Conformation-selective synthesis and binding properties of N-benzylhexahomotriaza-p-chlorocalix[3]trinaphthylamide

Article abstract of DOI:10.1021/jo800461r

(Figure Presented) N-Benzylhexahomotriaza-p-chlorocalix[3]trinaphthylamide in partial cone conformation was selectively synthesized by appropriately controlling the steric effect during the amidation reactions of N-benzylhexahomotriaza-p-chlorocalix[3]tri

Full text of DOI:10.1021/jo800461r

Calixarenes and the related macrocycles have received a lot
of recent attention due to their molecular recognition properties.3,4
In recent years, the homocalixarenes, hexahomotrioxacalixarenes
(or oxacalix[3]arenes),5 hexahomotrithiacalixarenes (or thia-
calix[3]arenes),6 and hexahomotriazacalixarenes (or azacalix-
[3]arenes), have been synthesized as parts of a class of
compounds called expanded calixarenes.7 From a structural point
of view, they are of a similar size to 18-crown-6. However,
their topology provides 3-D cavities which can better envelop
the substrates. It is well-known that the more coordinating sites
that are present then, generally, the higher the complex stability.8
Therefore, to optimize the number of such binding sites, oxygen
and sulfur atoms on oxa- and thiacalix[3]arenes are typically
replaced with nitrogen in the azacalixarenes. Nevertheless, the
azacalixarenes have received relatively little attention, mainly
because they can only be synthesized in relatively low overall
yields. Thus, there are only a limited number of studies of the
solution conformations, solid-state structures, and complex
formation properties of these molecules and, unlike calixarenes,
the conditions for functionalization to provide a specific
conformation have rarely been reported. Previously, Hampton
andco-workers9showedthattheconformationsofazacalix[3]arenes
were cone and partial cone, based on NMR and X-ray single-
crystal studies, but most research has focused on studying only
the cone conformations.7–9 Metal complexes of the cone
conformation with an extraction method, such as UO22+ in the
presence of a high concentration of NaCl,7a lanthanide ions,7b
and alkali metals,7c have been reported. Moreover, Thue´ry et
al.10 prepared UO22+, Nd3+, and Yb3+ complexes of azacalix-
arenes without using any bases and obtained crystals of the
complexes suitable for crystallographic analyses.
Conformation-Selective Synthesis and Binding
Properties of N-Benzylhexahomotriaza-p-
chlorocalix[3]trinaphthylamide
Chatthai Kaewtong,† Nongnuj Muangsin,†
Narongsak Chaichit,‡ and Buncha Pulpoka*,†
Supramolecular Chemistry Research Unit and Organic
Synthesis Research Unit, Department of Chemistry, Faculty
of Science, Chulalongkorn UniVersity, Bangkok 10330,
Thailand, and Department of Physics, Faculty of Science
and Technology, Thammasat UniVersity (Rangsit Campus),
Pathumthani 12121, Thailand
buncha.p@chula.ac.th
ReceiVed March 5, 2008
Recently, we reported that the cone conformation of N7-
hexahomotriazacalix[3]cryptand (3) can serve as a highly
selective receptor for chloride ions.11 Its selectivity can be
altered to preferentially bind bromide ions over other halide
ions by complexing with zinc ions, presumably due to allosteric
and ion-pair effects as illustrated in Scheme 1. However, partial
cone conformation was not reported in this study. To further
N-Benzylhexahomotriaza-p-chlorocalix[3]trinaphthylamide in
partial cone conformation was selectively synthesized by
appropriately controlling the steric effect during the amida-
tion reactions of N-benzylhexahomotriaza-p-chlorocalix[3]tri-
(ethyl acetate) in cone or partial cone conformations with
use of 1-aminomethylnaphthalene. The conformation was
confirmed by 1H, 13C, and 2D NMR and X-ray single-crystal
analysis. Analyses of the complexes revealed that recognition
is strongly affected by Cd2+, Pb2+, and F- ions.
(4) Asfari, Z.; Bo¨hmer, V.; Harrowfield, J. Calixarenes 2001; Kluwer
Academic Publishers: Dordretch, The Netherlands, 2001.
(5) (a) Dhawan, B.; Gutsche, C. D. J. Org. Chem. 1983, 48, 1536. (b) Zerr,
P.; Mussrabi, M.; Vicens, J. Tetrahedron Lett. 1991, 32, 1879. (c) Hampton,
P. D.; Bencze, Z.; Tong, W.; Daitch, C. E. J. Org. Chem. 1994, 59, 4838. (d)
Ashram, M.; Mizyed, S.; Georghiou, P. E. J. Org. Chem. 2001, 66, 1473. (e)
Ashram, M. J. Inclusion Phenom. 2006, 54, 253. (f) Tsubaki, K.; Otsubo, T.;
Tanaka, K.; Fuji, K. J. Org. Chem. 1998, 63, 3260. (g) Tsubaki, K.; Mukoyoshi,
K.; Otsubo, T.; Fuji, K. Chem. Pharm. Bull. 2000, 48 (6), 882. (h) Tsubaki, K.;
Morimoto, T.; Otsubo, T.; Kinoshita, T.; Fuji, K. J. Org. Chem. 2001, 66, 4083.
(6) Masci, B.; Nierlich, M.; Thue´ry, P. New J. Chem. 2002, 26, 766.
(7) (a) Takemura, H.; Yoshimura, K.; Khan, I. U.; Shinmyozu, T.; Inazu, T.
Tetrahedron Lett. 1992, 33, 5775. (b) Takemura, H.; Shinmyozu, T.; Miyura,
H. J. Inclusion Phenom. Macrocyclic Chem. 1994, 19, 193. (c) Hampton, P. D.;
Tong, W. D.; Wu, S.; Duesler, E. N. J. Chem. Soc., Perkin Trans. 2. 1996,
1127.
On the basis of the concepts provided by host-guest
chemistry, cation and anion sensing has recently risen to a
dominant position in research devoted to the detection of
designated species.1 This rapid growth is derived from the
realization of the diverse roles played by cations and anions in
biological and environmental systems.2,3
† Chulalongkorn University.
‡ Thammasat University (Rangsit Campus).
(8) Schneider, H-J.; Yatsimirsky, A. K. Principle and methods in Supramo-
lecular Chemistry; Wiley: New York, 2000.
(1) (a) Lehn, J.-M. Supramolecular Chemistry, Concepts and PerspectiVes;
WCH:Weinheim, Germany, 1995. (b) Inoue,Y.; Gokel, G. W. Cation Binding
by Macrocycles, Complexation of Cationic Species by Crown Ether; Marcel
Dekker: New York, 1990.
(2) (a) Gutsche, C. D. Calixarenes, Monographs in Supramolecular Chem-
istry; Stoddart, J. F., Ed.; Royal Society of Chemistry: Cambridge, U.K., 1989;
Vol. 1. (b) Anslyn, E. V. J. Org. Chem. 2007, 72, 687.
(3) Lumetta, G. J.; Rogers, R. D.; Gopalan, A. S. Calixarenes for Separations;
American Chemical Society: Washington, DC, 2000.
(9) Chirakul, P.; Hampton, P. D.; Duesler, E. N. Tetrahedron Lett. 1998,
39, 5473.
(10) (a) Thue´ry, P.; Nierlich, M.; Vicens, J.; Takemura, H. J. Chem. Soc.,
Dalton Trans. 2000, 42, 279. (b) Thue´ry, P.; Nierlich, M.; Vicens, J.; Masci,
B.; Takemura, H. Eur. J. Inorg. Chem. 2001, 637. (c) Thue´ry, P.; Nierlich, M.;
Vicens, J.; Takemura, H. Polyhedron 2000, 19, 2673.
(11) Kaewtong, C.; Fuangswasdi, S.; Muangsin, N.; Chaichit, N.; Vicens,
J.; Pulpoka, B. Org. Lett. 2006, 8, 1561.
5574 J. Org. Chem. 2008, 73, 5574–5577
10.1021/jo800461r CCC: $40.75 2008 American Chemical Society
Published on Web 06/25/2008

SCHEME 1. Cone Conformation of
N7-Hexahomotriazacalix[3]cryptand (3) Can Serve As a
Highly Selective Receptor for Chloride Ions or Be Adapted
to Preferentially Bind Bromide Ions in the Present Zinc Ions
FIGURE 1. ORTEP drawing of (a) N-benzylhexahomotriaza-p-
chlorocalix[3]tri(ethyl acetate) (2a) and (b) N-benzylhexahomotriaza-
p-chlorocalix[3]trinaphthylamide (1). The displacement ellipsoids are
drawn at the 50% probability level.
SCHEME 2. Synthesis of 1a
5.00, 4.93, and 4.89 ppm with germinal coupling constants of
4.8, 5.6, 4.8, 4.8, and 5.2 Hz, respectively. In the parent
hexahomotriazacalix[3]arene, which adopts a regular C3V cone
conformation, the six protons of ArcalixH exists as a singlet at δ
7.01 ppm.10 In this case, the three singlets of ArcalixH are
observed at 6.51, 6.44, and 6.36 ppm. The 13C NMR spectrum
also confirms the partial cone conformation of the azacalix[3]arene
macroring of 1. ArnapCH2NH appears as two peaks (41.6, 41.2
ppm) and ArcalixCH2N splits into four peaks (72.8, 52.7, 52.5,
and 52.0 ppm). 13C signals of Arcalix connected with hydrogen
also have three peaks, at 130.2, 130.1, and 129.5 ppm. These
findings suggest that the three O-substituents have different
environments, which implies that 1 is in a stable partial cone
conformation. The X-ray single-crystal structure of 113 also
strongly supports the partial cone conformation, as shown in
Figure 1b. The results show the cavity of azacalix[3]arene
macroring (7.92 × 4.92 Å2) for cation and free N-H for anion
binding sites of 1.
It is well-known that hexahomotriazacalix[3]arene is a
strong metal ion complexing agent7,10 and an amide derivative
that can complex anions.11 Generally, a naphthylene-based
fluorophore can form a monomer and excimer13 that can be
observed in a fluorescent spectrum at wavelengths of 336
and 423 nm, respectively. However, the excimer formation
of fluorophores that contain more than one fluorogenic unit
can be either inter- or intramolecular, in which the former
depends on the concentration and solvent polarity. The ratio
of excimer to monomer can be observed by the ratio of
intensities of excimer to monomer (Iexcimer/Imonomer or Ie/Im).
From the fluorescent spectrum, it was observed that ligand
1 exhibits a strong monomer emission at 336 nm and an
excimer emission at 423 nm, suggesting that the two
naphthalene units are in a face-to-face π-stack so as to form
a dynamic excimer.14 The ratio of Ie/Im increases when the
concentration of fluorophore 1 decreases (Figure S1, Sup-
porting Information). This may be because, at low concentra-
a Reagents and conditions: (a) ethyl bromoacetate, NaH, THF, DMF,
reflux, 72 h, 2a (21%) and 2b (31%); (b) 1-aminomethylnaphthalene,
toluene:MeOH (1:1), rt, 3 d, 1 (41%); (c) 1-aminomethylnaphthalene,
toluene:MeOH (1:1), rt, 7 d, 1 (42%).
understand the properties of azacalix[3]arenes, this work reports
a conformational selective synthesis, the X-ray crystal structures,
and the binding properties of N-benzylhexahomotriaza-p-
chlorocalix[3]trinaphthylamide (1 in Scheme 2). To the best of
our knowledge, this is the first example showing the complex
formation ability of a partial cone azacalix[3]arene.
The synthesis of N-benzylhexahomotriaza-p-chlorocalix[3]-
trinaphthylamide (1) was carried out as schematically shown
in Scheme 2. Alkylation of N-benzylhexahomotriaza-p-
chlorocalix[3]arene with ethyl bromoacetate in the presence of
NaH in THF/DMF produced compound 2a (cone conformation,
21% yield) and compound 2b (partial cone conformation, 31%
yield). The reactions between 2a and 2b with 1-aminomethyl-
naphthalene afforded only the partial cone conformer of
N-benzylhexahomotriaza-p-chlorocalix[3]trinaphylamide (1) with
41% and 42% yields, respectively. More interestingly, during
the preparation of 1 by starting with 2a, the conformation
changed from cone to partial cone. This may be due to the small
energetic barrier of aromatic flipping by passing the para position
through the cavity for cone-to-partial cone inversion of
azacalix[3]arene, which provides a more stable partial cone
conformer as a result of the steric effect and solvent polarity.12
The structure of compound 2a was confirmed by X-ray single-
crystal analysis, as shown in Figure 1a.
(12) Iwamoto, K.; Ikeda, A.; Araki, K.; Harada, T.; Shinkai, S. Tetrahedron
Lett. 1993, 49, 9937.
(13) X-ray data were collected on a Bruker SMART CCD area detector. The
crystal structure was solved by direct methods and refined by full-matrix least-
squares. All non-hydrogen atoms were refined anisotropically, and hydrogen
atoms were refined by using the riding model. All calculations were performed
with a crystallographic software package, WinGX v1.64.05. Crystal data for 1:
The proposed partial cone conformation of N-benzylhexaho-
motriaza-p-chlorocalix[3]trinaphylamide (1) was confirmed by
1H, 13C, 2D NMR and X-ray single crystal studies (Supporting
1
j
C84H75Cl3N6O6 · 3H2O, Mr ) 1424.90, monoclinic, space group P1, a )
Information). In the H NMR spectrum of 1, the methylene
16.1795(3) Å, b ) 16.5809(3) Å, c ) 16.6482(2) Å, R ) 92.624(1)°, ꢀ )
105.880(1)°, γ ) 112.174(1)°, V ) 3921.97(11) Å3, Z ) 2, Fcalc ) 1.207 g
cm-3, 2θmax ) 30.54°, Mo KR (λ ) 0.71075 Å), µ ) 0.176 mm-1, θ-ω scans,
T ) 293(2) K, 28143 independent reflections, 20620 unique reflections (I >
2.0σ(I)), 924 refined parameters, R1 ) 0.1276, Rw ) 0.3142, ∆Fmax ) 1.204 e
Å-3, ∆Fmin )-0.395 e Å-3; CCDC 673516. See the Supporting Information for
crystallographic data in CIF format.
protons of the ArcalixCH2N bridges are presented as two AB
doublets at 3.91 (JH-H ) 15.0 Hz), 3.58 (JH-H ) 15.0 Hz),
2.57 (JH-H ) 13.4 Hz), and 2.28 (JH-H ) 13.4 Hz) ppm and as
a signal in a multiplet at 2.99-2.71 ppm. The other doublets
for the methylene protons of ArnapCH2NH appear at 5.11, 5.04,
J. Org. Chem. Vol. 73, No. 14, 2008 5575

TABLE 1. Stability Constants (log ꢀ)a of 1:1 Complexes of 1 with
Cations and Anions in DMSO by the UV-Vis Titration Method (T
) 25 °C, I ) 0.01 M Bu4NPF6)
cation
log ꢀ (M-1)
anion
log ꢀ (M-1)
Mg2+
Ca2+
Co2+
Ni2+
Cu2+
Zn2+
Cd2+
Hg2+
Pb2+
2.13 (0.01)b
2.01 (0.04)b
4.08 (0.09)b
1.83 (0.04)b
2.06 (0.08)b
3.23 (0.09)b
4.53 (0.04)b
2.12 (0.01)b
4.68 (0.04)b
F-
4.21 (0.09),b 9.71 (0.01)c
Cl-
Br-
I-
2.37 (0.05)b
not determined
not determined
2.03 (0.01)b
-
NO3
ClO4
H2PO4
AcO-
BzO-
2.20 (0.01)b
-
-
not determined
2.43 (0.02),b 9.29 (0.03)c
2.83 (0.01),b 9.43 (0.03)c
a Mean values of n g 3 (for cations) and n g 2 (for anions) of
independent determinations with standard deviation σn-1 on the mean in
parentheses. b 1:1 complex (AL). c 2:1 complex (A2L).
FIGURE 2. Fluorescence changes (I - Io) of 1 upon addition of various
metal ions. Conditions: 1 (1 µM) in DMSO, excitation at 285 nm, metal
nitrate and chloride (300 equiv) in DMSO. I is the fluorescence emission
intensity of complexes 1. Io is the fluorescence emission intensity of
free 1.
ion preferentially binds by nitrogen atoms of the azacalix[3]arene
macroring and is weakly chelated by the carbonyl groups from
both sides of azacalix[3]arene, and that consequently the PET
and heavy metal effects are excluded. The azacalix[3]arene
template, which has a similar structure to that of azacrown
ether,16 exhibits excellent binding with Cd2+ and shows, for
the first time, the advantage of the azacalixarene framework
over the parent calixarene.7 UV-vis spectroscopy was employed
to determine the stoichiometry and stability constants for the
complexes with use of the SIRKO program.17 According to the
extent of the observed absorption spectra changes, the associa-
tion constants of 1 were obtained, and are summarized in Table
1. The data indicate that ligand 1 binds strongly with Pb2+ (log
ꢀ ) 4.68 M-1) and Cd2+ (log ꢀ ) 4.53 M-1). The titration
profiles of absorption changes of 1 with Cd2+ and Pb2+ are
shown in Figures S3 and S4 (Supporting Information) which
showthedifferentpatterns.Theabsorptionsoftheazacalix[3]arene
unit in receptor 1 at wavelengths of 285 and 296 nm strongly
decrease upon an addition of Cd2+. In case of Pb2+, the
decreases of absorption of these two wavelengths are less
pronounced, while the absorption at a wavelength around 265
nm strongly increases. This result confirms that both cations
were bound with different modes.
FIGURE 3. Fluorescence emission spectra of 1 upon addition of
various anions. Conditions: 1 (0.1 µM) in DMSO, excitation at 285
nm, TBAX (300 equiv) in DMSO.
tions where there is a low percentage of intermolecular
interaction, the two naphthyl groups which are on the same
side of the azacalix[3]arene platform form an intramolecular
excimer and give an excimer emission at 423 nm.
The other naphthyl moiety, where no intermolecular interac-
tion occurs, remains a monomer, but its monomer emission at
336 nm is quenched because the nitrogen atoms are sharing
electrons with PET. At higher concentrations, the intermolecular
interaction increases, leading to the formation of a hydrogen
bond between the amide groups from a side containing a single
residue. This hydrogen bond formation prevents the face-to-
face stacking of naphthyl moieties and the PET process, leading
to increased monomer emission.
For the anion sensor study, the fluorescence reveals a
quenching effect from a PET mechanism on the monomer peak.
The excimer peak, however, has a much lower effect, indicating
that allosteric effect-induced conformation changes do not favor
1
the binding of anions. The H MNR spectra of 1 anions also
strongly support this notion revealing that only the signals of
amide protons shift (Figure S2, Supporting Information), and
thus that anions were likely bound by hydrogen bonds with the
amide groups.
To obtain an insight into the selectivity of anion binding,
UV-vis spectroscopy was employed to study the interaction
The fluorescence intensity changes of 1 were investigated to
determine the cation (Figure 2) and anion (Figure 3) binding
abilities. In the case of cations, it was found that 1 exhibits
Pb2+, Hg2+ and Co2+ (strong quenching), and Cd2+ (strong
enhancing) selectivity over the other metal cations studied, as
shown in Figure 2. These data imply that 1 binds metal ions
with different modes. In the case of Pb2+, only excimer
fluorescence is strongly quenched, which is likely to be due
not only to the reverse PET from the naphthyl groups to the
electron-deficient carbonyl oxygen atoms but also to a heavy-
metal ion effect.15 This may then suggest that Pb2+ is strongly
bound in a cavity on the side containing two naphthylamide
units.
(14) (a) Galindo, F.; Becerril, J.; Burguete, M. I.; Luis, S. V.; Vigara, L.
Tetrahedron Lett. 2004, 45, 1659. (b) Roy, M. B.; Samanta, S.; Chattopadhyay,
G.; Ghosh, S. J. Lumin. 2004, 106, 141.
(15) (a) Kim, J. S.; Quang, D. T. Chem. ReV. 2007, 107, 3780. (b) Kim,
S. K.; Kim, S. H.; Kim, H. J.; Lee, S. H.; Lee, S. W.; Ko, J.; Bartsch, R. A.;
Kim, J. S. Inorg. Chem. 2005, 44, 7866. (c) Choi, J. K.; Kim, S. H.; Yoon, J.;
Lee, K.-H.; Bartsch, R. A.; Kim, J. S. J. Org. Chem. 2006, 71, 8011. (d) Kim,
J. S.; Kim, H. J.; Kim, H. M.; Kim, S. H.; Lee, J. W.; Kim, S. K.; Cho, B. R.
J. Org. Chem. 2006, 71, 8016.
(16) (a) Cakir, U.; Cicek, B. Transition Metal. Chem. 2004, 29, 263. (b)
Costero, A. M.; Salvador Gil, S.; Sanchis, J.; Perans´ı, S.; Sanz, V.; Williams,
J. A. G. Tetrahedron 2004, 60, 6327. (c) Liang, X.; Parkinson, J. A.; Parsons,
S.; Weisha¨upl, M.; Sadler, P. J. Inorg. Chem. 2002, 41, 4539. (d) Costero, A. M.;
Monrabal, E.; Sanjuan, F. Tetrahedron 1999, 55, 15141. (e) Nelson, J.; Mckee,
V.; Morgan, G. Prog. Inorg. Chem. 2007, 47, 167–316.
In the case of Cd2+, both monomer and excimer emissions
increased with its presence, strongly suggesting that the Cd2+
(17) Vetrogon, V. I.; Lukyanenko, N. G.; Schwing-well, M. J.; Arnaud-Neu,
F. Talanta 1994, 41, 2105.
5576 J. Org. Chem. Vol. 73, No. 14, 2008

+ H]+. Anal. Calcd for for C57H60Cl3N3O9: C, 65.99; H, 5.83; N,
4.05. Found: C, 65.82; H, 5.92; N, 3.93.
of compounds 1 with anionic guests. Upon the addition of
anions, the absorption spectra of 1 changed (see Table S1,
Supporting Information). From the derived stability constants
(Table 1) of compound 1 complexes with anions, it can be
concluded that 1 prefers to complex F- over the other anions
tested by forming 1:1 complexes.
Synthesis of N-Benzylhexahomotriaza-p-chlorocalix[3]trinap-
thylamide (1). A solution of 2a (0.135 g, 0.130 mmol) was charged
with a solution of 1-napthymethylamine (0.072 g, 0.456 mmol) in
1:1 methanol:toluene mixture (10 mL). The solution was refluxed
for 3 days. After removing the solvents, the crude mixture was
purified by column chromatography of the precipitate on silica gel
(hexane/EtOAc ) 3:2, v/v), which gave 1 (0.073 g, 0.053 mmol,
41%) as a white solid. A solution of 2b (0.207 g, 0.200 mmol)
was charged with a solution of 1-napthymethylamine (0.207 g, 0.700
mmol) in 1:1 methanol:toluene mixture (10 mL). The solution was
refluxed for 7 days. After removing the solvents, the crude mixture
was purified by column chromatography of the precipitate on silica
gel (hexane/EtOAc ) 3:2, v/v), which gave 1 (0.114 g, 0.087 mmol,
In summary, the partial-cone conformation of N-benzyl-
hexahomotriaza-p-chlorocalix[3]trinaphthylamide (1) was se-
lectively synthesized from both cone and partial-cone triester
intermediates coupling with 1-aminomethylnaphthalene. The
crystal structures of 1 and 2a were confirmed by X-ray
1
crystallography. On the basis of fluorescent, UV-vis, and H
NMR spectra changes upon cation and anion complex formation,
it has been noted that 1 displays strong binding with Cd2+ (by
using nitrogen at the azacalix[3]arene framework), Pb2+ and
Co2+ (by using the carbonyl of amide groups from the side of
azacaliz[3]arene containing two naphthyl groups), and F- (by
using hydrogen bonds between the NH part of the amide with
anions).
1
42%) as a white solid: H NMR (400 MHz, CDCl3) δ 8.10-8.08
(m, 3H, ArHnap), 8.01-7.97 (m, 4H, ArHnap), 7.91 (d, JH-H ) 7.2
Hz, 2H, ArHnap), 7.64-7.57 (m, 8H, ArHnap), 7.64-7.57 (m, 4H,
ArHnap), 7.32-7.21 (m, 9H, ArHcalix), 7.14 (d, JH-H ) 6.8 Hz, 2H,
ArHcalix), 7.09 (d, JH-H ) 7.6 Hz, 4H, ArHcalix), 7.02 (s, 1H,
CH2NHCO), 6.86 (s, 2H, CH2NHCO), 6.51 (s, 2H, ArHcalix), 6.44
(s, 2H, ArHcalix), 6.36 (s, 2H, ArHcalix), 5.11 (d, JH-H ) 4.8 Hz,
2H, ArCH2NH), 5.04 (d, JH-H ) 5.6 Hz, 1H, ArCH2NH), 5.00 (d,
JH-H ) 4.8 Hz, 1H, ArCH2NH), 4.93 (d, JH-H ) 4.8 Hz, 1H,
ArCH2NH), 4.89 (d, JH-H ) 5.2 Hz, 1H, ArCH2NH), 3.91 (d, JH-H
Experimental Section
Synthesis of N-Benzylhexahomotriaza-p-chlorocalix[3]tri(ethyl
acetate) (2). The synthetic procedures of 2a and 2b have been
modified from our previous work11 by replacing the methyl
bromoacetate with ethyl bromoacetate. Column chromatography on
silica gel (hexane/EtOAc ) 9:1, v/v) of crude product afforded a
21% yield of 2a (X-ray data demonstrated in the Supporting
) 15.2 Hz, 2H, ArCH2N), 3.80 (s, 2H, OCH2CO), 3.58 (d, JH-H
)
14.8 Hz, 2H, ArCH2N), 3.09 (s, 2H, OCH2CO), 2.99-2.71 (m,
12H, ArCH2N and OCH2CO), 2.57 (d, JH-H ) 12.8 Hz, 2H,
ArCH2N), 2.28 (d, JH-H ) 14.0 Hz, 2H, ArCH2N); 13C NMR (100
MHZ, CDCl3) δ 167.3, 167.2, 153.1, 152.0, 138.6, 137.8, 134.2,
134.1, 133.5, 133.3, 133.1, 132.5, 131.7, 131.5, 130.2, 130.1, 129.7,
129.5, 129.3, 129.2, 129.1, 129.0, 128.8, 128.7, 128.5, 128.4, 128.3,
127.7, 127.5, 127.1, 127.0, 126.4, 126.3, 126.0, 125.5, 123.9, 123.6,
72.8, 71.4, 63.0, 60.0, 52.7, 52.5, 52.0, 41.6, 41.2; IR (KBr) ν 3419,
3059, 2921, 2837, 2810, 1679, 1594, 1524, 1436, 1364, 1251, 1193,
1124, 1041, 884, 797, 789, 745, 701 cm-1; MS (MALDI-TOF)
calcd for [C84H75Cl.3N6O6]+ m/z 1368.48, found 1369.67 [M + H]+.
Anal. Calcd for C84H75Cl.3N6O6: C, 73.59; H, 5.51; N, 6.31. Found:
C, 73.56; H, 5.53; N, 6.14.
1
Information) (0.135 g, 0.130 mmol) as a deep yellow oil. 2a: H
NMR (400 MHz, CDCl3) δ 7.34-7.26 (m, 12H, ArH), 7.18 (t,
3H, JH-H ) 7.2 Hz, ArH), 6.90 (s, 6H, ArH), 4.28 (s, 6H,
OCH2CO), 4.22 (q, 6H, JH-H ) 7.6 Hz, OCH2CH3), 3.61 (s, 6H,
NCH2Ar), 3.44 (dd, 12H, JH-H ) 14.4, 7.6 Hz, NCH2Ar), 1.28 (t,
9H, JH-H ) 7.2 Hz, OCH2CH3); 13C NMR (100 MHZ, CDCl3) δ
169.1, 152.3, 139.2, 133.9, 130.1, 129.0, 128.9, 128.9, 128.6, 127.3,
71.0, 62.4, 52.5, 52.1, 14.4; IR (KBr) ν 3063, 3028, 2981, 2929,
2803, 1757, 1448, 1372, 1292, 1188, 1118, 1065, 1030, 879, 743,
701 cm-1; MS (MALDI-TOF) calcd for [C57H60Cl3N3O9]+ m/z
1035.34, found 1036.92 [M + H]+. Anal. Calcd for C57H60Cl3N3O9:
C, 65.99; H, 5.83; N, 4.05. Found: C, 65.95; H, 5.71; N, 4.00. 2b
Acknowledgment. The authors gratefully acknowledge the
ThailandResearchFund(TRF)forfinancialsupport(RMU4880041
and RTA4880008) and the Royal Golden Jubilee Ph.D. Program
of TRF (PHD/0137/2546).
1
(pale yellow solid, 31%): H NMR (400 MHz, CDCl3) δ 7.57 (d,
J ) 7.6 Hz, 2H, ArH), 7.31 (t, J ) 7.6 Hz, 3H, ArH), 7.38-7.30
(m, 10H, ArH), 7.02 (s, 4H, ArH), 6.98 (s, 2H, ArH), 4.31 (br d,
2H, OCH2CO), 4.15 (s, 4H, OCH2CH3), 4.13 (s, 2H, OCH2CH3),
4.11 (br d, 2H, OCH2CO), 3.79-3.22 (m, 20H, OCH2CO and
NCH2Ar), 1.24 (m, 9H, OCH2CH3); 13C NMR (100 MHz, CDCl3)
δ 169.1, 169.0, 155.8, 154.1, 139.4, 138.6, 134.8, 133.4, 132.9,
131.6, 130.4, 129.6, 129.3, 129.2, 128.8, 128.5, 128.4, 128.1, 127.4,
127.3, 70.8, 70.3, 63.0, 60.9, 59.4, 53.0, 52.7, 52.4, 14.4, 14.3; IR
(KBr) ν 3063, 3028, 2981, 2922, 2852, 2804, 1756, 1446, 1376,
1291, 1187, 1121, 1063, 1030, 891, 743, 700 cm-1; MS (MALDI-
TOF) calcd for [C54H54Cl3N3O9]+ m/z 1035.34, found 1036.92 [M
Supporting Information Available: Experimental proce-
dures and spectroscopic data for all new compounds including
NMR spectra and crystal structures of N-benzylhexahomotri-
aza-p-chlorocalix[3]trinaphthylamide (1) (CIF) and N-benzyl-
hexahomotriaza-p-chlorocalix[3]tri(ethyl acetate) (2a) (CIF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO800461R
J. Org. Chem. Vol. 73, No. 14, 2008 5577