Crystal structure of 2,4-di-tert-butyl-6-(hydroxymethyl)phenol

The crystal structure of 2,4-di-tert-butyl-6-hydroxymethylphenol is presented.


Chemical context
The addition of pendent arms to ligands, which possess donor atoms that are capable of ligating to a metal ion, aid the stabilization of the resulting complex formed. In particular, the use of phenol-based ligands are of interest because they are used to form stable phenoxyl radicals, which are found in some enzymatic active sites, such as photosystem II and galactose oxidase (Rogers & Dooley, 2003;Pujols-Ayala & Barry, 2004). Synthesis of pendent arms containing phenolate moieties have been used for the creation of biomimetic complexes and for the study of their redox properties (Zhu et al., 1996;Kimura et al., 2001;Esteves et al., 2013;Sokolowski et al., 1997). The creation of pendent arms that possess functional groups, which can be easily manipulated to give possible tethering points (such as the transformation of an alcohol to the corresponding alkyl halide), or groups that are easily protected to prevent unwanted side reactions are, therefore, highly desirable.
As part of our work on the synthesis of macrocyclic ligand systems bearing phenolate pendent arms, we report the crystal structure of 2,4-di-tert-butyl-6-hydroxymethylphenol, (I), which is an intermediary in a pendent-arm synthesis.

Structural commentary
The molecule of (I) possesses an intramolecular hydrogen bond (Table 1). This interaction does not cause any sizable deviation from the idealized bond angle, as the bond angle for C6-C15-O2 is 111.99 (13) , whilst the bond angle for C6-C1-O1 is 119.21 (13) . Furthermore, the formation of an intramolecular hydrogen bond within the structure creates a six-membered ring system that involves C1, C6, C15, O2, H1O1 and O1. This six-membered ring has a half-chair conformation. The phenolic C-O bond length is 1.3820 (19) Å , which is shorter than the alcoholic C-O bond length [1.447 (2) Å ] due to conjugation with the aromatic ring. The aromatic ring is planar, as expected, and has internal bond angles that range from 116.49 (14) to 123.95 (14) . The bond lengths from the quaternary atoms of the tert-butyl group to the nearest aromatic ring carbon are very similar (the average bond length is 1.54 Å ).

Supramolecular features
In the crystal structure of (I) (Fig. 1), molecules are linked by intermolecular hydrogen bonds that are much shorter than the intramolecular hydrogen bonds (see Table 1). Intermolecular hydrogen bonds are formed between molecules that are related by a 3 1 screw axis which generates chains along the caxis direction (Figs. 2 and 3). The intermolecular hydrogen bond is stronger than the intramolecular bond due to colli-nearity between the proton donor group (O2-H1O2) and the proton acceptor (O2 i ). The bond angle for O2-H1O2Á Á ÁO2 i is 178 (2) , which contrasts strongly with the weaker intramolecular hydrogen bond, which is 146 (2) (O1-H1O1Á Á ÁO2). The presence of intermolecular hydrogen bonding is the only interaction that stabilizes the 1D structure, as there are nostacking interactions present; the aromatic rings are separated by more than 6 Å .

Figure 2
The crystal packing of compound (I), viewed along the c-axis direction.
The hydrogen bonds are shown as dashed lines.

Figure 1
The molecular structure of compound (I), showing the atom labelling and displacement ellipsoids drawn at the 50% probability level. The intramolecular hydrogen bond is shown by the dashed bond.
CH 2 group of (I) have been replaced by CF 3 /C 6 F 5 groups to coordinate to titanium(IV) centres [ZUNWOW and ZUNWUC (Tuskaev et al., 2015); XEMBAU and XEMREY (Solov'ev et al., 2011)]. ZUNWOW is noteworthy because fluorine also acts as a ligand to a coordinated lithium ion. Two oxazole structures that contain the title compound were also identified [KUTQUM (Campbell et al., 2010); LUYSIU (Błocka et al., 2010)], although neither used (I) as a starting material. The only structure that utilizes 2,4-di-tert-butyl-6hydroxymethylphenol without modification is a complex that contains two titanium(IV) centres, four 2,4-di-tert-butyl-6-hydroxymethylphenol ligands and two chloride ligands (BAFFOG; Gagieva et al., 2014). Two of the 2,4-di-tert-butyl-6-hydroxymethylphenol ligands display bridging through the alcoholic oxygen to both Ti IV centres. The C-O bond lengths are comparable to those of (I); the phenolic C-O bond length in BAFFOG shows the largest difference in that it contracts by 0.015 Å relative to (I). Furthermore, the bond lengths of the six-membered ring that is formed between the ligand and the Ti IV centre also closely resembles that of (I); the only noteworthy difference between the two structures are the two bond lengths that involve oxygen to either Ti IV or H1O1. In the former they are 2.003 and 1.832 Å whereas in (I) they are 2.03 (2) and 0.84 (2) Å .

Synthesis and crystallization
The synthesis of 2,4-di-tert-butyl-6-hydroxymethylphenol is based on a reported literature procedure (Wang et al., 2014). 2,4-Di-tert-butylphenol (5 g, 0.024 mol) and LiOHÁH 2 O (0.083 g, 0.002 mol) were dissolved in methanol (10 mL), and a suspension of paraformaldehyde (4.50 g, 0.15 mol) in methanol (10 mL) was added at room temperature. The reaction mixture was heated to reflux for 24 hr. After being allowed to cool to room temperature, the solvent was removed under reduced pressure and the white residue was dissolved in diethyl ether. The organic layer was washed with water (3 x 50 mL). The organic layer was collected and dried with magnesium sulfate. The solvent was removed by rotary evaporation to yield a white powder (2.3 g, 40%). Part of the purified product was re-dissolved in n-hexane and placed in a refrigerator. The crystal packing of compound (I) showing the helical chains along the c axis. Hydrogen bonds are shown as dashed lines.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2. All hydrogen atoms are placed in calculated positions [C-H = 0.98-0.99Å ; U iso (H) = 1.2 or 1.5U eq (C)], except for H1O1 and H1O2 which were located in a difference map and their positions freely refined with U iso (H) = 0.05 for both. The absolute structure could not be determined from the X-ray data.

2,4-Di-tert-butyl-6-(hydroxymethyl)phenol
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. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.