Sinthopweha Wichai, Khamto Nopawit, Rithchumpon Puracheth, Meepowpan Puttinan
Department of Chemistry, Faculty of Science, Chiang Mai University 239 Huay Kaew Road Chiang Mai 50200 Thailand
Multidisciplinary and Interdisciplinary School, Chiang Mai University 239 Huay Kaew Road Chiang Mai 50200 Thailand.
RSC Adv. 2025 Aug 6;15(34):28063-28074. doi: 10.1039/d5ra04790k. eCollection 2025 Aug 1.
1,1'-bi-2-naphthols (BINOLs) and their derivatives have been extensively studied over the years. Enantiopure BINOLs are crucial in asymmetric synthesis, circularly polarized luminescent dyes, and charge transfer host systems. Several methods, including asymmetric oxidative coupling, enzymatic resolution, and chemical resolution, have been explored to prepare enantiopure BINOLs. Chemical resolution by chromatography offers the advantage of obtaining both enantiomers with high purity. Herein, we employed methyl itaconate-anthracene adducts (MIAs) as chiral resolving agents (CRAs) for the resolution of racemic BINOLs. Diastereomers were obtained esterification in yields ranging from 37% to 62%. H NMR revealed distinct H proton behaviors, correlating with the orientation of the second naphthol ring as predicted by DFT calculations. In the diastereomers without 3,3'-dibromo-substituted BINOLs, the H protons were shielded from the anisotropic effect, whereas 3,3'-dibromo-substituted BINOLs diastereomers exhibited the opposite effect. MIAs effectively resolved racemic BINOLs on TLC, showing significant differences in retardation factor ( ). Molecular dynamics simulations predicted TLC resolution trends by examining the number of hydrogen bonds between diastereomers and silica gel. For diastereomers without 3,3'-dibromo-substituted BINOLs, the (,)-diastereomers formed more hydrogen bonds than the (,)-diastereomers, resulting in lower values. Conversely, for diastereomers of 3,3'-dibromo-substituted BINOLs, the (,)-diastereomers exhibited stronger hydrogen bonding.
多年来，1,1'-联二萘酚（BINOLs）及其衍生物一直受到广泛研究。对映体纯的BINOLs在不对称合成、圆偏振发光染料和电荷转移主体体系中至关重要。人们探索了多种方法来制备对映体纯的BINOLs，包括不对称氧化偶联、酶促拆分和化学拆分。通过色谱法进行化学拆分具有获得两种高纯度对映体的优势。在此，我们使用衣康酸甲酯 - 蒽加合物（MIAs）作为手性拆分剂（CRAs）来拆分外消旋BINOLs。通过酯化反应得到非对映异构体，产率在37%至62%之间。核磁共振氢谱（¹H NMR）揭示了不同的¹H质子行为，这与密度泛函理论（DFT）计算预测的第二个萘环的取向相关。在没有3,3'-二溴取代的BINOLs的非对映异构体中，¹H质子受到各向异性效应的屏蔽，而3,3'-二溴取代的BINOLs非对映异构体则表现出相反的效果。MIAs在薄层色谱（TLC）上有效地拆分了外消旋BINOLs，显示出在比移值（Rf）上有显著差异。分子动力学模拟通过检查非对映异构体与硅胶之间的氢键数量预测了TLC拆分趋势。对于没有3,3'-二溴取代的BINOLs的非对映异构体，（+，+）-非对映异构体比（-，-）-非对映异构体形成更多的氢键，导致Rf值更低。相反，对于3,3'-二溴取代的BINOLs的非对映异构体，（-，-）-非对映异构体表现出更强的氢键作用。
