Synthesis, structure, and reactions of NH-bridged calix[m]arene[n]pyridines

Article abstract of DOI:10.1021/jo900826n

(Chemical Equation Presented) NH-bridged calix[1]arene[3]pyridine and calix[2]arene[2]pyridine were synthesized readily from efficient deprotection of N-Boc groups of NBoc-bridged calix[m]arene[n]pyridine derivatives which were prepared by a macrocyclic c

Full text of DOI:10.1021/jo900826n

pubs.acs.org/joc
Synthesis, Structure, and Reactions of NH-Bridged
Calix[m]arene[n]pyridines
Bo Yao, De-Xian Wang, Han-Yuan Gong, Zhi-Tang Huang, and Mei-Xiang Wang*
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and
Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
mxwang@iccas.ac.cn
Received April 22, 2009
NH-bridged calix[1]arene[3]pyridine and calix[2]arene[2]pyridine were synthesized readily from efficient
deprotection of N-Boc groups of NBoc-bridged calix[m]arene[n]pyridine derivatives which were
prepared by a macrocyclic coupling reaction between NBoc-linked trimers and 1,3-phenylenediamine.
In the solid state, calix[2]arene[2]pyridine adopted the flattened saddle conformation, while NH-bridged
calix[1]arene[3]pyridine gave a slightly twisted 1,3-alternate conformer. In both cases, all NH bridges
formed partial conjugation with both pyridine and benzene rings, whereas in solution they gave
symmetric conformational structures in which the conjugation of bridging NH units with pyridine ring
was stronger than with benzene ring. In the presence of NaH, NH-bridged calix[2]arene[2]pyridine
reacted efficiently with methyl iodide and allyl bromide to afford the corresponding N-alkylated products
in almost quantitative yield. Upon treatment of NH- and NMe-bridged calix[2]arene[2]pyridines with
CF3CO2D and CuBr2, deuteration and bromination reactions took place selectively on the pyridine ring,
producing respectively the pyridine ring-deuterated and -brominated macrocyclic products.
Introduction
of supramolecular chemistry based on calix[n]arenes since
the pioneering work of Gutsche in the 1970s.2 Because of
their easy availability, unique conformational structures,
and molecular recognition properties, calix[n]arenes have
become an indispensable part of supramolecular chemistry.3
Heterocalixaromatics,4-8 heteroatom-bridged calixaromatics,
The design and synthesis of novel and functional macro-
cyclic host molecules have always been one of the driving
forces to promote the major advances of supramolecular
science.1 One of the well-known examples is the development
(1) Comprehensive Supramolecular Chemistry; Atwood, J. L., Davies,
€
J. E. D., MacNicol, D. D., Vogtle, F., Eds.; Pergamon Press: New York,
(5) 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; Kanbara, T.; Yamamoto, T. Tetra-
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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,
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Y.; Yanagi, T.; Kanbara, T.; Yamamoto, T. Synlett 2005, 2, 263. (k) Ishibashi,
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(2) (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.
(3) (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,
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DC, 2000. (c) Calixarenes 2001; Asfari, Z., Bohmer, V., Harrowfield, J.,
Vicens, J., Saadioui, M., Eds.; Kluwer Academic Publishers: Dordrect, The
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DOI: 10.1021/jo900826n Published on Web 06/04/2009
r
J. Org. Chem. 2009, 74, 5361–5368 5361
2009 American Chemical Society

Yao et al.
JOCArticle
have attracted considerable interest in recent years. Intro-
duction of heteroatoms such as nitrogen,5 oxygen,6 and
sulfur7 into the bridging positions of calixaromatics leads
to the emergence of a new generation of macrocyclic host
molecules in comparison to the conventional calix[n]arenes.
Because the heteroatoms can adopt different electronic con-
figurations and form different degrees of conjugation with
their adjacent aromatic rings, the conformation and the
cavity structures of the heterocalixaromatics are fine-tuned
by the bond lengths and bond angles of the bridging hetero-
atoms. For example, by the formation of marginally differ-
ent conjugations between the bridging nitrogen atoms and
their neighboring pyridines, tetramethylazacalix[4]pyridine
has been found to give cavities of different sizes to interact
with the different guest species.5e,5f,5l,5o In addition, the
various electronic effects of the heteroatoms also influence
the electron density of aromatic rings, yielding the cavity of
varied electronic features. The nitrogen-bridged calixpyri-
dines, for instance, are able to interact with fullerenes C60
and C70,5d,5e,5m,5n whereas the oxygen-bridged calix[2]arene
[2]triazines complex halides through anion-π interactions.9
Furthermore, the heterocalixaromatics are readily function-
alized not only on the aromatic rings10 but also on the
bridging positions,11 allowing the construction of polyfunc-
tionalized host molecules. Moreover, the powerful and
efficient fragment coupling approaches would facilitate the
generation of numerous heterocalixaromatics when the
combinations of varied (hetero)aromatic dinucleophilic
and dielectrophilic reactants are employed.4
unexplored. Only several NH-bridged calixaromatics have
been synthesized from the reaction of 1,3-phenylenediamines
with very reactive dielectrophiles such as cyanuric chloride
and 1,5-difluoro-2,4-dinitrobenzenes. For example, using
the fragment coupling method, we6a previously prepared
NH-bridged calix[2]arene[2]triazines from 1,3-phenylenedia-
mine and cyanuric chloride. Siri12 and Konishi13 independently
reported the synthesis of NH-bridged calix[4]arenes by reacting
of 1,3-phenylenediamine with 1,5-difluoro-2,4-dinitroben-
zenes. The use of 1,3-dibromobenzenes and 2,6-dibromo-
pyridines as dielectrophiles in the reaction with 1,3-pheny-
lenediamine led to no or very low yields of NH-bridged
calixaromatics.5h Very recently, Rajca and co-workers14 repor-
ted the synthesis of NH-bridged calix[n]arenes from exhaustive
debenzylayion of NBn-bridged calix[n]arenes.
For years, we have been investigating heterocalixpyridine
derivatives because of their interesting cavity structures and
versatile properties in recognizing various metal cations
and neutral molecules.4a,5d-5f,5l-5o It is desirable to have
the NH-bridged calixpyridine derivatives in order to under-
stand the substituent effect of the bridging nitrogen atoms on
the structure and property of azacalixpyridines. We report
herein the synthesis of NH-bridged calix[1]arene[3]pyridine
and calix[2]arene[2]pyridine from N-Boc-protected calix[1]-
arene[3]pyridine and calix[2]arene[2]pyridine. Their confor-
mational structures, along with those of NBoc-linked ana-
logues, will be presented. We will also show the N-alkylation
reactions with methyl iodide and allyl bromide and unex-
pected selective deuteration and bromination reactions of
NH-bridged calix[2]arene[2]pyridine with CF3CO2D and
CuBr2, respectively.
Although a variety of heterocalixaromatics have been
reported, the NH-bridged calixaromatics still remain largely
(6) 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) Wang, Q.-Q.;
Wang, D.-X.; Zheng, Q.-Y.; Wang, M.-X. Org. Lett. 2007, 9, 2847. (l) Katz,
J. L.; Geller, B. J.; Foster, P. D. Chem. Commun. 2007, 1026. (m) Zhang, C.;
Chen, C.-F. J. Org. Chem. 2007, 72, 3880. (n) Van Rossom, W.; Maes, W.;
Kishore, L.; Ovaere, M.; Van Meervelt, L.; Dehaen, W. Org. Lett. 2008,
10, 585.
Results and Discussion
Synthesis. We initially attempted a straightforward synthesis
of NH-bridged calix[4]pyridine utilizing a macrocyclization
coupling approach. Following our previous method5d,5e for
the synthesis of NMe-bridged calix[4]pyridine, the Pd-catalyzed
reaction between N2,N6-bis(6-bromopyridin-2-yl)pyridine-
2,6-diamine 1a and 2,6-diaminopyridine 2a was performed in
refluxing toluene (Scheme 1). The reaction proceeded slowly.
The increase of catalyst loading [Pd2(dba)3 16 mol % and dppp
40 mol %] and the use of benzo-18-crown-6 did not improve the
conversion of starting materials. Unfortunately, instead of the
desired NH-bridged calix[4]pyridine, the reaction produced
only a mixture of inseparable linear oligomers. Under the same
catalytic conditions, the reaction of N1,N3-bis(6-bromopyridin-
2-yl)benzene-1,3-diamine 1b with 1,3-phenylenediamine 2b gave
a mixture of products, and among them the target molecule
NH-bridged calix[2]arene[2]pyridine 3b was isolated in 12%
yield. To enhance the efficiency for the formation of macrocyclic
product 3b, template effects using alkali and alkaline earth metal
ions, Cu2+ and Ag+, high dilution reaction conditions, and
other solvents such as tetrahydrofuran (THF) were examined.
Disappointingly, no noticeable improvement was observed.
It should also be pointed out that the isolation of 3b from the
linear oligomeric mixtures was very tedious and not practical,
requiring iterative column chromatography.
(7) For a very recent review on thiacalixarenes, see: Morohashi, N.;
Narumi, F.; Iki, N.; Hattori, T.; Miyano, S. Chem. Rev. 2006, 106, 5291.
(8) For examples of other heteroatom bridged calixaromatics, see: (a)
€
€
Konig, B.; Rodel, M.; Bubenitschek, P.; Jones, P. G.; Thondorf, I. J. Org.
€
€
Chem. 1995, 60, 7406. (b) Konig, B.; Rodel, 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.
(9) Wang, D.-X.; Zheng, Q.-Y.; Wang, Q.-Q.; Wang, M.-X. Angew.
Chem., Int. Ed. 2008, 47, 7485.
(10) (a) Yang, H.-B.; Wang, D.-X.; Wang, Q.-Q.; Wang, M.-X. J. Org.
Chem. 2007, 72, 3757. (b) Hou, B.-Y.; Wang, D.-X.; Yang, H.-B.; Zheng,
Q.-Y.; Wang, M.-X. J. Org. Chem. 2007, 72, 5218. (c) Hou, B.-Y.; Zheng,
Q.-Y.; Wang, D.-X.; Wang, M.-X. Tetrahedron 2007, 63, 10801. (d) Hou,
B.-Y.; Zheng, Q.-Y.; Wang, D.-X.; Huang, Z.-T.; Wang, M.-X. Chem.
Commun. 2008, 3864. (e) Yao, B.; Wang, D.-X.; Huang, Z.-T.; Wang,
M.-X. Chem. Commun. 2009, 2899.
(11) The N-arylation of NH-bridged calix[2]arene[2]triazine was re-
ported. Wang, Q.-Q.; Wang, D.-X.; Ma, H.-W.; Wang, M.-X. Org. Lett.
2006, 8, 5967.
(12) Touil, M.; Lachkar, M.; Siri, O. Tetrahedron Lett. 2008, 49, 7250.
(13) Konishi, H.;Hashimoto, S.;Sakakibara, T.;Matsubara, S.;Yasukawa,
Y.; Morikawa, O.; Kobayashi, K. Tetrahedron Lett. 2009, 50, 620.
(14) Vale, M.; Pink, M.; Rajca, S.; Rajca, A. J. Org. Chem. 2008, 73, 27.
5362 J. Org. Chem. Vol. 74, No. 15, 2009

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SCHEME 1. Attempted Synthesis of NH-Bridged Calixpyridines
SCHEME 2. Synthesis of 5a and 5b
Inspired by the synthesis of NH-bridged calix[m]arenes
from exhaustive N-debenzylation of NBn-bridged calix[m]-
arenes,14 we then investigated the synthesis of NH-bridged
calixpyridines using the N-tert-butyloxycarbonyl (N-Boc)
protection and deprotection strategy. The reaction of 1 with
Boc2O in the presence of 4-dimethylaminopyridine (DMAP)
proceeded smoothly in refluxing THF to afford N-Boc-
protected products 4a and 4b in 89% and 99% yields,
respectively. To our delight, catalyzed by Pd2(dba)3/dppp
in the presence of an excess amount of cesium carbonate,
N-Boc-protected linear trimer 4a was found to react with
1,3-phenylenediamine 2b in refluxing 1,4-dioxane to afford
azacalix[1]arene[3]pyridine 5a in 30% yield. Analogously,
azacalix[2]arene[2]pyridine 5b was obtained nicely in a high-
er chemical yield when 4b was treated with 2b (Scheme 2).
To prepare azacalix[4]pyridine, the reaction of 4a with
2,6-diaminopyridine 2a was tested. Under the identi-
cal catalytic conditions, however, no reaction took place
between 4a and 2a. This is probably attributable to the lower
nucleophilicity of 2,6-diaminopyridine 2a than that of
1,3-phenylenediamine 2b. Employment of forcing reaction
conditions such as using potassium tert-butoxide as a base
did not effect the formation of macrocyclic compound either.
Instead, we observed the formation of 1a from N-deprotec-
tion of 4a, along with the formation of a mixture of linear
oligomers. The higher tendency of N-Boc-protected trimer 4
than trimer 1 to undergo macrocyclic coupling reaction with
1,3-phenylenediamine 2b was intriguing. While the exact
reason awaits further study, it is most likely that the presence
of bulk tert-butyloxycarbonyl groups on the linking nitrogen
atoms led to the conformation of the linear precursor pre-
ferable for cyclization.
SCHEME 3. Synthesis of NH-Bridged Calix[1]arene[3]pyridine
3a and Calix[2]arene[2]pyridine 3b
furnishing NH-bridged calixpyridines 3a and 3b in excellent
yields (Scheme 3).
Structure. NH-bridged calix[m]arene[n]pyridine products
are crystalline products, and they gave high-quality single
crystals suitable for X-ray diffraction analysis (Table 1). The
X-ray crystal structures revealed that introduction of NH
linkage into the bridging positions of calix[m]arene[n]pyri-
dines led to interesting conformational structures in the solid
state. We have previously shown that tetramethylazacalix[2]-
arene[2]pyridine, NMe-bridged calix[2]arene[2]pyridine, gives a
slightly twisted 1,3-alternate conformation with two benzene
rings being face-to-face parallel and two pyridine rings being
edge-to-edge aligned.5d In contrast to tetramethylazacalix[2]-
arene[2]pyridine, both discrete NH-bridged calix[2]arene[2]-
pyridine molecules 3b, which only differ slightly in bond
lengths and bond angles (Figure S1, Supporting Informa-
tion), in a single unit cell adopted the flattened saddle
conformation (Figure 1). While all bridging nitrogen atoms
only form conjugations with their adjacent pyridine rings in
NMe-bridged calix[2]arene[2]pyridine, all NH bridges in 3b,
which are sp2 electronically configured, form partial conjuga-
tion with both pyridine and benzene rings. As judged
by the mean distances between bridging nitrogen and the
Both basic and acidic conditions were applied to remove
Boc group from the bridging nitrogen atoms of compounds
5a and 5b. When refluxed with a large excess amount of
sodium tert-butoxide (15-20 equiv) in 1,4-dioxane for 12 h,
5a and 5b underwent Boc deprotection from linking nitrogen
to produce NH-bridged calix[1]arene[3]pyridine 3a and
calix[2]arene[2]pyridine 3b in 63% and 91%, respectively.
The more efficient Boc cleavage was effected when com-
pounds 5a and 5b were refluxed in acetic acid for 12 h,
˚
pyridine carbon (d=1.402 A) and between bridging nitrogen
˚
and benzene carbon (d =1.408 A), the conjugation between
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Yao et al.
JOCArticle
TABLE 1. X-ray Crystallographic Data of NH-Bridged Calix[m]arene[n]pyridines
compd
emp formula
Mr
3b
C22 H18 N6
366.42
0.42 Â 0.30 Â 0.29
triclinic
P-1
8.3972(17)
10.175(2)
21.221(4)
98.76(3)
101.25(3)
97.86(3)
1.406
3a 4C4H8O2
C37 H49 N7 O8
719.83
0.22 Â 0.20 Â 0.10
tetragonal
I4(1)/a
15.300(2)
15.300(2)
14.684(3)
90
90
90
1.391
4
113(2)
5b
C32 H34 N6 O4
566.65
0.63 Â 0.55 Â 0.05
monoclinic
P2(1)/c
9.4503(19)
25.929(5)
23.646(5)
90
96.66(3)
90
1.308
8
293(2)
5a H2O
C31 H35 N7 O5
585.66
0.41 Â 0.11 Â 0.02
triclinic
P-1
9.3910(19)
11.235(2)
15.836(3)
78.30(3)
86.16(3)
67.25(3)
1.289
3
3
cryst size (mm3)
cryst system
space group
˚
a (A)
˚
b (A)
˚
c (A)
R (deg)
β (deg)
γ (deg)
D (g/cm3)
Z
4
173(2)
2
293(2)
T (K)
R1, wR2 [I > 2σ(I)] R1 = 0.0627, wR2 = 0.1436 R1 = 0.0470, wR2 = 0.1156 R1 = 0.0571, wR2 = 0.1195 R1 = 0.1400, wR2 = 0.1588
R1, wR2 [all data]
quality of fit
R1 = 0.0829, wR2 = 0.1529 R1 = 0.0512, wR2 = 0.1190 R1 = 0.1167, wR2 = 0.1407 R1 = 0.2779, wR2 = 0.1929
1.123 1.075 0.945 1.190
NH-bridged calix[1]arene[3]pyridine 3a, which was illu-
strated in Figure S2 (see the Supporting Information), the
macrocycle adopted a flattened and slightly twisted 1,3-
alternate conformation with an approximate S4 symmetry.
All nitrogen atoms in the linking positions again formed partial
conjugations with both adjacent aromatic rings.
The solid-state structures of NH-bridged calix[2]arene[2]-
pyridine 5b and calix[1]arene[3]pyridine 5a were also worth
addressing. Bearing two Boc protection groups on the brid-
ging nitrogen atoms, both macrocycles gave a partial cone
conformation (Schemes S3 and S4, Supporting Information).
All nitrogen atoms adopted an sp2 electronic configuration.
The bridging nitrogen atoms attached by Boc formed strong
conjugation with the carbonyl group rather than aromatic
rings, and two bulky Boc groups were trans-orientated. While
the partial conjugation between one of the NH bridges and its
linking aromatic rings was observed, the other NH linking
unit formed strong conjugation with its two neighboring
aromatic rings to yield a nearly planar Ar-NH-Ar segment
(Schemes S3 and S4, Supporting Information).
Although in the solid state NH-bridged calix[m]arene[n]-
pyridines 3 and 5 exist in certain conformations with differ-
ent conjugation systems being observed, these macrocycles
may not be able to retain these stable conformational
structures in the solution. In both 1H and 13C NMR spectra,
only one set of proton and carbon resonance signals was
observed for NH-bridged calix[m]arene[n]pyridines 3 and 5
in solution. For example, NH-bridged calix[2]arene[2]pyr-
idine 3b gives two pairs of coupled triplet and doublet peaks
of the protons of meta-substituted benzene and 2,6-disubsti-
tuted pyridine rings, whereas three pairs of coupled triplet
and doublet peaks corresponding to protons of one 2,6-
disubstituted pyridine, one meta-substituted benzene, and
another two identical 2,6-disubstituted pyridine rings were
observed in 3a. In the case of Boc-protected NH-calix[m]-
arene[n]pyridines 5a and 5b, only one type of tert-butyl group
FIGURE 1. X-ray crystal structure of NH-bridged calix[2]arene[2]
pyridine 3b: (a) top view and (b) side view. Only one of the two dis-
crete molecules in a single unit cell is shown. Selected bond lengths
˚
(A): N(2A)-C(6A) 1.403(4); N(2A)-C(5A) 1.404(4); N(3A)-C(12A)
1.412(4); N(3A)-C(10A) 1.440(3); N(5A)-C(16A) 1.390(4); N(5A)-
C(17A) 1.407(3); N(6A)-C(1A) 1.389(3); N(6A)-C(21A) 1.401(3).
(Hydrogen atoms are omitted for clarity.)
bridging nitrogen and pyridine ring is slightly stronger than
that between bridging nitrogen and benzene ring. The for-
mation of stronger conjugation of bridging nitrogen atoms
with pyridine rings led to the higher reactivity of pyridine
rings than benzene rings in aromatic electrophilic substitu-
tion reactions (vide infra). The tendency for NH-bridged
calix[2]arene[2]pyridine 3b to form a more flattened confor-
mation in comparison to 1,3-alternate tetramethylazacalix[2]-
arene[2]pyridine is most probably due to the least steric
effect of NH linkages. In the case of crystal structure of
1
was evidenced by H and 13C NMR spectra. These NMR
spectral characteristics indicated that all NH-bridged calix-
[m]arene[n]pyridine compounds 3 and 5 might adopt highly
symmetric conformational structures in solution. Most
probably, these macrocycles are very fluxional in solution,
and the rates of interconversion of various conformational
structures might be very rapid relative to the NMR time
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Yao et al.
JOCArticle
SCHEME 4. N-Alkylation of NH-Bridged Calix[2]arene[2]
pyridine 3b
SCHEME 5. Synthesis of All NBoc-Bridged Calix[2]arene[2]
pyridine 7
onto the bridging positions of 3b to furnish product 6b
quantitatively (Scheme 4). Product 6b should be amenable
to further functionalizations using various functional
group transformations of allyl group. Another example of
N-functionalization was illustrated in Scheme 5. Starting
with N-Boc protected NH-calix[2]arene[2]pyridine 5b, the
N-acylation reaction with Boc2O afforded all NBoc-bridged
calix[2]arene[2]pyridine in 94% yield.
scale. The high conformational mobility of these NH-
bridged calix[m]arene[n]pyridines is most likely due to the
lack of steric hindrance and intramolecular hydrogen bonds,
both being key factors in stabilizing conformational struc-
tures of conventional calix[n]arenes2 in solution. The stabi-
lity gained from the conjugation effect of the linking nitrogen
atoms with their adjacent aromatic rings seems insufficient
to prevent the rotation of aromatic rings around the meta-
meta axes or through the annulus. It is interesting to note that
the protons at 3- and 5-positions of the pyridine ring in
3b appeared at 6.33 ppm, upfield shifted in comparison to
the protons of the benzene ring in 3b which resonated at
6.58 ppm. That is indicative of the stronger conjugation
effect between NH-bridges and pyridine rings than between
NH-bridges and benzene rings in 3b in solution.
Reaction. To explore the applications of heterocalixaro-
matics in molecular recognition and molecular assembly,
constructions of functional macrocycles are highly desirable.
Although a large number of heterocalixaromatics have been
prepared in recent years, the functionalized heterocalixaro-
matics,4,6n,10,11 the macrocycles which are installed with func-
tional groups for molecular recognition and assembly, are still
very rare. We10a-10c have previously synthesized tetraoxacalix-
[2]arene[2]triazines that contain metal ion-chelating ligands,
azacrown ethers, and fluorescence moieties at the larger rim.
Dehaen and co-workers6n have also reported the larger rim
functionalization of tetraoxacalix[2]arene[2]pyrimidine with
a benzo-crown ether and with L-cysteine ethyl ester groups.
Very recently, direct and diverse functionalizations of benzene
ring of tetramethylazacalix[1]arene[3]pyridine were achieved
through the arene C-H activation by copper(II).10e NH-
bridged calix[m]arene[n]pyridines obtained are nice substrates
for further functionalizations because the chemical manipula-
tions can be implemented on both aromatic rings and the
bridging nitrogen atoms.
Considering the delocalization of electrons of bridging
nitrogen atoms into the aromatic rings due to conjugation
effect, electrophilic aromatic substitution reactions of aza-
calix[2]arene[2]pyridines 3b and 6a were investigated. To
understand the reactivity of electrophilic aromatic substitu-
tion reactions, deuteration of 3b and 6a was conducted and
monitored by 1H NMR spectroscopy using CF3CO2D as a
deuterating reagent. As illustrated in Figure 2, interaction of
both NH- and NMe-bridged calix[2]arene[2]pyridines with
CF3CO2D led to the gradual disappearance of doublet
signals at 6.57 ppm for 3b and at 6.47 ppm for 6a. Con-
comitantly, the triplet signals at 7.86 ppm for 3b and at
8.02 ppm for 6a (see the Supporting Information) changed
into a mixture of triplet, doublet, and singlet signals of
different intensity, which appeared like a quintet peak and
then a singlet peak (Figure 2a). On the basis of intensity of
doublet signals at 6.57 ppm, the deuteration of 3b finished
30% in 10 min and 98% in 5 h. Deuteration proceeded slower
for 6a, with 59%, 84%, and 96% deuteration being observed
in 2, 5, and 12 h, respectively. Surprisingly, careful scrutiny
of 1H NMR spectra revealed that it was the protons of
pyridine rings that underwent deuteration at the 3 and 5
positions, and the protons of the benzene rings remained
intact under the reaction conditions. The unusual reaction
outcomes, viz. pyridine moiety showing higher reactivity
than benzene moiety in deuteration with CF3CO2D, were
intriguing. It has been shown that, in the crystalline state and
in solution, bridging nitrogen atoms in both NH-bridged
calix[2]arene[2]pyridine 3b (vide supra) and NMe-bridged
calix[2]arene[2]pyridine 6a5e formed stronger conjugation
with pyridine rings than with benzene rings. In other words,
it is the formation of conjugation between bridging nitrogen
atoms and pyridine rings that lead to delocalization of
nitrogen lone pair electrons into the pyridine ring. As a
consequence, electrophilic aromatic deuteration took place
on pyridine rather than benzene rings of azacalix[2]arene[2]-
pyridines 3b and 6a.
To demonstrate the functionalization on the bridge posi-
tions, we first carried out the N-alkylation reaction of NH-
bridged calix[2]arene[2]pyridine 3b (Scheme 4). With the
aid of sodium hydride, compound 3b underwent efficient
N-methylation reaction with methyl iodide at ambient tem-
perature to produce tetramethylazacalix[2]arene[2]pyridine
6a in 99% yield. It is noteworthy that compound 6a was
previously prepared from a 3 + 1 fragment coupling reaction
between N1,N3-bis(6-bromopyridin-2-yl)-N1,N3-dimethyl-
benzene-1,3-diamine and N1,N3-dimethylbenzene-1,3-dia-
mine. The chemical yield is around 20%, and the sepa-
ration is tedious.5d The current method, however, offered
an easy entry to 6a in an improved yield. Under the identical
conditions, four allyl groups were introduced successfully
Encouraged by the facile deuteration of the pyridine rings
of azacalix[2]arene[2]pyridines, we then tried the bromina-
tion of NH- and NMe-bridged calix[2]arene[2]pyridines.
Reaction of 3b and 6a with N-bromosuccinimde (NBS)
occurred rapidly at room temperature in organic solvent
J. Org. Chem. Vol. 74, No. 15, 2009 5365

Yao et al.
JOCArticle
SCHEME 6. Bromination of Azacalix[2]arene[2]pyridines 3b
and 6a
such as in refluxing THF, reaction gave a mixture of products,
and among which the dibrominated products 10 and 11
were isolated in 48% and 14% yield, respectively (Scheme 6).
The same reaction performed in other solvents including
CHCl3, 1,4-dioxane, acetonitrile, and DMF led to much
lower chemical yields of products. The easier bromination of
NH-bridged calix[2]arene[2]pyridine 3b than NMe-bridged
calix[2]arene[2]pyridine 6a is consistent with the fact that the
formermacrocycle forms better conjugationbetween bridging
nitrogen atoms and pyridine rings in solution.
Conclusion
In summary, we have developed an efficient method for the
synthesis of all NH-bridged calix[1]arene[3]pyridine and calix-
[2]arene[2]pyridine from deprotection of N-Boc groups of
NBoc-bridged calix[m]arene[n]pyridine derivatives which were
prepared by macrocyclic coupling reaction between NBoc-
linked trimers and 1,3-phenylenediamine. In the solid state,
calix[2]arene[2]pyridine adopted the flattened saddle confor-
mation, while NH-bridged calix[1]arene[3]pyridine gave a
slightly twisted 1,3-alternate conformer. In both cases, all
NH bridges formed partial conjugation with both pyridine
and benzene rings, whereas in solution they gave symmetric
conformational structures in which the conjugation of brid-
ging NH units with pyridine ring was stronger than with
benzene ring. We have also shown that NH-bridged calix[2]-
arene[2]pyridine was able to undergo efficient reactions with
alkyl halides and CuBr2 to afford, respectively, the bridging
N-functionalized and the pyridine ring-functionalized azacalix
[2]arene[2]pyridine derivatives. The easy preparation of NH-
bridged calixaromatics and their efficient reactions on bridging
NH units and on aromatic rings would open a new avenue to
the diverse functionalized macrocyclic host molecules useful in
supramolecular chemistry.
FIGURE 2. Deuteration of azacalix[2]arene[2]pyridines 3b and 6a.
such as CH2Cl2, CH3CN and DMF. Unfortunately, the
reaction gave a mixture of products which were difficult to
separate using column chromatography. The reaction was not
improved either when acids including CH3CO2H, CF3CO2H
and para-toluenesulfonic acid were used to deactivate the
pyridine moieties. We then found that CuBr2 was an efficient
halogenation reagent15 to brominate azacalix[2]arene[2]-
pyridines. Under very mild conditions such as in THF at
ambient temperature, interaction ofNH-bridgedcalix[2]arene
[2]pyridine 3b with CuBr2 led to the monobromination on the
pyridine ring of the macrocycle to afford 9 as the major
product in 41% yield (Scheme 6). The reaction between
NMe-bridged calix[2]arene[2]pyridine 6a with CuBr2 did not
proceed at room temperature. At an elevated temperature
(15) Use of CuBr2 as a bromination reagent was reported in the literature.
(a) Nonhebel, D. C. J. Chem. Soc. 1963, 1216. (b) Kodomari, M.; Satoh, H.;
Yoshitomi, S. J. Org. Chem. 1988, 53, 2093 and references cited therein.
5366 J. Org. Chem. Vol. 74, No. 15, 2009

Yao et al.
JOCArticle
Experimental Section
for C32H34N6O4: C, 67.83; H, 6.05; N, 14.83. Found: C, 67.94;
H, 6.21; N, 14.47.
General Procedure for the Synthesis of N-Boc-Protected Lin-
ear Trimers 4a and 4b. To a mixture of NH-linked trimer 1a or 1b
(100 mmol), which was prepared according to a literature
method,5e and DMAP (20 mmol) in THF (500 mL) was added
slowly (Boc)2O (300 mmol) at room temperature. After release
of the gas evolved, the resulting mixture was refluxed for several
hours until the starting material was consumed. The solvent was
then removed under vacuum. The residue was dissolved in ethyl
acetate (500 mL) and washed with saturated NaHCO3 aqueous
solution (3 Â 500 mL) and brine (3 Â 500 mL). The organic layer
was dried over with anhydrous magnesium sulfate. After re-
moval of solvent, the residue was subjected to a silica gel column
eluting with a mixture of petroleum ether and ethyl acetate
(10:1) to give pure product 4a or 4b.
General Procedure for the Synthesis of NH-Bridged Calix[m]-
arene[n]pyridines 3a and 3b. Method A: A mixture of 5a or 5b
(1 mmol) and sodium tert-butoxide (15 mmol) in anhydrous
1,4-dioxane (100 mL) was refluxed for 12 h. A few drops of water
was added slowly to quench the reaction. After filtration, the
solvent was removed, and the residue was subjected to a silica
gel column with a mixture of petroleum ether and acetone as
eluent to give pure product 3a (63%) or 3b (91%). Method B:
A mixture of 5a or 5b (1 mmol) in glacial acetic acid (15 mL) was
refluxed for 12 h. Then the solvent was removed under vacuum.
The residue was subjected to a silica gel column with a mixture of
petroleum ether and acetone as eluent to give pure product 3a
(82%) or 3b (99%).
1
3a: H NMR (300 MHz, acetone-d6) δ 8.54 (t, J = 2.0 Hz,
4a: yield 89%; mp 159-160 °C; 1H NMR (300 MHz, CDCl3)
δ 7.73 (t, J = 8.3 Hz, 1H), 7.55 (d, J = 8.1 Hz, 2H), 7.47 (t, J =
7.8 Hz, 2H), 7.22 (d, J = 7.7 Hz, 2H), 7.02 (d, J = 7.8 Hz, 2H),
1.38 (s, 18H); 13C NMR (75 MHz, CDCl3) δ 28.0, 82.5, 114.1,
121.6, 125.6, 139.1, 139.2, 152.0, 152.3, 154.1; IR (KBr) ν 2980
(w), 1725 (s) cm-1; MS (EI) m/z 619 (3), 621(6), 623 (3) [M]+,
519 (5), 521 (10), 523 (5) [M - Boc]+, 419 (50), 421 (100), 423
(50) [M - 2Boc]+. Anal. Calcd for C25H27Br2N5O4: C, 48.33;
H, 4.38; N, 11.27. Found: C, 48.44; H, 4.45; N 10.95.
1H), 7.71 (s, 2H, deuterium exchangeable), 7.55 (s, 2H, deuter-
ium exchangeable), 7.42 (t, J = 7.8 Hz 1H), 7.35 (t, J = 7.8 Hz,
2H), 6.94 (t, J = 7.8 Hz, 1H), 6.48 (d, J = 7.8 Hz, 1H), 6.41 (dd,
J = 7.9 Hz, J = 2.1 Hz, 2H), 6.30 (d, J = 7.9 Hz, 2H), 6.29 (d,
J = 7.7 Hz, 2H); 13C NMR (75 MHz, acetone-d6) δ 156.8, 156.6,
156.3, 144.4, 139.3, 139.1, 128.7, 112.5, 110.0, 109.8, 105.0,
104.7; IR (KBr) ν 3406 (w), 3295 (w), 1577 (s); ESI-MS m/z
368.2 [M + H]+, 390.2 [M + Na]+, 406.2 [M + K]+. Anal.
Calcd. for C21H17N7 0.5H2O: C, 67.01; H, 4.82; N, 26.05.
Found: C, 67.48; H, 4.74; N, 26.05.
4b: yield 99%; mp 101-102 °C; 1H NMR (300 MHz, CDCl3)
δ 7.52 (t, J = 7.9 Hz, 2H), 7.44 (dd, J = 0.7 Hz, J = 7.9 Hz, 2H),
7.34 (t, J = 8.1 Hz, 1H), 7.23 (dd, J = 0.6 Hz, J = 7.5 Hz, 2H),
7.13 (dd, J = 2.0 Hz, J = 8.0 Hz, 2H), 7.00 (t, J = 2.0 Hz, 1H),
1.42 (s, 18H); 13C NMR (75 MHz, CDCl3) δ 28.1, 82.2, 118.7,
124.5, 126.1, 127.2, 128.9, 139.5, 141.5, 153.1, 155.0; IR (KBr) ν
2927 (w), 1720 (s) cm-1; MS (EI) m/z 618 (5), 620 (10), 622 (5)
[M]+, 518 (4), 520 (8), 522 (4) [M - Boc]+, 418 (50), 420 (100),
422 (50) [M - 2Boc]+. Anal. Calcd for C26H28Br2N4O4: C,
50.34; H, 4.55; N, 9.03. Found: C, 50.26; H, 4.60; N, 8.83.
GeneralProcedure for theSynthesisofNBoc-BridgedAzacalix-
[m]arene[n]pyridines 5a and 5b. Under argon protection, a mixture
of trimer 4a or 4b (2 mmol), benzene-1,3-diamine (2 mmol),
Pd2(dba)3 (276 mg, 0.3 mmol), DPPP (246 mg, 0.6 mmol), and
cesium carbonate powder (5.216 g, 16 mmol) in anhydrous
1, 4-dioxane (500 mL) was refluxed for 24 h. The reaction mixture
was filtered and concentrated under reduced pressure. The residue
was dissolved in dichloromethane (15 mL) and washed with brine
(3 Â 15 mL). The organic phase was dried over with anhydrous
magnesium sulfate. The solvent was removed, and the residue was
subjected to a basic aluminum oxide column with a mixture of
petroleum ether and ethyl acetate (3:1) as eluent to give pure
product 5a or 5b.
3
1
3b: H NMR (300 MHz, acetone-d6) δ 8.69 (t, J = 2.0 Hz,
2H), 7.57 (s, 4H, deuterium exchangeable), 7.33 (t, J = 7.8, 2H),
7.01 (t, J = 7.9, 2H), 6.57 (dd, J = 2.0 Hz, J = 7.9 Hz, 4H), 6.32
(d, J = 7.8 Hz, 4H); 13C NMR (75 MHz, acetone-d6) δ 157.4,
144.6, 139.0, 128.9, 113.8, 111.8, 103.4; IR(KBr) ν 3363 (m),
3378 (m), 1591 (s); ESI-MS m/z 367.2 [M + H]+. Anal. Calcd
for C22H18N6: C, 72.11; H, 4.95; N, 22.94. Found: C, 72.11; H,
5.03; N, 22.84.
General Procedure for N-Alkylation of 3b. To a solution of 3b
(1 mmol) in anhydrous THF (100 mL) was added slowly sodium
hydride (15-20 mmol). The reaction mixture was refluxed for
3 h. After the solution was cooled to room temperature, methyl
iodide or allyl bromide (10 mmol) was slowly added into the
mixture during several minutes. The resulting mixture was then
refluxed for another 10 h until 3b was consumed. After being
cooled to room temperature, the mixture was filtered through a
Celite pad. The solvent was then removed, and the residue was
subjected to a silica gel column with petroleum ether and ethyl
acetate as eluent (3:1) to give pure product 6a5d or 6b in 99%
yield.
6b: mp 112-113 °C; 1H NMR (300 MHz, CDCl3) δ 7.32 (t,
J = 8.0 Hz, 2H), 7.01 (t, J = 7.9 Hz, 2H), 6.74 (dd, J = 7.9 Hz,
J = 2.0 Hz, 4H), 6.66 (t, J = 1.9 Hz, 2H), 5.96 (d, J = 8.0 Hz,
4H), 5.93-5.80 (m, 4H), 5.21 (dd, J = 17.2 Hz, J = 1.6 Hz, 4H),
5.10 (dd, J = 10.2 Hz, J = 1.5 Hz, 4H), 4.12 (d, J = 5.1 Hz, 8H);
13C NMR (75 MHz, CDCl3) δ 157.7, 147.4, 138.6, 134.3, 128.8,
128.7, 126.7, 116.0, 94.7, 54.0; IR (KBr) ν 1570 (s), 1464 (s);
MALDI-TOF m/z 527.4 [M + H]+. Anal. Calcd. for C34H34N6:
C, 77.54; H, 6.51; N, 15.96. Found: C, 77.53; H, 6.60; N,
15.87.
Synthesis of 7. A mixture of 5b (28.3 mg, 0.05 mmol), Boc2O
(65.4 mg, 0.3 mmol), and DMAP (2.5 mg, 0.02 mmol) in
1,4-dioxane (6 mL) was refluxed for 2 h. Then the solvent was
removed and the residue was subjected to a silica gel column
with petroleum ether and ethyl acetate (5:1) as eluent to give
pure product 7 (36.2 mg, 94%): mp 219-220 °C; 1H NMR
(300 MHz, CDCl3) δ 7.65 (dt, J = 1.0 Hz, J = 7.5 Hz, 2H), 7.47
(d, J = 8.1 Hz, 4H), 6.99 (d, J = 8.1 Hz, 2H), 6.73 (dd, J =
8.0 Hz, J = 1.9 Hz, 4H), 6.63 (t, J = 1.8 Hz, 2H), 1.39 (s, 36H);
13C NMR (75 MHz, CDCl3) δ 153.3, 153.1, 141.6, 138.0, 128.3,
127.9, 127.0, 113.8, 81.5, 28.1; IR (KBr) ν 1711 (s); ESI-MS m/z
767.5 [M + H]+, 789.5 [M + Na]+, 805.5 [M + K]+. Anal. Calcd.
5a: yield 30%; mp 195-196 °C; 1H NMR (300 MHz, acetone-
d6) δ 8.23 (t, J = 2.0 Hz, 1H), 7.83 (s, 2H, deuterium exchange-
able), 7.65 (t, J = 7.9 Hz, 1H), 7.56 (t, J = 7.9 Hz, 2H), 7.12 (d,
J = 7.9 Hz, 2H), 6.98 (t, J = 7.9 Hz, 1H), 6.91 (d, J = 7.6 Hz,
2H), 6.56 (d, J = 7.9 Hz, 2H), 6.44 (dd, J = 7.9, J = 2.0 Hz, 2H),
1.40 (s, 18H); 13C NMR (75 MHz, acetone-d6) δ 156.2, 154.6,
154.2, 153.9, 143.5, 139.3, 139.1, 129.2, 118.1, 113.8, 112.3,
109.8, 109.3, 81.6, 28.3; IR (KBr) ν 3349 (s), 1686 (s), 1590 (s);
ESI-MS m/z 568.4 [M + H]+. Anal. Calcd. for C31H33N7O4.
H2O: C, 63.58; H, 6.02; N, 16.74. Found: C, 63.86; H, 6.19;
N, 16.79.
5b: yield 57%; mp 233-234 °C; 1H NMR (300 MHz, DMSO-
d6) δ 9.11 (s, 2H, deuterium exchangeable), 8.75 (s, 1H), 7.79
(s, 1H), 7.61 (t, J = 7.7 Hz, 2H), 7.31-7.30 (m, 3H), 7.16 (t, J =
8.0 Hz, 1H), 6.76 (d, J = 8.1 Hz, 2H), 6.70 (d, J = 7.3 Hz, 2H),
6.61 (dd, J = 1.9 Hz, J = 8.0 Hz, 2H), 1.30 (s, 18H); 13C NMR
(75 MHz, DMSO-d6) δ 155.4, 152.7, 152.2, 141.4, 141.1, 139.2,
128.5, 128.1, 123.3, 122.6, 112.8, 112.4, 110.3, 108.4, 80.5, 27.8;
IR (KBr) ν 3370 (m), 1696 (s), 1594 (s) cm-1; MALDI-TOF m/z
567.6 [M + H]+, 589.6 [M + Na]+, 605.6 [M + K]+. Anal. Calcd.
J. Org. Chem. Vol. 74, No. 15, 2009 5367

Yao et al.
JOCArticle
for C42H50N6O8: C, 65.78; H, 6.57; N, 10.96. Found: C, 65.79;
H, 6.61; N, 10.72.
10: 1H NMR (400 MHz, CF3COOD) δ 8.20 (d, J = 9.6 Hz,
2H), 7.53 (t, J = 8.0 Hz, 2H), 7.00 (d, J = 9.6 Hz, 2H), 6.91 (d,
J = 8.4 Hz, 2H), 6.81 (d, J = 8.0 Hz, 2H), 6.41 (s, 2H), 3.46
(s, 6H), 3.24 (s, 6H); 13C NMR (100 MHz, CF3COOD) δ 153.2,
151.0, 148.0, 145.4, 140.5, 133.9, 118.1, 113.9, 110.3, 105.3, 40.3,
37.4; IR (KBr) ν 1602 (s), 1572 (s); ESI-MS m/z 581.1 [M + H]+.
Anal. Calcd for C26H24Br2N6: C, 53.81; H, 4.17; N, 14.48.
Found: C, 53.58; H, 4.27; N, 14.08.
General Procedure for Bromination of 3b and 6a. A mixture of
3b or 6a (0.1 mmol) and CuBr2 (0.2 mmol) in THF (5 mL) was
stirred at room temperature or refluxed until reactant 3b or 6a
was consumed. The solvent was removed, and water (5 mL) was
added. The resulting mixture was extracted with dichloro-
methane (3 Â 5 mL). The organic phase was dried over with
anhydrous magnesium sulfate. After removal of the solvent, the
residue was subjected to a silica gel column. For 9, a mixture of
petroleum ether, acetone, and dichloromethane (15/3/2) was
used as eluent. For 10 and 11, a mixture of petroleum ether, ethyl
acetate, and dichloromethane (4/1/1) was used as eluent.
9: 1H NMR (300 MHz, DMSO-d6) δ 8.46 (s, 1H, deuterium
exchangeable), 8.34 (s, 1H, deuterium exchangeable), 8.27 (s,
1H, deuterium exchangeable), 8.02 (s, 1H (Ph)), 7.93 (s, 1H
(Ph)), 7.65 (d, J = 8.4 Hz, 1H (Py)), 7.34 (t, J = 7.9 Hz, 1H (Py)),
7.32 (s, 1H, deuterium exchangeable), 7.08 (t, J = 8.1 Hz, 1H
(Ph)), 7.06 (t, J = 8.2 Hz, 1H (Ph)), 6.66 (d, J = 8.0 Hz, 1H
(Ph)), 6.59 (d, J = 8.0 Hz, 1H (Ph)), 6.54-6.49 (m, 2H (Ph)),
6.29 (d, J = 8.4 Hz, 1H (Py)), 6.23 (d, J = 7.8 Hz, 1H (Py)), 6.22
(d, J = 7.8 Hz, 1H (Py)); 13C NMR (75 MHz, DMSO-d6)
δ 155.7, 155.5, 154.8, 151.5, 143.0, 142.9, 142.5, 142.1, 141.4,
138.3, 128.4, 128.3, 114.4, 114.2, 113.2, 112.8, 111.8, 109.9,
105.3, 102.1, 102.0, 95.3; IR (KBr) ν 3396 (br), 1591 (s); ESI-
MS m/z 447.1 [M + H]+, 469.1 [M + Na]+, 485.1 [M + K]+.
Anal. Calcd for C22H17BrN6: C, 59.34; H, 3.85; N, 18.87.
Found: C, 59.08; H, 3.91; N, 18.94.
11: mp 182-183 °C; 1H NMR (300 MHz, DMSO-d6) δ 7.89
(d, J = 8.5 Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 7.07 (t, J = 8.0 Hz,
1H), 6.77 (dd, J = 1.9 Hz, J = 8.0 Hz, 2H), 6.65 (d, J = 8.5 Hz,
2H), 6.41 (dd, J = 1.9 Hz, J = 8.0 Hz, 2H), 6.15 (s, 1H), 5.60
(s, 1H), 3.14 (s, 6H), 3.00 (s, 6H); 13C NMR (75 MHz, DMSO-d6)
δ 157.7, 156.3, 148.5, 148.4, 144.1, 129.8, 128.9, 117.8, 116.7,
111.6, 109.6, 108.5, 106.6, 39.4, 38.6; IR(KBr) ν 1573 (s), 1559 (s);
ESI-MS m/z 581.1 [M + H]+, 603.1 [M + Na]+. Anal. Calcd
for C26H24Br2N6: C, 53.81; H, 4.17; N, 14.48. Found: C, 53.54;
H, 4.09; N, 14.21
Acknowledgment. We thank the Natural Science Founda-
tion of China, Ministry of Science and Technology (2007CB-
808005) and the Chinese Academy of Sciences for financial
support.
Supporting Information Available: Experimental details,
1H and 13C NMR spectra of products, and X-ray structures
of 3a, 3b, 5a, and 5b (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
5368 J. Org. Chem. Vol. 74, No. 15, 2009