Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-4-cyano-6-hydroxy-8-(4-methoxyphenyl)-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetic acid ethyl ester

The 4-methoxyphenyl group is disposed on one side of the bicyclic core and the oxygen atoms of the hydroxyl and acetyl groups are disposed on the other. The unsaturated portion of the core adopts an envelope conformation. In the crystal, O—H⋯O and C—H⋯O hydrogen bonds form chains extending along the a-axis direction. These are linked into layers parallel to the ac plane by additional C—H⋯O hydrogen bonds and C—H⋯π(ring) interactions.


Chemical context
Some tetrahydroisoquinoline (THISQ) based compounds are of medicinal and biological importance, being used as antitumoral (Pingaew et al., 2014;Castillo et al., 2018), antifungal (Scott et al., 2002) and anti-inflammatory agents (Siegfried et al., 1989). Other tetrahydroisoquinolines were used as inhibitors including B-raf V600E or p38 kinase inhibitors (Lu et al., 2016;Rosales et al., 2007). The THISQ core can easily be functionalized to build other heterocyclic rings on the carbocyclic ring (Xu et al., 2002;Carroll et al., 2007;Demers et al., 2008, Marae et al., 2021a. Recently, we have used some compounds related to THISQ as durable fluorescent dyes for cotton (Marae et al., 2021b). The widespread importance of these compounds motivated us to further study the THISQ core. Here we report the synthesis and crystal structure determination of the title compound. ISSN 2056-9890

Hirshfeld surface analysis
Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) was carried out using CrystalExplorer17.5 (Turner et al., 2017). The Hirshfeld surface and their associated two-dimensional fingerprint plots were used to quantify the various intermolecular interactions in the title compound. In the Hirshfeld surface plotted over d norm in the range À0.4903 (red) to +1.6396 (blue) a.u. (Fig. 4), the white areas indicate contacts with distances equal to the sum of van der Waals radii, and the red and blue areas indicate distances shorter (in close contact) or longer (distinct contact) than the van der Waals radii, respectively (Venkatesan et al., 2016). The bright-red spots indicate their roles as the respective donors and/or acceptors.

Figure 2
A portion of one chain viewed along the b-axis direction. O-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds are depicted by red and black dashed lines, respectively.

Figure 1
The title molecule with labelling scheme and 50% probability ellipsoids.

Figure 3
Packing viewed along the c-axis direction giving an elevation view of one layer. Hydrogen bonds are depicted as in Fig. 2 while C-HÁ Á Á(ring) interactions are indicated by green dashed lines.
2.34 Àx, 2 À y, 1 À z 1.91 g) and sodium acetate trihydrate (1.36 g, 10 mmol) were suspended in 50 ml of absolute ethanol, then 0.55 ml of ethyl chloroacetate (5.3 mmol) were added and the mixture was refluxed for one h. During reflux, the yellow colour disappeared gradually over time to afford a colourless reaction mixture. The reaction mixture was then left to cool at room temperature and the formed precipitate was collected by fiitration, washed with water, dried in air and recystallized from ethanol to give the title compound as cubic crystals, yield 2.11 g (94%); m.p.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. All C-bound H atoms were placed in geometrically idealized positions (C-H = 0.95-1.00 Å ) while the hydrogen atom attached to O3 was found from a difference map, and was subsequently refined isotropically [O3-H3 = 0.903 (17) Å ] with U iso (H) = 1.5U eq (O). All Cbound H atoms were included as riding contributions with isotropic displacement parameters 1.2 times those of the parent atoms (1.5 for methyl groups).

Special details
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, colllected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = -30.00 and 210.00°. The scan time was 10 sec/frame. 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. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -1.00 Å) while that attached to oxygen was placed in a location derived from a difference map and its coordinates adjusted to give O-H = 0.87 %A. All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms.