Polymer-supported calix[4]arenes for sensing and conversion of NO 2/N2O4

Article abstract of DOI:10.1016/j.tet.2004.08.063

The use of simple calix[4]arenes 1a,b for NO₂/N ₂O₄ sensing and conversion is demonstrated, both in solution and in the solid state. Upon reacting with these gases, compounds 1a,b encapsulate reactive NO⁺ cation

Full text of DOI:10.1016/j.tet.2004.08.063

Tetrahedron 60 (2004) 11219–11225
Polymer-supported calix[4]arenes for sensing
and conversion of NO2/N2O4
*
Yanlong Kang and Dmitry M. Rudkevich
Department of Chemistry and Biochemistry, University of Texas at Arlington, PO Box 19065, Arlington, TX 76019-0065, USA
Received 16 February 2004; revised 30 June 2004; accepted 20 August 2004
Available online 16 September 2004
Abstract—The use of simple calix[4]arenes 1a,b for NO2/N2O4 sensing and conversion is demonstrated, both in solution and in the solid
state. Upon reacting with these gases, compounds 1a,b encapsulate reactive NOC cations within their cavities with the formation of deeply
colored (lmaxw570 nm) charge-transfer complexes 2a,b. Further functionalization of the calix[4]arene platform is reported for attachment to
solid supports. Polymer-supported calixarene material 3 was prepared, which reversibly traps NO2/N2O4 with the formation of nitrosonium
storing polymer 4. Material 4 was effectively used for nitrosation of amides.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
We recently reported that simple calix[4]arenes such as 1a,b
reversibly interact with NO2/N2O4 and entrap reactive
nitrosonium cation (NOC) within their cavities (Fig. 1).6
NOC is generated from N2O4 upon its disproportionation.
Deeply colored charge-transfer complexes 2a,b formed. In
this paper, we further explore our findings. We submit the
solution studies of the NO2/N2O4 entrapment by calixarenes
for potential sensing applications, and also report on the
synthesis of functionalized calix[4]arenes for attachment to
polymeric supports. We further demonstrate the use of
calixarene-based materials 3 (Fig. 1) for detection, entrap-
ment and release of NOC. Finally, we show that polymeric
nitrosating reagent 4 can be effectively used in syntheses of
N-nitrosamides.
NOX gases are the sum of NO, NO2, N2O3 (NO$NO2), N2O4
(NO2$NO2), and N2O5.1 These are atmospheric pollutants,
originated in large quantities from fuel combustion and
large-scale industrial processes. NOX are involved in the
formation of ground-level ozone.
They form toxic chemicals and acid rains, and participate in
global warming. NOX are also involved in various
nitrosation processes with biomolecules, causing cancers
and other diseases.2,3 According to the US Environmental
Protection Agency,1 national emissions of NOX have
increased over the past 30 years by w10%. Extensive
NOX circulation in the atmosphere, industry, and agriculture
requires their systematic monitoring and also necessitates
the development of improved methods for their conversion
and utilization. We specifically target nitrogen dioxide
(NO2). Current NO2 sensors are mostly electrochemical and
monitor changes of potential upon exposure metal surfaces
to the gas.4 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.5 At the same time, the
reversibility is difficult to achieve.
2. Results and discussion
2.1. Design and synthesis
NO2 is a paramagnetic gas of a brown-orange color. It
reversibly dimerizes into colorless dinitrogen tetroxide
(N2O4).7 The position of the equilibrium between NO2
and N2O4 varies with temperature. At the same time, N2O4
may disproportionate to ionic NOCNO3K upon reacting with
aromatic compounds.7,8
Calix[4]arenes are popular building blocks in molecular
recognition. They are widely used in the construction of
various receptors, sensors and molecular containers.9
Calix[4]arenes in a 1,3-alternate conformation (see for
example, 1a,b) are ideally preorganized to complex NOC,
Keywords: Calixarenes; Nitrogen oxides; Polymers; Sensors; Supramole-
cular chemistry.
* Corresponding author. Tel.: C1-817-272-5245; fax: C1-817-272-3808;
e-mail: rudkevich@uta.edu
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.063

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Y. Kang, D. M. Rudkevich / Tetrahedron 60 (2004) 11219–11225
Figure 1. Chemical fixation of NO2/N2O4 by calix[4]arenes; formation of calixarene–nitrosonium complexes.
generated from NO2/N2O4. They possess a cylindrical,
p-electron rich inner tunnel, defined by two cofacial pairs of
phenol rings, which are oriented orthogonal along the cavity
axis (see 2a,b, Fig. 1). According to numerous X-ray
the two-step alkylation of parent calix[4]arene 5 with either
n-propyl or n-hexyl bromide, using successively K2CO3 and
then Cs2CO3 in boiling MeCN.6,11 The synthesis of
terminally functionalized calixarenes starts with mono-
alkylation of 5 with n-propyl bromide using K2CO3 as a
base in boiling MeCN (Scheme 1).
10
˚
studies, this tunnel is w5–6 A in diameter.
For solution studies, 1,3-alternate tetrakis(O-alkyl)calix[4]-
arenes 1a,b were resynthesized. Their preparation includes
The resulting calixarene 612 was further alkylated with allyl
Scheme 1. (a) n-PrBr, K2CO3, MeCN, reflux, 59%; (b) AllBr, K2CO3, MeCN, reflux, 67%; (c) n-PrBr, Cs2CO3, MeCN, reflux, 70%; (d) BH3$THF, THF, then
NaOH, H2O2, 95%; (e) MeOCH2(CH2OCH2CH2)nOMs (10), t-BuOK, THF, w55%.

Y. Kang, D. M. Rudkevich / Tetrahedron 60 (2004) 11219–11225
11221
bromide to afford diametrically substituted product 7
(K2CO3, MeCN, reflux, 67%). The next step includes
formation of calixarene 8, which is a CsC-templated
alkylation of 7 with an excess n-propyl bromide (Cs2CO3,
MeCN, reflux, 70%). This reaction proceeds with the
conformation conversion from a cone to a 1,3-alternate. The
allyl double bond in 8 was hydroxylated under the standard
hydroboration conditions (BH3$THF, THF, then aq NaOH,
H2O2) to afford calixarene 9 in 95% yield. Compound 9 is
the key derivative for preparation of polymer-supported
materials for NO2/N2O4 sensing and fixation. It has the
structural features of typical 1,3-alternates and also
bridge CH2 protons of 1b were recorded as a singlet at
3.73 ppm. In complex 2b, this was seen at 3.60 ppm. The
methylene OCH2 triplet in 1b is situated at 3.38 (JZ
7.5 Hz), while it shifted to 3.77 ppm in complex 2b.
Spectral changes for 2a are analogous. Independent
structural evidence for 2a,b came from the complexation
experiments between calixarenes 1a,b and commercially
available NOCSbF6K salt (CDCl3, 295 K).14 The corre-
sponding complexation induced changes were in agreement
with the data presented above for complex 2a,b (Fig. 2),
once again confirming the disproportionation of N2O4 to
NOCNOK3 by calixarenes. Addition of water destroys the
nitrosonium complexes, quantitatively recovering empty
calixarenes 1a,b.
possesses a terminal hydroxyl group for further
functionalization.
TheUV–visspectraof2a,bshowedbroadcharge-transfer14,15
2.2. Solution studies
band at lmaxw560–580 nm (3Z8!103 MK1 cmK1
)
(Fig. 3). While neither calixarenes 1a,b nor NO2 absorb in
this region, addition of as little as w1 equiv NO2 (w5!
10K5 M in CH2Cl2) to the solution of 1a (6!10K5 M in
CH2Cl2) results in appearance of the charge-transfer band.
Its absorbance grows upon addition of larger quantities of
NO2 and reaches saturation when w10 equiv NO2 (e.g.,
5 equiv N2O4) is added. From the titration experiments,
the apparent Kassoc value of w104 MK1 was estimated.
Accordingly, calixarenes can detect NO2 already at
micromolar concentrations.
When a stream of NO2/N2O4 was passed through the CHCl3
solution of calix[4]arenes 1a,b, deeply colored, purple
nitrosonium complexes 2a,b formed within seconds (O95%
yield, Fig. 1).6,13
The 1H NMR spectra of 2a,b showed new sets of the
calixarene signals, different from 1a,b (Fig. 2). For
example, aromatic CH protons of guest-free 1b were seen
as a singlet at 6.95 ppm. In nitrosonium complex 2b, it was
transformed into a singlet at 7.02 ppm. The methylene
Figure 3. UV–vis spectroscopic titration experiments (CH2Cl2, 295G1 K)
with calix[4]arene 1a and NO2/N2O. [1a]Z6!10K5 M, [NO2]Z0K1.2!
10K3 M; lmaxw565 nm.
Importantly for potential sensing, the calix[4]arene–NO2
interactions (a) are reversible, (b) result in rapid and
dramatic color changes and (c) are unique and specific for
NO2. This should guaranty its detection in the presence of
such gases as H2O, O2, HCl, HBr, SOX, and NH3. Indeed,
calixarenes are chemoselective for NO2, and none of these
vapors/gases undergoes such reactions with calixarenes.
Neat nitric oxide (NO) gas also does not react with
calixarenes. In their excellent work on NO sensing,14
Kochi, Rathore and co-workers showed that calixarenes had
to be oxidized first, to form the corresponding cation-
radicals, prior complexing NO within their interiors.
2.3. Toward polymer-supported calixarenes
For potential application in sensing technology, receptor
molecules must be readily immobilizable on solid supports
or surfaces. Although a wide variety of polymers is now
commercially available, NO2 (and NOX in general) react
with many of them, causing destruction and aging.16 As a
1
Figure 2. Portions of the H NMR spectra (500 MHz, CDCl3, 295G1 K)
of: (A) calix[4]arene 1b; (B) nitrosonium complex 2b prepared from 1b and
NO2/N2O; (C) nitrosonium complex, prepared upon addition of NOCSbF6K
to calixarene 1b. The residual CHCl3 signals are marked ‘†’. Similar
spectra were obtained for calixarene 1a and complex 2a.

11222
Y. Kang, D. M. Rudkevich / Tetrahedron 60 (2004) 11219–11225
free radical NO2 readily attacks double bonds in poly-
butadienes, polyisoprenes and their copolymers, ester
groups in poly(methyl)methacrylate, and also amide frag-
ments in polyamides and polyurethanes. Furthermore,
NOC, generated from various NOX, reacts with alkenes
and other double bond containing structures.17
suspensions in hexanes) and in the solid state. Similar to
monomeric calixarenes 1a,b, the UV–vis spectrum of
mixtures of polymer 3 and excess NO2/N2O4 in CH2Cl2
showed broad charge-transfer band at lmaxw575 nm,
indicating the formation of calix–nitrosonium complex 4.
Starting PEG polymer does not exhibit any UV–vis spectral
changes upon addition of NO2/N2O4.
In these studies, the use of calixarene module 9 in the
preparation of NO2-sensitive and NO2-trapping materials
was demonstrated for polyethylene glycol (PEG) polymers.
Specifically, commercial PEG 50000 monomethyl ether
(w5000 Da molecular weight; Fluka) quantitatively reacted
with MeSO2Cl in CH2Cl2 to give the corresponding
a-methyl-u-mesyl derivative 10,18 which was then coupled
with 9 in THF using t-BuOK as a base to yield polymer 3
(Scheme 1). While the MALDI TOF spectra of 3 appeared
to be rather complex, the presence of a calix[4]arene
fragment was confirmed by the appearance of an intense
n(CHarom) absorption band at w2950 cmK1 in the FTIR
spectrum (KBr disks). By integrating the calixarene
In the NO2 entrapment experiments, stream of the gas was
passed through the Pasteur pipettes, loaded with starting
PEG monomethyl ether and material 3 (Fig. 4). In one
pipette, dry polymer 3 was loaded; the other pipette with 3
was preliminary flashed with hexanes. Both pipettes
containing 3 instantly turned dark purple, indicating the
NOC complexation. The color of the wetted material
appeared to be deeper and it stayed for hours. The dry
material bleached faster. As expected, no coloration was
observed for the pipette loaded with the starting PEG
polymer. This once again emphasizes the role of calixarene
cavities in the described processes and directly points at the
use of polymer 3 for NO2 detection and separation of other
nitrogen oxides, especially NO, from NO2.
1
aromatic signals vs the PEG OMe group in the H NMR
spectrum of 3 in CDCl3, the loading of w55% was
estimated. Such rather modest number may be due to the
steric bulkiness of the calixarene fragment.
2.4. Nitrosation
We previously reported, that calixarene–nitrosonium com-
plexes 2a,b may release NOC and thus act as nitrosating
agents for secondary amides.13 Nitrosamides/amines are of
great biomedical interest as potential NO-releasing drugs.19
We are now exploring calixarene-containing polymer 3 for
synthetic purposes.
Upon exposure to NO2/N2O4, material 3 turns deep purple,
both in apolar solution (chlorinated solvents, or even
Among the advantages of reagents immobilized on
polymeric supports20 are the ease of their separation from
the reaction mixture, their recycling, and the simplification
of handling toxic and odorous chemicals. Particularly useful
are so-called soluble polymers, as they allow to overcome
problems associated with the heterogeneous nature of the
reaction conditions. At the same time, likewise with
insoluble polymers, isolation of these polymers from the
reaction mixture also includes precipitation.
Nitrosonium-storing polymer 4 (Fig. 5) was prepared upon
bubbling NO2/N2O4 through the solution of 3 in CH2Cl2 for
2–3 min, followed by flashing with N2 for 10 min to remove
the remaining NO2/N2O4 gases. Deeply colored material
formed (Fig. 4). When added to equimolar solutions of
Figure 4. NO2 entrapment experiments. The columns were prepared as
follows: (A) loaded with starting PEG monomethyl ether (Fluka);
(B) loaded with dry polymer 3; (C) loaded with 3 and flashed with
hexanes. All three columns were then flashed with NO2 for 30 s.
Figure 5. Nitrosation of amides 11a–c with polymer 4.

Y. Kang, D. M. Rudkevich / Tetrahedron 60 (2004) 11219–11225
11223
amides CH3(CH2)6C(O)NHR 11a–c (RZMe, Et, Pr,
3. Conclusions and outlook
respectively) in CH2Cl2, it reacted quickly (2–3 h) at room
temperature, yielding corresponding N-nitrosamides 12a–c
(Fig. 5). The solution’s color discharged, thus visually indi-
cating the reaction progress. Polymer 3 was subsequently
recovered by precipitating with hexanes and filtered off.
Yields of nitrosamides 12a–c were determined by 1H NMR
spectroscopy, integrating signals of the product vs the
starting compounds. Signals for amides 11a–c decrease, and
characteristic signals for N-nitrosamides 12a–c appear and
grow. For example, a triplet at w3.2 ppm (C(O)CH2) and a
singlet at w3.1 ppm (N(NO)–CH3) were clearly registered
for nitrosoamide 12a; these were identical to those obtained
upon nitrosation of 11a with neat NO2/N2O4 and different
from the starting amide 11a (Fig. 6).
Calix[4]arene derivatives can be effectively used for
chemoselective colorimetric sensing of NO2/N2O4 gases
both in solution and in the solid state. They also convert
NO2/N2O4 into nitrosating reagents for organic synthesis.
Immobilization of calixarenes on solid supports opens even
wider opportunities for practical applications. We are
currently preparing various calixarene-based polymers for
NO2/N2O4 sensing and conversion and also exploring
synthetic capabilities of the calixarene modules. Of
particular interest are chiral calixarenes for stereoselective
nitrosation and also calixarene-based nanotubes for
NO2/N2O4 sensing and fixation. We are also looking at
other NOX gases.
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded in CDCl3 at 295G
1 8C on a JEOL Eclipse 500 MHz spectrometer. Chemical
shifts were measured relative to residual non-deuterated
solvent resonances. FTIR spectra were recorded on a
Bruker Vector 22 FTIR spectrometer. UV–vis spectra
were measured on a Varian Cary-50 spectrophotometer.
HRMS MALDI spectra were obtained on an Ion Spec
Ultima FTMS. Elemental analysis was performed on a
Perkin–Elmer 2400 CHN analyzer. All experiments with
moisture- and/or air-sensitive compounds were run under a
dried nitrogen atmosphere. For column chromatography,
˚
silica gel 60 A was used (Sorbent Technologies, Inc.; 200–
425 mesh). Tetrahydroxycalix[4]arene 521 and 1,3-alter-
nates 1a,b6,11 were prepared according to the published
procedures. Amides 11a–c and N-nitrosamides 12a–c were
synthesized as reported earlier.13 NO2/N2O4 was generated
from copper and concd HNO3.
Caution 1: NO2 has an irritating odor and is very toxic!
Caution 2: N-Nitrosoamides are carcinogens3 and should
be treated with extreme care!
4.1.1. 5,11,17,23-Tetrakis(t-butyl)-25,26,27-trihydroxy-
28-(n-propyloxy)calix[4]arene 6. In the modified pro-
cedure, to the solution of t-butyl calix[4]arene 5 (10.0 g,
15.41 mmol) in MeCN (300 mL), K2CO3 (1.07 g,
7.71 mmol) was added. The mixture was refluxed for
15 min, and then n-propyl bromide (14 mL, 154.1 mmol)
was added. The mixture was further refluxed for 24 h, and
the solvent was evaporated under reduced pressure. The
residue was taken up with CH2Cl2 (200 mL), washed with
1 M HCl (2!200 mL) and H2O (200 mL), and dried over
MgSO4. The solvent was evaporated, and the residual solid
was recrystallized from CHCl3/CH3OH to afford product 6
as white crystals (59%). The spectral data are in agreement
with the previously published.12 1H NMR: dZ10.20 (s, 1H),
9.61 (s, 2H), 7.06 (m, 8H), 4.37 (d, JZ12.5 Hz, 2H), 4.27
(d, JZ12.5 Hz, 2H), 4.10 (t, JZ7.5 Hz, 2H), 3.44 (d, JZ
12.5 Hz, 2H), 3.42 (d, JZ12.5 Hz, 2H), 2.18 (m, 2H), 1.24
(t, JZ7.5 Hz, 3H), 1.21 (s, 9H), 1.19 (s, 27H).
Figure 6. Fragments of the 1H NMR spectra (500 MHz, CDCl3, 295G1 K):
(A) N-methylamide 11a; (B) N-methyl-N-nitrosamide 12a obtained from
11a and NO2/N2O4;13 (C) N-methyl-N-nitrosamide 12a obtained from 11a
and polymer 4.
After at least five runs, the averaged yields of 12 varied
between 40% for 12c to 60% for 12b and 80% for 12a,
indicating the preference for less bulky substrates. At the
same time, polymeric reagent 4 is obviously less size-shape
selective, compared to monomeric species 2, which showed
exclusive selectivity for smaller N-Me derivative 11a.13 In
control experiments, involving starting PEG polymer
and amide 11a, only trace amounts of 12a were detected
(!5%), again emphasizing the role of calixarene cavity in
the described reaction.

11224
Y. Kang, D. M. Rudkevich / Tetrahedron 60 (2004) 11219–11225
1
4.1.2. 5,11,17,23-Tetrakis(t-butyl)-25-allyloxy-26,28-
dihydroxy-27-(n-propyloxy)calix[4]-arene 7. To the solu-
tion of calixarene 6 (4.0 g, 5.79 mmol) in MeCN (150 mL),
K2CO3 (3.2 g, 23.16 mmol) was added, and the mixture was
refluxed under nitrogen for 15 min. Allyl bromide (9.5 mL,
10.58 mmol) was then added, and the mixture was further
refluxed for 24 h. The solvent was evaporated under reduced
pressure, the residue was redissolved in CH2Cl2 (100 mL),
washed with 1 M HCl (2!50 mL), H2O (50 mL), and dried
over MgSO4. The solvent was evaporated, and the residual
solid was recrystallized from CHCl3/CH3OH to afford 7
white crystals (95%); mp O275 8C; H NMR: dZ7.00 (d,
JZ2.5 Hz, 2H), 6.98 (m, 4H), 6.95 (s, 2H), 3.82 (m, 8H),
3.32 (m, 10H), 1.39 (m, 2H), 1.26 (s, 18H), 1.24 (s, 18H),
1.03 (m, 2H), 0.92 (m, 4H), 0.61 (m, 9H); 13C NMR: dZ
154.9, 154.6, 143.9, 143.8, 133.5, 133.3, 132.9, 126.1,
126.0, 125.8, 125.5; 72.0, 71.8, 68.6, 60.9, 39.4, 39.2, 34.0,
33.97, 33.95, 32.5, 31.7, 22.6, 22.1, 10.2, 10.0; FTIR (KBr,
cmK1): nZ3468, 2955, 2935, 2923, 2863, 1594, 1475,
1199, 1012. Anal. Calcd for C56H80O5$0.5H2O: C, 79.86;
H, 9.69. Found: C 79.70, H 10.01; MALDI-FTMS, m/z:
855.5886 [(MCNa)C, calcd for C56H82O5 855.5903].
1
as white crystals in 67% yield; mp 187–190 8C; H NMR:
dZ7.64 (s, 2H), 7.03 (s, 4H), 6.83 (s, 2H), 6.82 (s, 2H), 6.23
(m, 1H), 5.75 (d, JZ15 Hz, 1H), 5.36 (d, JZ15 Hz, 1H),
4.52 (d, JZ2.0 Hz, 2H), 4.28 (d, JZ12.5 Hz, 4H), 3.95 (t,
JZ7.5 Hz, 3H), 3.29 (d, JZ12.5 Hz, 4H), 2.02 (m, 2H),
1.27 (s, 18H), 1.24 (t, JZ7.5 Hz, 3H), 0.98 (s, 18H); 13C
NMR: dZ150.8, 150.0, 149.9, 146.9, 146.8, 141.4, 133.2,
132.9, 127.9, 127.8, 125.6, 125.5, 125.1, 117.5, 33.9, 31.9,
31.8, 31.2, 23.5, 11.0; FTIR (KBr, cmK1): nZ3413, 2961,
2904, 1643, 1486, 1361, 1196. Anal. Calcd for C50H66O4:
C, 82.15; H, 9.10. Found: C 81.82, H 9.34; MALDI-FTMS,
m/z: 753.4837 [(MCNa)C, calcd for C50H66O4 753.4853].
4.1.5. Polymer 3. PEG monomethyl ether (10.0 g, 2 mmol)
was dissolved in dry CH2Cl2 (100 mL). The solution was
cooled to 0 8C, and then Et3N (0.54 mL, 4 mmol) and
methanesulfonyl chloride (0.5 mL, 4 mmol) were conse-
quently added. The reaction mixture was stirred at 0–5 8C
for 2 h, washed with water (2!40 mL) and treated with
brine (40 mL). The organic layer was separated and dried
with MgSO4, and the solvent was evaporated in vacuo. The
residue was washed with hexanes to afford product 10
(98%). 1H NMR: dZ3.65 (m, 513H), 3.36 (s, 3H), 3.07 (s,
3H). To the solution of calixarene 9 (1.0 g, 1.2 mmol) in dry
THF (100 mL) potassium tert-butoxide (0.81 g, 7.2 mmol)
was added under nitrogen, and the resulting mixture was
stirred at 50 8C for 20 min. After cooling to rt, polymer 10
(3.0 g, 0.59 mmol) in dry THF (100 mL) was added
dropwise, and the mixture was stirred at 50 8C for 60 h.
The solvent was evaporated; the residue was redissolved in
CH2Cl2 (50 mL), washed with water (2!20 mL), brine
(20 mL), and dried over MgSO4. The solvent was
evaporated under reduced pressure, and the residual solid
was washed thoroughly with diethyl ether to remove
unreacted calixarene (TLC control). The resulted product
4.1.3. 5,11,17,23-Tetrakis(t-butyl)-25-allyloxy-26,27,28-
tris-(n-propyloxy)calix[4]arene, 1,3-alternate 8. To the
solution of calixarene 7 (5.0 g, 6.84 mmol) in MeCN
(400 mL), Cs2CO3 (17.83 g, 54.74 mmol) was added, and
the mixture was refluxed under nitrogen for 15 min.
n-Propyl bromide (6.2 mL, 68.4 mmol) was then added,
and the mixture was further refluxed for 36 h. The solvent
was evaporated under reduced pressure. The residue was
redissolved in CH2Cl2 (100 mL), washed with 1 M HCl
(2!50 mL), H2O (50 mL), and dried over MgSO4. The
solvent was evaporated to afford calixarene 8 as white
crystals in 70% yield; mp 243–245 8C; 1H NMR: dZ6.97 (s,
2H), 6.95 (s, 2H), 6.94 (d, JZ2.5 Hz, 2H), 6.92 (d, JZ
2.5 Hz, 2H), 5.38 (m, 1H), 4.76 (d, JZ2 Hz, 1H), 4.72 (s,
1H), 3.79 (s, 4H), 3.78 (s, 4H), 3.71 (m, 2H), 3.33 (m, 6H),
1.26 (s, 18H), 1.22 (s, 18H), 1.08 (m, 6H), 0.66 (t, JZ
7.5 Hz, 9H); 13C NMR: dZ154.9, 154.7, 154.5, 143.6,
143.5, 135.1, 133.5, 133.3, 133.2, 133.1, 126.3, 126.0,
125.7, 114.5, 72.0, 71.9, 71.6, 70.6, 39.3, 29.1, 34.0, 31.7,
22.7, 22.4, 22.35, 10.1; FTIR (KBr, cmK1): nZ2961, 2900,
2872, 1482, 1211. Anal. Calcd for C56H78O4: C, 82.51; H,
9.64. Found: C 82.19, H 9.99; MALDI-FTMS, m/z:
837.5778 [(MCNa)C, calcd for C56H78O4 837.5792].
1
3 was air dried and then dried in vacuo for 12 h. H NMR:
dZ6.96 (m, 4.39H), 3.36 (s, 3H), 1.24 (m, 21.7H), 0.97 (m),
0.59 (m); Calcd loading is 55%. FTIR (KBr, cmK1): nZ
2948, 2885, 2741, 2695, 2238, 1967, 1468, 1414, 1360,
1343, 1281, 1242, 1149, 1110, 1060, 962, 947, 842, 529.
4.1.6. Nitrosation. NO2/N2O4 was bubbled through the
solution of polymer 3 (1 g, 0.17 mmol calixarene) in dry
CH2Cl2 (10 mL) for 2–3 min, after which N2 was bubbled
through the solution for 10–15 min. The resulting dark
solution was divided into three equal parts. N-methyl
octanamide 11a (5.4 mg, 0.034 mmol), N-ethyl octanamide
11b (5.9 mg, 0.034 mmol), and N-propyl octanamide 11c
(6.3 mg, 0.034 mmol) were separately added to each
solution, and the reaction mixtures were kept at rt for
2–3 h. The solvent was evaporated at rt under reduced
pressure. Hexanes (10 mL) were added, and the mixture was
stirred for 10 min, followed by filtration of the recovered
polymer 3. The solvent was evaporated at rt under reduced
pressure, and the residue was dried for 3 h in vacuo. The
4.1.4. 5,11,17,23-Tetrakis(t-butyl)-25-(30-hydroxypropyl-
oxy)-26,27,28-tris-(n-propyloxy)-calix[4]arene, 1,3-alter-
nate 9. Solution of BH3$THF in THF (1.0 M, 36 mL) was
added dropwise to a stirred solution of compound 8 (3.0 g,
3.68 mmol) in dry THF (200 mL) at K10 8C under nitrogen.
The reaction mixture was stirred for 1 h while warming to rt,
then stirred for another 2.5 h. 1 M aq NaOH (20 mL) was
added dropwise over 10 min, followed by H2O2 (30%,
11 mL) and H2O (2 mL). The mixture was stirred at rt for
1 h and then at 40 8C for 12 h. Brine was added, and the
organic layer was separated. The aqueous layer was
extracted with THF (2!20 mL), and the combined organic
solution was washed with brine (3!30 mL) and dried over
MgSO4. The solvent was evaporated, and the residue was
crystallized from CHCl3/CH3OH to afford product 9 as
1
product yield was determined by H NMR spectroscopy,
using previously reported spectral data.13 Selected data:
1
N-methyloctanoylamide (11a). H NMR dZ6.13 (bs, 1H,
NH), 2.73 (d, 3H, JZ5 Hz, NCH3), 2.12 (t, 2H, JZ7.5 Hz,
CH2), 1.53–1.58 (m, 2H, CH2), 1.22–1.28 (m, 8H, 4!CH2),
0.83 (t, 3H, JZ7.5 Hz, CH3). N-Ethyloctanoylamide (11b).
1H NMR dZ5.41 (bs, 1H, NH), 3.24–3.32 (m, 2H, CH2),
2.13 (t, 2H, JZ7.5 Hz, CH2), 1.52–1.64 (m, 2H, CH2),
1.20–1.34 (m, 8H, CH2), 1.12 (t, 3H, JZ7.5 Hz, CH3), 0.68

Y. Kang, D. M. Rudkevich / Tetrahedron 60 (2004) 11219–11225
11225
1
T. 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.; Capobianchi, A.; Falai, A.;
Mencaglia, A. A.; Pennesi, G. Sens. Actuators, B 2001, 74,
12–17. (d) Nezel, T.; Fakler, A.; Zhylyak, G.; Mohr, G. J.;
Spichiger-Keller, U. E. Sens. Actuators, B 2000, 70, 165–169.
(e) Capone, S.; Mongelli, S.; Rella, R.; Siciliano, P.; Valli, L.
Langmuir 1999, 15, 1748–1753. (f) Tanaka, T.; Ohyama, T.;
Maruo, Y. Y.; Hayashi, T. Sens. Actuators, B 1998, 47, 65–69.
(g) Hu, W. P.; Liu, Y. Q.; Liu, S. G.; Zhou, S. Q.; Zhu,
D. B. Supramol. Sci. 1998, 5, 507–510.
(t, 3H, JZ7.5 Hz, CH3). N-Propyloctanoylamide (11c). H
NMR dZ5.24 (bs, 1H, NH), 3.17–3.23 (m, 2H, CH2), 2.14
(t, 2H, JZ7.5 Hz, CH2), 1.63 (m, 2H, CH2), 1.47–1.56 (m,
2H, CH2), 1.20–1.34 (m, 8H, CH2), 0.93 (t, 3H, JZ7.5 Hz,
CH3), 0.84 (t, 3H, JZ7.5 Hz, CH3). N-Methyl-N-nitroso-
1
octanoylamide (12a). H NMR dZ3.19 (t, 2H, JZ7.5 Hz,
CH2C(O)), 3.12 (s, 3H, N(NO)CH3), 1.72–1.81 (m, 2H,
CH2), 1.26–1.41 (m, 8H, (CH2)4), 0.86 (t, 3H, JZ7.5 Hz,
CH3). N-Ethyl-N-nitrosooctanoylamide (12b). 1H NMR dZ
3.80 (q, 2H, JZ7.5 Hz, N(NO)CH2), 3.12 (t, 2H, JZ7.5 Hz,
CH2C(O)), 1.75–1.82 (m, 2H, CH2), 1.26–1.41 (m, 8H,
CH2), 0.96 (t, 3H, JZ7.5 Hz, CH3), 0.87 (t, 3H, JZ7.5 Hz,
CH3). N-Propyl-N-nitrosooctanoylamide (12c). 1H NMR
dZ3.72 (t, 2H, JZ7.5 Hz, N(NO)CH2), 3.13 (t, 2H, JZ
7.5 Hz, CH2C(O)), 1.75–1.82 (m, 2H, CH2), 1.36–1.42 (m,
2H, CH2), 1.26–1.41 (m, 8H, CH2), 0.87 (t, 3H, JZ7.5 Hz,
CH3), 0.81 (t, 3H, JZ7.5 Hz, CH3).
6. (a) Zyryanov, G. V.; Kang, Y.; Stampp, S. P.; Rudkevich,
D. M. Chem. Commun. 2002, 2792–2793. (b) Zyryanov, G. V.;
Kang, Y.; Rudkevich, D. M. J. Am. Chem. Soc. 2003, 125,
2997–3007.
7. Addison, C. C. Chem. Rev. 1980, 80, 21–39.
8. (a) Bosch, E.; Kochi, J. K. J. Org. Chem. 1994, 59, 3314–3325.
(b) Rathore, R.; Bosch, E.; Kochi, J. K. Tetrahedron 1994, 50,
6727–6758 and references therein.
4.2. UV–vis spectroscopy measurements
9. (a) Rudkevich, D. M. Bull. Chem. Soc. Jpn 2002, 75, 393–413.
¨
(b) Calixarene 2001; Asfari, Z., Bohmer, V., Harrowfield, J.,
The measurements with compounds 1–4 were performed at
295G1 K in CH2Cl2. In the titration studies, the UV–vis
spectra were recorded at 6!10K5 M concentration of
calixarene 1a and concentration of NO2 varied within
w5!10K5–1.2!10K3 M range. The apparent association
constant was estimated from the changes in the absorbance
at lmaxZ565 nm (charge-transfer band in complex 2a). All
measurements were performed at least in duplicate.
Vicens, J., Eds.; Kluwer Academic: Dordrecht, 2001.
(c) Gutsche, C. D. Calixarenes Revisited; Royal Society of
Chemistry: Cambridge, 1998.
10. (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. 1998, 37, 1534–1537.
Acknowledgements
Financial support was kindly provided by the American
Cancer Society Institutional Research Grant to the
University of North Texas Health Science Center and
the Texas Higher Education Coordinating Board—
Advanced Technology Program (003656-0146-2003).
11. 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.
12. Iwamoto, K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47,
4325–4342.
13. Zyryanov, G. V.;Rudkevich, D. M. Org. Lett. 2003,5, 1253–1256.
14. Kochi and co-workers obtained similar calix[4]arene–NOC
complexes from either NOCSbCl–6 and free calixarene or NO
gas and the calixarene cation-radical, see: Rathore, R.;
Lindeman, S. V.; Rao, K. S. S.; Sun, D.; Kochi, J. K.
Angew., Chem. Int. Ed. 2000, 39, 2123–2127.
References and notes
1. US EPA publications: http://www.epa.gov/air/urbanair/nox/
index.html.
15. Review on arene–nitrosonium complexes: Borodkin, G. I.;
Shubin, V. G. Russ. Chem. Rev. 2001, 70, 211–230.
16. Pariiskii, G. B.; Gaponova, I. S.; Davydov, E. Ya. Russ. Chem.
Rev. 2000, 69, 985–999.
2. (a) Lerdau, M. T.; Munger, J. W.; Jacob, D. J. Science 2000,
5488, 2291–2293. (b) Kirsch, M.; Korth, H.-G.; Sustmann, R.;
de Groot, H. Biol. Chem. 2002, 383, 389–399.
17. Stepanov, A. V.; Veselovsky, V. V. Russ. Chem. Rev. (Russ.
Ed.) 2003, 72, 363–378.
3. (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.1999, 38, 1714–1731.(d)Butler,A. R.;Williams,
D. L. H. Chem. Soc. Rev. 1993, 233–241. (e) Tamir, S.; Burney,
S.; Tannenbaum, S. R. Chem. Res. Toxicol. 1996, 9, 821–827.
18. Kosior, M.; Malinowska, M.; Jozwik, J.; Caille, J.; Jurczak, J.
Tetrahedron: Asymmetry 2003, 14, 239.
19. (a) Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.;
Janczuk, A. J. Chem. Rev. 2002, 102, 1091–1134. (b) Megson,
I. I.; Webb, D. J. Expert Opin. Investig. Drugs 2002, 11,
587–601. (c) Granik, V. G.; Grigor’ev, N. B. Russ. Chem.
Bull., Int. Ed. 2002, 51, 1375–1422.
´
¨
4. (a) Filippini, D.; Rosch, M.; Aragon, R.; Weimar, U. Sens.
Actuators, B 2001, 81, 83–87. (b) Steffes, H.; Imawan, C.;
Solzbacher, F.; Obermeier, E. Sens. Actuators, B 2001, 78,
106–112. (c) Pijolat, C.; Pupier, C.; Sauvan, M.; Tournier, G.;
Lalauze, R. Sens. Actuators, B 1999, 59, 195–202. (d) Law,
M.; Kind, H.; Messer, B.; Kim, F.; Yang, P. Angew. Chem., Int.
Ed. 2002, 41, 2405–2408.
20. (a) McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. Rev.
2002, 102, 3275–3300. (b) Dickerson, T. J.; Reed, N. N.;
Janda, K. D. Chem. Rev. 2002, 102, 3325–3344.
(c) Bergbreiter, D. E. Chem. Rev. 2002, 102, 3345–3384.
21. (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.
5. (a) Bradford, A.; Drake, P. L.; Worsfold, O.; Peterson, I. R.;
Walton, D. J.; Price, G. J. Phys. Chem. Chem. Phys. 2001, 3,
1750–1754. (b) Dooling, C. M.; Worsfold, O.; Richardson,