Synthesis and crystal structures of two solvates of 1-{[2,6-bis(hydroxymethyl)-4-methylphenoxy]methyl}-3,5-bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzene

In the crystal structures of the formamide monosolvate (1a) and the n-propanol/water solvate/hydrate (1b), the host molecules adopt similar geometries with an alternating arrangement of the substituents above and below the plane of the central arene ring.

In the crystal structures of the formamide monosolvate (1a) and the n-propanol/ H 2 O solvate/hydrate (1b) of the title compound, C 38 H 50 N 4 O 3 (1), the tripodal host molecule adopts a conformation in which the substituents attached to the central benzene ring are arranged in an alternating order above and below the ring plane.As a result of the different nature of the involved guest species, the crystal components in 1a create a three-dimensional supramolecular architecture, while the crystal structure of 1b consists of two-dimensional supramolecular aggregates extending parallel to the crystallographic ab plane.

Chemical context
1,3,5-Trisubstituted 2,4,6-triethylbenzene derivatives with functionalized side-arms can serve as artificial receptors for molecular recognition of carbohydrates.In addition to the development of acyclic receptor molecules, the triethylbenzene scaffold was found to be valuable for the construction of macrocyclic systems.The possibilities for functionalization of acyclic and macrocyclic molecules of this type are manifold, allowing the synthesis of a whole range of compounds for systematic binding studies.Some examples of suitable functional groups, which can act as recognition units and have been considered in our studies, are heteroaromatic units such as pyridine-, pyrimidine- (Lippe et al., 2015), pyrazole- (Koch et al., 2016), purine- (Kaiser et al., 2019) or phenanthroline-based recognition groups (Ko ¨hler et al., 2020), (cyclo)alkylamino groups (Stapf et al., 2020a;Leibiger et al., 2022) as well as subunits containing hydroxy groups.Among the molecules with the latter groups, studies of the binding properties of acyclic (Mazik & Kuschel, 2008a) and macrocyclic (Amrhein et al., 2016) compounds bearing a hydroxymethyl group at the triethylbenzene core should be mentioned.These binding studies included NMR spectroscopic titrations and microcalorimetric investigations (ITC experiments).Similarly, chip calorimetry experiments were performed with one of our receptor compounds possessing [1-(hydroxymethyl)cyclopent-1-yl]amino moieties (Lerchner et al., 2022).Further compounds bearing hydroxy groups, whose crystal structures we have recently discussed (Stapf et al., 2020b(Stapf et al., , 2022)), are currently being investigated for their ability to act as receptors for carbohydrates.In this article, we describe the crystal structures of the formamide monosolvate and the n-propanol/ H 2 O solvate/hydrate of compound 1 containing the 2,6-bis-(hydroxymethyl)-4-methylphenoxy moiety, which represents a new structural unit for the design of carbohydrate receptors.

Structural commentary
The formamide solvate (1a) and the n-propanol/H 2 O solvate/ hydrate (1b) of the title compound, C 38 H 50 N 4 O 3 , crystallize in the triclinic system (P1, Z = 2).The model for the leastsquares refinement includes positional disorder for one of the (4,6-dimethylpyridin-2-yl)amino moieties of the structure of 1b with occupancies of 0.78/0.22.The perspective views of the host-guest complexes shown in Fig. 1 and Fig. 2 reveal similar geometries of the tripodal host molecule with the three functionalized side-arms located on one side of the central benzene ring, while the ethyl substituents are oriented in the opposite direction.The inclination angles of the aromatic rings of the substituents with reference to the central benzene ring are 50.9(1), 85.5 (1), 87.2 (1) � for 1a and 61.3 (1), 81.3 (1), 80.7 (1)/88.4(3) � for 1b.Despite the large number of strong Perspective view of the host-guest complex 1a including atom labelling.Anisotropic displacement ellipsoids are drawn at the 50% probability level.Intermolecular hydrogen bonds between the host molecule and the formamide are shown as dashed lines.

Figure 2
Perspective view of the host-guest complex 1b including atom labelling.Anisotropic displacement ellipsoids are drawn at the 50% probability level.Intermolecular hydrogen bonds are shown as dashed lines.

Supramolecular features
In the complex structure of 1a (Fig. 3), the formamide molecule is connected to the host molecule by an N-H� � �N hydrogen bond [d(H� � �N) = 2.12 (1) A ˚] and a weak C-H� � �N bond (Desiraju & Steiner, 1999) (Nishio et al., 2009(Nishio et al., , 2012) ) [d(H� � �Cg) = 2.71-2.81A ˚] and �-� stacking (Dance, 2004;Salonen et al., 2011) [Cg� � �Cg distance = 3.475 (1) A ˚], the latter formed by the hydroxymethyl-substituted aromatic rings of inversion-related molecules.Within this three-dimensional supramolecular network, the solvent molecules form N-H� � �O bonded dimers [d(H� � �O) = 2.01 (1) A ˚] of the graph-set motif R 2 2 (8) (Etter, 1991;Bernstein et al., 1995).The colourless rod-like crystals obtained from n-propanol proved to be an inclusion compound of 1 with n-PrOH and H 2 O possessing a host/guest stoichiometric ratio of 1:0.78:0.22.The model for least-squares refinement assumes partial occupancies for the alcohol and water molecules, i.e. the solvent species are distributed in a statistical manner in the voids of the host lattice.Despite the presence of strong donors/acceptors, the disordered moiety of the host hardly participates in molecular association.Only the minor disorder component of this residue is involved in any intermolecular interactions, by forming a weak C-H� � �O bond to the water oxygen [d(H� � �O) = 2.16 A ˚] (see Fig. 4b).As shown in Fig. 4a, the oxygen atom of the alcohol molecule is linked to one of the hydroxy hydrogens of the host [O2-H2� � �O1A, d(H� � �O) = 1.86 (2) A ˚].In an analogous way, this hydrogen acts as a donor site for hydrogen bonding to the water molecule [O2-H2� � �O1W, d(H� � �O) = 1.97 (2) A ˚]. Unfortunately, the positions of the water hydrogen atoms could not be obtained from the difference electron-density map, so that the complete pattern of hydrogen bonding in the crystal of 1b could not be elucidated.Nevertheless, a striking motif of hydrogen bonds is present, involving a total of three hydroxy groups of the host and the propanol molecules [oxygen atoms O1A, O2 and O3; d(H� � �O/N) = 1.86 (2)-2.21(1) A ˚].They form chain-like synthons in the direction of the b axis, bounded by an amine H and a ring N atom, and can be described by the graph set    C 4 4 (10) (Fig. 5).Taking into account these interactions, the crystal structure (Fig. 5) can be regarded as being composed of layered supramolecular aggregates extending parallel to the crystallographic ab plane.As the surfaces of the two-dimensional aggregates are defined by the non-polar molecular parts, interlayer interactions are restricted to van der Waals forces.

Synthesis and crystallization
A suspension of 2,6-bis(hydroxymethyl)-4-methylphenol (102 mg, 0.61 mmol) and potassium carbonate (142 mg, 1.03 mmol) in 30 mL of THF/CH 3 CN (1:1, v/v) was stirred for 30 minutes.Subsequently, a solution of 1-(bromomethyl)-3,5bis[(4,6-dimethylpyridin-2-yl)aminomethyl]-2,4,6-triethylbenzene (265 mg, 0.51 mmol) in 30 mL of THF/CH 3 CN (1:1, v/v) was added dropwise and the resulting mixture was stirred at room temperature and under the exclusion of light (the progress of the reaction was monitored by TLC).After filtration, the solvents were evaporated at reduced pressure and the yellow oil was treated with THF/water.The oil was separated from the aqueous phase and dissolved again in THF, dried over MgSO 4 and the solvent was removed.By treating the oily residue with diethyl ether/n-hexane, the product was obtained as a white solid in 88% yield (271 mg, 0.44 mmol).Crystals of the title compound suitable for single crystal X-ray diffraction were grown by slow evaporation of an ethyl acetate/formamide (1:1, v/v) solution (1a) or a n-propanol solution (1b) at ambient temperature.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.The non-hydrogen atoms were refined anisotropically.The positions of the N-H and O-H hydrogen atoms were extracted from difference-Fourier maps.All other hydrogen atoms were positioned geometrically and refined isotropically using a riding model with C-H = 0.95-0.99A ˚(alkyl), 0.95 A ˚(aryl); U iso (H) = 1.2-1.5Ueq (C).(Sheldrick, 2015); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

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 3
Figure 3Packing diagram of the formamide monosolvate of the title compound 1a.Dashed lines represent hydrogen-bond interactions.

Figure 4
Figure 4Perspective views of the structures of the n-propanol solvate (a) and the monohydrate (b) of the title compound.

Figure 5
Figure 5Packing diagram of the host-guest complex 1b looking in the crystallographic c-axis direction.For clarity, the water molecules are not shown.Dashed lines represent hydrogen-bond interactions.

Table 3
Experimental details.