Synthesis and ESR behaviors of nitroxide monoradical based on calix[4]arene

Article abstract of DOI:10.1016/j.tetlet.2006.08.034

A novel paramagnetic calix[4]arene 6 with an N-O monoradical on the upper rim was synthesized and studied by ESR spectroscopy. Its ESR behaviors were mainly induced by its intrinsic conformational flexibility. The effects of varying temperature and comple

Full text of DOI:10.1016/j.tetlet.2006.08.034

Tetrahedron Letters 47 (2006) 7463–7465
Synthesis and ESR behaviors of nitroxide monoradical
based on calix[4]arene
*
Xiaojun Hu, Yong Li, Haijun Yang and Yanghe Luo
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education),
Department of Chemistry, Tsinghua University, Beijing 100084, PR China
Received 29 May 2006; revised 4 August 2006; accepted 11 August 2006
Abstract—A novel paramagnetic calix[4]arene 6 with an N–O monoradical on the upper rim was synthesized and studied by ESR
spectroscopy. Its ESR behaviors were mainly induced by its intrinsic conformational flexibility. The effects of varying temperature
and complexation of silver ions on its ESR behaviors were also investigated.
Ó 2006 Elsevier Ltd. All rights reserved.
The covalent attachment of stable nitroxide radicals to
specific sites on calixarenes could provide valuable infor-
mation portraying the local environment and, in partic-
ular, about dynamic conformational transformations by
the exchange interaction among different N–O radicals,
such as the geometrical changes induced by complexa-
tion of metal ions to the cavity of lower rims functional-
Paramagnetic calix[4]arene 6 was prepared according to
Scheme 1 with selective benzoyl-protected calix[4]arene
4
1 as the precursor. Compound 5 was yielded through
the halogen–lithium exchange reaction of 4 followed
by the reaction with 2-methyl-2-nitrosopropane
(MNP), and easily oxidized in solution upon exposing
to air. Due to the instability of compound 5, 5 was di-
rectly oxidized into the final product 6 for characteriza-
tion. Compound 6 was obtained as a red powder
1
ized with N–O radicals. We firstly investigated the
intramolecular spin–spin exchange interaction of two
nitroxide radicals on the upper rims of calix[4]arene.2
Magnetic studies of stable nitroxide tetraradicals on
the upper rim of calix[4]arene, which were conforma-
through the phase-transfer oxidation of 5 with PbO
and characterized by ESI-MS, H NMR, HPLC, and
2
1
elemental analysis.
3
tionally immobilized as a cone, were also reported.
But almost all these valuable information describing
the local environment was afforded by intramolecular
exchange interaction among different spin centers.
Could a monoradical attached on calixarene provide
any information about the local environment? Here we
report the synthesis of a novel paramagnetic calix[4]-
arene with an N–O monoradical on the upper rim and
its ESR behaviors on the conformational alternation
and complexation of silver ion. We hope that the present
study will provide potential to conformational research
of heteroatom-bridged calixarenes in which the methy-
lene bridges are replaced by heteroatoms such as S
and O, whereas NMR studies on the bridging groups
The ESR measurements of 6 were carried out in toluene
at a high dilution. A typical symmetrical ESR spectrum
of nitroxide monoradical was observed, as having a
broad equivalent triplet at g = 2.0058 with a nitrogen
hyperfine coupling constant A = 14.4 G. When the
N
toluene solution of 6 was bubbled with nitrogen gas,
another ESR splitting pattern (Fig. 1) of 6 was observed
(similar to that in the degassed solution). There re-
mained the triplet corresponding to nitrogen hyperfine
coupling, but each broad peak of the triplet was split
into three narrow peaks due to the hyperfine coupling
of the two equivalent ortho hydrogen nuclei of the
phenyl ring. However, a careful examination of the
unsymmetrical ESR spectrum of 6 suggested that it
was produced by superposition of at least two kinds of
monoradical nine-line ESR spectra, in which one set
of signals at g = 2.0064 was the major species with
A = 14.6 G, A = 1.5 G and another set at
CH are usually carried out for determining conforma-
2
tions of common calixarenes in solution.
N
H
Keywords: Calix[4]arene; Nitroxide radical; Conformation; ESR.
*
Corresponding author. Tel.: +86 10 6278 8971; fax: +86 10 6277
149; e-mail: liy@chem.tsinghua.edu.cn
g = 2.0061 was the minor species with A = 13.0 G,
A = 1.7 G. This superposed ESR spectrum of 6 was
H
N
1
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.034

7464
X. Hu et al. / Tetrahedron Letters 47 (2006) 7463–7465
Br
Br
C
H
C
H
I
C
H
C
H
II
3
2
C
H
C
H
3
2
3
2
2
O
OH
2
OH
O
2
OH
OH
C=O
C=O
1
2
3
III
O
OH
N
Br
N
IV
V
C
H
C
H
C
H
C
C
H
C
3
2
3
3
H
2
H
2
OMe
2
OMe
OMe 2
OMe
2
OMe
OMe
4
5
6
2 3
Scheme 1. The synthesis route of 6. Reagents and yields: (I) Br , 90%; (II) NaOH, MeOH, THF, 98%; (III) CH I, THF, DMF, 68%; (IV) n-BuLi,
2
-methyl-2-nitrosopropane (MNP); (V) PbO , benzene, 35% for (IV) and (V).
2
2
,7
of tetramethyloxycalix[4]arene. As for line shapes of
H NMR spectra in CDCl , the CH and CH O signals
1
3
2
3
of 6 were very similar to those of 4 and both have the
same molecular backbone other than the mono-substi-
tuted functional group. Then it could be deduced that
the conformational distribution pattern of 6 was analo-
gous to that of 4 to some extent. When calix[4]arene 6
exhibited a cone and two partial-cone conformations
in which the nitroxide radical was placed above the
bridging CH mean plane, the N–O monoradical posi-
2
tioned in the magnetic atmosphere of phenyl rings corre-
sponding to the major ESR signal at g = 2.0064. A small
difference in the magnetic environment results in a small
broadening of the ESR spectrum line which cannot be
distinguished. However, the ESR signal at g = 2.0061
may arise from 6 in the third partial-cone conformation,
in which the phenyl ring with the nitroxide monoradical
pointed opposite of the other three phenyl rings. Thus,
the two kinds of N–O monoradical ESR spectra
overlapped on the observed ESR spectrum of 6 in
toluene.
Figure 1. The ESR spectra in toluene under nitrogen at different
temperatures and the simulated ESR spectrum at 290 K.
When the toluene solution of 6 was heated, the ESR
signals of two different nitroxide monoradicals were
enhanced and began to close up. As the solution was
heated up to 370 K, the two ESR signals coalesced grad-
ually. This suggested that conformational exchanges
among the different conformational isomers of 6 were
accelerated upon heating, the upside-down rotation of
nitroxide radical along with the phenyl ring was also
speeded up. The nitroxide radical experienced a fast
transition of the magnetic environment between phenyl
rings and methoxyl groups. The ESR spectra of 6 in
340 and 370 K were also simulated, in which the ratios
of the two kinds of different N–O monoradical changed
along with the increase of temperature.
well simulated using the WINEPR program and the
proportion of the major monoradical was estimated to
be more than 75% (Fig. 1).
This phenomenon could be ascribed to the conforma-
tional mobility of 6. The methoxy groups on the lower
rims of 6 were too small to inhibit the oxygen-
5
through-the-annulus rotation, giving rise to a confor-
mational equilibrium in solution between several
discrete conformations. The variation of conformation
caused a magnetic environment around the nitroxide
radical to change, resulting in different ESR behaviors.
1
The H NMR spectrum of 6 was broadened by para-
+
magnetism of the radical and could not afford valuable
information to distinguish among different conforma-
tions. But 1D and 2D NMR spectra of 4 in toluene-d3
showed that calix[4]arene 4 adopted four kinds of dis-
crete conformations in different percentages: cone (ca.
The extraction of Ag ion with a toluene solution of 6
from an aqueous AgNO3 solution caused moderate
changes in its ESR spectrum. This may suggest that
+
the complexation of Ag ion made the conformation
of calix[4]arene 6 modified and the ratio of the two kinds
of N–O monoradicals changed, leading its ESR signal to
change. Furthermore, addition of an organic salt of
silver (AgNS C H ) directly into a dichloromethane
3
4.5%) and three partial-cone (ca. 65.5%) conforma-
6
tions. The partial cone was the predominant conforma-
tion as reported by other conformational investigations
2
5
10

X. Hu et al. / Tetrahedron Letters 47 (2006) 7463–7465
7465
2
conformational transition. The present ESR behaviors
belong to the calixarene with an N–O monoradical
and were mainly induced by its intrinsic conformational
flexibility. It is reasonably anticipated that an ESR study
on this kind of mono-spin labeled calixarenes may pro-
vide valuable basic concepts for the understanding of
conformational transformations and exchange interac-
tion between intermolecular radicals.
Supplementary data
Synthesis procedure for 6, other ESR simulation data,
NMR, and ESI-MS spectra. Supplementary data asso-
ciated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2006.08.034. See http://
www.sciencedirect.com.
Figure 2. The ESR spectra of 6 in toluene before (a) and after (b)
+
extracting the Ag ion; the ESR spectra of 6 in CH
after (d) including the Ag ion.
2
Cl
2
before (c) and
+
solution of 6 also caused a larger change on the ESR
spectrum of 6 (Fig. 2), whereas addition of the same
organic salt of zinc had almost no effect. This means
References and notes
+
calix[4]arene 6 has a selective complexation for Ag
ion, and may be used as a selective chemical sensor for
the Ag ion. To confirm this selective complexation,
1
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Chem. Soc., Chem. Commun. 1995, 20, 2121–2122; (b)
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kr o¨ ck, L.; Shivanyuk, A.; Goodin, D. B.; Rebek, J. Chem.
Commun. 2004, 272–273.
+
we made ESI-MS measurements on the complex solu-
+
2+
tions of Ag and Zn ions, respectively. Interestingly,
there was a strong signal observed indicative of a
2
+
calix[4]arene 6 including two Ag ions (see Supplemen-
3
tary data), and no signal corresponding to the complex
2
+
8
Zn ion was detected. Although some investigations
+
on the complexation of an Ag ion by a tetrame-
thoxycalix[4]arene molecule have been reported, there
are no findings about whether one analogous molecule
4
. Gravett, D. M.; Guillet, J. E. Macromolecules 1996, 29,
6
17–624.
+
of tetramethoxycalix[4]arene could include two Ag
5. Araki, K.; Iwamoto, K.; Shinkai, S.; Matsuda, T. Chem.
Lett. 1989, 1747–1750.
6. Three partial-cone conformations arise from the molecular
asymmetry of 4 and 6, the molecular structures of the three
partial-cone conformations are presented in the Supple-
mentary data.
ions. This may be attributed to the desirable conforma-
tion of 6, but the exact reason for this is under
investigation.
In conclusion, a novel paramagnetic calix[4]arene with
an N–O monoradical was synthesized and studied by
ESR spectroscopy. Although there are some investiga-
tions on ESR behaviors of paramagnetic calixarenes
bearing an N–O multiradical, they all concern the
spin–spin exchange interaction among different radical
7
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Bauer, L. J. Tetrahedron 1983, 39, 409–426; (b) Iwamoto,
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4
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phatt, R. J. Organometallics 1994, 13, 3054–3062.
1
sites controlled by the metal-binding event or reversible