First hydrogen-bonded adduct of sterically hindered 2-tert-butyl-4-methylphenol (TBMP) with 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane (TATD) via coupling of classical hydrogen bonds and C—H⋯π non-covalent interactions

Hydrogen bonding links the donor alcohol functional groups of two 2-tert-butyl-4-methylphenol molecules to the central acceptor polyamine aminal cage TATD yielding the three molecule adduct, half of which comprises the asymmetric unit in this crystal structure.


Chemical context
Co-crystals of phenols with various nitrogen bases are model systems often used for studying the nature of the hydrogen bond (Majerz et al., 2007). In this context, not only the initial formation of a hydrogen-bonded adduct was investigated between a Mannich preformed reagent and the phenolic substrate (Burckhalter & Leib, 1961), but also the great interest in and chemical importance of the aminoalkylation of aromatic substrates via the Mannich reaction was addressed (Tramontini et al., 1988). For a long time we have directed continuing efforts to the systematic study of hydrogen bonding and other non-covalent interactions of phenols with aminal cages (preformed Mannich bases) (Rivera et al., 2007(Rivera et al., , 2015a(Rivera et al., ,b, 2017a(Rivera et al., ,b, 2019. Herein we report the mechanochemical preparation and crystal structure of the title adduct prepared by mixing in an agate mortar the sterically hindered 2-tertbutyl-4-methylphenol (TBMP) with 1, 3,6,8-tetraazatricyclo[4.4.1.1 3,8 ]dodecane (TATD) in a 2:1 ratio. The crystallographic information available for pure 2-tert-butyl-4methylphenol (Beckmann et al., 2004) does not report O-HÁ Á ÁO hydrogen bonds, which are commonly found in the crystal structures of alcohols, suggesting that the alcohol is sterically protected. The reaction of TBMP with TATD, in notable contrast to this, proceeds cleanly to give the title O-HÁ Á ÁN hydrogen-bonded adduct exclusively. A search of the Cambridge Structural Database (version 5.42; Groom et al., 2016) for crystal structures containing hydrogen-bonded TBMP co-crystals with a hydrogen-bond acceptor resulted in zero hits, emphasizing the general rarity of this observation.
The resultant crystal structure reported here also exhibits C-HÁ Á ÁO hydrogen-bonding interactions, which constitute a fundamental force in maintaining crystal and three-dimensional chemical structures in chemistry and biology (Wang et al., 2019).

Supramolecular features
The most prominent supramolecular feature in this crystal structure is the formation of the expected three-molecule aggregate sustained by two hydroxy-O-HÁ Á ÁN hydrogen bonds (Fig. 2). In the crystal packing, roughly in the a-axis direction, adjacent aggregates are linked by C-HÁ Á Á interactions with a C-HÁ Á ÁCg distance of 3.851 (2) Å and a C-HÁ Á ÁCg angle of 163 , ( Table 1). The C-HÁ Á Á interaction is facilitated between one methylene group (C1-H1A) and a symmetry-derived ring (C11-C16; symmetry code: Àx + 1, Ày + 1, Àz + 1). These non-covalent interactions lead to the formation of a crystal packing pattern in which the phenol molecules are arranged in an alternating fashion, as is evident when viewed along the [101] direction (Fig. 3 Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
The crystal packing of the title compound viewed roughly along the b-axis direction, showing the intermolecular O-HÁ Á ÁN hydrogen bonds and selected C-HÁ Á Á interactions.

Figure 1
A view of the molecular structure of the title compound, showing the atom-labelling scheme, with displacement ellipsoids drawn at the 50% probability. H atoms bonded to C atoms are omitted for clarity. Hydrogen bonds are drawn as dashed lines. Atoms labelled with the suffix A are generated using the symmetry operator (Àx, y, Àz + 1 2 ).

Refinement
The structure of the title compound had been previously deposited by us and was thereby reported as a Private Communication (Bolte et al., 2021, refcode EWICAR). Crystal data, data collection and structure refinement details are summarized in Table 2. The oxygen-bound hydrogen atom was found and refined isotropically without restraints or constraints. Other hydrogen atoms were generated geometrically, and refined with a riding model with C-H = 0.98 Å , U iso (H) = 1.5U eq (C) for methyl, C-H = 0.99 Å , U iso (H) = 1.2U eq (C) for methylene, and C-H = 0.95 Å , U iso (H) = 1.2U eq (C) for aromatic 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.