Effects of Configuration Around the Chiral Carbon Atoms on the Crystal Properties of Ephedrinium and Pseudoephedrinium Salicylates

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Abstract
The physicochemical properties and crystal structures of the crystalline salts formed by the interaction of an achiral anion, salicylate, with homochiral and racemic ephedrinium and pseudoephedrinium cations were determined. The interaction of ephedrinium or pseudoephedrinium with salicylate in aqueous solution yielded crystalline salts with the notable exception of homochiral ephedrinium. Evaporation of the solvent from solutions of homochiral ephedrine and salicyclic acid in various organic solvents, as well as grinding together solid homochiral ephedrine and solid salicylic acid, yielded viscous semisolids suggesting that homochiral ephedrinium salicylate has a low melting point and/or a high aqueous solubility. Mixing of the two viscous solids, obtained by grinding each of the opposite enantiomers of ephedrine with equimolar salicylic acid, resulted in the formation of racemic ephedrine and subsequently, upon heating, in the formation of racemic ephedrinium salicylate. While racemic ephedrinium salicylate exists as a crystalline compound (P21/n space group) with an equal number of opposite enantiomers in the unit cell, its diastereomer, racemic pseudoephedrinium salicylate, exists as a conglomerate, i.e. a physical mixture, of the homochiral crystals of the opposite enantiomers (each P21 space group). The inability of homochiral ephedrinium to exist as a crystalline salicylate salt at 20–25°C is attributed to its high energy conformation and/or to the poor packing of homochiral ephedrinium salicylate molecules in the crystal lattice.