Resolution of sertraline with (R)‐mandelic acid: Chiral discrimination mechanism study

Abstract

The chiral discrimination mechanism in the resolution of sertraline with mandelic acid was investigated by examining the weak intermolecular interactions (such as hydrogen bond, CH/π, and van der Waals interactions) and molecular packing difference in crystal structures of the resulting diastereomeric salts. A new one-dimensional chain-like hydrogen-bonding network and unique supramolecular packing mode are disclosed. The investigation demonstrated that stable hydrogen-bonding pattern, herringbone-like arrangement of aromatic rings, and planar boundary surface in the hydrophobic region are the three most important structural characteristics expected in less soluble diastereomeric salts. The existence and magnitude of hydrogen bond, CH/π interaction, and van der Waals interaction related to three characteristic structures, determine the stability of diastereomeric salt. The hydrogen bond is not necessarily the dominant factor while the synergy and optimization of all weak intermolecular interactions attribute to the chiral recognition.

Resolution of 2‐chloromandelic acid with (R)‐(+)‐N‐benzyl‐1‐phenylethylamine: chiral discrimination mechanism

“…The concerned hydrogen‐bonding network in ( R )‐2‐ClMA·( R )‐BPA is also different from the chain‐like network formed between secondary amine sertraline and mandelic acid as depicted in Figure (c). In the case of less soluble salt of sertraline and mandelic acid, only one hydrogen‐bonding line formed, and the hydroxy groups were not involved in any hydrogen bond formation. The sertraline molecule was also much larger than mandelic acid molecule.…”

Naphthyl Groups in Chiral Recognition: Structures of Salts and Esters of 2‐Methoxy‐2‐naphthylpropanoic Acids

“…The columns were bound together by interactions between these aromatic groups. [19,44] The homo-aromatic CH···p interactions were observed between the 2-naphthyl groups. The distances between aromatic hydrogen atoms H11 and H12 and the neighboring 2-naphthyl group were both 2.9 (Figure 7 d); the interplanar angle between the 2-naphthyl groups was 478 (Figure 7 a).…”

EnantioselectiveLCanalysis and determination of selective serotonin reuptake inhibitors

“…The crystal structures of diastereomeric salts were determined by an X‐ray crystallographic analysis and structural characteristics and weak intermolecular interaction of the less soluble salt (I) were systematically examined. The chiral discrimination was well interpreted (He, Rohani, Zhu, & Gomaa, ) in terms of the contribution of various intermolecular interactions to the stability of (I). Besides, the thermal properties such as melting point, enthalpy of fusion and solubility of these salts were measured.…”