Crystal structure of a methanol solvate of a macrocycle bearing two flexible side-arms

In the crystal structure of di-tert-butyl N,N′-{[13,15,28,30,31,33-hexaethyl-3,10,18,25,32,34-hexaazapentacyclo[25.3.1.15,8.112,16.120,23]tetratriaconta-1(31),3,5,7,9,12 (33),13,15,18,20,22,24,27,29-tetradecaene-14,29-diyl]bis(methylene)}dicarbamate methanol disolvate, a pair of solvent molecules is located in the cavity of the host molecule.


Chemical context
Representatives of compounds consisting of a macrocyclic building block and two flexible side-arms have been shown to be able to act as powerful carbohydrate-binding agents (artificial carbohydrate receptors). Depending on the nature of their building blocks, various receptors with different binding properties could be developed (Lippe & Mazik, 2013, 2015Amrhein et al., 2016.). The design of such a receptor architecture was inspired by the results of our crystallographic studies, including the analyses of the binding motifs in complexes formed between acyclic receptors and monosaccharides, reported by us some time ago (Mazik et al., 2005). At this point it should be noted that, in contrast to numerous known crystal structures of protein-carbohydrate complexes, there are only individual literature reports on the crystal structures of complexes formed between artificial receptors and sugars (for a recent report on such crystalline complexes, see Kö hler et al., 2020). The syntheses of the above-mentioned receptors, combining a macrocyclic building block and flexible side-arms, involve the preparation of macrocyclic precursors containing four imine functionalities. The crystal structure of one of such macrocyclic precursors is described in this work. This macrocycle bears two identical side-arms, containing the tert-butyloxycarbonyl group (BOC group), and is composed of two triethylbenzene units connected by two bridges, each bearing one pyrrole moiety and two imine functionalities.

Structural commentary
The title compound was found to crystallize as a methanol solvate of the space group P2 1 /c with the asymmetric unit of

Supramolecular features
Within the 1:2 host-guest complex, each of the methanol molecules interacts with the host by a O-HÁ Á ÁN imine [d(HÁ Á ÁN) = 1.82 (3) Å ] and an N pyrrole -HÁ Á ÁO hydrogen bond [d(HÁ Á ÁO) = 2.10 (2) Å ] that generate a cyclic synthon with a R 2 2 (7) motif according to Etter's definition (Etter, 1990;Bernstein et al., 1995). Thus, the hydroxy group of each of the methanol molecules participates in cooperative hydrogen bonds. The host-guest complexes are connected primarily by interactions involving the carbonyl oxygen atoms. Here, O2 acts as a bifurcated acceptor for the formation of C-HÁ Á ÁO C bonds [d(HÁ Á ÁO) = 2.49, 2.52 Å ], in which the imine atom H24 (see Figs. 2 and 3) and the pyrrole atom H18 of different molecules are included. The second oxygen atom of the BOC group provides a weak C-HÁ Á ÁO bond involving the tert-butyl group of the neighboring molecule, which further participates in intermolecular C-HÁ Á Á interactions with the pyrrole unit of an adjacent host molecule, as shown in Fig. 3 [d(HÁ Á ÁCg) = 3.00 Å ]. In addition, the imine atom H16 contributes to formation of a C-HÁ Á Á contact (see Fig. 2 Perspective view of the 1:2 host-guest complex with methanol including the atom labeling. Anisotropic displacement ellipsoids are drawn at the 50% probability level. Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Part of the crystal structure of the 1:2 host-guest complex showing the mode of non-covalent intermolecular bonding. For the sake of clarity, the H atoms of the host molecule not involved in hydrogen-bonding interactions are omitted.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The non-hydrogen atoms were refined anisotropically. The NH and OH hydrogens were located in a difference-Fourier map and refined freely. All other hydrogen atoms were positioned geometrically and allowed to ride on their parent atoms: C-H = 0.95 Å for imine and pyrrol H atoms, C-H = 0.99 Å for methylene groups and C-H = 0.98 Å for methyl groups with U iso (H) = 1.5U eq (C) for methyl groups and U iso (H) = 1.2U eq (C) for other hydrogen atoms.

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.