Design and synthesis of a new kind of cavitand: Tetrapyrazolylcalix[4] arenes and their supramolecular assemblies

Article abstract of DOI:10.1055/s-0033-1341058

Two novel calix[4]arene-based tetrapyrazolyl cavitands with different cavity size were synthesized by multistep reactions. In the solid state, one of the cavitands forms an infinite chain by Aintermolecular hydrogen bonding. The other cavitand undergoes c

Full text of DOI:10.1055/s-0033-1341058

LETTER
▌1181
lDetteersign and Synthesis of a New Kind of Cavitand: Tetrapyrazolylcalix[4]arenes
and Their Supramolecular Assemblies
Tetrapyrazolylcalix[4]arenes and Their Supramolecular Assemblies
Xuan-Feng Jiang,a Yu-Xin Cui,b Shu-Yan Yu*a
a
Laboratory for Self-Assembly Chemistry, Department of Chemistry, Renmin University of China, Beijing 100872, P. R. of China
Fax +86(10)625166; E-mail: yusy@ruc.edu.cn
b
Medical and Health Analysis Center, Peking University, Beijing 100083, P. R. of China
Received: 21.12.2013; Accepted after revision: 02.03.2014
chitectures, including metallo-macrocycles, molecular
Abstract: Two novel calix[4]arene-based tetrapyrazolyl cavitands
capsules, and metallo-cages.6
with different cavity size were synthesized by multistep reactions.
In the solid state, one of the cavitands forms an infinite chain by
intermolecular hydrogen bonding. The other cavitand undergoes
coordination self-assembly with dimetal corners to form a supramo-
lecular cage.
Important methods for the synthesis of polypyrazolate
heterocycles included approaches based on the condensa-
tion of hydrazines with β-difunctional compounds or 1,3-
dipolar cycloaddition reactions of diazo compounds.5 For
example, Ramirez et al.6b developed a strategy for prepar-
ing β-diketones and their derivatives through the reaction
of 2,2,2-trimethoxy-4,5-dimethyl-1,3,2λ5-dioxaphospho-
le with aromatic aldehydes, followed by a molecular rear-
rangement in methanol.
Key words: cavitands, calixarenes, hydrogen bonding, self-assem-
bly, macrocycles
Over the past 30 years, the chemistry of container mole-
cules has become one of the most exciting and challeng-
ing fields of research in organic chemistry.1 In 1983,
Cram introduced the concept of a closed-surface binding
host, and synthesized the first examples of organic con-
tainer molecules, which were named ‘carcerands’. Carc-
erands are defined by the size of their inner cavities and
they have various applications in supramolecular chemis-
try.1 There is considerable demand for easily available
and synthetically versatile building blocks for the con-
struction of receptor molecules with high degrees of com-
plexity and specific supramolecular functions.2 As a new
class of useful building blocks, the calixarenes have been
recognized as promising candidates for the construction
of molecular receptors, molecular devices, molecular
switch systems, supramolecular materials, and the like.3,4
Calixarenes can be easily prepared by a one-pot reaction
of phenol with formaldehyde, and they can be selectively
functionalized on the upper and/or lower rim.
Here, we report the synthesis of two upper-rim function-
alized pyrazolylcalix[4]arenes 1 and 2 (Figure 1) with an
all-cone conformation through multistep reactions. Cavi-
tand 1 forms an infinite chain in the solid state by intermo-
lecular hydrogen bonding. Coordination self-assembly of
cavitand 2 with a dimetal motif results in the formation of
a supramolecular cage.
HN
N
NH
N
HN
NH
N
N
O
O
O
O
Among various functional building blocks, pyrazoles
have found a wide range of applications in the pharmaceu-
tical and agrochemical industries, in nonlinear optical ma-
terials, in photography, and in host–guest chemistry.5
Because of their varied coordination modes, pyrazoles
play important roles in inorganic, organometallic, and ma-
terials chemistry,6 and they can be used to construct pyr-
azolate-bridged multimetal and metal–metal bonding
coordination systems.5,6 In view of the potential applica-
tions of pyrazolate-bridged multimetal-coordination mac-
rocyclic and cage-like hosts,7 we have devoted great
efforts to the design and synthesis of novel polypyrazo-
late-functionalized calixarenes that can be used to build
new types of metal–organic functional supramolecular ar-
1
N
N
NH
NH
HN
N
HN
N
O
O
O
O
2
SYNLETT 2014, 25, 1181–1185
Advanced online publication: 07.04.2014
DOI: 10.1055/s-0033-1341058; Art ID: ST-2013-W1158-L
© Georg Thieme Verlag Stuttgart · New York
Figure 1 The structures of the cone-tetrapyrazolylcalix[4]arene cav-
itands 1 and 2
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

1182
X.-F. Jiang et al.
LETTER
The synthesis of compounds 1 and 2 is shown in Scheme tetrakis(3,5-dimethyl-1H-pyrazol-4-yl)-25,26,27,28-tetra-
1. Compounds 3–6 were prepared according to reported propoxycalix[4]arene (1) as a white powder in 89% yield.
procedures.2,8 The tetraformylated calix[4]arene 6 reacted
A new cavitand 2 with a deeper cavity was prepared by a
route based on the optimized procedure for the synthesis
of cavitand 1. To expand the internal cavity, four phenyl
rings were introduced as spacers on the upper rim of the
calix[4]arene backbone through a Suzuki cross-coupling
reaction of (4-formylphenyl)boronic acid with cone-
5,11,17,23-tetrabromo-25,26,27,28-tetrapropoxycalix[4]arene
with 2,2,2-trimethoxy-4,5-dimethyl-1,3,2λ5-dioxaphos-
phole in dichloromethane at room temperature to give the
polyphosphorane 7. The use of a tenfold excess of 2,2,2-
trimethoxy-4,5-dimethyl-1,3,2λ5-dioxaphosphole and a
relatively higher temperature (60 °C) promoted the reac-
tion toward compound 7, which could be further trans-
formed into the desired tetraenol tetraketone 8 in 40%
(9) in the presence of tetrakis(triphenylphosphine)palladi-
yield in a similar manner to that described in the litera-
um as a catalyst in toluene at 80 °C to give the desired
ture.6 The key intermediate 8 was treated with hydrazine
compound 10 with cone-conformation in 65% yield.
hydrate in ethanol at room temperature to give 5,11,17,23-
CHO
formaldehyde
NaOH
PrI
AlCl3
(CH2)6N4
TFA
toluene
NaH, DMF
OH
OH
OH
OPr
OPr
4
4
4
4
3
4
5
6
OMe
MeO
O
P
O
O
OH
N
NH
MeO
O
O
O
P
MeO
OMe
OMe
H2NNH2
EtOH
MeOH
reflux, 2 h
CH2Cl2
OPr
OPr
OPr
4
4
4
7
1
8
CHO
Br
CHO
Pd(PPh3)4
NBS
butanone
+
K2CO3
OPr
OPr
B(OH)2
4
4
5
9
OPr
4
10
OMe
MeO
MeO
O
P
O
O
OH
N
NH
O
O
O
P
MeO
OMe
OMe
MeOH
reflux, 2 h
H2NNH2
EtOH
CH2Cl2
OPr
OPr
OPr
4
4
4
12
2
11
Scheme 1 The synthesis of tetrakis(3,5-dimethyl-1H-pyrazol-4-yl)calix[4]arene-based compounds 1 and 2
Synlett 2014, 25, 1181–1185
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tetrapyrazolylcalix[4]arenes and Their Supramolecular Assemblies
1183
Compound 11 was synthesized by a similar route to com- distance of about 2.75 Å is shorter than the sum of their
pound 7. Subsequent methanolysis provided a mixture of van der Waals radii, which suggests the presence of
mono-, di-, tri-, and tetra-β-diketone derivatives of ca- strong intermolecular hydrogen-bonding interactions. As
lix[4]arenes. Column chromatography on silica gel and a result of the flexibility of the calix[4]arene backbone, a
subsequent recrystallization separated and purified the pinch-cone configuration is favorably adopted in the self-
tetraenol tetraketo calixarene 12 in a low yield. Condensa- assembly of the one-dimensional chains.
tion of compound 12 with hydrazine hydrate in ethanol at
room temperature gave 5,11,17,23-tetrakis[4-(3,5-di-
methyl-1H-pyrazol-4-yl)phenyl]-25,26,27,28-tetraprop-
oxycalix[4]arene as a white powder. Calixarenes 1 and 2
1
were characterized by means of H and 13C NMR spec-
troscopy, MALDI-TOF mass spectroscopy, X-ray single-
crystal diffraction, and elemental analysis.9
Small pyrazoles are widely used in the construction of su-
pramolecular oligomers with multiple protons transfers
Figure 3 Hydrogen-bonding motifs in the tetrapyrazolylca-
lix[4]arene cavitand 1
through kinetic hydrogen bonds in various interaction
modes.5 In this work, the two tetrapyrazolylcalixarenes-
based cavitands of different size were used as independent Besides the hydrogen-bonding self-assembly of com-
hydrogen-bonding units for the self-assembly of supra- pound 1 in solution, the larger cavitand 2 was initially
molecular architectures in solution. Suitable single crys- used as a functional organic ligand to prepare complex
tals of compound 1 were obtained by vapor diffusion of 13.8 As shown in the Supporting Information (Scheme
ethyl acetate into a solution of 1 in dimethyl sulfoxide– S1), the dimetal corner [(bpy)2Pd2(NO3)2](NO3)2 (38.5
acetonitrile at room temperature. Synchrotron X-ray mg, 0.05 mmol) was added to a suspension of compound
structural analysis revealed that compound 1 crystallized 2 (32.1 mg, 0.025 mmol) in water (10 mL), and the mix-
in the monoclinic space group C2/c and exhibited an inter- ture was stirred for four hours at room temperature. Ace-
esting linear chain structure with multiple intermolecular tone (3 mL) was then added and the mixture was stirred
hydrogen bonds.10 A ball-and-stick diagram of 1 is shown for 72 hours at 90 °C. The resulting clear solution was
in Figure 2 and in the Supporting Information (Figure evaporated to dryness to give yellow microcrystals. The
S14); two neighboring chains were arranged a crosswise hexafluorophosphate salt of complex 13 was quantitative-
manner in the two-dimensional sheet-like structure by a ly prepared by exchange with a tenfold excess of potassi-
self-complementary effect in the solid state (Supporting um hexafluorophosphate in aqueous solution at 60 °C.
–
Information; Figure S15).
Pure 13·8PF6 was obtained as a yellow microcrystalline
solid by the vapor diffusion of diethyl ether into a solution
of 13 in acetonitrile at room temperature. NMR spectros-
copy indicated the formation of a single product. As
1
shown in the temperature-dependent H NMR spectrum
of 13·8PF6 (Supporting Information; Figures S10 and
–
S11), the signals at 3.27 to 4.63 ppm were assigned to
methylene hydrogen atoms from the calix[4]arene li-
gands, whereas the protons of the bipyridyl ligand pre-
sented four sets of signals at 8.0–9.0 ppm in the downfield
region. The corresponding resonances observed at 6.61,
7.32, and 8.18 ppm were ascribed to the protons of aro-
matic groups of the calix[4]arene backbone. Further evi-
–
dence for the formation of cage 13·8PF6 was given by the
Figure 2 The crystal structure of tetrapyrazolylcalix[4]arene 1 con-
taining multiple hydrogen bonds; light gray and black: carbon; blue: CSI–TOF mass spectrum (Supporting Information; Fig-
nitrogen; red: oxygen; white: hydrogen
ure S13), in which the featured peaks corresponding to the
fragments with a general formula of [M – (bpy)2Pd2 –
–
–
n(PF6 ) + 2H2O + MeCN]n+ (n = 3, 4, 5, 6; M = 13·8PF6
The separation of the two opposite pyrazolyl groups (cen-
troid to centroid) in the 1- and 3-positions (4.199 Å) is
markedly different from those in the 2- and 4-positions
(13.39 Å), indicating that the calix[4]arene-based linker
adopts a 1,3-contracted 2,4-expanded conformation. Fur-
thermore, three tetrapyrazolylcalixarene moieties in the
asymmetric unit of 1 are held together by triple and qua-
druple cyclic hydrogen bonds, leading to the formation of
triangular and saddle-shaped N′–H–N donor–acceptor hy-
drogen bonding motifs (Figure 3). The average N′D···NA
). The correlated ion peaks were observed at m/z =
–
1542.02 [M – 3(PF6 )]3+ (calcd: 1542.28), 1120.03 [M –
–
–
4(PF6 )]4+ (1120.46), 867.04 [M – 5(PF6 )]5+ (867.38),
–
and 698.53 [M – 6(PF6 )]6+ (698.93).
On the basis of the results of the NMR spectroscopy and
the CSI–TOF mass spectrometric analyses of 13·8PF6 in
solution, we tentatively proposed a possible conformation
of a dimeric metallo-capsule {[(bpy)Pd]8L4}(PF6 )8
–
–
(where L is the deprotonated compound 2) with a deep
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1181–1185

1184
X.-F. Jiang et al.
LETTER
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volving spontaneous deprotonation of the 1H-tetrapyrazo-
lyl ligands. Therefore, by using the CAChe 6.1.1 program,
we constructed a visual model of the molecular structure
to evaluate the size and shape of 13. Cage 13 has a molec-
ular dimension of 22.9 × 19.4 × 19.2 Å and an interior
void volume of 4331 Å3, as shown in Figure 4.
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Figure 4 The modeled structure of the organometallic supramolec-
ular cage 13·8PF6– produced by using the CaChe 6.1.1 program. The
model is constructed from the deprotonated cavitand 2 and the dimet-
al coordination corners, and is drawn as a ball-and-stick model. (A:
side view; B: top view; light gray and black: carbon; blue: nitrogen;
red: oxygen; white: hydrogen; yellow: palladium).
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(9) 5,11,17,23-Tetrakis(3,5-dimethyl-1H-pyrazol-4-yl)-
25,26,27,28-tetrapropoxycalix[4]arene (1)
In conclusion, we synthesized several novel cone-tetra-β-
diketone and tetrapyrazolyl calix[4]arenes compounds 8,
1, 12, and 2 from simple starting materials. All new com-
pounds were characterized by 1H and 13C NMR spectros-
copy, elemental analysis, and CSI–TOF and MALDI–
TOF mass spectrometry. Compound 1 self-assembled to
form a one-dimensional chain through multiple intermo-
lecular hydrogen bonds in the solid state. Compound 2
was used to construct a metallo-cage compound with a
proposed [Pd8L2]-type structure containing a deep cavity
with dimetal corners. These cage-shaped compounds and
complexes with deep cavities might serve as hosts for
small guest molecules and anions. The self-assembly and
related function of tetrapyrazolyl compounds as bridging
ligands in metal-directed self-assembly are currently un-
der investigation.
White powder; yield: 546 mg (85%); mp 285–289 °C; 1H
NMR (400 MHz, DMSO-d6, 20 °C): δ = 11.86 (s, 4 H, HN-
pyrazole), 6.64 (s, 8 H, H-Ar), 4.44 and 3.24 (d, Ј = 12.1 Hz,
8 H, Ar-CH2-Ar), 3.82 (t, Ј = 8.6 Hz, 8 H, ArOCH2CH2CH3),
2.03 and 1.62 (s, 24 H, pyrazole-CH3), 1.96 (ψ-sextet, 8 H,
ArOCH2CH2CH3), 0.98 (t, J = 8.4 Hz, 12 H,
ArOCH2CH2CH3); 13C NMR (100 MHz, DMSO-d6, 25 °C):
δ = 135.6, 134.3, 128.9, 118.41, 79.26, 56.59, 23.31, 18.63,
10.52; MS (MALDI–TOF, MeOH): m/z: calcd for [M + Na]+
991.56; found 991.6.
Acknowledgment
5,11,17,23-Tetrakis[4-(3,5-dimethyl-1H-pyrazol-4-
yl)phenyl]-25,26,27,28-tetrapropoxycalix[4]arene (2)
White power; yield: 55 mg (75%); mp 233–240 °C; 1H NMR
(400 MHz, DMSO-d6, 25 °C): δ = 12.19 (s, 4 H, HN-
pyrazole), 7.34 (s, J = 8.8 Hz, 8 H, phenyl-H), 7.01–7.08 (d,
J = 8.4 Hz, 8 H, phenyl-H), 6.98 (s, 8 H, calixarene-Ar-H),
4.51 and 3.43 (d, J = 7.8 Hz, 8 H, ArCH2Ar), 3.98 (d, J =
12.8 Hz, 8 H, ArOCH2CH2CH3), 2.17 (s, 24 H, pyrazole-
CH3), 1.97–2.01 (4-sextet, J = 8.0 Hz, 8 H, ArOCH2CH2CH3),
1.00 (t, J = 7.4 Hz, 12 H, ArOCH2CH2CH3). 13C NMR (100
MHz, CDCl3, 25 °C): δ = 157.32, 146.72, 135.55, 134.46,
133.56, 129.92, 127.26, 126.74, 31.33, 23.34, 10.38. MS
(MALDI–TOF, MeOH–DMSO): m/z: calcd for [M + H2O +
H+]: 1291.7; found: 1290.1. Anal Calcd for
This work was supported by National Natural Science Foundation
of China (No. 91127039). We thank the BSRF (Beijing Synchrotron
Radiation Facility) for performing the crystal-structure determinati-
on by synchrotron radiation X-ray diffraction analysis. We are also
grateful to Professor Dr. Yizhi Li of Nanjing University for the
X-ray crystallography.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
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References
(1) (a) Lehn, J.-M. Supramolecular Chemistry: Concepts and
Perspectives; VCH: Weinheim, 1995. (b) Comprehensive
Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.;
Macnicol, D. D.; Vögtle, F., Eds.; Pergamon: Oxford, 1996.
C84H88N8O4·2H2O: C, 77.03; H, 7.08; N, 8.56. Found: C,
77.11, H, 7.06; N, 8.52.
Synlett 2014, 25, 1181–1185
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tetrapyrazolylcalix[4]arenes and Their Supramolecular Assemblies
1185
(10) Crystallographic data for compound 1 have been deposited
with the accession number CCDC 928591, and can be
obtained free of charge from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK;
Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk;
Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1181–1185

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