Enantiomerization barriers of atropisomeric amidinoquinoxaline N-oxides

JIMENA E. DÍAZ; MARTÍN J. RODRÍGUEZ SAÁ; HELENE RISPAUD; NICOLAS VANTHUYNE; CHRIATIAN ROUSSEL; LILIANA R. ORELLI

Cancun

Conferencia; 11th. Latin American Conference on Physical Organic Chemistry; 2011

CLAFQO

ENANTIOMERIZATION BARRIERS OF ATROPISOMERIC AMIDINOQUINOXALINE N-OXIDESJimena E. Díaz,a Martín J. Rodríguez Saá,a Hélène Rispaud,b Nicolas Vanthuyne,b Christian Roussel,b Liliana R. Orelliaa Facultad de Farmacia y Bioquimica. Universidad de Buenos Aires, CONICET, Junin 956, Buenos Aires, Argentina. Email: lorelli@ffyb.uba.arbLaboratoire de Stéréochimie Dynamique et Chiralité, ISM2, Université Paul Cézanne, Chirosciences, Marseille, FranceAtropisomerism is a property of some molecules that exist as enantiomeric forms due to restricted rotation around certain single bonds, which behave as chiral axes. In the last years, there is a growing interest for the development of stable non-biaryl atropisomers, due to their potential employment in stereo and enantioselective synthesis. 2,3-Dihydro-1H-pyrimido[1,2-a]quinoxaline N-oxides represent a heterocyclic core of wide interest due to the pharmacological properties of some members. Amidinoquinoxaline N-oxides with dissymmetrical aryl substituents are expected to have the plane of the ortho substituted aryl ring significantly twisted with respect to the heterocyclic ring system, entailing the existence of conformational enantiomers (atropisomers) [1]. Conversion of one enantiomer into the other, due to rotation around the restricted bond, entails an enantiomerization barrier (ΔG≠rot). In this work, we present the determination of the enantiomerization barriers of atropoisomeric quinoxaline N-oxides using chiral HPLC. We also discuss the influence of the ring size and the stereoelectronic nature of the substituents on the magnitude of the enantiomerization barriers.Compounds 1 were synthesized by the methodology previously described by our group [2]. The enantiomerization barriers of the compounds were calculated from the corresponding krot, which were determined by two alternative methods involving chiral HPLC. The classical kinetic measurements (?off column method?) were used for compounds for which baseline separation was achieved. For compounds undergoing interconversion during chiral separation, which yielded plateau-shaped chromatograms, krot was determined by analysis of the chromatographic parameters with the equation of Trapp and Schurig [3].References:[1] J. E. Díaz, M. B. García, L. R. Orelli, J. Mol. Struct., 982, 50 (2010).[2] M. B. García, L. R. Orelli, M. L. Magri, I. A. Perillo, Synthesis 18, 2687 (2002).[3] Trapp, O.; Schurig, V., J. Chromat. A, 2001, 911, 167.