Crystal structures of monohydrate and methanol solvate compounds of {1-[(3,5-bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzyl)amino]cyclopentyl}methanol

In the crystal structures of the monohydrate and methanol solvate title compounds, the host molecule adopts similar geometries with an alternating orientation of the substituents above and below the plane of the central arene ring.


Chemical context
Representatives of the class of 1,3,5-trisubstituted 2,4,6-trialkylbenzenes have been shown to have the ability to act as artificial carbohydrate receptors. Depending on the nature of their building blocks, these compounds display different, interesting binding efficiencies and selectivities towards carbohydrates (Mazik, 2009(Mazik, , 2012Stapf et al., 2020). Our systematic studies have shown the enormous potential of this acyclic receptor architecture for versatile structural modifications, which enable the identification of interesting structure-activity relationships. For example, we have observed that the combination of two 2-aminopyridine units with another recognition group provides receptors having a binding preference for -glucoside vs -galactoside (Mazik & Kuschel, 2008;Mazik & Geffert, 2011;Stapf et al., 2020).

Structural commentary
Compounds 1a and 1b crystallize in the space groups P2 1 /c and P1, respectively. The molecular structures depicted in Figs. 1 and 2 reveal similar host geometries with a fully alternating arrangement of the substituents above and below the plane of the central arene ring [ab'ab'ab' pattern, a = above, b = below (a 0 /b 0 = Et above/below); for a discussion on the conformations of triethylbenzene-based compounds, see: Koch et al., 2017;Schulze et al., 2017]. In other words, the three functionalized side arms point to one face of the central benzene ring and participate in the formation of hydrogen bonds with the guest solvent molecule, while the ethyl groups are directed to the opposite side. The heterocyclic units are inclined by 62.4 (1) and 73.0 (1) for 1a [78.9 (1) and 85.1 (1) for 1b] with respect to the benzene ring. The cyclopentane rings adopt a slightly distorted envelope conformation with C33 (1a) and C31 (1b) as the flap.

Supramolecular features
The crystal structures of 1a and 1b are composed of inversionsymmetric dimers of 1:1 host-guest complexes (Fig. 3). The donor/acceptor properties of the solvent species have, however, a marked influence on the patterns of hydrogenbonding interactions. In the crystal of 1a, the dimeric structural unit is held together by classical hydrogen bonds (N5-H5Á Á ÁO1W i and O1W-H2WÁ Á ÁN5; symmetry code as given in Table 1) that contribute to the formation of a cyclic supramolecular synthon with a graph-set motif R 4 4 (8). Within this dimeric unit, the oxygen atom of the water molecules acts as a trifurcated acceptor, as it is involved in the formation Ball-and-stick representations (side views) of the 1:1 host-guest complexes, 1a (a) and 1b (b).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. N-and O-bound H atoms in 1a were located in a difference-Fourier map and refined freely with distance restraints of N-H = 0.89 (1) Å and O-H = 0.85 (1) Å . For 1b, N-bound H atoms were refined freely, while O-bound H atoms were treated as riding with O-H = 0.84 Å . All other H atoms were positioned geometrically and refined as riding, with C-H = 0.93-0.99 Å , and with U iso (H) = 1.5U eq (C) for methyl groups and U iso (H) = 1.2U eq (C) for other H atoms. The crystal structure 1b contains highly disordered solvent molecules that could not be refined to an acceptable level. Thus, the SQUEEZE routine (Spek, 2015) in the PLATON (Spek, 2020) program was used to generate a modified data set in which the contribution of the disordered molecules to the structure amplitudes is eliminated. These solvent molecules are not considered in the given chemical formula. The void volume of 267.9 Å 3 occupied by the disordered solvent represents 14.3% of the cell volume, and the calculated electron count was 65 per void.

{1-[(3,5-Bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzyl)amino]cyclopentyl}methanol monohydrate (1a)
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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )