Sensing and fixation of NO2/N2O4 by calix[4]arenes

Article abstract of DOI:10.1021/ja029166l

An approach toward visual detection and chemical utilization of NO₂/N₂O₄ is proposed, which employs simple calix[4]arenes. Exposure of tetra-O-alkylated calix[4]arenes 1 and 2, possessing either a cone or a 1,3-alternate conformation, to NO₂/N₂O₄, both in chloroform solution and in the solid state, results in deeply colored calixarene-nitrosonium (NO⁺) complexes. In the presence of a Lewis acid, such as SnCl₄, stable calixarene-NO⁺ complexes 7 and 8 were isolated in a quantitative yield and characterized by UV-vis, FTIR, high-resolution ¹H NMR spectroscopy and elemental analysis. NO⁺ is found encapsulated within the calixarene cavity, and stable charge-transfer complexes result with K_ass > 10⁶ M^-1 (CDCl₃). The NO+ encapsulation was also demonstrated in titration experiments with calixarenes 1, 2, and 5 and commercially available NO⁺SbF₆^- salt in chloroform. The complexation process is reversible, and the complexes dissociate upon addition of water and alcohol, recovering the parent calixarenes. Attachment of functionalized calix[4]arenes to silica gel was demonstrated, which afforded a solid material 15 capable of visual detection and entrapment of NO₂/N₂O₄. Calixarene-NO⁺ complexes can be utilized for the NO⁺ transfer processes and nitrosation reactions. The NO⁺ guest transfer between two calixarene containers 2 and 5 was achieved and studied by UV-vis and ¹H NMR spectroscopy. Chemical fixation of NO₂/N₂O₄ was demonstrated through their quantitative transformation into the calixarene-NO⁺ complex and its use as a nitrosonium transfer agent in the synthesis of N-nitrosoamides. These results may lead toward novel nitrogen oxides storing materials.

Full text of DOI:10.1021/ja029166l

Published on Web 02/13/2003
2 2 4
Sensing and Fixation of NO /N O by Calix[4]Arenes
Grigory V. Zyryanov, Yanlong Kang, and Dmitry M. Rudkevich*
Contribution from the Department of Chemistry & Biochemistry, UniVersity of Texas at
Arlington, Arlington, Texas 76019
Received October 31, 2002 ; E-mail: rudkevich@uta.edu
2 2 4
Abstract: An approach toward visual detection and chemical utilization of NO /N O is proposed, which
employs simple calix[4]arenes. Exposure of tetra-O-alkylated calix[4]arenes 1 and 2, possessing either a
cone or a 1,3-alternate conformation, to NO
2
/N
2
O
4
, both in chloroform solution and in the solid state, results
+
in deeply colored calixarene-nitrosonium (NO ) complexes. In the presence of a Lewis acid, such as
+
SnCl
4
, stable calixarene-NO complexes 7 and 8 were isolated in a quantitative yield and characterized by
1
+
UV-vis, FTIR, high-resolution H NMR spectroscopy and elemental analysis. NO is found encapsulated
6
-1
within the calixarene cavity, and stable charge-transfer complexes result with Kass > 10 M (CDCl
3
). The
+
NO encapsulation was also demonstrated in titration experiments with calixarenes 1, 2, and 5 and
+
-
commercially available NO SbF
6
salt in chloroform. The complexation process is reversible, and the
complexes dissociate upon addition of water and alcohol, recovering the parent calixarenes. Attachment
of functionalized calix[4]arenes to silica gel was demonstrated, which afforded a solid material 15 capable
+
+
of visual detection and entrapment of NO
2 2
/N O
4
. Calixarene-NO complexes can be utilized for the NO
+
transfer processes and nitrosation reactions. The NO guest transfer between two calixarene containers
and 5 was achieved and studied by UV-vis and H NMR spectroscopy. Chemical fixation of NO
was demonstrated through their quantitative transformation into the calixarene-NO complex and its use
as a nitrosonium transfer agent in the synthesis of N-nitrosoamides. These results may lead toward novel
nitrogen oxides storing materials.
1
2
/N
2 2
O
4
+
3
Introduction
action between NO and simple calix[4]arenes (Figure 1). We
2
found that (a) calixarenes react with NO2 to form stable
Nitrogen dioxide (NO2) is a major component of so-called
NOX gases.1 NOX is the term used to describe the sum of nitric
oxide (NO), NO2 and other oxides of nitrogen. These are toxic
atmospheric pollutants derived from fossil fuel combustion,
power plants, and large-scale industrial processes. NOX’s are
involved in the formation of ground-level ozone, participate in
global warming, and also form toxic chemicals, nitrate particles
and acid rain/aerosols. NOX’s are aggressively involved in
various nitrosation processes in biological tissues. Free radical
NO rapidly reacts with oxygen, producing N2O3 (e.g., NO‚NO2)
and NO2/N2O4. These are powerful nitrosating agents, both in
the gas phase and in solution. The pathophysiological signifi-
cance of NOX derives from their ability to generate mutagenic
nitrosopeptides and further diazopeptides, to produce carcino-
genic nitrosoamines, and to nitrosate and further deaminate DNA
nucleobases. According to The United States Environmental
+
+
nitrosonium (NO ) complexes, (b) these calixarene-NO com-
plexes are deeply colored and can dissociate/bleach upon
addition of water, and (c) these complexes can be utilized for
,2
+
the NO transfer processes and nitrosation reactions. Accord-
ingly, our results offer a novel process of NO2 visual sensing
and chemical utilization and may also lead toward novel,
supramolecular NO2-storing materials.
Results and Discussion
Rationale and Design. Calix[4]arenes are popular building
blocks in molecular recognition and they are widely used in
the construction of molecular containers - cavitands, (hemi)-
4
carcerands, and capsules. Cone-shaped calix[4]arenes are ∼4
Å deep and ∼7 Å in diameter at the upper rim. Tetra-O-alkylated
cone calix[4]arenes exist in the pinched C2V symmetrical
conformation, with two opposite aromatic rings almost parallel
and situated ∼5 Å apart, and two others flattened. This
conformation is more preferable than the perfect cone C4V
conformation. Usually, the interconversion between two C2V
1
Protection Agency, national emissions of NOX have increased
over the past 20 years by 4%. Tolerable levels of NOX are e 5
ppm. Extensive NO2 circulation in the atmosphere requires not
only its systematic monitoring but also necessitates the develop-
ment of improved methods of the NO2 fixation and utilization.
Here, we describe host-guest complexes, formed upon inter-
(
3) Part of this work appeared as a preliminary communication, see: Zyryanov,
G. V.; Kang, Y.; Stampp, S. P.; Rudkevich, D. M. Chem. Commun. 2002,
2792-2793.
(
1) (a) Lerdau, M. T.; Munger, J. W.; Jacob, D. J. Science 2000, 5488, 2291-
2
293. (b) U. S. Environmental Protection Agency site: http://www.epa.gov/
(4) (a) Calixarene 2001; Asfari, Z., B o¨ hmer, V., Harrowfield, J., Vicens, J.,
Eds.; Kluwer Academic Publishers: Dordrecht, 2001. (b) Gutsche, C. D.
Calixarenes ReVisited; Royal Society of Chemistry: Cambridge, 1998. (c)
Rudkevich, D. M. Bull. Chem. Soc. Jpn. 2002, 75, 393-413.
air/urbanair/nox/index.html.
(2) Kirsch, M.; Korth, H.-G.; Sustmann, R.; de Groot, H. Biol. Chem. 2002,
3
83, 389-399.
10.1021/ja029166l CCC: $25.00 © 2003 American Chemical Society
J. AM. CHEM. SOC. 2003, 125, 2997-3007
9
2997

A R T I C L E S
Zyryanov et al.
Of particular importance for us, N2O4 may disproportionate to
+
-
10,11
ionic NO NO3 upon reacting with aromatic compounds.
Combining these features of NO2/N2O4 with unique com-
plexing abilities of calix[4]arenes, we expected that interactions
between them might lead to calixarene-nitrosonium complexes.
Below, we describe the sequence of experiments, elaborating
this idea, and also the chemical consequences, that follow.
Figure 1. Chemical fixation of NO2/N2O4 with calix[4]arenes, a cartoon
representation. Formation of encapsulated nitrosonium complexes.
5
structures is fast on the NMR time scale. Calix[4]arenes in a
12
Synthesis. Calix[4]arenes 1 and 2, possessing a cone and a
1
,3-alternate conformation are much more rigid and possess a
1
,3-alternate conformation, respectively, were synthesized
cylindrical inner tunnel, defined by two cofacial pairs of
aromatic rings oriented orthogonal along the cavity axis.
According to the number of X-ray studies, this tunnel is ∼5-6
through O-alkylation of the corresponding parent calix[4]arenes
with n-hexylbromide (Scheme 1). In the synthesis of 1, NaH
was employed as a base in hot DMF. Preparation of 2 includes
the two-step alkylation of de-tert-butylated calix[4]arene with
n-hexyl bromide, using successively K2CO3 and then Cs2CO3
6
Å in diameter.
Complexes of calix[4]arenes with neutral molecules are weak.
The cavities are obviously too small and they also lack additional
binding sites. In most of the crystal structures of the inclusion
complexes of calixarenes, the guest molecule is positioned not
inside but roughly above the plane defined by the upper carbon
atoms of the cyclic polyaromatic skeleton. On the other hand,
cations are known to more strongly interact with the calixarene
π-surface. Ammonium ions and metal cations were found
1
3
in boiling MeCN.
Bromination of 2 with NBS in acetone afforded tetrabromo-
calix[4]arene 3 in 53% yield (Scheme 2). Tetrahydroxylated
1,3-alternate derivative 4 was obtained through bromo-lithium
exchange in 3 (n-BuLi, THF, -78 °C), followed by treatment
with B(OMe)3 and oxidation with H2O2 and aq NaOH (40%
yield after three steps). Calixarene 4 was subsequently alkylated
with n-hexylbromide and NaH in hot DMF to yield octahexyloxy-
7
complexed within the cone-shaped cavities. 1,3-Alternates,
14
calix[4]arene 5 in 85%. Mesitylene derived 1,3-alternate 6 was
functionalized with appropriate binding sites on the phenol
+
+
+
obtained for comparison, according to the literature procedure
oxygens, bind metal cationssNa , K , and Ag sboth with
“
1
5,16
8
by Pappalardo
and subsequent O-alkylation with n-hexyl-
hard” oxygens and “soft” π-basic aromatic rings. Recently,
bromide (Scheme 3).
Kochi, Rathore an co-workers described very stable complexes
+
Interaction of Calix[4]arenes with NO2. Bubbling NO2
through the solutions of 1, 2, and 5 in CHCl3 resulted in instant,
deep coloration. Solutions of 1 and 5 turned dark blue, and
solution of 2 became deep purple. The UV-vis spectra changed
accordingly: the broad bands appeared at λmax ) 560, 512, and
between calix[4]arenes and nitrosonium (NO ) cation, both in
9
+
solution and in the solid state. The NO cation was found
encapsulated within the calixarene cavity (X-ray analysis), and
strong charge-transfer interactions with the π-surface of calix-
arene positioned the guest between the cofacial aromatic rings
at a distance 2.4 Å, which is much shorter than the typical van
der Waals contact (3.2 Å).
6
00 nm for NO2-exposed solutions of 1, 2, and 5, respectively.
This is in a striking contrast to colorless solutions of 1, 2, and
, and pale yellow solution of NO2 in CHCl3, and implies a
5
NO2 is a paramagnetic gas since it has an unpaired electron
on the nitrogen. It has an intense brown-orange color. Reacting
with itself, it forms the colorless dimer, dinitrogen tetroxide
charge-transfer mechanism.
In the experiments with noncyclic anisole (e.g., methoxy-
benzene), only pale coloration was observed upon exposure to
NO2. Moreover, when mesitylene derived, Pappalardo’s calix-
arene 6, with the sterically blocked and conformationally much
more rigid cavity, was tested, no coloration was observed either.
In 6, the pair of methyl groups in the ortho-positions to the
oxygen forces the methyl groups of the adjacent aromatic rings
toward each other, not only blocking an access to the cylindrical
inner cavity, but also significantly rigidifying it. The same effect
takes place on the other side of the calixarene 6, which makes
its interior completely hindered. These model experiments
emphasize the importance of caVities in the described transfor-
(
N2O4).10 The N-N bond in N2O4 is quite weak, and as the
temperature is raised it rapidly dissociates back to NO2. The
position of the equilibrium between the two compounds and
the color of the system vary with temperature. Below -21 °C,
only pure, solid N2O4 is present. Above 140 °C the system is
1
00% NO2. The dynamic interconversion between NO2 and
N2O4 makes it impossible to study either of these species alone.
(
5) (a) Arduini, A.; Fabbi, M.; Mirone, L.; Pochini, A.; Secchi, A.; Ungaro,
R. J. Org. Chem. 1995, 60, 1454-1458. (b) Conner, M.; Janout, V.; Regen,
S. L. J. Am. Chem. Soc. 1991, 113, 9670-9671. (c) Scheerder, J.;
Vreekamp, R. H.; Engbersen, J. F. J.; Verboom, W.; van Duynhoven, J. P.
M.; Reinhoudt, D. N. J. Org. Chem. 1996, 61, 3476-3481.
+
mations and suggest the possibility of the NO coordination
(
6) (a) Iwamoto, K.; Shinkai, S. J. Org. Chem. 1992, 57, 7066-7073. (b) Beer,
P. D.; Drew, M. G. B.; Gale, P. A.; Leeson, P. B.; Ogden, M. I. J. Chem.
Soc., Dalton Trans. 1994, 3479-3485. (c) Perez-Adelmar, J.-A.; Abraham,
H.; Sanchez, C.; Rissanen, K.; Prados, P.; de Mendoza, J. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1009-1011. (d) de Mendoza, J.; Cuevas, F.; Prados,
P.; Meadows, E. S.; Gokel, G. W. Angew. Chem., Int. Ed. Engl. 1998, 37,
inside 1, 2, and 5 (Figure 2, Figure 3, Figure 4).
(11) (a) Bosch, E.; Kochi, J. K. J. Org. Chem. 1994, 59, 3314-3325 and
references therein. (b) Evans, J. C.; Rinn, H. W.; Kuhn, S. J.; Olah, G.
Inorg. Chem. 1964, 3, 857-861.
(12) Kenis, P. J. A.; Noordman, O. F. J.; Schonherr, H.; Kerver, E. G.; Snellink-
Ruel, B. H. M.; van Hummel, G. J.; Harkema, S.; van der Vorst, C. P. J.
M.; Hare, J.; Picken, S. J.; Engbersen, J. F. J.; van Hulst, N. F.; Vancso,
G. J.; Reinhoudt, D. N. Chem. Eur. J. 1998, 4, 1225-1234.
(13) For a typical preparation of calix[4]arene 1,3-alternates, see: Casnati, A.;
Pochini, A.; Ungaro, R.; Ugozzoli, F.; Arnaud, F.; Fanni, S.; Schwing,
M.-J.; Egberink, R. J. M.; de Jong, F.; Reinhoudt, D. N. J. Am. Chem.
Soc. 1995, 117, 2767-2777.
1
534-1537.
(
7) (a) Ikeda, A.; Shinkai, S. Chem. ReV. 1997, 97, 1713-1734. (b) Lhotak,
P.; Shinkai, S. J. Phys. Org. Chem. 1997, 10, 273-285. (c) Assmus, R.;
B o¨ hmer, V.; Harrowfield, J. M.; Ogden, M. I.; Richmond, W. R.; Skelton,
B. W.; White, A. H. J. Chem. Soc., Dalton Trans. 1993, 2427-33.
8) (a) Ikeda, A.; Shinkai, S. J. Am. Chem. Soc. 1994, 116, 3102-3110. (b)
Ikeda, A.; Tsuzuki, H.; Shinkai, S. Tetrahedron Lett. 1994, 35, 8417-
(
8420. (c) Ikeda, A.; Shinkai, S. J. Chem. Soc., Chem. Commun. 1994,
2375-2376. (d) Ikeda, A.; Tsudera, T.; Shinkai, S. J. Org. Chem. 1997,
62, 3568-3574.
(14) For a typical procedure, see: Pellet-Rostaing, S.; Chitry, F.; Nicod, L.;
Lemaire, M. J. Chem. Soc., Perkin Trans. 2 2001, 1426-1432.
(15) Pappalardo, S.; Ferguson, G.; Gallagher, J. F. J. Org. Chem. 1992, 57,
7102-7109.
(16) Staffilani, M.; Bonvicini, G.; Steed, J. W.; Holman, K. T.; Atwood, J. L.;
Elsegood, M. R. J. Organometallics 1998, 17, 1732-1740.
(9) Rathore, R.; Lindeman, S. V.; Rao, K. S. S.; Sun, D.; Kochi, J. K. Angew.
Chem., Int. Ed. 2000, 39, 2123-2127.
(
10) Addison, C. C. Chem. ReV. 1980, 80, 21-39.
2
998 J. AM. CHEM. SOC. VOL. 125, NO. 10, 2003
9

Sensing and Fixation of NO
2
/N
2
O
4
A R T I C L E S
Scheme 1
(A) n-hexyl Bromide, NaH, DMF, 70 °C, 24 H, 75%. (B) n-hexyl Bromide, K2CO3, MeCN, 80 °C, 48 H, 84 %. (C) n-hexyl Bromide, Cs2CO3, MeCN,
8
0 °C, 48 H, 46%.
Scheme 2
(
A) NBS, Acetone, Rt, 48 H, 53% Yield. (B) n-BuLi (60 eq), THF, -78 °C, 0.5 h. (C) B(OMe)3, -78 °C to 0 °C. (D) H2O2, Aq NaOH, -78 °C to 25
°
C, 40%, Three Steps). (E) n-hexyl Bromide, NaH, DMF, 70 °C, 24 H, 85%.
Scheme 3
(
A) n-hexyl Bromide, NaH, DMF, 70 °C, 72 H, 50%.
Figure 2. Nitrosonium complexes of calix[4]arene 1; two methods of
+
-
According to molecular modeling,17 one NO cation can fit
inside the cavities 1, 2, and 5, and neither bent NO2 nor bulky
NO3 can be accommodated. Two parallel aromatic rings of a
cone calix[4]arene participate in the NO complexation, and
all four rings of a 1,3-alternate calixarene are involved. In
mesitylene derived calixarene 6, no NO encapsulation may
occur for steric reasons.
While the instant coloration implied charge-transfer between
the prereactive nitrosating/nitrating species and 1, 2, and 5, this
was difficult to monitor. Interaction of NO2 with 1, 2, and 5 is
very dynamic, and the initial H NMR analysis of the solutions
gave rather complex, quickly changing pictures. The NO2/N2O4
+
preparation. Left: addition of NO SbF6 to 1 in chloroform. Right: reaction
of NO2/N2O4 with 1 in the presence of SnCl4 in chloroform. Below:
+
MacroModel representation of the NO encapsulation process. The CH
-
hydrogen and long alkyl chains are omitted for viewing clarity.
+
Not surprisingly, the NO2-containing CHCl3 solutions of 1 and
2 bleached within 1-2 h, yielding mixtures of known p-nitrated
+
1
8
1
calixarenes (preparative TLC, H NMR). Calixarene 5, much
more activated for the electrophilic aromatic substitution, reacts
with NO2 even fasterswithin few minutes, producing a very
complex mixture of dealkylated and oxidized products.19
At the same time, when treated with SnCl4, solutions of 1, 2
and 2-3 equivs of NO2 did not yield the nitration products. It
1
2,10,11
mixture is known as an effective nitrosating/nitrating agent.
(
18) 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, 1075-1077.
(
17) MacroModel 7.1; MM2 and Amber* Force Field. See: Mohamadi, F.;
Richards, N. G.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.;
Chang, G.; Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440-
(19) Dealkylation and oxidation of phenol ethers upon nitrosation/nitration,
see: Rathore, R.; Bosch, E.; Kochi, J. K. Tetrahedron 1994, 50, 6727-
6758 and references therein.
4
67.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003 2999

A R T I C L E S
Zyryanov et al.
Table 1. Selected Spectroscopic Data for Calix[4]arenes 1, 2, and
a,b,c
5, and Their Nitrosonium Complexes
ν, cm-
1
λmax, nm
compd
δ, ppm
1
2
6.76 (s, arom), 4.41,
3
.12 (2 × d, CH2)
6.92 (d, arom), 6.68
t, arom), 3.62 (s, CH2),
.54 (t, OCH2)
6.55 (s, arom), 3.83
t, OCH2), 3.62 (s, CH2),
.35 (t, OCH2)
6.54 (s, arom), 3.93
t, OCH2), 3.76 (t, OCH2),
.44 (s, CH2)
6.99 (s, arom), 4.39,
.44 (2 × d, CH2)
7.17 (t, arom), 7.08
d, arom), 3.87 (t, OCH2)
.60 (s, CH2)
(
3
5
5
(
3
+
-
‚NO SbF6
1876
600
(
3
7
8
1923
1955
563
524
3
Figure 3. Nitrosonium complexes of calix[4]arene 2; two methods of
synthesis. Below: MacroModel representation of the NO encapsulation
+
(
3
process. The CH hydrogen and long alkyl chains are omitted for viewing
clarity.
a
b
At 295 ( 1 K. The above-reported spectral features of complexes
+
-
+
-
+
-
1
‚NO SbF6 , 2‚NO SbF6 , and 5‚NO SbF6 are similar to those of 7, 8,
and 9, respectively. In CDCl3 for H NMR and FTIR, and in CHCl3 for
UV-vis.
c
1
Figure 4. Mesitylene-derived calixarene 6 does not encapsulate NO+.
Left: space-filling representation of 6; the long alkyl chains are omitted
for viewing clarity.
is known that Lewis acids stabilize arene-nitrosonium charge-
transfer complexes.10,11 Precipitation with hexanes resulted in
deeply colored, moisture sensitive solids, assigned to nitroso-
nium complexes 7 and 8 (>90% yield, Figures 2-4). These
complexes are very stable and can be stored, in the absence of
moisture, for several weeks, both in CHCl3 solution and in the
solid state. Complex 7 is dark blue, and complex 8 is deep
purple.
Analysis and Characterization. Selected spectral features
of the obtained nitrosonium complexes are presented in Table
2
0,21
1
. The UV-vis spectra showed broad charge-transfer
at λmax ∼ 563 and 524 nm, and the FTIR spectra exhibited
characteristic arene-NO stretching at ν ) 1923 and 1955
bands
2
0
+
-
1
1
cm for 7 and 8, respectively. The H NMR spectra of 7 and
8
exhibited new sets of the calixarene signals as well (Figure
5). In particular, aromatic CH protons of guest-free 1 were seen
as a singlet at 6.76 ppm. In nitrosonium complex 7, these were
transformed into a singlet at 6.99 ppm. The methylene bridge
CH2 protons of 1 were recorded as doublets at 4.41 and 3.12
ppm (J ) 12.5 Hz). In complex 7, these were seen as doublets
at 4.39 and 3.44 ppm (J ) 13 Hz). The aromatic protons of
free 2 were seen as a doublet and a triplet, 2:1, at 6.92 and 6.68
ppm, respectively (J ) 7.5 Hz). In nitrosonium complex 8, these
were transformed into a triplet and a doublet, 1:2, at 7.17 and
1
Figure 5. Portions of the H NMR spectra (500 MHz, CDCl3, 295 ( 1 K)
of: (a) calix[4]arene 1. (b) nitrosonium complex 7; the identical spectrum
was obtained upon addition of NO SbF6 to 1. (c) calix[4]arene 2. (d)
nitrosonium complex 8; the identical spectrum was obtained upon addition
+
-
+
-
of NO SbF6 to 2. The residual CHCl3 signals are marked “b”.
moisture sensitive and thermally unstable 7 and 8 proved to be
difficult but reproducibly showed the CHN ratios corresponding
to the presence of only one NO cation in both structures.
Independent structural evidence came from the complexation
experiments between calixarenes 1 and 2 and commercially
available NO SbF6 salt (Figure 2, Figure 3). Specifically, the
CDCl3 solutions of 1 and 2 were treated with NO SbF6 at
7.08 ppm, respectively (J ) 7.5 Hz). The methylene bridge CH2
+
and OCH2 protons of 2 were seen as a singlet and a triplet, 1:1,
at 3.62 and 3.54 (J ) 7.5 Hz), respectively. In complex 8, these
were transformed into a singlet and a triplet, 1:1, at 3.60 and
+
-
3.87 (J ) 7.5 Hz), respectively. Elemental analysis of extremely
+
-
2
95 K and the complexation induced changes in the UV-vis,
(
20) Borodkin, G. I.; Shubin, V. G. Russ. Chem. ReV. 2001, 70, 211-230.
21) Rosokha, S. V.; Kochi, J. K. J. Am. Chem. Soc. 2001, 123, 8985-8999.
1
(
FTIR, and H NMR spectra were recorded. Under these
3000 J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003

Sensing and Fixation of NO
2
/N
2
O
4
A R T I C L E S
conditions, the complexation process proved to be rather slow,
however after ∼20 h no starting calixarenes 1,2 were observed
1
and the corresponding UV-vis, FTIR, and H NMR spectra
exhibited features similar to those of nitrosonium complexes
7
,8. These spectral data are in agreement with the Kochi and
9
Rathore spectral observations.
Analogously, a nitrosonium complex of calixarene 5 was
obtained. The UV-vis spectrum of dark blue complex
+
-
5
‚NO SbF6 showed broad band at λmax ≈ 600 nm, and the
20
+
FTIR spectrum exhibited characteristic arene-NO stretching
-
1
1
+
-
at 1876 cm . The H NMR spectrum of 5‚NO SbF6 is
different from 5 as well. For example, the methylene bridge
CH2 and both OCH2 protons of 5 were seen as a singlet and
two triplets, 1:1:1, at 3.62, 3.83 (J ) 7 Hz), and 3.35 ppm (J )
+
-
7
Hz), respectively. In complex 5‚NO SbF6 , these were
observed at 3.44, 3.93 (J ) 7.5 Hz), and 3.76 ppm (J ) 7.5
Hz), respectively.
Figure 6. Proposed host-guest dynamics in calix[4]arene-NO+ complexes.
Summarizing, reactions between NO2/N2O4 and O-alkylated
The association constants for the above complexes were too
1
high to be measured by the H NMR technique. Even slight
+
-
excess of NO SbF6 results in the complete complex formation
+
calix[4]arenes proceed via the NO encapsulation. Calix[4]-
in CDCl3, and no free calixarenes 1,2, and 5 were observed
arene-nitrosonium complexes can be significantly stabilized by
Lewis acids.
6
-1
295
after equilibration. The Kass values >10 M (∆G > 8 kcal
-1
mol ) for the complexes were estimated, which is in agreement
1
Host-Guest Dynamics. As evident from the H NMR data,
9
with the published values in CH2Cl2. Although complexes
+
the NO exchange in and out of the cavity is slow on the NMR
+
-
+
-
1
‚NO SbF6 and 2‚NO SbF6 formed slowly, over ∼20 h, it
time scale. For example, in the titration experiments between
+ -
took only few minutes to form complex 5‚NO SbF6 . More-
+
-
calixarenes 1 and 2 and NO SbF6 , both free and complexed
+
over, highly electrophilic NO tends to further react with
‚NO SbF6 , and unidentified impurities were seen in the NMR
2
3
species can be observed separately. This is typical for the
host-guest complexes with high Kass > 10 M values. On
the other hand, the NO guest, with the van der Waals
dimensions <2 Å, freely migrates within the cavity at room
+
-
5
6
-1
spectrum already after several minutes. Unlike complexes
+
+
-
+
-
1
‚NO SbF6 and 2‚NO SbF6 , which are chemically stable for
2
0
+
-
1
weeks, complex 5‚NO SbF6 decomposes within a day ( H
NMR).
1
temperatures (Figure 6). Indeed, the H NMR spectra of
1
9
complexes 7,8 possess the same symmetry as guest-free
calixarenes 1,2, which in principle should be reduced upon
Addition of H2O or MeOH to the freshly prepared CHCl3
solutions of 7 and 8 and the nitrosonium complexes prepared
+
complexation with nonsymmetrical NO .
+
-
from 1, 2, and 5 and NO SbF6 , resulted in the complete
Cone calix[4]arene complex 7 should have a pinched, C2V
complex dissociation and recovery of calixarenes 1, 2, and 5
symmetrical conformation, since only two opposite, cofacial
1
(
preparative TLC, UV-vis, H NMR).
+
aromatic rings trap NO . Instead, the observed at room-
With the above information in hands, we subsequently
reexamined the spectral data for the reactions between 1 and 2
temperature NMR spectrum exhibits a C4V symmetry, indicating
a fast on the NMR time scale exchange between two C2V
structures. 1,3-Alternate calix[4]arene complex 8 should exhibit
a C2V symmetry, with two different top and bottom halves of
the skeleton. Instead, the apparent at room-temperature sym-
and NO2, in the absence of SnCl4. As excess NO2 was passed
+
-
through the solution of 1, nitrosonium complex [1‚NO ]NO3
1
was clearly seen (UV-vis, H NMR), along with the mixture
of nitration products. For 2, no signals for nitrosonium complex
2
4
metry is S4, with equal top and bottom halves.
+
-
22
[
2‚NO ]NO3 were detected. Apparently, while formed these
At the same time, the complexation process is reversible, and
nitrosonium species quickly react with an excess NO2. Overall,
both reactions subsequently yield p-nitrated calixarenes.
+
the NO guest can still leave the calixarene cavity. Addition of
H2O to the freshly prepared CHCl3 solutions of 7,8 resulted in
the complete dissociation and recovery of calixarenes 1,2.
Interestingly, complex 8 bleached within seconds, but it took
(
22) In the experiments between calixarene 2, SnCl
of NO /N , one more prereactive complex was detected, which we
assigned to nitronium species [2‚NO
spectrum, a broad charge-transfer band at λmax ) 512 nm was recorded.
4
and larger (∼50-fold) excess
2
2 4
O
+
-
2
]NO
3
4
SnCl . In the UV-vis
2
5
several minutes to decompose complex 7. We propose, that
the kinetics is responsible. Apparently, t-Bu groups at the upper
-1
The FTIR spectrum showed stretches at ν ) 2356 cm , characteristic for
+
1
+
-
NO
2
species. In the H NMR spectrum, complex [2‚NO
2
]NO
3
SnCl
4
exhibits a broader doublet and a triplet, 2:1, at 7.10 and 7.00, respectively.
As one possible explanation, initially formed nitrosonium complex 8 yields
(23) Typical examples of slow exchange in open-ended host-guest complexes
with cavitands: (a) Rudkevich, D. M.; Hilmersson, G.; Rebek, J., Jr. J.
Am. Chem. Soc. 1998, 120, 12 216-12 225. (b) L u¨ cking, U.; Tucci, F. C.;
Rudkevich, D. M.; Rebek, J., Jr. J. Am. Chem. Soc. 2000, 122, 8880-
8889.
+•
-
the electron-transfer complex [2 ‚NO]NO
3
and releases NO. The resulting
, producing
+
•
-
3
cation-radical 2 NO
reacts with an excess of NO
and further charge-transfer nitronium complex [2‚NO
The structure was independently confirmed by complexation between 2
2
+•
-
+
-
3
[
2 ‚NO
2
]NO
3
2
]NO .
+
-
1
and NO
spectra were similar to those of the complex obtained from 2, NO
and SnCl . As an excess NO was passed through the solution of 2, no
signals for nitrosonium complex [2‚NO ]NO
2
SbF
6
in CDCl
3
. The obtained UV-vis, FTIR, and H NMR
(24) This observation also appeared in ref 9. Even at very low temperatures, i+t
was impossible to discriminate between two halves of 1,3-alternate-NO
complex.
2
/N O
2 4
4
2
+
-
3
were seen, but nitronium
was detected. Complexation studies with calixarene
in CDCl revealed the formation of kinetically stable
. Judging from the intense coloration, the calixarene
(25) In a typical experiment, deeply colored solutions of complexes 7 and 8 in
+
-
complex [2‚NO
2
]NO
3
CHCl
3
(1-2 mL, 5-25 mmol concentration range) were mixed with 1
+
-
1
and NO
complex [1‚NO
walls, most probably, encapsulate NO
calixarene-nitronium complexes will be published separately.
2
SbF
6
3
mL of H O and vigorously stirred until decoloration. Complex 8 bleached
2
+
-
2
]SbF
6
within 30 ( 15 s, and it took 2-3 min to decompose complex 7. The
+
2
. Detailed description of observed
experiments were run at least in triplicate. The concentrations of complexes
1
7 and 8 were determined by H NMR spectroscopy prior measurements.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003 3001

A R T I C L E S
Zyryanov et al.
Figure 7. Left: NO+ transfer between calixarene containers, a cartoon representation. Right: formation of complex 9 from complex 8.
Figure 8. Nitrosonium transfer experiment. Portions of the UV-vis spectra
-
6
(
[8] ) [5] ) 10 M, CHCl3, 295 ( 1 K). Band at λmax ≈ 524 nm belongs
to nitrosonium complex 8, band at λmax ≈ 600 nm is assigned to complex
. Visually, the exchange results in a color change from purple (left vial)
9
to blue (right vial).
rim of the latter complex pose significant steric hindrances and
+
protect the encapsulated NO species from the entering H2O.
+
20
Such stability of the arene-NO complex is without precedent.
+
On the other hand, NO guest can be transferred from one
calixarene container to another (Figure 7). Calixarene 5 was
specifically designed to promote such transfer from the pre-
formed complex 8. Four additional, electron donating O(CH2)5-
CH3 groups were introduced in p-positions to the initial set of
O(CH2)5CH3 groups. This makes cavity 5 significantly more
π-electron rich and dramatically increases its affinity toward
1
Figure 9. Portions of the H NMR spectra (500 MHz, CDCl3, 295 ( 1 K)
of: (a) nitrosonium complex 8, obtained from 2, NO2 and SnCl4. (b) mixture
of complex 8 and calixarene 5 after 20 min; ∼30% conversion to 9. (c) the
same mixture after 1 h; complex 9 is formed with >95% conversion. (d)
+
positively charged NO .
For the exchange experiments, we obtained 8 by treating
calixarene 2 with 3 equivalents NO2 and 1 eq SnCl4 in CHCl3.
Further, complex 8 and “empty” host 5 were mixed in a 1:1
+
-
nitrosonium complex 5‚NO SbF6 , independently obtained from 5 and
+
-
NO SbF6 . The residual CHCl3 signals are marked as before, the
1
ratio at 295 K in dry chloroform, and the UV-vis and H NMR
decomposition products of 5 are marked “*”.
spectra were recorded over 2 h. Due to the strong affinity of 2
+
copy, the NO+ exchange resulted in clean transformation of
the spectra from mixture 8 + 5 to mixture 2 + 9 (Figure 9).
For example, the methylene bridge CH2 and OCH2 protons of
8, seen as a singlet and a triplet, 1:1, at 3.60 and 3.87 ppm (J
) 7.5 Hz), slowly decrease in intensity. Instead, two OCH2
triplets at 3.93 and 3.76 ppm (J ) 7.5 Hz) and the methylene
bridge CH2 singlet at 3.44 ppm appear and grow. These were
assigned to complex 9 and confirmed in the series of indepen-
toward NO , the guest presence outside the cavity, in a bulk
+
solution, was considered negligible, and the only source of NO
was 8.
1
Initially, the H NMR spectrum exhibited only sets of signals
for 8 and free calixarene 5, and the corresponding UV-vis
spectrum showed only the characteristic absorption for charge-
transfer in 8. Within minutes however, the guest transfer was
clearly detected. The band at λmax ≈ 524 nm, assigned to
complex 8, systematically decreased and a new band at λmax ≈
+
-
dent experiments between 5 and NO SbF6 . Signals for “empty”
calixarene 2 also appear, although slightly shifted due to the
presence of SnCl4, and signals for 8 disappear. Within an hour
6
00 nm, corresponding to new complex 9, appeared.
The nitrosonium transfer can even be observed visually. The
1
purple solution of 8 in CHCl3 turns blue upon addition of
the nitrosonium transfer was completed; both the H NMR and
1
calixarene 5 (Figure 8). When followed by H NMR spectros-
UV-vis spectra exhibited only the signals of complex 9 and
3002 J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003

Sensing and Fixation of NO
2
/N
2
O
4
A R T I C L E S
Scheme 4
(
A) BrCH2C(O)Oc2H5, Na2CO3, MeCN, 80 °C, 12 H, 89 %. (B) KOH, THF-H2O, 100 °C, 12 H, Then Aq HCl, >95%. (C) N-hydroxy Succinimide,
DCC, DMAP, THF, Rt, 12 H, 83%. (D) CH3(CH2)7-NH2, Et3N, THF, Rt, 12 H, 65%.
free calixarene 2. No traces of initial complex 8 were detected.
To our knowledge, this is the first case of a quantitative guest
2
6
transfer between two different molecular containers. Such
behavior has a potential for information storage and processing
since the color can be switched between two distinguishable
states.
Functionalized Silica Gel. Presented here calix[4]arene-NO2
interactions (a) are reversible, (b) result in dramatic color
changes, and (c) are unique and specific for NO2, which should
guaranty its detection in the presence of such gases as H2O,
O2, HCl, HBr, SOX, and NH3. Indeed, none of these vapors/
gases undergoes such interactions/reactions with calixarenes!
Even NO gas does not interact with calixarenes. In their
excellent work on NO sensing by tetra-O-alkylated calix[4]-
Figure 10. Left: preparation of calix[4]arene functionalized silica gel 15:
a) Et3N, THF, rt, 12 h. Right: NO2 entrapment “chromatography”
experiments. The columns were prepared as follows: (a) loaded with starting
aminopropyl functionalized silica gel; (b) loaded with dry silica gel 15; (c)
loaded with 15 and flashed with CHCl3. All three columns were then flashed
with NO2 (∼30 s), and the pictures were made after ∼2-3 min afterward.
(
9
arenes, Kochi and Rathore showed that calixarenes had to be
oxidatively activated, e.g., to form the corresponding cation-
radicals, prior complexing NO.
Current NO2 sensors are mostly electrochemical and monitor
2
7
changes of potential upon exposure metal surfaces to NO2. In
many cases however, other vapors - H2O, O2, HCl, HBr, SOX,
and NH3 significantly influence the detection selectivity and
therefore sensitivity. Optical sensors, which are based on
coloration reaction between NO2 and certain organic compounds,
are more selective as the reactions are specific.28 At the same
time, reversibility of such sensing processes is not easy to
achieve.
readily immobilizable on larger (macro)molecules, solid supports
or surfaces. A wide variety of polymers and nanomaterials are
now commercially available. Here, we used 3-aminopropylated
silica gel from Aldrich and functionalized it with calixarene
modules. As follows from molecular modeling, calix[4]arene
fragments are ∼10 × 10 Å in their dimensions, so their
attachment via lower rim should guaranty the proper configu-
ration of the upper rim to sufficiently respond to the presence
of the gas analyte.
For potential application in sensing technology, receptor
molecules must not only be synthetically available, but also
Synthetically, tris-O-substituted calixarene 10, prepared by
selective alkylation of the parent calix[4]arene with n-hexyl-
(
26) Usually, exchange studies follow guest’s motion in and out of the cavity,
see: (a) Cram, D. J.; Blanda, M. T.; Paek, K.; Knobler, C. B. J. Am. Chem.
Soc. 1992, 114, 7765-7773. (b) Mogck, O.; Pons, M.; B o¨ hmer, V.; Vogt,
W. J. Am. Chem. Soc. 1997, 119, 5706-5712. See also ref 23. In
competition experiments, involving two or more different guest molecules,
these replace each other within one given host-container, see: (a)
Santamaria, J.; Martin, T.; Hilmersson, G.; Craig, S. L.; Rebek, J., Jr. Proc.
Natl. Acad. Sci. U.S.A. 1999, 96, 8344-8347. (b) Heinz, T.; Rudkevich,
D. M.; Rebek, J., Jr. Nature 1998, 394, 764-766. (c) Tucci, F. C.;
Rudkevich, D. M.; Rebek, J., Jr. J. Am. Chem. Soc. 1999, 121, 4928-
29
bromide and BaO/Ba(OH)2 in DMF (69%), was further
alkylated with ethyl bromoacetate to afford derivative 11 (Na2-
CO3, MeCN, 89%) (Scheme 4). This was hydrolyzed with KOH
in THF-H2O mixture, resulting calixarene acid 12 in a
quantitative yield. Acid 12 was further activated with N-
bromosuccinimide (DCC, DMAP, THF) to afford active ester
13 (83%). Compound 13 readily reacts with amines. Thus, amide
4
929. For a combinatorial selection of capsules for one given guest see:
Hof, F.; Nuckolls, C.; Rebek, J., Jr. J. Am. Chem. Soc. 2000, 122, 4251-
252.
27) Recent papers: (a) Filippini, D.; R o¨ sch, M.; Arag o´ n, R.; Weimar, U. Sensors
14 was prepared from 13 and n-octylamine (Et3N, THF, 65%)
and used for control experiments. Analogously, ester 13 was
coupled to 3-aminopropyl-functionalized silica gel in THF in
the presence of Et3N to afford material 15 (Figure 10). The
presence of a calix[4]arene fragment in 15 was confirmed by
4
(
&
Actuators B 2001, 81, 83-87. (b) Steffes, H.; Imawan, C.; Solzbacher,
F.; Obermeier, E. Sensors & Actuators B 2001, 78, 106-112. (c) Pijolat,
C.; Pupier, C.; Sauvan, M.; Tournier, G.; Lalauze, R. Sensors & Actuators
B 1999, 59, 195-202. (d) Law, M.; Kind, H.; Messer, B.; Kim, F.; Yang,
P. Angew. Chem., Int. Ed. Engl. 2002, 41, 2405-2408.
-
1
(28) Recent optical sensors for NO
2
: (a) Bradford, A.; Drake, P. L.; Worsfold,
the FTIR analysis in KBr disks: ν(CH) ≈ 2960 cm and ν-
O.; Peterson, I. R.; Walton, D. J.; Price, G. J. Phys. Chem. Chem. Phys.
-1
(
CdO) ≈ 1650 cm were recorded, which are similar to the
2
001, 3, 1750-1754. (b) Dooling, C. M.; Worsfold, O.; Richardson, T.
-1
H.; Tregonning, R.; Vysotsky, M. O.; Hunter, C. A.; Kato, K.; Shinbo, K.;
Kaneko, F. J. Mater. Chem. 2001, 11, 392-398. (c) Baldini, F.; Capobi-
anchi, A.; Falai, A.; Mencaglia, A. A.; Pennesi, G. Sensors & Actuators B
stretching of model calixarene amide 14: ν(CH) ) 2964 cm
-1
and ν(CdO) ) 1680 cm . From the CHN analysis, only ∼17%
calixarene loading was achieved, which may be due to the steric
bulkiness of the calixarene fragment.
2
001, 74, 12-17. (d) Nezel, T.; Fakler, A.; Zhylyak, G.; Mohr, G. J.;
Spichiger-Keller, U. E. Sensors & Actuators B 2000, 70, 165-169. (e)
Capone, S.; Mongelli, S.; Rella, R.; Siciliano, P.; Valli, L. Langmuir 1999,
1
5, 1748-1753. (f) Tanaka, T.; Ohyama, T.; Maruo, Y. Y.; Hayashi, T.
Sensors & Actuators B 1998, 47, 65-69. (g) Hu, W. P.; Liu, Y. Q.; Liu,
(29) For a typical procedure, see: Iwamoto, K.; Fujimoto, K.; Matsuda, T.;
S. G.; Zhou, S. Q.; Zhu, D. B. Supramolecular Science 1998, 5, 507-510.
Shinkai, S. Tetrahedron Lett. 1990, 31, 7169-7172.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003 3003

A R T I C L E S
Zyryanov et al.
In the NO2 entrapment experiments, stream of the gas was
passed through Pasteur pipets, loaded with silica gel 15 (Figure
1
0). In one pipet, dry silica gel 15 was loaded, and the other
contained 15 preliminary wetted with CHCl3. Both silica gels
+
instantly turned dark purple, indicating the NO complexation.
The color of the wetted material appeared to be deeper and it
stayed for hours. The dry material bleached within minutes. The
FTIR spectrum, recorded in KBr disks, gave weak but reproduc-
-
1
ible stretch at ν ≈ 1920 cm , indicating the presence arene-
+
NO complexes. No coloration was observed for the pipet
loaded with the starting, 3-aminopropylated silica gel. This once
again emphasizes the role of calixarene cavities in the described
processes.
Although requiring further synthetic optimization, silica gel
1
5 may still be used for NO2 detection and even for purification
Figure 11. N-Nitrosation of secondary amides 16a-c with complex 8;
formation of N-nitrosoamides 17a-c. Two probable prereactive complexes
are depicted.
of other nitrogen oxides, especially NO.
Nitrosating Reagents. Described in this paper, processes
involve chemical fixation of nitrogen dioxide (NO2)sits conver-
sion to encapsulated nitrosonium (NO ) complexes, and sub-
sequent NO transfer to the substrate. We noticed, that primary
and secondary amides also reacted with 7 and 8, which implies
that these complexes may act as nitrosating reagents.
It is known, that reactions between NO+ generating agents
+
rate limiting formation of the nitroso intermediates, most
probably, should take place within the calixarene cavity, prior
+
+
to the NO dissociation. Once formed, these sterically bulky
species leave the interior, and undergo further transformations
in bulk solution.
These transformations provide with an additional structural
(e.g., NOCl, N2O3, NO2/N2O4, nitrosonium salts, etc.) and
+
evidense for the discovered calixarene-NO complexes. More
amides and short peptides proceed via N-nitrosation and yield
biologically important nitroso-derivatives.30 Nitrosation of pep-
tides may be used in analytical protocols of protein sequencing.
More importantly however, these reactions have a biological
relevance, because NOX are widely spread atmospheric pollut-
ants and frequently interact with biological tissues and fluids.
The corresponding reaction mechanisms typically incorporate
an electrophilic attack of NO on a nucleophilic oxygen or
nitrogen of the substrate.32
important however, they open new perspectives to use calix-
arenes as supramolecular/encapsulated nitrosating reagents.33
Here, we refer to encapsulated reagents as to highly reactive
species, reversibly entrapped within the host cavity, which can
be released to the reaction mixture under subtle control.34 The
cavity offers protection from the bulk environment and thus
controls the reaction rates. Reactions with encapsulated reagents
may occur either within the cavity interior, or outside, upon
release. As far as delicate, noncovalent forces holding the
molecule-within-molecule complex together are concerned,
temperature, solvent polarity and the substrate-caVity size-shape
fit are the critical factors responsible for the reagent release and
for the reaction to occur. Described here, complexes may serve
as such unique encapsulated reagents for nitrosation. Supramo-
lecular effects in these processes must be much more pro-
3
1
+
Preparatively, 1,3-alternate based nitrosonium complex 8 was
mixed with AlkC(O)NHMe 16a-c (Alk ) n-Pr, n-Hex, n-Hept)
in dry CHCl3 and stirred at room temperature for several hours
(
(
Figure 11). The corresponding N-nitrosoamides AlkC(O)N-
NO)Me (17a-c) were formed in 30-40% yield. Under the
same conditions, the cone calixarene complex 7 reacts very slow,
and only traces of the N-nitrosoamide products were detected
by H NMR spectroscopy. Likewise with water, t-Bu groups at
the upper rim of 7, probably, impose steric hindrances and
4
c
nounced in deeper calixarenes, where the cavities could
accommodate the reaction intermediates. We are currently
preparing such structures and will report on the results in the
future.
1
+
protect the encapsulated NO species from the substrate. The
(
30) (a) Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk,
A. J. Chem. ReV. 2002, 102, 1091-1134. (b) Garcia, J.; Gonzalez, J.;
Segura, R.; Vilarrasa, J. Tetrahedron 1984, 40, 3121-3127 and literature
therein.
Summary and Outlook
A novel NO2 sensing and fixation process is now available,
which employs simple calix[4]arenes. Calixarenes conveniently
transmit the information about NO2 binding via visible light
signals. The described charge-transfer interactions are unique
for NO2 and would guaranty its detection in the presence of
such gases as H2O, O2, HCl, SOX, NH3, and even NO. In
principle, the resulting complexes can be used as vehicles for
nitrosonium transfer and encapsulated nitrosating reagents.
(31) (a) Hood, D. B.; Gettins, P.; Johnson, D. A. Arch. Biochem. Biophys. 1991,
3
04, 17-26. (b) Espey, M. G.; Miranda, K. M.; Thomas, D. D.; Wink, D.
A. J. Biol. Chem. 2001, 276, 30 085-30 091. (c) Itoh, T.; Nagata, K.;
Matsuya, Y.; Miyazaki, M.; Ohsawa, A. Tetrahedron Lett. 1997, 38, 5017-
5
020.
(32) (a) Darbeau, R. W.; Pease, R. S.; Perez, E. V. J. Org. Chem. 2002, 67,
2
942-2947. (b) White, E. H. J. Am. Chem. Soc. 1955, 77, 6008-6010.
N-Nitrosation of amides may occur via two pathways. The first mechanism
includes a direct attack by the lone pair of electrons of the amide nitrogen
on the nitrosating agent. Subsequent deprotonation of the resulting
ammonium ion yields the corresponding N-nitrosoamide. This mechanism
is somewhat questionable, because the nonbonding pair of electrons on
the amide nitrogen is delocalized over the N-C-O system. In addition,
the N-protonated nitrosoamide intermediate is a high-energy species because
the positive charge on the nitrogen is adjacent to both a carbonyl and a
nitrosyl group, possessing significant positive dipoles. The more likely
mechanism involves attack by the carbonyl oxygen on the nitrosating agent
to generate the O-nitroso species. Rapid deprotonation, rotation around the
C-O bond and inversion through the nitrogen derives the intermediate, in
which both the nitrogen lone pair and the NO group are properly oriented
for the isomerization to the N-nitrosoamide.
2 2 4
(33) NO /N O is known to react with 18-crown-6 with the formation of the
+
crown-NO complex. This was used in N-nitrosation of amines, see:
Zolfigol, M. A.; Zebarjadian, M. H.; Chehardoli, G.; Keypour, H.;
Salehzadeh, S.; Shamsipur, M. J. Org. Chem. 2001, 66, 3619-3620.
(34) For rare examples of encapsulated reagents, see: (a) Chen, J.; K o¨ rner, S.;
Craig, S. L.; Rudkevich, D. M.; Rebek, J., Jr. Nature 2002, 415, 385-386
(encapsulated DCC). (b) K o¨ rner, S. K.; Tucci, F. C.; Rudkevich, D. M.;
Heinz, T.; Rebek, J., Jr. Chem. Eur. J. 2000, 6, 187-195 (encapsulated
benzoyl peroxide).
3004 J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003

Sensing and Fixation of NO
2
/N
2
O
4
A R T I C L E S
These findings open wider possibilities toward more sophisti-
cated NO2/NOX sensing and storing materials. We are currently
exploring all these directions.
g, 0.83 mmol) in freshly distilled over Na and oxygen-free THF (150
mL) n-BuLi (30 mL of 2M solution in pentane, 60 mmol) was added
at -78 °C, and the mixture was stirred at this temperature for 75 min.
Trimethyl borate (14 mL, 145 mmol) was then added at -78 °C, and
the mixture was allowed to warm to room temperature. After 5 h, the
Experimental Section
reaction mixture was cooled again to -78 °C, and H
2 2
O (15 mL of
General. Melting points were determined on a Mel-Temp apparatus
3
0% aq solution) and NaOH (35 mL of 3N aq solution) was added.
(
1
Laboratory Devices, Inc.) and a Buchi apparatus and are uncorrected.
The resulting solution was stirred overnight at room temperature, after
which the precipitate was filtered off. The mother liquor was cooled
13
H and C NMR spectra were recorded in CDCl at 295 ( 1 °C, unless
3
stated otherwise, on JEOL Eclipse 500 MHz spectrometer. Chemical
shifts were measured relative to residual nondeuterated solvent
resonances. FTIR spectra were recorded on a Bruker Vector 22 FTIR
spectrometer. UV-vis spectra were measured on a JASCO V-530
spectrophotometer. Matrix-assisted laser desorption/ionization mass
spectrometry (MALDI-TOF) was performed on a Bruker BiFLEX I
linear time-of-flight mass spectrometer operated in delayed extraction
mode. Elemental analysis was performed on a Perkin-Elmer 2400 CHN
analyzer. For column chromatography, Silica Gel 60 Å (Sorbent
Technologies, Inc.; 200-425 mesh) was used. All experiments with
moisture- or air-sensitive compounds were run in freshly distilled,
anhydrous solvents under a dried nitrogen atmosphere. Molecular
2 3
to 0 °C and treated with NaS O (25 g), after which the mixture was
filtered and the filtrate was concentrated in vacuo. The residue was
treated with 5% aq HCl (100 mL), and the colorless precipitate of 4
was filtered off and washed with MeOH (50 mL). Yield 0.274 g (40%).
1
Mp 230 °C; H NMR (DMSO-d
6
): δ 8.39 (bs, 4 H), 6.34 (s, 8 H),
3
.50 (s, 8 H), 3.02 (t, J ) 7.5 Hz, 8 H), 1.3-1.25 (m, 8 H), 1.25-1.1
(
m, 16 H), 1.1-1.0 (m, 8 H), 0.87 (t, J ) 7 Hz, 12 H); MALDI-TOF
+
MS, m/z 847 ([M+Na ], Calcd for C52
72 8
H O 847).
5
,11,17,23,25,26,27,28-Octa(n-hexyloxy)calix[4]arene-1,3-alter-
nate (5). To a suspension of 4 (0.3 g, 0.36 mmol) and NaH (0.15 g of
0% (wt.) suspension in mineral oil, 3.6 mmol) in freshly distilled DMF
50 mL) n-hexylbromide (0.46 mL, 3.2 mmol) was added, and the
6
(
1
7
modeling was performed using MacroModel 7.1.
Parent tetrahydroxycalix[4]arenes were prepared according to the
reaction mixture was stirred at 70 °C under nitrogen for 24 h. The
precipitate was filtered off, and the mother liquor was treated with a
3
5
published procedures. NO
concentrated HNO or sodium nitrate and concentrated H
NO has an irritating odor and is Very toxic.
5,26,27,28-Tetra (n-hexyloxy)calix[4]arene-1,3-alternate (2). To
2
/N
2
O
4
was generated from copper and
mixture of crushed ice (50 g), water (50 mL) and CH
The organic layer was separated, washed with water (2 × 100 mL),
dried over MgSO and evaporated. The residue was recrystallized from
MeOH-CHCl , 10:1 to yield calixarene 5 (0.35 g, 85%). Mp 111 °C,
2 2
Cl (100 mL).
3
2
SO . Caution:
4
2
4
2
3
3
5b
a suspension of 25,27,26,28-tetrahydroxycalix[4]arene (4.24 g, 0.01
mol) and K CO (4.2 g, 0.03 mol) in MeCN (200 mL) n-hexylbromide
4.2 mL, 0.03 mol) was added, and the reaction mixture was refluxed
under nitrogen for 48 h. The precipitate was filtered off, and the solution
was evaporated to dryness. The residue was redissolved in CH Cl (200
mL), and the solution was washed with water (3 × 150 mL) and dried
over MgSO . After evaporation, the solid residue was treated with
MeOH (200 mL) to yield pure 25,27-bis(n-hehyloxy)-26,28-hydroxycalix-
1
H NMR: δ 6.55 (s, 8 H), 3.83 (t, J ) 7 Hz, 8 H), 3.62 (s, 8 H), 3.35
t, J ) 7 Hz, 8 H), 1.7 (m, 16 H), 1.4-1.2 (m, 48 H), 0.89 (t, J ) 7
2
3
(
(
13
Hz, 24 H); C NMR: δ 153.6, 150.7, 134.4, 115.2, 71.6, 68.1, 37.8,
3
2.3, 31.8, 29.8, 26.0, 25.9, 22.9, 22.7, 14.3, 14.1; MALDI-TOF MS,
2
2
+
m/z 1182 ([M+Na ], Calcd for C76
120 8
H O 1183).
Tetrakis(O-n-hexyloxy)cyclophane (6). NaH (0.11 g of 60%
suspension in mineral oil, 2.7 mmol) was added to the solution of
Pappalardo’s cyclophane1 (0.2 g, 0.34 mmol) in freshly distilled DMF
4
5,16
1
[
4]arene as a white solid (5.0 g, 84%). H NMR: δ 8.23 (bs, 2 H),
(20 mL), and the mixture was stirred under nitrogen for 30 min.
7.06 (d, J ) 8 Hz, 4 H), 6.91 (d, J ) 8 Hz, 4 H), 6.73 (t, J ) 8 Hz,
2 H), 6.65 (t, J ) 8 Hz, 2 H), 4.32 (d, J ) 13 Hz, 4 H), 4.00 (t, J )
7 Hz, 4 H), 3.37 (d, J ) 13 Hz, 4 H), 2.1-2.0 (m, 4 H), 1.75-1.7 (m,
4 H), 1.45-1.4 (m, 8 H), 0.95 (t, J ) 7 Hz, 6 H). To a suspension of
25,27-bis(n-hehyloxy)-26,28-hydroxycalix[4]arene (5.92 g, 0.01 mol)
n-Hexylbromide (0.3 mL, 2.04 mmol) was then added, and the reaction
mixture was stirred at 70 °C for 3 d. The precipitate was collected and
dissolved in CH
20 mL), dried over MgSO
recrystallized from MeOH-CHCl
2 2
Cl (20 mL). The solution was washed with water (3
×
4
and evaporated. The residue was
to afford 6 as a white powder. Yield
3
2 3
and Cs CO (50 g, 0.15 mol) in MeCN (300 mL) n-hexylbromide (5.74
mL, 0.04 mol) was added, and the reaction mixture was refluxed under
nitrogen for 48 h. After cooling, the precipitate was filtered off and
1
0.157 g (50%); H NMR: δ 3.89 (s, 8 H), 3.58 (t, J ) 7 Hz, 8 H),
.30 (s, 24 H), 1.8-1.7 (m, 8 H), 1.6-1.5 (m, 16 H), 1.4-1.35 (m, 8
2
13
H), 1.07 (s, 12 H), 0.91 (t, J ) 7 Hz, 12 H); C NMR: d 153.9, 138.4,
31.4, 126.7, 73.2, 32.8, 32.0, 30.4, 26.0, 22.8, 17.7, 14.2, 13.7. Anal.
Calcd for C64 : C 82.70; H 10.41. Found: C, 82.37; H, 10.25.
Preparation of Calix[4]arene-Nitrosonium Complexes. Procedure
. Stock solutions of NO were freshly prepared upon bubbling through
CHCl ; the gas concentration was determined gravimetrically. In a
typical procedure, solution of calixarene 1 (1 eq) in dry, freshly distilled
CHCl was mixed with the stock solution of NO
(∼3 eq) in CHCl
and SnCl (1.5 eq) at room temperature. After 1 h, complex 7 was
precipitated upon addition of hexane, filtered off, washed with hexane
treated with a mixture of water (100 mL) and CH
organic layer was separated, washed with water (2 × 100 mL), dried
over MgSO , and evaporated. The residue was recrystallized from
MeOH-CHCl
NMR: δ 6.92 (d, J ) 7.5 Hz, 8 H), 6.68 (t, J ) 7.5 Hz, 4 H), 3.62 (s,
2 2
Cl (100 mL). The
1
96 4
H O
4
1
3
, 10:1 to give pure 2 (3.50 g, 46%). Mp 119 °C; H
1
2
3
8
H), 3.54 (t, J ) 7.5 Hz, 8 H), 1.89 (m, 8 H), 1.35 (m, 24 H), 0.85 (t,
+
J ) 7 Hz, 12 H); MALDI-TOF MS, m/z 783.9 ([M+Na ], calcd for
3
2
3
C
52
H
72
O
4
783.9). Anal. Calcd for C52
Found: C, 81.61; H, 9.58.
,11,17,23-Tetrabromo-25,26,27,28-tetrakis(n-hexyloxy)calix[4]-
72 4
H O : C, 82.06; H, 9.53.
4
5
1
(
2×), and dried in vacuo. H NMR: δ 6.99 (s, 8 H), 4.39 (d, J ) 13
arene-1,3-alternate (3). N-Bromosuccinimide (3.0 g, 0.017 mol) was
added to a suspension of calixarene 2 (2.0 g, 2.6 mmol) in acetone
Hz, 4 H), 4.02 (t, J ) 7.5 Hz, 8 H), 3.44 (d, J ) 13 Hz, 4 H), 2.0-1.9
(
(
(
m, 8 H), 1.5-1.3 (m, 24 H), 0.93 (t, J ) 7 Hz, 12 H); UV-vis
(500 mL), and the mixture was stirred at room temperature for 48 h
+
CHCl
3
): λmax 563; FTIR (CDCl
3
): ν 1923 (NO ), 1461, 1298, 1047
exposed to the laboratory light. The formed solid was filtered off,
-
+
-
3
NO
3
); Anal. Calcd for C68
H O
104 4
‚NO NO
4
‚1.8SnCl : C, 52.81; N,
washed with acetone (2 × 100 mL) and used in the next step without
1
1.81; H, 6.78. Found: C, 52.60; N, 1.67; H, 7.55. Complex 8 was
obtained analogously: 1H NMR: δ 7.17 (t, J ) 7.5 Hz, 4 H), 7.08 (d,
J ) 7.5 Hz, 8 H), 3.87 (t, J ) 7.5 Hz, 8 H), 3.60 (s, 8 H), 1.9-1.8 (m,
further purification. Yield 1.5 g (53%). H NMR: δ 7.12 (s, 8 H),
3
2
.56 (s, 8 H), 3.52 (t, J ) 7.5 Hz, 8 H), 1.6-1.4 (m, 8 H), 1.4-1.3 (m,
4 H), 0.93 (t, J ) 7 Hz, 12 H).
8
H), 1.4-1.3 (m, 24 H), 0.93 (t, J ) 7 Hz, 12 H); UV-vis (CHCl
3
-
):
);
5,11,17,23-Tetrahydroxy-25,26,27,28-tetrakis(n-hexyloxy)calix[4]-
+
λ
max 524 nm; FTIR (CDCl
‚NO NO
.83. Found: C, 50.23; N, 1.82; H, 5.99. Complex 9 cannot be prepared
using this protocol; only dealkylation/oxidation products were detected.
3
): ν 1955 (NO ), 1438, 1246, 1091 (NO
3
arene-1,3-alternate (4). To a solution of tetrabromo derivative 3 (0.9
+
-
Anal. Calcd for C52
H
72
O
4
3
4
‚1.5SnCl : C, 50.21; N, 2.25; H,
5
(
35) (a) Gutsche, C. D.; Iqbal, M. Org. Synth. 1990, 68, 234-237. (b) Gutsche,
C. D.; Levine, J. A.; Sujeeth, P. K. J. Org. Chem. 1985, 50, 5802-5806.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003 3005

A R T I C L E S
Zyryanov et al.
For spectroscopic characterization, complex 9 was generated in the
exchange experiment between nitrosonium complex 8 and free calix-
arene 5, as depicted in Figure 7.
6.92 (s, 2 H), 6.62 (d, J ) 2.5 Hz, 2 H), 6.56 (d, J ) 2.5 Hz, 2 H),
5.28 (s, 2 H), 4.56 (d, J ) 13 Hz, 2 H), 4.41 (d, J ) 13 Hz, 2 H), 3.89
(t, J ) 8 Hz, 2 H), 3.79 (t, J ) 8 Hz, 2 H), 3.75 (t, J ) 8 Hz, 2 H),
3.18 (d, J ) 13 Hz, 2 H), 3.12 (d, J ) 13 Hz, 2 H), 2.82 (s, 4 H),
2.15-2.1 (m, 2 H), 1.95-1.85 (m, 4 H), 1.45-1.35 (m, 18 H), 1.20,
1.19 (2 × s, 18 H), 0.93 (s, 18 H), 0.9-0.8 (m, 9 H). Ester 13 appeared
to be relatively unstable, and attempts to obtain the MALDI-TOF and/
or CHN analytical data failed. The structure of 13 was confirmed
through its transformation to calixarene amide 14.
Procedure 2. Calix[4]arene-nitrosonium complexes were obtained
+
-
upon mixing 1,2 or 5 with an excess NO SbF
6
in dry CHCl
3
.
+
-
+
-
Complexes 1‚NO SbF
6
and 2‚NO SbF
6
formed within 20 h. The
1
UV-vis, FTIR and H NMR spectra are identical with the respective
+
-
6
formed immediately upon
complexes 7 and 8. Complex 5‚NO SbF
1
mixing: H NMR: δ 6.54 (s, 8 H), 3.93 (t, J ) 7.5 Hz, 8 H), 3.76 (t,
J ) 7.5 Hz, 8 H), 3.44 (s, 8 H), 1.8-1.75 (m, 8 H), 1.9-1.8 (m, 8 H),
25-[(n-Octylcarbamoylmethoxy)-26,27,28-trihexyloxy-p-tert-butyl-
calix[4]arene (14). To the solution of ester 13 (75 mg, 70 µmol) in
THF (10 mL), n-octylamine (18 mg, 0.14 mmol) and Et N (70 mg, 0.7
3
1
.5-1.2 (m, 48 H), 0.95 (t, J ) 7 Hz, 12 H), 0.89 (t, J ) 7.5 Hz, 12
+
H); UV-vis (CHCl
3
): λmax 600; FTIR (CDCl
3
): ν (NO ) 1876.
mmol) were added, and the reaction mixture was stirred at room
temperature for 12 h. The precipitate was filtered off, and the solution
2
5-Hydroxy-26,27,28-trihexyloxy-p-tert-butylcalix[4]arene (10). A
35a
mixture of 25,26,27,28-tetrahydroxy-p-tert-butylcalix[4]arene (4.0 g,
.2 mmol), freshly distilled anhydrous DMF (80 mL), Ba(OH) ‚8H
6.8 g, 21.6 mmol), and BaO (6.36 g, 41.5 mmol) was stirred at room
temperature for 15 min. n-Hexylbromide (21 mL, 184 mmol) was
added, and the suspension was stirred at room temperature for another
2 h. The mixture was diluted with water (100 mL), and the product
was extraced with CH Cl
(3 × 100 mL). The organic layer was washed
with water (2 × 100 mL), dried over Na SO and evaporated under
reduced pressure. The residue was recrystallized from MeOH to give
pure 10 as a white solid. Yield 69%; mp 134-136 °C; H NMR: δ
.11 (s, 2 H), 7.03(s, 2 H), 6.51 (d, J ) 2.3 Hz, 2 H), 6.49 (d, J ) 2.3
Hz, 2 H), 5.72 (s, 1 H), 4.36 (d, J ) 13 Hz, 2 H), 4.32 (d, J ) 13 Hz,
H), 3.89 (t, J ) 8 Hz, 2 H), 3.78 (t, J ) 8 Hz, 4 H), 3.22 (d, J ) 13
was evaporated. The residue was redissolved in CH
washed with 2 M aq HCl (2 × 5 mL) and water (5 mL), and dried
over Na SO . The organic layer was then evaporated and the residue
was recrystallized from CH CN to afford 14 as a white solid. Yield
5%; H NMR: δ 8.43 (t, J ) 6 Hz, 1 H), 6.99 (s, 2 H), 6.97 (s, 2 H),
2 2
Cl (20 mL),
6
(
2
2
O
2
4
3
1
6
6
3
1
.57 (s, 4 H), 4.71 (s, 2 H), 4.38, 4.35 (2 × d, J ) 13 Hz, 4 H), 3.9-
2
2
.7 (2 × m, 6 H), 3.42 (dt, J ) 6 Hz, J ) 7 Hz, 2 H), 3.23 (d, J ) 13
2
4
Hz, 2 H), 3.14 (d, J ) 13 Hz, 2 H), 2.0-1.8 (3 × m, 8 H), 1.5-1.3
1
(m, 30 H), 1.25 (s, 9 H), 1.23 (s, 9 H), 0.93 (s, 18 H), 0.95-0.85 (m,
1
2 H). FTIR (KBr): ν 3346 (NH), 2964, 1680 (CdO), 1537, 1473.
Anal. Calcd for C72 ‚0.5CH CN: C, 80.35; H, 10.39; N, 1.93.
Found: C 80.02; H 10.09; N, 1.91. Compound 14 was also indepen-
dently synthesized from the acid chloride of 12 (prepared with SOCl ),
n-octylamine and Et N in CHCl
7
H111NO
5
3
2
Hz, 2 H), 3.16 (d, J ) 13 Hz, 2 H), 2.3-2.2 (m, 2 H), 2.0-1.8 (m, 4
H), 1.4-1.3 (m, 18 H), 1.32 (s, 9 H), 1.31 (s, 9 H), 0.92 (t, J ) 7 Hz,
2
3
3
.
Calix[4]arene Functionalized Silica Gel (15). A suspension of ester
3 (100 mg, 95 µmol), 3- aminopropyl-functionalized silica gel
3
H), 0.90 (m, 6 H), 0.81 (s, 18 H).
5-[(Ethoxycarbonyl)methoxy]-26,27,28-trihexyloxy-p-tert-butyl-
calix[4]arene (11). A mixture of calix[4]arene 10 (5.0 g, 5.6 mmol)
and Na CO (10.0 g, 94 mmol) in CH CN (150 mL) was refluxed for
5 min, after which ethyl bromoacetate (10 mL, 90 mmol) was added,
and the reflux continued for 12 h. The inorganic salts were filtered,
and the solvent was evaporated. The residue was dissolved in CH Cl
1
2
(
(
Aldrich) (226 mg, 155 µmol) and Et
50 mL) was stirred at room temperature for 12 h. The solid was filtered
Cl , MeOH, water, MeCN, and THF, and then
dried under reduced pressure for 3 days. Afford white powder. FTIR
KBr): ν 3383, 2960, 1650, 1556, 1477. Anal. Found for 3-aminopropyl
silica gel (0.687 meq/g, C Si): C, 7.42; H, 1.80; N, 1.91. Anal.
Calcd for silica gel 15 (17% loading, 0.117 meq/g, C73 Si): C,
15.43; H, 2.68; N, 1.82. Found: C 15.34; H 2.97; N, 1.70.
3
N (92.9 mg, 0.92 mmol) in THF
2
3
3
off, washed with CH
2
2
1
(
2
2
9 3
H23NO
(
100 mL) and washed with water (3 × 50 mL). The solvent was
H115NO
8
evaporated, and the product was recrystallized from MeOH. Yield 89%;
1
mp 121-123 °C; H NMR: δ 6.91(s, 2 H), 6.90 (s, 2 H), 6.63 (d, J )
Hz, 2 H), 6.61 (d, J ) 2 Hz, 2 H), 4.86 (s, 2 H), 4.66 (d, J ) 12.5
Hz, 2 H), 4.38 (d, J ) 12.5 Hz, 2 H), 4.18 (q, J ) 7 Hz, 2 H), 3.83 (t,
J ) 8 Hz, 4 H), 3.75 (t, J ) 8 Hz, 2 H), 3.15 (d, J ) 12.5 Hz, 2 H),
.10 (d, J ) 12.5 Hz, 2 H), 2.2-2.1 (m, 2 H), 2.0-1.9 (m, 4 H), 1.4-
.3 (m, 18 H), 1.27 (t, J ) 7 Hz, 3 H), 1.18 (s, 9 H), 1.17 (s, 9 H),
.96 (s, 18 H), 0.9-0.8 (m, 9 H).
N-Nitrosation of Amides by Calix[4]arene-Nitrosonium Com-
2
plexes; General Procedure. Caution: N-Nitrosoamides are Potential
36
Carcinogens and Should be Treated with Extreme Care. Complex
(1 eq) was added to the solution of amide AlkC(O)NHMe 16a-c
2-3 eq) in freshly distilled CHCl , and the reaction mixture was stirred
8
3
1
0
(
3
at room temperature for 5 h. The solvent was evaporated, and the residue
was analyzed by 1H NMR spectroscopy and further separated by
preparative TLC. The spectral data for the obtained N-nitroso com-
pounds AlkC(O)N(NO)Me 17a-c were identical with those indepen-
2
5-(Carbomethoxy)-26,27,28-trihexyloxy-p-tert-butylcalix[4]-
arene (12). A mixture of 11 (2.0 g 2 mmol), THF-H O, 5:1 (100 mL)
and KOH (1.0 g, 17.8 mmol) was refluxed for 12 h. The pH was
adjusted to 4 with aq 2 M HCl. The product was extracted with CH
Cl SO and
(2 × 50 mL), and the organic layer was dried over Na
evaporated to give 12 as a white solid. Yield > 95%; mp 136-137
2
+
-
6
, and
dently obtained from AlkC(O)NHMe and NO
also previously published.37 CH
(CH C(O)NHCH
δ 6.13 (bs, 1 H, NH), 2.73 (d, J ) 5 Hz, 3 H, N-CH
7.5 Hz, 2 H, C(O)CH ), 1.6-1.5 (m, 2 H, CH ), 1.3-1.1 (m, 8 H,
CH ), 0.83 (t, J ) 7.5 Hz, 3 H, CH ). CH (CH C(O)N(NO)CH
17b): 1H NMR: δ 3.13 (t, J ) 8 Hz, 2 H, C(O)CH
), 3.03 (s, 3 H,
N(NO)-CH ), 1.8-1.7 (m, 2 H, CH ), 1.4-1.2 (m, 8 H, CH ), 0.84 (t,
J ) 7.5 Hz, 3 H, CH ).
2
/N
2
O
4
or NO SbF
(16b): 1H NMR:
), 2.13 (t, J )
2
-
3
2
)
6
3
2
2
4
3
1
2
2
°
C; H NMR: δ 11.28 (s, 1 H), 7.16 (s, 2 H), 7.14 (s, 2 H), 6.59 (d,
J ) 2.5 Hz, 2 H), 6.49 (d, J ) 2.5 Hz, 2 H), 4.67 (s, 2 H), 4.45 (d, J
12 Hz, 2 H), 4.23 (d, J ) 12 Hz, 2 H), 4.08 (t, J ) 7 Hz, 2 H),
.8-3.7 (m, 4H), 3.24 (d, J ) 12 Hz, 2 H), 3.16 (d, J ) 12 Hz, 2 H),
.95-1.8 (m, 6 H), 1.45-1.2 (m, 18 H), 0.90 (t, J ) 7 Hz, 9 H), 0.83
2
3
3
2
)
6
3
(
2
)
3
1
(
3
2
2
3
+
s, 18 H); MALDI-TOF MS, m/z 959.2 (M , Calcd for C64
Anal. Calcd for C64H O : C 80.12; H 9.88. Found: C, 80.27; H, 9.88.
94 6
H O
94 6
960.4).
Acknowledgment. Financial support is acknowledged from
the University of Texas at Arlington and, in part, from the
donors of the Petroleum Research Fund, administered by the
N-Succinimide Ester of 25-(Carbomethoxy)-26,27,28-trihexyloxy-
p-tert-butylcalix[4]arene (13). A suspension of 12 (1.0 g, 1.05 mmol),
N-hydroxy succinimide (1.0 g, 8.70 mmol), DCC (210 mg 1.05 mmol)
and DMAP (40 mg, 0.32 mmol) in THF (50 mL) was stirred at room
temperature for 12 h under nitrogen. After filtration, the solvent was
evaporated, and the residue was redissolved in hexane (50 mL) and
filtered again. The hexane solution was evaporated and the residue was
(
36) (a) Mirvish, S. S. Cancer Lett. 1995, 93, 17-48. (b) Hoffman, D.; Hoffman,
I.; El-Bayoumy, K. Chem. Res. Toxicol. 2001, 14, 767-790. (c) Pfeiffer,
S.; Mayer, B.; Hemmens, B. Angew. Chem., Int. Ed. Engl. 1999, 38, 1714-
1
731. (d) Tamir, S.; Burney, S.; Tannenbaum, S. R. Chem. Res. Toxicol.
1996, 9, 821-827. (e) Lewis, R. S.; Tannenbaum, S. R.; Deen, W. M. J.
Am. Chem. Soc. 1995, 117, 3933-3939. (f) Kirsch, M.; Korth, H.-G.;
Sustmann, R.; de Groot, H. Chem. Res. Toxicol. 2000, 13, 451-461.
37) Garcia, J.; Gonzalez, J.; Segura, R.; Urpi, F.; Vilarrasa, J. J. Org. Chem.
1984, 49, 3322-3327.
purified by column chromatography (CH
as a white solid. Yield 83%; mp 75-78 °C; H NMR: δ 6.95 (s, 2 H),
2 2
Cl -hexane, 1:1) to afford 13
(
1
3
006 J. AM. CHEM. SOC. VOL. 125, NO. 10, 2003
9

Sensing and Fixation of NO
2
/N
2
O
4
A R T I C L E S
American Chemical Society. We are grateful to Prof. Gary R.
Kinsel and Jiang Zhang for the expert MALDI-TOF analysis
and also thank Stephen P. Stampp and Heng Xu for experimental
advice. Prof. Wim Verboom is acknowledged for advice on the
calix[4]arene preparation. We also thank Profs. V. G. Shubin
and M. Kirsch for providing reprints of their valuable work.
This paper is dedicated to Prof. C. David Gutsche on the
occasion of his retirement.
JA029166L
J. AM. CHEM. SOC.
9
VOL. 125, NO. 10, 2003 3007