Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA
Ano de defesa: | 2015 |
---|---|
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
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química
|
Departamento: |
Química
|
País: |
BR
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | 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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2017-05-152017-05-152015-08-19PITTALUGA, 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/1/4274This 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.Esta 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em QuímicaUFSMBRQuímicaFluoraçãoPirazóisQuímicaCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAEstudo 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 MFSDAinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBonacorso, 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/1999826579939679http://lattes.cnpq.br/9861629877388118Pittaluga, Everton Pedebos10060000000040030030030030030030006c852ad-d805-43c3-99d6-93a6a86f507ce36593ac-be1c-47e5-9fc8-221ad7973ab4fa2e7141-9b4f-43d6-a7af-6718960f91a72f7bd6ce-78fa-4968-ac66-2d1407e90f60e7f4492f-46f8-436e-b78d-5bee588e11e42a22b094-e5c8-4206-9e98-00ec38939b46info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALPITTALUGA, EVERTON PEDEBOS.pdfapplication/pdf11161545http://repositorio.ufsm.br/bitstream/1/4274/1/PITTALUGA%2c%20EVERTON%20PEDEBOS.pdff6c553cb2f6a0863cdabd6c37d9d18eaMD51TEXTPITTALUGA, EVERTON PEDEBOS.pdf.txtPITTALUGA, EVERTON PEDEBOS.pdf.txtExtracted texttext/plain252338http://repositorio.ufsm.br/bitstream/1/4274/2/PITTALUGA%2c%20EVERTON%20PEDEBOS.pdf.txt973de5d1c29133ac929c963df8abcf8aMD52THUMBNAILPITTALUGA, EVERTON PEDEBOS.pdf.jpgPITTALUGA, EVERTON PEDEBOS.pdf.jpgIM Thumbnailimage/jpeg5134http://repositorio.ufsm.br/bitstream/1/4274/3/PITTALUGA%2c%20EVERTON%20PEDEBOS.pdf.jpgb84cdbd5d169bfb71deb137d8207652fMD531/42742023-10-18 11:03:23.03oai: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:2023-10-18T14:03:23Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Estudo de reações de flúor-inserção em 1H-pirazóis utilizando os reagentes fluorantes selectfluor, DAST e MFSDA |
dc.title.alternative.eng.fl_str_mv |
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.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.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/7385210507816401 |
dc.contributor.referee2.fl_str_mv |
Zanatta, Nilo |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0719465062354576 |
dc.contributor.referee3.fl_str_mv |
Rodrigues, Oscar Endrigo Dorneles |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/6536519955416085 |
dc.contributor.referee4.fl_str_mv |
Severo Filho, Wolmar Alípio |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/1999826579939679 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/9861629877388118 |
dc.contributor.author.fl_str_mv |
Pittaluga, Everton Pedebos |
contributor_str_mv |
Bonacorso, Helio Gauze Merlo, Aloir Antonio Zanatta, Nilo Rodrigues, Oscar Endrigo Dorneles Severo Filho, Wolmar Alípio |
dc.subject.por.fl_str_mv |
Fluoração Pirazóis Química |
topic |
Fluoração Pirazóis Química CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.cnpq.fl_str_mv |
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.issued.fl_str_mv |
2015-08-19 |
dc.date.accessioned.fl_str_mv |
2017-05-15 |
dc.date.available.fl_str_mv |
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.citation.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. |
dc.identifier.uri.fl_str_mv |
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 |
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por |
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100600000000 |
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400 300 300 300 300 300 300 |
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Programa de Pós-Graduação em Química |
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UFSM |
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Universidade Federal de Santa Maria |
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