Towards a rational design for resolving agents. Part V: Substituent effects in the resolution of ephedrine using a series of cyclic phosphoric acids

Abstract

Abstract. The effects of various aromatic substituents in both ephedrine and a cyclic phosphoric acid on the quality of resolution via diastereomeric salt formation are investigated. The diastereoselective synthesis of a novel series of chloro-substituted ephedrines is described. These chloroephedrines can be resolved efficiently with some of the cyclic phosphoric acids. By studying the physical properties of nineteen pairs of diastereomeric salts, we show that the quality o f the resolution depends mainly on the aromatic substituent o f the cyclic phosphoric acid, whereas substituents at the phenyl ring of ephedrine play a secondary role.

Family of Conglomerate-Forming Systems Composed of Chlocyphos and Alkyl-amine. Assessment of Their Resolution Performances by Using Various Modes of Preferential Crystallization

“…The enantiomers of chlocyphos are of great interest as several cyclic phosphoric acids, including phencyphos and anicyphos, are used as effective resolving agents in preparing optically pure amines , (ephedrine, valine, etc.). Diastereomeric salt formation process is often used to resolve these phosphoric acids, but this method sometimes fails due, for example, to the formation of an oil, a gel, or a solid solution . Furthermore, this method does not always fit with industrial needs (i.e., low cost, high enantiomeric excess, and high productivity).…”