Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , |
Tipo de documento: | Artigo de conferência |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10174/19756 |
Resumo: | 1,2,4,5-Tetrazines are six-membered heterocyclic compounds in which the four nitrogen atoms are displayed in a symmetric fashion. Their reactivity is quite different from other heterocyclic aromatic systems due to its unique electron-withdrawing character, comparable to tetra-nitrobenzene. 1 In particular, 1,2,4,5- tetrazines are known to take part in [4+2] inverse-Diels–Alder cycloaddition processes which efficiently lead to the construction of substituted pyridazine systems that are important in drug development and biomarker applications. 2 However, the electronic character of 1,2,4,5-tetrazines hampered the development of 3- ethynyl- and 3,6-diethynyl-1,2,4,5-tetrazine derivatives for molecular electronic applications, proved by the scarcity of examples found in the literature. 3 Herein, we describe the synthesis and characterization of two novel ethynyl-based 1,2,4,5-tetrazine derivatives. Synthesis of 3,6-(4-bromophenyl)-1,2,4,5-tetrazine precursor (1) was achieved in good yield by Pinner’s method, starting from 4-bromobenzonitrile. Despite its low solubility in common organic solvents, this precursor was found to react smoothly under typical Sonogashira coupling conditions to selectively afford the 3-ethynyl (2) and 3,6-diethynyl (3) protected derivatives (Figure 1). Reaction conditions were evaluated in order to provide the best yields and to promote selectivity of the mono- or disubstituted ethynyl derivatives. Finally, deprotection was achieved affording, in the case of compound 3, an unprecedented 3,6- diethynyl-1,2,4,5-tetrazine compound. Time-Dependent Density Functional Theory (TDDFT) calculations for both deprotected ethynyl derivatives were used to simulate electronic spectra. A deep knowledge of the relevant electronic transitions involved and quantitatively satisfactory results of the calculated electronic excitations in comparison with experimental data were obtained. |
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Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives1,2,4,5-Tetrazines are six-membered heterocyclic compounds in which the four nitrogen atoms are displayed in a symmetric fashion. Their reactivity is quite different from other heterocyclic aromatic systems due to its unique electron-withdrawing character, comparable to tetra-nitrobenzene. 1 In particular, 1,2,4,5- tetrazines are known to take part in [4+2] inverse-Diels–Alder cycloaddition processes which efficiently lead to the construction of substituted pyridazine systems that are important in drug development and biomarker applications. 2 However, the electronic character of 1,2,4,5-tetrazines hampered the development of 3- ethynyl- and 3,6-diethynyl-1,2,4,5-tetrazine derivatives for molecular electronic applications, proved by the scarcity of examples found in the literature. 3 Herein, we describe the synthesis and characterization of two novel ethynyl-based 1,2,4,5-tetrazine derivatives. Synthesis of 3,6-(4-bromophenyl)-1,2,4,5-tetrazine precursor (1) was achieved in good yield by Pinner’s method, starting from 4-bromobenzonitrile. Despite its low solubility in common organic solvents, this precursor was found to react smoothly under typical Sonogashira coupling conditions to selectively afford the 3-ethynyl (2) and 3,6-diethynyl (3) protected derivatives (Figure 1). Reaction conditions were evaluated in order to provide the best yields and to promote selectivity of the mono- or disubstituted ethynyl derivatives. Finally, deprotection was achieved affording, in the case of compound 3, an unprecedented 3,6- diethynyl-1,2,4,5-tetrazine compound. Time-Dependent Density Functional Theory (TDDFT) calculations for both deprotected ethynyl derivatives were used to simulate electronic spectra. A deep knowledge of the relevant electronic transitions involved and quantitatively satisfactory results of the calculated electronic excitations in comparison with experimental data were obtained.2017-01-12T17:22:28Z2017-01-122015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjecthttp://hdl.handle.net/10174/19756http://hdl.handle.net/10174/19756engPaulo J. G. Mendes, Tiago J. L. Silva, M. Helena Garcia. Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives., International Symposium on Synthesis and Catalysis, 2-4 Sep 2015, Évora, Portugal. Book of Abstracts P91, p.215http://isysycat.eventos.chemistry.pt/naonaosimQUIpjgm@uevora.pttjlsilva@gmail.commhgarcia@fc.ul.ptMendes, Paulo J.Silva, Tiago J.L.Garcia, M. Helenainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-03T19:09:13Zoai:dspace.uevora.pt:10174/19756Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:11:24.363901Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
title |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
spellingShingle |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives Mendes, Paulo J. |
title_short |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
title_full |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
title_fullStr |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
title_full_unstemmed |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
title_sort |
Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives |
author |
Mendes, Paulo J. |
author_facet |
Mendes, Paulo J. Silva, Tiago J.L. Garcia, M. Helena |
author_role |
author |
author2 |
Silva, Tiago J.L. Garcia, M. Helena |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Mendes, Paulo J. Silva, Tiago J.L. Garcia, M. Helena |
description |
1,2,4,5-Tetrazines are six-membered heterocyclic compounds in which the four nitrogen atoms are displayed in a symmetric fashion. Their reactivity is quite different from other heterocyclic aromatic systems due to its unique electron-withdrawing character, comparable to tetra-nitrobenzene. 1 In particular, 1,2,4,5- tetrazines are known to take part in [4+2] inverse-Diels–Alder cycloaddition processes which efficiently lead to the construction of substituted pyridazine systems that are important in drug development and biomarker applications. 2 However, the electronic character of 1,2,4,5-tetrazines hampered the development of 3- ethynyl- and 3,6-diethynyl-1,2,4,5-tetrazine derivatives for molecular electronic applications, proved by the scarcity of examples found in the literature. 3 Herein, we describe the synthesis and characterization of two novel ethynyl-based 1,2,4,5-tetrazine derivatives. Synthesis of 3,6-(4-bromophenyl)-1,2,4,5-tetrazine precursor (1) was achieved in good yield by Pinner’s method, starting from 4-bromobenzonitrile. Despite its low solubility in common organic solvents, this precursor was found to react smoothly under typical Sonogashira coupling conditions to selectively afford the 3-ethynyl (2) and 3,6-diethynyl (3) protected derivatives (Figure 1). Reaction conditions were evaluated in order to provide the best yields and to promote selectivity of the mono- or disubstituted ethynyl derivatives. Finally, deprotection was achieved affording, in the case of compound 3, an unprecedented 3,6- diethynyl-1,2,4,5-tetrazine compound. Time-Dependent Density Functional Theory (TDDFT) calculations for both deprotected ethynyl derivatives were used to simulate electronic spectra. A deep knowledge of the relevant electronic transitions involved and quantitatively satisfactory results of the calculated electronic excitations in comparison with experimental data were obtained. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-01-01T00:00:00Z 2017-01-12T17:22:28Z 2017-01-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/conferenceObject |
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conferenceObject |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10174/19756 http://hdl.handle.net/10174/19756 |
url |
http://hdl.handle.net/10174/19756 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Paulo J. G. Mendes, Tiago J. L. Silva, M. Helena Garcia. Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives., International Symposium on Synthesis and Catalysis, 2-4 Sep 2015, Évora, Portugal. Book of Abstracts P91, p.215 http://isysycat.eventos.chemistry.pt/ nao nao sim QUI pjgm@uevora.pt tjlsilva@gmail.com mhgarcia@fc.ul.pt |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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