A general and high yielding fragment coupling synthesis of heteroatom-bridged calixarenes and the unprecedented examples of calixarene cavity fine-tuned by bridging heteroatoms

Article abstract of DOI:10.1021/ja0465092

A number of aza- and/or oxo-bridged calix[2]arene[2]triazines have been synthesized through an unusually high yielding and efficient fragment coupling approach starting from cyanuric chloride and resorcinol, 3-aminophenol, m-phenylenediamine, and N,N-dime

Full text of DOI:10.1021/ja0465092

Published on Web 11/06/2004
A General and High Yielding Fragment Coupling Synthesis of
Heteroatom-Bridged Calixarenes and the Unprecedented
Examples of Calixarene Cavity Fine-Tuned by Bridging
Heteroatoms
Mei-Xiang Wang* and Hai-Bo Yang
Contribution from the Laboratory of Chemical Biology, Center for Molecular Science,
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China
Received June 13, 2004; E-mail: mxwang@iccas.ac.cn
Abstract: A number of aza- and/or oxo-bridged calix[2]arene[2]triazines have been synthesized through
an unusually high yielding and efficient fragment coupling approach starting from cyanuric chloride and
resorcinol, 3-aminophenol, m-phenylenediamine, and N,N′-dimethyl-m-phenylenediamine. These novel
macrocycles, which belong to the next generation of calixarenes or cyclophanes, form a unique cavity that
is resulted from two isolated benzene planes and two bis-heteroatom-conjugated triazine planes in a 1,3-
alternate fashion. The nature of the bridging heteroatoms, i.e., combination of the electronic, conjugative,
and steric effects of the nitrogen and oxygen atoms, strongly regulates the cavity size, generating a set of
fine-tuned cavities in which the distance between two benzene rings at the upper rim ranges from 5.011
to 7.979 Å. The multiple intermolecular hydrogen bond interactions among N,N′-dimethylated tetraazacalix-
[2]arene[2]triazines and among tetraazacalix[2]arene[2]triazines lead to the formation of infinite one-
dimensional chain structure and two-dimensional zigzag layered structure, respectively, in the solid state.
The ease of preparation and further chemical manipulations, and the readily tunable cavity structures render
these aza- and/or oxo-bridged calix[2]arene[2]triazines the unique platforms in the study of supramolecular
chemistry.
Introduction
coarse-tuned macrocyclic molecules, construction of calixarenes
with a fine-tuned cavity by substitution of the methylene bridges
The sophistication of the design and synthesis of novel and
functional macrocyclic host molecules has always been one
driving force to promote the major advances in supramolecular
chemistry. One of the recent examples is the explosive studies
of calixarene chemistry1 following Gutsche’s pioneering work2
of synthesis and structural elucidation of calix[n]arenes. Because
of the easy availability, unique conformational and cavity
structures, and recognition properties, calixarenens have been
developed into an indispensable part of supramolecular chem-
istry.1 While the effort to derivatize the fundamental calixarene
skeletons is still increasing,3 one of the recent developments in
this area is the construction of new calixarenes by replacing
their phenol units with other heteroaromatics, to tune the cavity
and therefore to improve their efficiency and selectivity toward
recognizing various guest species including cations, anions, and
neutral molecules. This has in fact resulted in a few intriguing
macrocycles such as calixpyrroles,4 calixpyridines,5 and other
calixheteroaromatics.6 In particular, calixpyrroles4 have been
shown to be powerful anion receptors. In contrast to these
with heteroatoms has been scatteringly investigated7 because
of synthetic obstacles except for thiacalixarenes.8 For example,
reaction of 1,3-dichloro-4,6-dinitrobenzene with resorcinol gave
(3) For recent examples of derivatization of calixarenes, see: (a) Webber, P.
R. A.; Cowley, A.; Drew, M. G. B.; Beer, P. D. Chem.sEur. J. 2003, 9,
2439. (b) Vysotsky, M. O.; Botle, M.; Thondorf, I.; Bo¨hmer, V. Chem.s
Eur. J. 2003, 9, 3375. (c) Botana, E.; Na¨ttinen, K.; Prados, P.; Rissanen,
K.; Der Mendoza, J. Org. Lett. 2004, 6, 1091. (d) Cao, Y.-D.; Luo, J.;
Zheng, Q.-Y.; Chen, C.-F.; Wang, M.-X.; Huang, Z.-T. J. Org. Chem. 2004,
69, 206. (e) Webber, P. R. A.; Beer, P. D.; Chen, G. Z.; Felix, V.; Drew,
M. G. B. J. Am. Chem. Soc. 2003, 125, 5774. (f) Mattews, S. E.; Schmitt,
P.; Felix, V.; Drew, M. G. B.; Beer, P. D. J. Am. Chem. Soc. 2002, 124,
1341. (g) Zheng, Y.-S.; Zhang, C. Org. Lett. 2004, 6, 1189. (h) Makha,
M.; McKinnon, I. R.; Raston, C. L. J. Chem. Soc., Perkin Trans. 2 2002,
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1228. (j) Biali, S. E. Synlett 2003, 1. Casnati, A.; Sansone, F.; Ungaro, R.
Acc. Chem. Res. 2003, 36, 246.
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(1) (a) Calixarenes 2001; Asfari, Z., Bo¨hmer, V., Harrowfield, J., Vicens, J.,
Saadioui, M., Eds.; Kluwer Academic Publishers: The Netherlands, 2001.
(b) Gutsche, C. D. Calixarenes ReVisited; The Royal Society of Chemis-
try: Cambridge, 1998. (c) Calixarenes in Action; Mandolini, L., Ungaro,
R., Eds.; Imperial College Press: London, 2000. (d) Lumetta, G. J.; Rogers,
R. D.; Gopalan, A. S. Calixarenes for Separation; ACS: Washington, DC,
2000.
(5) (a) Kra´l, V.; Gale, P. A.; Anzenbacher, P.; Jursikova´, K.; Lynch, V.; Sessler,
J. L. Chem. Commun. 1998, 9. (b) Sessler, J. L.; Cho, W.-S.; Lynch, V.;
Kra´l, V. Chem.sEur. J. 2002, 8, 1134.
(6) (a) Dave, P. R.; Doyle, G. J. Org. Chem. 1995, 60, 6946. (b) Avarvari, N.;
Mezailles, N.; Richard, L.; Le Floch, P.; Mathey, F. Science 1998, 280,
1587. (c) Vogel, E.; Pohl, M.; Herrmann, A.; Wiss, T.; Ko¨nig, C.; Lex, J.;
Gross, M.; Gisselbrecht, J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 1520.
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(2) For a monograph, see: Gutsche, C. D. Calixarenes; The Royal Society of
Chemistry: Cambridge, 1989.
9
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J. AM. CHEM. SOC. 2004, 126, 15412-15422
10.1021/ja0465092 CCC: $27.50 © 2004 American Chemical Society

Coupling Synthesis of Heteroatom-Bridged Calixarenes
A R T I C L E S
13% yield of tetranitro-substituted tetraoxocalix[4]arene,9 while
the Pd(0)-catalyzed amination of 3-bromo-N-methylaniline
produced a mixture of azacalix[n]arenes (n ) 3-8) in very low
yields.10 Silicon-bridged calixarenes were synthesized by cou-
pling phenol or 1,3-dibromobenzene with dichlorodimethylsilane
in 16% or 12% yield, respectively.11 By incorporating hetero-
atoms with heteroaromatics, a few heteroatom-bridged calix-
heteroaromatics have also been prepared.7 Among them, silicon-
bridged calix[n]phosphaarenes are noticeable because they act
as ligands with strong π-acceptor properties.12 In almost all
cases, however, very low and unpractical chemical yields
(<20%) were obtained for heteroatom-bridged macrocyclic
compounds.7-13 As a consequence of difficulty of synthesis and
functionalization, the structures and recognition properties of
these appealing heteroatom-bridged calix(hetero)aromatics have
remained largely unexplored.
We envisioned that the introduction of oxygen and/or nitrogen
atoms as the bridge linkages in calix(hetero)aromatics would
result in a wide variety of fine-bridge-tuned macrocyclic cavities
because oxygen and, particularly, nitrogen atoms might adopt
sp3 and/or sp2 hybrid configurations with and/or without forming
conjugation with the neighboring (hetero)aromatics. Very
recently, we have established a fragment coupling approach to
synthesize azacalix[m]arene[n]pyridines (m ) n ) 2, 4) in a
total yield of 48%.14 The nitrogen-bridged calix[4]arene[4]-
pyridine prepared has been shown to exhibit indeed intriguing
structural property and remarkable capability to recognize [60]-
and [70]-fullerenes.14 Herein, we report a general, efficient, and
convenient synthesis of oxo- and/or azacalix[2]arene[2]triazines
based on the fragment coupling strategy. We will also show
that the bridging heteroatoms play indeed an important part in
determining the structural and spectroscopic properties of these
novel macrocycles.
reactivity of a cyanuric halide toward nucleophilic reagents in
a controlled fashion, we envisioned the synthetic advantages
of cyanuric halides in the construction of desired heteroatom-
bridged calix(hetero)aromatics.
Experimental Section
Melting points are uncorrected. Elemental analyses were performed
at the Analytical Laboratory of the Institute. All chemicals were dried
or purified according to standard procedures prior to use.
1,3-Bis(dichloro-s-triazinyloxy)benzene (3). To an ice-bath cooled
solution of cyanuric chloride 2 (5.55 g, 30 mmol) in tetrahydrofuran
(100 mL) was added dropwise a mixture of resorcinol 1 (1.65 g, 15
mmol) and diisopropylethylamine (4.48 g, 37.5 mmol) in tetrahydro-
furan (75 mL) during 2 h. The reaction mixture was stirred for another
2.5 h. After removal of diisopropylethylamine hydrochloride salt
through filtration, the filtrate was concentrated and chromatographed
on a silica gel column with a mixture of petroleum ether and ethyl
acetate as the mobile phase to give pure 1,3-bis(dichloro-s-triazinylox)-
benzene 3 (4.77 g, 78.3%) as a white solid: mp 140-142 °C (lit.22 mp
141-143 °C); IR (KBr) ν 1536, 1505, 1406 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.57 (t, J ) 8.2 Hz, 1H), 7.21 (dd, J ) 8.2 Hz, J ) 2.3 Hz,
2H), 7.11 (t, J ) 2.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 173.3,
170.7, 151.4, 130.9, 119.8, 115.0; MS (EI) m/z (%) 410 (4) (M+ + 6),
408 (14) (M+ + 4) 406 (18) (M+ + 2), 404 (26) (M+). Anal. Calcd for
C12H4Cl4N6O2: C, 35.50; H, 0.99; N, 20.70. Found: C, 35.49; H, 1.18;
N, 20.57.
N,N′-Bis(dichloro-s-triazinyl)-m-phenylenediamine (11). Follow-
ing the procedure for the preparation of 3, the reaction of m-
phenylenediamine 5 (1.08 g, 10 mmol) with 2 (3.69 g, 20 mmol) in
the presence of diisopropylethylamine (3.23 g, 25 mmol) gave pure
N,N′-bis(dichloro-s-triazinyl)-m-phenylenediamine 11 (3.34 g, 82.7%)
as a white solid: mp 244-245 °C (lit.23 mp 230-231 °C); IR (KBr)
1
ν 3251, 3135, 1583, 1541, 1389 cm-1; H NMR (300 MHz, DMSO-
d6) δ 11.25 (s, 2H), 7.89 (t, J ) 1.8 Hz, 1H), 7.42-7.46 (m, 3H); 13
C
NMR (75 MHz, DMSO-d6) δ 169.7, 168.8, 163.8, 137.3, 129.2, 118.2,
114.6; MS (EI) m/z (%) 408 (5) (M+ + 6), 406 (37) (M+ + 4), 404
(100) (M+ + 2), 402 (68) (M+). Anal. Calcd for C12H6Cl4N8: C, 35.67;
H, 1.50; N, 27.73. Found: C, 35.44; H, 1.39; N, 27.70.
Triazine is a valuable element in molecular recognition and
self-assembly because triazine-based molecules including
melamine derivatives can act as both hydrogen bond donor and
acceptor to bind guest molecules such as carbohydrates, cyanuric
acid, and uracil derivatives through multiple hydrogen bond
interactions.15 Besides, recent theoretical calculations16 and
single-crystal molecular structure of a copper(II)-triazine
complex17 have indicated a potential application of triazine as
an electron-deficient π-aromatic component to interact with
anion species. Although a triazine element has been incorporated
into a few macrocyclic molecules,18-21 construction of calix-
arene scaffolds utilizing triazine as the skeleton building blocks
has been underestimated.20,21 Having considered the high
N-(Dichloro-s-triazinyl)-3-(dichloro-s-triazinyloxy)aniline (15).
Following the procedure for the preparation of 3, the reaction of
3-aminophenol 4 (1.1 g, 10 mmol) with 2 (3.7 g, 20 mmol) in the
presence of diisopropylethylamine (3.23 g, 25 mmol) gave pure
N-(dichloro-s-triazinyl)-3-(dichloro-s-triazinyloxy)aniline 15 (3.03 g,
74.8%) as a white solid: mp 205-207 °C (lit.24 mp 199-200 °C); IR
1
(KBr) ν 3289, 1610, 1575, 1536, 1510 cm-1; H NMR (300 MHz,
CDCl3) δ 7.62-7.64 (m, 2H), 7.49 (t, J ) 8.1 Hz, 1H), 7.41-7.44 (m,
(15) For leading references of melamine-cyanurate assemblies, see: (a)
Whitesides, G. M.; Mathias, J. P.; Seto, C. T. Science 1991, 254, 1312. (b)
Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc. 1993, 115, 905. (c) Seto,
C. T.; Mathias, J. P.; Whitesides, G. M. J. Am. Chem. Soc. 1993, 115,
1321. (d) Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc. 1993, 115,
1330. (e) Mathias, J. P.; Simanek, E. E.; Whitesides, G. M. J. Am. Chem.
Soc. 1994, 116, 4326. (f) Prins, L. J.; Huskens, J.; De Jong, F.; Timmerman,
P. Reinhoudt, D. N. Nature 1999, 398, 498. (g) Prins, L. J.; De Jong, F.;
Timmerman, P.; Reinhoudt, D. N. Nature 2000, 408, 181. (h) Prins, L. J.;
Joliffe, K. A.; Hulst, R. Timmerman, P.; Reinhoudt, D. N. J. Am. Chem.
Soc. 2000, 122, 3617. (i) Bielejewska, A. G.; Marjo, C. E.; Prins, L. J.;
Timmerman, P.; De Jong, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 2001,
123, 7518. (j) Kawasaki, T.; Tokuhiro, M.; Kimizuka, N.; Kunitake, T. J.
Am. Chem. Soc. 2001, 123, 6792.
(7) For a useful overview of heteroatom-bridged calixarenes, see: Ko¨nig, B.;
Fonseca, M. H. Eur. J. Inorg. Chem. 2000, 2303.
(8) (a) Kumagai, H.; Hasegawa, M.; Miyanari, S.; Sugawa, Y.; Sato, Y.; Hori,
T.; Ueda, S.; Kamiyama, H.; Miyano, S. Tetrahedron Lett. 1997, 38, 3971.
(b) Iki, H.; Kabuto, C.; Fukushima, T.; Kumagai, H.; Takeya, H.; Miyanari,
S.; Miyashi, T.; Miyano, S. Tetrahedron 2000, 56, 1437. (c) Akdas, H.;
Bringel, L.; Graf, E.; Hosseini, M. W.; Mislin, G.; Pansanel, J.; De Cian,
A.; Fischer, J. Tetrahedron Lett. 1998, 39, 2311.
(9) Boros, E. E.; Andrews, C. W.; Davis, A. O. J. Org. Chem. 1996, 61, 2553.
(10) (a) Ito, A.; Ono, Y.; Tanaka, K. New J. Chem. 1998, 22, 779. (b) Ito, A.;
Ono, Y.; Tanaka, K. J. Org. Chem. 1999, 64, 8236.
(16) Mascal, M.; Armstrong, A.; Bartberger, M. D. J. Am. Chem. Soc. 2002,
124, 6274.
(11) (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. Engl. 1995, 34, 661. (c) Yoshida, M.;
Goto, M.; Nakanishi, F. Organometallics 1999, 18, 1465.
(12) (a) Avarvari, N.; Mezailles, N.; Ricard, L.; Le Floch, P.; Mathey, F. Science
1998, 280, 1587. (b) Avarvari, N.; Maigrot, N.; Ricard, L.; Mathey, F.; Le
Floch, P. Chem.sEur. J. 1999, 5, 2109.
(13) Miyazaki, Y.; Kanbara, T.; Yamamoto, T. Tetrahedron Lett. 2002, 43, 7945.
(14) Wang, M.-X.; Zhang, X.-H.; Zheng, Q.-Y. Angew. Chem., Int. Ed. 2004,
43, 838.
(17) Demeshko, S.; Dechert, S.; Meyer, F. J. Am. Chem. Soc. 2004, 126, 4508.
(18) Anelli, P. L.; Lunazzi, L.; Montanari, F.; Quici, S. J. Org. Chem. 1984,
49, 4197.
(19) Lo¨wik, D. W. P.; Lowe, C. R. Eur. J. Org. Chem. 2001, 2825.
(20) Graubaum, H.; Lutze, G.; Tittelbach, F.; Bartoazek, M. J. Prakt. Chem./
Chem.-Ztg. 1995, 337, 401.
(21) Graubaum, H.; Lutze, G. Costisella, B. J. Prakt. Chem./Chem.-Ztg. 1997,
339, 266.
(22) Mangini, A.; Mazzanti, G.; Tundo, A. U.S. Patent 3,454,551, 1969.
(23) Beech, W. F. J. Chem. Soc. C 1967, 466.
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A R T I C L E S
Wang and Yang
1H), 7.03-7.06 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 173.2, 170.9,
164.1, 151.4, 137.4, 130.5, 119.3, 118.1, 114.0; MS (EI) m/z (%) 409
(7) (M+ + 6), 407 (26) (M+ + 4), 405 (59) (M+ + 2), 403 (47) (M+).
Anal. Calcd for C12H5Cl4N7O: C, 35.58; H, 1.24; N, 24.21. Found:
C, 35.65; H, 1.47; N, 24.04.
N,N′-Bis(dichloro-s-triazinyl)-N,N′-dimethyl-m-phenylenedi-
amine (17). Following the procedure for the preparation of 3, the
reaction of N,N′-dimethyl-m-phenylenediamine 6 (0.41 g, 3 mmol) with
2 (1.33 g, 7.2 mmol) in the presence of diisopropylethylamine (0.93 g,
7.2 mmol) gave pure N,N′-bis(dichloro-s-triazinyl)-N,N′-dimethyl-m-
phenylenediamine 17 (1.0 g, 77.2%) as a white solid: mp 200-202
1
°C; IR (KBr) ν 1611, 1556, 1492, 1441, 1404 cm-1; H NMR (300
MHz, CDCl3) δ 7.55 (t, J ) 8.2 Hz, 1H), 7.24-7.30 (m, 3H), 3.61 (s,
6H); 13C NMR (75 MHz, CDCl3) δ 170.6, 170.1, 165.1, 142.8, 130.3,
125.2, 124.3, 39.1; MS (EI) m/z (%) 436 (6) (M+ + 6), 434 (27) (M+
+ 4), 432 (64) (M+ + 2), 430 (53) (M+). Anal. Calcd for
C14H10Cl4N8: C, 38.92; H, 2.33; N, 25.93. Found: C, 38.92; H, 2.40;
N, 25.71.
General Procedure for the Preparation of Oxo- and/or Aza-
Bridged Calix[2]arene[2]triazines. At room temperature, both solu-
tions of resorcinol, or diamine or 3-aminophenol (1 mmol), in acetone
(90 mL) and the trimer 3, 11, 15, or 17 (1 mmol) in acetone (90 mL)
were added dropwise at the same time and the same rate to a solution
of diisopropylethylamine (0.31 g, 2.4 mmol) in acetone (200 mL). In
the case of synthesis of 12 and 18, a mixture of K2CO3 (0.331 g, 2.4
mmol), water (40 mL), and acetone (160 mL) was used instead of diiso-
propylethylamine solution in acetone. After addition of two reactants,
which took about 3-10 h depending on the structure of substrates, the
resulting mixture was stirred for another 12-48 h until the starting
materials were consumed. The solvents were removed, and the residue
was chromatographed on a silica gel column to give pure product.
Tetraoxocalix[2]arene[2]triazine 7: 3 + 36 h; yield 46.5%; mp >
300 °C (colorless prisms from n-hexane/ethyl acetate) (Figure 1); IR
1
(KBr) ν 1551, 1440, 1387 cm-1; H NMR (300 MHz, CDCl3) δ 7.32
(t, J ) 8.2 Hz, 2H), 6.92 (dd, J ) 8.2 Hz, J ) 2.1 Hz, 4H), 6.72 (t, J
) 2.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 174.5, 172.4, 151.6,
130.8, 119.5, 115.9; MS (EI) m/z (%) 446 (9) (M+ + 4), 444 (43)
(M+ + 2), 442 (66) (M+), 409 (34), 407(100). Anal. Calcd for
C18H8Cl2N6O4: C, 48.78; H, 1.82; N, 18.96. Found: C, 48.97; H, 1.64;
N, 18.80.
Azatrioxocalix[2]arene[2]triazine 8: 8 + 12 h; yield 62%; mp >
300 °C (colorless needles from n-hexane/dichloromethane) (Figure 2);
IR (KBr) ν 3252, 1571, 1542, 1459, 1415 cm-1; 1H NMR (300 MHz,
DMSO-d6) δ 10.66 (s, 1H, NH), 7.40 (t, J ) 8.2 Hz, 1H), 7.35 (t, J )
8.0 Hz, 1H), 7.29 (t, J ) 2.2 Hz, 1H), 7.25 (t, J ) 2.1 Hz, 1H), 7.00-
7.09 (m, 3H), 6.91-6.93 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 172.5,
171.8, 170.9, 170.6, 170.4, 165.7, 151.6, 151.3, 150.8, 137.3, 130.7,
130.1, 122.7, 119.3, 119.2, 118.5, 118.4, 116.6; MS (EI) m/z (%) 445
(14) (M+ + 4), 443 (69) (M+ + 2), 441 (100) (M+), 408 (18), 407
(27), 406 (40), 405 (49). Anal. Calcd for C18H9Cl2N7O3: C, 48.89; H,
2.05; N, 22.17. Found: C, 48.95; H, 2.05; N, 22.27.
Diazadioxocalix[2]arene[2]triazine 9: 10 + 12 h; yield 79%; mp
> 300 °C (colorless needles from n-hexane/ethyl acetate) (Figure 3);
IR (KBr) ν 3383, 3275, 1569, 1550, 1420 cm-1; 1H NMR (300 MHz,
DMSO-d6) δ 10.56 (s, 2H, NH), 7.36-7.44 (m, 3H), 7.25 (t, J ) 8.0
Hz, 1H), 7.05 (dd, J ) 8.2 Hz, J ) 2.2 Hz, 2H), 6.83 (dd, J ) 8.0 Hz,
J ) 1.9 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 170.8, 170.2, 164.8,
151.6, 137.1, 130.7, 129.1, 120.2, 118.9, 118.4, 117.4; MS (EI) m/z
(%) 444 (13) (M+ + 4), 442 (68) (M+ + 2), 440 (100) (M+), 406 (17),
405 (25), 404 (38). Anal. Calcd for C18H10N8O2Cl2: C, 49.00; H, 2.28;
N, 25.40. Found: C, 48.93; H, 2.13; N, 25.15.
Figure 1. Crystal structure of tetraoxocalix[2]arene[2]triazine 7: (a) top
view and (b and c) side views. Distances between C(1) and C(9), C(4) and
C(12), N(3) and N(6), and C(15) and C(17) are 5.011, 4.441, 4.460, and
9.489 Å, respectively.
DMSO-d6) δ 7.39 (t, J ) 8.0 Hz, 1H), 7.27 (t, J ) 8.3 Hz, 1H), 7.15
(dd, J ) 7.9 Hz, J ) 1.6 Hz, 2H), 7.06 (d, J ) 1.7 Hz, 1H), 6.89-6.92
(m, 3H), 5.76 (s, 0.5H, CH2Cl2), 3.36 (s, 6H); 13C NMR (75 MHz,
DMSO-d6) δ 170.4, 169.9, 165.8, 151.7, 143.3, 130.7, 130.1, 126.5,
125.7, 118.9, 116.4, 54.9 (CH2Cl2), 38.8; MS (EI) m/z (%) 472 (13)
(M+ + 4), 470 (65) (M+ + 2), 468 (100) (M+), 435 (26), 433(71).
Anal. Calcd for C20H14Cl2N8O2‚(0.5CH2Cl2): C, 48.11; H, 2.95; N,
21.90. Found: C, 48.47; H, 2.90; N, 21.72.
Oxotriazacalix[2]arene[2]triazine 12: 12 + 48 h; yield 46%; mp
> 300 °C (white powder from n-hexane/hetrahydrofuran); IR (KBr) ν
3266, 1591, 1572, 1523, 1421, 1396 cm-1; 1H NMR (300 MHz, DMSO-
d6) δ 10.57 (s, 1H, NH), 10.07 (s, 1H, NH), 9.95 (s, 1H, NH), 7.62 (s,
1H), 7.53 (s, 1H), 7.34 (t, J ) 8.0 Hz, 1H), 7.24 (t, J ) 8.0 Hz, 1H),
6.97 (dd, J ) 8.1 Hz, J ) 1.3 Hz, 1H), 6.90 (d, J ) 8.1 Hz, 1H), 6.80
(d, J ) 7.4 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 170.1, 170.0,
168.3, 165.2, 164.9, 164.2, 151.1, 138.0, 137.9, 137.1, 129.8, 129.0,
122.0, 120.6, 119.9, 119.2, 118.4, 117.9; MS (EI) m/z (%) 443 (3) (M+
+ 4), 441 (14) (M+ + 2), 439 (23) (M+), 405 (4), 403 (10). Anal.
Calcd for C18H11Cl2N9O‚(0.25C4H8O): C, 49.80; H, 2.86; N, 27.51.
Found: C, 49.79; H, 2.70; N, 27.30.
Dimethylazadioxocalix[2]arene[2]triazine 10: 5 + 12 h; yield
57%; mp > 300 °C (colorless prisms from dichloromethane/acetone)
1
(Figure 4); IR (KBr) ν 1574, 1508, 1386 cm-1; H NMR (300 Hz,
Tetraazacalix[2]arene[2]triazine 13: 8 + 48 h; yield 58%; mp >
300 °C (colorless prisms obtained from the diffusion of diethyl ether
to DMF solution of product) (lit.20 mp > 300 °C) (Figure 5); IR (KBr)
(24) Harayama, T.; Sekiguchi, S.; Matsui, K. J. Heterocycl. Chem. 1970, 7,
975.
9
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Coupling Synthesis of Heteroatom-Bridged Calixarenes
A R T I C L E S
Figure 3. Crystal structure of diazadioxocalix[2]arene[2]triazine 9: (a) top
view and (b and c) side views. Distances between C(33) and C(43), C(36)
and C(46), N(11) and N(21), and C(12) and C(22) are 7.979, 4.213, 4.544,
and 9.328 Å, respectively.
Figure 2. Crystal structure of azatrioxocalix[2]arene[2]triazine 8: (a) top
view and (b and c) side views. Distances between C(8) and C(17), C(5)
and C(14), N(2) and N(4), and C(1) and C(11) are 6.533, 4.328, 4.619, and
9.200 Å, respectively.
1
ν 3246, 1596, 1576, 1558, 1388 cm-1; H NMR (300 MHz, DMSO-
(0.25C4H8O): C, 51.97; H, 3.74; N, 28.86. Found: C, 51.90; H, 3.64;
N, 28.70.
d6) δ 10.02 (s, 4H, NH), 7.78 (s, 2H), 7.23 (t, J ) 8.0 Hz, 2H), 6.81
(dd, J ) 8.0 Hz, J ) 1.8 Hz, 4H); 13C NMR (75 MHz, DMSO-d6) δ
168.0, 164.2, 137.9, 128.9, 118.7, 118.0; MS (MALDI-TOF) m/z 443
(M+ + 1 + 4), 441 (M+ + 1 + 2), 439 (M+ + 1). Anal. Calcd for
C18H12Cl2N10: C, 49.22; H, 2.75; N, 31.89. Found: C, 49.25; H, 2.91;
N, 31.69.
Azadimethylazaoxocalix[2]arene[2]triazine 16: 8 + 48 h; yield
34%; mp > 300 °C (colorless prisms from dichloromethane/acetone)
1
(Figure 7); IR (KBr) ν 3225, 1576, 1514, 1405, 1373 cm-1; H NMR
(300 MHz, DMSO-d6) δ 9.75 (s, 1H, NH), 7.39 (t, J ) 7.9 Hz, 1H),
7.11-7.26 (m, 4H), 7.05 (t, J ) 1.9 Hz, 1H), 6.85 (dd, J ) 7.9 Hz, J
) 1.9 Hz, 1H), 6.79 (d, J ) 8.0 Hz, 1H), 3.38 (s, 3H), 3.32 (s, 3H);
13C NMR (75 MHz, DMSO-d6) δ 170.3, 168.9, 168.5, 166.0, 165.4,
164.2, 151.1, 144.4, 143.3, 138.2, 130.7, 129.5, 127.1, 125.6, 124.9,
122.1, 119.6, 117.7, 39.4, 38.4; MS (EI) m/z (%) 471 (12) (M+ + 4),
469 (66) (M+ + 2), 467 (100) (M+), 434 (17), 432 (51). Anal. Calcd
for C20H15Cl2N9O: C, 51.40; H, 3.23; N, 26.92. Found: C, 51.34; H,
3.26; N, 26.50.
Diazadimethylazacalix[2]arene[2]triazine 14: 10 + 12 h; yield
55%; mp > 300 °C (colorless prisms from n-hexane/tetrahydrofuran)
(Figure 6); IR (KBr) ν 3237, 3073, 1575, 1541, 1514, 1405 cm-1; H
1
NMR (300 MHz, C4D8O) δ 8.85 (s, 2H, NH), 7.51 (d, J ) 1.8 Hz,
1H), 7.37 (t, J ) 8.1 Hz, 1H), 7.30 (s, 1H), 7.03-7.08 (m, 3H), 7.62
(dd, J ) 8.1 Hz, J ) 2.1 Hz, 2H), 3.42 (s, 6H);13C NMR (75 MHz,
C4D8O) δ 167.2, 164.5, 161.9, 143.0, 136.9, 128.6, 126.5, 126.4, 123.1,
115.8, 114.8, 36.2; MS (EI) m/z (%) 470 (12) (M+ + 4), 468 (69) (M+
+ 2), 466 (100) (M+), 431 (18). Anal. Calcd for C20H16Cl2N10‚
Tetramethylazacalix[2]arene[2]triazine 18: 4 + 36 h; yield 46%;
mp > 300 °C (colorless prisms from n-hexane/dichloromethane) (Figure
9
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A R T I C L E S
Wang and Yang
Figure 4. Crystal structure of dimethylazadioxocalix[2]arene[2]triazine
10: (a) top view and (b and c) side views. Distances between C(4) and
C(14), C(7) and C(17), N(4) and N(8), and C(10) and C(20) are 5.175,
4.449, 4.665, and 9.032 Å, respectively.
1
8); IR (KBr) ν 1573, 1559, 1485, 1398 cm-1; H NMR (300 MHz,
CDCl3) δ 7.19 (t, J ) 8.0 Hz, 2H), 6.84 (dd, J ) 7.9 Hz, J ) 2.0 Hz,
4H), 6.71 (t, J ) 1.9 Hz, 2H), 3.36 (s, 12H); 13C NMR (75 MHz,
CDCl3) δ 169.5, 165.3, 145.1, 130.1, 127.0, 125.8, 38.0; MS (EI) m/z
(%) 498 (13) (M+ + 4), 496 (68) (M+ + 2), 494 (100) (M+), 459 (22).
Anal. Calcd for C22H20Cl2N10: C, 53.34; H, 4.07; N, 28.27. Found: C,
53.39; H, 4.11; N, 28.12.
Figure 5. Crystal structure of tetraazacalix[2]arene[2]triazine 13: (a) top
view and (b and c) side views. Distances between C(5) and C(5A), C(8)
and C(8A), N(1) and N(6), and C(1) and C(10) are 7.392, 4.217, 4.648,
and 9.035 Å, respectively.
(t, J ) 8.0 Hz, 1H), 6.89 (dd, J ) 8.1 Hz, J ) 2.2 Hz, 2H), 6.67 (dd,
J ) 8.0 Hz, J ) 1.8 Hz, 2H), 4.75-4.84 (m, 4H), 3.63-3.70 (m, 16H);
13C NMR (75 MHz, DMSO-d6) δ 170.7, 166.1, 164.8, 164.7, 152.2,
138.9, 138.8, 130.0, 128.4, 118.2, 118.1, 117.7, 117.2, 117.0, 58.9,
58.7, 50.0; MS (MALDI-TOF) m/z 579.3 (M+ + 1), 601.2 (M+ + 23),
617.1 (M+ + 39). Anal. Calcd for C28H30N10O6‚0.5H2O: C, 53.15; H,
5.32; N, 23.84. Found: C, 53.04; H, 5.14; N, 23.62.
Reaction of Diazadioxocalix[2]arene[2]triazine 9 with Dietha-
nolamine: A mixture of diethanolamine (1 mmol) and diisopropyl-
ethylamine (2.2 mmol) in THF (20 mL) was stirred at 70 °C for 30
min. A solution of diazadioxocalix[2]arerne[2]triazine 9 (0.5 mmol)
in THF (20 mL) was then added during 30 min. The reaction mixture
was refluxed for 36 h. After removal of the solvent, the residue was
subjected to silica gel column chromatography with a mixture of
acetone, petroleum ether, and methanol (30:15:2) as an eluent to give
product 19 (0.208 g, 72%) as a white solid: mp 233-235 °C; IR (KBr)
Results and Discussion
1
ν 3427, 1584 cm-1; H NMR (300 MHz, DMSO-d6) δ 9.23 (s, 2H),
The synthesis of tetraoxo-bridged calix[2]arene[2]triazine 7
was first attempted by directly reacting resorcinol 1 with 1 equiv
7.37 (d, J ) 1.6 Hz, 1H), 7.31 (t, J ) 8.1 Hz, 1H), 7.15 (s, 1H), 7.09
9
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Coupling Synthesis of Heteroatom-Bridged Calixarenes
A R T I C L E S
Figure 7. Crystal structure of N,N′-dimethylated oxotriazacalix[2]arene-
[2]triazine 16: (a) top view and (b and c) side views. Distances between
C(6) and C(17), C(9) and C(14), N(2) and N(6), and C(1) and C(11) are
5.559, 4.421, 4.681, and 9.135 Å, respectively.
Figure 6. Crystal structure of N,N′-dimethylated tetraazacalix[2]arene[2]-
triazine 14: (a) top view and (b and c) side views. Distances between C(6)
and C(15), C(9) and C(18), N(1) and N(8), and C(2) and C(11) are 7.393,
4.356, 4.677, and 9.467 Å, respectively.
either oligomers or other byproducts. The macrocyclizative
coupling reaction between resorcinol 1 and the linear trimer 3
took place effectively at room temperature, and tetraoxocalix-
[2]arene[2]triazine 7 was obtained in 46.5% yield in acetone
solution with DIPEA as a base (Scheme 1). A one-pot synthesis
of tetraoxocalix[2]arene[2]triazine 7 by the room-temperature
macrocyclic coupling reaction of resorcinol with the linear trimer
3, which was resulted initially from the condensation of
resorcinol with cyanuric chloride at 0 °C without isolation and
purification, gave an overall chemical yield of 18%. Because
of the ease of preparation and purification of the linear trimer
3 and its high reactivity toward other annulation reagents in
the construction of heteroatom-bridged calix(hetero)aromatics
(vide infra) and because of good chemical yields of individual
coupling reactions, the stepwise fragment coupling approach
to desired macrocyclic molecules appears more advantageous
and practical.
of cyanuric chloride 2. Under various conditions examined,
however, the maximum chemical yield of desired product 7 was
only 11%. In many cases, the reaction produced a mixture of
oligomers. A stepwise strategy, the fragment coupling approach,
was then investigated. We found by trial and error that, in the
presence of diisopropylethylamine (DIPEA) as an acid scav-
enger, the reaction between resorcinol and 2 equiv of cyanuric
chloride in tetrahydrofuran proceeded smoothly and efficiently
at 0 °C to afford linear trimer product, 1,3-bis(dichloro-s-
triazinyloxy)benzene 322 in 78%. The chemical yield can be
improved slightly when a large excess amount of cyanuric
chloride was employed. It should be noted that the use of
acetone or a mixture of acetone and water as the solvent and
the use of NaOH, Na2CO3, triethylamine, and collidine instead
of DIPEA had detrimental effects on the formation of 3, yielding
9
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A R T I C L E S
Wang and Yang
Scheme 1
between cyanuric chloride 2 and m-phenylenediamine 5, 3-ami-
nophenol 4, and N,N′-m-phenylenediamine 6, respectively. Being
a reactive intermediate, N,N′-bis(dichloro-s-triazinyl)-m-phe-
nylenediamine 11 underwent macrocyclizative coupling reac-
tions with 3-aminophenol 4 and m-phenylenediamines 5 and 6
to produce the desired hetereoatom-bridged calix[2]arene[2]-
triazines 12, 13,20 and 14 in 46-58% yields (Scheme 2). Both
linear trimeric fragments 15 and 17 were found analogously
reactive to interact with N,N′-m-phenylenediamine 6, yielding
N,N′-dimethylated oxotriazacalix[2]arene[2]triazine 16 and
tetramethylazacalix[2]arene[2]triazine 18, albeit in lower chemi-
cal yield in the former case (Schemes 3 and 4). In the cases of
synthesis of oxotriazacalix[2]arene[2]triazine 12 and tetra-
methylazacalix[2]arene[2]triazine 18, however, the best results
were obtained when K2CO3 was applied as a base and a mixture
of water and acetone (1:4) was used as the reaction media
(Schemes 2 and 4). It is particularly worth noting that the
stepwise fragment coupling approach is practically applicable
in the multigram scale synthesis of aza- and/or oxo-bridged
calix[2]arene[2]triazines. For example, the macrocyclizative
coupling reaction between 3 and resorcinol 1 in 2 L of reaction
medium gave 2.6 g of pure tetraoxocalix[2]arene[2]triazine 7.
The structures of all oxo- and/or aza-bridged calix[2]arene-
[2]triazines synthesized were confirmed on the basis of spec-
troscopic data and elemental analysis. It was noticeable that all
macrocyclic molecules exhibit only one set of signals in both
1H and 13C NMR spectra. For example, both tetraoxocalix[2]-
arene[2]triazine 7 and tetraazacalix[2]arene[2]triazine 13 give
three types of proton signals in 1H NMR and six carbon
resonance peaks in 13C NMR, the results being in agreement to
a highly symmetric structure having two meta disubstituted
benzene and s-triazine moieties. In the case of tetramethylazacalix-
[2]arene[2]triazine 18, in addition to the proton signals of a meta
Figure 8. Crystal structure of tetramethylazacalix[2]arene[2]triazine 18:
(a) top view and (b and c) side views. Distances between C(6) and C(6A),
C(9) and C(9A), N(4) and N(4A), and C(2) and C(2A) are 6.046, 4.289,
4.721, and 9.465 Å, respectively.
At ambient temperature, the linear trimer 3 underwent equally
efficient macrocyclizative coupling reactions with 3-amino-
phenol 5, m-phenylenediamine 6, and N,N′-dimethyl-m-phe-
nylenediamine 7, respectively, to produce the corresponding
azatrioxocalix[2]arene[2]triazine 8, diazadioxocalix[2]arene[2]-
triazine 9, and dimethyazadioxocalix[2]arene[2]triazine 10 in
the chemical yields ranging from 57% to 79% (Scheme 1).
To further examine the generality of the fragment coupling
approach and also to prepare oxo-triaza-, tetraaza-, and tetram-
ethylaza-bridged calix[2]arene[2]triazine analogues, other linear
trimeric fragments were synthesized. Similar to the synthesis
of 3, N,N′-bis(dichloro-s-triazinyl)-m-phenylenediamine 11,23
N,O-bis(dichloro-s-triazinyl)-3-aminophenol 15,24 and N,N′-bis-
(dichloro-s-triazinyl)-N,N′-dimethyl-m-phenylenediamine 17 were
readily and high yieldingly prepared from the coupling reaction
9
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Coupling Synthesis of Heteroatom-Bridged Calixarenes
A R T I C L E S
Scheme 2
Except for tetraoxo- and azatrioxocalix[2]arene[2]triazines 7
and 8, all of the heteroatom-bridged calix[2]arene[2]triazines
have low solubility in most common polar and nonpolar
solvents. Surprisingly, however, most of them dissolve very well
in tetrahydrofuran. It is also worth noting that, for calix[2]arene-
[2]triazines bearing more than three oxygen bridging atoms, such
as 7 and 8, no absorption band was observed in their UV-vis
spectra, while the rest of calix[2]arene[2]triazine compounds
absorbed UV light in the range 239-279 nm (Figure SI1). More
interestingly, calix[2]arene[2]triazines bridged by more than two
methlyaza (MeN) groups displayed an absorption band at around
240 nm. With the increase of aza (NH) bridges from 2 to 4, the
absorption band shifted bathochromically from 239 to 279 nm.
The outcomes of UV-vis absorption spectra reflected the
conjugation state of the bridging heteroatoms with their
neighboring aromatic rings. In other words, the electron-donating
nature and less steric hindrance rendered the aza (NH) linkage
conjugate easily with the aromatic rings, leading to a batho-
chromic effect in the UV-vis spectrum. The presence of a
methyl group on the bridging nitrogen atom (MeN), on the other
hand, might cause the macrocyclic ring to be more folded to
release the steric hindrance around the bridging nitrogen and,
therefore, preclude methylaza (MeN) from effectively conjugat-
ing with the aromatics.
To investigate the solid-state structures of heteroatom-bridged
calix[2]arene[2]triazines and also to examine the effect of a
bridging heteroatom on the conformational structures of the
macrocycles, single-crystal molecular structures of 7-10, 12,
13, 16, and 18 were determined (Table 1). Some intriguing
structural features are noticed. First, all heteroatom-bridged
calix[2]arene[2]triazines adopt a 1,3-alternate conformation in
the solid state (Figures 1-8). This is different from calixarene,2
calixpyridine,5 and calixpyrroles.4 Second, four bridging atoms
are located nearly in the same plane with the deviation of less
than 0.2395 Å. Additionally, it is always a pair of benzene rings
that stand up to form a cliplike conformation, while a pair of
opposite triazine rings always tends to be roughly coplanar and
edge-to-edge orientated and is well separated. Furthermore, both
the bond lengths between heteroatom and its connecting
(hetero)aromatic carbons and bond angles of bridging atoms
disubstituted benzene moiety, there is only one sharp singlet
peak at 3.36 ppm corresponding to 12 protons of four bridging
methylamino groups. Only one sharp singlet peak of two methyl
protons was also observed in the range 3.36-3.42 ppm for
dimethylazadioxocalix[2]arene[2]triazine 9 and dimethylated
tetraazacalix[2]arene[2]triazine 14. No peak split or other
changes were observed when 1H NMR spectra of dimethylaza-
dioxocalix[2]arene[2]triazine 10, N,N′-dimethylated tetraazacalix-
[2]arene[2]triazine 14, and tetramethylazacalix[2]arene[2]triazine
18 were recorded at -50 °C. The spectroscopic characteristics
observed suggest that either these macrocyclic molecules adopt
stable symmetric conformations or these macrocycles are
conformationally flexible and all conformations interconvert
rapidly on the NMR time scale above -50 °C.
Scheme 3
Scheme 4
9
J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004 15419

A R T I C L E S
Wang and Yang
indicate that heteroatoms form conjugation with a triazine ring
rather than with a benzene ring. The cavity of heteroatom-
bridged calix[2]arene[2]triazines can therefore be viewed as
resulting from a cyclic array of two isolated benzene rings and
two conjugated 2,6-diaza-, 2,6-dioxo-, or 2-aza-6-oxo-substituted
triazine segments in a 1,3-alternate fashion. Finally, the nature
of the bridging units influences the inclined angles of both
benzene and triazine rings to the plane of the four linking
heteroatoms. In other words, the cavity of the heteroatom-
bridged calix[2]arene[2]triazines was controlled by the nature
of the bridging heteroatoms. For example, two benzene rings
in tetraoxocalix[2]arene[2]triazine 7 are almost perpendicular
to the plane formed by four bridging oxygen atoms, with the
inclined angles being 89.3° and 77.4°, respectively (Figure 1).
The distance of two face-to-face paralleled benzene rings ranges
from 4.441 Å at the low rim to 5.011 Å at the upper rim,
suggesting a weak π-π stacking interaction. A similar heavily
folded 1,3-alternate conformation was also observed for
dimethylazadioxocalix[2]arene[2]triazine 16, in which the dis-
tance between two benzene rings is from 4.449 Å (low rim) to
5.175 Å (upper rim) and the inclined angles of two benzene
rings are 83.6° and 81.2°, respectively (Figure 7). Replacement
of oxygen linkages by methylaza (MeN) or aza (NH) groups
led to the opening of the upper rim of two paralleled benzene
rings. This was exemplified by the extreme case of molecule 9
in which the inclined angles of diaza-linked and dioxo-linked
benzene rings were 27.8° and 63.7°, respectively, and the
distance of the upper rim of two benzene rings spanned 7.979
Å (Figure 3). The inclined angles of triazine rings remain in a
narrow range between 20.5° and 36°, and the distance between
two triazines rings at the upper rim ranges from 9.032 to 9.489
Å (Figures 1-8).
The crystal structural features of heteroatom-bridged calix-
[2]arene[2]triazines are most probably resulted from the com-
bination of electronic and steric effects of both bridging
heteroatoms and (hetero)aromatics. Because of the lack of intra-
annular hydrogen bonds that exist in calixarene,2 all heteroatom-
bridged calix[2]arene[2]triazines synthesized do not adopt the
corn conformation. Moreover, to avoid possible steric hindrance
arisen from the corn conformation, heteroatom-bridged calix-
[2]arene[2]triazines adopt a 1,3-alternate conformation. This is
the same for the situation of azacalix[2]arene[2]pyridine14 which
adopts the 1,3-alternate as the most energetically stable
conformation. The strong electron-withdrawing nature of tri-
azinyl and less steric repulsion between triazinyl and the
bridging moiety, methylaza (NMe) in particular, may be
responsible for the favored formation of conjugation of a
bridging heteroatom with a triazine ring rather than with a
benzene ring. Therefore the cavity of all heteroatom-bridged
calix[2]arene[2]triazines are resulted from four planar segments,
two isolated benzene rings, and two diheteroatom-conjugated
triazine rings, in a 1,3-alternate pattern. Since a triazine ring is
a π-deficient aromatic ring with a positive charge,16 two opposite
triazine rings in all calix[2]arene[2]triazines tend to be roughly
coplanar and keep apart from each other. In contrast, however,
two opposite benzene rings tend to align in parallel, such as
those observed in 7 (Figure 1) and 10 (Figure 4), that might
bring in extra stabilization of the molecule due to weak π-π
stacking interaction. The combined steric and electronic effects
of bridging heteroatoms and (hetero)aromatics result in the
2.
Table
9
15420 J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004

Coupling Synthesis of Heteroatom-Bridged Calixarenes
A R T I C L E S
Scheme 5
Figure 9. Intermolecular hydrogen bond formation of 16 in the solid state.
d(D-H) ) 0.860 Å, d(H‚‚‚A) ) 2.094 Å, D-H‚‚‚A ) 173.7°, d(D‚‚‚A) ) 2.950
Å.
structures. For example, a pair of intermolecular hydrogen bonds
were evidenced in N,N′-dimethylated oxotriazacalix[2]arene[2]-
triazine 16 (Figure 9), whereas no intermolecular interaction
was observed at all in the crystal structure of azatrioxocalix-
[2]arene[2]triazine 8. In the case of diazadioxocalix[2]arene-
[2]triazine 9, there was only one pair of intermolecular hydrogen
bonds formed, leading to a layered structure consisting of an
intermolecular hydrogen bonded dimer repeating unit (Figure
10). In contrast, one N,N′-dimethylated tetraazacalix[2]arene-
[2]triazine molecule 14 formed two pairs of hydrogen bonds
intermolecularly with its neighboring two molecules, yielding
a one-dimensional infinite chain structure (Figure 11). The per-
fect and multiple, i.e., four pairs or eight, hydrogen bonds were
formed for each of the tetraazacalix[2]arene[2]triazine melocules
13 with its neighboring four molecules and, therefore, produced
a two-dimensional zigzag layered structure (Figure 12).
All heteroatom-bridged calix[2]arene[2]triazines can serve as
versatile platforms for the construction of more sophisticated
and functionalized host molecules, since the chlorine substituents
on both triazine rings can be readily displaced by a variety of
nucleophiles. In the presence of diisopropylethylamine, for
example, diazadioxocalix[2]arene[2]triazine 9 underwent an
efficient nucleophilic substitution reaction with diethanolamine
to furnish product 19 in 72% yield. Having being functionalized
with four hydroxy groups, the new macrocyclic molecule 19
shows dramatically improved solubility in methanol (Scheme
5).
Figure 10. Intermolecular hydrogen bonding between two molecules of 9
in a layered structure. d(D-H) ) 0.860 Å, d(H‚‚‚A) ) 2.211 Å, D-H‚‚‚A )
161.2°, d(D‚‚‚A) ) 3.038 Å.
formation of a set of calix[2]arene[2]triazines of varied cavities
in which the distances between two benzene rings at the upper
rim span from 5.011 to 7.979 Å (Figures 1-8).
Being amino-substituted triazine species, it was not surprising
to observe the intermolecular hydrogen bonding effect of the
aza (NH)-bridged calix[2]arene[2]triazines in the solid state.
However, the formation of intermolecular hydrogen bond(s) was
strongly influenced by intrinsic structure of the rest heteroatoms,
and different intermolecular hydrogen bond formation affected
dramatically molecular packing patterns yielding various solid
Conclusion
We have developed an efficient and convenient stepwise
fragment coupling approach to the synthesis of aza- and/or oxo-
Figure 11. One-dimensional chain structure of 14 formed through intermolecular hydrogen bonds in the solid state. d[N(5D)-H(5D)] ) 0.860 Å, d[H(5D)...N(3A)]
) 2.164 Å, N(5D)-H(5D)‚‚‚N(3A) ) 173.5°, d[N(5D)‚‚‚N(3A)] ) 3.020 Å, d[N(4A)-H(4A)] ) 0.860 Å, d[H(4A)‚‚‚N(6D)] ) 2.425 Å, N(4A)-H(4A)‚‚‚N(6D) )
160.8°, d[N(4A)‚‚‚N(6D)] ) 3.250 Å.
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A R T I C L E S
Wang and Yang
linked calix(hetero)aromatics if different fragments are used.
In addition, the aza- and/or oxo-bridged calix[2]arene[2]triazines
are versatile macrocyclic platforms for the construction of more
sophisticated and functionalized molecular architectures because
of the ease of elaboration of benzene rings and chloro-substituted
triazine rings. This has been exemplified by the efficient
conversion of the parent diazadioxocalix[2]arene[2]triazine 9
into its bis(dihydroxyethylamino)-substituted derivative 19.
Aza- and/or oxo-bridged calix[2]arene[2]triazines obtained
adopt a 1,3-alternate conformation, with a pair of triazine rings
being roughly coplanar while a pair of benzene rings were
perpendicular to the plane defined by four bridging heteroatoms.
Because of the electronic and steric effects, the bridging
heteroatoms tend to form conjugation with a triazine ring rather
than a benzene ring, and the cavity of heteroatom-bridged calix-
[2]arene[2]triazines can therefore be viewed as being resulted
from two isolated benzene planes and two bis-heteroatom-
conjugated triazine planes in a 1,3-alternate fashion. The cavity
of the heteroatom-bridged calix[2]arene[2]triazines, such as the
distances between two opposite (hetero)aromatic rings and the
inclined angles of (hetero)aromatic rings to the plane of four
bridging heteroatoms, is determined strongly by the nature of
the bridging heteroatoms. The upper rim distances between two
benzene rings range widely from 5.011 to 7.979 Å when
heteroatoms varied from four oxygen atoms to two oxygen and
two nitrogen atoms. To our knowledge, this is probably the first
example that the cavity of calixarene species is regulated by
the bridge linkages. That might open an avenue for one to
coarse- and fine-regulate the cavity of these macrocycles by
modifying not only the (hetero)aromatic rings but also the
bridging heteroatoms as well. In the solid state, different patterns
of intermolecular hydrogen bonds were observed. The multiple
intermolecular hydrogen bond interactions among N,N′-dim-
ethylated tetraazacalix[2]arene[2]triazine 14 and among tetra-
azacalix[2]arene[2]triazine 13 led to the formation of an infinite
one-dimensional chain structure and a two-dimensional zigzag
layered structure, respectively. The readily tunable cavity
structures and the unique electronic feature of the surface of
the cavity, i.e., 1,3-alternative electron-rich and electron-deficient
π-aromatics, should render heteroatom-bridged calix[2]arene-
[2]triazines and their derivatives intriguing macrocyclic host
molecules in the study of molecular recognition.
Figure 12. Two-dimensional zigzag layered structure of 13 formed through
multiple intermolecular hydrogen bonds in the solid state: (a) along a axis
and (b) along b axis. d(D-H) ) 0.860 Å, d(H‚‚‚A) ) 2.284 Å, D-H‚‚‚A )
159.0°, d(D‚‚‚A) ) 3.103 Å.
bridged calix[2]arene[2]triazines. In the presence of diisopro-
pylethylamine in tetrahydrofuran at 0 °C, resorcinol 1, m-phe-
nylenediamine 5, 3-aminophenol 4, and N,N′-dimethyl-m-
phenylenediamine 6 underwent, respectively, a coupling reaction
with cyanuric chloride 2 to give the corresponding linear trimers
3, 11, 15, and 17 in the chemical yields ranging from 75% to
83%. Macrocyclizative coupling reaction of the linear trimers
3, 11, 15, and 17 with respective resorcinol 1, m-phenylenedi-
amine 5, 3-aminophenol 4, and N,N′-dimethyl-m-phenylenedi-
amine 6 proceeded smoothly and efficiently in acetone at room
temperature to afford good yields of heteroatom-bridged calix-
[2]arene[2]triazines. The high yielding fragment coupling ap-
proach established in this study should be generally applicable
in the preparation of various heteroatom-bridged calix(hetero)-
aromatics when substituted (hetero)aromatic diamine, diphenol,
and aminophenol derivatives are employed. The method should
also have potential in the synthesis of unsymmetric heteroatom-
Acknowledgment. The work was partially supported by funds
from the National Natural Science Foundation of China,
Ministry of Science and Technology of China (Grant No.
2002CCA03100) and Chinese Academy of Sciences. We thank
Dr. H.-W. Ma for determining the crystal structures of products
and Q.-Q. Wang, B.-Y. Hou, and M.-H. Huang for their
technical assistance.
Supporting Information Available: 1H and 13C NMR spectra
and UV-vis spectra of aza- and/or oxo-bridged calix[2]arene-
[2]triazines. This material is available free of charge via the
Internet at http://pubs.acs.org.
JA0465092
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15422 J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004