the fluorescent properties and UV-Vis absorption in different solvents were investigated, and as a result, it was found that all compounds show high fluorescence in solution. Furthermore, solid-state stabilities were evaluated via thermogravimetric analysis. Compounds (11) were then used as starting materials for the synthesis of heterocycles produced in the second part of this study, which evaluated the reactivity of position 3 of the pyrazolo[1,5-a]pyrimidine system (11) with the insertion of halogens and derivatization through the study of Sonogashira reactions. Halogenation reactions using NBS and NIS as the halogenating reagent allowed for obtaining 3-bromo and 3-iodo derivatives (12, 14). In sequence, the regioselectivity of C-C bond formation was studied using Sonogashira reactions, which provided the phenylacetylene derivatives 15-16 in yields of 45-79%. Furthermore, the novel compounds 2-methyl-3-iodo-5-aryl-pyrazolo[1,5-a]pyrimidines (14), led to the formation ix of substituted bis-trifluoromethyl systems, 2-methyl-5-aryl(heteroaryl)-3,7-bis(trifluoromethyl)pyrazolo[1,5- a]pyrimidine (17), in 30-85% yields, using MFSDA as the trifluoromethylating agent. As final derivatizations, the following were applied: a classical formylation reaction (Vilsmeier-Haack) functionalizing the 3-position of compounds 11, which provided the formation of an unprecedented series of 3-formyl-2-methyl-5-(aryl/heteroaryl)- 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (18) in yields between 60-90%, and (ii) reaction of aldehydes 18 with malononitrile. This final reaction enabled the synthesis of a novel series of 2-((2-methyl-5-(aryl/heteroaryl)- 7-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl)methylene)malononitriles (19) in yield of 40-85%. All chemical compounds related to the unpublished series produced in this thesis were characterized by melting point and structurally elucidated via routine spectroscopic and spectrometric techniques, that is, ¹H, ¹³C, and 19F NMR, oneand two-dimensional (HSQC, HMBC), CHN or HRMS elemental analysis, and single-crystal X-ray diffraction (CCDC recording) when appropriate. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-11-04T12:34:09Z |
dc.date.available.fl_str_mv |
2022-11-04T12:34:09Z |
dc.date.issued.fl_str_mv |
2022-08-19 |
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/1/26747 |
url |
http://repositorio.ufsm.br/handle/1/26747 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
100600000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
06c852ad-d805-43c3-99d6-93a6a86f507c b51e5b9a-37ea-4550-8a4c-fa623585e740 fa2e7141-9b4f-43d6-a7af-6718960f91a7 bef0481f-6297-4683-a6d3-ce04e5d709e3 bbf4c9f1-b597-4547-81c3-a11a31ce856e e3edfd90-e2a3-4aa7-9f4f-c6afc921f98f |
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 |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/26747/3/license.txt http://repositorio.ufsm.br/bitstream/1/26747/1/TES_PPGQU%c3%8dMICA_2022_STEFANELLO_FELIPE.pdf http://repositorio.ufsm.br/bitstream/1/26747/2/license_rdf |
bitstream.checksum.fl_str_mv |
2f0571ecee68693bd5cd3f17c1e075df 971d3f481a80ed184bc3b249e978ce9b 4460e5956bc1d1639be9ae6146a50347 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1793240051177488384 |