A Study of Diastereomeric Mandelate Salts of Cinchonidine and the Relation to Their Quasidiastereomeric Analogues

The crystal structures have been determined for the diastereomeric salts formed by cinchonidine and the two enantiomers of mandelic acid using low-temperature [122 (1) K] X-ray diffraction data. The less soluble salt is cinchonidinium (S)-mandelate, C₁₉H₂₃N₂₀O⁺.C₈H₇O₃^-, M_r = 446.53, monoclinic, C2, a = 21.400 (2), b = 6.2777 (6), c = 17.853 (2) Å³, = 109.304 (8)°, V = 2263.6 (4) Å³, Z = 4, D_x = 1.310 g cm^-3, (Cu K = 1.54184 Å, Z = 7.08 cm^-1, F(000) = 952, R₁ = 0.0259 for 2684 observed reflections. The cinchonidine salt with (R)-mandelic acid, C₁₉H₂₃N₂O⁺.C₈H₇O₃, has Mr = 446.53, monoclinic, P2₁, a = 6.410 (3), b = 32.808 (11), c = 11.222 (2) Å, = 100.67 (2)°, V = 2319.2 (13) Å³, Z = 4, D_x = 1.279 g cm^-3, (Cu K) = 1.54184 Å, \mu = 6.91 cm^-1, F(000) = 952, R₁ = 0.0380 for 8951 observed reflections. The two salts have virtually identical hydrogen-bond patterns and similar herringbone stacking of the quinoline ring systems. The crystal packing of the two salts differ only with respect to the packing of the phenyl groups. The packing of the cinchonidinium mandelates is significantly different from the crystal packing in the corresponding mandelates of cinchonine. The lack of a quasidiastereomeric relationship between the two sets of salts can be attributed to the steric effects of the vinyl group. The similarities between the two cinchonidinium mandelate structures is a possible explanation to the similar solubilities of the salts. DSC and NMR measurements showed that the cinchonidinium salts undergo a chemical opening reaction in the solid state. The arrangement of hydrogen-bonded chains of alternating cations and anions appear to be important for the solid-state reaction to take place.

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