Halogen Interactions in Macrocyclic Thiacalix[4]arene Systems

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Halogen Interactions in Macrocyclic Thiacalix[4]arene Systems Manabu Yamada, and Fumio Hamada Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.5b00065 • Publication Date (Web): 17 Feb 2015 Downloaded from http://pubs.acs.org on February 18, 2015

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Crystal Growth & Design

Halogen Interactions in Macrocyclic Thiacalix[4]arene Systems Manabu Yamada*,† and Fumio Hamada*,§ †Research Center for Engineering Science, Graduate School of Engineering and Resource Science, Akita University, 1-1 Tegatagakuen-machi, Akita 010-8502, Japan. §Department of Applied Chemistry, Graduate School of Engineering and Resource Science, Akita University, 1-1 Tegatagakuen-machi, Akita 010-8502, Japan. ABSTRACT: The crystalline supramolecular assemblies of brominated thiacalix[4]arene alkyl ethers were studied by single-crystal X-ray diffraction and computational analysis. Eight compounds were synthesized that exhibited linear alkyl groups of varying lengths projecting from the thiacalixarene lower rims (-CH3: 4, -CH2CH3: 5, -(CH2)4CH3) - -(CH2)9CH3): 6-11) in order to study the intermolecular halogen interactions between the macrocycles. These crystals displayed remarkably different assemblies, which was rationalized as an effect of varying alkyl chain length on the stabilization afforded by the halogen interactions. The two compounds with the shortest alkyl chains, 4 and 5, assembled primarily through the influence of halogen–π interactions between distinct molecules. In contrast, the compounds with the longest chains, 8-11, assembled primarily through the influence of halogen-sulfur halogen bonding. Oddly, 6 and 7 did not follow this pattern in that they showed no major assembly motivated by halogen interactions. Finally, the supramolecular assemblies were found to be stabilized by additional intermolecular interactions, including hydrogen bonding, S-π, CH-π, and Br‒H interactions.

INTRODUCTION Understanding non-covalent intra- and intermolecular interactions between artificial molecules and/or biomolecules provides key insights into the formation of molecular assemblies and the resulting behavior in

supramolecular chemical and biological systems. These interactions can, among other things, trigger biomolecular activities via molecular recognition;1-4 the behavior of supramolecules, which include artificial macrocyclic hosts and host-guest protein complexes, is therefore largely responsible for the activity of living systems.5-10 As a result, hydrogen bonding, electrostatic, and van der Waals interactions have all been intensely investigated in the past decade, and have shown potential uses in molecular recognition and the construction of solid, liquid, and gas assemblies. Halogen atoms undergo three kinds of weak non-covalent interactions, specifically halogen bonding,11-20 halogen– halogen interactions,21-26 and halogen–π interactions27-32. These short-range interactions have a high tendency to occur along the extended C–X (X = halogen) axis, and have become increasingly popular in crystal engineering and solution chemistry (Figure S1). 11-32

Figure 1. Structural formulas of thiacalix[4]arene derivatives 1-11.

Resnati and co-workers have reported extensively on interactions involving solid-state halogen bonding in biomolecules, halogenated alkanes, halogenated phenols, and host molecule–polymer macromolecules by relying on crystallography data;33-39 they have shown that halogens have a tendency to form Lewis acid-base pairs with both electron acceptors and electron-donating heteroatoms, yielding bond angles between 140-180° and bond lengths of less than the sum of the van der Waals radii. Meanwhile, Espinosa and co-workers have used high resolution X-ray experiments to elucidate charge density on the halogen atoms of halogenated aromatic rings,

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identifying two types of halogen–halogen contacts, which they called Type I and Type II.23 Again, these interactions necessarily show a C–X···X–C inter-halogen distance of less than the sum of the van der Waals radii and result from the polarization and dispersion–repulsion interactions in the crystalline state.21-26 The two types of interactions are distinguished by the two angles centered on the halogen atoms; θ1 = θ2 = 140–180° for Type I, while θ1 = 150– 180° and θ2 = 90–120° for Type II. Finally, halogen–π interactions are non-covalent interactions of aromatic donors with halogenated organic molecules; these are similar to the more common CH–π interactions.27-32 These interactions are of importance in the electrophilic halogenation of aromatic systems. Recent research in optical materials and crystal engineering has taken advantage of this interaction, with additional applications reported in supramolecular assemblies and molecular recognition that indicate that I–π contact is induced by bond polarization. Overall, though, this kind of interaction still holds significant, unexplored potential in advanced materials, among other avenues of research. Thiacalixarenes, a group of cyclophane compounds, hold the potential for intermolecular interactions in the crystalline state because their bridging sulfur moieties are capable of forming continuous non-covalent interactions, with hydrogen bonding, halogen interactions, and metal coordination all showing potential.40-46 In the past, we have used both crystallography and computation to demonstrate halogen interactions between heteromacrocyclic host compounds, such as 5,11,17,23tetrabromo-25,26,27,28-tetrabutoxythiacalix[4]arene (1),47 5,11,17,23-tetraiodo-25,26,27,28tetrapropoxythiacalix[4]arene (2),48 and 5,11,17,23tetraiodo-25,26,27,28-tetrabutoxythiacalix[4]arene (3)48. Interestingly, crystals of 1 showed a repeat, open-network structure formed by triangular Br3 synthon-type halogen– halogen contacts, leading to the formation of a supramolecular assembly via complementary intermolecular CH– Br, S–π, and CH–π interactions. Similarly, crystals of 2 exhibited I–I interactions between each molecule, with S– π and CH–I interactions also observed in the obtained three-dimensional assembly. On the other hand, crystals of 3 showed S–I halogen bonds, with hydrogen bonding evident in the extended structure in addition to the previously mentioned interactions. Despite the common appearance of halogen interactions in facilitating chemical and biological functions, no calixarene or thiacalixarene supramolecular assemblies consisting of only macrocyclic host molecules based on them have been reported. Therefore, in this work, we analyze halogen bonding and halogen–π interactions in 5,11,17,23tetrabromo-25,26,27,28-tetraalkoxythiacalix[4]arenes (Figure 1: -CH3 and –CH2CH3: 4 and 5; -(CH2)4CH3 - (CH2)9CH3: 6-11) through crystallographic and computational techniques, showing that the nature of supramolecular assemblies constructed via preferential intermolecular halogen bonding and halogen-π interactions are affected by changes in the length of linear alkyl groups.

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EXPERIMENTAL SECTION General Methods. All solvents were purchased from commercial sources, and used as received. The reactions were carried out in nitrogen atmosphere. 25,26,27,28Tetrahydroxythiacalix[4]arene49,50 was obtained from the de-tert-butylation reaction of 5,11,17,23-tetra-tertbutylthiacalix[4]arene, which was prepared according to our previously reported procedures.51-53 5,11,17,23tetrabromo-25,26,27,28-tetrahydroxythiacalix[4]arene was also synthesized according to the literature.49 NMR data were recorded on JEOL 600SSS ECA-600 instrument. The FT-IR spectra were measured using a Thermo Fisher Scientific Nicolet iS5 spectrophotometer. Elemental analysis was performed on a Systems Engineering CE-440M CHN/O/S elemental analyzer. Synthetic procedures of 4-11 Thiacalixarenes 4-11 were synthesized as follows: suspensions of 5,11,17,23-tetrabromo-25,26,27,28tetrahydroxythiacalix[4]arenes were refluxed with potassium carbonate and the appropriate alkyl halide in acetone under a nitrogen atmosphere, affording the crude brown products of 4-11 (See Experimental section in the Supporting Information). The resulting solids were recrystallized in mixtures of chloroform and either /cyclohexane, chloroform/acetone, or chloroform/methanol; pure, colorless crystals were obtained and characterized by single-crystal X-ray diffraction and other appropriate methods.

Crystallographic analysis of 4-11 Eight single crystals of 4-11 suitable for single-crystal Xray diffraction studies were formed. The crystals in mother liquid were picked up with a pipette, and dropped in paraffin oil. The single crystals coated with oil were isolated on MicroMounts, and the crystals were immediately placed in a cold nitrogen stream. X-Ray diffraction data for these crystals were collected on a Rigaku PAXIS RAPID imaging plate diffractometer with graphitemonochromated Mo Kα radiation. The structures were solved by direct methods using SHELXS-9754 and refined using the full-matrix least-squares method on F2 using the SHELXL-9755 Program. All materials for publication were prepared by CrystalStructure 4.0 and Yadokari-XG 2009 software. All non-hydrogen atoms were refined anisotropically. The positions of all hydrogen atoms were calculated geometrically and refined as a riding model.

DFT calculations of 4, 5 and 8-11 The single-point energy calculations from geometries of the X-ray structures of 4, 5 and 8-11 were carried out as density functional theory (DFT) calculations at the B3LYP level using the ab initio 6-31G(*) basis set with Spartan 14 software.56 The disordered moieties in 9-11 (octyl groups in 9, nonyl groups in 10, and decyl groups in 11) were omitted from the calculations based on the X-ray structures of 9-11. Because the H–C bonds are short in the Xray structures of 4, 5 and 8-11, only the heavier atoms


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Figure 2. (a) Stick diagram and space-filling representation of 4. (b) Stick diagram showing Br···π interactions (pink dotted lines) a and CH···π interactions in the crystal structure of 4. Symmetry operation: −1/2+x, y, 1/2−z. Br = brown, S = yellow, O = red, C = dark gray, H = light gray. (c) Ab initio calculations showing the electrostatic potential surfaces of the molecular (upper) and the dimeric unit (lower) of 4. Electron deficient regions are shown in blue, with electron density increasing from green to yellow to −1 red. The potential energies are presented only in the −100.0000 to +100.0000 kJ mol range to emphasize the variation in electrostatic potential associated with the bromine atoms and aromatic rings.

were frozen; the molecular structures and two-molecule structures of 4, 5 and 8-11 were then minimized, where upon the positions of the hydrogen atoms were relaxed.

RESULTS AND DISCUSSION The guest-free crystals of 4 were obtained as colorless block crystals in the orthorhombic space group Pbca, while the asymmetrical unit comprised one thiacalixarene molecule (Figure 2(a)). Symmetry expansion of the crystal structure revealed a layer-assembled supramolecular structure formed mainly from Br-π and CH-π interactions, with additional interactions between layers. The A aromatic π electrons and the neighboring A methyl moiety of the methoxy group were included in the groove of the base molecule, as the 1,3-alternate conformation induced layer-formation through Br-π and CH-π interactions along the [101] plane (Figure 2(b)). Specifically, the Br-π interaction was observed between the C bromo group and the neighboring A aromatic π electrons. The Br(3)···C(1)a distance and C(13)-Br(3)-C(1)a angle are 3.487(4) Å and 145.1(1)°, respectively, making the sum of the van der

Waals radii about 1.8% shorter than they would be separately. The Br-π interaction results in a polarized Brδ+ region directed toward the center of a πδ– region. Specifically, the C(25)a-H(25A)a···π (C(1)) distance is 2.702 Å. The Br-O distance is particularly short, with a value of 3.321(2) Å; however, this likely is not attributed to halogen interactions given the outlying defined C(1)-Br(1)-O(1)a angle of 87.8(1)° and Brδ-···Oδ– electrostatic repulsion, thus suggesting the influence of crystal packing and preferential CH–π interactions. In addition, two Br–H interactions were observed in a neighboring molecule along the [101] plane, with C(1)-Br(1) ···H(27C)b and C(7)-Br(2)···H(27B)b distances of 3.016 Å and 3.029 Å, respectively (Figure S2). Two CH–π interactions were also accounted for in the [110] plane (Figure S3); these occur between the B and D aromatic rings in the base thiacalixarene and the hydrogen atoms of methyl groups B and D on the two adjacent thiacalixarene molecules, with bond lengths of 2.610 and 2.668 Å, respectively.



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Figure 3. (a) Stick diagram and space-filling representation of 5. (b) Stick diagram showing Br···π interactions (pink dotted lines) a and Br···H interactions (light blue dotted lines) in the crystal structure of 5. Symmetry operation: 1−x, 1−y, −z. Br = brown, S = yellow, O = red, C = dark gray, H = light gray. (c) Ab initio calculations showing the electrostatic potential surfaces of the molecular (upper) and the dimeric unit (lower) of 5. Electron deficient regions are shown in blue, with electron density increasing −1 from green to yellow to red. The potential energies are presented only in the −100.0000 to +100.0000 kJ mol range to emphasize the variation in electrostatic potential associated with the bromine atoms and aromatic rings.

We further investigated the Br–π interaction in 4 using a computational approach. The electrostatic potential surfaces of both a single-molecule unit and a two-molecule unit were calculated by DFT (B3LYP/6-31G(*) level) using Spartan 14, based on the obtained X-ray structure (Figure 2(c)).56 The single-molecule simulation showed both electron-rich and electron-deficient regions for the bromine atoms and an electron-rich π surface for arene A. Meanwhile, the dimer simulation showed that the electrondeficient region of the horizontal aromatic bromine atom in the base thiacalixarene interacted with the electronrich aromatic moiety of the adjacent molecule. Guest-free crystals of 5 were obtained as colorless block crystals in the triclinic space group P21/c, yielding the partial-cone conformer. The asymmetric unit was composed of one thiacalixarene molecule, with no observed solvent incorporation (Figure 3(a)). The adjacent A and C aromatic rings are flipped slightly inward, with Br(1)– O(1)–O(3) and Br(3)–O(3)–O(1) angles of 80.95(7) and85.97(8)°, respectively, whereas the B aromatic ring is flipped considerably outward, with a Br(2)–O(2)–C(23)

angle of 145.3(1)°. Meanwhile, arene D is turned to the opposite side of the other rings. These various orientations allow for a short Br–π and two Br–H interactions to contribute to the formation of the self-assembled dimer (Figure 3(b)). The Br(1)···π (between C(8)a-C(9)a) bond distance and angle are 3.344 Å and 162.58°, respectively, compared to the 3.550 Å sum of the respective atomic radii, while the Br(1)···H(13)a and Br(3)···H(3)a bond distances are 3.047 and 2.886 Å, respectively. Overall, this polarization-induced Br–π interaction results in a 5.8% decrease in length. Furthermore, symmetric expansion of the crystal structure reveals S–π and S–H hydrogen bonding interactions between dimeric units (Figure S4). According to a report by Mak and colleagues,57 S–π interactions can be categorized into three types based on the bond angles and distances; in this case, the interactions can be classified as Type II because the sulfur atoms are located on the edges of the aromatic rings (Figure S5). The r distance from S to arene C, the nearest ring, is 4.026 Å, while the d distance from S to the nearest edge of arene C is 3.361 Å; this value is 4.0% shorter than it would be if


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Figure 4. (a) Stick diagram and space-filling representation 8. (b) Stick diagram showing Br···S halogen bonding (pink dotted a lines) in the crystal structure of 8. Symmetry operation: −1−x, −y, −z. Br = brown, S = yellow, O = red, C = dark gray, H = light gray. (c) Ab initio calculations showing the electrostatic potential surfaces of the molecular (upper) and the dimeric unit (lower) of 8. Electron deficient regions are shown in blue, with electron density increasing from green to yellow to red. The potential −1 energies are presented only in the −100.0000 to +100.0000 kJ mol range to emphasize the variation in electrostatic potential associated with the bromine and sulfur atoms.

no interaction were present. Meanwhile, the corresponding angles are 71.38 (α) and 167.31° (α´), respectively, while the S···π–edge carbon atom φ angle is 40.09°. S–H hydrogen bonding was also evident between the sulfur thiacalixarene base and the methyl moieties of the ethoxy groups of neighboring molecules, with a S(2)···H(32A)c distance of 2.882 Å. Two weak Br–π interactions are observed in the extended structure of both 4 and 5. Even though changing alkyl chain length at the lower rim does not prevent these weak interactions, it does seem to influence their relative strengths due to steric interference; this in turn contributes to the differences in conformation. However, previous reports show that significantly longer alkyl chains, as with the butyl groups present in 1, prevent Br–π interaction by fully blocking the approach of bromine to the aromatic π electrons. Furthermore, we have already demonstrated that crystals of 5,11,17,23tetrabromo-25,26,27,28-tetrapropoxythiacalix[4]arenes incorporating cyclohexane guest molecules constructed channel-type supramolecular assemblies via conventional non-covalent interactions without relying on halogen interactions at all.58 These realizations are overall con-

sistent with the current crystallographic analysis, which seem to suggest that alkyl chain length is a significant factor in the formation of halogen–π and halogen– halogen interactions within the crystal structure. A computational approach was also utilized to study the Br–π interactions of 5 (Figure 3(c)); as expected, the results were identical to those for 4. Guest-free crystals of 6 were obtained as colorless block crystals in the monoclinic space group C2/c. Half of a thiacalixarene molecule comprises the asymmetric unit in this case, with 6 existing as the 1,3-alternate conformer (Figure S6). Unlike the shorter chains in 4 and 5, the pentyl moieties at the lower rims of 6 force a column-like arrangement that precludes non-covalent interactions, allowing only Br-H interactions between the packed structures. Symmetry expansion of the crystal structure revealed that weak Br-H interactions connect the columns when viewed along the [011] plane (Figure S7). The Br(2) ···H(6)a distance in the crystals is 3.035 Å. Guest-free crystals of 7 were colorless block crystals in the triclinic space group P21/n, where the asymmetric unit



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Figure 5. (a) Stick diagram and space-filling representation of 9. (b) Stick diagram showing Br···S halogen bonding (pink dotted a lines) in the crystal structure of 9. Symmetry operations: −x, 1−y, 1−z. Disordered moieties have been removed for clarity. Br = brown, S = yellow, O = red, C = dark gray, H = light gray. (c) Ab initio calculations showing the electrostatic potential surfaces of the molecular (upper) and the dimeric unit (lower) of 9. Electron deficient regions are shown in blue, with electron density in−1 creasing from green to yellow to red. The potential energies are presented only in the −100.0000 to +100.0000 kJ mol range to emphasize the variation in electrostatic potential associated with the bromine and sulfur atoms.

was composed of one thiacalixarene molecule stabilized in a 1,3-alternate conformation (Figure S8). The D aromatic ring is flipped slightly inward, with a Br(4)–O(4)– O(2) bond angle of 87.66(5)°, whereas the neighboring A, B, and C aromatic rings are flipped slightly outward, with Br(1)–O(1)–O(3), Br(2)–O(2)–O(4), and Br(3)–O(3)–O(1) angles of 95.17(4)°, 103.57(5)°, and 102.19(5)°, respectively. Meanwhile, the hexyl moieties of arenes A and D are found within the molecule, while those of arenes B and C protrude outward. Like 6, no halogen interactions are observed; however, other intermolecular interactions are present. Interestingly, despite the skewed structure, 7 forms an assembly in its extended structure. While this structure superficially appears similar to 6, the base hexyl groups are surprisingly preferred as bromine donors over neighboring hexyl groups in the [011] plane (Figure S9). Note that the hexyl moiety of arene B does not participate in these interactions. The assembly is also supported by SH hydrogen bonding between the linking sulfur of the molecule base and the terminal methyl moiety of the hexyl group projecting from the arene A unit, adjacent along the [110] plane; the resulting S(2)···H(30C)b distance is

2.876 Å. Additionally, Br-H interactions are observed in same plane, with the bromine atom of arene D interacting with a methylene moiety in the hexyl group projecting from arene A; of the resulting Br(4)b···H(27B) distance is 3.0249 Å. CH-π interactions were retained between aromatic ring A and the neighboring methylene moiety of arene A along the [101] plane, yielding a C(25)H(H25B)···C(18)c distance of 2.825 Å (Figure S10). Guest-free crystals of 8 were colorless block crystals in the triclinic space group P-1, with the asymmetric unit consisting of one thiacalixarene molecule. 8 adopts a 1,3alternate conformation (Figure 4(a)). Both the aromatic rings and the heptyl moieties of arenes B and C are flipped slightly outward, whereas the heptyl groups of arenes A and D project slightly inward. Meanwhile, 8 demonstrates Br–S interactions because the longer alkylchain blocks bromine from interacting with other halogens or aromatic rings; this distinguishes it from 6 and 7, which showed only hydrogen bonding, Br–H, and CH–π interactions. Overall, alkyl chain length seems to play a central role in determining which halogen interactions take place. Symmetric expansion of 8 reveals that the


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Figure 6. (a) Stick diagram and space-filling representation of 10. (b) Stick diagram showing Br···S halogen bonding (pink dotted e lines) in the crystal structure of 10. Symmetry operations: 1−x, 2−y, 2−z. Br = brown, S = yellow, O = red, C = dark gray, H = light gray. (c) Ab initio calculations showing the electrostatic potential surfaces of the molecular (upper) and the dimeric unit (lower) of 10. Electron deficient regions are shown in blue, with electron density increasing from green to yellow to red. The potential −1 energies are presented only in the −100.0000 to +100.0000 kJ mol range to emphasize the variation in electrostatic potential associated with the bromine and sulfur atoms.

linking sulfur atoms of arene B interact with the base bromine atoms on arene B of the adjacent molecule (Figure 4(b)). The Br(2)···S(2)a distance and C(7)-Br(2)···S(2)a angle are 3.564(2) Å and 111.8(3)°, respectively; overall, the distance between the nuclei is 2.5% shorter than the sum of the standard radii. This is a weaker interaction than is typical, suggesting steric interference from the heptyl moieties. The 8 can be classified as lone pair–possessing species in Lewis acid–base pairs. The architecture of 8 was formed from pillar-like arrangements, with Br–H interactions contributing substantially within each crystal (Figure S11); the Br(1)···H(H31C)b distance was found to be 2.899 Å. Br–S and Br–H interactions are also observed along the [011] plane between each column (Figure S12). Two Br–H interactions are present, with the first taking place between Br(1) of arene A and H(46B)c of arene D of the adjacent molecule, and the second being observed between Br(4) of arene D and H(26A)d of arene A of the adjacent molecule; distances are 2.964 and 2.981 Å, respectively (Figure S12). Increasing alkyl chain length allows for CH–π interactions as well (Figures S13). Stabilizing edge-to-face CH–π interactions are also observed

along the [110] plane, with a C(2)-H(2)···C(14)e distance of 2.86 Å. Computation was used to further investigate the Br···S interactions (Figure 4(c)). Bromine atoms served as the electrophilic species, while sulfur donated electron density from the free lone pairs to form Lewis acid–base pairs. As such, the angle between bromine and the sulfur lone pairs is important in determining the strength of the interaction; in this case, the observed C-Br-S angle of 111.8(3)° is outside of the range of 140-180° typically ascribed to halogen bonding due to steric interference. This explains the weaker interaction previously observed. Guest-free crystals of 9 were colorless prism crystals in the triclinic space group P-1; in this case, the asymmetric unit consisted of one thiacalixarene molecule. Compound 9 adopts a 1,3-alternate conformation, which includes one disordered octyl group and one disordered octoxy group appended to arenes C and D, respectively (Figure 5(a)). The molecular structure of 9 is similar to that of 8, but the assembly is somewhat different. Each aromatic ring is flipped slightly outward due to steric concerns, whereas the octyl moieties of arenes B and C are flipped slightly



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Figure 7. (a) Stick diagram and space-filling representation of 11. (b) Stick diagram showing Br···S halogen bonding (pink dotted c lines) in the crystal structure of 11. Symmetry operations: 1−x, 1−y, 1−z. Br = brown, S = yellow, O = red, C = dark gray, H = light gray. (c) Ab initio calculations showing the electrostatic potential surfaces of the molecular (upper) and the dimeric unit (lower) of 11. Electron deficient regions are shown in blue, with electron density increasing from green to yellow to red. The potential −1 energies are presented only in the −100.0000 to +100.0000 kJ mol range to emphasize the variation in electrostatic potential associated with the bromine and sulfur atoms.

inward and those of arenes A and D are flipped slightly outward. Symmetric expansion of 9 revealed Br–S interactions between arene D moieties along the [011] plane (Figure 5(b)). The Br(4)···S(3)a distance and the C(22)Br(4)···S(3)a angle are 3.635(2) Å and 105.3(2)°; the 0.4% decrease in distance when compared to the potential value for no interaction indicates only very weak interactions, especially when compared to those observed in 8. The assembly is also stabilized through S–H, Br–S, and Br–H interactions along the [011] plane (Figure S14). The S(2) atom in arene B interacted with the disordered H(48A)c methylene group in arene C of the adjacent molecule, yielding a distance of 2.813 Å. Similarly, a Br–H interaction was present between the Br(2) atom in arene A and the disordered H(44B)c methyl group in arene D in the neighboring molecule, with an observed distance of 2.921 Å. An edge-to-face CH-π interaction was also observed between adjacent thiacalixarene molecules along the [110] plane (Figure S15), with a C(17)-H(17)···C(5)d distance of 2.857 Å.

Computational methods were again applied to study Br···S bonding (Figure 5(c)). Overall, the polarity of the interactions between bromine and sulfur atoms were comparable to those observed for 8, with the angle again playing a major role; in fact, the observed angle of 105.3(2)° is even more pronounced than in the previous sample, in turn leading to an even weaker interaction. Guest-free crystals of 10 were colorless prisms, which crystallized in the triclinic space group P-1. A single thiacalixarene molecule comprised the asymmetric unit, adopting the 1,3-alternate conformation and exhibiting a disordered nonyl group on arene D (Figure 6(a)). The B, C, and D aromatic rings were flipped slightly inward, with Br(2)–O(3)–O(4), Br(3)–O(3)–O(1), and Br(4)–O(4)–O(2) angles of 99.24(5)°, 105.77(6)°, and 112.16(6)°, respectively, whereas the A aromatic ring was flipped slightly outward, with a Br(1)–O(1)–O(4) angle of 119.25(6)°. The orientations of adjacent A arene moieties in the extended crystal structure seem to increase the potential for Br–S interactions. The pendant nonyl moieties have a slightly different effect, however, distinguishing 10 from 6-9. Specifical-


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ly, the groups on arenes A and C do not show a specific orientation, whereas those on arenes B and D orient themselves inward and outward, with Br(2)–O(2)–C(42) and Br(4)–O(4)–C(60) angles of 154.21° and 231.62°, respectively. This results in a “wavy” assembly, stabilized by S–π and Br–H interactions (Figure S16). Note that the S–π interaction here can be classified as Type II (Figure S17).57 The r distance from S to the nearest aromatic ring center of arene B is 3.608 Å, while the d distance from S to the nearest ring-edge carbon atom of arene B (between C(8)a and C(9)a) is 3.332 Å; this accounts for a distance that is 4.8% shorter than the sum of the ideal, non-interacting radii. In addition, the C–S–π (arene B) angles are 106.79° (α) and 146.84° (α´), respectively, while the S–π–edge (arene B) φ angle is 67.22°. Interestingly, the bromine atoms of arenes B, C, and D all participated in Br–H interactions (Figure S16). The bromine on arene B interacted with the methyl group of arene A of the neighboring molecule, giving a Br(2)···H(33A)b distance of 3.076 Å. Meanwhile, the bromine atom on arene C interacts with the methyl groups of both arenes B and D of the adjacent molecule, with Br(3)···H(42A)c and Br(3)···H(60C)c distances of 2.774 and 3.027 Å, respectively. Finally, the bromine atom on arene D interacts with the methyl group on arene A of the adjacent molecule, yielding a Br(4)···H(33A)d distance of 3.008 Å. Meanwhile, Br–S halogen bonding exists between neighboring arene A moieties in the larger structure (Figure 6(b)); the Br(1)···S(2)e distance and C(2)-Br(1)···S(2)e angle are 3.550(1) Å and 116.5(1)°, respectively, yielding a 2.7% decrease when compared to two non-interacting species. Note that this decrease is much larger than it was for 9, indicating a much stronger interaction. Finally, in addition to the other interactions, the bromine atom of arene B interacted with the nonyl group of arene C in the adjacent molecule, yielding a Br(2)···H(43)f distance of 2.940 Å (Figure S18). An S–H hydrogen bond is also observed between the bridging sulfur atom and the adjacent aromatic hydrogen atom on arene A, giving a S(1)···H(6)g distance of 2.927 Å. As with the other crystals, Br–S halogen bonding in 10 was studied using a computational model (Figure 6(c)). Again, polarization of the Br–S interaction within and between molecules was effectively identical to both 8 and 9. Guest-free crystals of 11 were colorless prism crystals in the triclinic space group P-1, in which a thiacalixarene molecule comprised the asymmetric unit (Figure 7(a)). 11 adopted a 1,3-alternate conformation, which included the disordered decyl moiety of arene D. Interestingly, the supramolecular assembly is constructed along the same motif as 10; the B, C, and D aromatic rings flip slightly inward, with Br(2)–O(3)–O(4), Br(3)–O(3)–O(1), and Br(4)–O(4)–O(2) angles of 100.74(5)°, 105.57(6)°, and 109.88(5)°, respectively, whereas the A aromatic ring flips slightly outward, with a Br(1)–O(1)–O(4) angle of 114.74(6)°. Accordingly, this structure favors Br–S interactions; the outward orientation of arene A places this portion of each molecule in close proximity to the other within the crystal structure. The orientation of the decyl

groups was identical to that of the nonyl groups in 10; constituents of arenes A and C showed no consistent orientation, whereas those of arenes B and D were oriented inward and outward, with Br(2)–O(2)–C(44) and Br(4)– O(4)–C(64) angles of 159.59 and 231.29°, respectively. Also, 11 adopts a “wavy” assembly (Figure S19), with Type II S–π interactions between adjacent molecules of both arenes B and D (Figure S20).57 The r distance from S to the center of arene B, the nearest aromatic ring, is 3.631 Å, while the d distance from S to the corresponding ring edge (between C(11)a and C(12)a) is 3.405 Å; this corresponds to a 2.7% decrease in the total expected nuclear radii. The C– S–π (arene B) angles are 102.62° (α) and 150.81° (α´), respectively, while the S–π–edge (arene B) φ angle is 69.65°. As before, increased alkyl chain length seems to limit Br– H interactions between adjacent molecules. Only one interaction was observed, occurring between Br(3) and H(63A)b, on arene D, of adjacent molecules; the corresponding distance was 3.015 Å. Three intermolecular interactions were observed between adjacent molecules along the [011] plane (Figure S21). First, Br–S interactions were present between arene A moieties, with a Br(1)···S(2)c distance and C(2)-Br(1)-S(2)c angle of 3.548(1) Å and 118.8(1)°, respectively, (Figure 7(b)); this accounts for a 2.8% decrease. The bromine atom of arene C and decyl group of arene A also interact, with a Br(3)···H(31B)d distance of 3.043 Å. Notably, arene C decyl groups in the same molecule were favored as bromine donors over the arene B decyl groups of the adjoining one. Unsurprisingly, the computational analysis of 11 (Figure 7(c)) provided effectively identical results as obtained for 8, 9, and 10.

CONCLUSIONS We have demonstrated the presence of intermolecular interactions involving halogen atoms through crystallographic and computational approaches in eight tetrabromothiacalix[4]arene derivatives. Changes in alkyl chain length and the resulting steric congestion led to two types of halogen interaction motifs. Specifically, weak Br–π interactions were observed in 4 and 5, with a 2.8 and 5.8% decrease in distance between the nuclei when compared to the sum of the respective radii. In addition, Br–S halogen bonding was observed in 8-11, with reductions in distance of 2.5, 0.4, 2.7, and 2.8%, respectively. Notably, 6 and 7 showed neither of the aforementioned interactions. Overall, these data, combined with the results of our previous report, seem to suggest that shorter alkyl groups, such as those in 4 and 5, lead to Br–π interactions, medium-length alkyl chains, such as those in 1, yield Br–Br interactions, and longer alkyl groups, such as those in 811, prefer Br–S interactions. These interactions are clearly dependent on the proximity of the sulfur atoms to the aromatic moieties – again, this is directly influenced by the steric congestion of the alkyl chains. Note that 6 and 7 do not follow this pattern. The structural properties of thiacalixarene derivatives are known to have a profound effect on their supramolecular assembly; as such, the hal-



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ogen-based intermolecular interactions observed in this study, which are particularly rare in solely macrocyclic compounds, can contribute to improved material design.

ASSOCIATED CONTENT Supporting Information 1 Synthetic procedures, and spectral characterization data ( H, 13 C NMR, IR, and elemental analysis), and X-ray data (CCDC 1004092- 1004099) for 4-11, atomic numbering, DFT calculations, and supporting figures. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author Tel +81 18 889 3068; fax: +81 18 889 3068 [email protected] Tel +81 18 889 2440; fax: +81 18 889 2440 [email protected]

Notes The authors declare no competing financial interests.

ACKNOWLEDGMENT This work was supported by “Program to Disseminate Tenure Tracking System” of Japan. We thank Dr. Hiroshi Katagiri (Graduate School of Science and Engineering, Yamagata University, Japan) and Mr. Noritaka Uchida (Wavefunction, Inc.; Japan Branch Office) for their valuable discussions and technical support on single-crystal Xray diffraction studies and quantum chemical calculations.

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“For Table of Contents Use Only” Halogen Interactions in Macrocyclic Thiacalix[4]arene Systems Manabu Yamada* and Fumio Hamada*

ABSTRACT: The crystalline supramolecular assemblies of brominated thiacalix[4]arene alkyl ethers were studied by single-crystal X-ray diffraction and computational analysis. Eight compounds were synthesized that exhibited linear alkyl groups of varying lengths projecting from the thiacalixarene lower rims (-CH3: 4, -CH2CH3: 5, (CH2)4CH3) - -(CH2)9CH3): 6-11) in order to study the intermolecular halogen interactions between the macrocycles. These crystals displayed remarkably different assemblies, which was rationalized as an effect of varying alkyl chain length on the stabilization afforded by the halogen interactions. The two compounds with the shortest alkyl chains, 4 and 5, assembled primarily through the influence of halogen–π interactions between distinct molecules. In contrast, the compounds with the longest chains, 8-11, assembled primarily through the influence of halogen-sulfur halogen bonding. Oddly, 6 and 7 did not follow this pattern in that they showed no major assembly motivated by halogen interactions. Finally, the supramolecular assemblies were found to be stabilized by additional intermolecular interactions, including hydrogen bonding, S-π, CH-π, and Br‒H interactions.

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Halogen Interactions in Macrocyclic Thiacalix[4]arene Systems

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