Synthesis and Crystal Structure of 9,12-Dibromo-ortho-Carborane

Synthesis, NMR spectral data and crystal structure of 9,12-dibromo derivative of ortho-carborane

In this contribution we describe the synthesis of 9,12-dibromo-ortho-carborane and its characterization by NMR spectroscopy and single crystal X-ray diffraction.

Results and Discussion
Despite the fact that the bromination of orthoand meta-carboranes was first described back in the mid-1960s [44], neither the yield of bromination products nor their characterization (with the exception of X-ray diffraction data for crystals from the same syntheses [50][51][52][53]) have been described until recently. For the sake of fairness, it is worth noting an attempt to characterize the obtained bromo derivatives of ortho-carborane using 11 B NMR spectroscopy, however, due to the very limited instrumental capabilities of that time, at the present it is rather of historical interest [54]. Synthesis and NMR spectra of 9-bromo-and 9,12-dibromo-meta-carboranes were recently reported by Spokoyny et al. [45]. The NMR spectral data of 9-bromo-ortho-carborane, as well as its crystal and gas phase structures, were recently reported by Hnyk et al. [49,55]. As for 9,12-dibromo-ortho-carborane, its The NMR spectral data of 9-bromo-ortho-carborane, as well as its crystal and gas phase structures, were recently reported by Hnyk et al. [49,55]. As for 9,12-dibromo-ortho-carborane, its preparation was also mentioned relatively recently [56]; however, only numerical characteristics of the NMR spectra were reported without their assignment.
The main problem of the 9,12-dibromo-ortho-carborane synthesis is the purification of the target product. It was demonstrated that bromination of ortho-carborane, regardless of the Lewis acid and solvent used, gives, together with the desired 9-bromo-ortho-carborane, approx. 10 mol.% of 8-bromo-ortho-carborane. At the second stage, this leads to the crude product containing approx. 80% of 9,12-dibromo-ortho-carborane, together with significant amount of the 8,9-dibromo and traces of the 8,10-dibromo derivatives [57]. Impurities of 9-bromo-and 8,9,12-tribromo derivatives may also be present in the reaction mixture, which greatly complicates the purification of the target product [58]. Unfortunately, all our attempts to purify the target compound using chromatography methods failed. Therefore, we purified 9,12-dibromo-ortho-carborane by fraction crystallization from chloroform that produced a rather low (22%) yield of pure product (Scheme 1). It should be noted that the structure of 9,12-dibromo-ortho-carborane was determined in 1966 [50] at room temperature. The quality of that experiment was evidently low and was mostly concentrated on the description of molecular geometry. Therefore, in the present study, we redetermined its structure at low temperature (110 K) focusing on both molecular structure ( Figure 1) and, especially, the crystal packing. It should be noted that the structure of 9,12-dibromo-ortho-carborane was determined in 1966 [50] at room temperature. The quality of that experiment was evidently low and was mostly concentrated on the description of molecular geometry. Therefore, in the present study, we redetermined its structure at low temperature (110 K) focusing on both molecular structure ( Figure 1) and, especially, the crystal packing. The NMR spectral data of 9-bromo-ortho-carborane, as well as its crystal and gas phase structures, were recently reported by Hnyk et al. [49,55]. As for 9,12-dibromo-ortho-carborane, its preparation was also mentioned relatively recently [56]; however, only numerical characteristics of the NMR spectra were reported without their assignment. The main problem of the 9,12-dibromo-ortho-carborane synthesis is the purification of the target product. It was demonstrated that bromination of ortho-carborane, regardless of the Lewis acid and solvent used, gives, together with the desired 9-bromo-ortho-carborane, approx. 10 mol.% of 8-bromo-ortho-carborane. At the second stage, this leads to the crude product containing approx. 80% of 9,12-dibromo-ortho-carborane, together with significant amount of the 8,9-dibromo and traces of the 8,10-dibromo derivatives [57]. Impurities of 9-bromo-and 8,9,12-tribromo derivatives may also be present in the reaction mixture, which greatly complicates the purification of the target product [58]. Unfortunately, all our attempts to purify the target compound using chromatography methods failed. Therefore, we purified 9,12-dibromo-ortho-carborane by fraction crystallization from chloroform that produced a rather low (22%) yield of pure product (Scheme 1). It should be noted that the structure of 9,12-dibromo-ortho-carborane was determined in 1966 [50] at room temperature. The quality of that experiment was evidently low and was mostly concentrated on the description of molecular geometry. Therefore, in the present study, we redetermined its structure at low temperature (110 K) focusing on both molecular structure ( Figure 1) and, especially, the crystal packing.  The presence of two bromine atoms might imply a formation of the Br . . . Br halogen bond in the crystal structure of 9,12-dibromo-ortho-carborane. At the same time, in our recent study [42] we showed that halogen substituent at the B9 and B12 positions of the ortho-carborane cage can act as a good donor of the lone pair (LP), however, its acceptor ability is low, and therefore, a formation of any strong halogen bond in the crystal is hardly expected. Moreover, in recently studied 1,12-Br 2 -ortho-C 2 B 10 H 10 , the C-H . . . Br interactions were found to be structure-forming while no halogen bonds were observed [49]. It means that it is difficult to predict a priori what type of intermolecular interactions will be predominant in the crystal structure stabilization of dihalogen carboranes. The X-ray study of 9,12-Br 2 -ortho-C 2 B 10 H 10 has revealed that both Br . . . Br halogen bond of type II and C-H . . . Br hydrogen bonds are formed in the crystal (Figure 2). The halogen bond is rather weak and strongly distorted (the Br(1) . . . Br (2)  The presence of two bromine atoms might imply a formation of the Br…Br halogen bond in the crystal structure of 9,12-dibromo-ortho-carborane. At the same time, in our recent study [42] we showed that halogen substituent at the B9 and B12 positions of the ortho-carborane cage can act as a good donor of the lone pair (LP), however, its acceptor ability is low, and therefore, a formation of any strong halogen bond in the crystal is hardly expected. Moreover, in recently studied 1,12-Br2-ortho-C2B10H10, the C-H…Br interactions were found to be structure-forming while no halogen bonds were observed [49]. It means that it is difficult to predict a priori what type of intermolecular interactions will be predominant in the crystal structure stabilization of dihalogen carboranes. The X-ray study of 9,12-Br2-ortho-C2B10H10 has revealed that both Br…Br halogen bond of type II and C-H…Br hydrogen bonds are formed in the crystal (Figure 2). The halogen bond is rather weak and strongly distorted (the Br(1)…Br(2) distance is 3.796(2) Å, the B(9)-Br(1)…Br (2) and B(12)-Br(2)…Br(1) angles are 92.5(3)° and 148.4°, respectively); the Br(1) atom acts as LP donor while the Br(2) atom is LP acceptor. Each molecule has two halogen-bonded neighbors and four C-H…Br bonded ones which leads to a formation of layers parallel to the bc plane. In order to understand which interactions play a predominant role in the crystal structure formation, we carried out energetic analysis of the crystal packing by estimation of the dimeric interaction energies Each molecule has two halogen-bonded neighbors and four C-H . . . Br bonded ones which leads to a formation of layers parallel to the bc plane. In order to understand which interactions play a predominant role in the crystal structure formation, we carried out energetic analysis of the crystal packing by estimation of the dimeric interaction energies [42,[59][60][61]. Such dimers are formed by the central molecule and the molecule taken from the closest environment of the central molecule. Here, we considered only those molecular pairs which are linked by the C-H . . . Br and Br . . . Br interactions because all the other intermolecular interactions are of van der Waals type. Calculations were carried out with the GAUSSIAN program [62] using PBE0 functional and triple-zeta basis set which were found to be reliable for analysis of halogen and hydrogen bonds [63][64][65].

CH BH
As it is seen in Figure 2, the C-H . . . Br interactions are much stronger than Br . . . Br halogen bonds and can be viewed as structure-forming interactions in the crystal of 9,12-Br 2 -ortho-C 2 B 10 H 10 . The weakness of the observed halogen bond is also confirmed by near equivalence of the B(9)-Br(1) (1.955(5) Å) and B(9)-Br(2) (1.963(5) Å) bond lengths. In the case of a strong halogen bond, the latter must be significantly longer because the Br(2) atom acts as LP acceptor.

Materials and Methods
All reactions were carried out under argon atmosphere. Dichloromethane was dried using standard procedures [66]. The reaction progress was monitored by thin layer chromatography (Merck F254 silica gel on aluminum plates; n-hexane: chloroform 4: 1 (v/v)) and visualized using 0.5 % PdCl 2 in 1% HCl in aq. MeOH (1:10). The NMR spectra at 400 MHz ( 1 H), 128 MHz ( 11 B), and 100 MHz ( 13 C) were recorded with Varian Inova 400 spectrometer. The residual signal of the NMR solvent relative to Me 4 Si was taken as the internal reference for 1 H and 13 C NMR spectra. 11 B NMR spectra were referenced using BF 3 ·Et 2 O as external standard. Mass spectra (MS) were measured using Shimadzu LCMS-2020 instrument with DUIS ionization (ESI-Electrospray ionization and APCI-Atmospheric pressure chemical ionization). The measurements were performed in a negative ion mode with mass range from m/z 50 to m/z 2000. Isotope distribution was calculated using Isotope Distribution Calculator and Mass Spec Plotter [67].
Anhydrous AlCl 3 (0.80 g, 6.0 mmol) was added to solution of ortho-carborane (5.0 g, 34.7 mmol) in dichloromethane (200 mL) and stirred for 15 min. A solution of Br 2 (1.78 mL, 5.55 g, 34.7 mmol) in dichloromethane (50 mL) was added dropwise and the reaction mixture was stirred until it became colorless. Then, a solution of Br 2 (1.78 mL, 5.55 g, 34.7 mmol) in dichloromethane (50 mL) was added dropwise and the reaction mixture was heated under reflux for 16 h. The reaction mixture was cooled and treated with a solution of Na 2 S 2 O 3 (30.00 g) in water (100 mL). The organic phase was separated, the aqueous fraction was extracted with dichloromethane (3 × 50 mL). The organic fractions were combined, dried with anhydrous Na 2 SO 4 , filtered, and evaporated to dryness to give 9.75 g (93%) of crude product. Fraction crystallization from chloroform gave 2.30 g (22% yield) of pure of 9,12-Br 2 -ortho-C 2 B 10 H 10 as colorless crystals. 1  The single crystals of 9,12-Br 2 -ortho-C 2 B 10 H 10 were grown by slow evaporation of a solution of the title compound in chloroform at room temperature. Single crystal X-ray diffraction experiment was carried out using SMART APEX2 CCD diffractometer (λ(Mo-Kα) = 0.71073 Å, graphite monochromator, ω-scans) at 110 K. Collected data were processed by the SAINT and SADABS programs incorporated into the APEX2 program package [68]. The structure was solved by the direct methods and refined by the full-matrix least-squares procedure against F 2 in anisotropic approximation. The refinement was carried out with the SHELXTL program [69]. The CCDC number 2132434 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif (accessed on 15 February 2022).