Wyatt Cole, Stephanie L. Hemmingson, Audrey C. Eisenberg, Catherine A. Ulman, Joseph M. Tanski and Yutan D. Y. L. Getzler

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1 ISSN: journals.iucr.org/c Synthesis and crystal structures of some bis(3-methyl-1h-indol-2-yl)(salicyl)methanes Wyatt Cole, Stephanie L. Hemmingson, Audrey C. Eisenberg, Catherine A. Ulman, Joseph M. Tanski and Yutan D. Y. L. Getzler Acta Cryst. (2019). C75, IUCr Journals CRYSTALLOGRAPHY JOURNALS ONLINE Copyright c International Union of Crystallography Author(s) of this paper may load this reprint on their own web site or institutional repository provided that this cover page is retained. Republication of this article or its storage in electronic databases other than as specified above is not permitted without prior permission in writing from the IUCr. For further information see Acta Cryst. (2019). C75, Cole et al. Four bis(3-methyl-1h -indol-2-yl)(salicyl)methanes

2 research papers Synthesis and crystal structures of some bis(3- methyl-1h-indol-2-yl)(salicyl)methanes ISSN Wyatt Cole, a Stephanie L. Hemmingson, a Audrey C. Eisenberg, a Catherine A. Ulman, a Joseph M. Tanski b and Yutan D. Y. L. Getzler a * a Department of Chemistry, Kenyon College, 200 North College Road, Gambier, OH , USA, and b 124 Received 31 October 2018 Accepted 14 December 2018 Edited by P. Fanwick, Purdue University, USA Keywords: indole; bisindolylmethane; BIM; polyindolylmethane; hydrogen-bonding chain; salicylaldehyde; acid catalysis; crystal structure. CCDC references: ; Supporting information: this article has at journals.iucr.org/c Raymond Avenue, Box 601, Poughkeepsie, New York , USA. *Correspondence getzlery@kenyon.edu Four 2,2 0 -bisindolylmethanes (BIMs), a useful class of polyindolyl species joined to a central carbon, were synthesized using salicylaldehyde derivatives and simple acid catalysis; these are 2-[bis(3-methyl-1H-indol-2-yl)methyl]-6-methylphenol, (IIa), 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4,6-dichlorophenol, (IIb), 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4-nitrophenol, (IIc), and 2-[bis(3-methyl- 1H-indol-2-yl)methyl]-4,6-di-tert-butylphenol, (IId). BIMs (IIa) and (IIb) were characterized crystallographically as the dimethyl sulfoxide (DMSO) disolvates, i.e. C 26 H 24 N 2 O2C 2 H 6 OS and C 25 H 20 Cl 2 N 2 O2C 2 H 6 OS, respectively. Both form strikingly similar one-dimensional hydrogen-bonding chain motifs with the DMSO solvent molecules. BIM (IIa) packs into double layers of chains whose orientations alternate every double layer, while (IIb) forms more simply packed chains along the a axis. BIM (IIa) has a remarkably long c axis. # 2019 International Union of Crystallography 1. Introduction Indole, (I) (Scheme 1), is among the oldest and most widely used frameworks of synthetic organic chemistry (Baeyer, 1868), leading to it being termed a privileged structure (Humphrey & Kuethe, 2006). Bis- and trisindolylmethanes (BIMs and TIMs, respectively) form a unique class of polyindolyl species joined to a central carbon at the indole 2- or 3-position, with the central carbon and indoles variously substituted (see Scheme 1). BIMs and TIMs have a diversity of uses, including cancer chemotherapy, cytodifferentiation, analgesis, anti-inflamation, radio-imaging contrast, colorimetric sensing, and metal analyte preconcentration (Shiri et al., 2010). The most commonly prepared and studied polyindolylmethanes are 3,3 0 -BIMs [see (a) in Scheme 1]. Among BIMs and TIMs, poly(indol-2-yl)methanes are the least studied [see (b) and (c) in Scheme 1]. Recently, 2,2 0, TIMs [see (b) in Scheme 1] and 2,2 0 -BIMs [see (c) in Scheme 1] have attracted greater interest because of their potential as ligands (Mason, 2003; Bakthadoss et al., 2015). Structural data has been reported for poly(indol-2-yl)methanes bonded through the indole N atom to main-group elements from group 13 (B, Al, and Ga) (Fneich et al., 2018; Song et al., 2012; Kingsley et al., 2010), group 14 (Si) (Mason, 2003), and group 15 (P and Sb) (Mason, 2003; Mallov et al., 2012). Similar bonding patterns have been reported for group 4 metals (Ti and Zr) (Mason, Fneich et al., 2003; Mason, 2003; Mason et al., 2005). Motivation for this may be driven by the reduction in -donating ability of the indolyl amido compared to compounds where the lone pair is not part of a -system. The same geometric factors that support the use of poly(indol-2- yl)methanes as ligands likely contribute to their effective use Acta Cryst. (2019). C75,

3 research papers in anion binding (Wei et al., 2010, 2015). Antitumor properties for 2,2 0 -BIMs have also been reported (Song et al., 2014). Table 1 Synthesis of bis(3-methyl-1h-indol-2-yl)(salicyl)methanes (Sal-2,2 0 - DIMs). Entry Compound R 1 R 2 Yield (g) Yield (%) M.p. ( C) 1 (IIa) Me H (IIb) Cl Cl (IIc) H NO (IId) t-bu t-bu There is a significant number of polyindolylmethane crystal structures in the literature where these compounds are ligated to metal atoms or main-group elements through the N atoms (vide supra) or pendant heteroatoms (Eisenberg et al., 2009), but there are few reports of the free molecules themselves (Mason, Barnard et al., 2003; Mason, 2003), which is the focus of this report. 2. Experimental 2.1. General considerations Solvents were of reagent grade and were used as received. Also used as received were chemicals purchased from Acros Organics (3,5-di-tert-butyl-2-hydroxybenzaldehyde, 99%), Alfa- Aesar (3,5-dichloro-2-hydroxybenzaldehyde, 98%; 2-hydroxy-5- nitrobenzaldehyde, 98%; salicylaldehyde, 99%), and Sigma Aldrich (2-hydroxy-3-methylbenzaldehyde, 98%; 3-methylindole, 98%). 1 H and 13 C{ 1 H} spectra were acquired on a Bruker Unity 300 NMR, processed with SpinWorks 2.1, and referenced to solvent residual peaks (Gottlieb et al., 1997). NMR solvents were purchased from Cambridge Isotope Laboratories. Melting points were determined using a Mel- Temp II and are uncalibrated Synthesis and crystallization BIMs are most commonly synthesized from two equivalents of the parent indole and an aldehyde with a simple acid catalyst (Dittmann & Pindur, 1986), a protocol which we followed [Bis(3-methyl-1H-indol-2-yl)methyl]-6-methylphenol, (IIa) (Table1). This compound was synthesized by dissolving 3-methylindole (1.472 g, 11.2 mmol, 2.01 equiv.) in a minimum of refluxing EtOH (15 ml). Upon dissolution, 2-hydroxy-3-methylbenzaldehyde (0.760 g, 5.58 mmol, 1.00 equiv.) was added, followed by EtOH (5 ml) and H 2 SO 4 (0.1 ml). The reaction turned deep red upon addition of the aldehyde and slightly cloudy upon addition of the acid. Significant quantities of a brown white solid began to form in the first hour and the reaction was left to proceed under reflux for 20 h. The product was isolated by vacuum filtration, rinsed with cold EtOH (2 15 ml), and dried to recover a white crystalline solid (yield: g, 4.88 mmol, 87%). Crystals were grown by evaporation from dimethyl sulfoxide (DMSO; 92 mg in 1.75 ml) left open to the atmosphere at room temperature, producing yellow cubic crystals after two months [Bis(3-methyl-1H-indol-2-yl)methyl]-4,6-dichlorophenol, (IIb) (Table 1). This compound was prepared in an analogous manner to (IIa). The isolated product (yield: 154 mg) was dissolved in toluene (0.31 ml) and DMSO (0.11 ml). After 2 d, additional (IIb) (53 mg) was added. After 5 d, light-yellow crystals of varying size had grown Spectroscopic and analytical data (IIa). 1 H NMR (300 MHz, DMSO-d 6 ): 2.00 (6H, s), 2.19 (3H, s), 6.29 (1H, s), 6.71 (1H, t, J = 7.6 Hz), (6H, m), 7.28 (2H, d, J = 8.4 Hz), 7.38 (2H, d, J = 7.7 Hz), 8.44 (1H, s), (2H, s); 13 C NMR (75 MHz, DMSO-d 6 ): 8.35, 16.84, 35.18, , , , , , , , , , , , , , (IIb). 1 H NMR (300 MHz, DMSO-d 6 ): 1.99 (6H, s), 6.26 (1H, s), (6H, m), 7.29 (2H, d, J = 8.3 Hz), 7.42 (2H, d, J = 10 Hz), 9.79 (1H, s), (2H, s); 13 C NMR (75 MHz, DMSO-d 6 ): 8.27, 35.57, , , , , , , , , , , , , , (IIc). 1 H NMR (300 MHz, DMSO-d 6 ): 2.00 (6H, s), 6.21 (1H, s), (6H, m), 7.29 (2H, d, J = 8.1 Hz), 7.42 (2H, d, J = 7.4 Hz), 7.90 (1H, d, J = 2.7 Hz), 8.09 (1H, dd, J = 8.9 Hz, 2.9 Hz), (2H, s), (1H, s); 13 C NMR (75 MHz, DMSO-d 6 ): 8.27, 34.76, , , , , , , , , , , , , (IId). 1 H NMR (300 MHz, DMSO-d 6 ): 1.23 (9H, s), 1.38 (9H, s), 1.92 (6H, s), 6.35 (1H, s), (4H, m), Cole et al. Four bis(3-methyl-1h-indol-2-yl)(salicyl)methanes Acta Cryst. (2019). C75, 65 69

4 research papers Table 2 Experimental details. (IIa) (IIb) Crystal data Chemical formula C 26 H 24 N 2 O2C 2 H 6 OS C 25 H 20 Cl 2 N 2 O2C 2 H 6 OS M r Crystal system, space group Tetragonal, P Triclinic, P1 Temperature (K) a, b, c (Å) (3), (3), (3) (9), (11), (16),, ( ) 90, 90, (2), (2), (2) V (Å 3 ) (4) (3) Z 8 2 Radiation type Cu K Mo K (mm 1 ) Crystal size (mm) Data collection Diffractometer Bruker APEXII CCD Bruker APEXII CCD Absorption correction Multi-scan (SADABS; Bruker, 2013) Multi-scan (SADABS; Bruker, 2013) T min, T max 0.62, , 0.99 No. of measured, independent and observed 78707, 5288, , 8941, 5592 [I >2(I)] reflections R int (sin /) max (Å 1 ) Refinement R[F 2 >2(F 2 )], wr(f 2 ), S 0.025, 0.066, , 0.120, 1.02 No. of reflections No. of parameters No. of restraints 3 3 H-atom treatment H atoms treated by a mixture of independent and constrained refinement max, min (e Å 3 ) 0.17, , 0.56 Absolute structure Refined as an inversion twin Absolute structure parameter (13) H atoms treated by a mixture of independent and constrained refinement Computer programs: APEX2 (Bruker, 2013), SAINT (Bruker, 2013), SHELXT2014 (Sheldrick, 2015a), SHELXL2014 (Sheldrick, 2015b), SHELXTL2014 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2008). (1H, d, J = 2.4 Hz), 7.13 (1H, d, J = 2.4 Hz), 7.29 (1H, d, J = 7.8 Hz), 7.38 (1H, d, J = 7.6 Hz), 7.90 (1H, s), (2H, s); 13 C NMR (75 MHz, DMSO-d 6 ): 8.28, 30.00, 31.40, 33.88, 34.77, 35.92, , , , , , , , , , , , , , Refinement Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms on C atoms were included in calculated positions and refined using a riding model, with C H = 0.95, 0.98, and 1.00 Å, and U iso (H) = 1.2, 1.5, and 1.2 times U eq (C) for the aryl, methyl, and methine C atoms, respectively. The positions of the hydroxy and indole H atoms were found in difference maps and were refined semifreely using distance restraints of O H = 0.84 Å, with U iso (H) = 1.2U eq (O), and N H = 0.88 Å, withu iso (H) = 1.2U eq (N). Sal-2,2 0 -DIM (IIa) was refined as a two-component inversion twin. 3. Results and discussion Salicylaldehyde and its derivatives are inexpensive, readily available, and widely used as starting materials in ligand syntheses. The reaction of salicylaldehydes with two equivalents of 3-methylindole in the presence of an acid catalyst yielded bis(indol-2-yl)(salicyl)methanes (IIa) (IId) (Table 1, Sal-2,2 0 -DIMs). This single-step synthesis proceeds under mild conditions, resulting in the selective formation of products that are easily isolated by vacuum filtration in high purities and moderate yields (Table 1). Reactions were monitored by thinlayer chromatography (TLC), as extended reaction times occasionally dramatically reduced the yield. Salicylaldehydes with a range of steric and electronic properties were used. The Sal-2,2 0 -DIMs synthesized are highly soluble in common organic solvents, such as CH 3 CN, tetrahydrofuran, EtOAc, and Et 2 O. The sparing solubility of some derivatives in CHCl 3 led to the use of DMSO-d 6 as a solvent for NMR studies. The miscibility of DMSO with water confirmed the exchange of protons with D 2 O. The formation of (II) can be identified by the unique methine resonance, which appears as a singlet between 6.0 and 7.0 ppm in the 1 H NMR (DMSO-d 6 ) spectrum. Indole N H and phenol O H protons exchange with water, as was confirmed by the addition of D 2 O to the NMR sample tube. Other integrations and shifts were appropriate for the target molecules, and 13 C NMR spectra are unremarkable. Solvatochromism was observed for these compounds. Sal-2,2 0 -DIM (IIa) and (IIb) most easily yielded X-rayquality crystals. In both cases, a careful mixture of toluene and DMSO with the appropriate amount of Sal-2,2 0 -DIM, left to sit, proved most effective. Acta Cryst. (2019). C75, Cole et al. Four bis(3-methyl-1h-indol-2-yl)(salicyl)methanes 67

5 research papers Figure 1 A view of (IIa), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Figure 2 A view of (IIb), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. The molecules of (IIa) and (IIb) both feature two indolyl groups and a phenol moiety derived from the salicylaldehydes arranged about the methine C atom into a three-bladed propeller-type structure with no intramolecular hydrogen bonding (Figs. 1 and 2). Rather, hydrogen bonding occurs with the DMSO solvent molecules to form one-dimensional chains. The molecules of (IIa) (Fig. 1) pack together in the solid state with DMSO solvent molecules via hydrogen bonding, forming one-dimensional chains (Fig. 3). One of the two unique DMSO molecules engages in hydrogen bonding to bridge the hydroxy group (O1 H3BO3) and one of the indole groups [N2 H2BO3 i ; symmetry code: (i) x 1, y, z] on the neighboring molecule in the chain, while the second unbridging DMSO molecule is simply hydrogen bonded to the second indole group (N1 H1BO2). The hydrogenbonding chains pack into double layers running parallel to (110), with the direction of the hydrogen-bonding chains alternating every double layer. Given the double layers and the space-group symmetry, the packing of the chains in (IIa) results in a remarkably long c axis. The molecules of (IIb) (Fig. 2) pack together in the solid state with DMSO solvent molecules via hydrogen bonding in a very similar fashion to (IIa), forming one-dimensional chains running parallel to the crystallographic a axis (Fig. 4). One of the two unique DMSO molecules engages in hydrogen bonding to bridge the hydroxy group (O1 H1O3) and one of the indole groups (N2 H2O3 i ) on the neighboring molecule in the chain, while the second DMSO molecule also bridges the same two molecules via hydrogen bonding to the other indole group (N1 H3O2) and a ClO contact (O2Cl1 i ), with a distance of (2) Å, which is shorter than the sum of the van der Waals radii of chlorine and oxygen (3.27 Å; Bondi, 1964). The ClO contact in (IIb), which is absent in (IIa), results in a different orientation of the second DMSO molecule in (IIb), perhaps resulting in the lowering of the space-group symmetry given that the molecular shape and Figure 3 A view of the molecular packing of (IIa), showing the hydrogen bonding (dashed lines) between the (IIa) and DMSO solvent molecules, forming onedimensional chains running parallel to the crystallographic a axis. [Symmetry code: (i) x 1, y, z.] 68 Cole et al. Four bis(3-methyl-1h-indol-2-yl)(salicyl)methanes Acta Cryst. (2019). C75, 65 69

6 research papers Figure 4 A view of the molecular packing of (IIb), showing the hydrogen bonding (dashed lines) between the (IIb) and DMSO solvent molecules, forming onedimensional chains running parallel to the crystallographic a axis. [Symmetry code: (i) x 1, y, z.] Figure 5 An overlay of (IIa) and (IIb), showing the similarities and differences in the hydrogen bonding (dashed lines) and packing. hydrogen-bonding chain motifs in (IIa) and (IIb) are otherwise very similar (Fig. 5). In conclusion, we have synthesized and characterized four previously unreported Sal-2,2 0 -BIMs, obtaining X-ray structures for two of them. Among the extensively studied diversity of polyindolylmethanes, 2,2 0 -BIMs and 2,2 0,2 00 -TIMs stand out for the paucity of reports. Funding information Funding for this research was provided by: American Chemical Society Petroleum Research Fund (grant No GB 7 to YDYLG); National Science Foundation, Division of Chemistry (grant No to JMT); Kenyon College (award No. KSSSP to SLH and ACE). References Baeyer, A. (1868). Ber. Dtsch Chem. Ges. 1, Bakthadoss, M., Devaraj, A. & Srinivasan, J. (2015). J. Heterocycl. Chem. 52, Bondi, A. (1964). J. Phys. Chem. 68, Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Dittmann, K. & Pindur, U. (1986). Heterocycles, 24, Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, Eisenberg, A. C., Tanski, J. M. & Getzler, Y. D. Y. L. (2009). Acta Cryst. E65, m1353. Fneich, B. N., Das, A., Kirschbaum, K. & Mason, M. R. (2018). J. Organomet. Chem. 872, Gottlieb, H. E., Kotlyar, V. & Nudelman, A. (1997). J. Org. Chem. 62, Humphrey, G. R. & Kuethe, J. T. (2006). Chem. Rev. 106, Kingsley, N. B., Kirschbaum, K. & Mason, M. R. (2010). Organometallics, 29, Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, Mallov, I., Spinney, H., Jurca, T., Gorelsky, S., Burchell, T. & Richeson, D. (2012). Inorg. Chim. Acta, 392, 5 9. Mason, M. R. (2003). Chemtracts Inorg. Chem. 16, Mason, M. R., Barnard, T. S., Segla, M. F., Xie, B. H. & Kirschbaum, K. (2003). J. Chem. Crystallogr. 33, Mason, M. R., Fneich, B. N. & Kirschbaum, K. (2003). Inorg. Chem. 42, Mason, M. R., Ogrin, D., Fneich, B., Barnard, T. S. & Kirschbaum, K. (2005). J. Organomet. Chem. 690, Sheldrick, G. M. (2008). Acta Cryst. A64, Sheldrick, G. M. (2015). Acta Cryst. C71, 3 8. Shiri, M., Zolfigol, M. A., Kruger, H. G. & Tanbakouchian, Z. (2010). Chem. Rev. 110, Song, B., Kirschbaum, K. & Mason, M. R. (2012). Organometallics, 31, Song, B., Qu, X., Zhang, L., Han, K., Wu, D., Xiang, C., Wu, H., Wang, T., Teng, Y. & Yu, P. (2014). J. Chem. Pharm. Res. 6, Wei, W., Guo, Y., Xu, J. & Shao, S. (2010). Spectrochim. Acta Part A, 77, Wei, W., Shao, S. J. & Guo, Y. (2015). Spectrochim. Acta Part A, 149, Acta Cryst. (2019). C75, Cole et al. Four bis(3-methyl-1h-indol-2-yl)(salicyl)methanes 69

7 [ Synthesis and crystal structures of some bis(3-methyl-1h-indol-2-yl) (salicyl)methanes Wyatt Cole, Stephanie L. Hemmingson, Audrey C. Eisenberg, Catherine A. Ulman, Joseph M. Tanski and Yutan D. Y. L. Getzler Computing details For both structures, data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: SHELXTL2014 (Sheldrick, 2008); software used to prepare material for publication: SHELXTL2014 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2008). 2-[Bis(3-methyl-1H-indol-2-yl)methyl]-6-methylphenol dimethyl sulfoxide disolvate (IIa) Crystal data C 26 H 24 N 2 O 2C 2 H 6 OS M r = Tetragonal, P a = (3) Å c = (3) Å V = (4) Å 3 Z = 8 F(000) = 2288 Data collection Bruker APEXII CCD diffractometer Radiation source: Cu IuS micro-focus source Detector resolution: pixels mm -1 φ and ω scans Absorption correction: multi-scan (SADABS; Bruker, 2013) T min = 0.62, T max = 0.74 Refinement Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = wr(f 2 ) = S = reflections 351 parameters D x = Mg m 3 Cu Kα radiation, λ = Å Cell parameters from 9904 reflections θ = µ = 1.97 mm 1 T = 125 K Block, colourless mm measured reflections 5288 independent reflections 5266 reflections with I > 2σ(I) R int = θ max = 70.1, θ min = 2.6 h = k = l = restraints Hydrogen site location: mixed H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o2 ) + (0.0328P) P] where P = (F o 2 + 2F c2 )/3 (Δ/σ) max = sup-1

8 Δρ max = 0.17 e Å 3 Δρ min = 0.27 e Å 3 Absolute structure: Refined as an inversion twin Absolute structure parameter: (13) 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. Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 ) x y z U iso */U eq S (5) (5) (2) (11) S (5) (6) (2) (12) O (15) (15) (2) (3) H3B (2) (3) (3) 0.028* O (14) (15) (2) (3) O (15) (15) (2) (3) N (16) (17) (2) (3) H1B (2) (2) (3) 0.019* N (17) (19) (2) (3) H2B (3) (2) (3) 0.024* C (19) (19) (2) (3) H1C * C (19) (19) (2) (3) C (19) (2) (2) (4) C (2) (2) (3) (4) H4A * H4B * H4C * C (19) (2) (2) (4) C (2) (2) (3) (4) H6A * C (2) (2) (3) (4) H7A * C (2) (2) (3) (4) H8A * C (2) (2) (3) (4) H9A * C (2) (2) (2) (4) C (2) (2) (2) (3) C (2) (2) (2) (4) C (2) (2) (3) (4) H13A * H13B * H13C * C (2) (2) (2) (4) sup-2

9 C (3) (2) (3) (4) H15A * C (3) (3) (3) (5) H16A * C (3) (3) (3) (5) H17A * C (2) (3) (3) (5) H18A * C (2) (2) (3) (4) C (19) (2) (2) (3) C (19) (2) (2) (4) C (2) (2) (2) (4) C (2) (3) (3) (4) H23A * H23B * H23C * C (2) (2) (2) (4) H24A * C (2) (2) (3) (4) H25A * C (2) (2) (2) (4) H26A * C (3) (3) (3) (5) H27A * H27B * H27C * C (2) (2) (3) (4) H28A * H28B * H28C * C (4) (3) (4) (7) H29A * H29B * H29C * C (3) (3) (4) (7) H30A * H30B * H30C * Atomic displacement parameters (Å 2 ) U 11 U 22 U 33 U 12 U 13 U 23 S (2) (2) (2) (16) (17) (16) S (2) (3) (2) (19) (19) (19) O (6) (7) (7) (5) (5) (5) O (6) (7) (6) (6) (5) (5) O (7) (7) (7) (6) (6) (6) N (7) (7) (7) (6) (6) (6) sup-3

10 N (8) (8) (7) (6) (6) (6) C (8) (9) (8) (6) (7) (7) C (8) (9) (7) (6) (6) (6) C (9) (9) (8) (7) (7) (7) C (10) (10) (9) (8) (8) (7) C (8) (9) (8) (7) (6) (7) C (9) (9) (9) (7) (7) (7) C (9) (10) (10) (7) (8) (8) C (9) (10) (9) (8) (7) (8) C (9) (10) (8) (7) (7) (7) C (8) (9) (8) (7) (7) (7) C (9) (9) (8) (7) (7) (6) C (10) (10) (8) (7) (7) (7) C (11) (11) (9) (9) (8) (8) C (10) (10) (8) (8) (7) (7) C (12) (11) (8) (9) (8) (8) C (14) (13) (9) (10) (9) (8) C (12) (14) (10) (11) (9) (10) C (11) (13) (10) (9) (8) (9) C (10) (10) (8) (8) (7) (7) C (8) (9) (7) (7) (6) (6) C (8) (9) (7) (7) (6) (7) C (9) (10) (8) (8) (7) (7) C (10) (12) (10) (8) (8) (8) C (10) (10) (8) (8) (7) (7) C (10) (9) (8) (7) (7) (7) C (9) (9) (8) (7) (7) (7) C (12) (14) (10) (10) (9) (9) C (10) (11) (9) (8) (8) (8) C (2) (16) (12) (14) (13) (11) C (18) (15) (15) (13) (14) (13) Geometric parameters (Å, º) S1 O (13) C13 H13B 0.98 S1 C (2) C13 H13C 0.98 S1 C (2) C14 C (3) S2 O (14) C14 C (3) S2 C (3) C15 C (3) S2 C (3) C15 H15A 0.95 O1 C (2) C16 C (4) O1 H3B (19) C16 H16A 0.95 N1 C (2) C17 C (3) N1 C (2) C17 H17A 0.95 N1 H1B (18) C18 C (3) N2 C (2) C18 H18A 0.95 N2 C (2) C20 C (3) N2 H2B (18) C20 C (3) sup-4

11 C1 C (2) C21 C (3) C1 C (2) C22 C (3) C1 C (2) C22 C (3) C1 H1C 1.0 C23 H23A 0.98 C2 C (3) C23 H23B 0.98 C3 C (2) C23 H23C 0.98 C3 C (2) C24 C (3) C4 H4A 0.98 C24 H24A 0.95 C4 H4B 0.98 C25 C (3) C4 H4C 0.98 C25 H25A 0.95 C5 C (3) C26 H26A 0.95 C5 C (2) C27 H27A 0.98 C6 C (3) C27 H27B 0.98 C6 H6A 0.95 C27 H27C 0.98 C7 C (3) C28 H28A 0.98 C7 H7A 0.95 C28 H28B 0.98 C8 C (3) C28 H28C 0.98 C8 H8A 0.95 C29 H29A 0.98 C9 C (3) C29 H29B 0.98 C9 H9A 0.95 C29 H29C 0.98 C11 C (3) C30 H30A 0.98 C12 C (3) C30 H30B 0.98 C12 C (3) C30 H30C 0.98 C13 H13A 0.98 O2 S1 C (9) C16 C15 C (2) O2 S1 C (10) C16 C15 H15A C28 S1 C (11) C14 C15 H15A O3 S2 C (12) C15 C16 C (2) O3 S2 C (11) C15 C16 H16A C30 S2 C (15) C17 C16 H16A C21 O1 H3B (17) C18 C17 C (2) C10 N1 C (15) C18 C17 H17A C10 N1 H1B (15) C16 C17 H17A C2 N1 H1B (15) C17 C18 C (2) C19 N2 C (16) C17 C18 H18A C19 N2 H2B (16) C19 C18 H18A C11 N2 H2B (16) N2 C19 C (2) C2 C1 C (15) N2 C19 C (17) C2 C1 C (13) C18 C19 C (19) C11 C1 C (14) C26 C20 C (16) C2 C1 H1C C26 C20 C (16) C11 C1 H1C C21 C20 C (15) C20 C1 H1C O1 C21 C (15) C3 C2 N (16) O1 C21 C (16) C3 C2 C (16) C20 C21 C (17) N1 C2 C (15) C24 C22 C (17) C2 C3 C (15) C24 C22 C (17) sup-5

12 C2 C3 C (17) C21 C22 C (18) C5 C3 C (17) C22 C23 H23A C3 C4 H4A C22 C23 H23B C3 C4 H4B H23A C23 H23B H4A C4 H4B C22 C23 H23C C3 C4 H4C H23A C23 H23C H4A C4 H4C H23B C23 H23C H4B C4 H4C C25 C24 C (17) C6 C5 C (16) C25 C24 H24A C6 C5 C (17) C22 C24 H24A C10 C5 C (15) C24 C25 C (18) C7 C6 C (18) C24 C25 H25A C7 C6 H6A C26 C25 H25A C5 C6 H6A C20 C26 C (17) C6 C7 C (18) C20 C26 H26A C6 C7 H7A C25 C26 H26A C8 C7 H7A S1 C27 H27A C9 C8 C (17) S1 C27 H27B C9 C8 H8A H27A C27 H27B C7 C8 H8A S1 C27 H27C C8 C9 C (18) H27A C27 H27C C8 C9 H9A H27B C27 H27C C10 C9 H9A S1 C28 H28A N1 C10 C (17) S1 C28 H28B N1 C10 C (15) H28A C28 H28B C9 C10 C (17) S1 C28 H28C N2 C11 C (16) H28A C28 H28C N2 C11 C (16) H28B C28 H28C C12 C11 C (17) S2 C29 H29A C11 C12 C (17) S2 C29 H29B C11 C12 C (17) H29A C29 H29B C14 C12 C (17) S2 C29 H29C C12 C13 H13A H29A C29 H29C C12 C13 H13B H29B C29 H29C H13A C13 H13B S2 C30 H30A C12 C13 H13C S2 C30 H30B H13A C13 H13C H30A C30 H30B H13B C13 H13C S2 C30 H30C C15 C14 C (19) H30A C30 H30C C15 C14 C (2) H30B C30 H30C C19 C14 C (16) C10 N1 C2 C3 0.2 (2) C1 C11 C12 C (3) C10 N1 C2 C (15) C13 C12 C14 C (3) C11 C1 C2 C (2) C11 C12 C14 C (2) C20 C1 C2 C (19) C13 C12 C14 C (17) C11 C1 C2 N (2) C19 C14 C15 C (3) C20 C1 C2 N (2) C12 C14 C15 C (2) sup-6

13 N1 C2 C3 C5 0.3 (2) C14 C15 C16 C (3) C1 C2 C3 C (16) C15 C16 C17 C (3) N1 C2 C3 C (17) C16 C17 C18 C (3) C1 C2 C3 C4 0.3 (3) C11 N2 C19 C (2) C2 C3 C5 C (2) C11 N2 C19 C (2) C4 C3 C5 C6 0.9 (3) C17 C18 C19 N (2) C2 C3 C5 C (2) C17 C18 C19 C (3) C4 C3 C5 C (17) C15 C14 C19 N (16) C10 C5 C6 C7 0.3 (3) C12 C14 C19 N2 0.2 (2) C3 C5 C6 C (19) C15 C14 C19 C (3) C5 C6 C7 C8 0.3 (3) C12 C14 C19 C (18) C6 C7 C8 C9 0.1 (3) C2 C1 C20 C (19) C7 C8 C9 C (3) C11 C1 C20 C (2) C2 N1 C10 C (18) C2 C1 C20 C (18) C2 N1 C10 C (19) C11 C1 C20 C (16) C8 C9 C10 N (18) C26 C20 C21 O (15) C8 C9 C10 C5 0.3 (3) C1 C20 C21 O1 2.3 (2) C6 C5 C10 N (16) C26 C20 C21 C (2) C3 C5 C10 N (19) C1 C20 C21 C (15) C6 C5 C10 C9 0.0 (3) O1 C21 C22 C (16) C3 C5 C10 C (17) C20 C21 C22 C (2) C19 N2 C11 C (2) O1 C21 C22 C (3) C19 N2 C11 C (16) C20 C21 C22 C (17) C2 C1 C11 N2 7.9 (2) C21 C22 C24 C (3) C20 C1 C11 N (16) C23 C22 C24 C (17) C2 C1 C11 C (17) C22 C24 C25 C (3) C20 C1 C11 C (2) C21 C20 C26 C (2) N2 C11 C12 C (2) C1 C20 C26 C (16) C1 C11 C12 C (16) C24 C25 C26 C (3) N2 C11 C12 C (17) Hydrogen-bond geometry (Å, º) D H A D H H A D A D H A O1 H3B S (2) 2.92 (2) (14) 135 (2) O1 H3B O (2) 1.87 (2) (19) 161 (2) N1 H1B O (2) 2.07 (2) (2) 158 (2) N2 H2B S2 i 0.85 (2) 3.03 (2) (18) 147 (2) N2 H2B O3 i 0.85 (2) 2.02 (2) (2) 159 (2) C28 H28C S1 ii (2) 117 Symmetry codes: (i) x 1, y, z; (ii) x+1/2, y+1/2, z+3/4. 2-[Bis(3-methyl-1H-indol-2-yl)methyl]-4,6-dichlorophenol dimethyl sulfoxide disolvate (IIb) Crystal data C 25 H 20 Cl 2 N 2 O 2C 2 H 6 OS M r = Triclinic, P1 a = (9) Å b = (11) Å c = (16) Å sup-7

14 α = (2) β = (2) γ = (2) V = (3) Å 3 Z = 2 F(000) = 620 D x = Mg m 3 Data collection Bruker APEXII CCD diffractometer Radiation source: fine-focus sealed tube Graphite monochromator Detector resolution: pixels mm -1 φ and ω scans Absorption correction: multi-scan (SADABS; Bruker, 2013) T min = 0.88, T max = 0.99 Refinement Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = wr(f 2 ) = S = reflections 358 parameters 3 restraints Mo Kα radiation, λ = Å Cell parameters from 9925 reflections θ = µ = 0.40 mm 1 T = 125 K Needle, colourless mm measured reflections 8941 independent reflections 5592 reflections with I > 2σ(I) R int = θ max = 30.6, θ min = 2.0 h = k = l = Hydrogen site location: mixed H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o2 ) + (0.0502P) P] where P = (F o 2 + 2F c2 )/3 (Δ/σ) max < Δρ max = 0.44 e Å 3 Δρ min = 0.56 e Å 3 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. Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 ) x y z U iso */U eq Cl (5) (5) (4) (13) Cl (7) (5) (4) (14) O (16) (14) (10) (3) H (18) (2) (16) 0.03* N (19) (17) (11) (4) H (2) (17) (14) 0.024* N (18) (16) (11) (4) H (2) (18) (13) 0.023* C (2) (19) (13) (4) C (2) (19) (13) (4) C (2) (19) (13) (4) H3B * C (2) (19) (13) (4) C (2) (18) (13) (4) sup-8

15 H5A * C (2) (19) (13) (4) C (2) (19) (13) (4) H7A * C (2) (19) (13) (4) C (2) (19) (14) (4) C (2) (2) (15) (5) H10A * H10B * H10C * C (2) (19) (14) (4) C (3) (2) (16) (5) H12A * C (3) (2) (16) (6) H13A * C (3) (2) (16) (6) H14A * C (3) (2) (14) (5) H15A * C (2) (2) (14) (4) C (2) (19) (13) (4) C (2) (19) (13) (4) C (2) (2) (14) (5) H19A * H19B * H19C * C (2) (18) (13) (4) C (2) (2) (14) (4) H21A * C (2) (2) (14) (5) H22A * C (2) (2) (14) (5) H23A * C (2) (2) (14) (4) H24A * C (2) (18) (13) (4) S (7) (6) (4) (15) O (17) (15) (10) (4) C (6) (3) (2) (15) H26A * H26B * H26C * C (3) (3) (17) (7) H27A * H27B * H27C * S (6) (5) (4) (12) O (15) (14) (9) (3) sup-9

16 C (3) (2) (15) (5) H28A * H28B * H28C * C (3) (2) (16) (5) H29A * H29B * H29C * Atomic displacement parameters (Å 2 ) U 11 U 22 U 33 U 12 U 13 U 23 Cl (2) (3) (3) (2) (2) (2) Cl (3) (3) (3) (2) (3) (3) O (7) (8) (9) (6) (6) (7) N (9) (9) (9) (7) (7) (7) N (8) (9) (9) (7) (7) (7) C (9) (10) (10) (7) (8) (8) C (9) (10) (9) (8) (7) (8) C (10) (11) (10) (8) (8) (8) C (11) (10) (10) (8) (8) (8) C (9) (10) (10) (7) (8) (8) C (9) (10) (10) (7) (7) (8) C (9) (10) (10) (7) (7) (8) C (9) (10) (10) (7) (8) (8) C (9) (10) (11) (8) (8) (8) C (11) (12) (13) (9) (10) (10) C (10) (11) (11) (8) (8) (9) C (12) (11) (13) (9) (10) (10) C (14) (12) (14) (10) (11) (11) C (14) (15) (12) (11) (10) (11) C (12) (13) (11) (10) (9) (10) C (10) (11) (10) (8) (8) (9) C (9) (10) (10) (7) (7) (8) C (9) (10) (10) (7) (8) (8) C (11) (12) (11) (9) (9) (9) C (9) (10) (9) (7) (8) (8) C (10) (11) (10) (8) (8) (8) C (11) (11) (11) (9) (9) (9) C (10) (11) (12) (8) (9) (9) C (9) (11) (11) (8) (8) (9) C (9) (10) (10) (7) (7) (8) S (3) (4) (3) (3) (2) (3) O (9) (9) (8) (7) (7) (7) C (5) (19) (18) (2) (2) (16) C (16) (17) (15) (13) (12) (12) S (2) (3) (3) (2) (2) (2) O (7) (8) (8) (6) (6) (6) sup-10

17 C (12) (13) (12) (10) (9) (10) C (13) (12) (13) (10) (10) (10) Geometric parameters (Å, º) Cl1 C (2) C15 C (3) Cl2 C (2) C15 H15A 0.95 O1 C (2) C17 C (3) O1 H (16) C18 C (3) N1 C (3) C18 C (3) N1 C (3) C19 H19A 0.98 N1 H (15) C19 H19B 0.98 N2 C (3) C19 H19C 0.98 N2 C (2) C20 C (3) N2 H (15) C20 C (3) C1 C (3) C21 C (3) C1 C (3) C21 H21A 0.95 C2 C (3) C22 C (3) C3 C (3) C22 H22A 0.95 C3 H3B 0.95 C23 C (3) C4 C (3) C23 H23A 0.95 C5 C (3) C24 C (3) C5 H5A 0.95 C24 H24A 0.95 C6 C (3) S1 O (16) C7 C (3) S1 C (3) C7 C (3) S1 C (3) C7 H7A 1.0 C26 H26A 0.98 C8 C (3) C26 H26B 0.98 C9 C (3) C26 H26C 0.98 C9 C (3) C27 H27A 0.98 C10 H10A 0.98 C27 H27B 0.98 C10 H10B 0.98 C27 H27C 0.98 C10 H10C 0.98 S2 O (15) C11 C (3) S2 C (2) C11 C (3) S2 C (2) C12 C (3) C28 H28A 0.98 C12 H12A 0.95 C28 H28B 0.98 C13 C (4) C28 H28C 0.98 C13 H13A 0.95 C29 H29A 0.98 C14 C (3) C29 H29B 0.98 C14 H14A 0.95 C29 H29C 0.98 C1 O1 H (17) C18 C17 N (17) C16 N1 C (17) C18 C17 C (17) C16 N1 H (15) N2 C17 C (17) C8 N1 H (15) C17 C18 C (16) C25 N2 C (16) C17 C18 C (18) C25 N2 H (15) C20 C18 C (18) sup-11

18 C17 N2 H (15) C18 C19 H19A O1 C1 C (18) C18 C19 H19B O1 C1 C (17) H19A C19 H19B C2 C1 C (18) C18 C19 H19C C3 C2 C (18) H19A C19 H19C C3 C2 Cl (15) H19B C19 H19C C1 C2 Cl (15) C21 C20 C (18) C4 C3 C (18) C21 C20 C (18) C4 C3 H3B C25 C20 C (17) C2 C3 H3B C22 C21 C (19) C3 C4 C (19) C22 C21 H21A C3 C4 Cl (16) C20 C21 H21A C5 C4 Cl (16) C21 C22 C (19) C6 C5 C (18) C21 C22 H22A C6 C5 H5A C23 C22 H22A C4 C5 H5A C24 C23 C (19) C5 C6 C (18) C24 C23 H23A C5 C6 C (17) C22 C23 H23A C1 C6 C (17) C23 C24 C (19) C17 C7 C (15) C23 C24 H24A C17 C7 C (16) C25 C24 H24A C8 C7 C (16) N2 C25 C (18) C17 C7 H7A N2 C25 C (16) C8 C7 H7A C24 C25 C (18) C6 C7 H7A O2 S1 C (16) C9 C8 N (18) O2 S1 C (11) C9 C8 C (18) C26 S1 C (15) N1 C8 C (17) S1 C26 H26A C8 C9 C (18) S1 C26 H26B C8 C9 C (19) H26A C26 H26B C11 C9 C (19) S1 C26 H26C C9 C10 H10A H26A C26 H26C C9 C10 H10B H26B C26 H26C H10A C10 H10B S1 C27 H27A C9 C10 H10C S1 C27 H27B H10A C10 H10C H27A C27 H27B H10B C10 H10C S1 C27 H27C C12 C11 C (2) H27A C27 H27C C12 C11 C (2) H27B C27 H27C C16 C11 C (18) O3 S2 C (9) C13 C12 C (2) O3 S2 C (10) C13 C12 H12A C28 S2 C (11) C11 C12 H12A S2 C28 H28A C12 C13 C (2) S2 C28 H28B C12 C13 H13A H28A C28 H28B C14 C13 H13A S2 C28 H28C C15 C14 C (2) H28A C28 H28C C15 C14 H14A H28B C28 H28C sup-12

19 C13 C14 H14A S2 C29 H29A C14 C15 C (2) S2 C29 H29B C14 C15 H15A H29A C29 H29B C16 C15 H15A S2 C29 H29C N1 C16 C (2) H29A C29 H29C N1 C16 C (18) H29B C29 H29C C15 C16 C (2) O1 C1 C2 C (18) C12 C13 C14 C (4) C6 C1 C2 C3 0.6 (3) C13 C14 C15 C (3) O1 C1 C2 Cl1 1.0 (3) C8 N1 C16 C (2) C6 C1 C2 Cl (15) C8 N1 C16 C (2) C1 C2 C3 C4 0.5 (3) C14 C15 C16 N (2) Cl1 C2 C3 C (15) C14 C15 C16 C (3) C2 C3 C4 C5 1.0 (3) C12 C11 C16 N (18) C2 C3 C4 Cl (15) C9 C11 C16 N1 0.6 (2) C3 C4 C5 C6 0.4 (3) C12 C11 C16 C (3) Cl2 C4 C5 C (15) C9 C11 C16 C (19) C4 C5 C6 C1 0.8 (3) C25 N2 C17 C (2) C4 C5 C6 C (17) C25 N2 C17 C (17) O1 C1 C6 C (17) C8 C7 C17 C (19) C2 C1 C6 C5 1.3 (3) C6 C7 C17 C (2) O1 C1 C6 C7 0.2 (3) C8 C7 C17 N (3) C2 C1 C6 C (17) C6 C7 C17 N (2) C5 C6 C7 C (2) N2 C17 C18 C (2) C1 C6 C7 C (17) C7 C17 C18 C (18) C5 C6 C7 C (2) N2 C17 C18 C (18) C1 C6 C7 C (2) C7 C17 C18 C (3) C16 N1 C8 C9 0.3 (2) C17 C18 C20 C (2) C16 N1 C8 C (17) C19 C18 C20 C (4) C17 C7 C8 C (2) C17 C18 C20 C (2) C6 C7 C8 C (2) C19 C18 C20 C (19) C17 C7 C8 N (2) C25 C20 C21 C (3) C6 C7 C8 N (2) C18 C20 C21 C (2) N1 C8 C9 C (2) C20 C21 C22 C (3) C7 C8 C9 C (18) C21 C22 C23 C (3) N1 C8 C9 C (19) C22 C23 C24 C (3) C7 C8 C9 C (3) C17 N2 C25 C (2) C8 C9 C11 C (2) C17 N2 C25 C (2) C10 C9 C11 C (4) C23 C24 C25 N (2) C8 C9 C11 C (2) C23 C24 C25 C (3) C10 C9 C11 C (19) C21 C20 C25 N (17) C16 C11 C12 C (3) C18 C20 C25 N2 1.5 (2) C9 C11 C12 C (2) C21 C20 C25 C (3) C11 C12 C13 C (3) C18 C20 C25 C (18) sup-13

20 Hydrogen-bond geometry (Å, º) D H A D H H A D A D H A O1 H1 Cl (2) 2.63 (2) (15) 112 (2) O1 H1 S (2) 2.87 (2) (15) 124 (2) O1 H1 O (2) 1.84 (2) (19) 151 (2) N1 H3 S (2) 3.02 (2) (18) 139 (2) N1 H3 O (2) 2.03 (2) (2) 155 (2) N2 H2 S2 i 0.86 (2) 2.95 (2) (18) 137 (2) N2 H2 O3 i 0.86 (2) 1.98 (2) (2) 161 (2) Symmetry code: (i) x 1, y, z. sup-14