Crystal structure determination and Hirshfeld surface analysis of N-acetyl-N-3-methoxyphenyl and N-(2,5-dimethoxyphenyl)-N-phenylsulfonyl derivatives of N-[1-(phenylsulfonyl)-1H-indol-2-yl]methanamine

The crystal structures of two 1H-indole derivatives are described and the intermolecular contacts in the crystals are assessed and analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots.


Chemical context
Derivatives of indole exhibit antibacterial (Okabe & Adachi, 1998) and antitumour (Schollmeyer et al., 1995) activities.In particular, 1-(phenylsulfonyl)indoles are applicable to the synthesis of biologically active alkaloids, such as the anticancer alkaloid ellipticine, carbazoles, furoindoles, pyrroloindoles, indolocarbazoles and their analogues, including pyridocarbazoles.Some of the phenylsulfonyl indole compounds have been shown to inhibit the HIV-1 RT enzyme in vitro and HTLVIIIb viral spread in MT-4 human Tlymphoid cells (Williams et al., 1993).In such systems, the phenylsulfonyl moiety can act either as a protecting or an activating group (Jasinski et al., 2010).Ring-substituted acetanilides are valuable synthetic intermediates (Gowda et al., 2007) that are used as precursors for the preparation of many heterocyclic compounds (Wen et al., 2006).The amide linkage [-NHC(O)-] is known for its importance in maintaining protein architectures and it has been utilized in the development of molecular devices for a spectrum of purposes in organic chemistry (NizamMohideen, SubbiahPandi et al., 2009;NizamMohideen et al., 2009a,b).Benzenesulfonamide derivatives exhibit antitumor (Yang et al., 2002), anti-bacterial (Badr, 2008) and anti-fungal (Hanafy et al., 2007) activities.Recognizing the importance of such compounds for biochemical applications and drug discovery and our ongoing research into the construction of indole derivatives have prompted us to investigate a series of corresponding methoxyphenyl-substituted species.We report herein the crystal structure determination and Hirshfeld surface analysis of two new ( 1

Figure 1
The molecular structure of compound I, with atom labelling and displacement ellipsoids drawn at the 30% probability level.The dashed line indicates the intramolecular hydrogen bond.

Figure 2
The molecular structure of compound II, with atom labelling and displacement ellipsoids drawn at the 30% probability level.The dashed lines indicate the intramolecular hydrogen bonds.

Supramolecular features
With a lack of conventional hydrogen-bond donor functionality, the supramolecular structures of both compounds are dominated by C-H� � �O bonding (Tables 1 and 2), whereas �-� interactions are specific for I and weaker C-H� � �� bonds are relevant for II only.In the crystal of I, the shortest hydrogen-bond contacts are observed for acetyl O-atom acceptors [C17� � �O4 iii = 3.312 (4) A ˚, symmetry code: (iii) À x + 2, À y + 1, À z + 1].Such bonds assemble pairs of the molecules into centrosymmetric dimers (Fig. 3) with a cyclic R 2 2 (12) (Bernstein et al., 1995) ring motif.The dimers are further interconnected into chains propagating along the adirection through double �-� interactions of the indole ring systems (Fig. 3).The components of such stacks are related by inversion and therefore two indole systems are parallel, with interplanar separation of 3.517 (4) A ˚.However, the overlap is only partial, as it is indicated by relatively large intercentroid distances [Cg1� � �Cg2 iv = 3.801 (5) A ˚; Cg1 and Cg2 are the centroids of the N1/C1/C6-C8 and C1-C6 rings, respectively; symmetry code: (iv) À x + 1, À y + 1, À z + 1] and slippage angle of 22.3 (3) � .These parameters agree well with those for �-� interactions seen in the crystal structures of comparable 1-(phenylsulfonyl)-1H-indole derivatives (Madhan et al., 2024).Three C-H� � �O bonds with sulfone O-atom acceptors [C� � �O = 3.410 (5)-3.537(4) A ˚; Table 1] are important for connection of the above chains into layers parallel to the ac plane (Fig. 4) and separated by 9.890 A ˚, which is half of the baxis parameter of the unit cell.Only one C-H� � �O bond occurs between the layers, involving the sterically most

Figure 3
Fragment of non-covalent chain propagating along the a-axis direction in the structure of I, with the pairs of the inversion-related adjacent molecules linked by double C-H� � �O bonds (dotted blue lines) and double �-� interactions (solid blue lines).[Symmetry codes: Similar non-covalent layers parallel to the ac plane are also seen in compound II (Fig. 5).However, the bonding pattern differs as �-� interactions are replaced by C-H� � �� interactions (on both axial sides of the indole system) and more extensive C-H� � �O bonding (Table 2).This is in line with increased number of hydrogen-bond donors and acceptors due to the incorporation of the additional phenylsulfonyl groups.The layers are sustained by a number of C-H� � �O interactions, which are relatively weak and distal [C� � �O = 3.503 (9)-3.788(8)A ˚].Significantly shorter contacts adopted by methyl groups are also present: C23� � �O1 v = 3.199 (7) A ˚; symmetry code: (v) x, y, z + 1.As a result of inappropriate angles at the H atoms, these contacts are not regarded as hydrogen bonds, rather representing a kind of tetrel interaction CH 3 � � �O.A salient feature of the layer concerns C-H� � �� interactions involving the C1-C6 rings, which are appreciably short and directional [C25� � �Cg2 iv = 3.483 (5) A ˚; C25-H25� � �Cg2 iv = 147 � ; Cg2 is the C1-C6 ring centroid; symmetry code: (iv . The shortest interlayer interactions represent C-H� � �O bonds with the most polarized methylene donors [C15� � �O1 ii = 3.333 (8) A ˚; symmetry code: (ii) x, À y + 2, z + 1 2 ], which act in synergy with a set of longer C-H� � �O (phenyl) bonds and weak C-H� � �� bonds to the indole (N1/C1/C6-C8) acceptors (Fig. 6).In comparison with the structure of I, the much more extensive interactions in the present case result in a lower interlayer spacing of 8.596 A ˚, which is a half of the b-axis parameter of the unit cell.This contributes to a slightly higher packing index of 68.1% versus 66.9% for I.However, in both the cases, the packing indices approach the lower limit of the 65-75% range expected for organic solids (Dunitz, 1995), suggesting relatively loose packing of these sterically strained molecules.

Hirshfeld surface analysis
The Hirshfeld surface calculations and associated twodimensional fingerprint plots for I and II were performed in accord with established procedures (Tan et al., 2019) using Crystal Explorer (Spackman et al., 2021) to determine the influence of weak intermolecular interactions upon the molecular packing in the absence of conventional hydrogen bonds.The Hirshfeld surfaces for two compounds mapped over d norm using a fixed colour scale of À 0.249 (red) to 1.450 a.u.(blue) for I and À 0.096 (red) to 1.442 a.u.(blue) for II are shown in Fig. 7.One can note a relatively scarce landscape of short contacts that is particularly the case for II, which shows normal van der Waals separations only (denoted with several white regions on the surface).The few red spots present in the The Hirshfeld surfaces of compounds I and II mapped over d norm .
case I indicate intermolecular contacts involved in weak hydrogen bonding.
The two-dimensional fingerprint plots (Parkin et al., 2007) detailing the various interactions for the molecules are shown in Fig. 8.For both compounds, the Hirshfeld surfaces suggest dominance of contacts with hydrogen atoms, accounting for over 85% of the contacts.Beyond the largest fractions of H� � �H contacts (48.8 and 44.6%), these short separations are overwhelmingly O� � �H/H� � �O and C� � �H/H� � �C, which contribute 22.4 and 21.7%, respectively, to the Hirshfeld surface in I and 25.8 and 26.8%, respectively, in II, respectively.The plots also illustrate the finding discussed above that the structure of II exhibits a larger number, but essentially weaker C-H� � �O bonds.Thus, for I the O� � �H/H� � �O plot represents pair of broad spikes pointing to the lower left, with the shortest contact being 2.35 A ˚, whereas in the case of II the diffuse and faintly discernible spikes are much shorter (O� � �H = 2.70 A ˚).The larger contribution of C� � �H/H� � �C contacts for II (Fig. 8) reflects the increased significance of C-H� � �� interactions for the crystal packing, in line with increased number of aromatic groups.The small fraction of N� � �H/ H� � �N contacts (1.3%) is also a consequence of C-H� � �� bonding, namely with the pyrrole ring acceptor.An overlap between the parallel indole ring systems in I, due to the slipped �-� interactions, is clearly indicated by the plots for C� � �C, N� � �C/C� � �N and O� � �C/C� � �O (total contribution is 7.1%), in the form of the blue areas centered at ca d e = d i = 1.90A ˚and with shortest contacts of 3.50 A ˚(Fig. 8).This weak bonding complements the above interactions involving H atoms.For both compounds, the H� � �H intermolecular contacts predominate, followed by the C� � �H/H� � �C and O� � �H/H� � �O contacts.The Hirshfeld surface analysis confirms the importance of distal H-atom contacts (and contacts associated with the �-� interaction for I) in establishing the packing.

MohanaKrishnan
Computing details

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.

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.

Figure 4
Figure 4 Projection of the structure of I on the ac plane, showing the layer assembled with C-H� � �O and �-� bonds.[Symmetry codes: (i) x, y, z À 1; (v) x, y, z + 1.]

Figure 6
Figure 6Set of interlayer bonds in the structure of II, with the C-H� � �O and C-H� � �� bonds marked with dashed blue and red lines, respectively.Blue strips indicate two successive layers, which are nearly orthogonal to the plane of the drawing.[Symmetry codes: (ii) x, À y + 2, z + 1 2 ; (iv) x À 1 2 , À y + 3 2 , z + 1 2 .]

Table 3
Experimental details.