Calix[2]naphth[2]arene: A Class of Naphthalene–Phenol Hybrid Macrocyclic Hosts

Calix[2]naphth[2]arenes make up a new class of phenol–naphthalene hybrid macrocycles. X-ray studies show that calix[2]naphth[2]arene 1 adopts a 1,2-alternate conformation. Alkali metal cations are complexed by the calixnaphtharenes in a 1,2-alternate conformation, by cation···π interactions with the naphthalene walls, and by RO···M+ ion–dipole interactions. In the presence of Cs+, chiral complexes of calixnaphtharenes 5 and 6 were observed in which the cation is nested on one of the two faces of the macrocycle.


Complexation Studies
The complexes M +  calix [2]naphth [2]arene were prepared by mixing an equimolar quantity of macrocyclic host and M[B(Ar F )4] salt in CD2Cl2.

H NMR determination of K ass values. 4
The association constant values of the complexes were calculated by means of three methods:

X-Ray Details of 1
Colorless single crystals suitable for X-ray investigation were obtained by slow evaporation of CHCl3 / Hexane solutions containing 1. Data collection was carried out at the Macromolecular crystallography XRD1 beamline of the Elettra synchrotron (Trieste, Italy), employing the rotating-crystal method with a Dectris Pilatus 2M area detector. Single crystals investigated were dipped in a PEG 200 cryo-protectant, mounted on a loop and flash-frozen under a liquid nitrogen stream at 100 K. Diffraction data were indexed and integrated using the XDS package, 6 while scaling was carried out with XSCALE. 7 The structures were solved using the SHELXT package; 8 and structure refinement was performed with SHELXL-14, 9 operating through the WinGX GUI, 10 by full-matrix leastsquares (FMLS) methods on F 2 .
Derivative 1 crystallized in the centrosymmetric triclinic P-1 space group. The asymmetric unit contains a ½ molecule of 1 which lies on a center of inversion and one co-crystallized CHCl3 solvent molecule located outside of the ring. All non-hydrogen atoms of the wellordered structure were anisotropically refined with hydrogen atoms placed at the geometrically calculated positions using the riding model. Crystal data and final refinement details for the structures are reported in Table S2.

X-ray analysis of 1
Small colorless single crystals of 1 suitable for X-ray structure determination were analyzed using synchrotron radiation and cryo-cooling techniques.
The molecule crystallized in the centrosymmetric triclinic P-1 space group. The cyclic molecules lie on crystallographic centers of inversion (Ci molecular point symmetry) and the asymmetric unit contains a ½ molecule of 1, and one CHCl3 solvent molecules located outside of the macrocycle ( Figure S50a).
The mean planes of the oppositely oriented naphthalene moieties are almost orthogonal with respect to the mean plane defined by the four bridging methylene groups (dihedral angles of 84°); while the oppositely oriented phenyl ring t-butyl groups of are tilted outwards from the center of the molecule (dihedral angles between phenyl and methylene bridges of 57°). Interestingly, the mean planes of the naphthalene and phenyl moieties are near orthogonal (dihedral angle of 87°) and the aromatic walls define an oblique quadrangular prism ( Figure S50b). The distances between parallel phenyl rings and parallel naphthalene moieties are 5.3 Å and 5.0 Å respectively. Important intramolecular hydrogen bond interactions are observed between the hydroxy group donors and the adjacent methoxy oxygen acceptors with O•••O distances of 2.782 Å. The prismatic structure is closed above and below by methoxy and methyl groups which protrude towards the center of the macrocycle (Figure S50c). The chloroform solvent molecules form interesting symmetric intermolecular C−H···π H-bonds with the arene moieties of 1 ( Figure S50a). The distance between the H atom of CHCl3 and the barycenter of aromatic ring is 2.3 Å.   Figure S51. X-ray structure of 1. The unit cell contains one centrosymmetric molecule of 1 and two CHCl3 molecules. The asymmetric unit is half of the unit cell. Thermal ellipsoids at 50% probability.

Conformational Studies by DFT Calculations
The lowest energy structures for the 5 conformations of 5 in Figures       DFT optimized structures of Na +  5 complex Figure S54. DFT-optimized structures (B3LYP/6-31G/(d,p)) of the Na +  5 complex.
1) Atomic coordinates of Na +  5 complex.  2) Atomic coordinates of K +  5 complex.  3) Atomic coordinates of Cs +  5 complex.    Natural bond orbital (NBO) analyses were performed with NBO 3.1 version implemented in Gaussian 16 and second-order perturbation theory analysis was performed via single point energy calculations using the b3lyp/6-31G(d,p) level of theory and dichloromethane as solvent. The non-covalent interaction (NCI) analysis was performed with the Multiwfn program 12 and its plot was graphed with VMD program. 13 Plots ( Figures S57 and S58) of the RDG versus the electron density multiplied by the sign of the second Hessian eigenvalue (s = 0.5 a.u.; left) and gradient isosurfaces (s = 0.4 a.u.; right) for the complexes. The coloring scheme was chosen to assist in distinguishing the amplitude of the electron density corresponding to different types of interactions. Marked in green color represent medium-strong (cation•••π and Van der Waals) interactions. Figure S58. Plot of RDG versus sign(I2)r for Na +  5 complex (NCI-RDG isosurfaces with S = 0.5). Figure S59. Plot of RDG versus sign(I2)r for K +  5 complex (NCI-RDG isosurfaces with S = 0.5).