6736 J. Am. Chem. Soc., Vol. 120, No. 27, 1998
MolenVeld et al.
5,17-Diformyl-25,26,27,28-tetrakis(2-ethoxyethoxy)calix[4]-
arene (5). This compound was synthesized by an improved literature
procedure.21c To a solution of tetrakis(2-ethoxyethoxy)calix[4]arene
4 (8.00 g, 11.2 mmol) in CHCl3 (250 mL) cooled at -10 °C was added
1,1-dichlorodimethyl ether (34.0 mL, 333 mmol). The solution was
vigorously stirred, while tin tetrachloride (40.0 mL, 342 mmol) was
added rapidly. The reaction mixture was stirred at -10 °C for 30 min,
quenched carefully with water (600 mL), and vigorously stirred at room
temperature for an additional 30 min. The organic layer was separated,
washed with saturated Na2CO3 solution (300 mL) and water (2 × 300
mL), and dried over MgSO4. The solvent was removed under reduced
pressure, and the crude product was purified by column chromatography
(hexane/EtOAc, 3/2) to give 5 as a colorless oil (7.62 g, 87%).
Spectroscopic data were the same as reported.
25,26,27,28-Tetrakis(2-ethoxyethoxy)calix[4]arene-5,17-dicar-
boxylic Acid Diethyl Ester (7). A solution of calix[4]arenedicarboxylic
acid 630 (3.67 g, 4.58 mmol) and p-toluenesulfonic acid (174 mg, 0.92
mmol) in EtOH (150 mL) was refluxed for 5 days. The solvent was
removed under reduced pressure, and the residue was dissolved in CH2-
Cl2 (250 mL) and washed twice with saturated NaHCO3 solution (150
mL) and water (150 mL). The organic layer was dried over MgSO4,
and the solvent was removed under reduced pressure. The residue was
purified by column chromatography (CH2Cl2/EtOAc, 95/5) to give 7
as a colorless oil (3.85 g, 98%). 1H NMR (CDCl3, 250 MHz): δ (ppm)
7.77 (s, 4 H), 6.33-6.21 (m, 6 H), 4.54 and 3.23 (AB q, 8 H, J ) 13.5
Hz), 4.41-4.33 (m, 8 H), 3.97 (t, 4 H, J ) 4.8 Hz), 3.88 (t, 4 H, J )
5.8 Hz), 3.78 (t, 4 H, J ) 4.8 Hz), 3.58 (q, 4 H, J ) 7.0 Hz), 3.49 (q,
4 H, J ) 7.0 Hz), 1.41 (t, 6 H, J ) 7.1 Hz), 1.24 (t, 6 H, J ) 7.0 Hz),
1.15 (t, 6 H, J ) 7.0 Hz). 13C NMR (CDCl3, 250 MHz): δ (ppm)
166.9, 162.2, 154.8, 136.6, 132.9, 130.2, 124.1, 122.6, 73.9, 72.9, 69.9,
69.6, 66.5, 66.2, 60.6, 30.8, 15.3, 15.2, 14.5. FAB-MS m/z 827.4 ([M
- CH2CH3]+, calcd 827.4), 856.4 ([M]-, 856.4), 811.4 ([M -
OCH2CH3]-, 811.4).
MS m/z 313.2 ([M + H]+, calcd 313.2). Anal. Calcd for
C17H20N4O2: C, 65.37; H, 6.45; N, 17.94. Found: C, 65.04; H, 6.33;
N, 17.70.
Spectrophotometric Titrations. To a cuvet containing 2 mL of
35% EtOH/20 mM aqueous MES solution pH 6.0 (v/v, see kinetics)31
was added 3 µL of a 50 mM ligand (2 or 3) stock solution in EtOH.
The increase in absorbance at 274 nm at 25 °C by the ligand (ꢀ274
)
2.8 × 103) was followed upon the stepwise addition of 0.5 µL of 50
mM Cu(ClO4)2 in EtOH up to 4 equiv for dinuclear complex 2-[Cu-
(II)]2, and up to 2 equiv for formation of the mononuclear Cu(II)
complex 3-Cu(II). The concentration of the ligand before titration was
0.0749 mM. The absorbance was corrected for both dilution upon
titration and for the weak absorbance of free Cu(ClO4)2 (ꢀ274 ) 1.4 ×
102). Stability constants for Cu(II) complexation were estimated by
nonlinear least squares fitting32 of the titration curves to a 1:1 model
using the absorption end values at 274 nm.
Potentiometric pH Titrations. Solutions (50 mL) of calix[4]arene
ligand 2 (0.2 mM) in 0.1 M KNO3 in 35% EtOH/H2O (v/v), acidified
with HNO3 (1.2 mM), were titrated under N2 at 25.0 °C in the presence
and absence of 2 equiv of Cu(NO3)2. Solutions (50 mL) of ligand 3
(0.4 mM) in 0.1 M aqueous KNO3, or in 0.1 M KNO3 in 35% EtOH/
H2O (v/v), acidified with HNO3 (1.6 mM), were titrated under N2 at
20.0 °C in the presence and absence of equimolar amounts Cu(NO3)2.
The titrations were carried out with a Schott TPC2000 Titration System
at fixed titrant increments of 10 µL of NaOH solution (0.100 M). During
the titration the pH was measured with a Metrohm 6.0702.100 glass
electrode and a 6.0101.102 (NF) reference electrode. The titration
apparatus was calibrated with appropriate buffers immediately before
use and checked by the pKa determination of acetic acid. At least two
independent pairs of titrations were always made for pKa determinations.
For calculation of deprotonation constants and Cu(II) association
constants from the titration data a multiparameter curve fitting program
based on SUPERQUAD was used.34 The resulting equilibrium
constants could be interpreted as conditional constants at I ) 0.1 M.
The values for Kw () [H+][OH-]) at 25 °C were 10-13.78 and 10-14.26
in 0.1 M aqueous KNO3 and in 0.1 M KNO3 in 35% EtOH/H2O (v/v),
respectively.
X-ray Crystallography. (3)2Cu(ClO4)2: To a solution of 3 (100
mg, 0.32 mmol) and Cu(ClO4)2‚6H2O (118 mg, 0.32 mmol) in EtOH
(4 mL) was added Et2O (3 mL). The obtained blue crystals were
recrystallized by slow vapor diffusion of diisopropyl ether to a
methanolic solution (4 mL), resulting in the formation of crystals
suitable for X-ray crystal structure analysis. (3)Cu(CH3COO)2: To a
suspension of 3 (100 mg, 0.32 mmol) and Cu(CH3COO)2‚H2O (64 mg,
0.32 mmol) in acetonitrile (3 mL) was added MeOH (1 mL), yielding
a clear solution. Slow evaporation of the solution resulted in the
formation of blue crystals suitable for X-ray crystal structure analysis.
Pertinent data for the structure determinations are collected in Table
2. All data were collected on an Enraf-Nonius CAD4T diffractometer
on rotating anode (ω scan, T ) 150 K, Mo KR radiation, graphite
monochromator, λ ) 0.71073 Å). Accurate unit-cell parameters and
an orientation matrix were determined by least-squares fitting of the
setting angles of 25 well-centered reflections (SET4).47 The unit-cell
parameters were checked for the presence of higher lattice symmetry.48
Data were corrected for Lp effects and for the observed linear decay
of the reference reflections. Structures were solved with automated
Patterson and subsequent Fourier methods using SHELXS8649 and
refined on F2 using SHELXL-96.50 No observance criterion was applied
during refinement on F2. The hydroxyl hydrogen atoms were located
on a difference Fourier map, and their coordinates were included as
parameters in the refinement. (For (3)Cu(CH3COO)2 restraints were
introduced to ensure a correct valence angle of the hydroxyl oxygen
atom.) All other hydrogen atoms were included in the refinement on
calculated positions riding on their carrier atoms. The non-hydrogen
5,17-Bis(bis(1-methylimidazol-2-yl)hydroxymethyl)-25,26,27,28-
tetrakis(2-ethoxyethoxy)calix[4]arene (2). To a solution of 1-meth-
ylimidazole (0.17 mL, 2.1 mmol) in THF (20 mL) at -78 °C under Ar
was added n-BuLi (1.31 mL, 1.6 M, 2.1 mmol). After stirring for 1 h
at -78 °C, calix[4]arene diethyl ester 7 (300 mg, 0.35 mmol) in THF
(20 mL) was added dropwise. The reaction mixture was allowed to
warm to room temperature and stirred for 18 h. Brine (50 mL) was
added, and the solution was extracted with CH2Cl2 (3 × 50 mL). The
combined extracts were dried over Na2CO3, and the solvent was
removed under reduced pressure. The residue was purified by column
chromatography (CH2Cl2/MeOH, 95/5) to give 2 as a white foam (325
mg, 85%). 1H NMR (CDCl3, 250 MHz): δ (ppm) 6.94 (d, 4 H, J )
1.0 Hz), 6.84 (d, 4 H, J ) 1.0 Hz), 6.44 (m, 6 H), 6.53 (s, 4 H), 6.20
(br s, 2 H), 4.48 and 3.11 (AB q, 8 H, J ) 13.0 Hz), 4.14 (t, 4 H, J )
5.7 Hz), 4.09 (t, 4 H, J ) 5.5 Hz), 3.85 (t, 4 H, J ) 5.5 Hz), 3.83 (t,
4 H, J ) 5.7 Hz), 3.53 (q, 4 H, J ) 7.0 Hz), 3.52 (q, 4 H, J ) 7.0 Hz),
3.14 (s, 12 H), 1.20 (t, 6 H, J ) 7.0 Hz), 1.18 (t, 6 H, J ) 7.0 Hz). 13
C
NMR (CDCl3, 250 MHz): δ (ppm) 156.6, 155.6, 148.8, 135.3, 135.2,
134.6, 128.1, 127.8, 125.7, 123.4, 122.3, 74.5, 73.5, 73.2, 69.7, 69.5,
66.4, 66.3, 34.8, 30.8, 15.3. FAB-MS m/z 1093.8 ([M + H]+, calcd
1093.6). Anal. Calcd for C62H76N8O10‚2.5H2O: C, 65.42; H, 7.11;
N, 9.84. Found: C, 65.39; H, 6.88; N, 9.75.
Bis(1-methylimidazol-2-yl)-4-ethoxy-phenylhydroxymethane (3).
To a solution of 1-methylimidazole (5.18 mL, 65.0 mmol) in THF (300
mL) at -78 °C under Ar was added n-BuLi (40.6 mL, 1.6 M, 65.0
mmol). After stirring for 1 h at -78 °C, 4-ethoxybenzoic acid ethyl
ester46 (4.21 g, 21.7 mmol) in THF (50 mL) was added dropwise. The
reaction mixture was allowed to warm to room temperature and stirred
for 6 h. Brine (300 mL) was added, and the solution was extracted
with CH2Cl2 (3 × 200 mL). The combined extracts were dried over
Na2CO3, the solvent was removed under reduced pressure, and the
residue was triturated with diisopropyl ether. The resulting white
powder was recrystalized from CH2Cl2/diisopropyl ether to yield 3 (5.11
g, 75%). Mp 150-152 °C. 1H NMR (CDCl3, 250 MHz): δ (ppm)
6.96 (s, 2 H), 6.89 (s, 2 H), 6.83 (d, 2 H, J ) 8.6 Hz), 6.99 (d, 2 H, J
) 8.6 Hz), 6.50 (br s, 1 H), 4.01 (q, 2 H, J ) 6.9 Hz), 3.38 (s, 6 H),
1.39 (t, 3 H, J ) 6.9 Hz). 13C NMR (CDCl3, 250 MHz): δ (ppm)
158.8, 134.1, 128.7, 125.8, 123.4, 114.1, 74.6, 63.4, 34.7, 14.8. FAB-
(47) Boer, J. L. de; Duisenberg, A. J. M. Acta Crystallogr. 1984, A40,
C-410.
(48) Spek, A. L. J. Appl. Crystallogr. 1988, 21, 578.
(49) Sheldrick, G. M. SHELXS86 Program for crystal structure deter-
mination, University of Go¨ttingen, Germany, 1986.
(50) Sheldrick, G. M. SHELXL-96 Program for crystal structure refine-
ment, University of Go¨ttingen, Germany, 1996.