Switching the Conformation of 3,2′:6′,3″-tpy Domains in 4′-(4-n-Alkyloxyphenyl)-3,2′:6′,3″-Terpyridines

The preparation and characterization of 4′-(4-n-octyloxyphenyl)-3,2′:6′,3″-terpyridine (8) and 4′-(4-n-nonyloxyphenyl)-3,2′:6′,3″-terpyridine (9) are reported. The single crystal structures of 4′-(4-n-hexyloxyphenyl)-3,2′:6′,3″-terpyridine (6), 4′-(4-n-heptyloxyphenyl)-3,2′:6′,3″-terpyridine (7), and compounds 8 and 9 have been determined. The conformation of the 3,2′:6′,3″-tpy unit is trans,trans in 6 and 7, but switches to cis,trans in 8 and 9. This is associated with significant changes in the packing interactions with a more dominant role for van der Waals interactions between adjacent n-alkyloxy chains and C–Hmethylene... π interactions in 8 and 9. The solid-state structures of 6 and 7 with the n-hexyloxy and n-heptyloxy chains feature interwoven sheets of supramolecular assemblies of molecules, with pairs of n-alkyloxy chains threaded through cavities in an adjacent sheet.

Our observations that in metal coordination assemblies involving ligands 1-6, the 3,2′:6′,3′′-tpy conformation is influenced by the length of the 4-n-alkyloxy substituent motivated us to look at the structures of free 4′-(4-n-alkyloxyphenyl)-3,2′:6′,3′′-terpyridines. Here, we report the syntheses and characterizations of compounds 8 and 9 (Scheme 1b) and the crystal structures of compounds 6, 7, 8 and 9, and we discuss the factors that lead to a switch from conformation I to II as the n-alkyloxy chain increases in length.

Synthesis and Characterization of Compounds 8 and 9
Compounds 6 [25] and 7 [11] were prepared as previously described using the one-pot approach of Wang and Hanan [26], and this methodology was also used to synthesize compounds 8 and 9 (Scheme 2). The electrospray mass spectra of 8 and 9 (Figures S1 and S2 in Supplementary Materials) exhibited base peaks at m/z 438. 25   We focus now on the free ligands. The CSD contains the solid-state structures of only nine free and non-protonated 3,2 :6 ,3 -tpy ligands. In two structures, the 3,2 :6 ,3 -tpy domain is disordered. In the remaining structures, all of conformations I, II and III are observed (Table 1), but in none of these works has the preference for a given conformation of the 3,2 :6 ,3 -tpy been discussed. In our own report of the structure of 1-(3,2 :6 ,3 -terpyridin-4 -yl)ferrocene (refcode NEFVEC), we noted that close C-H...N contacts are dominant packing interactions [19]. Our observations that in metal coordination assemblies involving ligands 1-6, the 3,2 :6 ,3 -tpy conformation is influenced by the length of the 4-n-alkyloxy substituent motivated us to look at the structures of free 4 -(4-n-alkyloxyphenyl)-3,2 :6 ,3 -terpyridines. Here, we report the syntheses and characterizations of compounds 8 and 9 (Scheme 1b) and the crystal structures of compounds 6, 7, 8 and 9, and we discuss the factors that lead to a switch from conformation I to II as the n-alkyloxy chain increases in length.

Synthesis and Characterization of Compounds 8 and 9
Compounds 6 [25] and 7 [11] were prepared as previously described using the one-pot approach of Wang and Hanan [26], and this methodology was also used to synthesize compounds 8 and 9 (Scheme 2). The electrospray mass spectra of 8 and 9 (Figures S1 and S2 in Supplementary Materials) exhibited base peaks at m/z 438. 25 Table 2).

Crystal Structures
Colorless blocks of 6 were obtained by storing an EtOH solution of the compound for several weeks at 2-5 °C. X-ray quality colorless blocks of 7 were immediately obtained upon recrystallization from EtOH, while colorless blocks of 8 and 9 were obtained by dissolving the compounds in EtOH and storing the solutions for several days at 2-5 °C. Compounds 6, 7 and 8 crystallize in the monclinic space groups P21/n (6) and P21/c (7 and 8), while 9 crystallizes in the triclinic space group P-1. The Scheme 2. Synthesis of compound 8; 9 was prepared in a similar manner. Conditions: (i) KOH, EtOH; NH 3 (aqueous), room temperature. The numbering scheme for NMR assignments is shown; an analogous scheme is used for 9.
The solution absorption spectra of 8 and 9 are shown in Figure 1 and are compared with that of 6. Although compound 6 has been prepared previously [25], its absorption spectrum has not been reported. The bands arise predominantly from spin-allowed π*←π transitions, and absorption maxima are given in Table 2. The values of λ max compare with 226 and 272 nm in compound 7 [11]. and 2853 cm −1 in the C-H stretching region, and diagnostic strong absorptions in the fingerprint region at 1600, 1518, 1243, 1183, 1022, 704 and 604 cm −1 (these values are for 8).
Scheme 2. Synthesis of compound 8; 9 was prepared in a similar manner. Conditions: (i) KOH, EtOH; NH3 (aqueous), room temperature. The numbering scheme for NMR assignments is shown; an analogous scheme is used for 9.
The solution absorption spectra of 8 and 9 are shown in Figure 1 and are compared with that of 6. Although compound 6 has been prepared previously [25], its absorption spectrum has not been reported. The bands arise predominantly from spin-allowed * transitions, and absorption maxima are given in Table 2. The values of max compare with 226 and 272 nm in compound 7 [11].  Table 2).

Crystal Structures
Colorless blocks of 6 were obtained by storing an EtOH solution of the compound for several weeks at 2-5 °C. X-ray quality colorless blocks of 7 were immediately obtained upon recrystallization from EtOH, while colorless blocks of 8 and 9 were obtained by dissolving the compounds in EtOH and storing the solutions for several days at 2-5 °C. Compounds 6, 7 and 8 crystallize in the monclinic space groups P21/n (6) and P21/c (7 and 8), while 9 crystallizes in the triclinic space group P-1. The  Table 2). Table 2. Absorption maxima in the solution UV-VIS spectra of 6, 8 and 9 (MeCN, 5 × 10 −5 mol·dm −3 for 6 and 8, 2 × 10 −5 mol·dm −3 for 9).

Crystal Structures
Colorless blocks of 6 were obtained by storing an EtOH solution of the compound for several weeks at 2-5 • C. X-ray quality colorless blocks of 7 were immediately obtained upon recrystallization from EtOH, while colorless blocks of 8 and 9 were obtained by dissolving the compounds in EtOH and storing the solutions for several days at 2-5 • C. Compounds 6, 7 and 8 crystallize in the monclinic Molecules 2020, 25, 3162 4 of 13 space groups P2 1 /n (6) and P2 1 /c (7 and 8), while 9 crystallizes in the triclinic space group P -1. The asymmetric unit in each structure contains two independent, but structurally similar, molecules and Figures 2 and 3 depict one independent molecule of each compound. Bond lengths and angles are unexceptional. It is worth noting that the C phenylene -O bond is shorter than the C methylene -O bond (see captions to Figures 2 and 3), consistent with π-conjugation extending from the arene ring to the O atom; the C-O-C bond angles lie in the range 118.18 (13) • to 120. 10(14) • (captions to Figures 2 and 3) and these values are consistent with sp 2 hybridization at the O atom. The angles between the least squares planes through adjacent pairs of aromatic rings are compiled in Table 3. While the range of values is quite large, there is a general trend for the phenylene/pyridine twist angles to be larger than the pyridine/pyridine twist angles, an observation that is associated with π-stacking interactions between 3,2 :6 ,2 -tpy units (see below). The n-alkyloxy chain adopts an extended conformation in all the molecules. Again, this is associated with the packing interactions discussed later. Inspection of Figures 2 and 3 reveals that the conformation of the 3,2 :6 ,2 -tpy unit changes from I (Scheme 1) in compounds 6 and 7, to II (Scheme 1) in 8 and 9. A detailed look at the molecular packing gives an insight into the reasons for this conformational switch. There is no solvent in the crystal lattice in any of the structures, allowing us to make meaningful comparisons of the crystal packing. and these values are consistent with sp 2 hybridization at the O atom. The angles between the least squares planes through adjacent pairs of aromatic rings are compiled in Table 3. While the range of values is quite large, there is a general trend for the phenylene/pyridine twist angles to be larger than the pyridine/pyridine twist angles, an observation that is associated with -stacking interactions between 3,2′:6′,2′′-tpy units (see below). The n-alkyloxy chain adopts an extended conformation in all the molecules. Again, this is associated with the packing interactions discussed later. Inspection of Figures 2 and 3 reveals that the conformation of the 3,2′:6′,2′′-tpy unit changes from I (Scheme 1) in compounds 6 and 7, to II (Scheme 1) in 8 and 9. A detailed look at the molecular packing gives an insight into the reasons for this conformational switch. There is no solvent in the crystal lattice in any of the structures, allowing us to make meaningful comparisons of the crystal packing.    Table 3. While the range of values is quite large, there is a general trend for the phenylene/pyridine twist angles to be larger than the pyridine/pyridine twist angles, an observation that is associated with -stacking interactions between 3,2′:6′,2′′-tpy units (see below). The n-alkyloxy chain adopts an extended conformation in all the molecules. Again, this is associated with the packing interactions discussed later. Inspection of Figures 2 and 3 reveals that the conformation of the 3,2′:6′,2′′-tpy unit changes from I (Scheme 1) in compounds 6 and 7, to II (Scheme 1) in 8 and 9. A detailed look at the molecular packing gives an insight into the reasons for this conformational switch. There is no solvent in the crystal lattice in any of the structures, allowing us to make meaningful comparisons of the crystal packing.    We start with the packing of molecules of 6. Pairs of crystallographically independent molecules of 6 interact through C-H...N weak hydrogen bonds (Figure 4a, within the unit cell) with C...N separations of 3.753(2), 3.412(2) and 3.449(2) Å; H...N distances are in the range 2.55-2.83 Å, the H atom being in calculated positions. This motif extends into a ribbon-assembly through bifurcated hydrogen bonds [27] with atoms N3 and N6 acting as bifurcated acceptors with C...N distances of 3.412(2) and 3.753(2) Å for N3, and 3.622(2) and 3.720(2) Å for N6. We note that the N...H interactions are defined by the sum of the Bondi [28] N and H van der Waals radii in the program Mercury [29] with a default value of 1.20 Å for H; a value of 1.10 Å may be more realistic for organic structures [30]. The hydrogen-bonding pattern observed in Figure 4a reflects the fact that both of the independent 3,2 :6 ,2 -tpy units exhibit conformation I. Figure 4b illustrates centrosymmetric pairing of n-hexyloxy chains of adjacent ribbons. The assembly propagates into a non-planar sheet lying approximately in the ac-plane, and Figure 4b illustrates that the hydrogen-bonded 2D-network sheet contains voids. Each square-shaped cavity is bordered on two sides by n-hexyloxy chains. The voids are occupied by adjacent sheets being woven together (Figure 5a,b), although in a simpler manner than in established biaxial weavings [31]. The interwoven sheets are closely associated through offset face-to-face π-stacking of centrosymmetric pairs of the central pyridine rings of the 3,2 :6 ,2 -tpy units ( Figure S13 in the Supplementary Materials). For the crystallographically independent molecules of 6, the π-stacking interactions exhibit inter-plane distances of 3.56 Å and 3.48 Å, and centroid...centroid distances of 3.96 Å and 3.58 Å, respectively. We note that the head-to-tail arrangement of the offset-stacked pyridine rings is optimal in terms of the charge distribution in the pyridine rings [32].         The packing of the molecules in the lattice undergoes a major change on going from the n-hexyloxy and n-heptyloxy substituents in 6 and 7 to the longer chains in compounds 8 and 9, and associated with this is a switch in conformation of the 3,2 :6 ,3 -tpy units from I to II (Scheme 1). In compound 8, the two crystallographically independent molecules engage in an offset face-to-face π-stacking of the pyridine (py) rings containing N2 and N5 (Figure 7a). The angle between the ring-planes is 14.4 • and the centroid...centroid distance is 3.88 Å. This paired motif is a principal packing unit in the lattice. Molecules of 8 pack into 2D-layers with inter-layer py...py π-stacking (Figure 7b,c) being augmented by C-H methylene ... π interactions [33] as shown in Figure S14 (in the Supplementary Materials). The increase in the length of the n-alkyloxy chain leads to a greater role for van der Waals interactions compared to the packing in crystalline 6 and 7, and this is more important within a 2D-layer (Figure 8 and Figure S15) than between layers. Figure 8 also shows extensive C-H...N and C-H...O weak hydrogen bonding contacts within each 2D-layer, and optimization of these interactions clearly depends upon the conformation of the 3,2 :6 ,3 -tpy domain.  The packing of the molecules in the lattice undergoes a major change on going from the nhexyloxy and n-heptyloxy substituents in 6 and 7 to the longer chains in compounds 8 and 9, and associated with this is a switch in conformation of the 3,2′:6′,3′′-tpy units from I to II (Scheme 1). In compound 8, the two crystallographically independent molecules engage in an offset face-to-face stacking of the pyridine (py) rings containing N2 and N5 (Figure 7a). The angle between the ringplanes is 14.4° and the centroid...centroid distance is 3.88 Å. This paired motif is a principal packing unit in the lattice. Molecules of 8 pack into 2D-layers with inter-layer py...py -stacking (Figure 7b,c) being augmented by C-Hmethylene...  interactions [33] as shown in Figure S14 Figure S15 for a space-filling representation.
Despite the change in space group on going from 8 (P21/c) to 9 (P-1), there are many similar features in the lattices of the two compounds, indicating that the longer n-octyloxy and n-nonyloxy chains impart similar influences on the crystal packing. Firstly, the two crystallographically independent molecules of 9 engage in face-to-face -stacking. In contrast to the motif observed in 8 (Figure 7a), that in 9 involves stacking of the rings containing N1/N5 and those with N2/N4 (Figure Despite the change in space group on going from 8 (P2 1 /c) to 9 (P-1), there are many similar features in the lattices of the two compounds, indicating that the longer n-octyloxy and n-nonyloxy chains impart similar influences on the crystal packing. Firstly, the two crystallographically independent molecules of 9 engage in face-to-face π-stacking. In contrast to the motif observed in 8 (Figure 7a), that in 9 involves stacking of the rings containing N1/N5 and those with N2/N4 (Figure 9a). The angles between the planes of the pairs of pyridine rings with N1/N5 and N2/N4 are 8.0 • and 1.4 • , respectively, and each of the two centroid...centroid distances is 3.82 Å. The fact that each of the two independent 3,2 :6 ,2 -tpy domains adopts conformation II leads to a favorable arrangement of the stacked pairs of rings in terms of the charge distribution within the heterocycles [32], in keeping with our earlier comments concerning the crystal packing in 6. As in compound 8, molecules of 9 are organized in 2D-sheets in which van der Waals interactions between extended n-alkyloxy chains play a dominant role (Figure 9b). Figure 10 shows that the packing involves a combination of C-H...N and C-H...O weak hydrogen bonds and van der Waals interactions between n-nonyloxy chains. Despite the change in space group on going from 8 (P21/c) to 9 (P-1), there are many similar features in the lattices of the two compounds, indicating that the longer n-octyloxy and n-nonyloxy chains impart similar influences on the crystal packing. Firstly, the two crystallographically independent molecules of 9 engage in face-to-face -stacking. In contrast to the motif observed in 8 (Figure 7a), that in 9 involves stacking of the rings containing N1/N5 and those with N2/N4 ( Figure  9a). The angles between the planes of the pairs of pyridine rings with N1/N5 and N2/N4 are 8.0° and 1.4°, respectively, and each of the two centroid...centroid distances is 3.82 Å. The fact that each of the two independent 3,2′:6′,2′′-tpy domains adopts conformation II leads to a favorable arrangement of the stacked pairs of rings in terms of the charge distribution within the heterocycles [32], in keeping with our earlier comments concerning the crystal packing in 6. As in compound 8, molecules of 9 are organized in 2D-sheets in which van der Waals interactions between extended n-alkyloxy chains play a dominant role (Figures 9b). Figure 10 shows that the packing involves a combination of C-H...N and C-H...O weak hydrogen bonds and van der Waals interactions between n-nonyloxy chains.   Figure S16 (in the Supplementary Materials) shows this packing in a space-filling representation.

Conclusions
We have described the synthesis of compounds 8 and 9, extending the series of known 4 -(4-n-alkyloxyphenyl)-3,2 :6 ,3 -terpyridines. The compounds have been characterized by NMR, IR and absorption spectroscopies and mass spectrometry, and also by single-crystal X-ray crystallography. The structures of 6 and 7, which possess shorter n-alkyloxy chains than 8 and 9, have also been determined. At the molecular level, the structures of 6, 7, 8 and 9 are similar except for the conformation of the 3,2 :6 ,3 -tpy which switches from trans,trans in 6 and 7 (conformation I in Scheme 1) to cis,trans in 8 and 9 (conformation II). In all the compounds, the n-alkyloxy chain is in an extended conformation. The solid-state structures of 6 and 7 consist of interwoven pairs of supramolecular 2D-sheets; each sheet features C-H...N hydrogen-bonded interactions and van der Waals interaction between pairs of n-hexyloxy (in 6) or n-heptyloxy (in 7) chains. The n-alkyloxy chains are threaded through cavities in an adjacent sheet to produce the woven-sheet motifs. On going from 6 and 7, to 8 and 9, the lengthening of the n-alkyloxy chains leads to significant changes in the packing interactions with a more dominant role for van der Waals interactions between adjacent n-alkyloxy chains and C-H methylene ...π interactions. The structures of 8 and 9 comprise 2D-sheets supported by a combination of C-H...N and C-H...O weak hydrogen bonds, and van der Waals interactions between n-alkyloxy chains. The switch in 3,2 :6 ,3 -tpy conformation is intimately associated with the network of C-H...N weak hydrogen bonds in the supramolecular assembly.