Towards a rational design of resolving agents. Part III. structural study of two pairs of diastereomeric salts of ephedrine and a cyclic phosphoric acid

Abstract

Abstract. The crystal structures of two pairs of diastereomeric salts consisting of ephedrine and a cyclic phosphoric acid were analyzed in detail.. One pair (R = H; Figure 1) shows no difference in solubility, as reflected in identical non-bonded interaction patterns in the two salts. The other pair (R = C1; Figure 1) shows a significant solubility difference; the crystal packings of these two salts differ considerably. The less soluble salt shows far more favorable Van der Waals interactions, presenting further evidence that the result of optical resolutions by selective crystallization are determined by these weak interactions. This study, in combination with the results presented in the previous paper (Towards a rational design of resolving agents, Part 11), suggests that a model might be developed describing a (quantitative) relationship between the lattice energy difference in a diastereomeric pair and the resolution efficiency of the resolving agent.

Binary and Ternary Phase Diagrams as Routes to Salt Discovery: Ephedrine and Pimelic Acid

“…17 The extended conformation is the most common and lower energy state 23,24 and is displayed in the pure ephedrine, ephedrine hemihydrate, and both salt structures discussed in this paper. Salts of ephedrine previously formed, including the majority published by Collier et al, 17 appear to favor the extended conformation.…”

Crystal structure determination by combined synchrotronpowder X-ray diffraction and crystal structure prediction: 1 : 1 l-ephedrined-tartrate

“…31 The structure exhibits a typical double-layered sandwich feature as found frequently in other Eph salt structures. 4,33 It is held together by (i) primary Coulombic interaction between the acid anion and the Eph cation, (ii) extensive and complex intermolecular hydrogen bonding between neighbouring ions, and (iii) aromatic face-to-edge interaction between phenyl rings of adjacent L-Eph ions. The hydrogen bond between the ammonium group in Eph and the hydroxyl groups of Tar ions may appear unusual.…”

“…Crystal structure information, including hydrogen positions, is pivotal to understanding the properties of organic crystals and their crystallisation processes, both of which are a key part of crystal engineering. [1][2][3] Hydrogen positions are particularly important, although difficult to locate, in controlling the crystal packing arrangements of organic salts, [4][5][6] as they can adjust themselves to achieve a balance between the oftencompeting forces associated with ionic interactions, hydrogen bonding and van der Waals forces, leading to minimised lattice energy. Single-crystal X-ray diffraction (SXD) is, undoubtedly, the best method to determine structures, but suitable single crystals of sufficient size and quantity are not always available.…”