Synthesis of new aza-and thia-crown ethers and their metal ion templates synthesis as model case study

Four new thia-and four new aza-crown ethers were synthesized using the reaction of ethylene glycols ditosylated with 1,1´-(2,2´-dihydroxynaphthyl)sulfide ( DNS ) and 2,6-bis(3-hydroxyphenyl)-4-phenylpyridine in acetonitrile as solvent in the presence of bases (LiOH, NaOH, KOH and Cs 2 CO 3 ). In the synthesis of macrocycles based on DNS , the template effects of alkaline metal ions; Li + , Na + , K + and Cs + on the reaction yields were investigated. Sodium template generally was more effective for the synthesis of all four macrocycles. Relatively, good yields of 15-and 18-membered macrocycles were obtained in the presence of all kinds of applied cations. K + Cation was more effective template ion than Na + in the formation of 18-membered macrocycles due to their larger cavity size compared to the 15-membered cycles. The structures of macrocycles were confirmed by CHN/O analysis, IR, 1 H NMR, 13 C NMR and mass spectrometry.


Introduction
2][3] Due to their unique ability to complex particularly alkali and alkaline earth metal ions, they find wide applications in many fields of synthetic, analytical, and physical organic chemistry. 4Although molecular recognition is now verified by highly diversified and tailor-made structural component, [5][6] simple crown compounds are still attractive, for instance due to their generally good solubility in many solvents.The remarkably easy formation of large crown ether rings from noncyclic precursors using metal template-directed cyclizations by various modifications of the Williamson ether synthesis guarantees a general and usually high-yield access. 77][18][19] This character is due to transoid conformation which was found when X-ray crystallography was taken.4][25] All these observations in these series of macrocycles proved that the presence of sulfide atom play an important role in Host-Guest chemistry.
7][28][29][30][31] In fact, introduction of a pyridine moiety, strongly influences the thermodynamic properties and complexation kinetics by increasing the conformational rigidity of the macrocycles basicity modifications. 324][35] We have also examined such factors in DNS and pyridine based systems and studied them as host molecules in the presence of different metal cations in which the best selectivity and stability was found for Hg 2+ and Cu 2+ complexes. 24,36,37 Ithis work, we wish to report the effect of alkaline metal cations (Li + , Na + , K + , and Cs + ) anchors in the chemical template processes.

Results and Discussion
The synthesis of new thia crown ethers 3a-d and aza crown ethers 3e-f were performed by the reaction of ditosylated glycols 2a-d with DNS (1a) and 2,6-bis(3-hydroxyphenyl)-4-phenyl pyridine 1b (Scheme 1).The DNS (1a) was synthesized using 2-naphthol in 76% yield 38   Based on the template effect studies in the presence of alkaline metal ions shown in Table 2, it seems that macrocyclic effect is more enhanced in the presence of Na + compared to Li + and K + ions.This must be the result of ion-macrocycle interactions and preorganization of the macrocyclic ligands toward Na + ion.It is interesting that 15-membered ligand 3c does not have different behavior in the presence of Li + ion.This is not only because of preorganization of the macroring, but also may be due to HSAB conditions in which Li + ion behaves as hard acid.
The yields in Table 2 show that the template properties of the Na + is generally more effective for the synthesis of macrocycles 3a, 3c and 3d (Entry 1, 3 and 4).The macrorings 3c and 3d are generally synthesized in the presence of all kinds of applied cations in comparably higher yields.Relatively good yields in the template synthesis of larger ligands 3c and 3d (Entry 3, 4) in the presence of all four kinds of ions display that these two polyether rings are able to wrap themselves around the metal ions in a folded conformations which can promote the construction of systems of size exceeding the geometrical parameters of the matrix.There is generally strong relation between template ion size and the yield of the required macrocycle; we have observed this trend mostly for K + and Cs + ions.It seems that in these two cases the sizes of the template and macrocyclic compounds assembled are matched.
Due to "cesium effect" which is generally observed in the most macrocyclization processes, we expected to observe the highest yields in the presence of Cs + ion, but this trend was not completely expressed.This might be because of limitation of solubility of some of the compounds containing the template specially Cs2CO3 which determines the concentration of the template ion in the reaction mixture.

Experimental Section
General.All reactions were carried out on an efficient hood.The starting materials were purchased from Merck and Fluka chemical companies.Melting points were determined with a Branstead Electrothermal model 9200 apparatus and are uncorrected.IR spectra were recorded on a Perkin Elmer RX 1 Fourier transform infrared spectrometer.The 1 H and 13 C NMR spectra were recorded in DMSO-d 6 and CDCl 3 on Bruker Avance 300 MHz spectrometers.Elemental analyses were carried out by a Perkin Elmer 2400 series II CHN/O analyzer.Mass spectra were obtained by the Fisons Trio 1000 (70ev).