Crystal structure and Hirshfeld surface analysis of the product of the ring-opening reaction of a dihydrobenzoxazine: 6,6′-[(cyclohexylazanediyl)bis(methylene)]bis(2,4-dimethylphenol)

In the title unsymmetrical tertiary amine, which arose from the ring-opening reaction of a dihydrobenzoxazine, two 2,4-dimethylphenol moieties are linked by a 6,6′-(cyclohexylazanediyl)-bis(methylene) bridge: the dihedral angle between the phenol rings is 72.45 (7)°. The cyclohexyl ring adopts a chair conformation with the exocyclic C—N bond in an equatorial orientation.

In the title unsymmetrical tertiary amine, C 24 H 33 NO 2 , which arose from the ringopening reaction of a dihydrobenzoxazine, two 2,4-dimethylphenol moieties are linked by a 6,6 0 -(cyclohexylazanediyl)-bis(methylene) bridge: the dihedral angle between the dimethylphenol rings is 72.45 (7) . The cyclohexyl ring adopts a chair conformation with the exocyclic C-N bond in an equatorial orientation. One of the phenol OH groups forms an intramolecular O-HÁ Á ÁN hydrogen bond, generating an S(6) ring, and a short intramolecular C-HÁ Á ÁO contact is also present. In the crystal, O-HÁ Á ÁO hydrogen bonds link the molecules into C(10) chains propagating along the [100] direction. The Hirshfeld surface analysis of the title compound confirms the presence of these intra-and intermolecular interactions. The corresponding fingerprint plots indicate that the most significant contacts in the crystal packing are HÁ Á ÁH (76.4%), HÁ Á ÁC/ CÁ Á ÁH (16.3%), and HÁ Á ÁO/OÁ Á ÁH (7.2%).
Interestingly, the use of phenol derivatives as initiators for the ring-opening polymerization of 3,4-dihydro-2H-benzo[e]-1,3-oxaxines leads to the formation of small molecules instead ISSN 2056-9890 of polybenzoxazines (Chirachanchai et al., 2009). These small molecules (so-called dihydro-benzoxazine dimers), which generally possess an aza-methylene-phenol group, have been employed as models for describing polybenzoxazines (Hemvichian et al., 2002). In addition, the asymmetric Mannich reaction of the derivatives of dihydro-benzoxazine dimers, where only one OH group undergoes the ring-closure reaction has been reported (Laobuthee et al., 2001). As a result of these aza-methylene-phenol moieties, intermolecular and intramolecular hydrogen bonds are found in both the polybenzoxazines and the dihydro-benzoxazine dimers. They enhance the reactivity of the dihydro-benzoxazine dimers towards transition and rare-earth metal ions with respect to the common phenolic compounds. For instances, dihydrobenzoxazine dimers have been reported to be good chelating agents (Iguchi et al., 2018) for cerium ions (Veranitisagul et al., 2011) and copper ions (Phongtamrug et al., 2006).

Structural commentary
The non-hydrogen atoms of the 2,4-dimethylphenol moieties, namely C1-C8/O1 and C11-C18/O2, are almost planar (r.m.s. deviations = 0.030 and 0.017 Å , respectively) and their mean planes subtend a dihedral angle of 72.45 (7) . The C atoms in the methyl groups in the para-positions with respect to the OH groups deviate the most from the calculated mean planes with deviations of 0.043 (2) for C8 and À0.033 (2) Å for C17. The cyclohexyl group adopts a regular chair conformation as seen from the C-C-C bond angles, which are in the range 109.14 (17) to 111.59 (17) . The hydrogen atom bonded to C19 (H19) is in the axial position to allow the bulkier group (N1 tertiary-amine nitrogen atom) to be located at the equatorial position.
According to freely refined positions of the O-bound hydrogen atoms (H1 and H2), H1 points toward N1 to set up an intramolecular O-HÁ Á ÁN hydrogen bond with an S(6) graph-set motif (Table 1). This type of intramolecular O-HÁ Á ÁN hydrogen bond is commonly noticed in the compounds having -OH and azamethylene groups attached to the benzene ring in the ortho positions (Suramitr et al., 2020), especially dihydro-benzoxazine dimer derivatives Wattanathana et al., 2012Wattanathana et al., , 2016. In addition to the classical hydrogen bond, one of the hydrogen atoms on the methyl side chain at the ortho position to the O1 atom exhibits a C7-H7AÁ Á ÁO1 close contact (Table 1) The characteristics of specific interactions for compound (I) are displayed as a non-covalent interaction plot (NCIPLOT) (Johnson et al., 2010;Contreras-García et al., 2011) in Table 1 Hydrogen-bond geometry (Å , ). Symmetry code: (i) x À 1 2 ; Ày þ 1 2 ; z.

Figure 2
A view down [001] illustrating part of a [100] C(10) chain of O-HÁ Á ÁO hydrogen bonds in the extended structure of (I).

Figure 1
The molecular structure of (I) with displacement ellipsoids drawn at the 50% probability level. The O-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds are shown as yellow and magenta dashed lines, respectively.
The structure overlay of the title compound (green compound) and its structural isomer with only ethyl groups at the para-positions of the phenol rings (CEGYUK; Wattanathana et al., 2012) is displayed in Fig. 3. For CEGYUK, both O1 and O2 point toward the same side of the molecule to form the R 2 2 (20) hydrogen-bond motif just mentioned, while the O1 and O2 atoms of (I) are oriented in the opposite direction in order to reduce the steric effect. Therefore, the title molecules are joined together in an end-to-end packing mode into [100] chains ( Fig. 2), where it may be seen that the bulky substituent groups are arrayed in an alternating fashion along the chain.

Hirshfeld analysis
To better understand and visualize the interactions within the crystal of the title compound, a Hirshfeld surface (HS) analysis (Spackman & Jayatilaka, 2009) was carried out using Crystal Explorer 17.5 software (Turner et al., 2017). The HS plotted over the given range of d norm from À0.56 to 1.39 a.u.

Figure 4
A view of the three-dimensional Hirshfeld surface of (I) plotted over d norm in the range À0.56 to 1.39 a.u.

Figure 5
The full two-dimensional fingerprint plots for (I), showing (a) all interactions, and those delineated into OÁ Á ÁC, show no effect on the crystal packing due to the contribution of 0.0%.

Database survey
A search for structures containing the bis(phenol) linked by a bis(methylene)aza bridge in the Cambridge Structural Database (CSD version 5.41, November 2019 + two updates; Groom et al., 2016) showed 156 match entries. Structural diversity of the dihydro-benzoxazine derivatives is observed as a result of the variation of the substituent groups on both the phenol moieties and tertiary-amine nitrogen atom. Several crystal structures of dihydro-benzoxazine dimer derivatives with no other substituent groups on both the phenol rings have been reported (BUZWUP; Abrahams et al., 2009;KEJRAU;Kuźnik et al., 2012). The crystal structures of dihydro-benzoxazine dimer derivatives with ortho substituents have also been reported, e.g., tert-butyl substituents (CIJLEN; Kelly et al., 2007) and methoxy substituents (SILROV; Liu et al., 2007). However, no crystal structures of dihydro-benzoxazine dimers possessing meta substituents have been reported. This might be due to the ortho and para directing property of the phenolic -OH groups. Dihydro-benzoxazine dimer derivatives with para substituents are very common, viz.  Redjel et al., 2018). Apart from the monosubstituted derivatives, there are some reports on the crystal structures of ortho and para disubstituted derivatives, e.g., HEPZOU (Zhang et al., 2018) and RACMEP (Lionetti et al., 2010). Moreover, dihydrobenzoxazine dimers can also have different substituents on both the phenol rings as in AMEFUT, AMEGAA and AMEGEE (Sony et al., 2003), resulting in considerable structural variety.
An equimolar amount of 2,4-dimethylphenol was then mixed with (II) and the mixture was heated at 333 K overnight. After the reaction was complete, the yellow viscous liquid turned into a yellow solid, which was washed using diethyl ether, giving rise to a white precipitate of the title compound, which was separated from the yellow solution by decantation and rinsing with diethyl ether. The white precipitate was recrystallized from propan-2-ol solution to yield colourless blocks of (I).
M  Fig. S2 in the supporting information) between the measured PXRD pattern of (I) and the calculated pattern based on the single crystal data indicates the high degree of crystal homogeneity and crystallinity of the obtained compound. For full details of the spectroscopic and powder diffraction measurements, see the supporting information.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The O-bound H atoms (H1 and H2) were located in a difference map and their positions were freely refined. The C-bound H atoms were placed in idealized positions (C-H = 0.95-1.00 Å depending on hybridization) and refined as riding atoms. The methyl groups were allowed to rotate, but not to tip, to best fit the electron density. The constraint U iso (H) = 1.2U eq (carrier) or 1.5U eq (methyl C) was applied in all cases. The absolute structure of (I) was indeterminate in the present refinement.

6,6′-[(Cyclohexylazanediyl)bis(methylene)]bis(2,4-dimethylphenol)
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.