Introduction

It is well known that crown ethers can be considered as molecular receptors for selective binding of ionic and molecular guests forming host–guest complexes or supramolecular species [1–3]. Crown ether derivatives with different functional groups have received much attention in the last few years both in chemistry and biology [4–7]. For example, crown ether derivatives with ether or anionic groups on the periphery of the macrocycles have been synthesized, in order to increase metal ion selectivity and complex stability in analytical and separation methods as well as in biological membranes [8–10]. As biologic model compounds, crown ethers can interact with many guests including metal ions, organic cations and neutral polar molecules by weak non-covalent interactions [11]. For several years, various simple or complicated chemical systems have been used as model mimics of natural enzymes [12–14]. The crown ethers are generally considered as the first generation organism of mimetic enzyme in the theory of enzymology due to their recognition function of guests and hosts.

The primary crown ethers, which contain only oxygen binding sites have high affinity toward the alkali metal ions. In other words, crown ethers, which contain a hydrophobic ethylenic residues that surround a hydrophilic cavity of ether oxygen atoms, are able to bind selectively a range of alkali and alkaline earth metal cations [15–18]. The cation-polyether complexes are formed by ion–dipole interaction between the cation and the negatively charged oxygens symmetrically arranged in the polyether ring. If the diameter of the cation is too large to fit inside the available crown cavity, formation of so called “sandwich” complexes with 1:2 and 2:3 metal:crown ether ratios can occur [19, 20].

In this paper, we describe the syntheses and characterization of a series of novel double-armed and bi-macrocyclic ethers and complexes, containing benzo-15-crown-5 moieties. We report (i) the syntheses of double-armed crown ether having two formyl residues (1 and 2) (Scheme 1); (ii) the syntheses and characterization of Schiff bases containing with two macrorings (3–6) (Scheme 2); (iii) complexation of sodium cation within the crown ether cavity (1a–6a) (Scheme 3); (iv) sandwich complexes with potassium (1b–6b) (Scheme 3) and (v) analytical, physical and spectral (IR, 1H-, 13C-NMR and MS) data.

Scheme 1
scheme 1

Syntheses of dialdehydes (1 and 2)

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Scheme 2
scheme 2

Syntheses of Schiff bases (3–6)

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Scheme 3
scheme 3

Proposed structures of a sodium complexes (1a–6a), b potassium complexes (1b–6b)

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Experimental

Materials and methods

1-Chloro-2-{2-[2-(2-chloroethoxy)ethoxy]ethoxy}ethane [21], benzo-15-crown-5 [22] and 4′,5′-bis(bromomethyl)benzo-15-crown-5 [23] were prepared according to the literature. 2-Hydroxy-3-methoxybenzaldehyde (o-vanillin) and 2-hydroxy-5-methoxybenzaldehyde were purchased from Aldrich and used without further purification. Solvents were dried and distilled before use according to the standard procedures.

Melting points were measured on a Thomas-Hoover apparatus using a capillary tube. 1H- and 13C-NMR spectra were recorded on a Varian Mercury, High Performance Digital FT-NMR (400 MHz) spectrometer (SiMe4 as an internal standard). Chemical shifts for proton and carbon resonances were reported in ppm (δ). IR spectra were obtained from PEL-DATA spectrum 100 series spectrometer KBr pellets. Elemental analyses (C, H, N) were conducted using the Elemental Analyser LECO CHNS-932; the results were found to be in good agreement (±0.2 %) with the calculated values. Mass spectrometric analyses were performed on the Waters 2695 Allonce ZQ LC/MS spectrometer.

2,2′-[2,3,5,6,8,9,11,12-Octahydro-1,4,7,10,13-benzopentaoxacyclopentadecine-15,16-diyl bis(methyleneoxy)]bis(3-methoxybenzaldehyde) (1)

2-Hydroxy-3-methoxybenzaldehyde (0.50 g, 3.29 mmol) was dissolved in DMF (50 cm3). NaOH (0.13 g, 3.29 mmol) was added in small portions and the resulting reaction mixture was refluxed for 1 h. Subsequently, 4′,5′-bis(bromomethyl)benzo-15-crown-5 (0.75 g, 1.65 mmol) in DMF (20 cm3) was added dropwise to the reaction mixture. The resulting solution was refluxed for 10 h until the complete consumption of the starting material was observed by TLC (silicagel, eluent: CHCl3). Then water was added until the solution turned cloudy. The beige precipitate formed was isolated and recrystallized from ethanol. Properties of compound (1) are given in Table 1.

Table 1 Analytical data and experimental details of compounds (1–6, 1a–6a and 1b–6b)
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2,2′-[2,3,5,6,8,9,11,12-Octahydro-1,4,7,10,13-benzopentaoxacyclopentadecine-15,16-diyl bis(methyleneoxy)]bis(5-methoxybenzaldehyde) (2)

Compound 2 was prepared analogously to compound 1 as above by using a solution of 2-hydroxy-5-methoxybenzaldehyde (0.50 g, 3.29 mmol). After recrystallization from EtOH, beige needle crystals were obtained. Data for compound (2) are given in Table 1.

General methods for preparing Schiff bases (3–6)

The corresponding amines (1,3-diaminopropane or 1,4-diaminobutane) (2.0 mmol) were dissolved in EtOH (20 mL). Crown aldehydes (1.0 mmol) were dissolved in EtOH and added dropwise to the amine solution. The resulting solution was stirred under reflux for 3 h and the reaction mixture was allowed to stand for 2 h at room temperature. The crude product was recrystallized from EtOH, Table 1.

General methods for preparing sodium complexes (1a–6a)

The respective crown ethers (1–6) (1.00 mmol) and NaClO4 (1.00 mmol) were dissolved in dry EtOH (20 mL) and refluxed for 2 h. The crude complexes were filtered and washed with diethyl ether. For characteristic see Table 1.

General methods for preparing potassium complexes (1b–6b)

The respective crown ethers (1–6) (2.00 mmol) and KI (1.00 mmol) were dissolved in dry EtOH (50 mL) and refluxed for 2 h. Crude complexes were filtered and washed with diethyl ether, Table 1.

Results and discussion

Syntheses

The synthetic procedure for the preparation of the crown ether aldehydes (1 and 2) proceeds in two steps. Firstly, 2-hydroxy-3-methoxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde were reacted with NaOH in DMF to give the corresponding sodium alkoxide. Secondly, the obtained sodium salts were converted into the corresponding new crown ether aldehydes (1 and 2) by reacting with 4′,5′-bis(bromomethyl)benzo-15-crown-5. Compounds (1 and 2) were successfully synthesized with yields in the range of 47–32 %, respectively.

Direct reaction of one equivalent of 1 or 2 with one equivalent of the appropriate amine (1,3-diaminopropane or 1,4-diaminobutane) in ethanol gives the corresponding double-macrocyclic Schiff bases (3–6).

The sodium complexes (1a–6a) were prepared (Na+:ligand (1:1) “filling complex”) by treating a solution of one mole of compounds (1–6) with one mole NaClO4. But potassium complexes were prepared [K+:ligand (1:2) “sandwich complex”] by treating a solution of two moles of compounds (1–6) with one mole KI. The elemental analyses confirm the potassium complexes are of 1:2 (K+:ligand) stoichiometry. Free ligands (1–6) are soluble in EtOH, CHCl3, THF, acetone, DMSO, CH3CN, n-hexane and n-heptane, whereas sodium and potassium complexes (5a, 6a, 3b–6b) are insoluble in CHCl3 and EtOH. The structures of the ligands, sodium and potassium complexes were verified by the elemental analysis, FT-IR, 1H-, 13C-NMR and mass spectra. Analytical data and experimental details for compounds (1–6, 1a–6a and 1b–6b) are given in Table 1. Various attempts to obtain single crystals of the ligands and complexes have so far been unsuccessful.

IR spectra

Selected IR data of the crown ethers and alkali metal complexes are shown in Table 2. In the infrared spectra of crown ether aldehydes (1, 2, 1a, 2a, 1b and 2b) strong bands in the 1,666–1,699 cm−1 region can be assigned to the ν(C=O) stretching, which disappear for imine compounds (3–6, 3a–6a and 3b–6b) indicating the condensation of the aldehyde groups. The characteristic imine (νC=N) stretching bands attributable to the azomethine group (HC=N) were observed at 1,634–1,639 cm−1 for ligands (3–6) and complexes (3a–6a and 3b–6b). The intense bands at 1,616–1,457 cm−1 correspond to the stretching vibrations of the benzene rings (νC=C) of the compounds. The asymmetric and symmetric νC–O–C stretching vibration bands are observed at 1389, 1281 and at 1123; 1084 cm−1 both for ligands and complexes. The 3–OCH3 substituted compounds (1, 3, 5, 1a, 3a, 5a, 1b, 3b and 5b) show C=C and C–O–C(arom.) stretching vibration bands at 1,580–1,585 and 1,360–1,380 cm−1 while the corresponding C=C and C–O–C(arom.) bands of the 5–OCH3 substituted compounds (2, 4, 6, 2a, 4a, 6a, 2b, 4b and 6b) are shifted to higher frequencies (1,606–1,616 and 1,371–1,389 cm−1). The frequencies for the ligands (1–6) and complexes (1a–6a and 1b–6b) were almost of the same frequency.

Table 2 Selected IR bands
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1H- and 13C-NMR spectroscopy in CDCl3, DMSO, and CDCl3 + DMSO

The 1H-NMR spectral data are summarized in Table 3. In the 1H-NMR spectra, the integral ratio of the aliphatic and aromatic protons for all compounds (1–6, 1a–6a and 1b–6b) indicates the molecules to be symmetric.

Table 3 1H-NMR spectral data
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The 1H-NMR spectra of the aldehydes (1 and 2), imines (3–6) and complexes (1a–6a and 1b–6b) show singlets corresponding to –OCH3 protons. The singlets at 10.21, 10.23, 10.24, 10.21, 10.14 and 10.38 ppm for aldehyde protons (–CHO) (for 1, 2, 1a, 2a, 1b and 2b) disappear after the condensation with diamines. The azomethine protons were observed as singlets at 8.69, 8.46, 8.38 and 8.55 (for 3–6), at 8.62, 8.45, 8.29 and 8.41 (for 3a–6a) and at 8.32, 8.38 and 8.44 (for 3b–6b). The benzylic protons (–OCH2–) were seen as singlets at 4.87–5.26 ppm. 1H-NMR spectra of all compounds show the aromatic protons as multiplets between 6.87 and 7.59 ppm, whereas the crown ether protons (OCH2–CH2O) appear as multiplets between 3.52 and 4.26 ppm. Considering the –C–CH2– proton chemical shifts for the Schiff bases (3 and 5) and (4 and 6), we note a shielding of 0.64 and 0.52 ppm on passing from –(CH2)2– to –(CH2)3– for the alkylene groups of the corresponding Schiff bases, respectively.

For sodium complexes (3a and 5a) and (4a and 6a) these shielding were found to be equal 0.61 and 0.78 ppm, respectively. The 1H-NMR spectra of the sodium and potassium complexes are approximately the same as spectra of the corresponding ligands, but the 1H-NMR spectra provide compelling evidence for the ligand and their sodium or potassium complexes, because different shape of multiplet peaks was seen for OCH2–CH2O region (between 3.5 and 4.5 ppm) of the ligand and each sodium and potassium complexes [24] (Figs. 1, 2). Although three multiplet peaks were seen for the ligands (1, 3), four peaks were seen for the sodium and potassium complexes (1a, 3a and 1b, 3b) for crown ether proton peaks region.

Fig. 1
figure 1

1H-NMR spectra of the crown ether OCH2–CH2O protons for a sodium complex (1a), b free ligand (1), c potassium complex (1b) in CDCL3

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Fig. 2
figure 2

1H-NMR spectra of the crown ether protons (OCH2–CH2O), a sodium complex (3a), b free ligand (3), c potassium complex (3b) in CDCL3

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In our study, the presence of two isomers was detected by the 1H-NMR spectroscopy for 5–OCH3 substituted crown ether Schiff bases (4 and 6). The presence of two sets of signals for each HC=N, –OCH2– and Ar–H groups indicates the existence of different possible geometrical isomers. The mono-imine Schiff bases can have two possible configurations: E and Z. Hence two imine bonds of the Schiff bases can have three possible configurations, (E, E), (Z, Z) and (E, Z)/(Z, E) [25, 26] (Scheme 4).

Scheme 4
scheme 4

Possible isomers for compounds (4 and 6); n 1, 2

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The 1H-NMR spectra of compounds 4 and 6 give two singlets attributed to the HC=N protons, two singlets due to the –OCH2– protons and two different multiplets due to Ar–H protons. Two different sets of signals present in the 1H-NMR spectra of the 5–OCH3 substituted crown Schiff bases 4 and 6 show the presence of both E and Z isomers. These two peaks suggested the presence of a mixture of isomers (probably EE and ZZ). Peak integrations indicated the ratio of the %E and %Z isomer.

The 1H-NMR spectra of compounds 4 and 6 were registered at different time intervals and we have seen the different peak intensities of (E) and (Z) isomer (Fig. 3) (in this figure, each isomer peak was marked with X and Y). One minute after dissolution, the 1H-NMR spectra showed that the X isomer ratio was higher than the Y one (Fig. 3a). Thirty minutes after dissolution, X and Y isomer ratio were approximately same (Fig. 3b), but after next 30 min Y isomer ratio increased (Fig. 3b, c). 18 h after dissolution, the X isomer practically disappears and Y isomer ratio was ~100 % (Fig. 3d).

Fig. 3
figure 3

1H-NMR spectra of compound (4) (registered at different time intervals); a after 1 min; b after 30 min; c after 2 h; d after 18 h. X and Y: E or Z isomer peaks (X is related the one isomer while Y is related the another isomer)

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The 13C-NMR spectral data are summarized in Table 4. The aldehyde carbons (–CHO) of compounds 1 and 2 were observed at 191.0 and 189.13 ppm, respectively. The azomethine carbons were detected at 157.28, 157.37 and 158.88 ppm for compounds 3–5, respectively. In the 13C-NMR spectra, four crown ether carbon (OCH2–CH2O) peaks, aliphatic and aromatic carbons indicate that the molecules 1–5 are symmetric.

Table 4 Selected 13C-NMR spectral data (δ, ppm; in CDCl3)
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Mass spectra

The fragmentation patterns of the compounds were in good agreement with the suggested structures. For compound (1) molecular peak was not observed, but important fragments were detected at m/z 326.2 (20 %), 325.1 (100 %), 295.2 (28.1 %), 237.1 (6.25 %), 207.1 (12.5 %) and 163.1 (21.9 %). The major fragments for compounds (2, 3 and 5) at m/z 614.2 (81.25 %), 671.3 (100 %) and 685.2 (97 %) corresponding to the [M + H2O]+, [M + H + 2H2O]+, and [M + H + 2H2O]+, respectively.

In the API-ES mass spectra of complexes (3a and 3b) the dominant peak at m/z 329.9 (100 %) corresponds to the [C16H24O7 + H]+. For sodium complex (3a) the peak at m/z 657.9 (34 %) corresponds to the ligand plus sodium [M + Na]+. For sodium and potassium complexes (3a and 3b) important fragments at m/z 635.9 correspond to the [M + H]+ (ligand molecular ion peak). All of the mass spectra show that this fragmentation pattern proceeds by the loss of ether chains in accordance with literature [27–30]. The molecular ion peaks and fragments of the ligands and complexes support the proposed structures.