Crystal structure of (1S,2R)-2-hydroxy-1,2-diphenylethan-1-aminium (S)-2-azaniumylbutanedioate monohydrate

The title diastereomeric salt, formed between 2-amino-1,2-diphenylethanol (ADE) and aspartic acid (ASP), crystallizes as a monohydrate. In the crystal, the ASP anions are linked via N—H⋯O hydrogen bonds to form a 21 helix along the b-axis direction.


Chemical context
The production of chiral compounds has great importance in the pharmaceutical industry, and diastereomeric salt separation is still widely applied in the process. A synthetic optical resolving agent, chiral 2-amino-1,2-diphenylethanol (ADE) (Read & Steele, 1927), has been widely tried and used in diastereomeric salt-separation methods for chiral alcohols or organic acids. l-(S)-aspartic acid (ASP) is a known neurotransmitter, and d-(R)-ASP is a non-essential amino acid, one of two d-amino acids commonly found in mammals. d-ASP has also attracted attention as residue in the antifungal bacitracin, while N-methyl-d-aspartic acid (NMDA) acts as a specific agonist at the NMDA receptor. d-amino acids are mainly resolved enzymatically with d-aminoacylase (EC 3.5.1.14) in industrial applications. The optical separation of ASP with cis-ADE was introduced without chemical modification. The crystal structure of the title molecular salt, formed between l-(S)-ASP and (1R,2S)-cis-ADE, is reported herein. ISSN 2056-9890

Structural commentary
The molecular structures of the components of the title salt are shown in Fig. 1, and selected torsion angles are given in Table 1. It can be seen that the hydroxy and protonated amino groups of cis-ADE form a tweezer-like motif. The dihedral angle between the phenyl rings (A and B; Fig.1) is 48.71 (9) and the torsion angle O1A-C1A-C2A-N1A is À65.0 (2) . The hydroxy group adopts a gauche conformation [O1A-C1A-C2A-C9A = 60.1 (2) ] with respect to phenyl ring B. Thus, the tweezer-like motif is twisted with respect to the phenyl groups. This arrangement is similar to that found in racemic cis-ADE (Fujii, 2015) and the diastereomeric salts formed with cis-enantiomers.

Figure 2
A view along the c axis of the right-handed 2 1 -helix of ASP anions. Hydrogen bonds are shown as dashed lines (see Table 2) and C-bound H atoms have been omitted. Table 2 Hydrogen-bond geometry (Å , ).

Figure 1
A view of the molecular structure of (1S,2R)-cis-ADEÁ(S)-ASP monohydrate, with the atom and ring labelling. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate the hydrogen bonds (see Table 2).

Figure 3
A partial view along the b axis of the crystal packing of the ASP helices linked by the ADE cations. Hydrogen bonds are shown as dashed lines (see Table 2) and C-bound H atoms have been omitted.

Figure 4
A view along the b axis of the crystal packing of (1S,2R)-cis-ADEÁ(S)-ASP monohydrate. Hydrogen bonds are shown as dashed lines (see Table 2) and C-bound H atoms have been omitted.

Synthesis and crystallization
(1R,2S)-cis-2-Amino-1,2-diphenylethanol (ADE) and aspartic acid (ASP) were purchased from Sigma-Aldrich Co. Ltd. The title molecular salt was obtained from an aqueous ethanol solution of racemic-ASP and (1R,2S)-cis-ADE in a 2:1 molar ratio, heated to 333 K under stirring. On slow cooling to ambient temperature and slow evaporation of the solvent, colourless rod-shaped crystals were obtained.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. All the H atoms were located in difference-Fourier maps. The NH 3 + , OH, and water H atoms were freely refined. The C-bound H atoms were included in calculated positions and treated as riding atoms: C-H = 0.93-0.98 Å with U iso (H) = 1.2U eq (C).