Discrimination in resolving systems: ephedrine-mandelic acid

Resolution of mandelic acid with (-)-(1R,2S)-ephedrine in water and ethanol produces intermediate diastereomeric salts with greatly disparate solubilities and melting points. Single crystal X-ray analysis of the less (L) and more (M) soluble (-)-ephedrinium mandelates (I, II) shows crystal structures which are isosteric, each crystallizing in the monoclinic system, space group C2. Protonated ephedrines occupy the same relative positions in the L- and M-salts, and mandelates are in the same general locations. Hydrogen bonds link alternating protonated ephedrine nitrogens and mandelate carboxylate oxygens in each salt forming columns of ions. The helical H-bonded chain winds down the crystallographic 2-fold screw axis. Additional H-bonds form between 2-fold related mandelates in the L-salt. Mixed crystals, containing both mandelate isomers, (2R)- and (2S)-mandelates, are obtained from the resolving system partly depleted of the L-salt. A specimen with nearly equal amounts of the mandelates (III) is also isosteric with the commensurate structures. I (294K), L-salt: a = 18.160(7), b = 6.538(2), c = 13.898(4) A, beta = 92.02(3) degrees, V = 1649.1(9) A3; IIa (294K), M-salt: a = 17.978(11), b = 7.164(4), c = 13.574(6)A, beta = 96.41(4) degrees, V = 1737.3(16) A3; IIb (223K), M-salt: a = 17.805(8), b = 7.115(2), c = 13.50(5) A, beta = 96.89(3) degrees, V = 1697.9(15) A3; III (294K), mixed-salt: a = 18.184(22), b = 6.792(7), c = 13.808(19) A, beta = 93.74(10) degrees, V = 1701.7(35) A3.