Calixarene Metalloreceptors. Synthesis and Molecular Recognition Properties of Upper-Rim Functionalized Calix[4]arenes Containing an Organopalladium Binding Site

Article abstract of DOI:10.1021/ic9705913

The compound 5,17-bis(2-chloroacetamido)-25,26,27,28-tetrapropoxycalix[4]arene, 4, was prepared in the cone conformation by the published method. Compound 4 was reacted with α,α'-m-xylenedithiol and sodium ethoxide under high-dilution conditions in ethanol solution. The resulting macrobicyclic calix[4]arene, HL¹, 5, contains a symmetrically disposed macrocyclic loop across the upper rim of the calix[4]arene. Palladation of 5 yielded [Pd(L¹)(CH₃CN)][BF₄], 6. Similarly 5,17-bis[2-(4-(chloromethyl)phenoxy)acetamido]-25,26,27,28-tetrapropoxycalix[4] arene, 8, was used to prepare HL², 9. Compound 9 is similar to 5 but contains an aromatic spacer group separating the xylyl fragment from the calixarene unit. Palladation of 9 yielded [Pd(L²)(CH₃CN)][BF₄], 11. All new compounds and complexes were characterized in solution by ¹H NMR spectroscopy, and the molecular structure of 5 was verified by a single-crystal X-ray diffraction study. Compound 5 crystallized in the space group P2₁/c with a = 23.5095(1) A?, b = 9.9090(1) A?, c = 23.3586(1) A?, β= 91.53(1)°, V = 5439.59(8) A?³, and Z = 4. The structure was refined to R(F) = 10.13% and R_W(F²) = 21.91% for 5799 reflections with F₀² > 2α(F₀²). Compounds 6 and 11 are calix[4]arene-based metalloreceptors containing an organopalladium binding site and a hydrophobic cavity provided by the calix[4]arene. Binding of a substrate through α-bonding to the palladium center and interaction within the hydrophobic site were demonstrated in solution by ¹H NMR spectroscopy. These multiple receptor-substrate interactions are used by 11 for the molecular recognition of 4-phenylpyridine in the presence of 2-phenylpyridine or 3-phenylpyridine.

Full text of DOI:10.1021/ic9705913

5498
Inorg. Chem. 1997, 36, 5498-5504
Calixarene Metalloreceptors. Synthesis and Molecular Recognition Properties of
Upper-Rim Functionalized Calix[4]arenes Containing an Organopalladium Binding Site
Beth R. Cameron, Stephen J. Loeb,* and Glenn P. A. Yap
Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada N9B 3P4
ReceiVed May 16, 1997X
The compound 5,17-bis(2-chloroacetamido)-25,26,27,28-tetrapropoxycalix[4]arene, 4, was prepared in the cone
conformation by the published method. Compound 4 was reacted with R,R′-m-xylenedithiol and sodium ethoxide
under high-dilution conditions in ethanol solution. The resulting macrobicyclic calix[4]arene, HL1, 5, contains a
symmetrically disposed macrocyclic loop across the upper rim of the calix[4]arene. Palladation of 5 yielded
[Pd(L1)(CH3CN)][BF4], 6. Similarly 5,17-bis[2-(4-(chloromethyl)phenoxy)acetamido]-25,26,27,28-tetrapropoxycalix-
[4]arene, 8, was used to prepare HL2, 9. Compound 9 is similar to 5 but contains an aromatic spacer group
separating the xylyl fragment from the calixarene unit. Palladation of 9 yielded [Pd(L2)(CH3CN)][BF4], 11. All
1
new compounds and complexes were characterized in solution by H NMR spectroscopy, and the molecular
structure of 5 was verified by a single-crystal X-ray diffraction study. Compound 5 crystallized in the space
group P21/c with a ) 23.5095(1) Å, b ) 9.9090(1) Å, c ) 23.3586(1) Å, â ) 91.53(1)°, V ) 5439.59(8) Å3, and
2
Z ) 4. The structure was refined to R(F) ) 10.13% and Rw(F2) ) 21.91% for 5799 reflections with Fo
>
2
2σ(Fo ). Compounds 6 and 11 are calix[4]arene-based metalloreceptors containing an organopalladium binding
site and a hydrophobic cavity provided by the calix[4]arene. Binding of a substrate through σ-bonding to the
palladium center and interaction within the hydrophobic site were demonstrated in solution by 1H NMR
spectroscopy. These multiple receptor-substrate interactions are used by 11 for the molecular recognition of
4-phenylpyridine in the presence of 2-phenylpyridine or 3-phenylpyridine.
Introduction
hydrophobic cavity.14 Our strategy was the construction of a
“handle” on the top of the calixarene “basket”. This would
Metal complexes which contain a ligand with additional sites
for noncovalent binding have been employed as hosts for a
variety of neutral, cationic, and anionic guests. These complexes
are often referred to as metalloreceptors.1,2 In previous reports,
we have described a series of organopalladium-based metallo-
receptors with peripheral sites capable of hydrogen-bonding and/
or π-stacking interactions. These complexes have been suc-
cessfully applied to the molecular recognition of aliphatic
amines,2 aromatic amines,3 hydrazines,4 and DNA nucleobases.5
In an effort to increase the scope of these metalloreceptors
for a range of substrates, we designed a series of receptors in
which the subunit for second-sphere, noncovalent interaction
is a calix[4]arene unit.6 Calix[4]arenes7 are known to act as
receptors for cationic,7,8 anionic,9-11 or neutral12,13 substrates
by providing a platform for the attachment of convergent binding
groups, at the upper15,12 or lower rim,8,9,13 or by utilizing the
bowl-shaped arrangement of the four aromatic groups as a
allow for the possibility that a peripherally coordinated metal
center (handle) would have a binding site oriented toward the
hydrophobic cavity of the calix[4]arene (basket). A substrate
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Calixarenes: A Versatile Class of Macrocyclic Compounds; Kluwer
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(10) Beer, P. D.; Drew, M. G. B.; Hazelwood, C.; Hesek, D.; Hodacova,
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J. Chem. Soc., Chem. Commun. 1995, 1727. (b) van Loon, J.-D.; Heida,
J. F.; Verboom, W.; Reinhoudt, D. N. Recl. TraV. Chim. Pays-Bas
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57, 4527.
(13) (a) Beer, P. D.; Chen, Z.; Goulden, A. J.; Grieve, A.; Hesek, D.;
Szemes, F.; Wear, T. J. Chem. Soc., Chem. Commun. 1994, 1269. (b)
Giannini, L.; Solari, E.; Zanotti-Gerosa, A.; Floriani, C.; Chiesi-Villa,
A.; Rizzoli, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2825. (c) Xu,
B.; Carroll, P. J.; Swager, T. M. Angew. Chem., Int. Ed. Engl. 1996,
35, 2094. (d) Giannini, L.; Solari, E.; Zanotti-Gerosa, A.; Floriani,
C.; Chiesi-Villa, A.; Rizzoli, C. Angew. Chem., Int. Ed. Engl. 1996,
35, 85. (e) Stolmar, M.; Floriani, C.; Chiesi-Villa, A.; Rizzoli, C. Inorg.
Chem. 1997, 36, 1074.
X Abstract published in AdVance ACS Abstracts, October 15, 1997.
(1) (a) van Staveren, C. J. M.; van Veggel, J. F. C.; Harkema, S.;
Reinhoudt, D. N. J. Am. Chem. Soc. 1988, 110, 4994. (b) van Doorn,
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Reetz, M. T.; Niemeyer, C. M.; Hermes, M.; Goddard, M. Angew.
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2003.
S0020-1669(97)00591-0 CCC: $14.00 © 1997 American Chemical Society

Calixarene Metalloreceptors
Inorganic Chemistry, Vol. 36, No. 24, 1997 5499
79.82, 77.82, 45.91 (br), 45.25 (br), 31.96, 24.61, 24.28, 11.23, 10.27.
LSI-MS: [M - CH3CN - BF4]+ m/z 978. Anal. Calcd for
C54H62BF4N3O6PdS2‚CHCl3‚CH3OH: C, 53.53; H, 5.44; N, 3.35.
Found: C, 53.56; H, 5.49; N, 2.92.
could potentially interact simultaneously with the metal center
and the calixarene cavity. The synthesis of these new metallo-
receptors is reported herein along with preliminary studies to
demonstrate molecular recognition of bound substrate using
phenyl-substituted aromatic amines.
Preparation of 5,17-Bis[2-(4-(hydroxymethyl)phenoxy)acetamido]-
25,26,27,28-tetrapropoxycalix[4]arene (7). 4-Hydroxybenzyl alcohol
(0.0384 g, 0.31 mmol) and K2CO3 (0.0257 g, 0.186 mmol) were
refluxed in acetonitrile (10 mL) for 1 h. Compound 4 (0.120 g, 0.155
mmol) in acetonitrile (5 mL) was added, and the reaction mixture was
refluxed 12 h. The solvent was removed under vacuum, and the residue
was dissolved in CH2Cl2. This solution was washed with 0.1 M HCl
(three times) and H2O (once). The organic layer was dried over
anhydrous MgSO4 and filtered. The white solid product was isolated
after removal of the solvent. Yield: 0.128 g (87%). 1H NMR
(CDCl3): δ (ppm) 7.94 (s, NH, 2H), 7.24 (d, Ar H, 4H), 6.84 (m, Ar
H, 8H), 6.59 (m, Ar H, 6H), 4.60 (s, CH2OH, 4H), 4.43 (d, ArCH2,
4H), 4.36 (s, CH2CO, 4H), 3.82 (m, ArOCH2, 8H), 3.14 (d, ArCH2,
4H), 1.89 (m, CH2, 8H), 0.97 (m, CH3, 12H). 13C NMR (CDCl3): δ
(ppm) 165.64 (CdO), 156.51, 156.32, 154.09, 135.81, 134.84, 134.49,
130.41, 128.76, 128.18, 122.20, 120.80, 114.89 (Ar C), 76.79 (OCH2),
67.56 (CH2CdO), 64.70 (CH2OH), 31.03 (ArCH2), 23.21 (CH2), 10.33
(CH3). LSI-MS: [M+1] ) 951. Anal. Calcd for C58H66N2O10: C,
73.23; H, 7.01; N, 2.95. Found: C, 73.36; H, 7.12; N, 2.92.
Preparation of 5,17-Bis[2-(4-(chloromethyl)phenoxy)acetamido]-
25,26,27,28-tetrapropoxycalix[4]arene (8). Compound 7 (0.12 g,
0.127 mmol) was dissolved in CH2Cl2 (5 mL), and the solution was
cooled in an ice bath to 0 °C. Thionyl chloride (100 µL) was added
to the above solution, and stirring was continued for 1 h at room
temperature. Solvent and excess thionyl chloride were removed under
vacuum. The residue was dissolved in CH2Cl2 and washed with 1 M
Na2CO3 (three times). The organic layer was dried over MgSO4 and
filtered, and the solvent was removed to yield a white solid product.
Yield: 0.11 g (90%). 1H NMR (CDCl3): δ (ppm) 7.91 (s, NH, 2H),
7.31 (d, Ar H, 4H), 6.86 (m, Ar H, 8H), 6.56 (m, Ar H, 6H), 4.55 (s,
CH2Cl, 4H), 4.43 (m, ArCH2 + CH2CO, 8H), 3.81 (m, ArOCH2, 8H),
3.14 (d, ArCH2, 4H), 1.90 (m, CH2, 8H), 0.98 (m, CH3, 12H). 13C
NMR (CDCl3): δ (ppm) 165.50 (CO), 157.30, 156.50, 154.20, 136.02,
134.53, 131.45, 130.46, 128.26, 122.31, 120.89, 115.16 (Ar C), 6.90
(OCH2), 67.63 (CH2CO), 45.92 (CH2Cl), 31.14 (ArCH2), 23.35, 23.26
(CH2), 10.47, 10.37 (CH3). LSI-MS: [M+1] ) 988. Anal. Calcd
for C58H64Cl2N2O8: C, 70.49; H, 6.54; N, 2.84. Found: C, 70.66; H,
6.66; N, 2.91.
Preparation of Macrobicyclic Ligand HL2 (9). Method A.
Ethanol solutions (50 mL) of R,R′-m-xylenedithiol (0.0427 g, 0.25
mmol) and 7 (0.248 g, 0.25 mmol) were added dropwise to a solution
of Na (0.0115 g, 0.5 mmol) in EtOH (100 mL) over a 12 h period at
room temperature. The reaction mixture was stirred an additional 12
h, after which the solvent was removed and the residue was dissolved
in ethyl acetate and washed with H2O. The organic extracts were dried
over anhydrous MgSO4 and the solvent removed. The crude product
was purified by chromatography (SiO2; eluent 1% MeOH/CH2Cl2).
Yield: 0.045 g (17%).
Method B. Diol 10 (0.53 g, 1.4 mmol) and NaH (2.8 mmol) were
suspended in CH3CN (500 mL), and the suspension was brought to
reflux. A solution of 4 (1.08 g, 1.4 mmol) in CH3CN (150 mL) and
CH2Cl2 (minimum amount to dissolve 4) was added dropwise over a
period of 12 h. The resulting mixture was refluxed for an additional
48 h. After cooling to room temperature and removal of solvent, the
residue was dissolved in CH2Cl2 and washed with 1.0 M HCl (twice)
and H2O (once). The organic extracts were dried over anhydrous
MgSO4, and the solvent was removed. The crude product was purified
by chromatography (SiO2; eluent 2% MeOH/CH2Cl2); Rf ) 0.48.
Yield: 0.38 g (25%). 1H NMR (CDCl3): δ (ppm) 7.80 (s, NH, 2H),
7.28 (m, Ar H, 2H), 7.14 (m, Ar H, 8H), 7.00 (m, Ar H, 3H), 6.81 (s,
Ar H, 1H), 6.64 (d, Ar H, 4H), 6.31 (s, Ar H, 4H), 4.47 (d, ArCH2,
4H), 4.20 (s, CH2CO, 4H), 4.08 (t, OCH2, 4H), 3.80 (s, CH3OH, 3H),
3.65 (t, OCH2, 4H), 3.53 (s, CH2S, 4H), 3.50 (s, CH2S, 4H), 3.17 (d,
ArCH2, 4H), 2.00 (m, CH2, 4H), 1.88 (m, CH2, 4H), 1.09 (t, CH3, 6H),
0.89 (t, CH3, 6H). 13C NMR (CDCl3): δ (ppm) 165.22 (CO), 157.75,
155.71, 152.86, 137.48, 136.56, 133.55, 131.48, 130.68, 130.32, 130.15,
129.02, 127.57, 122.26, 121.55, 114.53 (Ar C), 77.18, 76.45 (ArOCH2),
67.07 (CH2CO), 44.40 (CH3OH), 35.02, 34.31 (CH2S), 31.04 (ArCH2),
Experimental Section
All starting materials were purchased from Aldrich and used without
further purification, except acetonitrile, which was distilled from CaH2
under N2(g). All reactions were performed under an atmosphere of
N2(g). 1H NMR and 13C NMR spectra were recorded on a Bruker
AC300 spectrometer locked to the deuterated solvent at 300.1 and 75.5
MHz, respectively. LSI-MS and EI-MS spectra were recorded on a
Kratos Profile mass spectrometer Elemental analyses were performed
by Canadian Microanalytical Service, Delta, British Columbia, Canada.
Preparation of 5,17-Bis(2-chloroacetamido)-25,26,27,28-tetra-
propoxycalix[4]arene (4). This material was prepared from 3 by the
method of Reinhoudt15 and characterized as follows. 1H NMR
(CDCl3): δ (ppm) 7.90 (s, NH, 2H), 6.78 (s, Ar H, 4H), 6.60 (m, Ar
H, 6H), 4.43 (d, ArCH2, 4H), 4.08 (s, CH2Cl, 4H), 3.82 (m, ArOCH2,
8H), 3.13 (d, ArCH2, 4H), 1.90 (m, CH2, 8H), 0.97 (m, CH3, 12H).
Preparation of Macrobicyclic Ligand HL1 (5). R,R′-m-Xylene-
dithiol (57.8 µL, 0.39 mmol) was dissolved in a freshly prepared
ethanolic solution (100 mL) of sodium ethoxide (Na: 0.018 g, 0.78
mmol). 4 (0.303 g, 0.39 mmol) in ethanol (50 mL) was added dropwise
over a 4 h period. The reaction mixture was stirred an additional 12
h at room temperature. The solvent was removed, and the residue was
dissolved in CH2Cl2 and washed successively with 1.0 M HCl, H2O,
and NaHCO3 solutions. The organic extracts were dried over anhydrous
MgSO4, and the solvent was removed. The crude product was
recrystallized from CH2Cl2/CH3CN. Yield: 0.336 g (86%). 1H NMR
(CDCl3): δ (ppm) 7.79 (s, NH, 2H), 7.28-7.11 (m, Ar H, 8H), 6.93
(t, Ar H, 2H), 5.96 (s, Ar H, 4H), 4.42 (d, ArCH2, 4H), 4.03 (t, OCH2,
4H), 3.68-3.59 (m, OCH2 + SCH2, 8H), 3.42 (s, 3H, CH3OH), 3.14
(d, ArCH2, 4H), 2.90 (s, CH2S, 4H), 1.99-1.84 (m, CH2, 8H), 1.09 (t,
CH3, 6H), 0.87 (t, CH3, 6H). 13C NMR (CDCl3): δ (ppm) 167.00
(CO), 157.92, 153.78, 137.12, 136.72, 133.79, 130.36, 130.00, 129.58,
129.05, 128.26, 124.44, 122.33 (Ar C), 77.33, 76.58 (OCH2), 47.54
(CH3OH), 35.52, 34.03 (CH2S), 31.12 (ArCH2), 23.60, 22.98 (CH2),
10.93, 9.87 (CH3). LSI-MS: [M + 1]+ m/z 873. Anal. Calcd for
C52H60N2O6S2‚CH3OH: C, 70.32; H, 7.13; N, 3.10. Found: C, 70.48;
H, 6.75; N, 3.48.
Preparation of Metalloreceptor [Pd(L1)(CH3CN)][BF4] (6). Calix-
arene 5 (0.1 g, 0.12 mmol) was suspended in acetonitrile (50 mL), and
the suspension was heated to reflux. Once 5 had completely dissolved,
a solution of [Pd(CH3CN)4][BF4]2 in acetonitrile was added dropwise
over a period of 15 min. The reaction mixture was refluxed 2 h, and
cooled to room temperature, and the solvent was removed. Yield: 0.12
g (93%). 1H NMR (CD3CN): δ (ppm) 8.29 (s, NH, 2H), 7.69 (br s,
Ar H, 2H), 7.23 (d, Ar H, 4H) 7.05 (s, Ar H, 3H), 6.95 (t, Ar H, 2H),
6.54 (br s, Ar H, 2H), 4.48 (d, ArCH2, 4H), 4.38 (br s, CH2S, 4H),
4.07 (m, CH2S + OCH2, 8H), 3.69 (t, OCH2, 4H), 3.29 (d, ArCH2,
4H), 2.12 (m, CH2, 4H), 1.95 (m, CH2, 4H), 1.02 (t, CH3, 6H), 0.94 (t,
CH3, 6H). 1H NMR (CD3NO2): δ (ppm) 8.09 (s, NH, 2H), 7.72 (br s,
Ar H, 2H), 7.28 (d, Ar H, 4H), 7.08 (m, Ar H, 3H), 7.00 (t, ArCH2,
2H), 6.67 (br s, ArCH2, 2H), 4.59 (d, ArCH2, 4H), 4.45 (br s, CH2S,
4H), 4.21 (s, CH2S, 4H), 4.18 (t, OCH2, 4H), 3.78 (t, OCH2, 4H), 3.33
(d, ArCH2, 4H), 2.21 (m, CH2, 4H), 1.98 (m, CH2, 4H), 1.09 (t, CH3,
6H), 1.01 (t, CH3, 6H), -1.80 (br s, MeCN, 3H). 13C NMR
(CD3NO2): δ (ppm) 164.90 (br), 158.58, 154.92, 148.93 (br), 137.44,
136.11, 134.16 (br), 130.95 (br), 127.76 (br), 124.58 (br), 121.48 (br),
(14) (a) Atwood, J. L.; Orr, G. W.; Bott, S. G.; Robinson, K. D. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1093. (b) McKervey, M. A.; Seward,
E. M.; Ferguson, G.; Ruhl, B. L. J. Org. Chem. 1986, 51, 133. (c)
Andreetti, G. O.; Ungaro, R.; Pochini, A. J. Chem. Soc., Chem.
Commun. 1979, 1005. (d) Gutsche, C. D.; Bauer, L. J. J. Am. Chem.
Soc. 1985, 107, 6052. (e) Bott, S. G.; Coleman, A. W.; Atwood, J. L.
J. Am. Chem. Soc. 1988, 110, 610.
(15) Rudkevich, D. M.; Verboom, W.; Reinhoudt, D. N. J. Org. Chem.
1994, 59, 3683.

5500 Inorganic Chemistry, Vol. 36, No. 24, 1997
Cameron et al.
23.44, 22.85 (CH2), 10.78, 9.75 (CH3). LSI-MS: [M+1] ) 1085. Anal.
Calcd for C66H72N2O8S2‚CH3OH: C, 72.01; H, 6.86; N, 2.51. Found:
C, 71.96; H, 6.54; N, 2.48.
Table 1. Crystallographic Data for 5‚2CH3CN
formula
fw
a, Å
C56H66N4O6S2
955.25
23.5095(1)
9.9090(1)
F, g cm-3
Z
1.17
4
1.49
25
1.208
10.13
21.91
µ, cm-1
T, °C
Preparation of Dithioether Diol (10). 4-Hydroxybenzyl alcohol
(1.46 g, 11.76 mmol), R,R′-m-xylenedithiol (0.5 g, 2.94 mmol), and a
catalytic amount of p-toluenesulfonic acid were refluxed in CH3CN
for 24 h. The solvent was removed under vacuum, the residue dissolved
in CH2Cl2, and the excess 4-hydroxybenzyl alcohol removed by
filtration. The filtrate was dried over anhydrous MgSO4 and the solvent
removed. The crude product was triturated with anhydrous ethanol
and purified by chromatography (SiO2; eluent 10% MeOH/CH2Cl2).
b, Å
c, Å
23.3586(2)
91.53(1)
P21/c (No. 14)
5439.59(8)
goodness of fit
â, deg
space group
V, Å3
R(F), %a
Rw(F2), %b
a R(F) ) ∑∆/∑(Fo); ∆ ) |Fo - Fc|. b Rw(F2) ) ∑[w(Fo - Fc2)2].
2
1
Yield: 0.61 g (54%) H NMR (CD3CN): δ (ppm) 7.14 (m, Ar H,
The isolated solid was recrystallized from CHCl3/Et2O. Yield: 0.091
g (99%). 1H NMR (CD3NO2): δ (ppm) 7.49 (d, Ar H, 2H), 7.28 (d,
Ar H, 4H), 7.11-6.96 (m, Ar H, 13H), 6.88 (d, Ar H, 2H), 6.37 (s, Ar
H, 2H), 6.27 (d, Ar H, 4H), 4.73 (m, m-Phpy, 2H), 4.58 (d, ArCH2,
4H), 4.36 (s, OCH2CO, 4H), 4.24 (br s, CH2S, 4H), 4.19 (t, OCH2,
4H), 3.74 (s, CH2S, 4H), 3.67 (t, OCH2, 4H), 3.56 (t, p-Phpy, 1H),
3.26 (d, ArCH2, 4H), 2.25 (m, CH2, 4H), 1.92 (m, CH2, 4H), 1.02 (t,
CH3, 6H), 0.99 (t, CH3, 6H). 13C NMR (CD3NO2): δ (ppm) 165.38,
158.88, 157.96, 153.90, 153.41, 153.20, 138.09, 134.78, 134.14, 133.51,
133.16, 132.26, 130.88, 127.37, 126.83, 124.88, 124.32, 124.02, 122.45,
122.28, 115.83, 79.51, 77.85, 67.04, 47.14, 46.02, 32.06, 24.69, 24.40,
11.29, 10.35. LSI-MS: [M - BF4]+ m/z 1345. Anal. Calcd for
C77H80BF4N3O8PdS2‚CH2Cl2: C, 61.67; H, 5.45; N, 2.78. Found: C,
61.49; H, 5.50; N, 2.94.
Preparation of Model Ligand HL3 (15). Na (0.20 g, 8.8 mmol)
was dissolved in EtOH (80 mL). R,R′-m-Xylenedithiol (0.75 g, 4.4
mmol) was added to the NaOEt solution, and the mixture was stirred
for 1 h at room temperature. Chloroacetanilide (1.5 g, 8.8 mmol) was
added to the reaction mixture, and the solution was stirred for 12 h.
Yield: 1.85 g (96%). 1H NMR (CDCl3): δ (ppm) 8.59 (s, NH, 2H),
7.42 (d, Ar H, 4H), 7.26-7.09 (m, Ar H, 10H), 3.68 (s, CH2S, 4H),
3.20 (s, CH2S, 4H). 13C NMR (CDCl3): δ (ppm) 167.14, 137.62,
137.40, 129.56, 128.92, 128.14, 124.59, 119.86, 36.80, 36.17. Anal.
Calcd for C24H24N2O2S2: C, 66.04; H, 5.55; N, 6.42. Found: C, 65.87;
H, 5.55; N, 6.31.
Preparation of Model Metalloreceptor [Pd(L3)(MeCN)][BF4] (16).
Compound 15 (0.98 g, 2.25 mmol) and [Pd(CH3CN)4][BF4]2 (1.0 g,
2.25 mmol) were gently refluxed in CH3CN (50 mL) for 12 h. The
solution was concentrated under vacuum, and pure product was obtained
from crystallization at 4 °C. Yield: 1.37 g (91%). 1H NMR
(CD3CN): δ (ppm) 8.74 (s, NH, 2H), 7.52 (d, Ar H, 4H), 7.33 (t, Ar
H, 2H), 7.13 (t, Ar H, 1H), 6.98 (m, Ar H, 6H), 4.51 (br s, CH2S, 4H),
4.01 (s, CH2S, 4H), 2.25 (s, H2O, 2H). 13C NMR (CDCl3): δ (ppm)
164.06, 137.65, 129.07, 126.33, 124.90, 123.50, 120.02, 45.71 (br),
42.03. Anal. Calcd for C26H26BF4N3O2PdS2‚H2O: C, 45.40; H, 4.10;
N, 6.11. Found: C, 45.70; H, 3.93; N, 6.51.
7H), 7.00 (Ar H, 1H), 6.72 (m, Ar H, 4H), 5.06 (s, OH, 2H), 3.54,
3.52 (s, s, CH2S, 8H). 13C NMR (CD3CN): δ (ppm) 154.45, 138.37,
130.28, 129.69, 128.60, 127.60, 115.36, 35.37, 35.03. HR-EI-MS:
calcd for C22H22O2S2, m/z 382.106 13. Found, m/z 382.105 26.
Preparation of Metalloreceptor [Pd(L2)(CH3CN)][BF4] (11).
Calixarene 9 (0.100 g, 0.092 mmol) was suspended in CH3CN (100
mL), and the suspension was refluxed until complete dissolution. A
solution of [Pd(CH3CN)4][BF4]2 (0.041 g, 0.092 mmol) in CH3CN was
then added dropwise. The reaction mixture was refluxed for 6 h, after
which the solvent was removed. Yield: 0.117 g (96%). 1H NMR
(CD3CN): δ (ppm) 8.19 (s, NH, 2H), 7.38 (d, Ar H, 4H), 7.15 (d, Ar
H, 4H), 6.89 (m, Ar H, 9H), 6.61 (s, Ar H, 4H), 4.47 (d, ArCH2, 4H),
4.37 (s, CH2CO, 4H), 4.33 (br s, CH2S, 4H), 4.28 (s, CH2S, 4H), 4.08
(t, OCH2, 4H), 3.66 (t, OCH2, 4H), 3.20 (d, ArCH2, 4H), 2.05 (m, CH2,
4H), 1.90 (m, CH2, 4H), 1.07 (t, CH3, 6H), 0.91 (t, CH3, 6H). 13C
NMR (CD3CN): δ (ppm) 166.91 (CO), 158.43, 153.68, 151.38, 137.43,
134.88, 132.53, 130.05, 128.58, 123.66, 121.65, 115.93 (Ar C), 78.52,
77.31 (ArOCH2), 67.84 (CH2CO), 45.14, 43.49 (CH2S), 31.87 (ArCH2),
24.24, 23.79 (CH2), 11.14, 10.13 (CH3). LSI-MS: [M - CH3CN -
BF4 + H]+ m/z 1190. Anal. Calcd for C68H74BF4N3O8PdS2‚CH2Cl2:
C, 59.09; H, 5.47; N, 3.00. Found: C, 59.77, H, 5.51, N, 2.67.
Preparation of [Pd(L1)(py)][BF4] (12). Metalloreceptor 6 (0.05g,
0.045 mmol) was dissolved in CH3CN (50 mL), and an excess of
pyridine was added. The reaction mixture was warmed to 50 °C and
stirred for 2 h. The solvent was reduced, and the product was
precipitated with the addition of diethyl ether. The crude product was
recrystallized from CH2Cl2/Et2O. Yield: 0.040 g (77%). 1H NMR
(CD3NO2): δ (ppm) 8.86 (m, py, 1H), 8.75 (t, py, 1H), 8.17 (t, py,
1H), 7.52 (br s, NH + py, 4H), 7.37 (d, Ar H, 4H), 7.31 (br s, Ar H,
2H), 7.17 (t, Ar H, 2H), 7.07 (s, Ar H, 3H), 6.01 (br s, Ar H, 2H), 5.44
(s, 2H, CH2Cl2), 4.65 (d, ArCH2, 4H), 4.52 (br s, CH2S, 4H), 4.35 (br
s, CH2S, 4H), 3.93 (m, OCH2, 4H), 3.72 (t, OCH2, 4H), 3.32 (d, ArCH2,
4H), 2.24 (m, CH2, 4H), 1.99 (m, CH2, 4H), 1.11 (t, CH3, 6H), 0.99 (t,
CH3, 6H). 13C NMR (CD3NO2): δ (ppm) 163.34, 159.44, 154.92,
150.27, 148.34, 138.98, 137.84, 134.67, 134.16, 131.83, 127.72, 124.81,
124.20, 121.38 (br), 79.62, 77.82, 52.02, 47.72, 44.66, 32.51 (br), 24.64,
24.14, 11.20, 10.22. LSI-MS: [M - py - BF4]+ m/z 978. Anal. Calcd
for C57H64N3O6S2PdBF4‚CH2Cl2: C, 56.66; H, 5.41; N, 3.42. Found:
C, 56.83; H, 5.47; N, 3.46.
Preparation of [Pd(L1)Cl] (13). Metalloreceptor 6 (0.10 g, 0.09
mmol) was dissolved in CH3CN (25 mL). This solution was warmed
to 50 °C, and an excess of NH4Cl (0.05 g, 1.2 mmol) was added. The
product precipitated from solution and was isolated by filtration. The
crude product could be recrystallized from CHCl3/Et2O or chromato-
graphed on SiO2 (eluent 10% MeOH/CH2Cl2). Yield: 0.075 g (82%).
1H NMR (CD3NO2): δ (ppm) 8.15 (s, NH, 2H), 7.14 (d, Ar H, 4H),
7.06 (m, Ar H, 3H), 6.89 (t, Ar H, 2H), 6.37 (s, Ar H, 4H), 4.58 (d,
ArCH2, 4H), 4.47 (s, CH2S, 4H), 4.22 (t, OCH2, 4H), 3.89 (s, CH2S,
4H), 3.77 (t, OCH2, 4H), 3.22 (d, ArCH2, 4H), 2.10 (m, CH2, 4H),
1.96 (m, CH2, 4H), 1.16 (t, CH3, 6H), 0.99 (t, CH3, 6H). 13C NMR
(CD2Cl2): δ (ppm) 164.52, 157.93, 153.66, 136.75, 133.84, 130.82,
129.26 (br), 125.95, 123.35 (br), 122.47 (br), 77.80, 76.90, 46.46, 40.05,
31.23, 23.88, 23.23, 11.01, 9.93. LSI-MS: [M - Cl]+ m/z 978. Anal.
Calcd for C52H59ClN2O6PdS2: C, 61.58; H, 5.88; N, 2.76. Found: C,
61.75; H, 5.98; N, 2.83.
X-ray Diffraction Data Collection and Solution and Refinement
of the Structure of 5. Crystallographic data and refinement parameters
are summarized in Table 1. Crystals of 5 were obtained from slow
evaporation of a saturated acetonitrile solution of the compound.
Despite repeated attempts at recrystallization, all inspected crystals were
twinned or had satellites. The data crystal was obtained by sectioning
a larger multiple crystal. Approximately 10% of the observed
reflections were rejected as diffraction contributions of a minor twin
or satellite crystal. Unit-cell parameters were calculated from reflections
obtained from 60 data frames collected at different sections of the Ewald
sphere. The systematic absences in the diffraction data and the
determined unit-cell parameters were uniquely consistent for the
reported space group. A semiempirical absorption correction was
applied on the basis of redundant data at varying effective azimuthal
angles. Two acetonitrile solvent molecules were located in the
asymmetric unit. All non-hydrogen atoms were refined with anisotropic
displacement coefficients. All hydrogen atoms were treated as idealized
contributions. The structure was solved by direct methods, completed
by subsequent Fourier syntheses, and refined with full-matrix least-
squares methods. All scattering factors and anomalous dispersion
coefficients are contained in the SHELXTL 5.03 program library (G.
Sheldrick, Siemens XRD, Madison, WI).
Preparation of [Pd(L2)(4-Phpy)][BF4] (14). Compound 11 (0.085
g, 0.064 mmol) was dissolved in CHCl3, and the solution was warmed
to 50 °C. 4-Phenylpyridine (0.01 g, 0.064 mmol) was added, and the
reaction mixture was stirred an additional 2 h at 50 °C. The solvent
was reduced, and product precipitated upon addition of diethyl ether.

Calixarene Metalloreceptors
Inorganic Chemistry, Vol. 36, No. 24, 1997 5501
Scheme 1
Scheme 2
Results
Synthesis and Characterization of Calix[4]arene Ligands
5 and 9. The calix[4]arene-based ligands 5 and 9 were
synthesized by building upon an existing calix[4]arene platform.
Literature preparations were used to obtain the required 1,3-
substitution pattern by nitration16 of 1 to give 2 and reduction
to yield 3.15 Reaction of 3 with 2 equiv of chloroacetyl chloride,
according to the method of Reinhoudt et al., gave the diamide
4 in 65% yield.15
cyclization reaction was 25%. Method B, therefore, proved to
be a more efficient synthesis with higher yield and fewer steps.
The calix[4]arene molecules in this study have the lower rim
substituted with n-propoxy groups in order to inhibit inter-
conversion between the four possible conformations (cone,
partial cone, 1,3-alternate, and 1,2-alternate). Once the cone
conformation is isolated, the bulky nature of the propoxy groups
ensures retention of this conformation throughout the synthetic
1
sequence.17 The H NMR spectra of 5 and 9 show an AB
quartet for the methylene ArCH2Ar protons, typical for calix-
[4]arenes in the cone conformation.7 In addition, the ArCH2Ar
peak at ∼δ 31 ppm in the 13C NMR spectrum is indicative of
the cone conformation.18
X-ray Structure of 5. A perspective ORTEP drawing of 5
with an atom numbering scheme is shown in Figure 1. The
calix[4]arene portion of the molecule is in a pinched-cone
conformation in which the substituted aromatic groups of the
calix[4]arene are almost parallel; dihedral angle 19.5°. The loop
containing the xylyl unit is bent at the sulfur atoms with C-S-C
bond angles of 100.1(4) and 100.6(4)°, and the amido groups
The substituted calix[4]arene, 4, was converted directly to
the macrobicycle 5, in 86% yield, by treatment with R,R′-m-
xylenedithiol in Na/ethanol under high-dilution conditions
(Scheme 1).
Ligand 9 could be prepared by two methods. In method A,
similar to that used for the preparation of 5, the dibenzyl chloride
8 was reacted with R,R′-m-xylenedithiol in Na/ethanol under
high-dilution conditions to give the macrobicycle in 17% yield
(Scheme 2). Alternately, in method B, the R-chloroamide 4
was reacted with dithiaether 10 and NaH in acetonitrile under
high-dilution conditions (Scheme 3). The yield of 9 from this
(17) Arduini, A.; Fabbi, M.; Mantovani, M.; Mirone, L.; Pochini, A.; Secchi,
A.; Ungaro, R. J. Org. Chem. 1995, 60, 1454 and references therein.
(18) Jaime, C.; de Mendoza, J.; Prados, P.; Neito, P. M.; Sanchez, C. J.
Org. Chem. 1991, 56, 3372.
(16) Kelderman, E.; Derhaeg, L.; Heesink, G. J. T.; Verboom, W.;
Engbersen, J. F. J.; van Hulst, N. F.; Persoons, A.; Reinhoudt, D. N.
Angew. Chem., Int. Ed. Engl. 1992, 31, 1075.

5502 Inorganic Chemistry, Vol. 36, No. 24, 1997
Cameron et al.
are in a syn orientation. There are two molecules of acetonitrile
in the asymmetric unit, but neither interacts with 5; they simply
appear to fill void space in the lattice.
Synthesis and Characterization of Metalloreceptors 6 and
11. Palladation of 5 employing [Pd(CH3CN)4][BF4]2 in aceto-
nitrile solution yielded the metalloreceptor 6 in 93% yield.
Similarly, palladation of 9 produced the metalloreceptor 11 in
96% yield.
Figure 1. Perspective ORTEP drawing of 5 showing the atom-
numbering scheme. 30% thermal ellipsoids are shown for the non-
carbon atoms. All other atoms are shown as ideal spheres for clarity.
Scheme 3
The metalloreceptors 6 and 11 were isolated as pale yellow
solids and could be recrystallized from CH3CN/diethyl ether
solutions. All spectroscopic and analytical data are consistent
with palladation and the formula [Pd(L)(CH3CN)][BF4]. In
general, resonances for the benzylic CH2S protons are shifted
downfield and are broad in the 1H NMR spectrum compared to
those of the free ligand HL. The effect of palladation is also
evident in the 13C NMR spectrum, with the resonance for
benzylic carbon atoms shifted downfield by ca. 10 ppm. A
strong ion peak for [Pd(L)]+ was observed in the LSI mass
spectrum for both compounds.
1
The H NMR spectrum of 6 in CD3NO2 shows the coordi-
nated CH3CN group shifted significantly upfield at a chemical
shift of δ -1.80 ppm. This suggests that in solution the CH3
group is ensconced in the calix[4]arene cavity. There is also
an inequivalence of the aromatic protons on the substituted rings
of the calix[4]arene, suggesting some restricted rotation at room
temperature. When the sample is heated, this inequivalence
disappears. Also, the complex [Pd(L1)(Cl)], 13, with a smaller
Cl-, substrate does not exhibit this feature at any tem-
perature.
Synthesis and Characterization of [Pd(L)(Y)][BF4] (12:
L1, Y ) py) (14: L2, Y ) 4-Phpy). Examination of CPK

Calixarene Metalloreceptors
Inorganic Chemistry, Vol. 36, No. 24, 1997 5503
Figure 4. Drawing of 12 showing the labeling scheme for Figure 5
and illustrating the possible positioning of the py substrate inside the
calix[4]arene cavity.
Figure 2. Drawing of 14 illustrating the positioning of the 4-Phpy
substrate inside the calix[4]arene cavity.
Figure 3. 1H NMR spectrum of 14 (300 MHz, CD2Cl2/CD3NO2 (3:
1)), in the region δ 3.2-4.8 ppm, identifying the upfield shifted
resonances, m-Phpy and p-Phpy, indicative of binding 4-Phpy inside
the calix[4]arene cavity.
models suggested that pyridine (py) would be a suitable substrate
for 6, since formation of a Pd-N bond would orient the aromatic
moiety into the hydrophobic cavity provided by the calix[4]-
arene. Similarly, since the metalloreceptor 11 contains a much
larger overall cavity, 4-phenylpyridine (4-Phpy) was investigated
as a suitable substrate. Additional π-π stacking interactions
could occur between the pyridine ring and the aromatic spacer
of the metalloreceptor with the phenyl substituent oriented into
the calixarene cavity.
Both 12 and 14 were easily prepared in quantitative yield by
displacing the labile acetonitrile ligand with 1 equiv of the
substrate molecule. For both receptors, 1H NMR spectral data
exhibited (i) complexation shifts for the pyridine protons
consistent with binding to the palladium center via σ-donation
and (ii) distinct features indicative of substrate interaction with
the calix[4]arene moiety.
Figure 5. Variable-temperature NMR spectra of 12.
and 4.71 ppm as belonging to the aromatic protons of the phenyl
group of 4-Phpy. These protons are shifted upfield by 3.90 and
2.78 ppm relative to those of the free substrate. This almost
certainly arises from inclusion of the phenyl ring inside the calix-
[4]arene cavity.20 (See Figures 2 and 3.)
For 12, the pyridine protons are shifted downfield as a result
of coordination, but the only change to the calixarene portion
of the molecule is a splitting of the calixarene aromatic protons
on the substituted rings (labeled “a” in Figure 4). This splitting
is consistent with an asymmetric coordination of the pyridine
unit and suggests that py is too large for the receptor cavity.
That is, in solution a conformation is adopted which coordinates
py to the Pd center but not inside the calixarene cavity. A
1
variable-temperature H NMR study on this compound shows
The most dramatic effects were observed for 14. The protons
of the aromatic spacer on the metalloreceptor are shifted upfield
approximately 0.8 ppm, indicative of a π-stacking interaction,19
while a dramatic change is observed for the meta and para
protons on the phenyl ring of the 4-Phpy substrate. A 1H-13C
HETCOR NMR experiment identified proton resonances at 3.59
that the asymmetry observed at room temperature disappears
with increasing temperature until a symmetrical spectrum is
observed. (See Figure 5.) This may indicate a fluxional process
occurs in which the pyridine moves “in and out of” or “through”
the cavity. The symmetrical high-temperature structure ob-
served would simply be an average of the two conformations
in which the pyridine is coordinated to Pd but oriented outside
(19) (a) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112,
5525. (b) Burley, S. K.; Petsko, G. A. J. Am. Chem. Soc. 1986, 108,
7995.
(20) Komoto, T.; Ando, I.; Nakamoto, Y.; Ishida, S.-I. J. Chem. Soc., Chem.
Commun. 1988, 135.

5504 Inorganic Chemistry, Vol. 36, No. 24, 1997
Cameron et al.
Table 2. Competition Reactions Showing Molecular Recognition of
4-Phpy
the cavity. The lack of upfield shifts similar to that observed
for 14 is also evidence for this scenario.
selectivityb
Molecular Recognition of Phenyl-Substituted Pyridines.
Since solution and modeling studies show that 4-Phpy is an
excellent fit for receptor 11, it was reasoned that this comple-
mentarity could be used to effect molecular recognition of this
species over related Phpy compounds. Accordingly, competition
studies were performed between 4-Phpy and 2-Phpy or 3-Phpy.
In separate reactions, 1 equiv of 11 was mixed with 1 equiv of
4-Phpy and 1 equiv of either 2-Phpy or 3-Phpy. The 1H NMR
spectra were recorded, and the ratio of complexed to free 4-Phpy
was determined by integration of the p-Ph proton. As a
comparison, the same competition experiments were carried out
using 16, as a model receptor containing no calixarene unit.
substrate pair
16
11
4-Phpy/2-Phpy
4-Phpy/3-Phpy
50/50a
4/96
80/20
60/40
4
38
a Ratio of receptor-bound substrates in a 1/1/1 mixture of the two
competing substrates and the receptor. b The ratio for metalloreceptor
11 over the ratio for model receptor 16.
For 14, the marked upfield shifts of the phenyl protons must
surely result from shielding of these hydrogens by an aromatic
group inside the calixarene cavity.20 Figure 3 shows a
representation illustrating how this type of noncovalent interac-
tion occurs as a result of the strong, oriented binding provided
by the organopalladium center. In these new metalloreceptors,
the Pd atom provides two important attributes: (1) it acts as a
binding site for coordination of the substrate and (2) it directs
the substrate into the hydrophobic cavity of the calix[4]arene.
The first-sphere coordination via σ-donation to the organo-
palladium center anchors the substrate in place. Depending on
the size and shape of the substrate, this may position the
substrate inside the cavity, resulting in a second-sphere interac-
tion. As demonstrated herein, a complementary set of substrate-
receptor interactions has the potential to simultaneously provide
functional group, size, and shape selectivity in a molecular
recognition event.
The results are summarized in Table 2. A comparison of
the results for model receptor 16 with those for metalloreceptor
11 gave a measure of the ability of 11 to selectively recognize
4-Phpy. Thus, 11 exhibited a selectivity of 4 for 4-Phpy over
2-Phpy and a remarkable selectivity of 38 for 4-phenylpyridine
over 3-phenylpyridine.
Acknowledgment. We thank the Natural Sciences and
Engineering Council of Canada and the Petroleum Research
Fund, administered by the American Chemical Society, for
financial support of this research.
Supporting Information Available: An X-ray crystallographic file,
in CIF format, for compound 5 is available on the Internet only. Access
information is given on any current masthead page.
Discussion
The nature of the binding site in these new metalloreceptors
was investigated by H NMR spectroscopy and CPK models.
1
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