Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA

Detalhes bibliográficos
Autor(a) principal: Pittaluga, Everton Pedebos
Data de Publicação: 2015
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/4274
Resumo: This thesis describes the studies carried out using fluorinating reagents with different approaches: Selectfluor as an electrophilic fluorine source; DAST for nucleophilic fluorinations and MFSDA as a nucleophilic trifluoromethylating reagent. Fluorinations reactions were carried out in 1H-pyrazoles possessing different substituents in the C3 and C5 positions with the goal of explore the insertion of fluorine atoms and/or fluoroalkyl groups in the C4 position of these substrates. Initially, we design suitable starting materials for the fluorination reactions with Selectfluor and DAST. Thus, 3-aryl-4-formyl-1H-1-pyrazoles compounds were synthetized in two steps reactions from ketones and hydrazines followed by a subsequent Vilsmeier-Haack reaction and reacting the respective hydrazones with POCl3/DMF. Next, a new series of 3-aryl-4-hydroxymethyl-1H-1-pyrazoles was synthetized from 3-aryl-4-formyl-1H-1-pyrazoles compounds utilizing NaBH4 as carbonyl reducing agent. Subsequently, we carried out metal-free electrophilic fluorination, promoted by Selectfluor, of pyrazoles with methylene groups (-CH2-X) in which X = OH, Ome, F, N3, and NHMe at the C-4 position furnishing the 4-fluoro-pyrazole products from unexpected C-C bond cleavage, at moderate to good yields. Otherwise, under the same reaction conditions, when X = NEt2 or SPr the oxidation product 4-formyl-pyrazole was obtained. In continuation, a synthetic study of two new series of 4-fluorinated 1,3,5-substituted 1H-pyrazoles are described. Thus, an efficient synthesis of new series of 3-aryl-4-(di)fluoromethyl-1H-1-phenylpyrazoles, where [aryl = Ph, 4-NO2C6H4, 4-OCH3C6H4] is described, from deoxofluorination reactions of 4-(formyl)- and 4-(hydroxymethyl)-1H-1-phenylpyrazoles in dichloromethane as solvent at room temperature, employing diethylaminosulfur trifluoride (DAST) as fluorinating agent in 41 to 73 % yield. Finally, from 5-trifluoromethyl-1H-1-phenylpyrazoles previously obtained from the cyclocondesation reaction of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones [in which alkyl/aryl = CH3, C6H5], we performed the iodination using NIS and CF3OOH at the C4 position of these azoles. In a subsequent step, we applied the trifluormetilating reagent MFSDA to promote the trifluormethyl insertion to obtain examples of 4,5-(bis)-trifluoromethyl-1H-1phenylpyrazoles.
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spelling Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDAStudy of fluoro-insertions in 1h-pyrazoles promoted by the fluorinating reagents selectfluor, DAST and MFSDAFluoraçãoPirazóisQuímicaCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAThis thesis describes the studies carried out using fluorinating reagents with different approaches: Selectfluor as an electrophilic fluorine source; DAST for nucleophilic fluorinations and MFSDA as a nucleophilic trifluoromethylating reagent. Fluorinations reactions were carried out in 1H-pyrazoles possessing different substituents in the C3 and C5 positions with the goal of explore the insertion of fluorine atoms and/or fluoroalkyl groups in the C4 position of these substrates. Initially, we design suitable starting materials for the fluorination reactions with Selectfluor and DAST. Thus, 3-aryl-4-formyl-1H-1-pyrazoles compounds were synthetized in two steps reactions from ketones and hydrazines followed by a subsequent Vilsmeier-Haack reaction and reacting the respective hydrazones with POCl3/DMF. Next, a new series of 3-aryl-4-hydroxymethyl-1H-1-pyrazoles was synthetized from 3-aryl-4-formyl-1H-1-pyrazoles compounds utilizing NaBH4 as carbonyl reducing agent. Subsequently, we carried out metal-free electrophilic fluorination, promoted by Selectfluor, of pyrazoles with methylene groups (-CH2-X) in which X = OH, Ome, F, N3, and NHMe at the C-4 position furnishing the 4-fluoro-pyrazole products from unexpected C-C bond cleavage, at moderate to good yields. Otherwise, under the same reaction conditions, when X = NEt2 or SPr the oxidation product 4-formyl-pyrazole was obtained. In continuation, a synthetic study of two new series of 4-fluorinated 1,3,5-substituted 1H-pyrazoles are described. Thus, an efficient synthesis of new series of 3-aryl-4-(di)fluoromethyl-1H-1-phenylpyrazoles, where [aryl = Ph, 4-NO2C6H4, 4-OCH3C6H4] is described, from deoxofluorination reactions of 4-(formyl)- and 4-(hydroxymethyl)-1H-1-phenylpyrazoles in dichloromethane as solvent at room temperature, employing diethylaminosulfur trifluoride (DAST) as fluorinating agent in 41 to 73 % yield. Finally, from 5-trifluoromethyl-1H-1-phenylpyrazoles previously obtained from the cyclocondesation reaction of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones [in which alkyl/aryl = CH3, C6H5], we performed the iodination using NIS and CF3OOH at the C4 position of these azoles. In a subsequent step, we applied the trifluormetilating reagent MFSDA to promote the trifluormethyl insertion to obtain examples of 4,5-(bis)-trifluoromethyl-1H-1phenylpyrazoles.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEsta tese descreve os estudos realizados utilizando reagentes fluorantes com abordagens distintas: o Selectfluor como uma fonte eletrofílica de átomos de flúor; o DAST para as reações de fluoração nucleofílica e o MFSDA como um reagente trifluormetilante nucleofílico. As reações de fluoração foram realizadas em 1H-pirazóis que possuem diferentes substituintes nas posições C3 e C5 com o objetivo de explorar a inserção de átomos de flúor ou grupos fluorados na posição 4 desses substratos. Inicialmente, projetamos materiais de partida adequados paras as reações de fluoração com Selectfluor e DAST. Assim, foram sintetizados os compostos 3-aril-4-formil-1H-pirazóis em dois passos reacionais a partir de cetonas e hidrazinas seguido por uma consequente reação de formilação de Vilsmeier-Haack, reagindo as respectivas hidrazonas com POCl3 em DMF. A seguir, uma nova série de 3-aril-4-hidroximetil-1H-pirazóis foi sintetizada a partir dos compostos 3-aril-4-formil-1H-pirazóis utilizando NaBH4 como agente redutor de carbonilas. Subsequentemente, realizamos reações de fluoração eletrofílica promovida por Selectfluor, sem utilizar catálise metálica, de pirazóis possuindo grupos metilênicos (-CH2-X) no qual X = OH, Ome, F, N3 e NHMe na posição 4, fornecendo os produtos 4-flúor-pirazóis através de uma clivagem da ligação C-C entre o grupo metilênico e o pirazol, em rendimentos moderados. Por outro lado, sob as mesmas condições reacionais, quando X = Net2 ou SPr, foram obtidos os produtos de oxidação 4-formil-pirazóis. Em continuação, foi realizado um estudo sintético de duas séries novas de 1H-pirazóis 1,3,5-substituídos fluorados na posição 4. Assim, sintetizou-se uma série de 3-aril-4-(di)fluormetil-1H-1-fenilpirazóis a partir de reações de deoxofluoração de 3-aril-4-formil(hidroximetil)-1H-pirazóis em diclorometano como solvente a temperatura ambiente, empregando DAST como agente fluorante em rendimentos de 41 73 %. Finalmente, a partir de 5-trifluormetil-1H-1-fenilpirazóis obtidos previamente pela reação de ciclocondensação entre 4-alcóxi-4-alquil(aril)-1,1,1-trifluor-3-alquen-2-onas [onde alquil/aril = CH3, C6H5], foi realizada a iodação utilizando NIS e CF3COOH na posição 4 desses azóis. Em um passo reacional subsequente, foi aplicado o reagente trifluormetilante MFSDA para promover a inserção de um grupo triflurmetila e obter exemplos 4,5-(bis)-trifluormetil-1H-1-fenilpirazóis.Universidade Federal de Santa MariaBRQuímicaUFSMPrograma de Pós-Graduação em QuímicaBonacorso, Helio Gauzehttp://lattes.cnpq.br/7275608974248322Merlo, Aloir Antoniohttp://lattes.cnpq.br/7385210507816401Zanatta, Nilohttp://lattes.cnpq.br/0719465062354576Rodrigues, Oscar Endrigo Dorneleshttp://lattes.cnpq.br/6536519955416085Severo Filho, Wolmar Alípiohttp://lattes.cnpq.br/1999826579939679Pittaluga, Everton Pedebos2017-05-152017-05-152015-08-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfPITTALUGA, Everton Pedebos. Study of fluoro-insertions in 1h-pyrazoles promoted by the fluorinating reagents selectfluor, dast and mfsda. 2015. 235 f. Tese (Doutorado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2015.http://repositorio.ufsm.br/handle/1/4274porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2023-10-18T14:03:23Zoai:repositorio.ufsm.br:1/4274Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-10-18T14:03:23Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
Study of fluoro-insertions in 1h-pyrazoles promoted by the fluorinating reagents selectfluor, DAST and MFSDA
title Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
spellingShingle Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
Pittaluga, Everton Pedebos
Fluoração
Pirazóis
Química
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
title_short Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
title_full Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
title_fullStr Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
title_full_unstemmed Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
title_sort Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
author Pittaluga, Everton Pedebos
author_facet Pittaluga, Everton Pedebos
author_role author
dc.contributor.none.fl_str_mv Bonacorso, Helio Gauze
http://lattes.cnpq.br/7275608974248322
Merlo, Aloir Antonio
http://lattes.cnpq.br/7385210507816401
Zanatta, Nilo
http://lattes.cnpq.br/0719465062354576
Rodrigues, Oscar Endrigo Dorneles
http://lattes.cnpq.br/6536519955416085
Severo Filho, Wolmar Alípio
http://lattes.cnpq.br/1999826579939679
dc.contributor.author.fl_str_mv Pittaluga, Everton Pedebos
dc.subject.por.fl_str_mv Fluoração
Pirazóis
Química
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
topic Fluoração
Pirazóis
Química
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
description This thesis describes the studies carried out using fluorinating reagents with different approaches: Selectfluor as an electrophilic fluorine source; DAST for nucleophilic fluorinations and MFSDA as a nucleophilic trifluoromethylating reagent. Fluorinations reactions were carried out in 1H-pyrazoles possessing different substituents in the C3 and C5 positions with the goal of explore the insertion of fluorine atoms and/or fluoroalkyl groups in the C4 position of these substrates. Initially, we design suitable starting materials for the fluorination reactions with Selectfluor and DAST. Thus, 3-aryl-4-formyl-1H-1-pyrazoles compounds were synthetized in two steps reactions from ketones and hydrazines followed by a subsequent Vilsmeier-Haack reaction and reacting the respective hydrazones with POCl3/DMF. Next, a new series of 3-aryl-4-hydroxymethyl-1H-1-pyrazoles was synthetized from 3-aryl-4-formyl-1H-1-pyrazoles compounds utilizing NaBH4 as carbonyl reducing agent. Subsequently, we carried out metal-free electrophilic fluorination, promoted by Selectfluor, of pyrazoles with methylene groups (-CH2-X) in which X = OH, Ome, F, N3, and NHMe at the C-4 position furnishing the 4-fluoro-pyrazole products from unexpected C-C bond cleavage, at moderate to good yields. Otherwise, under the same reaction conditions, when X = NEt2 or SPr the oxidation product 4-formyl-pyrazole was obtained. In continuation, a synthetic study of two new series of 4-fluorinated 1,3,5-substituted 1H-pyrazoles are described. Thus, an efficient synthesis of new series of 3-aryl-4-(di)fluoromethyl-1H-1-phenylpyrazoles, where [aryl = Ph, 4-NO2C6H4, 4-OCH3C6H4] is described, from deoxofluorination reactions of 4-(formyl)- and 4-(hydroxymethyl)-1H-1-phenylpyrazoles in dichloromethane as solvent at room temperature, employing diethylaminosulfur trifluoride (DAST) as fluorinating agent in 41 to 73 % yield. Finally, from 5-trifluoromethyl-1H-1-phenylpyrazoles previously obtained from the cyclocondesation reaction of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones [in which alkyl/aryl = CH3, C6H5], we performed the iodination using NIS and CF3OOH at the C4 position of these azoles. In a subsequent step, we applied the trifluormetilating reagent MFSDA to promote the trifluormethyl insertion to obtain examples of 4,5-(bis)-trifluoromethyl-1H-1phenylpyrazoles.
publishDate 2015
dc.date.none.fl_str_mv 2015-08-19
2017-05-15
2017-05-15
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 PITTALUGA, Everton Pedebos. Study of fluoro-insertions in 1h-pyrazoles promoted by the fluorinating reagents selectfluor, dast and mfsda. 2015. 235 f. Tese (Doutorado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2015.
http://repositorio.ufsm.br/handle/1/4274
identifier_str_mv PITTALUGA, Everton Pedebos. Study of fluoro-insertions in 1h-pyrazoles promoted by the fluorinating reagents selectfluor, dast and mfsda. 2015. 235 f. Tese (Doutorado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2015.
url http://repositorio.ufsm.br/handle/1/4274
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Química
UFSM
Programa de Pós-Graduação em Química
publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Química
UFSM
Programa de Pós-Graduação em Química
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
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institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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