Synthesis, crystal structure, Hirshfeld surface analysis and DFT study of the 1,1′-(buta-1,3-diyne-1,4-diyl)bis(cyclohexan-1-ol)

The two crystallographically non-equivalent molecules in the title compound have C 2 and Ci symmetries. The crystal structure features strong intermolecular O—H⋯O hydrogen bonds, which form eight-membered rings with (8) graph-set motifs, linking the molecules into layers.


Chemical context
The presence of two triple C C bonds and two hydroxy groups in the molecules of diacetylene diols R 1 R 2 (OH)C-C C-C C-C(OH)R 3 R 4 , as well as substituents with different structures and functional groups containing heteroatoms, increases the possibilities of synthesis and the production of valuable, chemically stable and biologically active compounds based on such compounds (Cadierno, 2022). In particular, as the hydrogen atom adjacent to the strong C C bond is labile (Brü cner, 2010), terminal alkynes easily undergo nucleophilic addition reactions to the carbonyl group and terminal (Hosseini et al., 2020;Sum et al., 2013) or internal acetylene alcohols (Tanaka et al., 2011;Motoki et al., 2007) and diols (Ardila-Fierro et al., 2019) with various substituents. Diacetylene diols and polyacetylene diols (Shi Shun et al., 2006) can also be synthesized by performing dimerization processes. Many reactions, such as cyclization (Zhang et al., 2010) or substitution (Kuang et al., 2018), based on the hydroxy group (-OH) or its hydrogen atom in an acetylene alcohol, give opportunities to synthesize new biologically active substances. Hexa-2,4-diene-1,6-diol and its derivatives have been found to have anticancer chemotherapeutic properties (Lee et al., 2015). Moreover, some diacetylene diols and their derivatives have antibacterial (Ankisetty et al., 2012), antiviral (Geng et al., 2015) and neuritogenic (Wang et al., 2011) activities. Moreover, the above indicated substances behave as versatile host compounds accommodating many guest species (Weber et al., 1991) because the shape of their molecules is inefficient for close packing in crystals. Therefore, the preparation of such compounds in their pure form, i.e. a guestfree state, is of interest. This paper describes the preparation (Fig. 1), molecular and crystal structure, as well Hirshfeld surface analysis of the guest-free crystal of the title compound, (I).

Structural commentary
There are the principles of directed host design formulated by Weber (Weber et al., 1991), according to which bulky and rigid compounds are packed in crystals inefficiently, leaving suitable cavities for the accommodation of guest molecules. Indeed, host compounds with a 'wheel-and-axle' shape of the molecule easily include several guests (Weber et al., 2004). However, in the case of compound (I) belonging to this family, only one inclusion compound (with 1,4-diazabicyclo-[2.2.2]octane as the guest) has been structurally characterized (Chandrasekhar et al., 2013). In our experimental conditions we have obtained guest-free crystals of (I). They belong to the monoclinic system with space group P2/c. There are two crystallographically non-equivalent molecules, both situated on symmetry elements: molecule A is located on an inversion center while molecule B lies on a twofold axis. Thus there are two half-molecules in the asymmetric part of the unit cell. The rod-like 1,3-diyne fragment has the usual linear geometry and bond lengths (Weber et al., 1991(Weber et al., , 2004Chandrasekhar et al., 2013). The molecular structure of (I) is shown in Fig. 2. The cyclohexane moieties of both independent molecules adopt chair conformations, with atoms C1 and C4 deviating from the plane of the remaining four atoms by 0.655 and À0.657 Å , respectively, in molecule A, by 0.668 and À0.638 Å in B. The disposition of the cyclohexane rings relative to the 1,3-diyne chain is the same in molecules A and B, as shown by the similar distances C7AÁ Á ÁCg1 = 2.331 Å and C7BÁ Á ÁCg2 = 2.329 Å where Cg1 and Cg2 are the ring centroids. However, the orientation of the rings relative to each other is different (Fig. 2, inserts): trans in molecule A, gauche in B, both different from the nearly eclipsed disposition in the one known molecular complex of (I).

Supramolecular features
The molecule of (I) has two OH groups. Each group realises its proton-donor and proton-acceptor possibilities, forming intermolecular hydrogen bonds (Table 1)  The molecular structure of (I). Displacement ellipsoids are drawn at the 30% probability level, hydrogen bonds are shown as dotted lines. Symmetrically independent atoms are labelled, the rest are generated by the symmetry operations 1 À x, 1 À y, 1 À z (for A) and Àx, y, 3 2 À z (for B). Synthesis of compound (I).

Figure 3
Packing diagram of (I). Dotted lines indicate hydrogen bonds. Symmetry operation for primed atoms: 1 À x, y, 3 2 À z. Table 1 Hydrogen-bond geometry (Å , ). and O1B-H1BÁ Á ÁO1A with OÁ Á ÁO distances of 2.748 (1) and 2.771 (1) Å , respectively. As shown in Fig. 3, each molecule participates in two R 4 4 (8) rings of hydrogen bonds (Grell et al., 1999), each ring involving two molecules of type A and two of B. These bonds give rise to a two-dimensional supramolecular layer parallel to the ac plane. The layers are incorporated into a three-dimensional network by van der Waals interactions (Fig. 3).

Hirshfeld surface analysis
Hirshfeld surfaces were calculated and two-dimensional fingerprints generated using CrystalExplorer21 (Spackman et al., 2021). Hirshfeld surfaces were obtained using a standard (high) surface resolution with the three-dimensional d norm surfaces mapped over a fixed color scale of À0.5154 (red) to 1.9215 (blue) (Fig. 4). The only red spots on the surface (revealing strong interactions) correspond to the O-HÁ Á ÁO hydrogen bonds, the rest representing standard (white) or longer than standard (blue) van der Waals contacts. This agrees with the calculated electrostatic potential of the molecule (Fig. 5) where the only negative potential (acceptor) areas are around the O atoms. The two-dimensional fingerprint plots (in d e vs d i coordinates) (Fig. 6) show that molecules A and B have very similar environments, the major contributions being from contacts HÁ Á ÁH (70.6 for A, 71.1% for B), HÁ Á ÁC/CÁ Á ÁH (18.4 and 18.7%) and HÁ Á ÁO/OÁ Á ÁH (11.0 and 10.2%).

The analysis of DFT calculations
The co-presence of trans and gauche conformations of (I) in the crystal was mentioned above. In order to determine the intramolecular rotational barrier of a cyclohexan-1-ol fragment around the diyne rod (i.e. the Csp 3 -Csp bond), the relaxed scan calculation has been carried out in a vacuum by Three-dimensional Hirshfeld surfaces of molecules A and B of (I) plotted over d norm in the range À0.5154 to 1.9215 a.u.

Figure 5
Hirshfeld surfaces of molecules A and B plotted over electrostatic potential in the range À0.05 to 0.05 a.u. using the B3LYP/6-311 G(d,p) basis set at the Hartree-Fock level of theory. Blue and red regions indicate positive and negative potentials, respectively.

Figure 6
Complete two-dimensional fingerprint plots for molecules A (a) and B (b) of (I) with relative contributions of individual contacts. Note the 'spikes' indicating strong hydrogen bonds. B3LYP/def2-TZVP method using the ORCA program package (Neese, 2022). The initial geometry of (I) was taken from the crystal structure (CIF file) and the input files were prepared using Avogadro program package (Hanwell et al., 2012). The O1-C1Á Á ÁC1 0 -O1 0 torsion angle (!) was varied from 0 to 180 in 3 steps with full optimization of the molecular geometry at each step. Then single-point calculations were performed using the B3LYP-D3BJ/def2-TZVP basis set for the geometries obtained at each step, by including dispersion corrections (Grimme et al., 2011). Thus we observed energy minima at ! = 9, 30, 61, 85, 109, 146 and 180 (Fig. 7), the deepest one being at 61 by DFT/def2-TZVP calculations (or 64 by DFT-D3BJ/def2-TZVP); however, the rotation barrier was low, 0.7 or 0.9 kJ mol À1 1, respectively. Thus, an easy transition between conformations can occur in solution and, apparently, the intermolecular (packing) interactions played a decisive role in the implementation of the gauche (! = 85 ) and trans (! = 180 ) conformations in the crystal. To study the influence of ! variation on the electronic parameters, we analyzed the changes of HOMO and LUMO energies, and the energy gap upon varying ! from 0 to 180 . The energy and electron density at these orbitals are impor-tant in defining the molecule's chemistry (Fukui, 1982;Hoffmann et al., 1965), the HOMO correlating with the ionization potential and representing the electron-donating ability of a molecule, while the LUMO correlates with the electron affinity of a molecule and represents its electron-accepting ability. The energy difference (energy gap) between HOMO and LUMO is known to represent the stability or reactivity of a molecule in a series of related compounds (Pearson, 1988;Jahnke et al., 2010). For (I), the HOMO and LUMO energies and the energy gap change slightly with !, the former varying from À6.63 to À6.72 eV and the latter from À0.69 to À0.84 eV, while the energy gap varies from 5.79 to 5.99 eV (Fig. 8). The widest energy gap (5.99 eV) was found at energetically optimal conformation with ! = 61 or 64 (vide supra). Molecule (I) has a low-lying HOMO and a high-lying LUMO and consequently a wide HOMO-LUMO gap, which indicates the high thermodynamic stability and low reactivity of the molecule. Despite this, the highly unsaturated carbon chains could also exhibit various reaction properties (photoisomerization, nucleophilic addition of alcohols, thiols and amines to the triple bond) under special conditions (Shi et al., 2014). The reactivity of (I) toward nucleophiles can be inferred from the electron density on LUMO, which is predominantly the * orbital of diacetylene C atoms (Fig. 9). The HOMO is a -type MO and is mainly delocalized along the diacetylene fragment (Fig. 9). However, these atoms are unlikely to have an electron-donating ability to electrophile reagents because of the low-lying HOMO.
Thus, theoretical calculations showed that the rotation of hexanol-1 fragment around the Csp 3 -Csp bond can pass through several conformational minima that differ in !. However, all these conformations make a negligible difference to the total energies and the rotational barrier between them. The conformations observed in the crystal packing arose as a result of the action of intermolecular interaction forces.     could be expected from the propensity of 'wheel-and-axle'shaped molecules to form host-guest structures.

Synthesis and crystallization
The dimerization process of 1-ethynylcyclohexanol was conducted at 298 K for 48 h, based on a catalytic system with a copper(I) chloride catalyst, tetrachloromethane, N 1 ,N 1 ,N 2 ,N 2tetramethylethylenediamine as a ligand and ethanol as the solvent, following the general routine used by Tirkasheva et al. (2022) to prepare 8,13-dimethylcosa-9,11-diyne-8,13-diol. This yielded 1,1 0 -(buta-1,3-diyne-1,4-diyl)bis(cyclohexan-1-ol) (I) as a brown liquid. 25 mg (0.1 mmol) of (I) were dissolved in 2 ml of chloroform in a 50 ml round-bottom flask and the solvent was removed under vacuum. After the chloroform was completely removed, 2 ml of CH 2 Cl 2 and 1 ml of methanol were added to the flask. Brown single crystals of the title compound suitable for X-ray diffraction analysis were grown over three days by slow evaporation of the solvent, yield 76%, m.p. 448 K. Elemental analysis for C 16

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.