Rakesh
Puttreddy
a,
Ngong Kodiah
Beyeh
*ab and
Kari
Rissanen
*a
aDepartment of Chemistry, University of Jyvaskyla, Nanoscience Center, P.O. Box 35, FI-40014, Finland. E-mail: kari.t.rissanen@jyu.fi; Tel: +358 50 562 3721
bDepartment of Applied Physics, Aalto University School of Science, P.O. Box 11100, FI-00076, Finland. Fax: +358 9 855 4019; Tel: +358 9 47001
First published on 23rd December 2015
C
ethyl-2-Methylresorcinarene forms host–guest complexes with aromatic N-oxides through multiple intra- and intermolecular hydrogen bonds and C–H⋯π interactions. The host shows conformational flexibility to accommodate 3-methylpyridine N-oxide, while retaining a crown conformation for 2-methyl- and 4-methoxypyridine N-oxides highlighting the substituent effect of the guest. N-Methylmorpholine N-oxide, a 6-membered ring aliphatic N-oxide with a methyl at the N-oxide nitrogen, is bound by the equatorial −N–CH3 group located deep in the cavity. 2-Iodopyridine N-oxide is the only guest that manifests intermolecular N–O⋯I–C halogen bond interactions, which are broken down by the host resulting in a 2:
2 pseudocapsular complex stabilized by additional C–I⋯π interactions between the two 2-iodopyridine N-oxides located in two adjacent hosts. These host–guest complexes were analyzed in the solid state by single crystal X-ray crystallography and in solution by 1H NMR spectroscopy.
Pyridine N-oxides (PyNOs) are widely recognized as synthetic intermediates for the functionalization of pyridine rings in organic synthesis.7 This is due to the specific electronic nature of the +N–O− group which makes the aromatic ring electron deficient and thus a very interesting guest molecule with electron-rich host systems.8 Alternatively, the structural and electronic properties of these N-oxide compounds with the polar +N–O− group make them excellent hydrogen bond acceptors.9 In spite of the increasing number of reports on PyNO complexes with calixarenes8a,10 and cavitands,8b,11 reports on the host–guest chemistry of N-oxides and resorcinarenes are very rare.8c,12 The reports on host–guest complexes between Cethyl-2-methylresorcinarene and aromatic N-oxides have highlighted the importance of π⋯π and C–H⋯π interactions with the PyNOs located inside the Cethyl-2-methylresorcinarene cavity.8c These observations prompted us to further probe Cethyl-2-methylresorcinarene as a reaction vessel to control the coordination sphere of copper(II) in the multicomponent reactions of PyNO copper(II) complexes.12 The π⋯π, C–H⋯π and HB interactions held the PyNOs in the Cethyl-2-methylresorcinarene cavity thus controlling the geometry around copper(II).12 The π-rich nature of Cethyl-2-methylresorcinarene and the π-deficient nature of the PyNO guests with multiple HB interaction sites make them a perfect pair for host–guest complexation. Thus, exploring a range of structurally and electronically different aromatic N-oxides with subtle changes in their structure and the ability to template supramolecular host–guest complexes with π-rich host compounds will give a crystal engineering tool to study the intermolecular interactions involved. Despite the numerous literature reports on resorcinarenes, only a handful of crystal structures13 containing Cethyl-2-methylresorcinarene (1) can be found in the Cambridge Crystallographic Database (CSD). Furthermore, there has been no systematic study on host–guest complexes between PyNOs as guests and any member of the resorcinarene family as the host.
In the present study, we explore five different host–guest systems utilizing Cethyl-2-methylresorcinarene (1) as the host and five structurally and electronically different PyNOs as guests (Fig. 1). Cethyl-2-Methylresorcinarene (1) adopts the C4v crown conformation in the solid state.3a,8c,12 Initially, we used 2-methylpyridine N-oxide (2MePyNO) and 3-methylpyridine N-oxide (3MePyNO) to get insight into the effect of substituents on the structure of the host–guest complexes. 4-Methoxypyridine N-oxide (4MeOPyNO) was utilized to study the electronic influence of oxygen atom as a para-substituent. N-Methylmorpholine N-oxide (NMO) was also used as a guest to study the influence of the methyl group at the +N–O− group within an alicyclic ring system.
As the electron-deficient aromatic ring system in PyNOs will polarize the iodine atom in ortho-iodopyridine N-oxide (2-IPyNO) and thus induce possible halogen bonding,14 it was selected as the fifth and multifunctional guest. Based on previous reports, the halogen bond (XB) between the donor part (the iodine atom) and the XB acceptor part (the N-oxide oxygen) of 2-IPyNO was envisaged.15 Based on earlier studies on halo-PyNOs,15 the self-complementary XB between the XB donor part (the iodine atom) and the XB acceptor part (the N-oxide oxygen) of 2-IPyNO was envisaged. The hypothesis was to probe if in the complex between 2-IPyNO and Cethyl-2-methylresorcinarene the resorcinarene host would be able to break the moderately strong dimeric C–I⋯−O–N+ XB by forming a stronger 1:
1 2-IPyNO:1 complex. The obtained host–guest complexes were analysed in the solid state by single crystal X-ray diffraction and in solution by 1H NMR spectroscopy.
C
ethyl-2-Methylresorcinarene (1) exhibits remarkable conformational flexibility due to the positioning of the methyl substituents in 2MePyNO and 3MePyNO, thus resulting in varied C–H⋯π interactions.16 The para- and meta-protons of 2MePyNO (Fig. 3a) show C–H⋯π interactions at distances of ca. 2.785 Å [C–H⋯C, 149°] and 2.826 Å [
C–H⋯C, 163°], respectively. On the other hand, in complex 3MePyNO@1, the meta- and –CH3 hydrogens of 3MePyNO show C–H⋯π interactions at distances of ca. 2.752 Å [
C–H⋯C, 160°] and 2.863 Å [
C–H⋯C, 162°], respectively. As shown in Fig. 3c, the hydrogen of the –CH3 group to the centroid of the aromatic ring has the shortest contact at distances of ca. 2.715 Å [
C–H⋯π(centroid), 147°]. Guests with substituents close to the N–O group sit deep in the cavity. As a result, 2MePyNO sits at a height of 2.818 Å, while 3MePyNO at distances of 3.126 Å from the centroids of the lower rim carbon atoms of host 1. Furthermore, 2MePyNO with an approximately 60° angle between the N–O and methyl groups sits inside the host cavity without deformation resulting in near similar centroid-to-centroid [6.923 Å and 6.827 Å] distances between opposite aromatic rings (Fig. 3c). However, 3MePyNO with an approximately 120° angle caused significant changes in the host centroid-to-centroid distances between opposite aromatic rings [7.342 Å and 6.226 Å], as shown in Fig. 3d.
Complex 4MeOPyNO@1 forms a 2-D polymeric sheet structure with a 1:
1 host–guest ratio. In 4MeOPyNO@1, the N–O group of 4MeOPyNO is pointing up and is bidentate with N–O⋯(O–H)host and N–O⋯(O–H)CH3OH interactions at distances of 2.650(3) Å [
O–H⋯O, 158°] and 2.580(3) Å [
O–H⋯O, 175°], respectively (Fig. 4a). The extent of the HB interaction of 4MeOPyNO and 2MePyNO with the host –OH groups are very similar. Unlike 2MePyNO@1 and 3MePyNO@1, no C–H⋯π(host) interactions between the aromatic ring protons of 4MeOPyNO and Cethyl-2-methylresorcinarene (1) are observed. Moreover, the in-cavity –OCH3 group also assists the 3D crystal packing by weak O⋯H–C interactions with the adjacent Cethyl chain of the host.
Complex NMO@1 contains in-cavity and exo-cavity NMO molecules. The in-cavity N–O group and the host –OH group are connected by two methanol molecules while the exo-cavity NMO directly HB to the –OH group of host 1 (Fig. 4b). The difference in host cavity distortions depends on the guest height situated in the cavity, viz. 3.077 Å for 4MeOPyNO and 2.920 Å for NMO. In both cases, the guest molecules are situated to the corner of the host, stabilized via C–H⋯π interactions. In 4MeOPyNO@1, the –OCH3 group and the host aromatic ring are stabilized by C–H⋯π interactions at distances ranging between 2.919 Å and 3.129 Å, of which C–H⋯centroid was observed to have the shortest contact with a distance of 2.681 Å (Fig. S4a†). In NMO@1, the in-cavity NMO interacts with the host aromatic ring through C–H⋯π at distances of 2.937 Å and 3.221 Å (Fig. S4b†). The N–O group appears to be the reason for the presence of the in-cavity –N–CH3 group, which makes NMO a unique guest molecule from other N-oxides.
Complex 2-IPyNO@1 reveals a pseudo-capsular arrangement as shown in Fig. 5. The asymmetric unit contains two Cethyl-2-methylresorcinarenes, each accommodating 2-IPyNO molecules together with six exo-cavity water molecules. The N–O groups of in-cavity 2-IPyNO acts as bidentate and tridentate (Fig. S5†) HB acceptors for the exo-cavity water and adjacent host molecules in stabilizing the pseudo-capsular arrangements by O–H⋯O interactions. One of the iodines in the cavity of one host interacts with the phenyl ring of the 2-IPyNO located in the cavity of the second host through intermolecular C–I⋯π contacts at distances of 3.549 Å [C–I⋯π (centroid), 161° and
C–I⋯π (plane), 155°]. The height of the capsule, defined as the distance between the centroids of the lower rim carbons, is 13.479 Å (Fig. S6†),8c in which the two 2-IPyNO molecules are accommodated at heights of 2.720 Å and 3.153 Å. The hosts adopt a distorted crown conformation with centroid-to-centroid distances of 6.790/6.960 Å and 6.816/6.961 Å (Fig. S7†). The height and orientation of the 2-IPyNO molecules increase the number of C–H⋯π interactions with the host aromatic ring. The 2-IPyNO parallel to the host aromatic ring and situated at a height of 3.153 Å is stabilized by two C–H⋯π interactions, while the non-parallel 2-IPyNO situated deep in the cavity at a height of 2.720 Å is stabilized uniquely by three C–H⋯π interactions (Fig. S7†).
The orientation of the guest aromatic ring deep in the host cavity with the N–O group pointing up has been a primary prerequisite to encapsulate PyNOs by Cethyl-2-methylresorcinarene (1). As a consequence, the guest molecules become responsive to these interactions. As such, the self-assembly process can be controlled with respect to the guest interactions. To illustrate this, 2-IPyNO was crystallised under similar solvent conditions to compare the nature of guest interactions in the absence of Cethyl-2-methylresorcinarene (1). The crystal structure of 2-IPyNO (Fig. 6) displays a classical intermolecular N–O⋯I–C XB at distances of 2.791 Å with an XB ratio (RXB = dXB/(Xvdw + Bvdw)) of 0.791.14
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Fig. 6 (a) 1-D polymeric N–O⋯I interaction based XB complex of 2-IPyNO, and (b) confined C–I⋯π interactions between 2-IPyNO by Cethyl-2-methylresorcinarene (1) inside complex 2-IPyNO@1. |
The type and strength of the electron withdrawing group attached to the aromatic ring and its influence on the hybridization of the aromatic ring affect the polarization of the halogen atom (usually Br or I) acting either as an electron donor or acceptor. Although iodine has weak interactions with ortho-carbons [d(C–I⋯C), 3.716 Å; C–I⋯C, 141.30°] and nitrogen [d(C–I⋯N), 3.649 Å;
C–I⋯N, 141.28°] of the pyridine N-oxide ring, the centroid of the aromatic ring is influenced by the shortest contact with a distance of 3.549 Å. Thus, the iodine substituent clearly demonstrates the presence of weak C–I⋯π halogen type interactions which are enhanced inside the pseudo capsular arrangement.
A CCDC search was carried out to survey the type and nature of molecules involved during intermolecular C–I⋯aromatic ring interactions. The first search was limited to any 2-substituted iodo-aromatic compounds and their non-bonded interactions with an adjacent aromatic ring. In total, 22 hits were found,13d,17 and of all the structures, one of those reported constitutes the shortest distance of 3.321 Å.17o A search for perfluorinated iodobenzene related C–I⋯π interactions revealed zero hits. Consequently, individual surveys were carried out on compounds that have neutral aprotic electron-withdrawing groups (–F, –Cl, –NO2, –CN, –CF3, –CCl3 and –COCl) and electron donating groups (alkyl and –NR2) at the 2-substituted position of iodo-aromatic compounds. Only the chloro substituent retrieved one hit, which has a C–I⋯π distance of 3.537 Å.18
Significant complexation-induced shielding of the guest proton resonances was observed in all cases. The shielding effects of the aromatic rings of the bowl-shaped host cavity upon addition of the guest are responsible for this upfield shift and clearly point to a fast guest exchange on the NMR time scale. Taking the 1:
1 mixture between Cethyl-2-methylresorcinarene (1) and NMO as an example (Fig. 7), the methyl group protons (e) are the most shielded (0.76 ppm). These shift changes clearly confirm the orientation of the guest in the host cavity. The large shift change for the methyl protons suggests that the protons are situated deep in the cavity of the host. This is analogous to the X-ray structure (Fig. 4b).
Analyses of the 1:
1 mixture between Cethyl-2-methylresorcinarene (1) and 2-IPyNO (Fig. 8) reveal the aromatic protons (b, c) to be the most shielded (0.67–0.72 ppm) with the proton next to the –NO group the least shielded (0.31 ppm). This supports the orientation of the guest within the host cavity as seen from the X-ray structures (Fig. 5 and 6). The analyses of the 1H NMR results between the host and the other guests (2MePyNO, 3MePyNO and 4MeOPyNO) also confirm the orientation of the guests in the host cavity (Fig. S1–S3†) and support the structures observed from solid state analyses (Fig. 2 and 4). Additionally, the flexibility of the host when accommodating the guest is observed from the small changes in the host upper rim methyl groups and the aromatic protons upon complex formation. This again supports the observation from solid-state studies.
Footnote |
† Electronic supplementary information (ESI) available: Crystal structures and crystallographic data. CCDC numbers 1407237–1407242. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ce02354h |
This journal is © The Royal Society of Chemistry 2016 |