Crystal structure, Hirshfeld surface analysis and contact enrichment ratios of 5,5-dimethyl-2-(2,4,6-tris(trifluoromethyl)phenyl)-1,3,2-dioxaborinane

Abstract The title compound C14H12BF9O2 (1) was obtained as the sole product during a failed attempt to make a new organoboron compound. Characterization of the title compound by NMR (1H, 13C{1H}, 19F{1H}, and 11B) spectroscopy and single crystal X-ray diffractometry confirmed the formation of 1. Compound 1 crystallizes in the triclinic space group P-1, with a = 8.275(5) Å, b = 8.611(5) Å, c = 10.910(5) Å, α = 89.634(5)°, β = 89.637(5)°, γ = 87.403(5)°, V = 776.6(7) Å3, and Z = 2. The intermolecular interactions in 1 were analyzed using the Hirshfeld surface method including 2 D fingerprint plots and enrichment ratios (E), which shows that the most favorable intermolecular contacts are the Cπ···F–C and C–H···F–C interactions. The interaction energies between molecular pairs revealed the importance of these weak non-covalent interactions in stabilizing the molecular structure of 1. The title compound was also studied by DFT calculations and UV-Vis spectroscopy.


Introduction
Non-covalent interactions involving halogens play an important role in medicinal chemistry [1][2][3][4][5][6], crystal engineering [7][8][9][10][11][12], supramolecular chemistry [8,13,14], functional materials [15][16][17][18], and catalysis [19]; among these are fluorine-based interactions, where fluorine substituents e.g. -CF 3 can form different weak intermolecular C-FÁÁÁF-C, C p ÁÁÁF-C and C-HÁÁÁF-C interactions that can stabilize the crystal structure [20]. Unlike other halogens, the dominant interactions in organic fluorine compounds are C-HÁÁÁF interactions rather than C-FÁÁÁF-C contacts. These non-covalent interactions are most widely discussed in the context of the r-hole model [21], where electrostatic attraction takes place between a partially negative charge on a nucleophile and a partially positive charge on the hydrogen atom or a partially positive charge residing on the edge of the second halogen atom known as r-hole. Generally, fluorine can't form r-holes due to its low polarizability, therefore C-FÁÁÁF-C contacts are not very common. The C-HÁÁÁF-C interactions can play an important role in stabilizing crystal structures [22][23][24]and has been classified as a weak hydrogen bond according to the latest IUPAC definition [25]. On the other hand, the C p ÁÁÁF-C interactions has been a debated subject [26][27][28]. Nonetheless, it has been reported that, when the aromatic ring is substituted with electron-withdrawing groups e.g. CF 3 , the F-C groups tend to point toward the center of the electron-poor rings [29].
Herein, we report on the solid-state structure of a new fluorinated arylboronic ester, where the involved non-covalent interactions are studied using Hirshfeld surface analysis. In addition, the new compound was analyzed using different spectroscopic techniques and DFT calculations.

Synthesis of 1
The title compound 1 was obtained as the sole product of a sequence of reactions, which were designed to make a new organoboron compound. The targeted compound decomposed and was not further investigated Scheme 1, instead compound 1 was the sole product.
Reaction steps that led to the formation of the title compound: A solution of n-BuLi (1.6 M in hexane, 5.6 mL, 9.0 mmol) was added slowly to a dry Et 2 O (30 mL) solution of 1,3,5-tris(trifluoromethyl)-benzene (2.5 g, 1.7 mL, 8.8 mmol) at À78 C and mixed for 3 h at À78 C and left to mix over night at room temperature. The resulting orange solution was added via a cannula to a solution of BCl 3 (1.0 M in heptane, 3.0 mL, 3.0 mmol) at À78 C and stirred at the same temperature for 1 h and for another 2 h at room temperature. The resulting yellow suspension was filtered over celite under nitrogen and then a solution of lithiated 2-(4-bromophenyl)-5,5-dimethyl-1,3-dioxane (0.8 g, 3.0 mmol) in dry Et 2 O (50 mL) was added slowly at À78 C and mixed for 3 h at À78 C and left to mix over night at room temperature.
Solvents were evaporated under reduced pressure and the resulting residue was redissolved in CHCl 3 then washed with H 2 O and dried over anhydrous Na 2 SO 4 . Then CHCl 3 was evaporated under reduced pressure and the crude product was sonicated in hexanes, filtered, and kept in the freezer at À18 C to give (0.1) g of the title compound 1 as colorless needle-shaped crystals (Yield: 5.0% based on BCl 3 ) 1

Theoretical calculations
All computations were performed using ORCA code version 4.2.0 [31,32]. Full geometry optimizations at the DFT level of compound 1 were carried out using the perturbatively corrected double-hybrid functional B2PLYP [33] and the Ahlrichs def2-TZVPP [34] basis set, which is a triple-zeta basis with "enhanced" polarization functions. The effect of the dichloromethane solvent was considered in the geometry optimization for 1 using the conductor-like polarizable continuum model (CPCM) [35]. The lowest 20 singlet-singlet vertical electronic excitations based on B2PLYP optimized geometries were computed using the Time-Dependent Density Functional Theory (TD-DFT) formalism [36] in dichloromethane applying the conductor-like polarizable continuum model (CPCM) using the same level of theory as that used for the geometry optimizations, i.e., [B2PLYP/def2-TZVPP/CPCM(DCM)]. Gabedit program [37] was used to compute and draw the isosurface densities of the molecular orbitals. CrystalExplorer 17.5 package [38]was used to compute and visualize Hirshfeld surfaces and their associated 2-D fingerprint plots, enrichment ratios (E), and interaction energies (at the CE-B3LYP/6-13G(d,p) energy level). Scheme 1. Synthetic steps performed to get the target compound.

X-ray crystallographic analysis
Colorless needle-shaped crystals of 1 were obtained by cooling a hexanes solution containing the compound at À18 C. Crystals were mounted on a glass fiber and data collection was done on a Rigaku Xcalibur Ruby Gemini Ultra single-crystal X-ray diffractometer, with graphite-monochromated MoK a radiation. Data were processed using the CrysAlisPro software package and corrected for absorption effects. The molecular structures were solved by direct methods using SHELXS-18 [39] and refined by full-matrix least-squares procedures on F 2 using SHELXL-18 [40,41]. The dataset of the chosen crystal contained two major domains that were integrated independently and merged into a hklf5 file (BASF ¼ 0.49). All non-hydrogen atoms were refined anisotropically and a riding model was employed in the treatment of the hydrogen atom positions, except otherwise noted. Crystallographic data of 1 are summarized in 0.283 and À 0.251

Results and discussion
Scheme 1 shows the synthetic steps that lead to the formation of the title compound while Scheme 2 shows the proposed reaction that led to the formation of the title compound 1. We expect that the acetal used in this reaction may have contained some diol, which reacted with dichloroborane to form compound 1. It's worth mentioning that all steps were done in situ, that is no attempts were made to isolate intermediate products.
The title compound is stable at ambient conditions in the solid state and in solution. Also, it is soluble in polar organic solvents like tetrahydrofuran, chloroform, and dichloromethane, but hardly soluble in hexanes.
Compound 1 was identified by single crystal X-ray crystallography, and NMR ( 1 H, 13 Cf 1 Hg, 19 F, and 11 B) spectroscopies in CDCl 3 . The 1 H NMR spectra of 1, Fig. S1, is consistent with the molecular structure, showing resonances with the expected patterns for the CH 3 , CH 2 and CH moieties. The two CH protons of the phenyl ring are observed at 8.05 ppm as a singlet, while the aliphatic CH 2 protons appear as a singlet at 3.79 ppm. A singlet at 1.10 ppm is found for the CH 3 protons. The most pronounced signals in the 13 C NMR spectrum, Fig. S2, beside the aliphatic carbons, are the two quartets resulting from the 2 J C-F coupling of the ortho-and para-C 6 H 2 are at 135.1 and 131.8 ppm, respectively; in addition to the two quartets resulting from the 1 J C-F coupling of the ortho-and para-CF 3 are at 123.4 and 122.7 ppm, respectively. The 19 F NMR spectroscopy (Fig. S3) shows the characteristic signals of the trifluoromethyl aryl ligand: a resonance peak at around À60.04 ppm for the ortho-CF 3 groups, and a singlet at about À63.32 ppm corresponding to the para-CF 3 groups [42][43][44]. The 11 B NMR spectrum, Fig. S4, of 1 displays a singlet at 27.4 ppm, which appears in the region of literature reported C-B(OR) 2 connection pattern [44].
The crystallographic and refinement data of 1 are summarized in Table 1 and the molecular structure of 1 is shown in Fig. 1. Selected bond distances (Å), bond angles ( o ), and torsion angles ( o ) are given in the caption of Fig. 1. Compound 1 crystallizes in the triclinic space group P-1 with one molecule in the asymmetric unit. Rotational disorder was found for one of the ortho-CF 3 groups, which is usually observed in compounds containing this group [45,46,47,48,49]. The six-membered boronate ester ring adopts a half chair type conformation with the CMe 2 entity pointing out of the BO 2 C 2 plane by 45 (Fig. 1). The BO 2 motif and the benzene ring are rotated by 86.7(2) against each other to avoid repulsive interaction with the CF 3 substituents on both ortho positions, which in turn provide kinetic stability by effectively shielding the empty p-orbital on boron against attack by nucleophiles [50]. The B-C ph bond length to the partial orbital overlap. Together with C1-B1-O angles of 117.61(17) and 117.59 (16) they are in accordance with those reported for similar compounds [44,[51][52][53].
The solid-state crystal packing of 1 is stabilized by lone pair FÁÁÁp and FÁÁÁH-C intermolecular interactions that form a band-type structure along the crystallographic a-axis. The former exists between the ortho C7-labeled CF 3 entity and the arene (Fig. 2). The C9-labeled pendant instead, is not involved in intermolecular interactions. The shortest  FÁÁÁp contact is F2ÁÁÁC5 (at 3.085(5) Å), which is less than the sum of the corresponding vdW radii (C ¼ 1.70 Å, F ¼ 1.47 Ð, Ʃ C,F ¼ 3.17 Å). The disordered part the CF 3 group (34% occupancy) is rotated by 27 , resulting in a F3'ÁÁÁC5 distance of 3.130(17) Ð. Both fluorine atoms are positioned almost perpendicularly above the C5 atom, represented by the corresponding FÁÁÁC5-H5 angles of 100 . The interactions result in a dimeric structure, of which the major component is shown in Fig. 2 (green). The shortest distance between the fluorine atoms and the centroids of the phenyl rings is 3.1353 (19) Å between F2 and Cg2 in an angle of 143 , indicating a lone pair FÁ Á Áp interaction toward the centroid [54].
Weaker FÁ Á ÁC interactions of 3.161(3) (C10) and 3.134(3) Ð (C12) are observed between the para CF 3 substituent and both CH 2 entities of the boronic ester fragment (Fig. 2, blue). Thus, each molecule is stabilized by four contacts toward an adjacent molecule of 1 positioned along the crystallographic a-axis, resulting in a band-type structure. Therein, arene and boronate entities, as well as the ortho-CF 3 groups appear with alternating orientations, with the C9-labeled entity consequently facing the outside, while the C7-based group directs inwards.
The geometrical parameters of 1, i.e. bond angles and bond lengths, determined using DFT calculations, are in good agreement with the experimental values (Table S1). For example, the calculated C1-B1 bond length is 1.595 Å while the X-ray value is 1.598(3) Å. DFT calculations at the triple zeta double hybrid level shows that the electron density of the HOMO, LUMO, HOMO À1, and LUMO þ1 is mainly delocalized over the benezene ring. The isosurface density of the fronteir molecular orbitals of 1 are shown in Fig. S6. A DFT analysis of the calculated excited states of 1 reveals that the UV-Vis absorption band, with k max value found at 261 nm (see Fig. S5), is assigned to a HOMO ! LUMO, HOMO À1 ! LUMO, HOMO ! LUMO þ1, and HOMO À1 ! LUMO þ1, all of which corresponding to a typical p-p Ã transition.
The Hirshfeld surfaces and their associated 2 D fingerprint plots were generated with the CrystalExplorer17.5 program using the crystallographic information file (.cif) and were analyzed to identify the important intermolecular interactions and to better understand the overall crystal packing of 1. The Hirshfeld surfaces were mapped over the normalized contact distance (d norm ), which is defined in terms of d e , d i , and the vdW radii of the atoms, where d e and d i are the distances from a point on the surface to the nearest atom outside (external) and inside (internal), respectively. The Hirshfeld surface colors are used to visualize the inter-atomic contacts as: longer than vdW contacts (blue), equal to vdW (white), and shorter than vdW (red).
The colors of the points on the 2-D fingerprint plots correspond to the frequency of the d e and d i combinations on the Hirshfeld surface, where red represents a larger fraction or contribution and green to blue represent moderate to small contributions, respectively.
The Hirshfeld surfaces of 1, mapped over d norm , are shown in Fig. 3, the red spots in Fig. 3a are associated with CÁ Á ÁF interaction, while the red spots in Fig. 3b are associated with HÁ Á ÁF interactions; both types of interactions are also observed in the corresponding 2-D fingerprint plots (Fig. 4) as a pair of symmetrical spikes at (d e þ d i ) % 3.1 Å for the CÁ Á ÁF/FÁ Á ÁC contacts (10.1% of the total Hirshfeld surface) and % 2.7 Å for the FÁ Á ÁH/HÁ Á ÁF contacts (49.3% of the total Hirshfeld surface), which equals the sum of vdW radii of C/F and H/F, respectively. The full 2-D fingerprint plot for 1 and the decomposed contacts representing HÁ Á ÁH (16.1%), FÁ Á ÁF (14.5%), and OÁ Á ÁH (6.0%) interactions are shown in Fig. S7. In addition, the Hirshfeld surface was mapped with the shape-index property, where the blue bump shape represents the donor atom(s) and the red hollow shape represents the acceptor atom(s) of the intermolecular interaction. Fig. 5 shows the FÁÁÁp intermolecular interaction in the crystal packing, where the red hollow shape represents the electron poor aromatic surface and the blue bump shape represent the fluorine atoms.
The enrichment ratios (E), the ratio between the actual contacts proportion in the crystal and random contacts, were computed using the surface contact data derived from the Hirshfeld surface analysis [55]. Values of E > 1 indicate that the pair of elements involved have a high propensity to form contacts in the crystal structure, while an E < 1 value indicates that the propensity would be low. The contributions to the surfaces in 1 and the corresponding enrichment ratios are presented in Table 2. The  enrichment ratios of 1 show that the CÁÁÁF contacts (E CF ¼ 1.69) is the most favored contact in the crystal packing followed by the OÁÁÁH contacts (E OH ¼ 1.57), and HÁÁÁF contacts (E FH ¼ 1.25), respectively. While HÁÁÁF contacts cover almost half the total Hirshfeld surface of 1 (49.3%), the surface contacts of CÁÁÁF and OÁÁÁH cover only 10.1% and 6.0%, respectively, which illustrates the importance of the CÁÁÁF contacts in stabilizing the molecular packing of 1. Also, the high enrichment values of the CÁÁÁF contacts correlate very well with the interaction energies calculations, vide infra.
Intermolecular interaction energies were assessed with the CE-B3LYP model embedded in Crystal Explorer 17.5 to evaluate their role in stabilizing the molecular packing of 1 [56]. The interaction energies between molecular pairs were computed for a cluster of 3.8 Ð around a reference molecule. The molecular pairs interaction energies Figure 5. Hirshfeld surface of 1 mapped with shape-index property. Blue bump shape represents donor atom(s) and red hollow shape represents acceptor atom(s). Table 2. Percentages of surface contacts (S X ), random contacts (R XX and R XY ) and enrichment ratios E (E XX and E XY ) for 1. are expressed in terms of total energy (E_tot), electrostatic energy (E_ele), polarization energy (E_pol), dispersion energy (E_dis), and repulsion energy (E_rep). The values of these energies for 1 are listed in Table S2. The highest stabilized molecular pair in 1 (E tot ¼ À49.9 kJ/mol) is related to the pair of molecules (Fig. S8) linked by the CÁÁÁF short contacts (all within the sum of vdW radii), where the main stabilizing energy is due to E_dis contribution followed by E_ele. Similarly, the second highest stabilized molecular pairs in 1 (E tot ¼ À45.5 kJ/mol) is related to the pair of molecules linked by the CÁÁÁF short contacts (all within the sum of vdW radii), with the main stabilizing energy being E_dis followed by E_ele. In addition, the third highest stabilized molecular pairs in 1 (E tot ¼ À29.0 kJ/mol) is related to the pair of molecules linked by the HÁÁÁF short contacts (all within the sum of vdW radii), with the main stabilizing energy being E_dis followed by E_ele. These results support earlier studies which indicate that fluorine atoms can form stabilizing contacts with electron-deficient aromatic surfaces [57].

Conclusion
Single crystal X-ray analysis shows that the solid-state crystal packing of 1 maybe stabilized by C-HÁÁÁF and lone pair (F)ÁÁÁp. The large enrichment ratios of CÁÁÁF and HÁÁÁF contacts and their major participation in the stabilization energy of the molecular pairs, indicate that these intermolecular interactions are the most favored and play an important role in the crystal packing formation. Hirshfeld surface analysis of 1 has confirmed the ability of -CF 3 groups to form stabilizing interactions with electron-poor aromatic surfaces. Comparison of calculated and experimental values of bond lengths and bond angles showed very good agreement. The main UV-Vis absorption band is assigned to local p ! p Ã excitations, which mainly involves the conjugated benzene ring.