Optical resolution through diastereomeric salt formation: the crystal structures of cinchoninium (R)-mandelate and cinchoninium (S)-mandelate at low temperature

Abstract

The crystal structures of the diastereomeric salts formed between cinchonine and mandelic acid have been analysed. The more soluble of the two salts is cinchoninium (S)-mandelate, C19H23N20 +.C8H703--, Mr = 446.55, monoclinic, P21, T= 110 (1) K, a = 11.2478(10), b=7.0880(6), c=14.684(2) A, /3= 99.068 (7) °, V = 1156.0 (4)/~3, Z = 2, Ox = 1.283 g cm -3, A(Cu Ka) = 1.54184 A, # = 6.57cm-1, F(000)=476, R=0.029 for 2338 observed reflections. The less soluble salt is cinchoninium (R)-mandelate, CI9H23N20 +.CSH7Of, Mr = 446.55, orthorhombic, P212121, T = 122.0 (5)K, a = 12.078 (4), b = 17.423 (2), c = 22.136 (4),~, V= 4658 (3) A 3, z = 8, Dx = 1.273 gcm- 3, A(Cu Ka) = 1.54184 ,~, /1, = 6.52 cm- ~, F(000) = 1904, R = 0.055 for 4125 observed reflections. In the (R)-mandelate salt one of the two independent cinchoninium cations displays disorder of the --CH=CH2 moiety. Apart from variations in the conformation of the vinyl group the cinchoninium cations are alike. The difference in conformation of the (R)- and (S)mandelate ions can be related to differences in the hydrogen-bonding systems. Interionic interactions in the S salt stabilize it relative to the R salt. The differences in the melting enthalpies and entropies of the two diastereomeric salts are related to their structural differences.