1,4-Dibromo-2,5-bis(phenylalkoxy)benzene Derivatives: C–Br... π (arene) versus C–H...Br and Br...Br Interactions in the Solid State

: We have prepared and characterized 1,4-dibromo-2,5-bis(2-phenylethoxy)benzene ( 1 ) and 1,4-dibromo-2,5-bis(3-phenylpropoxy)benzene ( 2 ). Their single-crystal structures conﬁrm that, at the molecular level, they are similar with the phenylalkoxy chains in extended conformations. However, there are signiﬁcant differences in packing interactions. The packing in 1 is dominated by C–Br... π (arene) interactions, with each Br located over one C–C bond of the central arene ring of an adjacent molecule. In contrast, the packing of molecules of 2 involves a combination of C–H...Br hydrogen bonds, Br...Br interactions, and arene–arene π -stacking. The single-crystal structures of both orthorhombic and triclinic polymorphs of 1 have been determined and the packing interactions are shown to be essentially identical.


Introduction
In 2013, the IUPAC provided the following definition of a halogen bond [1]: "A halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity". Despite this definition, the nature of the halogen bond and the scope of close contacts that fall under this umbrella remain a subject of debate, and the IUPAC definition has been termed "elusive" in a recent review by Meyer and coworkers [2]. The relatively recent recognition of halogen bonding as an important supramolecular interaction in crystal engineering has spawned numerous reviews and data-mining overviews in the past few years [3][4][5][6][7][8][9][10]. Of particular note are discussions which demonstrate the distinction between a halogen bond and a halogen...halogen interaction [11,12]. When a halogen atom X forms a covalent bond, e.g., a C-X bond, the resulting electron distribution is such that atom X possesses an 'electrophilic cap' (also referred to as a 'σ-hole') located zenithal to the C-X covalent bond. This electron-poor region complements the electron-rich 'belt' around atom X, allowing X to act as either an electron acceptor or donor, respectively. The 'halogen bond' encompasses interactions in which the covalently bound halogen atom acts as an electrophile towards a heteroatom such as N, O, or S. In addition to halogen bonds, solid-state structures may exhibit close (≤the sum of the van der Waals radii) contacts between halogen atoms. Such interactions typically involve Cl, Br and I atoms and may be classified as type I or type II interactions as depicted in Scheme 1 [13]. Interactions are not confined to homonuclear interactions, although analysis of entries in the Cambridge Structural Database (CSD) reveal that Cl...Cl and Br...Br are the most common halogen...halogen contacts [11,13]. Analyses of scatter plots of angles θ 1 against θ 2 (defined in Scheme 1) by Desiraju and coworkers have illustrated that there is a clear distinction between type I and II interactions for I...I contacts. However, this becomes less well defined for Br...Br contacts, As well as encompassing hydrogen bonds, halogen bonds and halogen...halogen short contacts, supramolecular interactions involving halogen atoms also include halogen...π contacts. The role of C-I...π interactions in molecular crystals has recently been surveyed in detail by Tiekink [14]. The criteria used to define a 'delocalized C-I...π(arene)' contact were that the angle α (defined in Scheme 2a) was between 160° and 180°, and that the ring-centroid....I separation was ≤3.88 Å. This limit derives from the van der Waals radius of I (1.98 Å [15]) and half of the upper limit of an arene...arene π-stacking distance (half of ≈ 3.8 Å [16]). In addition to this 'delocalized' C-X...π(arene) interaction (X = any halogen), classifications of 'localized' and 'semi-localized' contacts have been introduced which place an emphasis on C...X separations (Scheme 2b) [17,18] rather than ring-centroid...X. The semi-localized and localized, rather than delocalized, interactions dominate in crystal packing. Significantly, C-X...π(arene) interactions with X = F are as numerous as those with X = Cl, Br and I [19,20]. Scheme 2. (a) Tiekink's [14] criteria for identifying a C-X...π(arene) interaction: 160° ≤ α ≤ 180°, and the ring-centroid....X distance is 3.88 Å. (b) Classification of localized and semi-localized C-X...π(arene) interactions; for the semi-localized interaction, d1(C-X) is close in value to d2(C-X) [17,18].
As well as encompassing hydrogen bonds, halogen bonds and halogen...halogen short contacts, supramolecular interactions involving halogen atoms also include halogen...π contacts. The role of C-I...π interactions in molecular crystals has recently been surveyed in detail by Tiekink [14]. The criteria used to define a 'delocalized C-I...π(arene)' contact were that the angle α (defined in Scheme 2a) was between 160 • and 180 • , and that the ring-centroid....I separation was ≤3.88 Å. This limit derives from the van der Waals radius of I (1.98 Å [15]) and half of the upper limit of an arene...arene π-stacking distance (half of ≈ 3.8 Å [16]). In addition to this 'delocalized' C-X...π(arene) interaction (X = any halogen), classifications of 'localized' and 'semi-localized' contacts have been introduced which place an emphasis on C...X separations (Scheme 2b) [17,18] rather than ring-centroid...X. The semi-localized and localized, rather than delocalized, interactions dominate in crystal packing. Significantly, C-X...π(arene) interactions with X = F are as numerous as those with X = Cl, Br and I [19,20]. illustrated that there is a clear distinction between type I and II interactions for I...I contacts. However, this becomes less well defined for Br...Br contacts, and even less so for Cl...Cl contacts [13]. Spilfogel et al. have similarly analysed plots of θ1 against θ2, and (with a restricted set of halogenated porphyrins) also demonstrated the difficulties in unambiguously assigning the structure type [11].
As well as encompassing hydrogen bonds, halogen bonds and halogen...halogen short contacts, supramolecular interactions involving halogen atoms also include halogen...π contacts. The role of C-I...π interactions in molecular crystals has recently been surveyed in detail by Tiekink [14]. The criteria used to define a 'delocalized C-I...π(arene)' contact were that the angle α (defined in Scheme 2a) was between 160° and 180°, and that the ring-centroid....I separation was ≤3.88 Å. This limit derives from the van der Waals radius of I (1.98 Å [15]) and half of the upper limit of an arene...arene π-stacking distance (half of ≈ 3.8 Å [16]). In addition to this 'delocalized' C-X...π(arene) interaction (X = any halogen), classifications of 'localized' and 'semi-localized' contacts have been introduced which place an emphasis on C...X separations (Scheme 2b) [17,18] rather than ring-centroid...X. The semi-localized and localized, rather than delocalized, interactions dominate in crystal packing. Significantly, C-X...π(arene) interactions with X = F are as numerous as those with X = Cl, Br and I [19,20].

1,4-Dibromo-2,5-bis(2-phenylethoxy)benzene, 1
Dry DMF (40 mL) was added to a mixture of anhydrous K 2 CO 3 (3.61 g, 26.1 mmol), 2,5-dibromobenzene-1,4-diol (2.00 g, 7.47 mmol) and (2-bromoethyl)benzene (3.66 mL, 26.1 mmol). The solution was stirred and heated to 100 • C under a nitrogen atmosphere for 22 h. The mixture was cooled to room temperature, poured onto ice water (200 mL) and stirred for 20 min. The resulting suspension was extracted with CHCl 3 (3 × 100 mL), dried with MgSO 4 and concentrated in vacuo. The red-brown solid was recrystallized from a hot mixture of MeOH and CHCl 3 (cooled down to room temperature). The filtrate was reduced to half its original volume, and then cooled to 5 • C to yield a second crop of crystalline product. Off-white crystals were isolated by filtration, washed with MeOH and then dried in vacuo for 2 days (2.  Dry DMF (40 mL) was added to a mixture of anhydrous K 2 CO 3 (3.61 g, 26.1 mmol), 2,5-dibromobenzene-1,4-diol (2.00 g, 7.47 mmol) and (3-bromopropyl)benzene (3.97 mL, 26.1 mmol). The yellow-brown suspension was stirred and heated to 100 • C under a nitrogen atmosphere for 22 h. The pale yellow mixture was cooled to room temperature, poured onto ice water (200 mL), and stirred for 20 min. The resulting suspension was extracted with CH 2 Cl 2 (3 × 100 mL), dried with MgSO 4 and concentrated in vacuo. The ochre solid was recrystallized from a hot mixture of MeOH and CHCl 3 which was cooled down to room temperature. Colorless crystals were isolated by filtration, washed with MeOH, and then dried in vacuo overnight

Crystallography
Single crystal data for 1 (polymorph I) and 2 were collected on a STOE StadiVari diffractometer equipped with a Pilatus300K detector with a Metaljet D2 source (GaKα radiation), the structures were solved using Superflip [22,23] and Olex2 [24], and the model was refined with ShelXL v. 2014/7 [25]. Single-crystal data for 1 (polymorph II) were collected using a Bruker APEX-II diffractometer (CuKα radiation) with data reduction, solution, and refinement using the programs APEX [26], ShelXT [27], Olex2 [24], and ShelXL v. 2014/7 [25]. All H atoms were included at geometrically calculated positions and refined using a riding model with U iso = 1.2 of the parent atom. Structure analysis used CSD Mercury 2020.1 [28]. Powder X-ray diffraction (PXRD) patterns were collected at~295 K in transmission mode on a Stoe Stadi P diffractometer with Cu Kα1 radiation (Ge(111) monochromator) and a DECTRIS MYTHEN 1K detector. Profile matching analysis [29][30][31] of the diffraction patterns was carried out using the program FULLPROF SUITE (version July 2019) [31,32] with an instrument resolution function based on a NIST640d standard that had previously been determined. The structural models were based on the single-crystal X-ray diffraction refinements. Refined parameters in Rietveld were: scale factor, zero shift, lattice parameters, and halogen atomic positions, background points and peaks shapes as a Thompson-Cox-Hastings pseudo-Voigt function. Preferred orientations as a March-Dollase multi-axial phenomenological model were included in the analysis.

Synthesis and Characterization
Compounds 1 and 2 were prepared by the route shown in Scheme 3 which we have previously used for the synthesis of related 1,4-dibromo-2,5-bis(alkyloxy)benzene derivatives [33]. We find this strategy more convenient than the general methodology described by Neil and coworkers [34]. The base peaks in the high-resolution electrospray mass spectra (Figures S1 and S2 in the Supporting Material) arose from the [M + Na] + ions at m/z = 498.9699 for 1, and m/z = 527.0017 for 2, and showed the characteristic dibromine isotope pattern. The 1 H and 13 C{ 1 H} NMR spectra were assigned using NOESY, COSY, HMBC and HMQC spectra and were in accord with the structures displayed in Scheme 3. Figures S3-S8 show the 1 H NMR, HMQC and HMBC spectra. The compounds were further characterized by FT-IR spectroscopy (Figures S9 and S10) and by solution absorption spectroscopy. The absorption spectra of 1 and 2 are similar ( Figure 1), with bands at λ max 210, 232, and 300 (for 1) or 302 (for 2) nm arising from π*←π and π*←n transitions. and refined using a riding model with Uiso = 1.2 of the parent atom. Structure analysis used CSD Mercury 2020.1 [28].
1 (polymorph I): C22H20Br2O2 Mr = 476.20, colorless block, triclinic, space group P-1, a = 8.2806 (13) Powder X-ray diffraction (PXRD) patterns were collected at ~295 K in transmission mode on a Stoe Stadi P diffractometer with Cu Kα1 radiation (Ge(111) monochromator) and a DECTRIS MYTHEN 1K detector. Profile matching analysis [29][30][31] of the diffraction patterns was carried out using the program FULLPROF SUITE (version July 2019) [31,32] with an instrument resolution function based on a NIST640d standard that had previously been determined. The structural models were based on the single-crystal X-ray diffraction refinements. Refined parameters in Rietveld were: scale factor, zero shift, lattice parameters, and halogen atomic positions, background points and peaks shapes as a Thompson-Cox-Hastings pseudo-Voigt function. Preferred orientations as a March-Dollase multi-axial phenomenological model were included in the analysis.

Synthesis and Characterization
Compounds 1 and 2 were prepared by the route shown in Scheme 3 which we have previously used for the synthesis of related 1,4-dibromo-2,5-bis(alkyloxy)benzene derivatives [33]. We find this strategy more convenient than the general methodology described by Neil and coworkers [34]. The base peaks in the high-resolution electrospray mass spectra (Figures S1 and S2 in the Supporting Material) arose from the [M + Na] + ions at m/z = 498.9699 for 1, and m/z = 527.0017 for 2, and showed the characteristic dibromine isotope pattern. The 1 H and 13 C{ 1 H} NMR spectra were assigned using NOESY, COSY, HMBC and HMQC spectra and were in accord with the structures displayed in Scheme 3. Figures S3-S8 show the 1 H NMR, HMQC and HMBC spectra. The compounds were further characterized by FT-IR spectroscopy (Figures S9 and S10) and by solution absorption spectroscopy. The absorption spectra of 1 and 2 are similar (Figure 1), with bands at λmax 210, 232, and 300 (for 1) or 302 (for 2) nm arising from π*←π and π*←n transitions.

Single Crystal Structures of 1 (Polymorph I) and 2
Single crystals of 1 (polymorph I) and 2 were grown from hot solutions of the compounds in a mixture of MeOH and CHCl3 which was allowed to cool to room temperature. Both compounds crystallize in the triclinic space group P-1. The asymmetric unit for 1 (polymorph I) contains four crystallographically independent half-molecules, the second half of each being related to the first by inversion (Wyckoff sites d, b, c, and h for the molecules containing Br1, Br2, Br3, and Br4, respectively). The four molecules are conformationally and dimensionally similar (Figures S11 and S12) and we therefore focus on the bond parameters (Table 1) in the molecule containing atom Br1 (Figure 2a). The asymmetric unit of 2 contains one molecule and one half-molecule which are crystallographically independent. One 3-phenylpropoxy chain in the molecule containing atoms Br1 and Br2 is disordered and has been modelled over two sites of equal occupancies. The disorder affects the propoxy chain and the disordered terminal phenyl rings lie in planes differing by 16.0°, and twisted with respect to one another, as shown in Figure S13. Anisotropic behavior of the C10-C15 ring also indicates some slight disorder but this could not be modelled. Figure 2b illustrates the structures of the two independent molecules of 2. In both 1 and 2, the phenylalkoxy chains are in extended conformations. The Carene-O-Calkyl bond angles in 1 (polymorph I) and 2, and the shorter Carene-O compared to Calkyl-O bond lengths (Table 1) are indicative of sp 2 hybridized O atoms and π-conjugation extending from the arene ring to the O atoms. In all independent molecules of 1 (polymorph I) and 2, the alkyloxy substituent adopts the same conformation relative to the central arene ring (Figure 2).

Single Crystal Structures of 1 (Polymorph I) and 2
Single crystals of 1 (polymorph I) and 2 were grown from hot solutions of the compounds in a mixture of MeOH and CHCl 3 which was allowed to cool to room temperature. Both compounds crystallize in the triclinic space group P-1. The asymmetric unit for 1 (polymorph I) contains four crystallographically independent half-molecules, the second half of each being related to the first by inversion (Wyckoff sites d, b, c, and h for the molecules containing Br1, Br2, Br3, and Br4, respectively). The four molecules are conformationally and dimensionally similar (Figures S11 and S12) and we therefore focus on the bond parameters (Table 1) in the molecule containing atom Br1 (Figure 2a). The asymmetric unit of 2 contains one molecule and one half-molecule which are crystallographically independent. One 3-phenylpropoxy chain in the molecule containing atoms Br1 and Br2 is disordered and has been modelled over two sites of equal occupancies. The disorder affects the propoxy chain and the disordered terminal phenyl rings lie in planes differing by 16.0 • , and twisted with respect to one another, as shown in Figure S13. Anisotropic behavior of the C10-C15 ring also indicates some slight disorder but this could not be modelled. Figure 2b illustrates the structures of the two independent molecules of 2. In both 1 and 2, the phenylalkoxy chains are in extended conformations. The C arene -O-C alkyl bond angles in 1 (polymorph I) and 2, and the shorter C arene -O compared to C alkyl -O bond lengths (Table 1) are indicative of sp 2 hybridized O atoms and π-conjugation extending from the arene ring to the O atoms. In all independent molecules of 1 (polymorph I) and 2, the alkyloxy substituent adopts the same conformation relative to the central arene ring (Figure 2). modelled. Figure 2b illustrates the structures of the two independent molecules of 2. In both 1 and 2, the phenylalkoxy chains are in extended conformations. The Carene-O-Calkyl bond angles in 1 (polymorph I) and 2, and the shorter Carene-O compared to Calkyl-O bond lengths (Table 1) are indicative of sp 2 hybridized O atoms and π-conjugation extending from the arene ring to the O atoms. In all independent molecules of 1 (polymorph I) and 2, the alkyloxy substituent adopts the same conformation relative to the central arene ring (Figure 2). Each molecule of 1 (polymorph I) and 2 can be considered as a rod-like entity extending between the two para-carbon atoms of the phenyl rings. The introduction of the extra CH 2 in each alkyloxy substituent leads to an elongation of the rod from ≈ 17.5 Å to 20.0 Å (distances between the para-C atoms of the terminal phenyl rings). This has a significant effect on the crystal packing. In polymorph I of 1, molecules containing Br1 and Br3 (see Figure S11 for atom labels) are arranged such that their central arene rings are approximately orthogonal with respect to each other (Figure 3a), and the same relationship is observed for molecules containing Br2 and Br4. This produces stacks of molecules (Figure 3a (8) • . Atoms Br2 and Br3 are involved in analogous interactions with arene rings containing C34 iv and C36 v , and C1 iv and C3 vi , respectively (symmetry codes: iv = x, 1 + y, z; v = 1 − x, 2 − y, 1 − z; vi = 1 − x, 1 − y, −z), at distances of 3.543(2), 3.449 (2), 3.541(2), and 3.516(2) Å and with C-Br . . . C angles of 176.14(8), 160.72(8), 176.14(8) and 161.28(8) • , respectively. Figure 3b illustrates the overall effect of these interactions within the lattice.  Each molecule of 1 (polymorph I) and 2 can be considered as a rod-like entity extending between the two para-carbon atoms of the phenyl rings. The introduction of the extra CH2 in each alkyloxy substituent leads to an elongation of the rod from ≈ 17.5 Å to 20.0 Å (distances between the para-C atoms of the terminal phenyl rings). This has a significant effect on the crystal packing. In polymorph I of 1, molecules containing Br1 and Br3 (see Figure S11 for atom labels) are arranged such that their central arene rings are approximately orthogonal with respect to each other (Figure 3a), and the same relationship is observed for molecules containing Br2 and Br4. This produces stacks of molecules ( Figure  3a (8) and 160.54(8)°. Atoms Br2 and Br3 are involved in analogous interactions with arene rings containing C34 iv and C36 v , and C1 iv and C3 vi , respectively (symmetry codes: iv = x, 1 + y, z; v = 1 − x, 2 − y, 1 − z; vi = 1 − x, 1 − y, −z), at distances of 3.543(2), 3.449 (2), 3.541(2), and 3.516(2) Å and with C-Br…C angles of 176.14(8), 160.72(8), 176.14(8) and 161.28(8)°, respectively. Figure 3b illustrates the overall effect of these interactions within the lattice.  In contrast to solid-state structure of 1, the crystal packing in 2 is dominated by a combination of arene-arene π-stacking, C-H...Br hydrogen bonds, and short Br....Br contacts. The two independent molecules of 2 are involved in a face-to-face π-stacking interaction. The central arene rings are offset with respect to each other (Figure 4a) and the ring plane-to-centroid distance is 3.58 Å, with an inter-centroid distance of 3.76 Å. Crystal packing involves extension of the stacks as displayed in Figure 4b. Weak C-H...Br and Br...Br contacts interconnect the crystallographically independent molecules into ribbons as shown in Figure 5. The molecule containing Br1 and Br2 engages in both Br...Br and Br...H-C interactions, while atom Br3 has no significant short-contacts. In the molecule containing Br3, the C34-H34 unit acts as a hydrogen-bond donor. (Note that, as defined by Steiner [35], the C-H group is considered as a hydrogen bond donor.) Pertinent distances (defined in Figure 5) are C34-H34...Br2ii = 2.87Å, angle C34-H34...Br2ii = 159 • , Br1ii...Br1iii = 3.4584 (6) Å. This Br...Br separation is less than the sum of the van der Waals radii (3.70 Å) [15], and lies within the range of contacts found in the CSD [11]. The C-Br...Br-C interaction shown in Figure 5 belongs to the type I category (Scheme 1), and each C-Br-Br angle is 150.6(1) • . In contrast to solid-state structure of 1, the crystal packing in 2 is dominated by a combination of arene-arene π-stacking, C-H...Br hydrogen bonds, and short Br....Br contacts. The two independent molecules of 2 are involved in a face-to-face π-stacking interaction. The central arene rings are offset with respect to each other (Figure 4a) and the ring plane-to-centroid distance is 3.58 Å, with an inter-centroid distance of 3.76 Å. Crystal packing involves extension of the stacks as displayed in Figure 4b. Weak C-H...Br and Br...Br contacts interconnect the crystallographically independent molecules into ribbons as shown in Figure 5. The molecule containing Br1 and Br2 engages in both Br...Br and Br...H-C interactions, while atom Br3 has no significant short-contacts. In the molecule containing Br3, the C34-H34 unit acts as a hydrogen-bond donor. (Note that, as defined by Steiner [35], the C-H group is considered as a hydrogen bond donor.) Pertinent distances (defined in Figure 5) are C34-H34...Br2ii = 2.87Å, angle C34-H34...Br2ii = 159°, Br1ii...Br1iii = 3.4584(6) Å. This Br...Br separation is less than the sum of the van der Waals radii (3.70 Å) [15], and lies within the range of contacts found in the CSD [11]. The C-Br...Br-C interaction shown in Figure 5 belongs to the type I category (Scheme 1), and each C-Br-Br angle is 150.6(1)°.     In contrast to solid-state structure of 1, the crystal packing in 2 is dominated by a combination of arene-arene π-stacking, C-H...Br hydrogen bonds, and short Br....Br contacts. The two independent molecules of 2 are involved in a face-to-face π-stacking interaction. The central arene rings are offset with respect to each other (Figure 4a) and the ring plane-to-centroid distance is 3.58 Å, with an inter-centroid distance of 3.76 Å. Crystal packing involves extension of the stacks as displayed in Figure 4b. Weak C-H...Br and Br...Br contacts interconnect the crystallographically independent molecules into ribbons as shown in Figure 5. The molecule containing Br1 and Br2 engages in both Br...Br and Br...H-C interactions, while atom Br3 has no significant short-contacts. In the molecule containing Br3, the C34-H34 unit acts as a hydrogen-bond donor. (Note that, as defined by Steiner [35], the C-H group is considered as a hydrogen bond donor.) Pertinent distances (defined in Figure 5) are C34-H34...Br2ii = 2.87Å, angle C34-H34...Br2ii = 159°, Br1ii...Br1iii = 3.4584(6) Å. This Br...Br separation is less than the sum of the van der Waals radii (3.70 Å) [15], and lies within the range of contacts found in the CSD [11]. The C-Br...Br-C interaction shown in Figure 5 belongs to the type I category (Scheme 1), and each C-Br-Br angle is 150.6(1)°.

Powder XRD of Bulk Materials and a Second Polymorph of Compound 1
Even though 1 and 2 differ in their rod-like dimensionalities (see above), we considered it important to rule out the possibility of polymorphism as being responsible for the differences in crystal packing. Thus, the bulk materials were analysed by PXRD. The refinement for 2 ( Figure 6) confirmed that the crystalline solid for 2 was representative of the crystal selected for single-crystal structural analysis. Peaks in the experimental plots match those in the fitted spectra, and the differences in intensities are explained in terms of differences in the preferred orientations.

Powder XRD of Bulk Materials and a Second Polymorph of Compound 1
Even though 1 and 2 differ in their rod-like dimensionalities (see above), we considered it important to rule out the possibility of polymorphism as being responsible for the differences in crystal packing. Thus, the bulk materials were analysed by PXRD. The refinement for 2 ( Figure 6) confirmed that the crystalline solid for 2 was representative of the crystal selected for single-crystal structural analysis. Peaks in the experimental plots match those in the fitted spectra, and the differences in intensities are explained in terms of differences in the preferred orientations. Figure 6. X-Ray diffraction (CuKα1 radiation) patterns (red circles) of the bulk crystalline material of 2 with fitting to the predicted pattern from single-crystal structure. The black lines correspond to the best fits from the Rietveld refinements, and green vertical lines show the Bragg peak positions. The blue line in each plot shows the difference between experimental and calculated points.
For compound 1, the PXRD of the bulk material was not commensurate with the predicted pattern from the single crystal structure described above (Figures 7a and S14). The high χ 2 value of 121.2 and the appearance of peaks in the residuals (blue lines) with no matches in the predicted pattern confirmed that the single crystal was not representative of the bulk sample. The peak at 2θ = 18.53° (Figure 7a), in particular, has no match in the predicted pattern. Recrystallization of the ground powder used for the bulk material PXRD from a hot solution of MeOH and CHCl3 cooled to room temperature, yielded Xray quality crystals. Cell checks on four crystals revealed a consistent set of cell parameters (Table 2) but the parameters differed slightly from those of the single crystal selected from the first batch of crystals (labelled polymorph I in Table 2). One crystal was, therefore, selected for single-crystal X-ray diffraction and the structure determination confirmed a second polymorph (II) of compound 1 which crystallized in the orthorhombic space group Pbca. The cell parameters are given in the last line of Table 2. The PXRD of this second recrystallized bulk sample was consistent with the pattern predicted from the single crystal structure data of polymorph II ( Figure S15) with every line in the experimental pattern having a match with a peak in the predicted pattern. Figure 7b shows a comparison of the PXRD patterns predicted from the single-crystal data of the triclinic and orthorhombic polymorphs of 1. From the low angle data, several peaks can be picked as being diagnostic of a specific polymorph, and, using the peak at 2θ = 18.53°, we were able to confirm the presence of both polymorphs in the initial bulk sample. For compound 1, the PXRD of the bulk material was not commensurate with the predicted pattern from the single crystal structure described above (Figure 7a and Figure S14). The high χ 2 value of 121.2 and the appearance of peaks in the residuals (blue lines) with no matches in the predicted pattern confirmed that the single crystal was not representative of the bulk sample. The peak at 2θ = 18.53 • (Figure 7a), in particular, has no match in the predicted pattern. Recrystallization of the ground powder used for the bulk material PXRD from a hot solution of MeOH and CHCl 3 cooled to room temperature, yielded X-ray quality crystals. Cell checks on four crystals revealed a consistent set of cell parameters (Table 2) but the parameters differed slightly from those of the single crystal selected from the first batch of crystals (labelled polymorph I in Table 2). One crystal was, therefore, selected for single-crystal X-ray diffraction and the structure determination confirmed a second polymorph (II) of compound 1 which crystallized in the orthorhombic space group Pbca. The cell parameters are given in the last line of Table 2. The PXRD of this second recrystallized bulk sample was consistent with the pattern predicted from the single crystal structure data of polymorph II ( Figure S15) with every line in the experimental pattern having a match with a peak in the predicted pattern. Figure 7b shows a comparison of the PXRD patterns predicted from the single-crystal data of the triclinic and orthorhombic polymorphs of 1. From the low angle data, several peaks can be picked as being diagnostic of a specific polymorph, and, using the peak at 2θ = 18.53 • , we were able to confirm the presence of both polymorphs in the initial bulk sample.

Figure 7.
(a) Comparison of the PXRD patterns (expansion of the range between 2θ = 5-30°) for the bulk sample from the first crystallization (grey) and the pattern predicted from the single-crystal data for the triclinic polymorph of 1 (red); the peak at 2θ = 18.53° arises from the second (orthorhombic) polymorph. (b) Comparison of the PXRD patterns (expansion of the range between 2θ = 5° and 30°, and normalized to maximum intensity = 100) predicted from the single-crystal data of the triclinic polymorph I of 1 (red) and of the orthorhombic polymorph II (blue); peaks at 2θ = 13.38° and 16.39° are representative of low angle data characteristic of polymorph I.
The geometric center of polymorph II of 1 lies on a crystallographic inversion center (Wyckoff site 4b) (Figure 8a). The conformation of the molecule and the bond lengths and angles (caption to Figure 8a) are essentially the same as those in polymorph I (Table 1). The angle between the planes of the phenyl ring containing C3 and arene ring with C9 is 82.3°, and this compares to a range of values from 81.1° to 82.6° for the corresponding angles for the four independent molecules in polymorph I (Table 1). Figure 8b illustrates an overlay of the four independent molecules of polymorph I of 1 and the molecule of polymorph II with additional symmetry-generated molecules. This confirms that the relative positions of the molecules in the lattice are the same in the two polymorphs, and the  The geometric center of polymorph II of 1 lies on a crystallographic inversion center (Wyckoff site 4b) (Figure 8a). The conformation of the molecule and the bond lengths and angles (caption to Figure 8a) are essentially the same as those in polymorph I (Table 1). The angle between the planes of the phenyl ring containing C3 and arene ring with C9 is 82.3 • , and this compares to a range of values from 81.1 • to 82.6 • for the corresponding angles for the four independent molecules in polymorph I (Table 1). Figure 8b illustrates an overlay of the four independent molecules of polymorph I of 1 and the molecule of polymorph II with additional symmetry-generated molecules. This confirms that the relative positions of the molecules in the lattice are the same in the two polymorphs, and the packing interactions in polymorph II involve C-Br...π(arene) contacts, just as in polymorph I. Thus, we have demonstrated that while compound 1 exhibits polymorphism, it is not this phenomenon that is responsible for the differences in crystal packing between 1 and 2.
Crystals 2021, 11, x FOR PEER REVIEW 10 of 12 packing interactions in polymorph II involve C-Br...π(arene) contacts, just as in polymorph I. Thus, we have demonstrated that while compound 1 exhibits polymorphism, it is not this phenomenon that is responsible for the differences in crystal packing between 1 and 2.

Conclusions
Two 1,4-dibromo-2,5-bis(phenylalkoxy)benzene derivatives 1 and 2 have been synthesized and characterized. Their single-crystal structures were determined, and the PXRD data for 2 confirmed that the single-crystal structure represents the bulk crystalline materials. For 1, analysis of the bulk material by PXRD led to the identification of two polymorphs (triclinic and orthorhombic) but with essentially the same molecular structures and the same packing interactions.
At the molecular level, 1 and 2 are similar with the phenylalkoxy chains in extended conformations, and the rod-like molecules have dimensions of ≈ 17.5 to 20.0 Å. This results in significant changes in the intermolecular interactions in the crystal lattices. The packing interactions in 1 are dominated by semi-localized C-Br...π(arene) contacts, with each Br located over one C-C bond of the central arene ring of an adjacent molecule. In 2, the packing involves a combination of C-H...Br hydrogen bonds, Br...Br interactions, and arene-arene π-stacking. We have also shown that while compound 1 exists in two polymorphic forms (I, triclinic, and II, orthorhombic), it is not this phenomenon that is responsible for the differences in crystal packing between 1 and 2.

Conclusions
Two 1,4-dibromo-2,5-bis(phenylalkoxy)benzene derivatives 1 and 2 have been synthesized and characterized. Their single-crystal structures were determined, and the PXRD data for 2 confirmed that the single-crystal structure represents the bulk crystalline materials. For 1, analysis of the bulk material by PXRD led to the identification of two polymorphs (triclinic and orthorhombic) but with essentially the same molecular structures and the same packing interactions.
At the molecular level, 1 and 2 are similar with the phenylalkoxy chains in extended conformations, and the rod-like molecules have dimensions of ≈ 17.5 to 20.0 Å. This results in significant changes in the intermolecular interactions in the crystal lattices. The packing interactions in 1 are dominated by semi-localized C-Br...π(arene) contacts, with each Br located over one C-C bond of the central arene ring of an adjacent molecule. In 2, the packing involves a combination of C-H...Br hydrogen bonds, Br...Br interactions, and arenearene π-stacking. We have also shown that while compound 1 exists in two polymorphic forms (I, triclinic, and II, orthorhombic), it is not this phenomenon that is responsible for the differences in crystal packing between 1 and 2.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author. The data are not publicly accessible at present.