Mofaddel N, Krajian H, Villemin D, Desbène P L
L.A.S.O.C. - IRCOF et IFRMP, Université de Rouen, 55 rue Saint Germain, 27000 Evreux, France.
J Chromatogr A. 2008 Nov 21;1211(1-2):142-50. doi: 10.1016/j.chroma.2008.09.099. Epub 2008 Oct 4.
Chiral binaphthols belong to the group of most effective ligands for asymmetrical catalysis. In this context, various binaphthols presenting original substituents have been synthesized. Their study through capillary electrophoresis is the object of this work. The literature dedicated to the separation of atropisomers by capillary electrophoresis, corresponding only to binaphthol, reveals that its enantioseparation is always delicate because of the influence of many factors and the resolutions obtained are weak. Therefore, for a structured optimization, we first successfully evaluated the acidity constants of different binaphthols by means of capillary electrophoresis. With these known physicochemical characteristics, we could successfully carry out enantiomeric separations of the different binaphthols at pH 11.5, practically in completely ionized form, in phosphate medium, and in the presence of cyclodextrin (CD), with analysis times lower than 8min. The nature of CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD), HP-beta-CD, HP-gamma-CD and trimethyl-beta-CD (TM-beta-CD)) and other factors in relation to enantiomeric resolution (applied voltage, nature and concentration of the electrolyte, and concentration of cyclodextrin) were optimized. These studies allowed us to determine the optimal conditions of separation (concentration and nature of CD) for each of the studied binaphthols. It is necessary to mention that, for the 1,1'-binaphthyl-2,2'-diol (Binol) at pH 11.5, the S atropisomer always migrated first, regardless of the nature and concentration of the cyclodextrin used. Moreover, an inversion in elution order of the two atropisomers as a function of pH was observed with gamma-CD (pH range: 10-11.5). The R atropisomer migrated first at pH 10. At pH 10.8 the migration order of the two atropisomers of Binol was reversed as a function of gamma-CD concentration. Finally, the addition of chiral ionic liquids (R(-)-1-hydroxy-N,N,N-trimethylbutan-2-aminium bis(trifluoromethylsulfonyl)imide and S(+)-tetrabutylammonium camphorsulfonate) was conducted. In the case of S(+)-tetrabutylammonium camphorsulfonate, a weak antagonistic effect was observed with modeling the evolution of enantiomeric resolution by means of the experimental design, while in the case of R(-)-1-hydroxy-N,N,N-trimethylbutan-2-aminium bis(trifluoromethylsulfonyl)imide the effect was neutral.
手性联萘酚属于不对称催化中最有效的配体类别。在此背景下，已合成了各种带有原始取代基的联萘酚。通过毛细管电泳对它们进行研究是本工作的目标。专门研究通过毛细管电泳分离阻转异构体（仅对应联萘酚）的文献表明，由于多种因素的影响，其对映体分离始终很棘手，且获得的分离度较弱。因此，为了进行结构化优化，我们首先通过毛细管电泳成功评估了不同联萘酚的酸度常数。利用这些已知的物理化学特性，我们能够在pH 11.5的磷酸盐介质中，在环糊精（CD）存在的情况下，以几乎完全电离的形式，在低于8分钟的分析时间内成功实现不同联萘酚的对映体分离。对CD的性质（α - CD、β - CD、γ - CD、羟丙基 - α - 环糊精（HP - α - CD）、HP - β - CD、HP - γ - CD和三甲基 - β - 环糊精（TM - β - CD））以及与对映体拆分相关的其他因素（施加电压、电解质的性质和浓度以及环糊精的浓度）进行了优化。这些研究使我们能够确定每种所研究联萘酚的最佳分离条件（CD的浓度和性质）。需要提及的是，对于1,1'-联萘基 - 2,2'-二醇（联萘酚）在pH 11.5时，无论所用环糊精的性质和浓度如何，S阻转异构体总是首先迁移。此外，观察到使用γ - CD时（pH范围：10 - 11.5），两种阻转异构体的洗脱顺序随pH发生反转。在pH 10时，R阻转异构体首先迁移。在pH 10.8时，联萘酚的两种阻转异构体的迁移顺序随γ - CD浓度而反转。最后，加入了手性离子液体（R(-)-1 - 羟基 - N,N,N - 三甲基丁 - 2 - 铵双（三氟甲基磺酰）亚胺和S(+)-四丁基铵樟脑磺酸盐）。在S(+)-四丁基铵樟脑磺酸盐的情况下，通过实验设计对映体拆分演变进行建模时观察到微弱的拮抗作用，而在R(-)-1 - 羟基 - N,N,N - 三甲基丁 - 2 - 铵双（三氟甲基磺酰）亚胺的情况下，该作用呈中性。
