Crystal structure of (1S,2R)-2-[(3R,4S)-3-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-2-yl]-1,2-diphenylethanol

The title chiral β-amino alcohol was isolated as one of two diastereomeric β-amino alcohols, the title molecule being found to be the (S,R) diastereoisomer. In the crystal, molecules are packed in a herringbone manner parallel to (103) and (10) via weak C—H⋯O and C—H⋯π(ring) interactions.

The synthesis and crystal structure of the title compound, C 30 H 29 NO, are described. This compound is a member of the chiral dihydroisoquinolinederived family, used as building blocks for functional materials and as source of chirality in asymmetric synthesis, and was isolated as one of two diastereomeric -amino alcohols, the title molecule being found to be the (S,R) diastereoisomer. In the crystal, molecules are packed in a herringbone manner parallel to (103) and (103) via weak C-HÁ Á ÁO and C-HÁ Á Á(ring) interactions. Hirshfeld surface analysis showed that the surface contacts are predominantly HÁ Á ÁH interactions (ca 75%). The crystal studied was refined as a two-component inversion twin.

Chemical context
-amino alcohols exhibit a broad spectrum of biological activities and are used as antibacterial and tuberculostatic agents (Yendapally & Lee, 2008). In particular, chiral -amino alcohols are very important chiral molecules that are used as building blocks and structural motifs in pharmaceutically active molecules and natural products and which serve as the main sources of chirality in asymmetric synthesis (Lee et al., 2003;Malkov et al., 2007;Guo et al., 2017).
Among this family of chiral amino-alcohols is the title compound, (I), which we prepared through the alkylation of tetrahydroisoquinoline by the opening racemic trans-stilbene oxide reaction. Two diastereoisomers were obtained in a 1:1 ratio as determined by 1 H NMR analysis on the crude mixture. These diastereoisomers were separated by column chromatography. The title molecule was found to be the (S,R) diastereoisomer.

Structural commentary
The structure of (I) was confirmed using single crystal X-ray diffraction. The asymmetric unit of the orthorhombic unit cell comprises a single molecule, shown in Fig. 1. The tetrahydroisoquinoline unit is substituted by a methyl group in position 3, a phenyl substituent in position 4 and a -alcohol substituent at the N atom. The heterocyclic ring exhibits a half-chair conformation, with atom C3 deviating by 0.706 (3) Å from the plane formed by atoms C1/N2/C4/C9/ C10. The substituents in positions 3 and 4 of the heterocyclic ring are in axial positions. The molecular structure of (I) is stabilized by an intramolecular hydrogen bond between the hydroxy O19-H19 group and atom N2, and to a lesser extent, between the aromatic C21-H21 and the phenyl group in position 4 (Table 1). By reference to two unchanging chiral C18 and C19 atoms, the molecule was found to be the (18R,19S) diastereoisomer resulting from the reaction of tetrahydroisoquinoline and the (S,S) trans-stilbene oxide enantiomer.
This structure was confirmed through the means of usual 1D and 2D NMR experiments. NMR data show that the trans diequatorial arrangement of H3 and H4 is suggested by the coupling constant between H3 and H4 in 1 H NMR (J 3,4 $0 Hz), so the substituents C3-methyl and C4-phenyl are in an axial disposition. The absolute configurations of carbon atoms C18 and C19 were deduced from the NOESY maps to be R and S, respectively (Fig. 2).

Supramolecular features
In the crystal, molecules of (I) pack with no classical hydrogen bonds: the potential donor hydroxyl group is involved in an intramolecular interaction with the N atom. However, the oxygen atom acts as an acceptor in the short contact C6-H6Á Á ÁO19 (Àx, 1 2 + y, 1 2 À z) with an O19Á Á ÁH distance of 2.57 Å , which is of the same order of magnitude of the HÁ Á ÁO van der Waals distance (2.60 Å ), whereas C-HÁ Á ÁO contacts are frequently reported with HÁ Á ÁO separations shorter than 2.4 Å (Taylor & Kennard, 1982). The N atom does not play a role in the packing as it is buried inside the structure. Nevertheless, these directed C-HÁ Á ÁO interactions make an 1400 Ben Ali and Retailleau C 30 H 29 NO Acta Cryst. (2019). E75, 1399-1402 research communications Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Selected NOESY correlations observed for compound (I).

Figure 3
The ribbon structure of (I) formed along the b-axis direction via C-HÁ Á ÁO interactions (cyan dashed lines) and C-HÁ Á Á interactions (blue dashed lines). The red spheres indicate the centroids of the phenyl rings.

Figure 1
The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented as small spheres of arbitrary radius. The dashed cyan line indicates the intramolecular hydrogen bond between the hydroxy group and the secondary amine.
important contribution to the packing: zigzagging along the [010] direction, they pair molecules in ribbons, placing the isoquinoline moieties parallel to the (103) plane on both sides but without overlapping. The ribbon cohesion is reinforced by C-HÁ Á Á interactions involving the phenyl group in position 4 and those attached to the -alcohol part and which flank the ribbon, as shown in Fig. 3. They stack in the [100] direction as columns arranged in a herringbone manner but avoiding -stacking ( Fig. 4).  (Davies et al., 2016), XOSDUE (Gzella et al., 2002), YEKKIK (Shi et al., 2012) and ZIFSUE (Guo et al., 2013). Except for the racemic VAHJOG, they all crystallize in the same P2 1 2 1 2 1 space group. The structures of ZIFSUE, TIBPIE, VAHJOG, JIPKEZ and (I) superimpose well over the heterobicycle with the same conformation, unlike ADAGOC and XOSDUE which have a different half-chair configuration. The amino alcohol TIBPIE is obviously the closest related structure, differing in the N substitution of a cyclohexane carrying the hydroxyl group which is involved in the intramolecular hydrogen bond.

Hirshfeld surface analysis
The intermolecular interactions were quantified using Hirshfeld surface analysis and the associated two-dimensional fingerprint plots using CrystalExplorer17.5 (Turner et al., 2017). The electrostatic potentials were calculated using TONTO, integrated within CrystalExplorer. The analysis of intermolecular interactions through the mapping of d norm presented in Fig. 5 compares the contact distances d i and d e from the Hirshfeld surface to the nearest atom inside and outside, respectively, with their respective van der Waals radii. The blue, white and red colour conventions recognize the interatomic contacts as longer, at van der Waals separations and short interatomic contacts. The C-HÁ Á ÁO contacts are identified in the d norm -mapped surface as two red spots showing the interaction between the neighbouring molecules (Fig. 5a). The overall two-dimensional fingerprint plot derived form the Hirshfeld surface is a useful method to summarize the frequency of each combination of d e and d i across the surface of the studied molecule, encompassing all intermolecular contacts (Fig. 5b). The delineated fingerprint plots ( Fig. 5b and 6a,c) focus on specific interactions, providing information about the major and minor percentage contribution of interatomic contacts in the compound. The HÁ Á ÁH interactions account for the three quarters of the total (73.7%) with an evident sting at about d i = d e = 1.1 Å (Fig. 5b). The CÁ Á ÁH/HÁ Á ÁC plot, which refers to the C-HÁ Á Á interactions previously described (22.7%,) shows two broad symmetrical wings at about d i + d e = 2.8 Å (Fig. 6a).    observed as red regions on the shape-index surface (Fig. 6b). The absence of CÁ Á ÁC contacts, highlighted by the Hirshfeld surface with high curvedness delineated by dark-blue edges, confirms that nostacking interactions take place in the crystal packing (Fig. 6c,d). The third marginal contribution is OÁ Á ÁH/HÁ Á ÁO (3.6%) with a pair of sharp spikes at about d i + d e = 2.4 Å , symmetrically disposed with respect to the diagonal, indicating the presence of intermolecular C-HÁ Á ÁO interactions, which play a role in ordering the molecules inside the crystal.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were placed in calculated positions (C-H = 0.93-0.98 Å ) and refined as riding with U iso (H) = 1.2U eq (C). The crystal studied was refined as a twocomponent inversion twin.    Extinction coefficient: 0.0139 (11) Absolute structure: Refined as an inversion twin.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refined as a 2-component inversion twin.