Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers

Autores
Díaz, Jimena Estela; Vanthuyne, Nicolas; Rispaud, Hélène; Roussel, Christian; Vega, Daniel Alberto; Orelli, Liliana Raquel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The atropisomerism of novel 2,3-dihydro1H-pyrimido[1,2-a]quinoxaline 6-oxides 1 bearing dissymmetric (ortho-substituted) 5-aryl residues and the homologous 1,2-dihydroimidazo[1,2-a]quinoxaline 5-oxides 2 was investigated. The existence of a chiral axis was demonstrated for compound 1a by X-ray diffraction and by DFT calculations of the ground state geometry. The resolution of the atropisomeric enantiomers on chiral stationary phases is reported. The barriers to enantiomerization were determined by off-line racemization studies and/or by treatment of the plateau-shape chromatograms during chromatography on chiral support. A clear ring size effect was evidenced. In all cases, six-membered amidine derivatives 1 showed higher barriers than the corresponding lower homologues 2, which also display lower sensitivity to the substituent size. Transition states for the interconversion of the atropisomers were located using DFT calculations, and involved the interaction of the ortho substituent with the formally sp2 nitrogen in the amidine moiety. In contrast, in the most favoured enantiomerization transition state of the 2-nitro derivative the ortho substituent is close to the N-oxide group.
Fil: Díaz, Jimena Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Aix Marseille Université; Francia
Fil: Vanthuyne, Nicolas. Aix Marseille Université; Francia
Fil: Rispaud, Hélène. Aix Marseille Université; Francia
Fil: Roussel, Christian. Aix Marseille Université; Francia
Fil: Vega, Daniel Alberto. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comision Nacional de Energia Atomica; Argentina
Fil: Orelli, Liliana Raquel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Atropisomerism
Chiral Hplc
Nitrogen Heterocycles
Enantiomerisation Barriers
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15919
Acceder
id CONICETDig_a5bd6cb50ca97ca58e913d67bd71a67c
oai_identifier_str oai:ri.conicet.gov.ar:11336/15919
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriersDíaz, Jimena EstelaVanthuyne, NicolasRispaud, HélèneRoussel, ChristianVega, Daniel AlbertoOrelli, Liliana RaquelAtropisomerismChiral HplcNitrogen HeterocyclesEnantiomerisation Barriershttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The atropisomerism of novel 2,3-dihydro1H-pyrimido[1,2-a]quinoxaline 6-oxides 1 bearing dissymmetric (ortho-substituted) 5-aryl residues and the homologous 1,2-dihydroimidazo[1,2-a]quinoxaline 5-oxides 2 was investigated. The existence of a chiral axis was demonstrated for compound 1a by X-ray diffraction and by DFT calculations of the ground state geometry. The resolution of the atropisomeric enantiomers on chiral stationary phases is reported. The barriers to enantiomerization were determined by off-line racemization studies and/or by treatment of the plateau-shape chromatograms during chromatography on chiral support. A clear ring size effect was evidenced. In all cases, six-membered amidine derivatives 1 showed higher barriers than the corresponding lower homologues 2, which also display lower sensitivity to the substituent size. Transition states for the interconversion of the atropisomers were located using DFT calculations, and involved the interaction of the ortho substituent with the formally sp2 nitrogen in the amidine moiety. In contrast, in the most favoured enantiomerization transition state of the 2-nitro derivative the ortho substituent is close to the N-oxide group.Fil: Díaz, Jimena Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Aix Marseille Université; FranciaFil: Vanthuyne, Nicolas. Aix Marseille Université; FranciaFil: Rispaud, Hélène. Aix Marseille Université; FranciaFil: Roussel, Christian. Aix Marseille Université; FranciaFil: Vega, Daniel Alberto. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comision Nacional de Energia Atomica; ArgentinaFil: Orelli, Liliana Raquel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Chemical Society2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15919Díaz, Jimena Estela; Vanthuyne, Nicolas; Rispaud, Hélène; Roussel, Christian; Vega, Daniel Alberto; et al.; Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers; American Chemical Society; Journal of Organic Chemistry; 80; 3; 1-2015; 1689-16950022-3263enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jo502626finfo:eu-repo/semantics/altIdentifier/doi/10.1021/jo502626finfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:31Zoai:ri.conicet.gov.ar:11336/15919instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:15:32.143CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
title Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
spellingShingle Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
Díaz, Jimena Estela
Atropisomerism
Chiral Hplc
Nitrogen Heterocycles
Enantiomerisation Barriers
title_short Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
title_full Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
title_fullStr Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
title_full_unstemmed Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
title_sort Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers
dc.creator.none.fl_str_mv Díaz, Jimena Estela
Vanthuyne, Nicolas
Rispaud, Hélène
Roussel, Christian
Vega, Daniel Alberto
Orelli, Liliana Raquel
author Díaz, Jimena Estela
author_facet Díaz, Jimena Estela
Vanthuyne, Nicolas
Rispaud, Hélène
Roussel, Christian
Vega, Daniel Alberto
Orelli, Liliana Raquel
author_role author
author2 Vanthuyne, Nicolas
Rispaud, Hélène
Roussel, Christian
Vega, Daniel Alberto
Orelli, Liliana Raquel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Atropisomerism
Chiral Hplc
Nitrogen Heterocycles
Enantiomerisation Barriers
topic Atropisomerism
Chiral Hplc
Nitrogen Heterocycles
Enantiomerisation Barriers
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The atropisomerism of novel 2,3-dihydro1H-pyrimido[1,2-a]quinoxaline 6-oxides 1 bearing dissymmetric (ortho-substituted) 5-aryl residues and the homologous 1,2-dihydroimidazo[1,2-a]quinoxaline 5-oxides 2 was investigated. The existence of a chiral axis was demonstrated for compound 1a by X-ray diffraction and by DFT calculations of the ground state geometry. The resolution of the atropisomeric enantiomers on chiral stationary phases is reported. The barriers to enantiomerization were determined by off-line racemization studies and/or by treatment of the plateau-shape chromatograms during chromatography on chiral support. A clear ring size effect was evidenced. In all cases, six-membered amidine derivatives 1 showed higher barriers than the corresponding lower homologues 2, which also display lower sensitivity to the substituent size. Transition states for the interconversion of the atropisomers were located using DFT calculations, and involved the interaction of the ortho substituent with the formally sp2 nitrogen in the amidine moiety. In contrast, in the most favoured enantiomerization transition state of the 2-nitro derivative the ortho substituent is close to the N-oxide group.
Fil: Díaz, Jimena Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Aix Marseille Université; Francia
Fil: Vanthuyne, Nicolas. Aix Marseille Université; Francia
Fil: Rispaud, Hélène. Aix Marseille Université; Francia
Fil: Roussel, Christian. Aix Marseille Université; Francia
Fil: Vega, Daniel Alberto. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comision Nacional de Energia Atomica; Argentina
Fil: Orelli, Liliana Raquel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The atropisomerism of novel 2,3-dihydro1H-pyrimido[1,2-a]quinoxaline 6-oxides 1 bearing dissymmetric (ortho-substituted) 5-aryl residues and the homologous 1,2-dihydroimidazo[1,2-a]quinoxaline 5-oxides 2 was investigated. The existence of a chiral axis was demonstrated for compound 1a by X-ray diffraction and by DFT calculations of the ground state geometry. The resolution of the atropisomeric enantiomers on chiral stationary phases is reported. The barriers to enantiomerization were determined by off-line racemization studies and/or by treatment of the plateau-shape chromatograms during chromatography on chiral support. A clear ring size effect was evidenced. In all cases, six-membered amidine derivatives 1 showed higher barriers than the corresponding lower homologues 2, which also display lower sensitivity to the substituent size. Transition states for the interconversion of the atropisomers were located using DFT calculations, and involved the interaction of the ortho substituent with the formally sp2 nitrogen in the amidine moiety. In contrast, in the most favoured enantiomerization transition state of the 2-nitro derivative the ortho substituent is close to the N-oxide group.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15919
Díaz, Jimena Estela; Vanthuyne, Nicolas; Rispaud, Hélène; Roussel, Christian; Vega, Daniel Alberto; et al.; Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers; American Chemical Society; Journal of Organic Chemistry; 80; 3; 1-2015; 1689-1695
0022-3263
url http://hdl.handle.net/11336/15919
identifier_str_mv Díaz, Jimena Estela; Vanthuyne, Nicolas; Rispaud, Hélène; Roussel, Christian; Vega, Daniel Alberto; et al.; Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and substituents on the enantiomerization barriers; American Chemical Society; Journal of Organic Chemistry; 80; 3; 1-2015; 1689-1695
0022-3263
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jo502626f
info:eu-repo/semantics/altIdentifier/doi/10.1021/jo502626f
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614092219744256
score 13.070432

Publicaciones similares