Toward Synthetic Tubes for NO2/N2O4: Design, Synthesis, and Host-Guest Chemistry

Article abstract of DOI:10.1021/ja0392869

Design of molecular nanotubes is proposed for entrapment and conversion of NO₂/N₂O₄ gases. Synthesis of 1,3-alternate bis-calix[4]arene tube 3 of 5 × 11 A internal dimensions is presented, and its reversible reactions with

Full text of DOI:10.1021/ja0392869

Published on Web 03/11/2004
Toward Synthetic Tubes for NO2/N2O4: Design, Synthesis,
and Host-Guest Chemistry
Grigory V. Zyryanov and Dmitry M. Rudkevich*
Contribution from the Department of Chemistry & Biochemistry,
UniVersity of Texas at Arlington, Arlington, Texas 76019-0065
Received October 28, 2003; E-mail: rudkevich@uta.edu
Abstract: Design of molecular nanotubes is proposed for entrapment and conversion of NO2/N2O4 gases.
Synthesis of 1,3-alternate bis-calix[4]arene tube 3 of 5 × 11 Å internal dimensions is presented, and its
reversible reactions with NO2/N2O4 in solution are studied. Exposure of 3 to NO2/N2O4 in chlorinated solvents
results in the rapid encapsulation of nitrosonium (NO+) cations within its interior. Mono- and dinitrosonium
1
complexes 4 and 5, respectively, were isolated and characterized by UV-vis, FTIR, and H NMR spec-
troscopies, and also molecular modeling. The NO+ entrapment process is reversible, and addition of water
quickly recovered starting tube 3. Encapsulated within the tube NO+ species act as nitrosating agents for
secondary amides. These findings open wider perspectives toward NO2/NOx storing and converting materials
and also offer a promise for further development of supramolecular chemistry of synthetic nanotubes.
Introduction
Recent studies have revealed that gases can be stored inside
single-walled carbon nanotubes (SWNTs). This is exciting. En-
trapping isotopes of noble gases by SWNTs may improve their
use in medical imaging, where it is desirable to physically con-
fine the gas before injection.1 SWNTs encapsulate N2, O2, NO,
and CF4.2 They have been shown to effectively detect O2, NH3,
and NO2.3 Upon exposure to gaseous molecules the electri-
cal resistance of SWNTs dramatically changes. Storage of H2
in SWNTs is extremely promising in the design of energy-rich
fuel-cell electric devices.4 Synthetic nanotubes are rare,5 and
their chemistry with gases is not known. This is surprising. Or-
ganic synthesis permits much greater structural variations and
control over the tube length/diameter, which is important for
the gas dynamics and for the design of potential gas storing
chambers and conversion/catalytic vessels. In this paper, we
(1) Gadd, G. E.; Blackford, M.; Moricca, S.; Webb, N.; Evans, P. J.; Smith,
A. M.; Jacobsen, G.; Leung, S.; Day, A.; Hua, Q. Science 1997, 277, 933-
936.
(2) (a) Byl, O.; Kondratyuk, P.; Forth, S. T.; FitzGerald, S. A.; Chen, L.;
Johnson, J. K.; Yates, J. T., Jr. J. Am. Chem. Soc. 2003, 125, 5889-5896.
(b) Byl, O.; Kondratyuk, P.; Yates, J. T., Jr. J. Phys. Chem. B 2003, 107,
4277-4279. (c) Fujiwara, A.; Ishii, K.; Suematsu, H.; Kataura, H.; Maniwa,
Y.; Suzuki, S.; Achiba, Y. Chem. Phys. Lett. 2001, 336, 205-211.
(3) (a) Kong, J.; Franklin, N. R.; Zhou, C.; Chapline, M. G.; Peng, S.; Cho,
K.; Dai, H. Science 2000, 287, 622-625. (b) Collins, P. G.; Bradley, K.;
Ishigami, M.; Zettl, A. Science 2000, 287, 1801-1804. (c) Peng, S.; Cho,
K. Nanotechnology 2000, 11, 57-60.
(4) For example: (a) Dillon, A. C.; Jones, K. M.; Bekkedahl, T. A.; Kiang, C.
H.; Bethune, D. S.; Heben, M. J. Nature 1997, 386, 377-379. (b) Liu, C.;
Fan, Y. Y.; Liu, M.; Cong, H. T.; Cheng, H. M.; Dresselhaus, M. S. Science
1999, 286, 1127-1129. (c) Du, W.-F.; Wilson, L.; Ripmeester, J.; Dutrisac,
R.; Simard, B.; Denommee, S. Nano Lett. 2002, 2, 343-346. (d) Volpe,
M.; Cleri, F. Chem. Phys. Lett. 2003, 371, 476-482.
(5) (a) Ikeda, A.; Shinkai, S. Chem. Commun. 1994, 2375-2376. (b) Ikeda,
A.; Kawaguchi, M.; Shinkai An. Quim. Int. Ed. 1997, 93, 408-414. (c)
Matthews, S. E.; Schmitt, P.; Felix, V.; Drew, M. G. B.; Beer, P. D. J.
Am. Chem. Soc. 2002, 124, 1341-1353. (d) Kim, S. K.; Sim, W.; Vicens,
J.; Kim, J. S. Tetrahedron Lett. 2003, 44, 805-809. (e) Cyclodextrine-
based nanotube: Harada, A.; Li, J.; Kamachi, M. Nature 1993, 364, 516-
518. (f) Self-assembling nanotubes: Bong, D. T.; Clark, T. D.; Granja, J.
R.; Ghadiri, M. R. Angew. Chem., Int. Ed. 2001, 40, 988-1011, and
references therein.
Figure 1. Molecular tubes for NO2/N2O4 fixation, a schematic representa-
tion. Upon exposure to polyaromatic surfaces of the tubes, N2O4 dispro-
portionates to NO+NO3-. Nanotubes encapsulate NO+ within their interiors.
In and out exchange of trapped NO+ species is possible, and this can be
applied for nitrosation reactions.
present the design of synthetic tubes for NO2/N2O4 fixation,
which is based on calixarenes (Figure 1, Figure 2).
Starting here with the first generation, we disclose the syn-
thesis and unique host-guest chemistry between NO2/N2O4 and
tube 3, and also chemical reactions with thus-obtained encap-
sulating complexes 4 and 5. Nitrogen dioxide (NO2) and its
dimersdinitrogen tetroxide (N2O4)sbelong to the family of NOx
gases.6 These are toxic environmental pollutants, originated in
large quantities from fuel combustion and large-scale indus-
trial processes. Their extensive circulation requires not only the
systematic monitoring but also necessitates the development of
9
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Toward Synthetic Tubes for NO /N O
2 4
A R T I C L E S
2
Figure 2. Calix[4]arenes 1a,b and tube 3 and their nitrosonium complexes 2a,b, 4, and 5.
improved methods of their fixation. In addition, we feel that
our approach may lead to further progress in supramolecular
chemistry of synthetic nanotubes, especially multiple guest en-
capsulation, their dynamics, and relations within enclosed
spaces.
Results and Discussion
Design and Synthesis. Calixarene-based nanotubes were
introduced by Shinkai 10 years ago.5a These were designed for
small metal ions and represented, probably, the first synthetic
nanotubes in molecular recognition. In contrast to cavitands,
carcerands, and self-assembling capsules,7 nanotubes are open
from both ends and, besides their larger dimensions, possess
different guest dynamics. We recently discovered that simple
calix[4]arenes, for example 1a,b (Figure 2), reversibly interact
with NO2/N2O4 and entrap highly reactive nitrosonium (NO+)
cation within their π-electron-rich interiors.8 NO+ is generated
from N2O4, which is known to disproportionate to NO+NO3
.
-
Stable nitrosonium complexes 2a,b were quantitatively isolated
upon addition of a Lewis acid SnCl4. Only one NO+ cation
was found per cavity; very high association constants Kassoc
.106 M-1 were determined.
In the design of nanotubes, several calix[4]arenes should be
rigidly connected from both sides of their rims, with at least
two symmetrical bridging units. This is possible for a 1,3-
alternate conformation. Calix[4]arenes in a 1,3-alternate con-
formation are much more rigid than other conformers and
possess a cylindrical inner tunnel, defined by two cofacial pairs
of aromatic rings oriented orthogonally along the cavity axis.
According to a number of X-ray studies, this tunnel is ∼5-6
Å in diameter. Two pairs of phenolic oxygens are oriented in
opposite directions, providing a diverse route to enhance the
tube length modularly.
Figure 3. MacroModel 7.1 (Amber* Force Field) representation of tubular
stricture 3 and its complex with NO+, side and top views. The alkyl chains
and hydrogens were removed for clarity. In complex 5, the front aromatic
ring is omitted to reveal the encapsulated species.
Described here molecule 3 is a bis-calixarene tube, designed
to entrap up to two NO+, one per each cavity. It possesses the
inner tunnel of ∼5 × 11 Å dimensions and thus represent a
first generation of calixarene nanotubes for NO2/N2O4 fixation
and conversion. Two 1,3-alternate calix[4]arenes in 3 are
connected via their phenolic oxygens through two diethylene
glycol bridges (Figure 3). By our calculations, the bridge length
is quite optimal: it not only provides relatively high confor-
(6) U. S. EPA site: http://www.epa.gov./air/urbanair/nox.
(7) Rudkevich, D. M. Bull. Chem. Soc. Jpn. 2002, 75, 393-413.
(8) (a) Zyryanov, G. V.; Kang, Y.; Rudkevich, D. M. J. Am. Chem. Soc. 2003,
125, 2997-3007. (b) Zyryanov, G. V.; Kang, Y.; Stampp, S. P.; Rudkevich,
D. M. Chem. Commun. 2002, 2792-2793.
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Scheme 1. (a) Cs2CO3, MeCN, Reflux, 48 H, 9%; (b) NaH, DMF, 80 °C, 48 H, 13%
mational rigidity of the tubular structure but also seals the walls,
minimizing the gaps between the calixarene modules.
The synthesis of tube 3 was accomplished by two independent
routesseither through alkylation of dipropyloxycalix[4]arene
69 with ditosylate 7 or by coupling of diol 8 and ditosylate 910
(Scheme 1). Ditosylate 7 was prepared in two steps from
calixarene 6 and diethylene glycol monotosylate (Cs2CO3,
MeCN, reflux), followed by the quantitative acylation of the
resulting diol with TsCl (NaOH, H2O-THF (THF ) tetrahy-
drofuran)). Diol 8 was obtained by the basic hydrolysis of known
ditosyl derivative 9 (KOH, H2O-DMSO (DMSO ) dimethyl
sulfoxide, 110 °C). Preparation of calixarene 1 included the two-
step alkylation of de-tert-butylated calix[4]arene with n-hexyl
bromide, using successively K2CO3 and then Cs2CO3 in boiling
MeCN.8 This was used for comparison and also in the guest
exchange experiments.
Host-Guest Chemistry. We found that tube 3 can be used
for fixation and conversion of NO2/N2O4. Upon bubbling NO2/
N2O4 through the solution of 3 in chlorinated solvents in the
presence of SnCl4, two nitrosonium complexes 4 and 5 were
identified and subsequently isolated in preparative quantities.
When performed in CHCl3, the reaction resulted in instant
precipitation of dark-purple solid, assigned as complex 4 (Figure
2). In (CHCl2)2 solution, complex 5 formed. The use of CH2-
Cl2 resulted in a mixture of 4 and 5.
Adducts 4 and 5 possess typical features of calixarene-NO+
complexes.11 In the UV-vis spectra of 4 and 5 in CH2Cl2, broad
charge-transfer bands at λmax ) 540 and 515 nm were recorded,
respectively, and the FTIR spectra exhibited a characteristic12
arene-NO+ stretching at ν ) 1932 and 1948 cm-1, respectively.
The 1H NMR spectra in (CDCl2)2 produce new sets of signals,
different from those of empty tube 3 (Figure 4). In particular,
the aromatic protons of free 3 were seen as a pair of doublets
at 7.21 and 7.02 ppm and a pair of triplets at 7.00 (overlap)
and 6.86 ppm. In complex 4, these were transformed into a
multiplet centered at ∼7.1 ppm and a triplet at 6.96 ppm. In
complex 5, these signals appeared as doublets at 7.26 and 7.10
ppm and triplets at 7.35 and 6.29 ppm. The CH2 methylene
bridge, the propyl OCH2, and the glycol CH2OCH2 and ArOCH2
protons of 3 were seen as an apparent singlet and three triplets,
2:1:1:1, at 3.88, 3.26, 3.55, and 2.59 ppm, respectively. In
1
Figure 4. Selected portions of the H NMR spectra (500 MHz, 295 ( 1
K) of (A) calix[4]arene tube 3 in CDCl3, (B) 3 in (CDCl2)2, (C)
mononitrosonium complex 4 in (CDCl2)2, and (D) dinitrosonium complex
5 in (CDCl2)2. The residual solvent signals are marked with “•”.
complexes 4 and 5, these changed and shifted. We will inspect
their behavior below.
The guest stoichiometry in 4 and 5 was estimated by 1H NMR
through NO+ exchange in (CDCl2)2.13 Specifically, when 5 was
mixed with empty 3, complex 4 formed exclusively. No spectral
changes were recorded upon mixing 3 and 4. Further, when
mixed with monomeric calixarene host 1b, complex 5 generated
nitrosonium complexes 2b and 4. At the same time, no exchange
was observed upon mixing 1b and 4. Accordingly, complex 4
possesses one NO+ guest, and complex 5 encapsulates two of
them. Further, upon bubbling NO2/N2O4 through the solution
of 4 and SnCl4 in (CDCl2)2, complex 5 emerges; this process
can be clearly followed by 1H NMR spectroscopy. Higher
stoichiometries of NO+ were ruled out: there is simply no room
to accommodate more than two electrostatically repulsive
cations.
(9) 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.
(10) Kim, J. S.; Shon, O. J.; Ko, J. W.; Cho, M. H.; Yu, I. Y.; Vicens, J. J.
Org. Chem. 2000, 65, 2386-2392.
(11) Kochi, Rathore, and co-workers generated calix[4]arene‚NO+ complexes
from nitric oxide (NO) and calixarene cation radicals and from NO+SbCl6
and calixarenes. In the solid state, the NO+ cation was found tightly
encapsulated within the calixarene cavity. See: Rathore, R.; Lindeman, S.
V.; Rao, K. S. S. P.; Sun, D.; Kochi, J. K. Angew. Chem., Int. Ed. 2000,
39, 2123-2127.
(13) Due to the high thermal and moisture sensitivity, attempts to obtain
satisfactory mass-spectrometry data on nitrosonium complexes 4 and 5 have
had a limited success. To date, a MALDI-TOF signal for 4 was detected
in (CDCl2)2 at m/z 1186 ([3 + NO]+, calcd for C76H84O10‚NO 1186.6)
along with decomposition and nitration products.
(12) Borodkin, G. I.; Shubin, V. G. Russ. Chem. ReV. 2001, 70, 211-230.
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Toward Synthetic Tubes for NO /N O
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Figure 5. Guest dynamics: (A) rotation and tumbling inside tube 3 and (B) in-out exchange.
For further structural identification, calixarene tube 3 was
mixed with the commercially available nitrosonium source,
NO+SbF6-, in (CDCl2)2, producing within 1-2 h a mixture of
mono- and dinitrosonium complexes, analogous to 4 and 5
suggests that the guest does not freely migrate along the tubular
inner space, hopping between two calixarene units.16
In dinitrosonium complex 5, the propyl Ar-O-CH2 protons
are seen downfield from those in empty 3. Similar shifts were
observed for the first generation of calixarene-NO+ complexes
2a8 and 2b. Obviously, two NO+ cations in 5 are electrostatically
pushed away from each other toward the ends of tube 3 (Figure
5B).
1
(UV-vis, H NMR; 295 ( 1 K).
Complexes 4 and 5 are stable in dry solution at room
temperature for days but can be readily destroyed with H2O,
quantitatively regenerating free 3.
1H NMR Spectroscopy. The guest(s) orientation, dynamics,
Electrostatic repulsions are most likely responsible for the
smooth NO+ exchange between 5 and 3, leading to 4, and
between 5 and 1b, leading to 4 and 2b. At the same time,
mononitrosonium species 4 are more stable and do not visibly
exchange with 1b for days. Accordingly, there is a communica-
tion between the two guests within the interior 5.17,18
and relations in tube-shaped complexes 4 and 5 were further
1
studied by H NMR spectroscopy, which proved to be a very
useful and delicate tool. The NO+ complexation apparently does
not influence the symmetry of the host 3 (at 295 ( 5 K). Despite
the nonequivalence of the methylene bridge, CH2 protons
becomes more pronounced, the number of the propyl OCH2,
the glycol CH2OCH2 and ArOCH2, and the aromatic 1H NMR
signals (Figure 4) for 4 and 5 does not change. This implies
that the NO+ guest(s), with the van der Waals dimensions ∼2
Å,12 freely rotates along the N-O axis and also tumbles within
the cavity at room temperatures (Figure 5A). Similar dynamics
was previously noticed for simpler calixarene-NO+ com-
plexes.8,11
-
Upon stepwise addition of NO+SbF6 or NO2/N2O4 to 3 in
(CDCl2)2, 1H NMR signals of 3-5 can be seen separately, sharp
and in slow exchange. This is typical for the host-guest
complexes with high exchange ∆Gq barriers (>15 kcal/mol)
and/or high Kassoc > 106 M-1 values.7,19 Molecular modeling
suggests that the first NO+ can enter the tube either through its
neck/bottom and then channel to the middle, or through the gate
between the two calixarenes (Figure 5B). Complex 4 thus forms.
To avoid electrostatic repulsions, the second NO+ can only enter
through the neck/bottom, thus further pushing the first guest
toward the tube end. This results in complex 5. The decom-
plexation sequence must be similar. Dinitrosonium complex 5
should release one NO+ through the neck, while the second
NO+ in thus generated complex 4 may exit either through the
Significant (>1 ppm) downfield shifts of the glycol chain
Ar-O-CH2 and CH2-O-CH2 protons in both complexes,
compared to empty 3 (Figure 4B-D), imply strong cation-
dipole interactions between the glycol oxygens and NO+.
Complexes between NO+ and simple crown ethers are
known.14-15 Apparently, NO+ is situated in the middle of
structure 4, simultaneously interacting with the tube benzene
edges and the glycol chains. In this arrangement, the propyl
Ar-O-CH2 protons in 4 appear far away from the complexed
NO+ and should not change their chemical shift compared to
empty tube 3. This is indeed the case (Figure 4C) and also
(16) For a detailed discussion of metal cation hopping between two calixarenes
within the Shinkai’s nanotubes, see ref 5b.
(17) This is in contrast to double-1,3-alternate-calixcrowns, where two calixarene
units complex metal ions independently from each other: Kim, S. K.;
Vicens, J.; Park, K.-M.; Kim, J. S. Tetrahedron Lett. 2003, 44, 993-997.
(18) For early examples of a multiple guests’ communication inside capsules,
see: (a) Tucci, F. C.; Rudkevich, D. M.; Rebek, J., Jr. J. Am. Chem. Soc.
1999, 121, 4928-4929. (b) Starnes, S. D.; Rudkevich, D. M.; Rebek, J.,
Jr. J. Am. Chem. Soc. 2001, 123, 4659-4669.
(14) Zolfigol, M. A.; Zebarjadian, M. H.; Chehardoli, G.; Keypour, H.;
Salehzadeh, S.; Shamsipur, M. J. Org. Chem. 2001, 66, 3619-3620.
(15) Preliminary account on encapsulated nitrosating reagents, which are
produced upon chemical fixation of NO2/N2O4 by calix[4]arenes: Zyryanov,
G. V.; Rudkevich, D. M. Org. Lett. 2003, 5, 1253-1256.
(19) 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, 12216-12225. (b) Lu¨cking, U.; Tucci, F. C.; Rudkevich, D. M.; Rebek,
J., Jr. J. Am. Chem. Soc. 2000, 122, 8880-8889.
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Figure 6. N-Nitrosation of amides 10 with encapsulated reagents 4 and 5. Right: proposed prereactice complexes for di- and mononitrosonium molecular
tubes.
middle gate or through the neck. These unique properties are
the direct result of an open-ended tubular structure of 3.
Chemical Reactions with Encapsulated Nitrosonium.
Chemical properties of the encapsulated within 4 and 5 NO+
species were also tested and found to be different from those in
bulk solution. They are controlled by the cavity. Highly reactive
NO+ species are protected from the bulk environment. Com-
plexes 4 and 5 are quite stable toward moisture and oxygen,
and can be handled, for hours without drybox and/or nitrogen
atmosphere. On the other hand, they can be quickly decomposed
by addition of large quantities of H2O, recovering free calixarene
3. Such stability of arene-nitrosonium complexes is remark-
able.12
We determined that complexes 4 and 5 may act as mild
nitrosating reagentssencapsulated reagents.15 When added to
the equimolar solution of secondary amide 10a,b in freshly
distilled CHCl3, they reacted instantly at room temperature,
yielding N-nitrosoamides 11a,b (Figure 6). Complex 4 reacts
with lower yields (∼10-15%), and much better results were
achieved with complex 5, where the yields are ∼50%. Dark-
purple solutions of 4 and 5 quickly discharged upon addition
of 10a,b, which serves as a visual test for the reaction. In the
1H NMR spectra of the reaction mixtures, signals for amides
10a,b and complexes 4 and 5 disappeared and characteristic
signals for N-nitrosoamides 11a,b at ∼3.2 ppm (2 H, t, C(O)-
CH2) and ∼3.1 ppm (s, 3 H, N(NO)-CH3) and for nitrosonium-
free calixarene 3 were detected (Figure 7).
Mechanistically, nitrosation of secondary amides incorporates
Figure 7. 1H NMR analysis of a nitrosation reaction (500 MHz, CDCl3,
295 ( 1 K): (A) N-nitrosoamide 11b, independently obtained from amide
10b and NO2/N2O4 for spectral comparison; (B) reaction mixtures 5 + 10b
an electrophilic attack of NO+ on a nucleophilic carbonyl
oxygen of the substrate, yielding the corresponding O-nitroso
species.20 Rapid deprotonation, rotation around the C-O bond,
after 1 h; (C) guest-free calixarene tube 3.
and inversion through the nitrogen results in the intermediate,
in which both the nitrogen lone pair and the NO group are
properly oriented for the isomerization to the N-nitrosoamide.
Substrates 10a,b thus approach tubes 4 and 5, facing them with
the carbonyl oxygen (Figure 6, right). In complex 4, the reaction
most probably occurs through the middle gate. Otherwise, the
NO+ should migrate first through the tube. In complex 5, the
reaction with the first NO+ should occur within the neck/bottom
of the tube. Such guest dynamics, probably, explains differences
between 4 and 5 in the nitrosation yields.
Once formed, the O-nitroso intermediate leaves the interior
and further collapses in bulk solution, as expected.20 Due to
the extremely strong binding of NO+ species in 4 and 5, the
rate-limiting formation of the O-nitrosation intermediates should
take place within the cavity, prior to the NO+ dissociation.
In organic chemistry, nitrosation holds a special place. Alkyl
nitrites, nitrosamines/amides, and nitrosothiols are used in
(20) Darbeau, R. W.; Pease, R. S.; Perez, E. V. J. Org. Chem. 2002, 67, 2942-
2947, and references therein.
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2
biomedicine as NO-releasing drugs.21 In total synthesis and
methodology, -NdO is an important activating group, allowing
elegant transformations of amides to carboxylic acids and their
derivatives.22 In addition, nitrosation mimics interactions be-
tween biological tissues and environmentally toxic NOx gases.23
Tube 3 thus converts NO2/N2O4 into mild and effective
nitrosating reagents. Tight but reversible encapsulation of NO+
species should offer regioselectivities and size-shape selectivi-
ties, previously unknown for existing, more aggressive nitro-
sating agents (e.g., NO+ salts, N2O3, NO2/N2O4, NO/O2, HNO2,
etc.).15
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 chromatog-
raphy, Silica Gel 60 Å (Sorbent Technologies, Inc.; 200-425 mesh)
was used. Parent tetrahydroxycalix[4]arene25 was prepared according
to the published procedures. NO2/N2O4 was generated from copper and
concentrated HNO3. Molecular modeling was performed using com-
mercial MacroModel 7.1 with Amber* Force Field.26
Caution 1: NO2 has an irritating odor and is very toxic! Caution 2:
N-Nitrosoamides are carcinogens27 and should be treated with
extreme care!
5,11,17,23-Tetra-t-butyl-25,26,27,28-tetrakis(n-hexyloxy)calix[4]-
arene, 1,3-Alternate (1b). Prepared by the two-step alkylating
procedure described in details in the previous studies.8 Yield 42%, mp
Conclusions and Outlook
1
232 °C; H NMR (CDCl3) δ 6.95 (s, 8 H), 3.73 (s, 8 H), 3.38 (t, J )
Synthetic nanotubes can now be prepared for chemical
entrapment and conversion of NO2/N2O4. These are based on
calix[4]arenes and take advantage of their extremely diverse
chemistry. Such nanotubes may act as encapsulated nitrosating
reagents, thus opening a novel opportunity for NO2/N2O4
utilization. There is also a potential sensory application, since
dramatic color changes are involved. Finally, in contrast to
cavitands, carcerands, and capsules,7 supramolecular chemistry
of synthetic nanotubes is unexplored. We are now utilizing our
design and strategy for the preparation of longer calixarene tubes
for supramolecular gas storage and fixation.24 We are also
exploring regio- and stereoselective nitrosation processes with
encapsulated nitrosonium guests.
7.5 Hz, 8 H), 1.28 (s, 36 H), 1.25-1.1 (m, 32 H), 0.86 (t, J ) 7.5 Hz,
12 H); 13C NMR (CDCl3) δ 154.8, 143.4, 133.1, 126.0, 70.8, 39.0,
33.9, 32.0, 31.8, 31.7, 29.7, 25.6, 23.0, 14.2; MALDI-TOF, m/z 985.71
([M + H]+; calcd for C68H105O4, 985.80), 1007.93 ([M + Na]+; calcd
for C68H104O4Na, 1007.78).
25,27-Bis(hydroxy(ethyloxyethyl)oxy)-26,28-bis(1-propyloxy)-
calix[4]arene, 1,3-Alternate. 25,27-Dihydroxy-26,28-bis(1-propyloxy)-
calix[4]arene (6;9 1 g, 1.96 mmol), diethylene glycol monotosylate (1.53
g, 5.88 mmol), and Cs2CO3 (9.59 g, 30 mmol) in MeCN (100 mL)
were refluxed under nitrogen for 24 h. The solution was evaporated to
dryness, diluted with CH2Cl2 (100 mL), and neutralized with 5%
aqueous HCl (100 mL). The organic layer was separated, washed with
water (3 × 100 mL), and evaporated. Column chromatography
(CHCl3-acetone, 8:2) afforded the product (Rf ) 0.21) as a colorless
1
oil. Yield 0.13 g (10%); H NMR (CDCl3) δ 7.07 (d, J ) 7.5 Hz, 4
Experimental Section
H), 7.03 (d, J ) 7.5 Hz, 4 H), 6.79 (t, J ) 7.5 Hz, 2 H), 6.74 (t, J )
7.5 Hz, 2 H), 3.79-3.76 (m, 8 H), 3.67 (2 × d, J ) 15.0 Hz, 8 H),
3.61-3.58 (m, 8 H), 3.52 (t, J ) 7.8 Hz, 4 H), 1.59-1.52 (m, 4 H),
0.87 (t, J ) 7.5 Hz, 6 H); 13C (CDCl3) δ 156.6, 155.9, 133.9, 130.4,
130.2, 122.7, 122.4, 73.0, 72.8, 71.3, 70.1, 61.7, 37.0, 23.2, 10.3;
MALDI-FTMS 707.3540 ([M + Na]+; calcd for C42H52O8Na,
707.3554).
1
General Methods. H and 13C NMR spectra were recorded at 295
( 1 °C on a 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 Varian Cary-50 spectrophotometer.
MALDI-TOF mass spectra were recorded on a delayed-extraction
MALDI-TOF mass spectrophotometer Voyager DE (Applied Biosys-
tems). HRMS MALDI spectra were obtained on an Ion Spec Ultima
25,27-Bis(2-p-toluenesulfonyl(bisoxyethyl)oxy)-26,28-bis(1-
propyloxy)calix[4]arene, 1,3-Alternate (7). A solution of NaOH (1.96
g, 49 mmol) in water (10 mL) was added dropwise to the mixture of
the above-described compound (1.34 g, 1.96 mmol) and TsCl (1.86 g,
9.8 mmol) in THF (100 mL), upon cooling on an ice bath. After 24 h
of stirring at room temperature, the solvents were evaporated. Column
chromatography on silica gel (EtOAc-hexane, 1:1) afforded product
7 (Rf ) 0.6) as a colorless oil. Yield 1.95 g (>95%); 1H NMR (CDCl3)
δ 7.80 (d, J ) 8.5 Hz, 4 H), 7.31 (d, J ) 8.5 Hz, 4 H), 6.98 (d, J )
7.5 Hz, 4 H), 6.96 (d, J ) 7.5 Hz, 4 H), 6.69 (t, J ) 7.5 Hz, 2 H), 6.61
(t, J ) 7.5 Hz, 2 H), 4.17 (t, J ) 7.0 Hz, 4 H), 3.64, 3.61 (2 × t, J )
7.0 Hz, 8 H), 3.59 (2 × d, J ) 15.0 Hz, 8 H), 3.50, 3.45 (2 × t, J )
7.0 Hz, 8 H), 1.61-1.55 (m, 4 H), 0.89 (t, J ) 7.5 Hz, 6 H).
(25,27-Bis(2-hidroxyethyloxy)-26,28-bis(1-propyloxy)calix[4]-
arene, 1,3-Alternate (8). 25,27-Bis(2-p-toluenesulfonyloxyethyloxy)-
26,28-bis(1-propyloxy)calix[4]arene (9;10 1.2 g, 1.3 mmol) was dis-
solved in DMSO (45 mL), KOH (1.54 g, 27.4 mmol), and water (10
mL). The reaction mixture was heated at 110 °C for 2-4 h and
monitored by thin-layer chromatography (TLC) (hexanes-EtOAc, 5:1),
then diluted with CH2Cl2 (100 mL), and cooled to -5 °C, after which
5% aqueous HCl (100 mL) was added. The organic layer was separated,
washed with water (3 × 100 mL), and evaporated. The residue was
passed through the column with silica gel (hexanes-EtOAc, 5:1) to
(21) (a) Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk,
A. J. Chem. ReV. 2002, 102, 1091-1134. (b) Granik, V. G.; Grigor’ev, N.
B. Russ. Chem. Bull. 2002, 51, 1375-1422.
(22) (a) White, E. H. J. Am. Chem. Soc. 1955, 77, 6008-6010. (b) White, E.
H. J. Am. Chem. Soc. 1955, 77, 6014-6022. (c) Olah, G. A.; Olah, J. A.
J. Org. Chem. 1965, 30, 2386-2387. (d) Nikolaides, N.; Ganem, B.
Tetrahedron Lett. 1990, 31, 1113-1116. (e) Kim, Y. H.; Kim, K.; Park,
Y. J. Tetrahedron Lett. 1990, 31, 3893-3894. (f) Glatzhofer, D. T.; Roy,
R. R.; Cossey, K. N. Org. Lett. 2002, 4, 2349-2352. (g) Garcia, J.;
Vilarassa, J. Tetrahedron Lett. 1982, 23, 1127-1128. (h) Berenguer, R.;
Garcia, J.; Vilarassa, J. Synthesis 1989, 305-306. (i) Saavedra, J. E. J.
Org. Chem. 1979, 44, 860-861. (j) Nikolaides, N.; Godfrey, A. G.; Ganem,
B. Tetrahedron Lett. 1990, 31, 6009-6012. (k) Darbeau, R. W.; White, E.
H. J. Org. Chem. 2000, 65, 1121-1131. (l) Wudl, F.; Lee, T. B. K. J. Am.
Chem. Soc. 1971, 93, 271-273. (m) Garcia, J.; Gonzalez, J.; Segura, R.;
Vilarrasa, J. Tetrahedron 1984, 40, 3121-3127, and literature therein. (n)
Garcia, J.; Gonzalez, J.; Segura, R.; Urpi, F.; Vilarrasa, J. J. Org. Chem.
1984, 49, 3322-3327. (o) Kelly, T. R.; Xu, W.; Ma, Z.; Li, Q.; Bhushan,
V. J. Am. Chem. Soc. 1993, 115, 5843-5844. (p) Kelly, T. R.; Jagoe, C.
T.; Li, Q. J. Am. Chem. Soc. 1989, 111, 4522-4524. (q) Karanewsky, D.
S.; Malley, M. F.; Gougoutas, J. Z. J. Org. Chem. 1991, 56, 3744-3747.
(r) Evans, D. A.; Carter, P. H.; Dinsmore, C. J.; Barrow, J. C.; Katz, J. L.;
Kung, D. W. Tetrahedron Lett. 1997, 38, 4535-4538. (s) Webster, F. X.;
Millar, J. G.; Silverstein, R. M. Tetrahedron Lett. 1986, 27, 4941-4944.
(t) Uskokovic, M.; Gutzwiller, J.; Henderson, T. J. Am. Chem. Soc. 1970,
92, 203-204.
(23) (a) Kirsch, M.; Korth, H.-G.; Sustmann, R.; de Groot, H. Biol. Chem. 2002,
383, 389-399. (b) Butler, A. R.; Williams, D. L. H. Chem. Soc. ReV. 1993,
233-241.
(24) Other publications on supramolecular chemistry of gases from this
laboratory: (a) Kang, Y.; Zyryanov, G. V.; Rudkevich, D. M. Chem.
Commun. 2003, 2470-2471 (NO2/N2O4). (b) Xu, H.; Hampe, E. M.;
Rudkevich, D. M. Chem. Commun. 2003, 2828-2829 (CO2). (c) Hampe,
E. M.; Rudkevich, D. M. Tetrahedron 2003, 59, 9619-9625 (CO2). (d)
Zyryanov, G. V.; Hampe, E. M.; Rudkevich, D. M. Angew. Chem., Int.
Ed. 2002, 41, 3854-3857 (N2O, CO2). (e) Hampe, E. M.; Rudkevich, D.
M. Chem. Commun. 2002, 1450-1451 (CO2).
(25) (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.
(26) 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-
467.
(27) Mirvish, S. S. Cancer Lett. 1995, 93, 17-48.
9
J. AM. CHEM. SOC. VOL. 126, NO. 13, 2004 4269

A R T I C L E S
Zyryanov and Rudkevich
1
afford 8 as a colorless oil. Yield 0.72 g (90%); H NMR (CDCl3) δ
7.05 (d, J ) 7.5 Hz, 4 H), 7.01 (d, J ) 7.5 Hz, 4 H), 6.82 (t, J ) 7.0
Hz, 2 H), 6.78 (t, J ) 7.0 Hz, 2 H), 3.83 (2 × d, J ) 16.5 Hz, 8 H),
3.58-3.61 (m, 4 H), 3.40 (t, J ) 7.0 Hz, 8 H), 3.02-2.99 (m, 4 H),
1.31-1.27 (m, 4 H), 0.68 (t, J ) 7.5 Hz, 6 H); 13C NMR (CDCl3) δ
157.1, 156.2, 133.9, 133.7, 129.5, 129.4, 122.9, 122.8, 72.0, 71.1, 61.3,
38.3, 22.3, 10.0; MALDI-FTMS, m/z 619.3061 ([M + Na+]; calcd
for C38H44O6Na, 619.3030).
dry nitrogen. The dark-blue precipitate was dissolved in dry CHCl3
(0.5-1.0 mL) and used for further reactions.
(B) Procedure 2. A stock solution of NO2 (∼3 equiv) in CHCl3
was added to the solution of 1b (1 equiv) and SnCl4 (1.5 equiv) in
CHCl3 at room temperature. After 1 h, complex 2b was precipitated
upon addition of hexanes, filtered off, washed with hexanes (2×), and
dried in vacuo. Yield >95%; 1H NMR δ 7.02 (s, 8 H), 3.77 (t, J ) 7.5
Hz, 8 H), 3.60 (s, 8 H), 1.38 (m, 32 H), 1.30 (s, 36 H), 0.92 (t, J ) 7.5
Hz, 12 H); UV-vis (CDCl3) λmax ) 578 nm; FTIR (CDCl3) ν (NO+)
) 1934 cm-1. Anal. Calcd for C68H104Cl4N2O8Sn: C, 61.04; H, 7.83;
N, 2.09. Found: C, 60.96; H, 7.88; N, 2.09.
Calix[4]arene Tube (3). (A) Procedure A. A mixture of 25,27-
dihydroxy-26,28-bis(1-propyloxy)calix[4]arene (6; 1 g, 1.96 mmol), 25,-
27-bis(2-p-toluenesulfonyl(bis(oxyethyl))oxy)-26,28-bis(1-propyloxy)-
calix[4]arene (7; 1.95 g, 1.96 mmol) and Cs2CO3 (9.59 g, 30 mmol) in
MeCN (100 mL) was refluxed under nitrogen for 36-48 h. The solvent
was evaporated, and the residue was diluted with CH2Cl2 (100 mL)
and 5% aqueous HCl (100 mL). The organic layer was then separated,
washed with water (3 × 100 mL), and evaporated. Column chroma-
tography (EtOAc-hexanes, 1:10) afforded product 3 (Rf ) 0.15) as a
white crystalline solid. Yield 0.2 g (9%); mp > 250 °C; 1H NMR
(CDCl3) δ 7.18 (d, J ) 7.5 Hz, 8 H), 7.03-6.99 (d + t, 12 H), 6.84 (t,
J ) 7.5 Hz, 4 H), 3.89 (2 × d, J ) 17.0 Hz, 16 H), 3.57 (t, J ) 7.0
Hz, 8 H), 3.31 (t, J ) 7.0 Hz, 8 H), 2.58 (t, J ) 7.5 Hz, 8 H), 1.09-
1.05 (m, 8 H), 0.56 (t, J ) 7.0 Hz, 12H); 13C NMR (C2D2Cl4) δ 157.5,
156.2, 134.2, 134.1, 123.3, 122.3, 120.0, 72.0, 71.6, 69.2, 66.5, 38.3,
30.3, 22.8, 10.5; MALDI-FTMS, m/z 1179.5939 ([M + Na+]; calcd
for C76H84O10Na, 1179.5956).
(B) Procedure B. 25,27-Bis(2-hydroxyethyloxy)-26,28-bis(1-pro-
pyloxy)calix[4]arene (8; 0.8 g, 1.3 mmol) was dissolved in dry DMF
(100 mL), after which NaH (60% suspension in mineral oil, 0.127 g,
5.2 mmol) was added. 25,27-Bis(2-p-toluenesulfonyloxyethyloxy)-26,-
28-bis(1-propyloxy)calix[4]arene (9; 1.2 g, 1.3 mmol) was separately
dissolved in dry DMF (100 mL). Thus-prepared solutions of 8 and 9
were added dropwise to dry DMF (200 mL) at 60-70 °C in a 30 min
period under nitrogen. The reaction mixture was stirred at 80-90 °C
for an additional 48 h, evaporated to dryness, suspended in CH2Cl2
(100 mL), and neutralized at -10 °C with 5% aqueous HCl (100 mL).
The organic layer was separated, washed with water (3 × 100 mL),
and evaporated. Crystallization from MeCN afforded product 3 as a
white crystalline solid. Yield 0.2 g (13%).
Nitrosation Procedure with Nitrosonium Complexes. Typical
nitrosation protocol with calixarene-nitrosonium complexes is de-
scribed previously.15 Complex 4 or 5 (1 equiv) was added to a solution
of amide 10a,b (3-5 equiv) in freshly distilled CHCl3, and the reaction
mixture was stirred at room temperature for 2-3 h. The solvent was
1
evaporated, and the residue was analyzed by H NMR spectroscopy.
All runs were performed at least in duplicate. The yields of N-nitroso
amides 11a,b were 10-15% for complex 4 as a nitrosating agent and
45-50% for complex 5 as a nitrosating agent. The spectral data for
thus-obtained N-nitroso amides 11a,b were identical with those
independently obtained from amides 10a,b and NO2/N2O4 in CHCl3
(>95% yields) following the literature protocols.28 The starting amides
10a,b were synthesized by the textbook procedure upon mixing
equimolar amounts of the corresponding amines and acid chlorides in
1:1 H2O-EtOAc in the presence of K2CO3 and purified by recrystal-
lization from MeOH. No traces of the solvent were present in samples
used for nitrosation (1H NMR, CDCl3).
(A) N-Methylvalerylamide (10a). Yield 62%; 1H NMR δ 6.43 (bs,
1 H, NH), 2.69 (d, 3 H, J ) 5 Hz, NCH3), 2.09 (t, 2 H, J ) 7.5 Hz,
CH2), 1.48-1.54 (m, 2 H, CH2), 1.22-1.28 (m, 2 H, CH2), 0.81 (t, 3
H, J ) 7.5 Hz, CH3).
1
(B) N-Methyloctanoylamide (10b). Yield 66%; H NMR δ 6.13
(bs, 1 H, NH), 2.73 (d, 3 H, J ) 5 Hz, NCH3), 2.12 (t, 2 H, J ) 7.5
Hz, CH2), 1.53-1.58 (m, 2 H, CH2), 1.22-1.28 (m, 8 H, 4 × CH2),
0.83 (t, 3 H, J ) 7.5 Hz, CH3).
(C) N-Methyl-N-nitrosovaleramide (11a).29 1H NMR d 3.17 (t, 2
H, J ) 8 Hz, CH2C(O)), 3.10 (s, 3 H, N(NO)CH3), 1.75-1.81 (m, 2
H, CH2), 1.40-1.47 (m, 2 H, CH2), 0.95 (t, 3 H, J ) 8 Hz, CH3).
(D) N-Methyl-N-nitrosooctanoylamide (11b).29,30 1H NMR d 3.19
(t, 2 H, J ) 7.5 Hz, CH2C(O)), 3.12 (s, 3 H, N(NO)CH3), 1.72-1.81
(m, 2 H, CH2), 1.26-1.41 (m, 8 H, (CH2)4), 0.86 (t, 3 H, J ) 7.5 Hz,
CH3).
Mononitrosonium Complex (4). To a solution of 3 (0.005 g, 4
µmol) in dry, freshly distilled CHCl3 (1 mL), SnCl4 (0.005 g, 20 µmol)
was added, and NO2 was bubbled for 25-40 s, until purple precipitate
formed. This was filtered, washed with CHCl3 (2 × 1 mL), and dried
1
under nitrogen flow. Yield >95%; H NMR (C2D2Cl4) δ 7.12-7.08
(m, 20 H), 6.96 (t, J ) 6.5 Hz, 4 H), 4.01 (m, 8 H), 3.92, 3.86 (2 ×
d, J ) 16.5 Hz, 16 H), 3.79 (m, 8 H), 3.34 (t, J ) 7.5 Hz, 8 H), 1.05-
1.01 (m, 8 H), 0.72 (t, J ) 8.0 Hz, 12 H); 13C NMR (C2D2Cl4) δ 156.0,
134.3, 133.4, 130.9, 130.2, 124.4, 72.2, 71.0, 38.5, 29.9, 22.2, 10.0;
UV-vis (CH2Cl2) λmax 540 nm; FTIR (C2D2Cl4) ν 1932 cm-1 (NO+).
Dinitrosonium Complex (5). To a solution of 3 (0.005 g, 4 µmol)
in (CDCl2)2 (2 mL), SnCl4 (0.005 g, 20 mmol) was added, and NO2/
N2O4 was bubbled for 40 s. 1H NMR (C2D2Cl4) δ 7.35 (t, J ) 7.5 Hz,
4 H), 7.26 (d, J ) 7.0 Hz, 8 H), 7.10 (d, J ) 8.0 Hz, 8 H), 6.29 (t, J
) 7.5 Hz, 4 H), 4.25 (m, 8 H), 4.02 (m, 8 H), 3.86 (t, J ) 7 Hz, 8 H),),
3.83, 3.64 (2 × d, J ) 14 Hz, 16 H), 1.91-1.87 (m, 8 H), 1.07 (t, J )
7.5 Hz, 12 H); 13C NMR (C2D2Cl4) δ 162.0, 152.6 133.6, 133.0, 132.9,
132.4, 129.1, 75.4, 75.2, 71.3, 36.6, 29.9, 24.0, 10.6; UV-vis (CH2-
Cl2) λmax 515 nm; FTIR (C2D2Cl4) ν 1948 cm-1 (NO+).
Acknowledgment. Financial support is acknowledged from
the University of Texas at Arlington (Faculty Research En-
hancement Award to D.M.R.), the Petroleum Research Fund,
administered by the American Chemical Society, and the Alfred
P. Sloan Foundation. We are grateful to Voltaire R. Organo for
experimental assistance.
JA0392869
(28) (a) Challis, B. C.; Milligan, J. R.; Mitchell, R. C. J. Chem. Soc., Chem.
Commun. 1984, 1050-1051. (b) Torra, N.; Urpf, F.; Vilarrasa, J.
Tetrahedron 1989, 45, 863-868. (c) Itoh, T.; Nagata, K.; Matsuya, Y.;
Miyazaki, M.; Ohsawa, A. Tetrahedron Lett. 1997, 38, 5017-5020. (d)
Romea, P.; Aragones, M.; Garcia, J.; Vilarrasa, J. J. Org. Chem. 1991, 56,
7038-7042. (e) Darbeau, R. W.; Pease, R. S.; Gibble, R. E. J. Org. Chem.
2001, 66, 5027-5032. See also refs 20 and 22a,n.
(29) Kuhn, L. P.; Kleinspehn, G. G.; Duckworth, A. C. J. Am. Chem. Soc. 1967,
89, 3858-3862.
(30) Schwaier, R.; Zimmermann, F. K.; Preussmann, R. Z. Vererbungsl. 1966,
98, 309-319.
Preparation of Nitrosonium Complex (2b). (A) Procedure 1. NO2/
N2O4 gas was bubbled for 20 s through the solution of calixarene 1b
(25 mg, 2.5 × 10-5 mol) and SnCl4 (3 mL, 2.6 × 10-5 mol) in dry
CHCl3 (0.5-1.0 mL). The solvent was evaporated under the steam of
9
4270 J. AM. CHEM. SOC. VOL. 126, NO. 13, 2004