How the Position of Substitution Affects Intermolecular Bonding in Halogen Derivatives of Carboranes: Crystal Structures of 1,2,3- and 8,9,12-Triiodo- and 8,9,12-Tribromo ortho-Carboranes

The crystal structures of two isomeric triiodo derivatives of ortho-carborane containing substituents in the three most electron-withdrawing positions of the carborane cage, 1,2,3-I3-1,2-C2B10H9, and the three most electron-donating positions, 8,9,12-I3-1,2-C2B10H9, as well as the crystal structure of 8,9,12-Br3-1,2-C2B10H9, were determined by single-crystal X-ray diffraction. In the structure of 1,2,3-I3-1,2-C2B10H9, an iodine atom attached to the boron atom (position 3) donates its lone pairs simultaneously to the σ-holes of both iodine atoms attached to the carbon atoms (positions 1 and 2) with the I⋯I distance of 3.554(2) Å and the C-I⋯I and B-I⋯I angles of 169.2(2)° and 92.2(2)°, respectively. The structure is additionally stabilized by a few B-H⋯I-shortened contacts. In the structure of 8,9,12-I3-1,2-C2B10H9, the I⋯I contacts of type II are very weak (the I⋯I distance is 4.268(4) Å, the B8-I8⋯I12 and B12-I12⋯I8 angles are 130.2(3)° and 92.2(3)°) and can only be regarded as dihalogen bonds formally. In comparison with the latter, the structure of 8,9,12-Br3-1,2-C2B10H9 demonstrates both similarities and differences. No Br⋯Br contacts of type II are observed, while there are two Br⋯Br halogen bonds of type I.


Introduction
The ability of halogens to form complexes with various electron pair donors was discovered over two hundred years ago [1][2][3], and the Nobel Prize laureate Odd Hassel provided crystallographic proof for the existence of such a bond, interpreting it as a charge-transfer interaction more than fifty years ago [4,5]. However, only at the beginning of the 21st century has halogen bonding grown from a scientific curiosity to one of the most interesting and actively studied non-covalent interactions for the construction of supramolecular assemblies [6][7][8][9][10].
This progress has been largely due to a better understanding of the principles on which the strength of the halogen bond depends. The performance of the halogen bond largely depends on the degree of polarization of the halogen atom; that is, the greater the positive electrostatic potential of the σ-hole, the more efficient the halogen bond donor will be [10][11][12]. The value of the positive potential of the σ-hole depends on the ability of the halogen atom to be polarized, which decreases in the following order: I > Br > Cl >> F [13,14]. The value of the positive potential of the σ-hole can be enhanced due to the electron-withdrawing ability of the fragment to which the halogen atom is attached.
For a halogen atom to be an electron acceptor in order to form a halogen bond, it must be bonded to an electron-withdrawing atom or group. Therefore, the sp hybridization of carbon atoms bearing a halogen is favored over sp 2 followed by sp 3 hybridization [15,16]. The For a halogen atom to be an electron acceptor in order to form a halogen bond, it must be bonded to an electron-withdrawing atom or group. Therefore, the sp hybridization of carbon atoms bearing a halogen is favored over sp 2 followed by sp 3 hybridization [15,16]. The hybridization of the carbon atom can be compensated by the electron-withdrawing effect of fluorine atoms, as evidenced by the close values of the σ-hole potential of the corresponding iodine atoms in 1-iodoethynyl-4-iodobenzene and 1,4-diiodoperfluoro-benzene (172 and 169 kJ/mol, respectively) [16]. The strength of the halogen bond is highly correlated with the degree of iodobenzene fluorination [17]. Therefore, it is not surprising that 1,4-diiodoperfluorobenzene and its analogs are widely used in the design of halogen-bonded supramolecular systems [18][19][20][21][22][23][24][25][26][27][28], although arylacetylene iodides also play an important role [16,[29][30][31][32][33][34][35]. In the absence of other electron density donors, the iodine atoms in these compounds are also able to play this role, which leads to the formation of I⋯I dihalogen bonds [36][37][38][39], and the number of such bonds, as a rule, increases with the number of iodine atoms in the molecule [40].
Icosahedral carboranes C2B10H12 are another class of compounds whose derivatives are promising as halogen bond donors. The predicted strength of the halogen bonds with the same electron donor (based on the σ-hole potential) is larger for C-vertex halogensubstituted carboranes than for their organic aromatic counterparts [41][42][43]. In contrast to the iodo aromatics, wherein all iodine atoms are equivalent, in the iodo derivatives of ortho-carborane iodine atoms, depending on their position, they can act preferentially as an acceptor or a donor of a halogen bond. A typical example is 1,12-diodo-ortho-carborane, in which one of the iodine atoms is bonded to the most electron-withdrawing position of the carborane cage (position 1), and the second to the most electron-donating position (position 12) ( Figure 1) [44]. The first of them is an electron acceptor, and the last one is a donor, which form an ideal intermolecular I⋯I dihalogen bond of type II [45]. In this contribution, we studied intermolecular bonding in two isomers of triiodoortho-carborane containing substituents in the three most electron-withdrawing positions of the carborane cage (1,2,3) and the three most electron-donating positions (8,9,12); in addition, a comparative analysis of the crystal packings of the 8,9,12-triiodo and 8,9,12tribromo derivatives of ortho-carborane was performed. In this contribution, we studied intermolecular bonding in two isomers of triiodo-orthocarborane containing substituents in the three most electron-withdrawing positions of the carborane cage (1,2,3) and the three most electron-donating positions (8,9,12); in addition, a comparative analysis of the crystal packings of the 8,9,12-triiodo and 8,9,12-tribromo derivatives of ortho-carborane was performed.
The formation of 8,9,12-I 3 -1,2-C 2 B 10 H 9 (1) was previously reported in the iodination of ortho-carborane with molecular iodine in acetic acid in the presence of a mixture of concentrated sulfuric and nitric acids [53]. We isolated the 8,9,12-triiodo derivative as a byproduct of the reaction of ortho-carborane with iodine in dichloromethane in the presence of AlCl 3 [54]. It should be noted that the unit cell parameters of 8,9,12-I 3 -1,2-C 2 B 10 H 9 (1) have been reported [55]; however, its structure has not been yet solved.
The formation of 8,9,12-I3-1,2-C2B10H9 (1) was previously reported in the iodination of ortho-carborane with molecular iodine in acetic acid in the presence of a mixture of concentrated sulfuric and nitric acids [53]. We isolated the 8,9,12-triiodo derivative as a by-product of the reaction of ortho-carborane with iodine in dichloromethane in the presence of AlCl3 [54]. It should be noted that the unit cell parameters of 8,9,12-I3-1,2-C2B10H9 (1) have been reported [55]; however, its structure has not been yet solved.
A crystal-packing fragment of 1 is depicted in Figure 3. Only weak intermolecular interactions are observed in the crystal structure. From a formal point of view, four types of intermolecular interactions are observed in the crystal of 1. Halogen atoms participate in both types (I and II) of halogen bonding, and I⋯H-C(B) hydrogen bonds as well as B-H ⋯H-B contacts are formed. It should be noted that all intermolecular contacts except for one are somewhat longer than the sum of the van-der-Waals radii. For instance, the type II halogen bond is very weak (the I⋯I distance is 4.268(4) Å, the B8-I8⋯I12 angle is 130.2(3)°, and the B12-I12⋯I8 angle is 92.2(3)°) ( Figure 3) and can only be regarded as a type II halogen bond formally. At the same time, the I9⋯I9 halogen bond of type I demonstrates an interhalogen distance (4.002(4) Å) shorter than the sum of the van-der-Waals radii (4.14 Å) [56]; however, halogen bonds of this type are usually relatively weak.  Therefore, it is impossible to choose one or two of the most important contacts that can be considered to be structure-forming. Interactions in the bc crystallographic plane are due to I· · · H-C(B) and H· · · H contacts, while in the crystallographic direction, a, molecules are linked mostly by I· · · I interactions. As a result, the crystal packing of 8,9,12-I 3 -1,2-C 2 B 10 H 9 can be considered to be nearly isotropic.
It would be interesting to compare the crystal packing of 8,9,12-triiodo-ortho-carborane with that of its closest analog, 8,9,12-tribromo-ortho-carborane 8,9,12-Br 3 -1,2-C 2 B 10 H 9 (2). Despite the fact that the bromination of ortho-carborane was first described as early as the mid-1960s [57], the chemistry of the bromo-derivatives of carborane has been studied to a much lesser extent compared to its iodo-derivatives due to the difficulty in isolating pure products. Recently, we published the synthesis and characterization of the 9,12-dibromo derivative of ortho-carborane [58]. Since the 8,9,12-tribromo derivative was one of the sideproducts of that reaction, we decided to increase the ratio of bromine to ortho-carborane (up to 3:1) and the reaction time. This allowed us to isolate the desired compound 8,9,12-Br 3 -1,2-C 2 B 10 H 9 (2) at a 17% yield (see Section 3.3) It should be noted that the signal of the CH carborane groups of in the 1 H NMR spectrum in CDCl 3 , which is a convenient indicator of the CH-acidity of carboranes [59,60], for compound 2 appears in a higher field at 3.87 ppm. compared to compound 1 (4.13 ppm). This indicates a lower acidity of the CH-carborane groups in the 8,9,12-tribromo derivative compared to the 8,9,12-triiodo derivative.
The crystal structure of 8,9,12-Br 3 -1,2-C 2 B 10 H 9 was determined by single-crystal X-ray diffraction. A general view of 2 is presented in Figure 4.
Therefore, it is impossible to choose one or two of the most important contacts that can be considered to be structure-forming. Interactions in the bc crystallographic plane are due to I⋯H-C(B) and H⋯H contacts, while in the crystallographic direction, a, molecules are linked mostly by I⋯I interactions. As a result, the crystal packing of 8,9,12-I3-1,2-C2B10H9 can be considered to be nearly isotropic.
It would be interesting to compare the crystal packing of 8,9,12-triiodo-ortho-carborane with that of its closest analog, 8,9,12-tribromo-ortho-carborane 8,9,12-Br3-1,2-C2B10H9 (2). Despite the fact that the bromination of ortho-carborane was first described as early as the mid-1960s [57], the chemistry of the bromo-derivatives of carborane has been studied to a much lesser extent compared to its iodo-derivatives due to the difficulty in isolating pure products. Recently, we published the synthesis and characterization of the 9,12-dibromo derivative of ortho-carborane [58]. Since the 8,9,12-tribromo derivative was one of the side-products of that reaction, we decided to increase the ratio of bromine to ortho-carborane (up to 3:1) and the reaction time. This allowed us to isolate the desired compound 8,9,12-Br3-1,2-C2B10H9 (2) at a 17% yield (see Section 3.3) It should be noted that the signal of the CH carborane groups of in the 1 H NMR spectrum in CDCl3, which is a convenient indicator of the CH-acidity of carboranes [59,60], for compound 2 appears in a higher field at 3.87 ppm. compared to compound 1 (4.13 ppm). This indicates a lower acidity of the CH-carborane groups in the 8,9,12-tribromo derivative compared to the 8,9,12-triiodo derivative.
A comparison of the crystal structures of 2 and 1 studied in this work demonstrates both similarities and differences. As in compound 1, a Br9· · · Br9 halogen bond of type I is observed in the crystal structure of 8,9,12-Br 3 -1,2-C 2 B 10 H 9 (the Br· · · Br distance is 3.586(2) Å, which is shorter than the sum of the van-der-Waals radii 3.79 Å) ( Figure 5). At the same time, there are no type II halogen bonds; however, one more halogen bond of type I is found between Br8 atoms, wherein the Br· · · Br distance (3.969(2) Å) is somewhat longer than the sum of the van-der-Waals radii. As in compound 1, all the other intermolecular interactions are Br· · · H-C(B) and H· · · H. The differences in the crystal-packing properties described above result in some redistribution of the contact types ( Figure 6): the contribution of Hal· · · Hal contacts increases, which leads to a decrease in the number of Hal· · · H contacts and to an increase in H· · · H ones.
A comparison of the crystal structures of 2 and 1 studied in this work demonstrates both similarities and differences. As in compound 1, a Br9...Br9 halogen bond of type I is observed in the crystal structure of 8,9,12-Br3-1,2-C2B10H9 (the Br...Br distance is 3.586(2) Å, which is shorter than the sum of the van-der-Waals radii 3.79 Å) ( Figure 5). At the same time, there are no type II halogen bonds; however, one more halogen bond of type I is found between Br8 atoms, wherein the Br...Br distance (3.969(2) Å) is somewhat longer than the sum of the van-der-Waals radii. As in compound 1, all the other intermolecular interactions are Br⋯H-C(B) and H⋯H. The differences in the crystal-packing properties described above result in some redistribution of the contact types ( Figure 6): the contribution of Hal⋯Hal contacts increases, which leads to a decrease in the number of Hal⋯H contacts and to an increase in H⋯H ones.   The observed similarities and dissimilarities in the crystal packing of 8,9,12-I3-1,2-C2B10H9 and 8,9,12-Br3-1,2-C2B10H9 can be clearly seen in Figure 7. Similar C-H⋯I(Br)bonded chains are formed in one direction, while in the perpendicular plane, the relative orientation of molecules is somewhat different. The 1,2,3-isomer 1,2,3-I3-1,2-C2B10H9 (3) was prepared by the deprotonation of 3-iodoortho-carborane followed by a treatment of molecular iodine (see below). The crystal structure of 1,2,3-I3-1,2-C2B10H9 was determined by single-crystal X-ray diffraction. A general view of 3 is presented in Figure 8. The molecule in the crystal occupies a special position, as it is located at the two-fold symmetry axis. The C-I distances are the same (due to symmetry) and equal to 2.103(4) Å, while the B-I bond is somewhat longer at 2.160(5) Å. These lengths are slightly shorter than the C1-I1 (2.121(2) Å) and B12-I12 (2.179(2) Å) bonds in 1,12-I2-closo-C2B10H10 [45].  The observed similarities and dissimilarities in the crystal packing of 8,9,12-I3-1,2-C2B10H9 and 8,9,12-Br3-1,2-C2B10H9 can be clearly seen in Figure 7. Similar C-H⋯I(Br)bonded chains are formed in one direction, while in the perpendicular plane, the relative orientation of molecules is somewhat different. The 1,2,3-isomer 1,2,3-I3-1,2-C2B10H9 (3) was prepared by the deprotonation of 3-iodoortho-carborane followed by a treatment of molecular iodine (see below). The crystal structure of 1,2,3-I3-1,2-C2B10H9 was determined by single-crystal X-ray diffraction. A general view of 3 is presented in Figure 8. The molecule in the crystal occupies a special position, as it is located at the two-fold symmetry axis. The C-I distances are the same (due to symmetry) and equal to 2.103(4) Å, while the B-I bond is somewhat longer at 2.160(5) Å. These lengths are slightly shorter than the C1-I1 (2.121(2) Å) and B12-I12 (2.179(2) Å) bonds in 1,12-I2-closo-C2B10H10 [45]. The observed similarities and dissimilarities in the crystal packing of 8,9,12-I 3 -1,2-C 2 B 10 H 9 and 8,9,12-Br 3 -1,2-C 2 B 10 H 9 can be clearly seen in Figure 7. Similar C-H· · · I(Br)bonded chains are formed in one direction, while in the perpendicular plane, the relative orientation of molecules is somewhat different.
In our recent study, we theoretically compared the dimer formation of 1,12-and 1,3diiodo-ortho-carboranes [45]. According to our calculations, it appeared that both dimers are stabilized by a type II halogen bond and B-H⋯I hydrogen bonds. The role of the halogen bond is more pronounced in both dimers; however, in the 1,3-isomer, the halogen bond is weaker (but only by 2.5 kJ/mol), while the hydrogen bonds are stronger (in total by 0.4 kcal/mol). This means that the probability of the formation of a type II halogen bond in a real crystal of 1,3-I2-1,2-C2B10H10 is somewhat low. Nevertheless, it is formed and is a structure-forming interaction in the crystal structure of 1,2,3-I3-1,2-C2B10H9. Indeed, there are no H⋯H shortened contacts. The structure is additionally stabilized by a few B-H⋯I shortened contacts. However, some of them are formed between molecules already linked by halogen bonds. For a better understanding of the intermolecular connection in the trimers, we optimized its structure using density functional theory (DFT) at the PBE0/def2tzvp level followed by a topological analysis of the calculated electron density in terms of the "Atoms in Molecules" theory [65]. The intermolecular interaction energies were estimated from their correlation with the potential energy density at the bond critical point [66,67] using the AIMAll program [68]. In our recent study, we theoretically compared the dimer formation of 1,12-and 1,3diiodo-ortho-carboranes [45]. According to our calculations, it appeared that both dimers are stabilized by a type II halogen bond and B-H· · · I hydrogen bonds. The role of the halogen bond is more pronounced in both dimers; however, in the 1,3-isomer, the halogen bond is weaker (but only by 2.5 kJ/mol), while the hydrogen bonds are stronger (in total by 0.4 kcal/mol). This means that the probability of the formation of a type II halogen bond in a real crystal of 1,3-I 2 -1,2-C 2 B 10 H 10 is somewhat low. Nevertheless, it is formed and is a structure-forming interaction in the crystal structure of 1,2,3-I 3 -1,2-C 2 B 10 H 9 . Indeed, there are no H· · · H shortened contacts. The structure is additionally stabilized by a few B-H· · · I shortened contacts. However, some of them are formed between molecules already linked by halogen bonds. For a better understanding of the intermolecular connection in the trimers, we optimized its structure using density functional theory (DFT) at the PBE0/def2tzvp level followed by a topological analysis of the calculated electron density in terms of the "Atoms in Molecules" theory [65]. The intermolecular interaction energies were estimated from their correlation with the potential energy density at the bond critical point [66,67] using the AIMAll program [68].
This method of investigating structural details was successfully utilized in our recent studies on noncovalent interactions [69][70][71]. Good agreement was obtained between the calculated and experimental structures. The interhalogen distances are nearly the same (Figure 9), and the calculated angles C1-I1· · · I2 (168.2 • ) and B3-I2· · · I1 (90.5 • ) also strongly agree with the experiment. The H· · · I distances are somewhat shorter, as predicted by theory. According to the calculations, the energy of the halogen bond is equal to 8.8 kJ/mol, while the energies of the H4· · · I1 and H4· · · I2 contacts are 2.5 and 2.1 kJ/mol, respectively. Therefore, the attraction energy of each two molecules in the layer is equal to (8.8 + 2.5 + 2.1) 13.4 kJ/mol, while only weak B-H· · · I contacts are observed between layers. This allows us to consider the crystal packing of compound 3 as anisotropic unlike the 8,9,12-isomer. It is interesting to note that the crystal density of the latter is somewhat higher than that of the 1,2,3-isomer. This can be explained by the increased role of the I· · · I interactions ( Figure 10). The presence of relatively strong I· · · I intermolecular interactions does not allow molecules to adjust their orientations to obtain closer packing.  Therefore, the attraction energy of each two molecules in the layer is equal to (8.8 + 2.5 + 2.1) 13.4 kJ/mol, while only weak B-H⋯I contacts are observed between layers. This allows us to consider the crystal packing of compound 3 as anisotropic unlike the 8,9,12-isomer. It is interesting to note that the crystal density of the latter is somewhat higher than that of the 1,2,3-isomer. This can be explained by the increased role of the I...I interactions (Figure 10). The presence of relatively strong I...I intermolecular interactions does not allow molecules to adjust their orientations to obtain closer packing. The same reasons can be used to explain the higher density of water in comparison to ice, and have also been used to explain the differences in the crystal-packing density of polynitro compounds [72,73].

General Methods
The reactions were carried under an inert atmosphere. 3-Iodo-ortho-carborane was prepared according to a procedure from the literature [74]. 1,2-Dimethoxyethane was dried using standard procedures [75]. All other chemical reagents were purchased from Sigma Aldrich, Acros Organics, and ABCR and used without purification. The reaction progress was monitored by thin-layer chromatography (Merck F254 silica gel on aluminum plates) and visualized using 0.5% PdCl2 in 1% HCl in aq. MeOH (1:10). Acros Organics silica gel (0.060-0.200 mm) was used for column chromatography. The NMR spectra at 400 MHz ( 1 H) and 128 MHz ( 11 B) were recorded with Varian Inova 400 spectrometer. The residual signal of the NMR solvent relative to Me4Si was taken as the internal reference for 1 H spectra. 11 B NMR spectra were referenced using BF3·Et2O as external standard. 8,9,9,9,12-I3-ortho-C2B10H9 was isolated as a by-product from the di-iodination reaction of ortho-carborane under standard conditions [51]. Iodine (3.553 g, 14.00 mmol) and anhydrous AlCl3 (0.400 g) were added to a solution of ortho-carborane (1.009 g, 7.00 mmol) in dichloromethane (30 mL) and heated under reflux for 8 h. Then, the reaction mixture was cooled and treated with a solution of Na2S2O3·5H2O (3.000 g) in water (50 mL). The organic phase was separated, and the aqueous fraction was extracted with dichloromethane (3 × 50 mL). The organic phases were combined, dried over Na2SO4, filtered, and concentrated The same reasons can be used to explain the higher density of water in comparison to ice, and have also been used to explain the differences in the crystal-packing density of polynitro compounds [72,73].

General Methods
The reactions were carried under an inert atmosphere. 3-Iodo-ortho-carborane was prepared according to a procedure from the literature [74]. 1,2-Dimethoxyethane was dried using standard procedures [75]. All other chemical reagents were purchased from Sigma Aldrich, Acros Organics, and ABCR and used without purification. The reaction progress was monitored by thin-layer chromatography (Merck F254 silica gel on aluminum plates) and visualized using 0.5% PdCl 2 in 1% HCl in aq. MeOH (1:10). Acros Organics silica gel (0.060-0.200 mm) was used for column chromatography. The NMR spectra at 400 MHz ( 1 H) and 128 MHz ( 11 B) 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 spectra. 11 B NMR spectra were referenced using BF 3 ·Et 2 O as external standard.

Single-Crystal X-ray Diffraction Study
Single-crystal X-ray diffraction experiments of 1, 2, and 3 (see Supplementary Materials) were carried out using SMART APEX2 CCD diffractometer (λ(Mo-Kα) = 0.71073 Å; graphite monochromator; ω-scans) at 120 K. Collected data were processed by the SAINT and SADABS programs incorporated into the APEX2 program package [76]. The structures were determined by 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 [77]. The CCDC numbers (2216663 for 1, 2234154 for 2, and 2216664 for 3) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.

Quantum Chemical Calculation
Quantum chemical optimization of halogen-bonded trimeric associate of 1,2,3-I 3 -1,2-C 2 B 10 H 9 was carried out using the Gaussian program [78]. The initial geometry for optimization was taken from the X-ray data. Optimization was carried out using PBE0 functional and triple-zeta basis set def2tzvp. For better agreement with experimental geometry, calculation was carried out within polarizable continuum model (PCM) using SCRF keyword in the Gaussian program and highly polar water molecule. It has recently been shown that such a method of calculation results in better agreement of the geometry for noncovalent interactions [45,69].