CrystEngComm

Clathrate inclusion behaviour of thia-substituted diquinoline host molecules

Solhe F. Alshahateet, Roger Bishop,* Donald C. Craig and Marcia L. Scudder
School of Chemistry, The University of New South Wales, Sydney 2052, Australia. E-mail: R.Bishop@unsw.edu.au

Continuing our search for new compounds which function as lattice inclusion hosts, the thia-substituted diquinoline derivatives 5 and 6 have been synthesised and the X-ray structures of (5)₆·(CH₃OH) and (6)·(benzene) determined. A literature survey on the thioether–1,3-peri aromatic hydrogen interaction reveals that this is reasonably common, but neither crystal structure contains this motif despite expectations from our earlier work on the oxygenated analogues 3 and 4. It is also significant that the commonly observed edge–edge aryl C–H···N dimer motif is absent in (5)₆·(CH₃OH) and only present in (6)·(benzene) as an ineffectual, long-range contact. Instead, opposite host enantiomers in (5)₆·(CH₃OH) are linked through aza–1,3-peri aromatic hydrogen interactions, and the prevalence of this motif in the literature is also surveyed. Six molecules of 5 surround the methanol guest which is disordered on a site. The benzene molecules in (6)·(benzene) assemble by means of aryl edge–face interactions to produce parallel columns. This arrangement is the same as part of the lattice structure in solid benzene.

We have described earlier the syntheses and crystal structures of the diquinoline derivatives 1 and 2.^1,2 While 1 packs efficiently without guest inclusion, its dibromo derivative 2 prefers to form clathrate inclusion compounds by inclusion of small polyhalogenated guests. Compound 2 is the prototype of a family of lattice inclusion hosts that have been designed using analyses of the molecular structure of 2 and knowledge of its intermolecular properties. These compounds are prepared in a simple modular fashion by condensing two aromatic wings onto a central cyclic linker group, and then completing the synthesis by placement of the benzylic bromo sensor groups.^3–6 A variety of weak host–host and host–guest non-covalent forces (such as face–face and edge–face aryl–aryl, halogen–halogen, halogen–nitrogen, and edge–edge C–H···N dimer interactions) compete for the combination of best overall energy in the resulting clathrate structure.

During this investigation the oxygenated analogues 3 and 4 were prepared but, to our surprise, the latter compound did not function as a host molecule.⁷ In both solid 3 and 4 the ether oxygen interacts efficiently with two 1,3-peri aromatic hydrogens of an adjacent molecule to produce an intermolecular six-membered cycle involving two C–H···O weak hydrogen bonds (Fig. 1).^8–10 In crystalline 4 this ether–1,3-peri aromatic hydrogen interaction (Fig. 2) played a key role in preventing inclusion behaviour. The frequency of occurrence of this motif in the crystallographic literature, and its observed geometries, have been surveyed by us.⁷

	Fig. 1 Schematic illustration of the ether–1,3-peri aromatic hydrogen interaction between an ether R2O and naphthalene.7

	Fig. 2 Part of the crystal structure of 4 showing the highly effective ether–1,3-peri aromatic hydrogen interaction. The bromine atoms are coloured red-brown, and the C–H···O weak hydrogen bonds indicated by red and white dashed lines.7

This present communication reports the very different solid state behaviour observed for the related thia-substituted analogues 5 and 6.

In light of our earlier work it seemed likely that the thioether–1,3-peri aromatic hydrogen interaction should exist as a supramolecular synthon, and a search of the Cambridge Structural Database (CSD)¹¹ confirmed this expectation. Only strict thioether or thiophene functional groups were considered and, since C–H···S distances should be slightly longer than C–H···O, an upper limit of 3.50 Å (rather than 3.30 Å) was applied to both lengths. Totals of 13 compounds and 14 interactions were located. These are presented in Fig. 3 as a plot of their H1···S versus H2···S distances (Å).¹²

	Fig. 3 Plot of H1···S and H2···S distances (H2···S > H1···S) (Å) for the thioether–1,3-peri aromatic hydrogen interactions obtained from the CSD survey.

Like the earlier oxygen case, the analogous sulfur motif can play a significant role in crystal packing but it is not especially commonplace. For the oxygen compounds the H1···O and H2···O distances tended to be roughly comparable, but the distribution obtained here reveals that lop-sided configurations are slightly more frequent for the sulfur interaction.

A good illustration of the thioether–1,3-peri aromatic hydrogen interaction is that present in the crystal structure of the 11 inclusion compound of hexakis(-naphthylthio)benzene with dioxane.¹³ Hexa-substituted benzene derivatives usually adopt threefold symmetry with their arms alternately above and below the plane of the central benzene ring. In this instance, however, a rather different arrangement is adopted. This is due, in part, to pairs of host molecules interacting through two identical thioether–1,3-peri aromatic hydrogen interactions as illustrated in Fig. 4.

	Fig. 4 The host packing in solid [hexakis(-naphthylthio)benzene]·(dioxane) (refcode BOCVEU)13 showing the two identical thioether–1,3-peri aromatic hydrogen interactions (C–H···S distances 2.86 and 3.04 Å) present between neighbouring molecules.

The racemic thia-substituted diquinoline 5¹⁴ was prepared through Friedländer condensation¹⁵ of o-aminobenzaldehyde¹⁶ and 9-thiabicyclo[3.3.1]nonane-2,6-dione^17,18 in methanol solution containing a small amount of sodium hydroxide. Regioselective and stereoselective benzylic bromination of 5 using N-bromosuccinimide in CCl₄ then afforded the required dibromide 6.¹⁹ So far we have determined the X-ray crystal structures of nine compounds containing either 5 or 6 but none of these involve the thioether–1,3-peri aromatic hydrogen interaction. In this communication we describe the behaviour of the representative examples (5)₆·(methanol) and (6)·(benzene).

Although compounds 1 and 3 were designed (and behaved) as non-hosts, we find that their close structural analogue 5 does include a few solvents as guests. For example, crystallisation of racemic 5 from methanol gave compound (5)₆·(CH₃OH), illustrated in Fig. 5, the numerical details of the solution and refinement of which are presented in Table 1.

	Fig. 5 The unit cell packing arrangement of (5)6·(CH3OH). For clarity, all hydrogen atoms are omitted and only one component of the disordered methanol guest is shown. This view shows the almost planar cycles of sulfur atoms (yellow lines) contributed by six 5 molecules which surround sites. In the region at the centre of the cell (and equivalent sites) there is a host–host dimer interaction (indicated by the dashed lines and described in detail later). Colour code: host C green, guest C pale blue, N dark blue, O red, S yellow. Click image or here to access a 3D representation.

Compound	(5)6·(methanol)	(6)·(benzene)
Formula	(C22H16N2S)6·CH4O	C22H14Br2N2S·C6H6
Formula mass	2074.7	576.3
Space group	R	P
a/Å	27.820(4)	9.952(5)
b/Å	27.820(4)	10.565(6)
c/Å	11.145(3)	12.032(7)
/°	90	102.37(3)
/°	90	92.09(3)
/°	120	107.83(2)
V/Å3	7470(2)	1169(1)
T/°C	21(1)	21(1)
Z	3	2
Dcalc/g cm–3	1.38	1.64
Radiationcalc, /Å	MoK, 0.7107	MoK, 0.7107
µ/mm–1	0.19	3.54
Scan mode	/2	/2
2max/°	50	50
No. of intensity measurements	2925	4102
Criterion for observed reflection	I/(I) > 3	I/(I) > 3
No. of indep. obsd. reflections	1722	2180
No. of reflections (m) and	1722	2180
Variables (n) in final refinement	231	274
R = m|F|/m|Fo|	0.039	0.032
Rw = [mw|F|2/mw|Fo|2]1/2	0.045	0.039
s = [mw|F|2/(m – n)]1/2	1.38	1.29
Crystal decay	None	None
Max., min. transmission coefficient	—	0.58, 0.73
R for multiple measurements	0.014	0.028
Largest peak in final diff. map/e Ŗ3	0.99	0.98
a Click here for full crystallographic data (CCDC nos. 173086 and 173085).

A cycle of six molecules of host 5 surrounds a small cavity of symmetry where the methanol guest molecule is located. The aryl wings of three hosts of the same handedness form a propeller-like motif (Fig. 6) at the top of the cavity, while three more molecules of the opposite handedness form a similar propeller of opposite chirality at the bottom of the cavity (Fig. 7). Within each propeller, the three blades are held together by a triplet of aryl edge–face interactions (EF)₃ located close to the hub. Interactions between Ph₃X groups have been extensively studied by Dance and Scudder,^20–22 who observed the abundant formation of the sixfold phenyl embrace. This is a bimolecular concert of six edge–face interactions (EF)₆ which progress back and forth between the two molecules, ideally surrounding a symmetry site. In (5)₆·(CH₃OH) there are six aryl rings in similar formation, but there is no direct interaction across the site which is occupied by the guest.

	Fig. 6 Assembly of three molecules of 5 of the same handedness into a threefold propeller structure in (5)6·(CH3OH). The three propeller blades are held together by a triplet of aryl edge–face interactions (EF)3 located close to the hub of the propeller. One disorder component of the guest methanol molecule is shown underneath the hub. Both its heavy atoms are coloured red and its hydrogens are omitted.

	Fig. 7 Space-filling and framework views of the methanol guest surrounded by the two propellers of opposite chirality and enclosed in the site between them in compound (5)6·(CH3OH). For clarity, only one disorder component of the guest is illustrated, both its heavy atoms are coloured red and its hydrogens are omitted. Click image or here to access a 3D representation.

The sulfur atom of one 5 molecule belonging to one propeller lies almost equidistantly from the two aryl surfaces of an adjacent molecule belonging to the other propeller (Fig. 8). The six sulfur atoms in the assembly surrounding the site are approximately planar, this motif being indicated by the solid yellow lines in the cell diagram (Fig. 5) above.

	Fig. 8 The aryl wings of the top and bottom propellers associate via a complementary concave–convex fit, with the sulfur atom of a 5 molecule belonging to one propeller being positioned almost equidistantly from the two aryl wings of the adjacent 5 molecule of opposite chirality and belonging to the other propeller.

A notable feature of the structure (5)₆·(CH₃OH) is the complete absence of the ubiquitous edge–edge aryl C–H···N dimer interaction so frequently observed in crystal structures of our V-shaped diquinoline or diquinoxaline hosts.^2–6 Instead opposite enantiomers of 5 abut in the manner shown in Fig. 9 utilising two identical nitrogen analogues of the ether–1,3-peri aromatic hydrogen interaction. We have not encountered this type of dimer motif previously during our work in this area.⁶

	Fig. 9 Centrosymmetric double aza–1,3-peri aromatic hydrogen interaction present between opposite enantiomers of host 5 in the structure (5)6·(CH3OH). The C–H···N distances are 2.62 and 2.77 Å in each motif.

Examples of the aza–1,3-peri aromatic hydrogen interaction were located by searching the CSD.¹¹ Only nitrogen heteroaromatic substrates were considered, and an upper limit of 3.30 Å was applied to both C–H···N distances. A total of 28 compounds and 33 interactions were located²³ and Fig. 10 shows these as a plot of their H1···N versus H2···N values. The lengths present in (5)₆·(CH₃OH), illustrated in Fig. 10 by the red dot, represent a near ideal case of this interaction. However, our CSD survey did not uncover any further dimer structures of this type.

	Fig. 10 Plot of the H1···N and H2···N distances (H2···N > H1···N) (Å) for the aza–1,3-peri aromatic hydrogen interactions obtained from the CSD survey. The additional point belonging to the (5)6·(CH3OH) structure is shown in red.

As found for both the oxygen and sulfur cases, the analogous nitrogen motif can play a significant role in crystal packing. It is more frequent but, once again, not particularly common. Since nitrogen has only one non-bonding electron pair, the ideal orthogonal geometry⁷ of the other interactions no longer applies. Indeed, a number of the observed cases now exhibit near coplanar configurations of the two molecular components. While many of the H1···N and H2···N distances are comparable in length, this is frequently not the case as can be seen from the considerable scatter present around the bottom right-hand corner of Fig. 10.

As anticipated, the new diquinoline derivative 6 acted as a host for a number of guest molecules, and the example of its inclusion compound with benzene is described here. The structure of (6)·(benzene) is illustrated in Fig. 11, and numerical details of its solution and refinement appear in Table 1.

	Fig. 11 Partial structure of (6)·(benzene) projected in the xz plane with the hydrogen atoms omitted for clarity. One aryl wing of 6 makes offset face–face (OFF) interactions, while the other accepts edge–face (EF) interactions from benzene on both sides. There are two wings of 6 in the correct orientation to form a centrosymmetric edge–edge Ar–H···N dimer (EE) but they are too far apart (C···N 4.32 Å). The chains of benzene guests make good edge–face contacts with each other. Colour code: Br red-brown, N dark blue, S yellow, host C green, and benzene guest C light blue. Click image or here to access a 3D representation.

Benzene guests form infinite chains along y, with the individual molecules being linked by aryl edge–face interactions and additional stabilisation being provided by aryl guest–host edge–face interactions. Goodwin²⁴ has observed rather similar aggregates of just three benzenes in the crystal structure of [Fe(pzapt)₂]·(C₆H₆)_1.5. Both of these inclusion arrangements are essentially small sections of the structure of pure solid benzene itself.²⁵ An alternative view of the guest enclosure in (6)·(benzene) is shown in Fig. 12. This shows one individual molecule only of a benzene chain, surrounded by a distorted molecular pen⁵ formed from two host 6 molecules. The aryl edge–face guest–host interactions present are near ideal, but the aryl face–face guest–host interactions are less satisfactory due to the tilted planes of the aromatic host molecules.

	Fig. 12 Guest inclusion of one individual molecule of a benzene chain within a distorted molecular pen5 formed by two host molecules in (6)·(benzene). The effective aryl edge–face guest–host interactions, and the less efficient aryl face–face guest–host interactions, are apparent.

In (6)·(benzene) one wing of the host 6 makes an aryl offset face–face interaction with another of opposite chirality, but the other aromatic wing instead accepts edge–face interactions with benzene molecules on each side.

In addition, there are two aromatic wings in this structure with the correct edge–edge geometry to form a near planar centrosymmetric aryl C–H···N dimer (see Fig. 11).² In our previously reported inclusion structures these C–H···N values have ranged between 3.38 and 3.75 Å.⁶ Here, however, the observed value is a huge 4.32 Å. We therefore conclude that the other host–host and host–guest attractions described earlier dominate the structure of (6)·(benzene), and that this particular long-range edge–edge dimer is an ineffectual contributor to the overall energetics.

Reflection data were measured with an Enraf-Nonius CAD-4 diffractometer. Data were corrected for absorption for (6)·(benzene), but not for (5)₆·(methanol).²⁶ The positions of all atoms in the asymmetric unit were determined by direct phasing (SIR92)²⁷ with hydrogen atoms included in calculated positions. Guest methanol in (5)₆·(methanol) was disordered about a site. The benzene guest molecule in (6)·(benzene) was refined as a rigid group. Full details of refinement²⁸ can be found in the crystallographic data (CCDC nos. 173086 and 173085).

Acknowledgements

We gratefully acknowledge financial support from the Australian Research Council.

References

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