Synthesis and crystal structure of 2-(2-hydroxyphenyl)-1,3-bis(4-methoxybenzyl)-1,3-diazinan-5-ol

The title compound resulted from the condensation reaction between 1,3-bis{[(4-methoxyphenyl)methyl]amino}propan-2-ol and 2-hydroxybenzaldehyde in CH3OH. The structure exhibits disorder of one of the 4-methoxybenzyl groups, the hydroxy group bonded to the 1,3-diazinan ring, and the methyl group of the methoxy residue. The crystal packing is sustained by C—H⋯O and O—H⋯π interactions, giving rise to infinite chains running along the b-axis direction.


Chemical context
Within the framework of a program intended to develop 1,2,3trisubstituted 1,3-diazinan-5-ol derivatives with conformational properties, we were interested in probing the relation between intramolecular hydrogen bonding and the final conformations of the title compound, which was synthesized by reacting 1,3-bis{[(4-methoxyphenyl)methyl]amino}propan-2-ol, easily obtained following the reported method , with 2-hydroxybenzaldehyde. Most six-membered heterocycles prefer to adopt chair conformations with equatorially situated substituent groups where the bulky groups attached to the heterocycles generally have a greater preference for the equatorial position than in the case of substituted cyclohexane (Wiberg et al., 2018). Consequently, the 1 H NMR spectrum (CDCl 3 ) of the title compound showed well-resolved signals for the axial and equatorial protons. It is noteworthy that the coupling constants with magnitudes between 2.9 and 3.1 Hz provide a strong evidence of the presence of an axial OH group. In this regard, it has been reported that the presence of an intramolecular hydrogen bond may stabilize the hydroxyl group in the otherwise non-preferred axial position (Koll et al., 2006). Therefore, the proton of the OH group in the 5 position of the 1,3-diazinan-5-ol ring might form an intramolecular hydrogen bond to either one or both endocyclic nitrogen atoms to stabilize its axial position; however, no such interactions were formed. Instead, the crystallographic analysis showed that the intramolecular hydrogen bonds are observed between the proton of the phenolic OH group and the nitrogen atoms of the 1,3-diazinan-5-ol ring.
As mentioned above, an intramolecular O-HÁ Á ÁN hydrogen bonds is formed between the N1 atom of the 1,3diazinan-5-ol ring and the OH group of the hydroxyphenyl substituent, resulting in an S(6) graph-set motif (Table1  Rivera et al. 2014], indicating that the introduction of the hydroxyphenyl group in the 2-position of the 1,3-diazinan-5-ol ring decreased the strength of the intramolecular hydrogen bonds in these compounds.

Supramolecular features
In contrast to the supramolecular structures observed in the previously reported related 1,3-diazinan-5-ol hydrates (Rivera, Miranda-Carvajal, Ríos-Motta & Bolte, 2016;Rivera et al. 2014), where the water molecules play a significant role in assembling the three-dimensional supramolecular architecture, the molecular structure of the title compound contains only the unsolvated main molecule.

Figure 1
The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. The intramolecular hydrogen bond is shown as a dashed line and, for clarity, only the major disorder components are included.

Figure 2
Overlay image of the molecular disorder of the title compound. The major occupancy sites are drawn with full bonds, while the minor occupancy sites with open bonds Table 1 Hydrogen-bond geometry (Å , ).

Synthesis and crystallization
To a stirred solution of 1,3-bis{[(4-methoxyphenyl)methyl]amino}propan-2-ol (661 mg, 2 mmol) in methanol (20 mL) salicylaldehyde (0.21 mL, 246 mg, 2 mmol) was added dropwise. The resulting mixture was heated at reflux for 2 h and allowed to cool to room temperature. The solvent was removed under vacuum and the crude solid was washed with cold methanol and dried in vacuo. The solid was dissolved in hexane-chloroform mixture and after standing for several days at room temperature, colorless crystals suitable for X-ray diffraction were obtained. Yield 652 mg (75%), m.p. 413 K.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms bonded to C were refined using a riding model. U iso values of methyl H atoms were set to 1.5U eq (C), while the U iso values of H atoms bonded to the remaining C atoms were set to 1.2U eq (C). The H atom bonded to O in the major occupied site was freely refined. The H atom bonded to O in the minor occupied site was refined using a riding model with U iso (H) set to 1.5U eq (O). In addition, the H-O-C-C torsion angle was allowed to refine. The displacement ellipsoids of O4 and O4 0 were restrained to be similar. The distances O4-C3 and O4 0 -C3 were restrained to be similar. Bond lengths and angles in the fragments C24-O2-C27 0 and C24-O2-C27 were restrained to be similar. The displacement ellipsoids of O2 and C27/C27 0 were restrained to be similar. Bond lengths, angles and displacement parameters in the fragments N2-  were restrained to be similar. The following restraints implemented in SHELXL (Sheldrick, 2015) were used to restrain the geometry (SADI, SAME) and U ij (SIMU, RIGU) of the disordered parts.

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.