Synthesis and structure of upper-rim 1,3-alternate tetraoxacalix[2]arene[2] triazine azacrowns and change of cavity in response to fluoride anion

Article abstract of DOI:10.1021/jo0706168

(Chemical Equation Presented) The upper-rim 1,3-alternate tetraoxacalix[2]arene[2]triazine azacrowns were constructed effectively by macrocyclic condensation reaction of diamines with dichlorinated tetraoxacalix[2]arene[2]triazine intermediates that were

Full text of DOI:10.1021/jo0706168

Synthesis and Structure of Upper-Rim 1,3-Alternate
Tetraoxacalix[2]arene[2]triazine Azacrowns and Change of Cavity in
Response to Fluoride Anion
Bao-Yong Hou, De-Xian Wang, Hai-Bo Yang, Qi-Yu Zheng, and Mei-Xiang Wang*
Beijing National Laboratory for Molecular Sciences, Laboratory of Chemical Biology,
Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100080, China
mxwang@iccas.ac.cn
ReceiVed March 24, 2007
The upper-rim 1,3-alternate tetraoxacalix[2]arene[2]triazine azacrowns were constructed effectively by
macrocyclic condensation reaction of diamines with dichlorinated tetraoxacalix[2]arene[2]triazine
intermediates that were synthesized from the stepwise fragment coupling reactions of 3,5-dihydroxybenzoic
acid esters with cyanuric chlorides. Because of the formation of conjugation of amino groups with triazine
rings, tetraoxacalix[2]arene[2]triazine azacrowns existed in a mixture of syn- and anti-isomeric forms.
Both fluorescence titration and 1H NMR spectroscopic study showed that tetraoxacalix[2]arene[2]triazine
azacrowns interacted with fluoride anion, leading to cavity changes of the host molecules.
Introduction
of a crown ether into calix[n]arenes has led to the generation
of calix[n]crowns, a new type of cavity molecules for selective
cation recognition.4,5 It is interesting to note that most of the
calix[n]crowns reported contain a lower-rim crown ether moiety
because of the advantageous reactivity of the phenol functional-
ity of the calix[n]arenes.4 The upper-rim calix[n]crowns,5
however, have only been scatteringly investigated, most prob-
ably because of the synthetic difficulties. Although the study
of calix[n]arenes and their analogous calixaromatics is still
increasing, there is a growing interest in heteroatom-bridged
calix(hetero)aromatics.6-10 By comparison with calix[n]arenes
and calixheteroarenes such as calixpyrroles,11 calixpyridines,12
Calix[n]arenes are useful macrocyclic host molecules in
supramolecular chemistry because of their easy availability,
various conformational structures, and powerful binding ability
toward different guest species.1-3 Calix[n]arenes also act as the
versatile platforms for the construction of elaborate host
molecules with desired functions.1-3 For example, incorporation
(1) (a) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry:
Cambridge, 1989. (b) Gutsche, C. D. Calixarenes ReVisited; The Royal
Society of Chemistry: Cambridge, 1998.
(2) (a) Calixarenes in Action; Mandolini, L., Ungaro, R., Eds.; Imperial
College Press: London, 2000. (b) Lumetta, G. J.; Rogers, R. D.; Gopalan,
A. S. Calixarenes for Separation; American Chemical Society: Washington,
DC, 2000.
(3) Calixarenes 2001; Asfari, Z., Bo¨hmer, V., Harrowfield, J., Vicens,
J., Saadioui, M., Eds.; Kluwer Academic Publishers: Dordrecht, The
Netherlands, 2001.
(4) For a review, see: Casnati, A.; Ungaro, R.; Asfari, Z.; Vicens, J.
Crown Ethers Derived from Calix[4]arenes. In Calixarenes 2001; Asfari,
Z., Bo¨hmer, V., Harrowfield, J., Vicens, J., Saadioui, M., Eds.; Kluwer
Academic Publishers: Dordrecht, The Netherlands, 2001; Chapter 20, pp
365-384 and references therein.
(5) (a) van Loon, J.-D.; Groenen, L. C.; Wijmenga, S. S.; Verboom, W.;
Reinhoudt, D. N. J. Am. Chem. Soc. 1991, 113, 2378. (b) Paek, K.; Ihm,
H. Chem. Lett. 1996, 311. (c) Ihm, H.; Kim, H.; Paek, K. J. Chem. Soc.,
Perkin Trans. 1 1997, 1997. (d) Wasikiewicz, W.; Rokicki, G.; Roz´niecka,
E.; Kielkiewicz, J.; Brzo´zka, Z.; Bo¨hmer, V. Monatsh. Chem. 1998, 129,
1169.
(6) For a useful overview of heteroatom-bridged calixarenes, see: Ko¨nig,
B.; Fonseca, M. H. Eur. J. Inorg. Chem. 2000, 2303.
(7) For a very recent review on thiacalixarenes, see: Morohashi, N.;
Narumi, F.; Iki, N.; Hattori, T.; Miyano, S. Chem. ReV. 2006, 106, 5291.
10.1021/jo0706168 CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/05/2007
5218
J. Org. Chem. 2007, 72, 5218-5226

1,3-Alternate Tetraoxacalix[2]arene[2]triazine Azacrowns
FIGURE 1. X-ray molecular structure of 11: top (left) and side (middle and right) views. Selected interatomic distances (Å): N(1)‚‚‚N(4) 4.591,
C(2)‚‚‚C(11) 9.240, Cl(1)‚‚‚Cl(2) 12.313, C(4)‚‚‚C(13) 4.579, C(7)‚‚‚C(16) 4.145, N(4)‚‚‚C(4), 3.284, C(4)‚‚‚N(1) 3.209, N(1)‚‚‚C(13) 3.274, C(13)‚
‚‚N(4) 3.200. Selected bond lengths (Å): C(10)‚‚‚O(2) 1.334, O(2)‚‚‚C(9) 1.413, C(5)‚‚‚O(1) 1.411, O(1)‚‚‚C(3) 1.345, C(1)‚‚‚O(4) 1.337, O(4)‚
‚‚C(18) 1.404, C(14)‚‚‚O(3) 1.410, O(3)‚‚‚C(12) 1.333. Selected bond angles: C(10)-O(2)-C(9) 116.3°, C(5)-O(1)-C(3) 116.7°, C(1)-O(4)-
C(18) 115.3°, C(14)-O(3)-C(12) 115.7°.
FIGURE 2. 1H NMR spectrum of a mixture of 14a and 14a′ in CDCl3 at 298 K. Inset: partial expansion of the spectrum.
SCHEME 1. Reaction of Tetraoxacalix[2]arene[2]triazine 1
with Diamine 2b
SCHEME 2. Synthesis of 3,5-Dihydroxybenzoic Acid Esters
4 and 7
and other calixaromatics13 in which the (hetero)arene units are
linked by methylenes, introduction of heteroatoms into the
bridging positions has led to a wide variety of macrocyclic
molecules. Because of the different electronic nature of het-
eroatoms from carbon, the heteroatom-bridged calix(hetero)-
aromatics exhibit interesting structure and molecular recognition
properties.6-10 For example, we9d-f have shown that, because
of the intrinsic nature of nitrogen that can adopt sp2 and/or sp3
electronic configurations to form or not to form conjugation
with its adjacent aromatic rings, azacalix[n]pyridines and
azacalix[m]arene[n]pyridines are able to pre-organize into
different conformational and cavity structures to interact with
metal ions,9f anions,9e fullerenes,9d,e and other small neutral
molecules. Very recently, we8a,k reported an efficient and high-
yielding synthesis of heteroatom-bridged calix[2]arene[2]-
triazines based on a fragment coupling approach using cheap
and readily available cyanuric chloride and different aromatic
dinucleophilic agents. The cavity of the resulting heteroatom-
bridged calix[2]arene[2]triazines can be tuned by the combina-
tion of bridging oxygen and nitrogen atoms and by the
substituents on linking nitrogen atoms. Having considered the
reactivity of the dichloro substituents on the triazine components
in heteroatom-bridged calix[2]arene[2]triazines, we envisioned
J. Org. Chem, Vol. 72, No. 14, 2007 5219

Hou et al.
SCHEME 3. Synthesis of Tetraoxacalix[2]arene[2]triazines 11 and 12
SCHEME 4. Synthesis of Upper-Rim Tetraoxacalix[2]arene[2]triazine Azacrowns
TABLE 1. Synthesis of Upper-Rim
arene[2]triazine 1, obtained readily from a two-step fragment
coupling stretagy,8a underwent reaction rapidly with diamine
2b. Unfortunately, no formation of crown product was observed.
Instead, the reaction gave a mixture of unseparable oligomers
(Scheme 1). The formation of oligomers rather than the desired
crown was most probably because calix[2]arene[2]triazine 1 was
very fluxional in solution.8a,k In other words, the rapid inter-
conversion of the conformers of 1 did not favor its macrocyclic
condensation with 2b. To decrease the flexibility of tetraoxacalix-
[2]arene[2]triazine macrocycle and therefore to increase the
chance of forming calixcrown structure, we then decided to
introduce a bulky group such as benzoxycarbonyl on the benzene
Tetraoxacalix[2]arene[2]triazine Azacrowns
entry
product
Ar
n
yield (%)a syn/antib syn/antib,c
1
2
3
4
5
6
7
8
14a + 14a′ phenyl
14b + 14b′ phenyl
14c + 14c′ phenyl
14d + 14d′ phenyl
15a + 15a′ 1-pyrenyl
15b + 15b′ 1-pyrenyl
15c + 15c′ 1-pyrenyl
15d + 15d′ 1-pyrenyl
4
2
1
0
4
2
1
0
79
79
56
29d
85
82
75
23
1.1:1
0:1
1.5:1
2:1
1:1
0:1
1.1:1
0:1
1.6:1
5:1
1:1
0:1
1.6:1
2.2:1
1.7:1
4.5:1
a Isolated yield. b Determined by 1H NMR spectrum in CDCl3 at 298 K.
c After treatment with D2O. d Product 16 was isolated in 19% yield.
that these novel heteroatom-bridged calixaromatics might
provide a useful scaffold for the construction of upper-rim
calixaromatic crowns. It was also expected that the interaction
of the crown with the external stimulus would result in the
molecular motion, namely, the change of conformational
structure. Herein, we report the construction of upper-rim 1,3-
alternate tetraoxacalix[2]arene[2]triazine azacrowns, their struc-
tures, and the change of cavity in response to the treatment of
fluoride anion.
(8) For recent examples of oxygen-bridged calixaromatics, see: (a) Wang,
M.-X.; Yang, H.-B. J. Am. Chem. Soc. 2004, 126, 15412. (b) Katz, J. L.;
Feldman, M. B.; Conry, R. R. Org. Lett. 2005, 7, 91. (c) Katz, J. L.; Selby,
K. J.; Conry, R. R. Org. Lett. 2005, 7, 3505. (d) Katz, J. L.; Geller, B. J.;
Conry, R. R. Org. Lett. 2006, 8, 2755. (e) Maes, W.; Van Rossom, W.;
Van Hecke, K.; Van Meervelt, L.; Dehaen, W. Org. Lett. 2006, 8, 4161.
(f) Hao, E.; Fronczek, F. R.; Vicente, M. G. H. J. Org. Chem. 2006, 71,
1233. (g) Chambers, R. D.; Hoskin, P. R.; Kenwright, A. R.; Khalil, A.;
Richmond, P.; Sandford, G.; Yufit, D. S.; Howard, J. A. K. Org. Biomol.
Chem. 2003, 2137. (h) Chambers, R. D.; Hoskin, P. R.; Khalil, A.;
Richmond, P.; Sandford, G.; Yufit, D. S.; Howard, J. A. K. J. Fluorine
Chem. 2002, 116, 19. (i) Li, X. H.; Upton, T. G.; Gibb, C. L. D.; Gibb, B.
C. J. Am. Chem. Soc. 2003, 125, 650. (j) Yang, F.; Yan, L.-W.; Ma, K.-Y.;
Yang, L.; Li, J.-H.; Chen, L.-J.; You, J.-S. Eur. J. Org. Chem. 2006, 1109.
(k) Konishi, H.; Tanaka, K.; Teshima, Y.; Mita, T.; Morikawa, O.;
Kobayashi, K. Tetrahedron Lett. 2006, 47, 4041. (l) Konishi, H.; Mita, T.;
Morikawa, O.; Kobayashi, K. Tetrahedron Lett. 2007, 48, 3029.
Results and Discussion
We began our investigation with the synthesis of tetraoxacalix-
[2]arene[2]triazine azacrowns. Dichlorinated tetraoxacalix[2]-
5220 J. Org. Chem., Vol. 72, No. 14, 2007

1,3-Alternate Tetraoxacalix[2]arene[2]triazine Azacrowns
FIGURE 3. 1H NMR spectrum of product 14b′. Inset: partial spectrum after D2O exchange.
ring. Benzyl 3,5-dihydroxybenzoate 4, obtained directly from
the reaction of 3,5-dihydroxybenzoic acid 3 with benzyl bromide
with the aid of K2CO3 in DMF at ambient temperature (Scheme
2), reacted smoothly with 2 equiv of cyanuric chloride 8 at 0 °C
in the presence of diisopropyl(ethyl)amine (DIPEA) to give
intermediate 9 in 55% yield. Macrocyclic coupling reaction of
9 with 4 proceeded effectively at room temperature to afford
tetraoxacalix[2]arene[2]triazine derivative 11 in 46% yield
(Scheme 3). To have fluorescent labeling groups on the
macrocyclic ring, pyren-1-ylmethyl 1,3-dihydroxybenzoate 7
was prepared following the route depicted in Scheme 2. Similar
to the synthesis of 11, the reaction of pyrenyl 1,3-dihydroxy-
benzoate 7 with 8 gave 81% yield of the intermediate 10, which
underwent macrocyclic condensation reaction with another
pyren-1-ylmethyl 1,3-dihydroxybenzoate 7 to furnish pyrenyl-
containing tetraoxacalix[2]arene[2]triazine derivative 12 in 48%.
The reaction also gave the ring an expanded homologue,
oxygen-bridged calix[3]arene[3]triazine 13, in 9% yield
(Scheme 3).
tion with an approximate C2V symmetry. Two benzene rings
are nearly face-to-face parallel with the distance ranging from
4.145 to 4.579 Å, while two triazine rings tend toward edge-
to-edge orientation. Both the bond lengths and bond angles (see
caption of Figure 1) of the bridging oxygen atoms indicate the
conjugation of all bridging oxygen atoms with their adjacent
triazines rather than benzene rings.
Bearing two benzyloxycarbonyl substituents on the benzene
rings on the upper-rim, the 1,3-alternate tetraoxacalix[2]arene-
[2]triazine 11 reacted efficiently with diamine 2b in the presence
of K2CO3 to afford the desired upper-rim calix[2]arene[2]triazine
azacrown 14b′ in 79% yield. Compound 11 then proved to be
a very good scaffold for the construction of crown architectures.
Larger and smaller azacrowns 14a and 14a′ and 14c and 14c′
were readily synthesized, respectively, from macrocyclic con-
densation reaction of 11 with diamines having a longer (2a) or
a shorter (2c) chain. The reaction of pyrenyl-substituted
tetraoxacalix[2]arene[2]triazine 12 with diamines 2a-c pro-
ceeded equally well, and the corresponding azacrown products
15a-c and 15a-c′ were produced in the yield of 75-85%. Even
with a diamine 2d derived from triglycol, condensation reaction
of 11 or 12 afforded azacrown 14d and 14d′ or 15d and 15d′,
albeit in a lower chemical yield (Table 1). From the reaction of
11 with 2d, a bis(tetraoxacalix[2]arene[2]triazine) product 16
was also isolated in 19% yield (Scheme 4).
The structures of the oxygen-bridged calixaromatics were
established on the basis of their spectroscopic data, microanaly-
ses, and X-ray single-crystal diffraction analysis. The X-ray
molecular structure of 11 (Figure 1) shows that the macrocyclic
skeleton of the product adopts almost a 1,3-alternate conforma-
(9) For recent examples of nitrogen-bridged calixaromatics, see: (a) Ito,
A.; Ono, Y.; Tanaka, K. New J. Chem. 1998, 779. (b) Ito, A.; Ono, Y.;
Tanaka, K. J. Org. Chem. 1999, 64, 8236. (c) Miyazaki, Y.; Kanbara, T.;
Yamamoto, T. Tetrahedron Lett. 2002, 43, 7945. (d) Wang, M.-X.; Zhang,
X.-H.; Zheng, Q.-Y. Angew. Chem., Int. Ed. 2004, 43, 838. (e) Gong, H.-
Y.; Zhang, X.-H.; Wang, D.-X.; Ma, H.-W.; Zheng, Q.-Y.; Wang, M.-X.
Chem.-Eur. J. 2006, 12, 9262. (f) Gong, H.-Y.; Zheng, Q.-Y.; Zhang, X.-
H.; Wang, D.-X.; Wang, M.-X. Org. Lett. 2006, 8, 4895. (g) Tsue, H.;
Ishibashi, K.; Takahashi, H.; Tamura, R. Org. Lett. 2005, 7, 11. (h)
Fukushima, W.; Kanbara, T.; Yamamoto, T. Synlett 2005, 19, 2931. (i)
Selby, T. D.; Blackstock, S. C. Org. Lett. 1999, 1, 2053. (j) Suzuki, Y.;
Yanagi, T.; Kanbara, T.; Yamamoto, T. Synlett 2005, 2, 263. (k) Ishibashi,
K.; Tsue, H.; Tokita, S.; Matsui, K.; Takahashi, H.; Tamura, R. Org. Lett.
2006, 8, 5991. (l) Wang, Q.-Q.; Wang, D.-X.; Ma, H.-W.; Wang, M.-X.
Org. Lett. 2006, 8, 5967.
(10) For examples of other heteroatom-bridged calixaromatics, see: (a)
Ko¨nig, B.; Ro¨del, M.; Bubenitschek, P.; Jones, P. G.; Thondorf, I. J. Org.
Chem. 1995, 60, 7406. (b) Ko¨nig, B.; Ro¨del, M.; Bubenitschek, P.; Jones,
P. G. Angew. Chem., Int. Ed. 1995, 34, 661. (c) Yoshida, M.; Goto, M.;
Nakanishi, F. Organometallics 1999, 18, 1465. (d) Avarvari, N.; Mezailles,
N.; Ricard, L.; Le Floch, P.; Mathey, F. Science 1998, 280, 1587. (e)
Avarvari, N.; Maigrot, N.; Ricard, L.; Mathey, F.; Le Floch, P. Chem.-
Eur. J. 1999, 5, 2109.
The structures of upper-rim tetraoxacalix[2]arene[2]triazine
azacrown products are worth addressing. Unlike both lower-
rim and upper-rim calix[n]crowns4,5 which give no stereoisomers
of the crown subunits, most of the upper-rim tetraoxacalix[2]-
arene[2]triazine azacrowns synthesized existed in a pair of syn-
and anti-stereoisomers because of the formation of conjugation
of amino groups with triazines which resulted in two different
orientations of the azacrown chain in solution (Scheme 4). This
has been shown clearly by their 1H and 13C NMR spectra, which
show two sets of the signals corresponding to syn- and anti-
isomers (see Supporting information). For example, the 1H NMR
spectrum of a mixture of 14a and 14a′ (Figure 2) gave three
triplet signals (J ) 2.1 Hz) centered at 7.03, 6.98, and 6.96
ppm, in which two (at 7.03 and 6.96 ppm) were of the same
intensity, corresponding to the aromatic protons at 2-position
of the resorcinol rings. The ratio of syn-isomer to anti-isomer,
which was listed in Table 1, was roughly estimated by means
of integrating the intensity of these signals. Tetraoxacalix[2]-
arene[2]triazine azacrown products 14b′ and 15b′ derived from
3,6,9,12-tetraoxatetradecane-1,14-diamine 2b gave one set of
proton signals in their 1H NMR spectra (Figure 3 and Supporting
information), and observation of only one peak at 6.78 or 6.72
(11) For a review of calixpyrroles, see: Gale, P. A.; Anzenbacher, P.;
Sessler, J. L. Coord. Chem. ReV. 2001, 222, 57.
(12) Sessler, J. L.; Cho, W.-S.; Lynch, V.; Kra´l, V. Chem.-Eur. J. 2002,
8, 1134 and references therein.
(13) For more examples, see a recent review: Kumar, S.; Paul, D.; Singh,
H. AdV. Heterocycl. Chem. 2005, 89, 65.
J. Org. Chem, Vol. 72, No. 14, 2007 5221

Hou et al.
FIGURE 4. X-ray molecular structure of 14a′: top (left) and side (middle and right) views.
TABLE 2. Association Constants (log Ka) for the 1:1 Interaction of 14 and 15d (15d′) with R4NF in a Mixture of CH3CN and CHCl3 (95:5) at
25 °C
14a (14a′)
14b (14b′)
14c (14c′)
14d (14d′)
15d (15d′)
nBu4NF
Et4NF
1.61 ( 0.01
1.88 ( 0.00
1.94 ( 0.01
1.88 ( 0.00
1.80 ( 0.00
1.91 ( 0.00
2.49 ( 0.00
2.69 ( 0.00
2.12 ( 0.00
ppm corresponding to two aromatic protons at 2-position of each
resorcinol ring suggested the anti-form of the products. As
indicated by the results in Table 1, the ratio of syn-isomer over
anti-isomer is dependent upon the length of the azacrown chain.
When the chain length is shorter than 13 non-hydrogen atoms
such as in the cases of 14c,d and 15c,d, the syn-isomer formed
preferably (entries 3, 4, 7, and 8). Only the anti-isomers 14b′
and 15b′ were observed when a diamine 2b derived from 3,6,9,-
12-tetraoxatetradecane-1,14-diol was incorporated into the
molecules (entries 2 and 6). Still longer aliphatic diamine 2a
led to the formation of an almost equal amount of syn- and
anti-isomers (entries 1 and 5). The dependence of the ratio of
syn-isomer over anti-isomer upon the length of the diamine most
probably reflects the steric effect of the upper-rim tetraoxacalix-
[2]arene[2]triazine azacrown products. Apparently, the calix-
azacrowns bearing a shorter azacrown moiety would tend to
adopt syn-configuration to reduce the steric strains in the anti-
form. The preference for syn-isomer in the cases of the short
azacrown chain-containing calixazacrowns was confirmed by
the observation of the further movement of the syn-anti
equilibrium to the syn-side after treatment with D2O (entries 4
and 8 in Table 1). To identify calix[2]arene[2]triazine azacrown
structure beyond doubt, X-ray diffraction analysis was at-
tempted. From slow evaporation of the solvent, a single crystal
of 14a′ was yielded and its X-ray diffraction data were collected
at 298 K. Most probably because of the disorder of the atoms
of the crown and benzyl moieties at room temperature, a less
satisfactory refinement [RF ) 0.2236 (I > 2σ(I)] was obtained.
Nevertheless, Figure 4 showed that the molecule 14a′ adopted
an anti-isomeric 1,3-alternate calix[2]arene[2]triazine azacrown
conformation in the solid state. All bridging oxygen atoms and
amino substituents are coplanar with their adjacent triazine rings.
To explore the molecular recognition property of the upper-
rim tetraoxacalix[2]arene[2]triazine azacrowns synthesized, we
initially examined the interaction of 14 with cations. Surpris-
ingly, no interaction at all was observed between all calixaza-
crown molecules with metal ions ranging from all alkali and
alkaline earth metal ions to Mn2+, Co2+, Ag+, Hg2+, and Pb2+
by means of spectrophotometric titration. By testing the interac-
tion with ammonium salts, we accidentally found that fluoride
anion can induce the changes of electronic absorption and
fluorescence emission of the host molecules 14 in acetonitrile
(see Supporting Information). For example, upon the titration
of fluoride, the intensity of fluorescence of 14d (14d′) at 335
nm was quenched with concomitance of the emerging of a new
and weak emission at 425 nm (Figure 5). The Job plot (inset in
Figure 5) indicated a 1:1 interaction model between 14 and
n-Bu4NF. On the basis of the fluorescence titration data, we
calculated the association constants for the 1:1 complexs of the
tetraoxacalix[2]arene[2]triazine azacrowns with n-Bu4NF or Et4-
NF using a Hyperquad2003 program. The results summarized
in Table 2 showed modest interactions of the hosts with fluoride,
and the strongest interaction was between fluoride and calix-
azacrown 14d (14d′), which derived from the shortest aliphatic
diamine 2d. It is worth noting that careful examination of the
UV-vis and fluorescence titrations with n-Bu4NX salts revealed
no interaction of all calixazacrowns 14 (14) with other anions,
including X ) Cl-, Br-, I-, CH3COO-, ClO4-, and PF6
.
-
The quench of fluorescence of tetraoxacalix[2]arene[2]triazine
azacrowns 14 (14′) by fluoride anion was most probably due
to the interaction of fluoride anion with the amino (NH) groups
of the azacrown subunit. As a hydrogen bond acceptor, for
example, fluoride might be able to form intermolecular hydrogen
bonds with both amino groups to form a N-H‚‚‚F-‚‚‚H-N
complex (Figure 6A). The other possible interaction model
might treat fluoride as a base to deprotonate one proton from
two amino groups, resulting in the formation of an intramo-
lecular hydrogen bond between amino and deprotonated amino
groups (N-H‚‚‚N- T N-‚‚‚H-N) (Figure 6B). Both interaction
mechanisms would pull two triazine rings in close proximity
and rigidify their motions. Concomitantly, the other two alternate
benzene rings in tetraoxacalix[2]arene[2]triazine azacrowns
would sit apart from each other and enjoy their motions more
freely, which would cause the decrease of fluorescence intensity.
To elucidate the interaction models, the fluorescence titration
of 14d (14d′) with n-Bu4NOH was conducted.14 As illustrated
in Figure S31, interaction of n-Bu4NOH with 14d (14d′) led to
almost identical spectral changes as observed from the interac-
tion between n-Bu4NF and 14d (14d′) (Figure 5). The outcome
(14) We thank one of the reviewers for the helpful suggestion.
5222 J. Org. Chem., Vol. 72, No. 14, 2007

1,3-Alternate Tetraoxacalix[2]arene[2]triazine Azacrowns
FIGURE 7. Fluorescence emission response of 15d (15d′) (5.41 ×
10-6 M) with n-Bu4NF in acetonitrile chloroform (v/v ) 95/5) solution
with increasing [F-] at 25 °C. The concentrations of F- for curves
from top to bottom (excimer) are 0, 0.1, 0.31, 0.72, 1.13, 1.54, 1.95,
2.36, 2.76, 3.17, 3.58, 3.99, 4.4, 4.81, 5.22, 5.63, 6.04, 6.45, 6.86, 7.88,
9.93, 13, 18.12, 23.24, 28.36, 33.48, 38.6, 43.72, 48.84, and 53.96 ×
10-3 M. λex ) 343 nm, and the excitation and emission band widths
are 10 nm. Inset: Job plot for 15d (15d′)-F- complex in a mixture of
acetonitrile and chloroform (v/v ) 9/1) ([15d (15d′)] + [F-] ) 3.28
× 10-5 M). λex ) 343 nm, and the excitation and emission band widths
are 5 nm.
FIGURE 5. Fluorescence emission response of 14d (14d′) (1.118 ×
10-4 M) with n-Bu4NF in acetonitrile solution with increasing [F-] at
25 °C. The concentrations of F- for curves from top to bottom are 0,
0.57, 1.70, 2.83, 5.09, 7.36, 9.62, 11.89, 14.15, 16.41, 18.68, 20.94,
23.21, 25.47, 27.73, 30.00, 32.26, 34.53, 36.79, 39.05, and 41.32 ×
10-4 M. λex ) 289 nm, and the excitation and emission band widths
are 10 nm. Inset: Job plot for 14d (14d′)-F- complex in a mixture of
acetonitrile and chloroform (v/v ) 9/1) solution ([14d (14d′)] + [F-]
) 4.983 × 10-4 M). λex ) 289 nm, and the excitation and emission
band widths are 5 nm.
FIGURE 6. Two proposed models for the interaction of calixazacrowns
14 (14′) with fluoride anion.
suggested therefore a deprotonation mechanism that was
depicted in Figure 6B.
The interaction of calixazacrowns with fluoride or a base
implied that the cavity or the cleft of tetraoxacalix[2]arene[2]-
triazines, namely the distance between two parallel benzene
rings, might be regulated by an external stimulus. To manifest
the change of the cavity in response to an external stimulus,
emission spectra of pyrene-labeled tetraoxacalix [2]arene[2]-
triazine azacrown 15d (15d′) were studied upon its interaction
with n-Bu4NF and n-Bu4NOH. In the absence of any guest
species, the fluorescence spectrum of 15d (15d′) in a mixture
of acetonitrile and chloroform (v/v ) 95/5) gave mainly the
emission band of pyrene excimer at 477 nm in addition to very
weak and structured emission bands of the pyrene monomer at
378-396 nm. With the increase of n-Bu4NF (Figure 7) and
n-Bu4NOH (Figure S32), the emission at 477 nm decreased and
eventually disappeared, while the emission bands in the region
of 378-396 nm increased. The changes of emission spectra
shown in Figure 7 demonstrated convincingly that a pair of face-
to-face parallel benzene rings moved separately when the
pendent azacrown interacted with 1 equiv of fluoride anion. In
FIGURE 8. Schematic presentation of tuning of the cavity of
tetraoxacalix[2]arene[2]triazine azacrown 15d (15d′) by an external
fluoride anion stimulant.
other words, the upper-rim tetraoxacalix[2]arene[2]triazine
azacrowns behaved like a molecular clip, and the cavity or the
cleft formed by two face-to-face aligned benzene rings expanded
J. Org. Chem, Vol. 72, No. 14, 2007 5223

Hou et al.
FIGURE 9. 1H NMR titration of 15d (15d′) with n-Bu4NF in CDCl3 at 298 K (blue 1: two NH proton signals; red b: the aromatic protons at
the 2-position of two resorcinol rings; black 9: signals of two CH2 protons).
when two triazine rings embedded in azacrown contracted in
response to an external fluoride anion stimulant (Figure 8).
To shed further light on the change of the cavity of
interaction led to the change of the cavity of calixazacrown host
molecules. The convenient and efficient construction of
tetraoxacalix[2]arene[2]triazine azacrowns and their conforma-
tional mobility in response to an external stimulant would render
host molecules in supramolecular assemblies and in the design
of molecular devices.
tetraoxacalix[2]arene[2]triazine azacrown 15d (15d′) upon the
1
treatment of fluoride anion, H NMR spectra of a mixture of
15d (15d′) and fluoride anion in different ratios were determined
(Figure 9). With the increase of the concentration of fluoride,
the amino proton signals of the azacrown shifted and broadened.
When the ratio reached 1:1, the amino proton signals were not
observed. More noticeably, increasing the fluoride concentration
also led to the proton signals of pyrenylmethyl and azacrown
moieties become more complicated. This indicated the destruc-
tion of parent 1,3-alternate conformational structure, which is
in agreement with the results of fluorescence titration. It should
be noted that tetraoxacalix[2]arene[2]triazine azacrown 15d
(15d′) was much more stable than tetranitro-substituted
tetraoxacalix[4]arene.8k,l As indicated by the thin layer chro-
matography analysis, the macrocyclic structure of 15d (15d′)
remained intact after interacting with fluoride anion.
Experimental Section
Synthesis of 9 and 10. To an ice-bath cooled solution of cyanuric
chloride 8 (9.23 g, 50 mmol) in THF (100 mL) was added dropwise
a mixture of 4 (6.1 g, 25 mmol) and diisopropyl(ethyl)amine (8.06
g, 62.5 mmol) in THF (50 mL) during 1 h. The resulting mixture
was stirred for another 2 h. After removal of diisopropyl(ethyl)-
amine hydrochloride salt through filtration, the filtrate was con-
centrated and chromatographed on a silica gel column (100-200
mesh) with a mixture of petroleum ether and acetone as the mobile
phase to give pure 9 (7.43 g, 55%) as white solid: mp 165-166 °C;
IR (KBr) ν 1729, 1528 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.89
(2H, d, J ) 2.2 Hz, CH), 7.38-7.45 (5H, m, CH), 7.30 (1H, t, J
) 2.2 Hz, CH), 5.38 (2H, s, CH2); 13C NMR (75 MHz, CDCl3) δ
173.4, 170.6, 163.9, 151.4, 135.1, 133.6, 128.7, 128.6, 128.4, 121.2,
119.5, 67.7; MS (EI) m/z (%) 542 (3), 540 (5), 538 (M+, 4), 433
(100), 431 (72), 406 (35), 404 (26), 91 (54). Anal. Calcd for C20H10-
Cl4N6O8: C, 44.47; H, 1.87; N, 15.56. Found: C, 44.44; H, 2.06;
N, 15.33. Following the same procedure, pure 10 (81%) was
obtained as pale yellow solid: mp 212-213 °C; IR (KBr) ν 1726,
Conclusion
In summary, we have shown an efficient method for the
construction of the upper-rim 1,3-alternate tetraoxacalix[2]arene-
[2]triazine azacrowns starting from the fragment coupling
preparation of dichlorinated tetraoxacalix[2]arene[2]triazine
intermediates followed by macrocyclic condensation reaction
with diamines. Because of the formation of conjugation of amino
groups with triazines, tetraoxacalix[2]arene[2]triazine azacrowns
existed in a mixture of syn- and anti-isomeric forms in solution.
We have also demonstrated by means of fluorescence titration
1
1535 cm-1; H NMR (300 MHz, CDCl3) δ 8.34 (1H, d, J ) 9.2
Hz, CH), 8.24-8.02 (8H, m, CH), 7.86 (2H, d, J ) 2.2 Hz, CH),
7.24 (1H, t, J ) 2.2 Hz, CH), 6.10 (2H, s, CH2); 13C NMR (75
MHz, CDCl3) δ 173.3, 170.5, 164.0, 151.3, 133.6, 132.1, 131.2,
130.6, 129.8, 128.6, 128.1, 128.08, 127.9, 127.3, 126.3, 125.8,
125.6, 124.9, 124.6, 122.6, 121.2, 119.5, 66.4; MS (MALDI-TOF)
m/z (%) 661.9 (M + H+, 71), 664.9 (35), 665.9 (87), 666.9 (32),
667.9 (21), 669.9 (4). Anal. Calcd for C30H14N6O4Cl4: C, 54.24;
H, 2.12; N, 12.65. Found: C, 53.88; H, 2.35; N, 12.84.
1
and H NMR spectroscopic study that the resulting calixazac-
rown host molecules can interact with fluoride anion. Such
5224 J. Org. Chem., Vol. 72, No. 14, 2007

1,3-Alternate Tetraoxacalix[2]arene[2]triazine Azacrowns
Synthesis of 11. At room temperature, both solutions of
monomer 4 (4 mmol) in acetone (200 mL) and the trimer 9 (4
mmol) in acetone (200 mL) were added dropwise at the same rate
to a solution of diisopropyl(ethyl)amine (1.24 g, 9.6 mmol) in
acetone (1400 mL). After addition of two reactants, which took
about 12 h, the resulting mixture was stirred at room temperature
for another 24 h. The solvent was then removed under vacuum,
and the residue was chromatographed on a silica gel column (200-
300 mesh) with a mixture of petroleum ether and acetone as the
mobile phase to give pure 11 (1.309 g, 46%) as white solid: mp
(0.96H, t, J ) 2.1 Hz, CH), 6.96 (0.52H, t, J ) 2.1 Hz, CH), 6.01-
5.99 (2H, m, NH), 5.30 (4H, s, CH2), 4.10-4.06 (2H, m, CH2),
3.76-3.75 (2H, m, CH2), 3.66-3.57 (22H, m, CH2), 3.31-3.29
(2H, m, CH2); 13C NMR (150 MHz, CDCl3) δ 172.1, 172.0, 171.4,
169.0, 164.6, 152.04, 152.0, 151.9, 135.4, 132.4, 128.6, 128.4,
128.3, 128.2, 121.5, 120.2, 70.7, 70.6, 70.5, 70.4, 70.3, 70.2, 69.4,
69.3, 67.2, 41.2, 41.1; MS (MALDI-TOF) m/z 963.1 (M + H+),
985.1 (M
+ +
Na+), 1001.0 (M K+). Anal. Calcd for
C48H50N8O14: C, 59.87; H, 5.23; N, 11.64. Found: C, 59.48; H,
5.28; N, 11.78. Evaporation of the solvent from the sample solution
in a mixture of dichloromethane and ethanol gave single crystals.
14b (14b′): mp 274-275 °C; IR (KBr) ν 3276, 3146, 1727, 1585
1
216-217 °C; IR (KBr) ν 1725, 1551 cm-1; H NMR (300 MHz,
CDCl3) δ 7.61 (4H, d, J ) 2.2 Hz, CH), 7.36-7.40 (10H, m, CH),
6.92 (2H, t, J ) 2.2 Hz, CH), 5.30 (4H, s, CH2); 13C NMR (75
MHz, CDCl3) δ 175.0, 172.1, 163.8, 151.4, 135.0, 133.6, 128.7,
128.6, 128.4, 121.0, 120.4, 67.7; MS (MALDI-TOF) m/z (%) 710.9
(M + H+, 100), 711.9 (42), 712.9 (70), 713.9 (26), 714.9 (16),
715.9 (6). Anal. Calcd for C34H20N6O8Cl2: C, 57.40; H, 2.83; N,
11.81. Found: C, 57.33; H, 3.12; N, 11.75. X-ray quality single
crystals were obtained from slow evaporation of solution of 11 in
a mixture of petroleum ether and ethyl acetate.
1
cm-1; H NMR (600 MHz, CDCl3) δ 7.58-7.56 (4H, m, CH),
7.42-7.33 (10H, m, CH), 6.79-6.78 (2H, m, CH), 6.17-6.15 (1H,
m, NH), 6.10-6.09 (1H, m, NH), 5.31 (4H, s, CH2), 4.34-4.33
(2H, m, CH2), 3.74-3.47 (16H, m, CH2), 3.15-3.13 (2H, m, CH2);
13C NMR (150 MHz, CDCl3) 172.1, 172.0, 171.5, 170.0, 164.6,
152.3, 152.1, 135.4, 132.6, 128.6, 128.4, 128.3, 120.8, 120.6, 120.1,
119.9, 71.1, 70.8, 70.5, 70.1, 70.0, 69.9, 69.7, 67.3, 40.7; MS
(MALDI-TOF) m/z 875.3 (M + H+), 897.3 (M + Na+), 913.3 (M
+ K+). Anal. Calcd for C44H42N8O12: C, 60.41; H, 4.84; N, 12.81.
Found: C, 60.52; H, 4.93; N, 12.79.
Synthesis of 12. To an ice-bath cooled solution of 7 (0.368 g, 1
mmol) and 10 (0.664 g, 1 mmol) in acetone (500 mL) was added
diisopropyl(ethyl)amine (0.323 g, 2.5 mmol). The resulting mixture
was stirred in an ice bath for 2 h. After addition of ice water (200
mL), hydrochloric acid (1 N) was added to the suspension until
the pH value of the mixture was around 7. After removal of acetone
under vacuum, the residue was extracted with CH2Cl2 (3 × 250
mL). The combined organic phases were then washed with water
(200 mL) and brine (200 mL). The organic phase was dried over
with anhydrous Na2SO4, filtered, and concentrated. The residue was
chromatographed on a silica gel column (200-300 mesh) with a
mixture of petroleum ether and acetone as the mobile phase to give
pure 12 (0.462 g, 48%) and 13 (90 mg, 9%). 12: pale yellow solid;
mp 215-216 °C; IR (KBr) ν 1727, 1550 cm-1; 1H NMR (300 MHz,
CDCl3) δ 8.24-7.97 (18H, m, CH), 7.52 (4H, d, J ) 2.2 Hz, CH),
6.60 (2H, t, J ) 2.2 Hz, CH), 5.96 (4H, s, CH2); 13C NMR (75
MHz, CDCl3) δ 174.8, 172.0, 163.9, 151.3, 133.5, 132.0, 131.1,
130.5, 129.7, 128.5, 128.1, 128.0, 127.8, 127.2, 126.2, 125.7, 125.6,
124.8, 124.6, 124.5, 122.5, 121.0, 120.3, 66.1; MS (MALDI-TOF)
m/z (%) 958.0 (M + H+, 100), 959.0 (62), 969.9 (39), 961.9 (19),
962.9 (8). Anal. Calcd for C54H28N6O8Cl2: C, 67.58; H, 2.94; N,
8.76. Found: C, 67.38; H, 3.04; N, 8.70. 13: Pale yellow solid;
mp 222-223 °C; IR (KBr) ν 1727, 1550 cm-1; 1H NMR (300 MHz,
CDCl3) δ 8.23-7.97 (27H, m, CH), 7.64 (6H, d, J ) 2.0 Hz, CH),
7.04 (3H, s, br, CH), 5.98 (6H, s, CH2); 13C NMR (75 MHz, CDCl3)
δ 174.4, 171.8, 163.9, 151.0, 133.4, 131.9, 131.1, 130.6, 129.6,
128.5, 128.0, 127.9, 127.8, 127.2, 126.2, 125.7, 125.6, 124.8, 124.6,
124.5, 122.5, 120.6, 120.3, 66.0; MS (MALDI-TOF) m/z (%) 1436.9
(67), 1437.9 (66), 1438.9 (M + H+, 100), 1440.9 (53), 1441.9 (29),
1442.9 (14), 1443.9 (7), 1444.9 (4), 1460.6 (M + Na+), 1477.9
(M + K+). Anal. Calcd for C81H42N9O12Cl3: C, 67.58; H, 2.94; N,
8.76. Found: C, 67.53; H, 3.28; N, 8.74.
14c (14c′): mp 248-249 °C; IR (KBr) ν 3274, 3144, 1729, 1589
1
cm-1; H NMR (600 MHz, CDCl3) δ 7.62-7.59 (4H, m, CH),
7.43-7.33 (10H, m, CH), 6.64 (0.6H, s, br, CH), 6.54 (0.6H, s, br,
CH), 6.47 (0.8H, s, br, CH), 5.88 (1H, s, br, NH), 5.82 (1H, s, br,
NH), 5.32 (4H, s, CH2), 4.42-4.34 (2H, m, CH2), 3.72-3.70 (2H,
m, CH2), 3.64-3.52 (6H, m, CH2), 3.43 (1H, s, br, CH2), 3.31-
3.29 (2H, m, CH2), 3.14-3.08 (3H, m, CH2); 13C NMR (150 MHz,
CDCl3) δ 172.1, 171.9, 171.5, 170.7, 164.6, 153.1, 152.8, 152.7,
152.2, 135.4, 132.9, 128.7, 128.5, 128.4, 128.3, 119.4, 119.1, 118.8,
71.2, 70.3, 69.2, 68.6, 67.3, 40.7, 40.4, 30.9; MS (MALDI-TOF)
m/z 831.3 (M + H+); Anal. Calcd for C42H38N8O11: C, 60.72; H,
4.61; N, 13.49. Found: C, 60.73; H, 4.62; N, 13.64.
14d (14d′): mp > 300 °C; IR (KBr) ν 3278, 3182, 3141, 1734,
1587 cm-1; 1H NMR (600 MHz, CDCl3) δ 7.61 (4H, s, CH), 7.42-
7.34 (10H, m, CH), 6.92 (1H, s, br, NH), 6.36 (0.66H, s, CH),
6.16 (0.66H, s, CH), 6.08 (0.68H, s, CH), 5.94 (1H, s, br, NH),
5.32 (4H, s, CH2), 4.23 (2H, s, br, CH2), 3.81 (1H, s, br, CH2),
3.73 (1H, s, br, CH2), 3.59 (2H, s, br, CH2), 3.47 (1H, s, br, CH2),
3.38 (2H, s, br, CH2), 3.22 (3H, s, br, CH2); 13C NMR (150 MHz,
CDCl3) δ 173.5, 172.8, 172.5, 172.0, 170.9, 164.6, 155.4, 155.0,
153.9, 135.4, 133.3, 129.2, 128.6, 128.4, 117.2, 117.0, 115.4, 114.4,
70.9, 69.7, 67.3, 41.7; MS (MALDI-TOF) m/z 787.2 (M + H+).
Anal. Calcd for C40H34N8O10: C, 61.07; H, 4.36; N, 14.24. Found:
C, 60.68; H, 4.72; N, 14.06.
16: mp 139-140 °C; IR (KBr) ν 3413, 3280, 1728, 1592 cm-1
;
1H NMR (300 MHz, d6-DMSO) δ 8.43 (2H, s, br, NH), 7.50-
7.34 (32H, m, CH), 5.26 (8H, s, CH2), 3.59-3.52 (12H, m, CH2);
13C NMR (75 MHz, d6-DMSO) δ 127.6, 171.6, 171.5, 171.3,
171.25, 171.2, 171.0, 170.6, 168.5, 168.0, 167.6, 164.8, 164.0,
163.7, 163.6, 161.4, 161.3, 158.7, 158.5, 152.64, 152.61, 152.3,
152.27, 152.2, 152.1, 152.05, 152.0, 151.3, 151.2, 151.0, 150.8,
149.9, 135.9, 135.67, 135.6, 135.5, 131.8, 131.7, 131.6, 131.5,
131.3, 128.5, 128.4, 128.3, 128.1, 128.0, 127.9, 121.9, 121.6, 121.1,
121.0, 120.7, 120.2, 120.1, 120.0, 119.9, 119.2, 114.2, 114.0, 113.4,
113.3, 113.1, 69.6, 69.2, 68.5, 68.0, 66.8, 66.4, 30.9, 22.0, 13.9;
MS (MALDI-TOF) m/z (%) 1497.0 (M + H+, 89), 1498.0 (84),
1499.0 (100), 1500.0 (66), 1501.0 (39), 1502.0 (19), 1503.0 (9),
1504.0 (4). Anal. Calcd for C74H54N14O18Cl2: C, 59.32; H, 3.63;
N, 13.09. Found: C, 59.59; H, 3.85; N, 12.80.
General Procedure for the Synthesis of the Upper-Rim 1,3-
Alternate Tetraoxacalix[2]arene[2]triazine Azacrowns 14a-d
(14a-d′) and 15a-c (15a-c′). Both solutions of a diamine 2 (0.5
mmol) in THF (100 mL) and a dichlorinated tetraoxacalix[2]arene-
[2]triazine 11 or 12 (0.5 mmol) in THF (100 mL) were added
dropwise at the same rate to a refluxing suspension of K2CO3 (0.212
g, 1.5 mmol) in THF (240 mL). After addition of the reactants,
which took about 10 h, the resulting mixture was refluxed for
another 12 h. Filtration removed the solids, and the filtrate was
concentrated under vacuum. The residue was then chromatographed
on a silica gel column (200-300 mesh) with a mixture of petroleum
ether and acetone as the mobile phase to give pure products 14a-d
(14a-d′) as white solids or 15a-c (15a-c′) as pale yellow solids.
In the case of synthesis of 14d (14d′), product 16 was also obtained.
14a (14a′): mp 244-245 °C; IR (KBr) ν 3277, 3151, 1728, 1583
15a (15a′): mp 176-177 °C; IR (KBr) ν 3281, 1725, 1585 cm-1
;
1H NMR (600 MHz, CDCl3) δ 8.26 (2H, d, J ) 9.1 Hz, CH), 8.17
(4H, d, J ) 7.6 Hz, CH), 8.12-8.10 (4H, m, CH), 8.06-8.04 (4H,
m, CH), 8.02-7.98 (4H, m, CH), 7.55-7.53 (4H, m, CH), 6.98
(0.5H, t, J ) 2.2 Hz, CH), 6.93 (1.0H, t, J ) 2.2 Hz, CH), 6.90
(0.5H, t, J ) 2.2 Hz, CH), 5.98 (4H, s, CH2), 5.94-5.93 (2H, m,
NH), 4.04-4.01 (2H, m, CH2), 3.72-3.70 (2H, m, CH2), 3.63-
3.54 (22H, m, CH2), 3.25-3.23 (2H, m, CH2); 13C NMR (75 MHz,
1
cm-1; H NMR (600 MHz, CDCl3) δ 7.57-7.55 (4H, m, CH),
7.41-7.33 (10H, m, CH), 7.03 (0.52H, t, J ) 2.1 Hz, CH), 6.98
J. Org. Chem, Vol. 72, No. 14, 2007 5225

Hou et al.
d6-DMSO) δ 171.1, 170.5, 170.4, 168.5, 163.9, 152.3, 152.2, 152.1,
131.6, 131.0, 130.6, 130.0, 128.8, 128.6, 128.0, 127.9, 127.6, 127.1,
126.5, 126.4, 126.2, 125.5, 125.4, 124.6, 123.8, 123.6, 122.8, 121.5,
118.7, 69.8, 69.78, 69.7, 69.6, 68.4, 65.1, 62.8, 40.4; MS (MALDI-
TOF) m/z 1212.3 (M + H+), 1234.3 (M + Na+), 1250.3 (M +
K+). Anal. Calcd for C68H58N8O14: C, 67.43; H, 4.83; N, 9.25.
Found: C, 67.06; H, 4.81; N, 9.03.
mg, 0.625 mmol), diamine 2d (92.5 mg, 0.625 mmol), and K2CO3
(1.725 g, 12.5 mmol) in dry THF (1800 mL) was refluxed with
stirring for 1 h. After removal of the solvent under vacuum, the
resulting residue was dissolved in CH2Cl2 (400 mL) and then
washed three times with water. The organic phase was dried over
with anhydrous Na2SO4. The solvent was removed under vacuum
to give a residue that was chromatographed on a silica gel column
(200-300 mesh) with a mixture of petroleum ether and acetone as
the mobile phase to afford pure 15d (15d′) (0.146 g, 23%) as pale
15b (15b′): mp 206-207 °C; IR (KBr) ν 3276, 1725, 1587 cm-1
;
1H NMR (600 MHz, CDCl3) δ 8.27 (2H, d, J ) 9.3 Hz, CH), 8.18
(4H, d, J ) 8.9 Hz, CH), 8.12-8.11 (4H, m, CH), 8.08-8.04 (4H,
m, CH), 7.99-7.94 (4H, m, CH), 7.55-7.54 (4H, m, CH), 6.72
(2H, s, br, CH), 5.99 (4H, s, CH2), 5.78-5.72 (2H, m, NH), 4.29-
4.27 (2H, m, CH2), 3.72-3.67 (4H, m, CH2), 3.61-3.42 (12H, m,
CH2), 3.11-3.08 (2H, m, CH2); 13C NMR (75 MHz, d6-DMSO) δ
171.3, 171.1, 170.7, 170.6, 169.1, 163.9, 153.0, 152.9, 152.8, 152.7,
131.9, 131.1, 130.6, 130.1, 128.8, 128.6, 128.1, 127.6, 127.2, 126.3,
125.5, 125.4, 124.6, 123.9, 123.7, 122.9, 117.8, 79.1, 70.1, 70.0,
69.8, 69.7, 69.6, 69.2, 68.9, 65.2; MS (MALDI-TOF) m/z 1123.6
(M + H+), 1145.6 (M + Na+), 1161.5 (M + K+); Anal. Calcd for
C64H50N8O12: C, 68.44; H, 4.49; N, 9.98. Found: C, 68.24; H,
4.85; N, 9.96.
yellow solid: mp 202-203 °C; IR (KBr) ν 3277, 1725, 1591 cm-1
;
1H NMR (600 MHz, CDCl3) δ 8.32 (2H, d, J ) 9.2 Hz, CH), 8.20
(4H, d, J ) 7.6 Hz, CH), 8.16 (4H, d, J ) 8.8 Hz, CH), 8.10-8.08
(4H, m, CH), 8.06 (2H, d, J ) 8.8 Hz, CH), 8.00 (2H, t, J ) 7.6
Hz, CH), 7.57 (4H, s, br, CH), 6.30 (1H, s, br, NH), 6.13 (0.6H, s,
br, CH), 6.06 (0.6H, s, br, CH), 6.02 (4H, s, CH2), 6.00 (0.8H, s,
br, CH), 5.86 (1H, s, br, NH), 4.15 (2H, s, br, CH2), 3.73 (2H, s,
br, CH2), 3.53 (2H, s, br, CH2), 3.35 (2H, s, br, CH2), 3.27 (2H, s,
br, CH2), 3.13 (2H, s, br, CH2); 13C NMR (75 MHz, d6-DMSO) δ
172.5, 171.6, 171.3, 170.5, 170.3, 170.2, 163.7, 155.4, 154.6, 153.6,
152.0, 133.1, 131.1, 130.6, 130.1, 128.9, 128.6, 128.1, 127.7, 127.2,
126.3, 125.5, 125.4, 124.6, 123.9, 123.7, 123.0, 119.1, 115.9, 115.5,
112.5, 70.2, 70.1, 69.1, 65.4, 41.0; MS (MALDI-TOF) m/z 1035.4
(M + H+), 1057.4 (M + Na+), 1073.4 (M + K+). Anal. Calcd for
C60H42N8O10‚H2O: C, 68.43; H, 4.21; N, 10.64. Found: C, 68.28;
H, 4.13; N, 10.46.
15c (15c′): mp 200-201 °C; IR (KBr) ν 3276, 1725, 1589 cm-1
;
1H NMR (600 MHz, CDCl3) δ 8.28 (2H, d, J ) 9.0 Hz, CH), 8.18
(4H, d, J ) 7.6 Hz, CH), 8.14-8.12 (4H, m, CH), 8.06 (4H, d, J
) 9.0 Hz, CH), 8.04-7.99 (4H, m, CH), 7.57 (4H, t, J ) 19.4 Hz,
CH), 6.58 (0.62H, s, br, CH), 6.48 (0.62H, s, br, CH), 6.42 (0.76H,
s, br, CH), 6.00 (4H, s, CH2), 5.75 (1.28H, s, br, NH), 5.71-5.70
(0.72H, m, NH), 4.37-4.30 (2H, m, CH2), 3.68-3.48 (8H, m, CH2),
3.39 (1H, s, br, CH2), 3.25 (2H, s, br, CH2), 3.09-3.03 (3H, m,
CH2); 13C NMR (75 MHz, d6-DMSO) δ 170.9, 169.8, 164.0, 163.9,
153.4, 153.2, 132.2, 131.9, 131.1, 130.6, 130.1, 128.8, 128.7, 128.1,
127.7, 127.6, 127.2, 126.3, 125.5, 125.4, 124.6, 123.9, 123.7, 122.9,
119.8, 117.8, 117.0, 70.4, 69.6, 69.1, 68.5, 68.1, 67.9, 65.2; MS
(MALDI-TOF) m/z 1080.2 (M + H+), 1102.2 (M + Na+), 1118.2
(M + K+). Anal. Calcd for C62H46N8O11: C, 69.01; H, 4.30; N,
10.38. Found: C, 68.71; H, 4.45; N, 10.38.
Acknowledgment. We thank the National Natural Science
Foundation of China, Ministry of Science and Technology, and
Chinese Academy of Sciences for financial support.
Supporting Information Available: Preparation of starting
1
materials, H and 13C NMR spectra of all products, fluorescence
spectra upon titration with fluoride anion, and X-ray structures of
11 and 14a′ (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
Preparation of the Upper-Rim 1,3-Alternate Tetraoxacalix-
[2]arene[2]triazine Azacrown 15d (15d′). A suspension of 12 (600
JO0706168
5226 J. Org. Chem., Vol. 72, No. 14, 2007