ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Chiral amino alcohol polydentate ligands: modular synthesis and application in the enantiodifferentiation of camphorsulfonic acid and other chiral carboxylic acids

Jie Shen, Jun Yin, Hao-Yue Xiang, and Feng-Liang Liu

College of Chemistry and Chemical Engineering, Central South University, Changsha, China

E-mail: 17872296844@163.com

Received: 10 December 2025  Accepted: 2 February 2026

Abstract:

A family of chiral tridentate amino alcohols was efficiently synthesized through modular strategies integrating pyridine or quinoline scaffolds with chiral amino alcohols. These ligands were evaluated as chiral solvating agents (CSAs) for the enantiodiscrimination of several representative analytes, including camphorsulfonic acid, amino acid derivatives, ibuprofen, and mandelic acid. Systematic ¹H NMR studies revealed that quinoline-based CSAs (ΔΔδ = 0.0048–0.060 ppm, 2.40–30.16 Hz) generally outperformed their pyridine counterparts (ΔΔδ = 0.0045–0.029 ppm, 2.24–14.72 Hz), likely due to enhanced anisotropic shielding from their extended π-conjugation. Interestingly, when sterically hindered tertiary alcohols were introduced, this structure activity trend reversed, and the pyridine-based tertiary alcohol ligand afforded a dramatically expanded discrimination range (ΔΔδ = 0.0067–0.19 ppm, 3.36–95.00 Hz), with the maximum value reaching 0.19 ppm (95.00 Hz). This work clarifies the structural determinants governing NMR-based chiral discrimination and offers practical molecular design principles for chiral solvating agents.

Graphical abstract

Keywords: Chiral solvating agents; Tridentate amino alcohols; Enantiodiscrimination; Camphorsulfonic acid; Amino acid derivatives

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04711-x

Chemical Papers 80 (5) 5295–5307 (2026)