Crystal structure determination and analyses of Hirshfeld surface, crystal voids, intermolecular interaction energies and energy frameworks of 1-benzyl-4-(methylsulfanyl)-3a,7a-dihydro-1H-pyrazolo[3,4-d]pyrimidine

In the title molecule, the pyrazolopyrimidine moiety is planar with the methylsulfanyl substituent lying essentially in the same plane, whereas the benzyl group is rotated well out of this plane giving the molecule an approximate L shape.


Structural commentary
The pyrazolopyrimidine moiety of (I) is essentially planar (root-mean-square deviation = 0.0046 A ˚), and the C7-C12 phenyl ring is inclined to this plane by 73.64 (6) � , giving the molecule an approximate L shape (Fig. 1).The methylsulfanyl substituent lies in the mean plane of the pyrazolopyrimidine moiety, as indicated by the N1-C1-S1-C13 torsion angle of À 0.32 (18) � .All bond lengths and angles in this molecule appear to be characteristic.

Figure 1
The molecular structure of (I) with the labelling scheme and displacement ellipsoids drawn at the 50% probability level.
Cg3 is the centroid of the C7-C12 phenyl ring.

Figure 2
Detail of a portion of one tube with C-H� � �S hydrogen-bonding interactions and C-H� � ��(ring) interactions shown, respectively, by purple and green dashed lines.

Figure 3
Packing giving an end view of three tubes seen along the b axis with C-H� � ��(ring) interactions shown as dashed lines.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of (I), a Hirshfeld surface (HS) analysis (Hirshfeld, 1977;Spackman & Jayatilaka, 2009) was carried out by using CrystalExplorer (Spackman et al., 2021).In the HS plotted over d norm (Fig. 4), the white surface indicates 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 (distant 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; they also appear as blue and red regions corresponding to positive and negative potentials on the HS mapped over electrostatic potential (Spackman et al., 2008;Jayatilaka et al., 2005), as shown in Fig. 5.The blue regions indicate positive electrostatic potential (hydrogen-bond donors), while the red regions indicate negative electrostatic potential (hydrogen-bond acceptors).The �-� stacking and C-H� � �� interactions were further visualized by the shape-index surface.This surface can be used to identify characteristic packing modes, in particular, planar stacking arrangements and the presence of aromatic stacking interactions.In this regard, the shape-index represents the C-H� � �� interactions as 'red p-holes', which are related to the electron ring interactions between the CH groups with the centroid of the aromatic rings of neighbouring molecules.Fig. 6a clearly suggests that there are C-H� � �� interactions in (I), and �-� stacking is indicated by the presence of adjacent red and blue triangles (Fig. 6b).
The overall two-dimensional fingerprint plot, Fig.    tions to the Hirshfeld surface.The most important interaction is H� � �H, contributing 47.0% to the overall crystal packing, which is reflected in Fig. 7b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.20 A ˚.The symmetrical pair of spikes resulting in the fingerprint plot delineated into H� � �N/N� � �H contacts (Fig. 7c) with a 17.6% contribution to the HS has the tips at d e + d i = 2.52 A ˚.In the presence of C-H� � �� interactions (Table 1, Fig. 6), the H� � �C/C� � �H contacts, contributing 17.0% to the overall crystal packing, are reflected in Fig. 7d with the tips at d e + d i = 2.73 A ˚.The H� � �S/S� � �H contacts (Fig. 7e) contribute 5.6% to the HS, and their symmetrical pair of spikes has the tips at d e + d i = 2.68 A ˚.The C� � �C contacts (Fig. 7f) have an arrow-shaped distribution of points, contributing 4.7% to the HS, with the tip at d e = d i = 1.68A ˚.The symmetrical pairs of C� � �S/S� � �C (Fig. 7g) and N� � �S/S� � �N (Fig. 7h) contacts contribute 3.7% and 2.4% to the HS, and they are observed with the tips at d e + d i = 3.58 A ånd d e + d i = 3.61A ˚, respectively.Finally, the C� � �N/N� � �C (Fig. 7i) and N� � �N (Fig. 7j) contacts, with 1.7% and 0.2% contributions to the HS, have very low abundance.
The nearest neighbour environment of a molecule can be determined from the colour patches on the HS based on how close to other molecules they are.The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the H� � �H, H� � �N/N� � �H and H� � �C/ C� � �H interactions in Fig. 8a-c, respectively.The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing.The large number of H� � �H, H� � �N/N� � �H and H� � �C/C� � �H interactions suggest that van der Waals interactions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015).

Crystal voids
The strength of the crystal packing is important for determining the response to an applied mechanical force.For checking the mechanical stability of the crystal, a void analysis was performed by adding up the electron densities of the spherically symmetric atoms comprised in the asymmetric unit (Turner et al., 2011).The void surface is defined as an isosurface of the procrystal electron density and is calculated for the whole unit cell where the void surface meets the boundary of the unit cell and capping faces are generated to create an enclosed volume.The volume of the crystal voids (Fig. 9a,b) and the percentage of free space in the unit cell are calculated as 76.45A ˚3 and 6.39%, respectively.Thus, the crystal packing appears compact and the mechanical stability should be substantial.

Interaction energy calculations and energy frameworks
The intermolecular interaction energies were calculated using the CE-B3LYP/6-31G(d,p) energy model available in Crys-  talExplorer (Spackman et al., 2021), where a cluster of molecules is generated by applying crystallographic symmetry operations with respect to a selected central molecule within the radius of 3.8 A ˚by default (Turner et al., 2014).The total intermolecular energy (E tot ) is the sum of electrostatic (E ele ), polarization (E pol ), dispersion (E dis ) and exchange-repulsion (E rep ) energies (Turner et al., 2015) with scale factors of 1.057, 0.740, 0.871 and 0.618, respectively (Mackenzie et al., 2017).Hydrogen-bonding interaction energies (in kJ mol À 1 ) were calculated to be À 30.3(E ele ), À 3.6 (E pol ), À 74.7 (E dis ), 70.9 (E rep ) and À 55.9 (E tot ) for the C2-H2� � �S1 hydrogenbonding interaction.Energy frameworks combine the calculation of intermolecular interaction energies with a graphical representation of their magnitude (Turner et al., 2015).Energies between molecular pairs are represented as cylinders joining the centroids of pairs of molecules with the cylinder radius proportional to the relative strength of the corresponding interaction energy.Energy frameworks were constructed for E ele (red cylinders) and E dis (green cylinders) (Fig. 10a,b).The evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated via the dispersion energy contributions in the crystal structure of (I).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms were located in difference-Fourier maps and were refined freely.The energy frameworks for a cluster of molecules of (I) viewed down the c axis showing (a) electrostatic energy and (b) dispersion energy diagrams.The cylindrical radius is proportional to the relative strength of the corresponding energies and they were adjusted to the same scale factor of 80 with cut-off value of 5 kJ mol À 1 within 2�2�2 unit cells.(Bruker, 2016), SAINT (Bruker, 2016), SHELXT/5 (Sheldrick, 2015a), SHELXL2018/3 (Sheldrick, 2015b), DIAMOND (Brandenburg & Putz, 2012) and SHELXTL (Sheldrick, 2008).

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.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. Fractional

Figure 4
Figure 4View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm .

Figure 5
Figure 5View of the three-dimensional Hirshfeld surface of the title compound plotted over electrostatic potential energy using the STO-3 G basis set at the Hartree-Fock level of theory.Hydrogen-bond donors and acceptors are shown as blue and red regions around the atoms corresponding to positive and negative potentials, respectively.

Figure 6
Figure 6Hirshfeld surface of the title compound plotted over shape-index for two orientations.

Figure 8 The
Figure 8 The Hirshfeld surface representations with the fragment patch plotted onto the surface for (a) H� � �H, (b) H� � �N/N� � �H and (c) H� � �C/C� � �H interactions.

Figure 9
Figure 9Graphical views of voids in the crystal packing of (I) (a) along the a axis and (b) along the b axis.The grey shaded areas represent the filled regions (electron densities), while the colourless regions represent the crystal voids (free spaces).
Figure 11Scheme used for the database search.

Table 2
Experimental details.
Computer programs: APEX3 and SAINT