Different N—H⋯π interactions in two indole derivatives

The most important intermolecular interactions in the two indole derivatives described here are N—H⋯π bonds, which lead to chains in one case and inversion dimers in the other; C—H⋯π interactions appear to reinforce the N—H⋯π bonds in each case.

We describe the syntheses and crystal structures of two indole derivatives, namely 6-isopropyl-3-(2-nitro-1-phenylethyl)-1H-indole, C 19 H 20 N 2 O 2 , (I), and 2-(4-methoxyphenyl)-3-(2-nitro-1-phenylethyl)-1H-indole, C 23 H 20 N 2 O 3 , (II); the latter crystallizes with two molecules (A and B) with similar conformations (r.m.s. overlay fit = 0.139 Å ) in the asymmetric unit. Despite the presence of O atoms as potential acceptors for classical hydrogen bonds, the dominant intermolecular interaction in each crystal is an N-HÁ Á Á bond, which generates chains in (I) and A+A and B+B inversion dimers in (II). A different aromatic ring acts as the acceptor in each case. The packing is consolidated by C-HÁ Á Á interactions in each case but aromaticstacking interactions are absent.

Chemical context
N-HÁ Á Á interactions are now a well-recognised type of 'nonclassical' weak bond (Desiraju & Steiner, 1999). They are of special significance in biological systems (Burley & Petsko, 1986;Levitt & Perutz, 1998) and are thought to play an important role in establishing protein secondary structures (Lavanya et al., 2014). They may even influence the chargetransport properties of organic semiconductors (Zhao et al., 2009). The presence of N-HÁ Á Á interactions in indole complexes with aromatic species has been investigated by IR spectroscopy (Muñ oz et al., 2004), and such bonds have also been observed in many crystal structures of indole derivatives (e.g. Krishna et al., 1999;Cordes et al., 2011).

Structural commentary
Compound (I) crystallizes in a Sohncke space group with one molecule in the asymmetric unit (Fig. 1). The absolute structure was indeterminate in the present study and C9 was assigned an arbitrary S configuration (given the synthesis, we presume that the bulk sample consists of a statistical mixture of enantiomers). The dihedral angle between the mean plane of the N1/C1-C8 indole ring system (r.m.s. deviation = 0.018 Å ) and the C11-C16 phenyl ring is 83.59 (11) . Atom C17 of the 6-isopropyl substituent deviates slightly from the indole plane, by À0.092 (6) Å . In terms of the terminal carbon atoms of this group, C18 and C19 deviate from the indole plane by À1.461 (6) and 1.030 (6) Å , respectively. Atom C9 shows a relatively large deviation from the indole plane of À0.084 (6) Å , perhaps because of steric crowding. In terms of the orientation of the substituents attached to C9, the C6-C7-C9-C10 torsion angle of 174.6 (5) (anti about C7-C9) indicates that the C10 atom of the CH 2 NO 2 group lies roughly in the plane of the indole ring, whereas the C6-C7-C9-C11 angle of À61.6 (7) (gauche about C7-C9) indicates that the pendant ring lies to one side of the indole plane. Finally, the C7-C9-C10-N2 torsion angle of À176.5 (4) indicates a near anti conformation about the C9-C10 bond.
There are two molecules, A (Fig. 2) and B, in the asymmetric unit of (II). The space group for (II) is centrosymmetric and the stereogenic centres (C9 in molecule A and C32 in molecule B) were arbitrarily assigned an S configuration for ease of comparison with compound (I).

Figure 2
The molecular structure of the N1 molecule in (II), showing 50% probability displacement ellipsoids. The molecular structure of the N3 molecule is very similar.

Figure 3
Overlay plot of the conformations of the N1 molecules (black) and N3 molecules (red) in the crystal of (II). completely different from the corresponding angle in (I). The corresponding torsion angles for the N3 molecule in (II) are À38.4 (2), 87.50 (19) and À56.24 (19) , respectively. In essence, the 2-nitro 1-phenyl ethyl substituent has rotated around the C7-C9 bond, so that the H atom attached to C9 and C32 in (II) lies approximately above C8 whereas in (I) the CH 2 NO 2 group takes on this role.

Supramolecular features
In the crystal of (I), the molecules are linked by N-HÁ Á Á interactions (Table 1, Fig. 4) to generate [010] chains, in which adjacent molecules are related by the 2 1 screw axis. The acceptor ring is the C1-C6 benzene ring of the indole system; the dihedral angle between any adjacent pair of indole ring systems in the chain is 68.89 (8) . The chain appears to be reinforced by a C-HÁ Á Á bond from the C2-H2 group of the benzene ring syn to the N-H group to the five-membered ring of the same adjacent molecule; the HÁ Á Á separation is actually marginally shorter for this bond than for the N-HÁ Á Á bond. Two further C-HÁ Á Á interactions (Fig. 5) also occur in the crystal of (I): based on their lengths, these are presumably significantly weaker than the C2-H2 bond. They arise from adjacent C-H groups on the pendant C11-C16 benzene ring with the acceptor rings being another C11-C16 ring and the C1-C6 indole ring of the same adjacent molecule. Taken together, the intermolecular interactions lead to (100) sheets in the crystal of (I).
In the crystal of (II), inversion dimers linked by pairs of N-HÁ Á Á interactions (Table 2, Fig. 6) occur for both independent molecules. In this case, the acceptor ring is the pendant C11-C16 or C34-C39 benzene ring for molecules A and B, respectively. This bonding mode possibly correlates with the different orientation of the substituents attached to C9 and C32, as described above. Again, the N-HÁ Á Á bonds appear to be reinforced, but this time by two pairs of C-HÁ Á Á interactions. As for (I), they arise from adjacent C-H groups in a benzene ring but this time they are part of the pendant   [Symmetry codes: (i) 1 À x, y À 1 2 , 1 À z; (ii) 1 À x, y + 1 2 , 1 À z.] All H atoms, except H1 and H2, have been omitted for clarity. The orange circles indicate ring centroids. Table 1 Hydrogen-bond geometry (Å , ) for (I).

Figure 5
Fragment of the packing for (I), showing C-HÁ Á Á bonds arising from adjacent C-H groups of the pendant benzene ring. All H atoms, except H14 and H15, have been omitted for clarity. [Symmetry code: (i) 1 À x, y + 1 2 , Àz.] The orange circles indicate ring centroids.
4-methoxybenzene ring at the indole 2-position. Further C-HÁ Á Á bonds link the A+A and B+B dimers into a threedimensional network in the crystal of (II).

Database survey
There are over 7000 crystal structures of indole derivatives in the Cambridge Structural Database (CSD; Groom et al., 2016), but none of them have an iso-propyl group at the 6-position. Six structures contain a p-methoxybenzene grouping at the 2position and four contain a 2-nitro-1-phenylethyl grouping at the 3-position; these latter structures are the ones recently described by us (Kerr et al., 2015).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The N-bound H atoms were located in difference maps and their positions were freely refined. The C-bound H atoms were geometrically placed (C-H = 0.93-0.98 Å ) and refined as riding atoms. The constraint U iso (H) = 1.2U eq (C, N carrier) or 1.5U eq (methyl carrier) was applied in all cases. The -CH 3 groups were allowed to rotate, but not to tip, to best fit the electron density. Due to the similarity in the a and c unit-cell parameters for (I), twinning models were applied, but no improvement in fit resulted.

(I) 6-Isopropyl-3-(2-nitro-1-phenylethyl)-1H-indole
Crystal data 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.