Chirality switching in the enantioseparation of 2-hydroxy-4-phenylbutyric acid: Role of solvents in selective crystallization of the diastereomeric salt. Issue 16 (16th April 2020)

• Record Type: Journal Article
• Authors: Kodama, Koichi; Yi, Meng; Shitara, Hiroaki; Hirose, Takuji
• Is Part Of: Tetrahedron letters. Volume 61:Issue 16(2020)
• Publication Date: 2020-04-16
• Subjects: Enantioseparation -- Diastereomeric salt -- Chirality -- Hydrogen bond; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2020.151773
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Optical resolution of a carboxylic acid by diastereomeric salt formation. Both diastereomeric salts were obtained only by changing crystallization solvents. Chirality switching was caused by solvent inclusion in the salt crystals. Multiple pseudo-polymorphic hydrated salt crystals are produced. Abstract: Chirality switching was induced by solvents in the enantioseparation of 2-hydroxy-4-phenylbutyric acid (HPBA) via diastereomeric salt formation with an enantiopure aminoalcohol. The ( S )-salt was crystallized from butanol solutions and the ( R )-salt was obtained from aqueous solutions. It was found from crystallographic analysis of the salts that solvent inclusion changed the solubility of both salts. In particular, the ( R )-salt afforded multiple pseudo-polymorphic hydrated crystals. Successive crystallization from two different solvents efficiently afforded both pure diastereomeric salts.