Synthesis, structure and metal ion binding of di-(1,8-naphtho)-16-crown-4 compounds

The syntheses of two di(1,8-naphtho)-16-crown-4 compounds are described. In the X-ray structure of di(1,8-naphtho)-16-crown-4, the compound crystallizes in the orthorhombic space group Pna 2 1 with four molecules per asymmetric unit. Alkali metal cation selectivities of the ionophores are assessed in solvent polymeric membrane electrodes.


Introduction
2][3][4] Small-ring crown ethers with four oxygens (i.e., crown-4 compounds) often exhibit selective complexation of Li + .6][7] Due to rigidity in this ligand system, solidstate structures of its complexes provide insight into interactions of Li + with oxygen donor atoms.To probe the effect of expanding the crown ether ring from one with two 2-carbon and two 3-carbon bridges in dibenzo-14-crown-4 to four 3-carbon bridges, the synthesis of di-(1,8naphtho)-16-crown-4 2 was undertaken.We now describe the results of the synthetic endeavors, as well as the solid-state structure of 2 and its alkali metal cation selectivity in synthetic polymeric membrane electrodes.

Synthesis
The preparative route to 2 is presented in Scheme 1. Reaction of commercially available 1,8-naphthosultone 3 with KOH at 250 o C for 2 hours followed by treatment of the resultant mixture with 6 N HCl gave a 54% yield of 1,8dihydroxynaphthalene 4. Dropwise addition of a solution of 4 and 0.5 equivalent of 1,3dibromopropane in MeCN to a mixture of K2CO3 in MeCN at reflux followed by refluxing for 8 hours produced a 71% yield of the dinaphthol ether 5. Slow addition by syringe pump of a solution of equivalent amounts of 5 and the dimesylate of 1,3-propanediol in MeCN to a mixture of Cs2CO3 in MeCN at reflux followed by overnight reflux gave a 71% yield of di-(1,8-naphtho)-16-crown-4 2.

Solid-state structure of 2
Compound 2 crystallized in the orthorhombic space group Pna21 with four molecules per asymmetric unit (Figure 2).While the 1,8-naphthalenedioxy moieties are well-behaved in all four independent molecules, the aliphatic 3-carbon bridges show signs of disorder (elongated thermal ellipsoids and relatively high residual electron density maxima in the vicinity).For the three of those disorders that could be resolved, the occupancy ratios of the two respective components were refined freely, while constraining the sum of the occupancies to unity.To counteract correlation effects arising from the disorders, similarity restraints on 1-2 and 1-3 distances and displacement parameters, as well as rigid bond restraints for anisotropic displacement parameters, were applied to all atoms.The disordered structure of one of the independent molecules is presented in Figure 3.
Altogether the structure of compound 2 is not well behaved.The diffraction pattern shows signs of non-merohedral twinning and the metric symmetry of the unit cell suggests the possibility of cell-doubling in the b-direction, especially when taking into account that the asymmetric unit contains four molecules.Neither suspicion could be corroborated, however.Extensive searches for alternative unit-cells and cell settings, as well as multiple orientations of the same unit-cell all performed with the program cell_now 8 did not yield any usable results.Nevertheless, the refinement is reasonably stable and we are confident that the molecular model determined by means of this diffraction experiment reflects the chemistry of the compound accurately.membranes, potentiometric selectivities for one of the alkali metal cation relative to another were determined by the fixed interference method. 10lthough it had been anticipated that the small cavity sizes of di-(1,8-naphtho)-16-crown-4 2 and sym-(methylene)-di-(1,8-naphtho)-16-crown-4 6 would favor complexation of small alkali metal cations, preliminary experiments determined the greatest potentiometric response to Cs + among the five alkali metal cations.Therefore, Cs + was employed as the primary ion to which the other alkali metal cation responses were compared.
The potentiometric selectivities for Cs + /M + (-log KCs,M Pot ) for crown ethers 2 and 6 are recorded in Table 1.A larger value of -log KCs,M Pot means a greater difference between the potentiometric response of the ionophore to the primary metal ion Cs + and that of the competing metal ion M + .The potentiometric selectivities reveal a metal ion binding strength ordering of Cs + > Rb + > K + > Li + > Na + for both 2 and 6.This ordering is consistent with 2:1 (crown ether:metal ion) complexation in which the metal ion is sandwiched between two crown ether molecules.

Synthesis of di-(1,8-naphtho)-16-crown-4 (2).
Under nitrogen, a solution of 5 (1.00 g, 2.77 mmol) and the dimesylate of 1,3-propanediol (0.64 g, 2.77 mmol) in MeCN (75 mL) was added with a syringe pump over an 8-h period to a flask (equipped with a condenser and a Dean-Stark trap) containing a refluxing and stirred mixture of Cs2CO3 (2.25 g, 6.92 mmol) and MeCN (15 mL).During the addition, the volume in the flask was maintained at 30-35 mL by removal of solvent with the Dean-Stark trap.After the addition was completed, the mixture was stirred overnight at 80 o C and then evaporated in vacuo.Water (30 mL) was added and the mixture was extracted with CH2Cl2 (4 X 50 mL).The combined extracts were dried over MgSO4 and the filtrate was passed through a short bed of alumina with CH2Cl2-hexane (1:5) as eluent.The eluate was evaporated in vacuo and the residue was crystallized from CH2Cl2-hexane to give a 71% yield of white solid with mp 194 o C (dec).

Synthesis of sym-(methylene)-di-(1,8-naphtho)-16-crown-4 (6).
Using the same procedure as described above for the synthesis of 2 but with 3-chloro-2-chloromethyl-1-propene in place of the dimesylate of 1,3-propanediol, the eluate from the short alumina column was evaporated in vacuo and the residue was crystallized from CH2Cl2-EtOAc to give a 71% yield of white crystals with mp 163 o C. Solid-state structure determination for (2).A suitable crystal for structure determination of 2 was obtained by crystallization from CH2Cl2-MeOH.Low temperature diffraction data were collected using a Siemens Platform three-circle diffractometer coupled to a Bruker-AXS Smart Apex CCD detector with graphite monochromated Mo Kα radiation (λ = 0.71073 Å), performing φ-and ω-scans.Data reduction was performed with the program SAINT, version 7.12 12 and semi-emperical absorption correction was performed using SADABS. 13The structure was solved by direct methods using SHELXL 14 and refined against F 2 on all data by full-matrix least squares with SHELXL-97. 15All non-hydrogen atoms were refined anisotropically; all hydrogen atoms were included into the model at their geometrically calculated positions and refined using a riding model.The crystal data and experimental details are listed in Table 2.

Figure 2 .
Figure2.Ball-and-stick representation of the four crytallographically independent molecules with atomic labeling schemes for three of them.In the interest of clarity, the labels for the fourth molecule were omitted, but the labeling scheme follows the same principle as those of the other three molecules.Hydrogen atoms and atoms of the minor components of the disorders were omitted, as well.

Figure 3 .
Figure 3. 50% probability representation of one of the four independent molecules, showing the disorder of the aliphatic linkers (open lines for bonds between atoms in the minor component of the disorders).Hydrogen atoms were omitted for clarity
a Standard deviations from four measurements, duplicate determinations with each of two ISEs.Synthesis of 1,8-dihydroxynaphthalene (4).KOH (30.0 g, 0.53 mol) was dissolved in water (10 mL) and added to a preheated ceramic crucible containing 1,8-naphthosultone (6.00 g, 29.12 mmol).The mixture was heated in an oven at 250 o C for 2 h.The black viscous mixture was ARKAT USA, Inc. cooled

Table 2 .
Crystallographic information about the structure and refinement of 2.The crystallographic data have been deposited with the Cambridge Crystallographic Data Centre (deposition number CCDC 623942) and can be obtained free of charge via www.ccdc.cam.ac.jk/data_request/cif.