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vol.49 issue4EDITORIALVANADIUM(III) COMPLEXES IN AQUEOUS SOLUTION WITH THE DICARBOXYLIC OXALIC, MALONIC AND SUCCINIC ACIDS author indexsubject indexarticles search
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Journal of the Chilean Chemical Society

On-line version ISSN 0717-9707

J. Chil. Chem. Soc. vol.49 no.4 Concepción Dec. 2004

http://dx.doi.org/10.4067/S0717-97072004000400002 

  J. Chil. Chem. Soc., 49, N 4 (2004): págs: 281-284

LOWER RIM p-TERT-BUTYLCALIX[4]ARENE DERIVATIVES CONTAINING GALACTITOL PENDANTS. COMPLEXATION OF 5,11,17,23-TETRAKIS-(1,1-DIMETHYLETHYL)-25,27-DIHYDROXY -26,28-BIS-2-N-(1-DEOXY-D-GALACTITYL)-AMINOETHOXYCALIX[4]ARENE WITH Pb(II) AND F(-I).

 

PABLO J. CACERES1, JUAN COSTAMAGNA1, ANGELA DANIL DE NAMOR2, AND BETTY MATSUHIRO1*

1Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.2Laboratory of Thermochemistry, Department of Chemistry, School of Physical Sciences, University of Surrey, Guildford, Surrey E-mail: bmatsuhi@lauca.usach.cl


ABSTRACT

Reductive amination of D-galactose with the bisubstituted p-tert-butylcalix[4]arylethylamine in the presence of sodium cyanoborohydride allowed the introduction of one or two galactitol residues as pendants on the lower rim. The bisubstituted secondary amine, 5,11,17,23-tetrakis-(1,1-dimethylethyl)-25,27-dihydroxy-26,28-bis-2-N-(1-deoxy-D-galactityl)-aminoethoxycalix[4]arene (III) was obtained in 24.1% yield. Complexation of this compound with Pb (II) and F(-I) was studied by 1H-NMR and spectrophotometric titration in acetonitrile, showing a stoichiometry of 1:2 (ligand:ion) with equilibrium constants of log K1=2.22 ± 0.08 and log K2=2.07 ± 0.07 for Pb(II), and log K1=1.21 ± 0.05 and log K2=1,17 ± 0.04 for F (-I) ion.

Keywords: calix-sugars, galactitol derivatives of calix[4]arenes, ligands, complexation


INTRODUCTION

Calixarenes are produced by base induced condensation of p-substituted phenols with formaldehyde. By modification of the reaction conditions it is possible to prepare calixarenes with 4-8 phenolic residues. Calix[4]arenes have recently received much attention, as they may adopt four different conformations (cone, partial cone, 1,2-alternate, and 1,3 alternate).1,2 By functionalization of lower and upper rims many derivatives have been prepared to meet different needs. Some of them may interact selectively with ionic or neutral species, such as metal cations, amines, aminoacids, carbohydrates and nucleic acids1,3-7. Sugar calixarenes were prepared by substitution of calix[4]arenes at the lower and upper rims with O-glycosyl groups. An upper rim modified calix[4]arene by four galactopyranosyl residues showed interaction with D-glucosamine hydrochloride while neutral carbohydrates were not complexed.8,9

Calixarene derivatives with sugar residues in the lower rim constitute interesting hosts for the selective complexation of ionic species.

EXPERIMENTAL

General procedures

Bromoacetonitrile, p-tert-butilcalix[4]arene, lithium aluminium hydride, lead (II) perchlorate, and acetonitrile-d3 were purchased from Aldrich. Sodium cyanoborohydride from Aldrich was purified according to the literature.10 Acetonitrile (Fisher) was purified by treatment with calcium hydride during 12 h and then refluxing for 4 h. The distillate was collected over molecular sieves (4Å) and used within 7 days. Tetrabutylammonium fluoride (Fluka) was dried over phosphorous pentoxide in vacuum at room temperature for 7 days. The reaction products were dried at 70 C and 0.2 mm Hg over phosphorus pentoxide. The melting points were determined using an Electrothermal apparatus and are not corrected. Microanalyses were performed at the Facultad de Química, Universidad Católica de Chile. UV-vis spectra were recorded using CECIL 8000 and Genesys 2 spectrophotometers. FT-IR spectra of KBr pellets were recorded in the 4000-400 cm-1 region on a Bruker IFS 66v instrument with a resolution of 4 cm-1. Raman spectra of the powdered samples packed into stainless-steel cups were recorded in the 3500-10 cm-1 region with a Bruker FRA 106 equipment interfaced to the IFS spectrometer. A Nd:YAG laser with a wavelength of 1064 nm was used. The NMR spectra were recorded on Bruker Avance DRX 400 spectrometer operating at 400.13 MHz (1H) and 100.62 MHz (13C) at 30 C. Two-dimensional spectra (COSY and HMQC) were measured using standard Bruker software.

5,11,17,23-tetrakis-(1,1-dimethylethyl)-25,27-dihydroxy-26,28-bis -cyanomethoxycalix[4]arene (I).

I was obtained in 67.5% yield by reaction of p-tert-butylcalix[4]arene with bromoacetonitrile as described in the literature11 as white needles, mp >300 °C, lit.11 mp >300 °C,. Raman cm-1: 2240 (n CN). 1H NMR, 300 MHz (CDCl3): d 7.12 (s, Ar-H, 4H), 6.72 (s, Ar-H, 4H), 5.55 (s, Ar-OH, 2H), 4.81 (s, O-CH2-CN, 4H), 4.22 (d, J 12.90 Hz, Hax, 4H), 3.45 (d, J 12.90 Hz, Heq 4H), 1.32 (s, C(CH3)3,18H), 0.88 (s, C(CH3)3,18H).

5,11,17,23-tetrakis-(1,1-dimethylethyl)-25,27-dihydroxy-26,28-bis -aminoethoxycalix[4]arene(II).

Reduction of I with lithium aluminum hydride was carried out according to Wen-Chun and Zhi-Tang.12 II was obtained in 80% yield as white crystals from MeOH-H2O (5:1), mp. 200-201 C, lit.11 mp 220-222 C. IR (KBr) cm-1: 3368 (n N-H).1H NMR 400 MHz(CDCl3): d 7.04 (s, Ar-H, 4H), 6.97 (s, Ar-H, 4H), 4.33 (d, J 12.90 Hz, Hax, 4H), 4.07 (t, J 4.7 Hz, O-CH2CH2-N, 4H, ), 3.37 (d, J 12.90 Hz, Heq, 4H), 3.31 (t, J 4.7 Hz, O-CH2CH2-N, 4H), 1.25 (s, C(CH3)3, 18H), 1.10 (s, C(CH3)3, 18H).

5,11,17,23-tetrakis-(1,1-dimethylethyl)-25,27-dihydroxy-26,28-bis -2-N-(1-deoxygalactityl)-aminoethoxycalix[4]arene (III) and 5,11,17,23-tetrakis-(1,1-dimethylethyl)-25,26,27-trihydroxy-28-2-N -(1-deoxygalactityl)-aminoethoxy-calix[4]arene (IV).

In a 10 mL two-necked flask equipped with a dropping funnel with a pressure-equalising side tube and a condenser, compound II (0.200 g, 0.27 mmol), 3 mL of MeOH and 135 mL of water were added. A solution of D-galactose (0.194 g, 1.08 mmol) in 3 mL of water, 0.020 g (0.27 mmol) of sodium cyanoborohydride and 11 mL of glacial acetic acid were placed in the dropping funnel. The reaction flask was heated, under nitrogen, in a water bath at 80 C and the content of the dropping funnel was added over a period of 10 minutes. The resulting mixture was refluxed for 10 h and then the solvent was removed in vacuo. The residue was suspended in 20 mL of EtOH and filtered. The filtrate was concentrated in vacuo and the resulting solid was recrystallized from EtOH:water (5:1) giving III as needles, mp. 120-121 C in 24.1 % yield. IR (KBr) cm-1: 3382 (O-H). Anal. Calcd. for C68H106N2O14 2H2O: C, 67.44; H, 9.09; N, 2.35. Found: C, 67.56; H, 8.99; N, 2.38. The residue of the first filtration was suspended in 20 mL of CH2Cl2, filtered, and the filtrate was concentrated in vacuo and purified using silica gel column chromatography (ethanol:dichloromethane 1:6 as eluent). The resulting solid was recrystallized from CH2Cl2-MeOH (4:1) to give crystals of IV mp. 145-147 °C in 6.0 % yield. IR (KBr) cm-1: 3494 (N-H), 3374 (O-H). Anal. Calcd. for C58H86N2O9 H2O: C, 71.60; H, 9.05; N, 2.88. Found: C, 71.87; H, 9.11, N, 2.24. A large amount of t-butylcalyx[4]arene (~60% yield), remained in the residue.

Ion addition shift in 1H NMR spectra

In an NMR tube, aliquots of 0.100 mL (±0.0001 mL) of a 0.03 mol L-1 solutions of Pb(II) (or F-) in acetonitrile-d3 were added to 0.500 mL of a 3 x 10-3 mol L-1 solution of III in acetonitrile-d3. The 1H NMR spectrum was recorded after every addition.

Spectrophotometric titration

The UV-spectrum of 2.00 mL of a 2 x 10-4 mol L-1 of III in acetonitrile was recorded in the 230-350 nm region. Aliquots of 0.015 mL (±0.0001 mL) of 4 x 10-3 mol L-1 solutions of Pb(II) (or F-) in acetonitrile were added to complete 0.3 mL, and the UV-spectrum was recorded in the same region after each addition. The [ion]/[ligand] ratio was determined from the absorbance versus concentrations curves. The equilibrium constants were calculated using the Hyperquad program.13

RESULTS AND DISCUSSION

Derivatization of the lower rim of calix[4]arene by reaction with bromoacetonitrile was accomplished as described in the literature. Compound I did not show the CN strechting band in the IR spectrum, but this band appeared at 2240.3 cm-1 in the Raman spectrum. This may be explained considering that the two cyano groups adopt opposite directions in the molecule, cancelling the individual dipole moments.11 Analysis of the 1H NMR spectrum of I showed a Dd value of 0.8 ppm between the axial and equatorial protons of the methylene bridge. This result indicates, according to Gutsche et al.,14 that only the cone conformer is present.

Reduction of the cyano derivative of calixarene I with lithium aluminum hydride gave the amine derivative II. Its melting point differs significantly from that reported by Collins et al.11, who mentioned that the product was recrystallized from EtOH-CH2Cl2. In this work, II was obtained from MeOH-H2O, its 1H NMR spectrum was fully assigned, and no signals due to impurities were found.

The reductive amination of monosaccharides with compound II was difficult to achieve. Products were obtained by using acetic acid to maintain an acidic medium.15 Satisfactory yields were obtained by reaction of II with D-galactose. Extraction of the reaction mixture with EtOH afforded, after recrystallization, compound III in a 24.1 % yield. The residue of the ethanolic extraction was dried and then the fraction soluble in dichloromethane was analyzed by TLC. Two major spots were found, indicating the presence of the starting calix[4]arene and other calixarene-derivatives. The dichloromethane fraction was then separated by silica-gel column chromatography. The total yield of the recrystallized reaction products is acceptable taking into consideration that the starting t-butylcalix[4]arene was recovered in ~60 % yield. The low yields of these reactions can be explained from several points of views. On one hand, there is a large difference in solubility, since II is soluble in ethanol but insoluble in water, and the monosaccharides are water soluble, but ethanol insoluble. The reaction was carried out in a mixture of ethanol-water, which increases slightly the solubility of both compounds, but in essence the reaction was carried out in a heterogeneous medium. On the other hand, II can be associated to a monosaccharide, which could cause steric interference of the functional groups, preventing the reaction from occurring.

The 1H NMR spectrum of III shows the signals correponding to the amine derivative of calixarene, essentially those assigned in compound II, and a series of signals between 4.3-3.3 ppm corresponding to the galactitol residue. Assignements of the signals due to the protons of the sugar residue is very difficult to achieve. It was found that the difference between the axial and equatorial protons of the methylene bridge Dd(Hax-Heq) is 0.80 ppm, which would be associated to a calixarene in perfect cone conformation or a calixarene derivative with two aromatic rings close to each other compared to the other two. The second option is the most possible conformation due to the electrostatic repulsion produced between the hydroxyl groups and the sugar residues.

The 1H NMR spectrum of compound IV is quite complex, but with the aid of the COSY 1H-1H spectrum (Fig. 1) the assignement of the methylene protons of the aminecalixarene residue was accomplished. No signal attributed to the anomeric protons of galactose were found. The NMR HMQC 13C-1H spectrum of IV (Fig. 2) shows the presence of various different aromatic and tert-butyl hydrogens as well as of the corresponding 13C atoms, which indicates that the symmetrical substitution pattern of the starting material, compound II, is lost.


 
Fig. 1.- NMR COSY 1H-1H spectrum of IV I n CDCl3, 400 MHz.


 
Fig. 2. NMR HMQC 13C- 1H spectrum of IV in CDCl3, 400 MHz.

These results, together with the microanalysis data, are consistent with the proposed structure for IV. Figure 3 shows the proposed structures for compounds III and IV.


 
Fig. 3. Proposed structures for compounds III and

Complexation studies

The Pb (II) and F(-I) ions were chosen to study the complexation with compound III, since it had been previously found that these two ions were good models in complexation studies with amide-derivatives of calix[4]arenes16.

The introduction of ions into III causes the modification of its structure. By addition of Pb(II) a Dd(Hax-Hec) = 0.61 ppm was obtained, which indicates the presence of an open cone conformation. On the other hand, addition of F(-I) produced a Dd(Hax-Hec) = 0.72 ppm. In the presence of Pb(II) a shift of the 1H NMR signals of III is produced (Table 1). The shift to lower field of the protons close to the nitrogen (Dd= 0.25 ppm) suggests that the interaction of the ligand and the ion can be produced in the cavities formed by both the secondary amine group and the methylene bridge atoms, and the alcohol groups of the two chains of sugar residues.


Table 1. 1H NMR complexation-induced shifts in compound III with Pb(II) and F-.

H D d (ppm)

  Pb2+ F-

a -0.020 -0.010
b 0.00 0.00
c 0.07 0.02
d 0.02 0.01
e 0.02 0.02
f 0.25 -0.040
g 0.26 -0.050
h - -
i 0.11 0.05
j -0.220 -0.030

The 1H NMR spectrum of III after the addition of F (-I) showed shifts to higher field of the f and g protons and of the protons of the galactitol residue (not quantified), as shown in Table 1, which indicates that in this case the interaction is produced by the hydrogens of the methylene groups linked to the N atom and of the bridge, and the sugar hydroxyl hydrogens.

The spectrophotometric titration of III with Pb(II) shows that the reaction in acetonitrile presents a 2:1 stoichiometry (Pb2+: III) (Fig. 4). In the same way, the reaction of III with F(-I) showed a stoichiometry of 2:1 (F-: III) (Fig. 5).


 
IV Fig. 4.- Spectrophotometric titration curves of III with Pb2+ in acetonitrile at 303.3 K.


 
Fig. 5.- Spectrophotometric titration curve of III with F- in acetonitrile, 302.3 °K

Based on the minimum square approximation for assumed equilibrium constants at each point of the titration curve, and other numerical approximations, the Hyperquad13 program can determine the value of the equilibrium constant for the process of incorporation of two ions. Thus, for the reaction of III with Pb(II) the equilibrium constants are: log K1=2.22 ± 0.08 and log K2=2.07 ± 0.07, while for the III and F(-I) reaction the equilibrium constants are log K1=1.21 ± 0.05; log K2=1.17 ± 0.04.

The equilibrium constants are of the same order as the equilibrium constants found for the complexation of the bisustituted t-butylcalix[4]arene-isopropylacetamide with divalent ions and fluoride ion in acetonitrile16. In the former case a 1:1 stoichiometry was found.

In summary, introduction of two monosaccharide residues into bisustituted p-tert-butylcalix[4]arylethylamine as pendants affords compounds potentially useful as extractants of contaminating agents.

 

ACKNOWLEDGEMENTS

Financial support by ERBIC 18CT970140 CEE and by the Dirección de Investigaciones of the Universidad de Santiago de Chile is gratefully acknowledged. P.J.Cáceres is indebted to CONICYT (Chile) for a fellowship during 2002. The authors thank Dr. Juan Guerrero and grant MECESUP USA-0007 for the NMR spectra.

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(Received: June 25, 2004 - Accepted: July 7, 2004)

 

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