Synthesis, structure and molecular recognition of functionalised tetraoxacalix[2]arene[2]triazines

Article abstract of DOI:10.1002/chem.201000003

Functionalised dialkoxy-substituted tetraoxacalix[2]arene[2]triazine macrocycles 6 have been readily synthesised by the fragment coupling approach using methyl 3,5-dihydroxy-4alkoxybenzoates and cyanuric chloride as the starting materials under very mild

Full text of DOI:10.1002/chem.201000003

FULL PAPER
DOI: 10.1002/chem.201000003
Synthesis, Structure and Molecular Recognition of Functionalised
Tetraoxacalix[2]arene[2]triazines
Qi-Qiang Wang,[a] De-Xian Wang,*[a] Hai-Bo Yang,[a] Zhi-Tang Huang,[a] and
Mei-Xiang Wang*[a, b]
Abstract: Functionalised dialkoxy-sub-
stituted tetraoxacalix[2]arene[2]triazine
macrocycles 6 have been readily syn-
thesised by the fragment coupling ap-
proach using methyl 3,5-dihydroxy-4-
alkoxybenzoates and cyanuric chloride
as the starting materials under very
mild conditions. AlCl3-mediated deally-
lation and debenzylation reactions af-
forded the lower-rim dihydroxy-substi-
tuted tetraoxacalix[2]arene[2]triazine
derivatives 11 and 13 in good yields.
Although dialkoxy-substituted tetraox-
ternate conformation with the bridging
oxygen atoms conjugated with the tri-
AHCTUNGTRENNUNG
This dihydroxylated macrocyclic host
molecule, a hydrogen-bond donor mac-
rocycle with a V-shaped cleft, interacts
with 2,2’-bipyridine, 4,4’-bipyridine and
1,10-phenanthroline guests. Although
in solution they form the correspond-
ing 1:1 complexes with binding con-
stants ranging from 37.7 to 213mÀ1, 2:2
host–guest complexes were observed in
the crystalline state. Hydrogen-bonding
interactions, along with other non-co-
valent interactions, such as lone-pair-
which gives a mixture of monomer and
dimer in solution according to a diffu-
sion NMR spectroscopy study, adopts a
1,3-alternate conformation and forms a
cyclic tetrameric assembly in the solid
state due to the formation of intermo-
lecular hydrogen-bonding networks.
À
electron–p and C H···p interactions,
Keywords: calixarenes · host–guest
systems · hydrogen bonds · mo-
acalix[2]arene[2]triazine
macrocycles
were found to be the driving force for
the formation of host–guest complexes.
are fluxional in solution on the NMR
spectroscopy timescale, they adopt a
symmetric or slightly distorted 1,3-al-
lecular recognition
elucidation
·
structure
Introduction
known crown ethers,[1] spherands[2] and cryptands.[3]
A
recent example is the extensive study of the supramolecular
chemistry of calixarenes[4] following Gutscheꢀs pioneering
work on the synthesis and structural elucidation of calix-
The design and synthesis of novel and functional macrocy-
clic molecules have always been one of the driving forces
for promoting major advances in supramolecular science.
This has been demonstrated through the synthesis of well-
AHCTUNGTRENNUNG
[n]arenes.[5] Because of their easy availability, unique confor-
mational and cavity structures, and powerful recognition
properties, calix[n]arenes have become classic macrocyclic
molecules.[4]
Along with the advances in the field of calix[n]arenes,
[a] Q.-Q. Wang, Dr. D.-X. Wang, H.-B. Yang, Prof. Z.-T. Huang,
Prof. Dr. M.-X. Wang
heterocalixaromatics,[6–10]
heteroatom-bridged
calix-
Beijing National Laboratory for Molecular Sciences
CAS Key Laboratory of Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences
Beijing 100190 (P.R. China)
Fax : (+86)10-62564723
E-mail: wangmx@tsinghua.edu.cn
AHCTUNGTREG(NNNU hetero)arenes, have emerged as a novel type of macrocyclic
host molecule in supramolecular chemistry. Owing to the
bridging heteroatoms, such as nitrogen, oxygen and sulfur,
which can adopt different electronic configurations and
form different degrees of conjugation with their neighbour-
ing aromatic rings, heterocalixaromatics are able to form
fine-tuneable conformation and cavity structures that inter-
act with various guest species. For example, azacalix[4]pyri-
dine forms coordination complexes selectively with transi-
tion- and heavy-metal cations.[7f,o] By forming intermolecular
hydrogen bonds, azacalix[4]pyridine forms a variety of com-
mxwang@iccas.ac.cn
[b] Prof. Dr. M.-X. Wang
The Key Laboratory of Bioorganic Phosphorus Chemistry &
Chemical Biology (Ministry of Education), Department of Chemistry
Tsinghua University, Beijing 100084 (P.R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000003.
Chem. Eur. J. 2010, 16, 7265 – 7275
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7265

plexes with aliphatic and aromatic monoalcohols and
diols.[7l] The large macrocyclic homologues, azacalix[n]pyri-
dines (n=5–10), exhibit a strong binding ability towards ful-
lerenes such as C60 and C70.[7e,m,n] Very recently, tetraoxaca-
lix[2]arene[2]triazines have been reported to recognise hal-
ides through the formation of anion–p interactions.[11]
obtained in 10% yield from the reaction of 5c with 4c
(Scheme 1).
Although a number of heterocalixaromatics have been
prepared in recent years, functionalised heterocalixaromat-
ics with functional groups for molecular recognition and as-
sembly are very rare. We previously synthesised tetraoxaca-
lix[2]arene[2]triazines that contain metal-ion-chelating li-
gands, azacrown ethers and fluorescence moieties on the
larger rim.[12] Dehaen and co-workers[13] have also reported
the larger-rim functionalisation of tetraoxacalix[2]arene[2]-
pyrimidine with a benzocrown ether and l-cysteine ethyl
ester groups. To explore the applications of heterocalixaro-
matics in molecular recognition and molecular assembly, the
construction of functional macrocycles is highly desirable.
Because the tetraoxacalix[2]arene[2]triazine macrocycle
generally adopts a 1,3-alternate conformation with two ben-
zene rings nearly face-to-face parallel and two triazine rings
tending to an edge-to-edge orientation,[8a] we envisioned
that the introduction of hydroxy groups on to the benzene
rings would give rise to a functionalised cavity. We report
herein the synthesis and structures of smaller-rim dihydroxy-
substituted tetraoxacalix[2]arene[2]triazine derivatives. The
resulting macrocyclic molecules provide a unique V-shaped
cavity that forms interesting complexes with 2,2’-bipyridine,
4,4’-bipyridine and 1,10-phenanthroline through hydrogen
Scheme 1. Synthesis of tetraoxacalix[2]arene[2]triazine derivatives 6.
À
bonding and C H···p and p–p interactions.
The formation of hexaoxacalix[3]arene[3]triazines 7a,c
from the 3+1 fragment coupling reactions between 5a,c
and 4a,c was intriguing. A plausible mechanism could in-
volve the formation of intermediate 8 (Scheme 2) from the
Results and Discussion
Synthesis: We have previously shown that the fragment cou-
pling approach is generally efficient and practical for the
synthesis of diverse heterocalixaromatics. We initiated our
study with the synthesis of 2,6-bis(4,6-dichloro-1,3,5-triazin-
2-yloxy)phenol, or “trimer” 3, by the reaction of 1,2,3-trihy-
droxybenzene (1a) or the methyl ester of gallic acid (1b)
with cyanuric chloride (2). However, a mixture of oligomers
was produced from the reaction instead of the target mole-
cule 3 (Scheme S1 in the Supporting Information).
We then attempted the reactions of 4a–c, gallic acid ester
derivatives with an allyl, benzyl and methyl protecting
group, respectively, on the 4-hydroxy group. In the presence
of diisopropylethylamine as an acid scavenger, all reactants
4a–c readily underwent nucleophilic aromatic substitution
reactions with cyanuric chloride (2; 2 equiv) at 08C to
afford the corresponding intermediates 5a–c in yields rang-
ing from 74 to 84%. A 3+1 macrocyclic cyclisation was
then performed. Treatment of the linear trimers 5a–c with
4a–c at room temperature led to the formation of tetraoxa-
calix[2]arene[2]triazine derivatives 6a–c in moderate yields.
Surprisingly, the reaction between 5a and 4a gave hexaoxa-
calix[3]arene[3]triazine 7a in a yield of 14% in addition to
6a. A similar larger macrocyclic ring analogue 7c was also
Scheme 2. Plausible reaction pathways for the formation of 7a,c.
7266
www.chemeurj.org
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 7265 – 7275

Functionalised Tetraoxacalix[2]arene[2]triazines
FULL PAPER
reaction between 4 and 5. Prior to intramolecular cyclisa-
tion, which afforded tetraoxacalix[2]arene[2]triazine 6, the
linear tetramer 8 was most probably cleaved by 4a and 4c
to produce a linear trimer intermediate 9 and a dimer inter-
mediate 10. Both a 3+3 fragment coupling of 9 with 5 and
a 2+4 fragment coupling of 10 with 8 would lead to hexaox-
acalix[3]arene[3]triazines 7. The cleavage of linear tetramer
8 by 4a and 4c is most likely due to the high reactivity of
À
the C O bond of the dichloro-substituted triazine ring. Note
that, because of the steric hindrance of methyl 4-benzyloxy-
3,5-dihydroxybenzoate (4b), no effective nucleophilic aro-
matic attack at 8 took place. Therefore, no hexaoxacalix[3]-
arene[3]triazine product was yielded.
Scheme 4. Synthesis of lower-rim dihydroxylated tetraoxacalix[2]arene[2]-
triazines 13.
To synthesise the target lower-rim dihydroxylated tetraox-
acalix[2]arene[2]triazine, compounds 6a and 6b were sub-
jected to deprotection. However, no deallylation reaction
was achieved by using a number of documented methods.
Catalytic hydrogenolysis of 6b under various conditions did
not remove the benzyl group either. We finally performed
the deprotection of 6a and 6b with an excess amount of
AlCl3 in dry toluene; both allyl and benzyl groups were
cleaved efficiently at ambient temperature. Under the reac-
tion conditions, the two triazine rings were also arylated by
toluene in a Friedel–Crafts reaction. The dihydroxy-substi-
tuted tetraoxacalix[2]arene[2]triazine 11 was obtained in
yields of 75 (R=Bn) and 89% (R=allyl; Scheme 3).
AlCl3. To synthesise tetraoxacalix[2]arene[2]triazine with
one hydroxy group at the lower rim, we studied the selective
O-benzylation of 13a. In the presence of K2CO3 in acetone,
compound 13a underwent benzylation with benzyl bromide
at ambient temperature to give mono- and dibenzylated
products 14 and 12a in yields of 22 and 30%, respectively
(Scheme 5). The use of an excess amount of benzyl bromide
(4 equiv) and K2CO3 (4 equiv) afforded 12a as the sole
product in a yield of 83%. The chemical yield of 12a was
further improved to 92% when the reaction was carried out
in acetone at reflux. The easy benzylation of the hydroxy
group of 13a implies a convenient route to tetraoxacalix[2]-
arene[2]triazines functionalised on the lower rim.
Scheme 5. Synthesis of lower-rim monohydroxylated tetraoxacalix[2]ar-
Scheme 3. Deallylation of 6a and debenzylation of 6b.
AHCTUNGTREGeNNNU ne[2]triazine 14.
To examine the generality of the AlCl3-mediated depro-
tection reaction and also to prepare other lower-rim dihy-
droxy-substituted tetraoxacalix[2]arene[2]triazine analogues,
O-benzylated tetraoxacalix[2]arene[2]triazine 12a was syn-
thesised from the reaction of 6b with di-n-propylamine in a
yield of 86%. Treatment of 12a with AlCl3 in dry toluene at
room temperature for 30 min gave the desired product 13a
in a quantitative yield. The debenzylation reaction proceed-
ed equally efficiently for the tert-butyl-substituted substrate
12b[8k] to afford the corresponding dihydroxylated tetraoxa-
calix[2]arene[2]triazine 13b in a yield of 91% (Scheme 4). It
is worth mentioning that AlCl3 is used to remove tert-butyl
groups from conventional calix[n]arenes derived from 4-tert-
butylphenol.[14]
Structure elucidation: All of the functionalised tetraoxaca-
lix[2]arene[2]triazine products synthesised were crystalline
compounds. High-quality single crystals of compounds 6a,
6b,[8k] 7a and 13b were obtained by slow evaporation of the
solvent from their solutions. X-ray diffraction analysis
(Table 1) thus allowed us to examine their structures in the
solid state. As we reported previously,[8a] the parent tetraox-
acalix[2]arene[2]triazine exists as a 1,3-alternate conformer
with C2v symmetry. The bridging oxygen atoms tend to con-
jugate with the triazine rings rather than the benzene rings.
As a result, the two benzene rings are almost face-to-face
parallel, whereas the two triazine rings tend to adopt an
edge-to-edge orientation. The introduction of functional
groups such as ester and alkoxy substituents on the benzene
rings led to a slight distortion of the 1,3-alternate conforma-
Note that the selective removal of one of the two benzyl
groups in 12 met with failure under the conditions using
Chem. Eur. J. 2010, 16, 7265 – 7275
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7267

D.-X. Wang, M.-X. Wang et al.
Table 1. X-ray crystallographic data for the macrocyclic host molecules and their complexes.
Compound
6a
C28H20Cl2N6O10 C42H30Cl3N9O15 C35.5H47.5N6O7
671.40 1007.10 670.30
0.30ꢃ0.20ꢃ0.16 0.45ꢃ0.35ꢃ0.10 0.20ꢃ0.18ꢃ0.16
7a
13b·0.25hexane·H2O 14
13b·1,10-phen
13b·4,4’-bipy
13b·2,2’-bipy
empirical formula
Mr
C41H46N8O10
810.86
C46H50N8O6
810.94
C44H50N8O6
786.92
C44H50N8O6
786.92
crystal size [mm3]
crystal system
space group
a [ꢂ]
0.30ꢃ0.30ꢃ0.25 0.23ꢃ0.23ꢃ0.18 0.14ꢃ0.09ꢃ0.08 0.24ꢃ0.22ꢃ0.14
monoclinic
C2/c
12.979(3)
24.289(5)
26.134(5)
90.00
101.16(3)
90.00
triclinic
P1
monoclinic
P21/n
tetragonal
P4/n
monoclinic
P21/n
10.378(2)
17.795(4)
24.280(57)
90.00
102.17(3)
90.00
4382.9(15)
1.229
monoclinic
P21/c
10.626(2)
18.268(4)
22.502(4)
90.00
96.46(3)
90.00
4340.3(15)
1.204
monoclinic
P121/c1
10.7382(5)
17.8451(7)
22.4369(11)
90.00
97.868(2)
90.00
4259.0(3)
1.227
¯
9.224(3)
12.949(4)
14.548(5)
66.660(5)
85.287(5)
72.483(5)
1520.1(8)
1.467
12.039(2)
15.317(3)
24.823(5)
90.00
90.36(3)
90.00
23.6877(12)
23.6877(12)
13.3531(8)
90.00
90.00
90.00
b [ꢂ]
c [ꢂ]
a [8]
b [8]
g [8]
V [ꢂ3]
4577.3(15)
1.461
7492.5(7)
1.188
8083(3)
1.333
8
d [gcmÀ3
Z
]
2
4
8
4
4
4
T [K]
293(2)
173(2)
0.1063
0.1178
1.185
113(2)
0.0775
0.0840
1.260
293(2)
0.1050
0.1734
1.473
173(2)
0.0806
0.0954
1.125
293(2)
0.1339
0.2668
1.115
113(2)
0.0627
0.0773
1.116
R factor [I>2s(I)] 0.0535
R factor (all data) 0.0974
quality of fit
CCDC no.
1.017
759599
759852
759949
759950
759951
759952
759953
tions of the products 6a and 6b (Figures 1 and 2), which in-
dicates that the tetraoxacalix[2]arene[2]triazine macrocycle
in general prefers a 1,3-alternate conformation. However,
Figure 2. Molecular structure of 6b (side view). Selected bond lengths
À
À
À
À
À
[ꢂ]: C1 O4 1.340, O4 C18 1.406, C3 O1 1.339, O1 C5 1.410, C10 O2
À
À
À
1.342, O2 C9 1.412, C12 O3 1.343, O3 C14 1.410. Distances of the
upper and lower rims of 6b [ꢂ]: C7···C16 4.647, C4···C13 4.510, C2···C11
8.911, N1···N4 4.599.
Figure 1. Molecular structure of 6a (side view). Selected bond lengths
À
À
À
À
À
[ꢂ]: C1 O1 1.339, O1 C20 1.408, C3 O2 1.334, O2 C4 1.408, C15 O3
À
À
À
1.344, O3 C6 1.408, C17 O4 1.332, O4 C18 1.407. Distances of the
upper and lower rims of 6a [ꢂ]: C8···C22 5.579, C5···C19 4.350, C2···C16
8.515, N1···N4 4.572.
hydrogen-bonding interactions between triazine nitrogen
atoms and hydrogen atoms of the benzene rings yielding an
infinite one-dimensional assembly (Figure S1 in the Support-
ing Information). Macrocycle 6b forms a similar one-dimen-
sional assembly in the crystal structure. In contrast to 6a,
however, intermolecular hydrogen bonds between the chlor-
ine atoms on the triazine rings and hydrogen atoms on the
benzene rings were observed in addition to p–p stacking in-
teractions between triazine rings (Figure S2 in the Support-
ing Information).
the cavity of the macrocycles 6a and 6b differ considerably.
For example, whereas the upper rim distance of 6a (dC8–C22
)
is 5.579 ꢂ, a much shorter distance was observed for 6b
(dC7–C16 =4.647 ꢂ) . Note also that one of the benzyl groups
on the lower rim in 6b tends to locate in the cleft formed by
the triazine rings (Figure 2). In the solid state of 6a, each
macrocycle interacts with another two molecules through p–
p stacking interactions between triazine rings and by weak
7268
www.chemeurj.org
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 7265 – 7275

Functionalised Tetraoxacalix[2]arene[2]triazines
FULL PAPER
Hexaoxacalix[3]arene[3]triazine 7a adopts a 1,3,5-alter-
nate conformation in the solid state (Figure 3). On the basis
of the bond lengths and angles of the bridging oxygen
Although dihydroxylated tetraoxacalix[2]arene[2]triazine
13b adopts a very slightly twisted 1,3-alternate conformation
(Figure 4) similar to that of compounds 6a and 6b, the two
Figure 4. Molecular structure of 13b (side view). Selected bond lengths
À
À
À
À
À
[ꢂ]: C7 O3 1.336, O3 C6 1.405, C9 O4 1.353, O4 C15 1.416, C16 O5
À
À
À
1.345, O5 C11 1.415, C18 O6 1.347, O6 C2 1.420. Distances of the
upper and lower rims of 13b [ꢂ]: C4···C13 5.460, C1···C10 4.368, C8···C17
9.022, N1···N4 4.579.
hydroxy groups on the lower rim form different hydrogen
bonds intra- and intermolecularly to give an interesting two-
dimensional assembly in the solid state. As shown in
Figure 5 (top), one of the hydroxy groups (OA1) of the mac-
rocyclic molecule A forms an intermolecular hydrogen bond
with triazine nitrogen NB2 of the neighbouring macrocycle
B, whereas the triazine nitrogen NA2 of macrocycle A forms
a hydrogen bond with the hydroxy group OD1 of molecule
D. Through the formation of four such intermolecular hy-
drogen bonds between macrocyclic molecules A–D in a
cyclic array, a hydrogen-bonded tetrameric structure is ob-
tained. Note that the distance between OA1 and NA1 within
one macrocycle is 3.028 ꢂ, which suggests a weak intramo-
lecular hydrogen bond between them. The other hydroxy
group (OA2) was found to hydrogen bond with a water mol-
ecule (O7) (Figure 5, bottom), which in turn forms a hydro-
gen bond with triazine nitrogen NA3. Moreover, the water
molecule O7 and the triazine nitrogen of the adjacent mac-
rocycle also forms a hydrogen bond. In other words, two
water molecules served as the bridges to connect two tet-
ramers through hydrogen-bonding interactions (Figure 5).
As a consequence, one tetramer assembly is linked to anoth-
er four tetrameric units through hydrogen-bonding networks
(see Figure S4 in the Supporting Information).
Figure 3. Molecular structure of 7a: A) side view and B) top view. Select-
À
À
À
À
ed bond lengths [ꢂ]: C3 O1 1.332, O1 C4 1.404, C1 O6 1.330, O6 C26
À
À
À
À
À
1.417, C21 O5 1.332, O5 C22 1.408, C19 O4 1.354, O4 C17 1.405, C12
À
À
À
O3, 1.346, O3 C13 1.412, C10 O2 1.328, O2 C8 1.413. Distances of the
upper and lower rims of 7a [ꢂ]: C6···C24 5.509, C6···C15 9.233, C24···C15
9.360, C9···C27 4.113, C9···C18 6.696, C27···C18 6.784, C2···C20 8.627,
C2···C11 8.490, C11···C20 8.690, N3···N7 6.773, N3···N6 6.873, N6···N7
3.995.
atoms, each of the triazine rings is conjugated with the at-
taching oxygen atoms. The benzene moieties, on the other
hand, are not conjugated with the bridging oxygen atoms.
The cavity of hexaoxacalix[3]arene[3]triazine 7a is con-
structed of a cyclic array of three isolated benzene rings and
three bis-oxa-conjugated triazine segments in a 1,3,5-alter-
nate manner. Similarly to 6a and 6b, hexaoxacalix[3]ar-
Compounds 6a, 6b, 7a and 13b might not retain their
solid-state structures in solution. This was evidenced by the
NMR spectra, which gave only one set of signals for each of
the macrocyclic compounds. These results are in agreement
with previous observations[6] and indicate the fluxionality of
the macrocycles in solution on the NMR spectroscopy time-
ACHTUNGTRENNUNGene[3]triazine 7a also yields an infinite one-dimensional as-
sembly through intermolecular p–p stacking effects between
1
scale. H NMR spectra of 13b were recorded at various con-
triazine rings (Figure S3 in the Supporting Information).
centrations to shed light on its association behaviour in solu-
Chem. Eur. J. 2010, 16, 7265 – 7275
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7269

D.-X. Wang, M.-X. Wang et al.
coefficient
7.89ꢃ10À10 m2 sÀ1
thus measured in a mixture of
CDCl3 and CD3OD (92:8, v/v)
was attributed to the unbound
species of 13b (Figure S7b in
the Supporting Information). In
CDCl3, however, we observed
two distinct diffusion coeffi-
cients 6.31ꢃ10À10 (D2) and
8.13ꢃ10À10 m2 sÀ1 (D1), with the
latter being slightly higher than
7.89ꢃ10À10 m2 sÀ1 (Figure S7a in
the Supporting Information).
Because the presence of
CD3OD increases the viscosity
of the solution and results in a
decrease in the diffusion coeffi-
cient, the observed diffusion co-
efficient 8.13ꢃ10À10 m2 sÀ1 in
CDCl3 is most probably attrib-
utable to the monomer. On the
assumption that the molecules
are spherical, the ratio of the
molecular weights of the two
species calculated from (D1/
D2)3 is 2.15:1.[15] This indicates
that dihydroxylated calix[2]are-
ne[2]triazine 13b exists in equi-
librium with its dimer (13b)2 in
CDCl3. The self-association of
13b was also evidenced by the
observation of the [13b+H]+,
[(13b2)+H]+ and [(13b)3 +
Na]+ ion peaks in the ESI mass
spectra (Figure S8 in the Sup-
porting Information).
Molecular recognition: The 1,3-
alternate dihydroxylated tet-
raoxacalix[2]arene[2]triazine
13b contains two hydroxy
groups in a V-shaped cleft com-
prising two conjugated triazine
rings. Because the hydroxy
Figure 5. Tetrameric 13b with a square cavity self-assembled through intermolecular hydrogen bonds (tert-
butyl groups have been omitted for clarity). Selected hydrogen-bonding distances [ꢂ]: O1···N2 2.809, O2···O7
2.712, O7···N3 2.980, O7···N5 2.875, O1···N3 3.028. Selected hydrogen-bonding angles [8]: O1–H···N2 167.8,
O2–H···O7 164.3, O7–H···N3 149.7, O7–H···N5 167.2.
tion. As illustrated in Figure S6 in the Supporting Informa-
tion, when the concentration of 13b was increased from
3.17ꢃ10À3 to 2.67ꢃ10À2 m, the proton signal of the hydroxy
groups was shifted downfield accompanied by a broadening
of the peak. This suggests that the hydroxy groups form in-
termolecular hydrogen bonds. We studied the self-aggrega-
tion behaviour of 13b in solution by NMR diffusion meas-
urements (Figure S7 in the Supporting Information). We
first measured the diffusion coefficient of 13b in a mixture
of CDCl3 and CD3OD (92:8, v/v). As a protonic solvent,
methanol is able to form hydrogen bonds with a polar solute
and would therefore cause disassociation of the hydrogen-
bonded aggregates of the host molecule 13b. The diffusion
group is a hydrogen-bond donor, we envisioned that this
functionalised macrocycle would act as a unique host, inter-
acting with guest molecules that are hydrogen-bond accept-
ors. To demonstrate its utility in molecular recognition, we
studied the interaction of 13b with 1,10-phenanthroline,
1
4,4’-bipyridine and 2,2’-bipyridine by H NMR titration ex-
periments. As a representative example, the proton NMR
spectral changes of 13b upon addition of an increasing
amount of 1,10-phenanthroline are shown in Figure 6. Only
one set of proton resonance signals was observed for host
13b after the addition of the guest, which indicates a fast
equilibrium between the host, guest and complex on the
NMR spectroscopy timescale. The interaction of the host
7270
www.chemeurj.org
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 7265 – 7275

Functionalised Tetraoxacalix[2]arene[2]triazines
FULL PAPER
with the guest led first to a downfield shift and then to the
disappearance of the proton signal of the hydroxy group of
the host (see Figure S9 in the Supporting information),
which indicates the nature of the hydrogen bonding between
the host and guest. Interestingly, the proton signals of the
benzene ring and the tBu moiety on the benzene ring were
shifted downfield, whereas the signal of the tBu on the tri-
AHCTUNGTREGaNNNU zine ring was shifted upfield (Figure 6B). The opposite
movements of the two tBu signals reflect the different de-
shielding and shielding effects experienced by the tBu
groups on the benzene and triazine moieties in the presence
of the guest molecule. The Job plot in Figure 6A reveals the
formation of a 1:1 complex between the host and guest mol-
ecules. Based on the NMR titration isotherms (Figure 6C
and Figures S11 and S14 in the Supporting Information), as-
sociation constants between the host and guests, which were
fitted by using the Hyperquad 2003 program,[16] are 37.7mÀ1
for 13b·2,2’-bipyridine, 200mÀ1 for 13b·1,10-phenanthroline
and 213mÀ1 for 13b·4,4’-bipyridine.
To understand the interaction between the host 13b and
guests on the molecular level, single crystals of the host–
guest complexes were cultivated by slow evaporation of sol-
vent from a solution of a mixture of 13b and the guest.
Their structures were analysed by X-ray diffraction analysis
and are depicted in Figure 7–9. As expected, the host mole-
cule interacts with all the guest species mainly by forming a
hydrogen bond through its hydroxy groups with the nitrogen
atoms of the N-heterocycles. Intriguingly, however, the
host–guest interaction led to 2+2 complexes in all cases in
the solid state. The two dihydroxy-substituted tetraoxaca-
lix[2]arene[2]triazine molecules, which adopt a 1,3-alternate
conformation, are aligned head-to-head to form a giant
cavity in which two guest molecules are included mainly
through the formation of hydrogen bonds.
In the case of the [13b·2,2’-bipyridine]2 complex, for ex-
ample, each of the included trans-configured 2,2’-bipyridines
forms one strong hydrogen bond with one of the hydroxy
groups of one host (dO1–N8 =2.694 ꢂ) and one relatively
weak hydrogen bond with one of the hydroxy groups of the
other host (dO2–N7 =2.896 ꢂ). In the middle of the cavity,
two pyridine rings of two guests are parallel displaced with
a face-to-face distance of 3.451 ꢂ (Figure 7). Figure 8 shows
that in the complex of 13b with 4,4’-bipyridine, two guest
molecules simply act as two bridges to link two host mole-
cules through the formation of two pairs of intermolecular
hydrogen bonds (dO5–N8 =2.731 ꢂ and dO6–N7 =2.696 ꢂ). Al-
though there is no p–p interaction between the two guest
molecules, the shorter distance between the aromatic carbon
C41 of one 4,4’-bipyridine molecule and the aromatic plane
Figure 6. A) Job plot of 13b and 1,10-phenanthroline. The total concen-
tration of 13b and 1,10-phenanthroline is 2.0 mm in CDCl3. B) Partial
1H NMR spectrum of host 13b (8.35ꢃ10À4 m) in the presence of an in-
creasing amount of guest 1,10-phenanthroline (0–16.987ꢃ10À3 m) at
1
2
3
~
&
*
298 K. ) Peak of H , ) peak of H , ) peak of H . C) NMR titration
1
2
3
~
&
^
isotherm. ) Peak of H , ) peak of H , ) peak of H . The assignment of
protons was determined by NOE experiments.
Chem. Eur. J. 2010, 16, 7265 – 7275
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7271

D.-X. Wang, M.-X. Wang et al.
À
guest through a C H···p interaction with the distance be-
tween C12 and the plane of the 1,10-phenanthroline being
3.601 ꢂ. In addition to the intermolecular hydrogen bonds,
a lone-pair-electron–p interaction between 1,10-phenanthro-
line and triazine of the host in [13b·1,10-phenanthroline]2 is
also observed with the distances between N8 and the plane
and the centroid of the triazine being 3.317 and 3.311 ꢂ, re-
spectively (Figure 9). Moreover, two guest molecules are p–
p displaced stacked and the distance between two anti-face-
to-face parallel 1,10-phenanthroline planes is 3.481 ꢂ.
Note that although the dihydroxylated tetraoxacalix[2]ar-
ene[2]triazine host 13b retains almost the same 1,3-alternate
Figure 7. Molecular structure of the complex formed between host 13b
and 2,2’-bipyridine. Selected interaction distances [ꢂ]: O1···N8 2.694,
O2···N7 2.896, pyridine rings p–p 3.451. Selected hydrogen-bonding
angles [8]: O1–H···N8 153.1, O2–H···N7 144.9.
of the other molecule [dC41–pyridine ring =3.328 ꢂ] suggests
À
C41aromatic H41A···p interactions. The multiple non-covalent
bond interactions in the complex of [13b·1,10-phenanthro-
line]2 are worth noting. First, one of the hydroxy groups of
the host forms an intermolecular hydrogen bond with one
nitrogen atom of 1,10-phenanthroline (dO6–N7 =2.648 ꢂ). The
other hydroxy group is probably intramolecularly hydrogen
bonded to an adjacent triazine nitrogen (dO5–N6 =3.013 ꢂ).
Figure 9. Molecular structure of the complex formed between host 13b
and 1,10-phenanthroline. Selected interaction distances [ꢂ]: O6···N7
À
À
In addition, weak C H···p (C39 H39···C31) and hydrogen-
À
2.648, O5···O6 3.176, N8···triazine plane 3.317, C12 H···p 3.601, p–p
À
bonding (C43 H43···O5) interactions are observed. Further-
stacking distance between 1,10-phenanthroline planes 3.481. Selected hy-
more, one of the tBu groups of the host interacts with the
drogen-bonding angles [8]: O6–H···N7 154.7, O5–H···O6 173.0.
conformation in the complex
structures (Figures 7–9), careful
scrutiny of the host molecule
structures in the three com-
plexes reveals that the cavity
size varies according to the
guest molecule included. The
upper rim distance between two
triazine rings, a parameter de-
fining the size of the tetraoxa-
calix[2]arene[2]triazine macro-
cycles, differs from 9.516 ꢂ for
[13b·2,2’-bipyridine]2 to 9.385 ꢂ
for [13b·4,4’-bipyridine]2 and to
9.285 ꢂ for [13b·1,10-phenan-
throline]2. These values contrast
with the upper rim distance be-
tween two triazine rings of the
Figure 8. Molecular structure of the complex formed between host 13b and 4,4’-bipyridine. Selected interac-
parent macrocycle 13b of
9.022 ꢂ (Figure 4). It is appa-
À
tion distances [ꢂ]: O6···N7 2.696, O5···N8 2.731, C41 H···p 3.328. Selected hydrogen-bonding angles [8]: O6–
H···N7 159.6, O5–H···N8 153.0.
7272
www.chemeurj.org
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 7265 – 7275

Functionalised Tetraoxacalix[2]arene[2]triazines
FULL PAPER
Methyl 4-(benzyloxy)-3,5-bis(4,6-dichloro-1,3,5-triazin-2-yloxy)benzoate
(5b): White solid; m.p. 173–1748C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=7.88 (s, 2H), 7.29–7.25 (m, 3H), 7.15–7.11 (m, 2H), 5.08 (s,
2H), 3.94 ppm (s, 3H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=
173.2, 170.6, 164.5, 146.3, 144.4, 135.1, 128.7, 128.5, 127.3, 126.4, 122.7,
76.1, 52.7 ppm; IR (KBr): n˜ =1730, 1524 cmÀ1; MS (EI): m/z (%): 574
(1), 572 (2), 570 (3), 568 (3) [M]+, 91 (100); elemental analysis calcd (%)
for C21H12N6O5Cl4: C 44.24, H 2.12, N 14.74; found: C 44.56, H, 2.11, N
14.87.
rently the guest species that induces the host to change its
cavity size during complexation. Nevertheless, it is the
oxygen bridges of the tetraoxacalix[2]arACTHNUTRGNEeNUG ne[2]triazine that
regulate their conjugation with the aromatic rings, leading
to fine-tuning of the cavity to achieve the best fit with the
guest molecules. The formation of 1+1 complexes between
the host and guests examined probably did not occur be-
cause of the short distance between the two nitrogen atoms,
the hydrogen-bond acceptors, of the guest molecule. Such a
short distance is energetically unfavourable for the forma-
tion of two hydrogen bonds with the hydroxy groups.
Methyl 3,5-bis(4,6-dichloro-1,3,5-triazin-2-yloxy)-4-methoxybenzoate (5c):
White solid; m.p. 110–1128C; 1H NMR (300 MHz, CDCl3, 258C, TMS):
d=7.89 (s, 2H), 3.94 (s, 3H), 3.82 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=173.3, 170.6, 164.5, 147.5, 144.3, 126.4, 122.7,
61.9, 52.8; IR (KBr): n˜ =1727, 1621, 1529 cmÀ1; MS (EI): m/z (%): 498
(4), 497 (3), 496 (16), 495 (6), 494 (36), 493 (5), 492 (26) [M]+, 465 (33),
464 (12), 463 (71), 462 (16), 461 (77), 460 (21), 459 (100), 458 (20), 457
(99); elemental analysis calcd (%) for C15H8Cl4N6O5: C 36.46, H 1.63, N
17.01; found: C 36.68, H 1.90, N 16.89.
Conclusion
We have established a simple method for the construction
of functionalised tetraoxacalix[2]arene[2]triazine macrocy-
cles by the fragment coupling approach using 1,2,3-trihy-
droxybenzene derivatives as the starting materials under
very mild conditions. Although a mixture of monomer and
dimer was observed in solution through a diffusion NMR
study, the lower-rim-dihydroxylated tetraoxacalix[2]are-
ne[2]triazine 13b adopts a 1,3-alternate conformation and
forms a cyclic tetrameric assembly in the solid state as a
result of the formation of an intermolecular hydrogen-bond
network. The dihydroxylated macrocyclic host molecule acts
as a hydrogen-bond donor to interact with 2,2’-bipyridine,
4,4’-bipyridine and 1,10-phenanthroline guests. Whereas
they form in solution the corresponding 1:1 complexes with
binding constants ranging from 37.7 to 213mÀ1, in the crys-
talline state 2+2 complexes were furnished between the
host and the guest. X-ray crystallography convincingly re-
vealed that it is predominantly the hydrogen-bonding inter-
actions that bring the host and guest molecules together. In
addition, non-covalent interactions such as lone-pair-elec-
General procedure for the synthesis of tetraoxacalix[2]arene[2]triazine
derivatives 6a–c: Acetone (250 mL) solutions of linear trimer 5c (0.79 g,
1.6 mmol) and methyl 4-methoxy-3,5-dihydroxybenzoate (4c; 0.317 g,
1.6 mmol) were added dropwise at the same rate to a well-stirred solu-
tion of diisopropylethylamine (0.50 g, 3.84 mmol) in acetone (200 mL) at
room temperature over 8–12 h. The resulting reaction mixture was stirred
for another 2 days at room temperature. After removal of the solvent
under reduced pressure, the residue was subjected to silica gel chroma-
tography eluting with a mixture of petroleum ether and dichloromethane
to give pure products.
Compound 6a: M.p. 293–2958C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=7.64 (s, 4H), 5.84–5.71 (m, 2H), 5.12 (s, 2H), 5.07 (d, J=
7.1 Hz, 2H), 4.42 (d, J=5.6 Hz, 4H), 3.89 ppm (s, 6H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d=174.3, 171.8, 164.6, 146.1, 144.7, 131.9,
126.2, 122.1, 118.7, 74.8, 52.6 ppm; IR (KBr): n˜ =1731, 1651, 1622,
1551 cmÀ1; MS (MALDI-TOF): m/z (%): 671.6 (100) [M+1]+, 672.6
(36), 673.6 (77), 674.6 (24), 675.6 (17); elemental analysis calcd (%) for
C28H20N6O10Cl2: C 50.09, H 3.00, N 12.52; found: C 50.21, H 3.05, N
12.40.
Compound 6b: M.p. 230–2328C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=7.62 (s, 4H), 7.30–7.19 (m, 6H), 7.08–7.04 (m, 4H), 4.89 (s,
4H), 3.88 ppm (s, 6H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=
174.2, 171.7, 164.6, 146.2, 144.6, 135.1, 128.7, 128.4, 127.7, 126.1, 122.1,
76.1, 52.6 ppm; IR (KBr): n˜ =1727, 1603, 1550 cmÀ1; MS (MALDI-TOF):
m/z (%): 771.2 (18) [M+1]+, 772.2 (10), 773.2 (15), 774.2 (6), 793.2 (100)
[M+Na]+, 794.2 (40), 795.2 (65), 796.2 (23), 797.2 (15); elemental analy-
sis calcd (%) for C36H24N6O10Cl2: C 56.04, H 3.14, N 10.89; found: C
56.20, H 3.09, N 10.91.
À
tron–p and C H···p interactions also contribute to the stabi-
lisation of the host–guest complexes.
Compound 6c: M.p. >3008C; 1H NMR (300 MHz, CDCl3, 258C, TMS):
d=7.62 (s, 4H), 3.88 (s, 6H), 3.75 ppm (s, 6H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=174.5, 171.9, 164.5, 147.7, 144.3, 125.9, 122.4,
61.8, 52.6 ppm; IR (KBr): n˜ =1733, 1622, 1553 cmÀ1; MS (FAB): m/z (%):
618 (93) [M]+, 619 (100), 620 (66), 621 (37), 622 (24); elemental analysis
calcd (%) for C26H16N6O10Cl2: C 46.54, H 2.60, N 13.57; found: C 46.35,
H 2.61, N 13.35.
Compound 7a: M.p. >3008C; 1H NMR (300 MHz, CDCl3, 258C, TMS):
d=7.70 (s, 6H), 5.70–5.59 (m, 3H), 5.11–4.94 (m, 6H), 4.43 (d, J=
3.8 Hz, 6H), 3.88 ppm (s, 9H); 13C NMR (75 MHz, CDCl3, 258C, TMS):
d=173.8, 171.6, 164.6, 147.1, 144.1, 132.2, 125.9, 122.1, 117.0, 73.8,
52.6 ppm; IR (KBr): n˜ =1727, 1620, 1553 cmÀ1; MS (MALDI-TOF): m/z
(%): 1006.2 (44) [M+1]+, 1007.2 (26), 1008.2 (50), 1009.2 (19), 1010.2
(23), 1028.2 (73) [M+Na]+, 1029.2 (36), 1030.2 (100), 1031.2 (41), 1032.2
(39); elemental analysis calcd (%) for C42H30N9O15Cl3: C 50.09, H 3.00, N
12.52; found: C 50.01, H 3.00, N 12.28.
Experimental Section
Preparation of methyl benzoates 5a–c: A solution of methyl 4-alkoxy-
3,5-dihydroxybenzoate (4a–c; 10 mmol) and diisopropylethylamine
(3.23 g, 25 mmol) in THF (40–200 mL) was added dropwise to an ice-
bath-cooled solution of cyanuric chloride (2; 4.06 g, 22 mmol) in THF
(60–150 mL) over 1–2 h. A white solid was precipitated from the reaction
solution. The resulting mixture was stirred for another 2 h at 08C. After
filtration, the filtrate was concentrated under reduced pressure and the
residue purified by chromatography using a silica gel column eluted with
a mixture of petroleum ether and ethyl acetate.
Methyl
3,5-bis(4,6-dichloro-1,3,5-triazin-2-yloxy)-4-(vinyloxy)benzoate
(5a): White solid; m.p. 112–1138C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=7.90 (s, 2H), 5.82–5.69 (m, 1H), 5.13 (d, J=3.5 Hz, 1H), 5.09
(s, 1H), 4.53 (d, J=5.7 Hz, 2H), 3.95 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=173.3, 170.7, 164.5, 146.2, 144.6, 131.8, 126.6,
122.6, 118.7, 75.0, 52.7 ppm; IR (KBr): n˜ =1727, 1620, 1529 cmÀ1; MS
(EI): m/z (%): 522 (3), 521 (1), 520 (6), 519 (1), 518 (5) [M]+, 356 (5),
354 (7), 87 (6), 41 (100), 32 (32); elemental analysis calcd (%) for
C17H10N6O5Cl4: C 39.26, H 1.94, N 16.16; found: C 39.15, H 2.00, N 16.12.
Compound 7c: M.p. >3008C; 1H NMR (300 MHz, CDCl3, 258C, TMS):
d=7.68 (s, 6H), 3.88 (s, 9H), 3.73 ppm (s, 9H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=174.0, 171.9, 164.6, 147.9, 143.8, 125.5, 122.3,
61.4, 52.6 ppm; IR (KBr): n˜ =1727, 1622, 1551 cmÀ1; MS (MALDI-TOF):
m/z (%): 950.2 (90) [M+Na]+, 951.2 (33), 952.2 (100), 953.2 (37), 954.2
Chem. Eur. J. 2010, 16, 7265 – 7275
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7273

D.-X. Wang, M.-X. Wang et al.
(32); elemental analysis calcd (%) for C36H24N9O15Cl3: C 46.54, H 2.60, N
13.57; found: C 46.59, H 2.71, N 13.34.
tion of a mixture of diethyl ether and hexane gave a single crystal of 13b
suitable for X-ray analysis. Single crystals of the complexes were ob-
tained by slow evaporation of solutions of 13b (10 mg) and 2,2’-bipyri-
dine (10 mg) in dichloromethane and hexane, 13b (10 mg) and 4,4’-bipyr-
idine (10 mg) in acetone and hexane, and 13b (10 mg) and 1,10-phenan-
throline (10 mg) in dichloromethane and hexane, respectively.
Synthesis of 12a from 6b: A solution of 6b (386 mg, 0.5 mmol) in THF
(20 mL) was added dropwise to a solution of di-n-propylamine (121 mg,
1.2 mmol) and diisopropylethylamine (284 mg, 2.2 mmol) in THF
(20 mL) at reflux over 30 min. After heating at reflux for another 6.5 h,
the reaction was stopped. The reaction mixture was then concentrated
and the residue was purified by chromatography on a silica gel column
eluting with a mixture of petroleum ether and ethyl acetate to afford
pure product 12a. M.p. 160–1618C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=7.50 (s, 4H), 7.13–7.03 (m, 10H), 4.89 (s, 4H), 3.84 (s, 6H),
3.64–3.45 (m, 8H), 1.65 (hex., J=7.3 Hz, 8H), 0.95 ppm (t, J=7.3 Hz,
12H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=171.6, 167.6, 165.4,
147.8, 145.1, 136.6, 128.0, 127.6, 127.4, 124.7, 122.2, 74.8, 52.2, 49.4, 20.8,
11.4 ppm; IR (KBr): n˜ =1727, 1605, 1577 cmÀ1; MS (MALDI-TOF): m/z
(%): 901.4 [M+1]+, 923.4 [M+Na]+, 939.4 [M+K]+; elemental analysis
calcd (%) for C48H52N8O10: C 63.99, H 5.82, N 12.44; found: C 63.69, H
5.59, N 12.49.
CCDC-759599 (6a), 759852 (7a), 759949 (13b·0.25hexane·H20), 759950
(14), 759951 (13b·1,10-phen), 759952 (13b·4,4’-bipy) and 759953
(13b·2,2’-bipy) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
We thank the National Science Foundation of China (NSFC, 20532030),
the Ministry of Science and Technology (MOST, 2007CB808005) and the
Chinese Academy of Sciences (CAS) for financial support. We also
thank Dr. X. Hao and T.-L. Liang for X-ray structure determination and
Dr. J.-F. Xiang for NMR measurements and discussions.
General procedure for the synthesis of the lower-rim-dihydroxylated tet-
raoxacalix[2]arene[2]triazines 11 and 13a,b: Under argon at room tem-
perature, anhydrous AlCl3 (2.0 g, 15 mmol) and dried toluene (100 mL)
were mixed together and stirred for 5–30 min. Macrocycle 6a, 6b, 12a or
12b (0.5 mmol) was then added and the resulting mixture was stirred at
room temperature for 0.5–12 h. The reaction mixture was then poured
into a mixture of crushed ice and water (100 mL) and dilute hydrochloric
acid (10%, 15 mL) was added. The organic layer was separated and the
aqueous layer extracted twice with ethyl acetate (2ꢃ150 mL). The com-
bined organic layers was dried over anhydrous sodium sulfate and con-
centrated under vacuum. Crystallisation of the residue from a mixture of
hexane and dichloromethane gave pure product 13a, whereas pure 11
and 13b were isolated by silica gel chromatography using a mixture of
petroleum ether and ethyl acetate as eluent.
Compound 11: M.p. >3008C; 1H NMR (300 MHz, [D6]DMSO, 258C,
TMS): d=10.87 (s, OH, 2H), 8.39 (d, J=8.2 Hz, 4H), 7.50 (s, 4H), 7.45
(d, J=8.2 Hz, 4H), 3.74 (s, 6H), 2.45 ppm (s, 6H); 13C NMR (75 MHz,
[D6]DMSO, 258C, TMS): d=175.2, 172.1, 164.6, 147.0, 143.9, 140.1, 131.5,
129.7, 128.7, 121.7, 119.2, 51.9, 21.2 ppm; IR (KBr): n˜ =3604, 3459, 1703,
1623, 1577, 1568 cmÀ1; MS (ESI, neg.): m/z (%): 701.1 [MÀ1]+; elemental
analysis calcd (%) for C36H26N6O10: C 61.54, H 3.73, N 11.96; found: C
61.31, H 3.96, N 11.95.
Compound 13a: M.p. 238–2408C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=7.55 (s, 4H), 5.62 (s, OH, 2H), 3.83 (s, 6H), 3.63–3.50 (m, 8H),
1.70 (hex., J=7.5 Hz, 8H), 0.96 ppm (t, J=7.4 Hz, 12H); 13C NMR
(300 MHz, [D6]DMSO, 258C, TMS): d=10.34 (s, OH, 2H), 7.27 (s, 4H),
3.72 (s, 6H), 3.56–3.51 (m, 8H), 1.65 (hex., J=7.3 Hz, 8H), 0.92 ppm (t,
J=7.3 Hz, 12H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=171.0,
167.4, 165.4, 145.0, 140.8, 122.4, 121.8, 52.2, 49.5, 20.8, 11.2 ppm; IR
(KBr): n˜ =3355, 1724, 1705, 1612, 1592 cmÀ1; MS (MALDI-TOF): m/z
(%): 721.9 [M+1]+, 743.9 [M+Na]+, 759.8 [M+K]+; elemental analysis
calcd (%) for C34H40N8O10: C 56.66, H 5.59, N 15.55; found: C 56.36, H
5.51, N 15.43.
Compound 13b: M.p. 210–2128C; 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=6.91 (s, 4H), 5.75 (s, OH, 2H), 1.38 (s, 18H), 1.13 ppm (s,
18H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=191.8, 171.6, 145.8,
141.8, 136.8, 116.5, 39.6, 34.3, 31.0, 28.6 ppm; IR (KBr): n˜ =3652, 3399,
3188, 1622, 1575, 1548 cmÀ1; MS (ESI, pos.): m/z (%): 631.5 [M+1]+,
653.4 [M+Na]+, 669.4 [M+K]+; elemental analysis calcd (%) for
C34H42N6O6: C 64.74, H 6.71, N 13.32; found: C 64.65, H 7.13, N 13.50.
[1] C. J. Pedersen, J. Am. Chem. Soc. 1967, 89, 7017–7036.
[2] D. J. Cram, Angew. Chem. 1986, 98, 1041–1060; Angew. Chem. Int.
Ed. Engl. 1986, 25, 1039–1057.
[3] B. Dietrich, J.-M. Lehn, J. P. Sauvage, Tetrahedron Lett. 1969, 10,
2885–2888.
[4] a) Calixarenes (Eds.: Z. Asfari, V. Bçhmer, J. Harrowfield, J. Vicens,
M. Saadioui), Kluwer Academic, Dordrecht, 2001; b) C. D. Gutsche,
Calixarenes Revisited, RSC, Cambridge, 1998; c) Calixarenes in
Action (Eds.: L. Mandolini, R. Ungaro), Imperial College Press,
London, 2000; d) G. J. Lumetta, R. D. Rogers, A. S. Gopalan, Calix-
arenes for Separation, ACS, Washington, 2000.
[5] For a monograph, see: C. D. Gutsche, Calixarenes, RSC, Cambridge,
1989.
[6] For useful reviews on heterocalixaromatics, see: a) M.-X. Wang,
Chem. Commun. 2008, 4541–4551; b) W. Maes, W. Dehaen, Chem.
Soc. Rev. 2008, 37, 2393–2402; c) H. Tsue, K. Ishibashi, R. Tamura,
Top. Heterocycl. Chem. 2008, 17, 73–96; d) B. Kçnig, M. H. Fonseca,
Eur. J. Inorg. Chem. 2000, 2303–2310.
[7] For recent examples of nitrogen-bridged calixaromatics, see: a) A.
Ito, Y. Ono, K. Tanaka, New J. Chem. 1998, 22, 779–781; b) A. Ito,
Y. Ono, K. Tanaka, J. Org. Chem. 1999, 64, 8236–8241; c) Y. Miya-
zaki, T. Kanbara, T. Yamamoto, Tetrahedron Lett. 2002, 43, 7945–
7948; d) M.-X. Wang, X.-H. Zhang, Q.-Y. Zheng, Angew. Chem.
2004, 116, 856–860; Angew. Chem. Int. Ed. 2004, 43, 838–842;
e) H.-Y. Gong, X.-H. Zhang, D.-X. Wang, H.-W. Ma, Q.-Y. Zheng,
M.-X. Wang, Chem. Eur. J. 2006, 12, 9262–9275; f) H.-Y. Gong, Q.-
Y. Zheng, X.-H. Zhang, D.-X. Wang, M.-X. Wang, Org. Lett. 2006,
8, 4895–4898; g) H. Tsue, K. Ishibashi, H. Takahashi, R. Tamura,
Org. Lett. 2005, 7, 2165–2168; h) W. Fukushima, T. Kanbara, T. Ya-
mamoto, Synlett 2005, 2931–2934; i) T. D. Selby, S. C. Blackstock,
Org. Lett. 1999, 1, 2053–2055; j) Y. Suzuki, T. Yanagi, T. Kanbara,
T. Yamamoto, Synlett 2005, 263–266; k) K. Ishibashi, H. Tsue, S.
Tokita, K. Matsui, H. Takahashi, R. Tamura, Org. Lett. 2006, 8,
5991–5994; l) H.-Y. Gong, D.-X. Wang, J.-F. Xiang, Q.-Y. Zheng,
M.-X. Wang, Chem. Eur. J. 2007, 13, 7791–7802; m) S.-Q. Liu, D.-X.
Wang, Q.-Y. Zheng, M.-X. Wang, Chem. Commun. 2007, 3856–3858;
n) E.-X. Zhang, D.-X. Wang, Q.-Y. Zheng, M.-X. Wang, Org. Lett.
2008, 10, 2565–2568; o) H.-Y. Gong, D.-X. Wang, Q.-Y. Zheng, M.-
X. Wang, Tetrahedron 2009, 65, 87–92; p) J. Clayden, S. J. M. Row-
bottom, W. J. Ebenezer, M. G. Hutchings, Org. Biomol. Chem. 2009,
7, 4871–4880; q) M. Xue, C. F. Chen, Org. Lett. 2009, 11, 5294–
5297; r) H. Konishi, S. Hashimoto, T. Sakakibara, S. Matsubara, Y.
Yasukawa, O. Morikawa, K. Kobayashi, Tetrahedron Lett. 2009, 50,
620–623.
1H NMR spectral titrations: In each 1H NMR titration experiment, the
concentration of host 13b was kept constant and the concentration of
guest was increased gradually from 0–16.987ꢃ10À3 m for 1,10-phenanthro-
line, 0–33.72ꢃ10À3 m for 4,4’-bipyridine and 0–34.00ꢃ10À3 m for 2,2’-bipyr-
idine. The stoichiometry of the complex was obtained by the Job plot
method. The association constants were calculated on the basis of
1H NMR experimental isotherms using Hyperquad 2003 program.
Preparation of single crystals: The single crystals of 6a, 6b, 7a, and 14
suitable for X-ray analysis were obtained by slow evaporation of a solu-
tion of dichloromethane and hexane at room temperature. Slow evapora-
7274
www.chemeurj.org
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 7265 – 7275

Functionalised Tetraoxacalix[2]arene[2]triazines
FULL PAPER
[8] For recent examples of oxygen-bridged calixaromatics, see: a) M.-X.
Wang, H.-B. Yang, J. Am. Chem. Soc. 2004, 126, 15412–15422;
b) J. L. Katz, M. B. Feldman, R. R. Conry, Org. Lett. 2005, 7, 91–94;
c) J. L. Katz, K. J. Selby, R. R. Conry, Org. Lett. 2005, 7, 3505–3507;
d) J. L. Katz, B. J. Geller, R. R. Conry, Org. Lett. 2006, 8, 2755–
2758; e) W. Maes, W. Van Rossom, K. Van Hecke, L. Van Meervelt,
W. Dehaen, Org. Lett. 2006, 8, 4161–4164; f) E. Hao, F. R. Fronc-
zek, M. G. H. Vicente, J. Org. Chem. 2006, 71, 1233–1236; g) R. D.
Chambers, P. R. Hoskin, A. R. Kenwright, A. Khalil, P. Richmond,
G. Sandford, D. S. Yufit, J. A. K. Howard, Org. Biomol. Chem. 2003,
1, 2137–2147; h) R. D. Chambers, P. R. Hoskin, A. Khalil, P. Rich-
mond, G. Sandford, D. S. Yufit, J. A. K. Howard, J. Fluorine Chem.
2002, 116, 19–22; i) X. H. Li, T. G. Upton, C. L. D. Gibb, B. C. Gibb,
J. Am. Chem. Soc. 2003, 125, 650–651; j) F. Yang, L.-W. Yan, K.-Y.
Ma, L. Yang, J.-H. Li, L.-J. Chen, J.-S. You, Eur. J. Org. Chem. 2006,
1109–1112; k) Q.-Q. Wang, D.-X. Wang, Q.-Y. Zheng, M.-X. Wang,
Org. Lett. 2007, 9, 2847–2850; l) J. L. Katz, B. J. Geller, P. D. Foster,
Chem. Commun. 2007, 1026–1028; m) C. Zhang, C.-F. Chen, J. Org.
Chem. 2007, 72, 3880–3888; n) W. Van Rossom, W. Maes, L. Kish-
ore, M. Ovaere, L. Van Meervelt, W. Dehaen, Org. Lett. 2008, 10,
585–588; o) M. Li, M. L. Ma, X. Y. Li, K. Wen, Tetrahedron 2009,
65, 4639–4643; p) W. Van Rossom, M. Ovaere, L. Van Meervelt, W.
Dehaen, W. Maes, Org. Lett. 2009, 11, 1681–1684; q) S. Akagi, Y.
Yasukawa, K. Kobayashi, H. Konishi, Tetrahedron 2009, 65, 9983–
9988.
[10] For examples of other heteroatom-bridged calixaromatics, see: a) B.
Koenig, M. Rçdel, P. Bubenitschek, P. G. Jones, I. Thondorf, J. Org.
Chem. 1995, 60, 7406–7410; b) B. Kçnig, M. Rçdel, P. Bubenitschek,
P. G. Jones, Angew. Chem. 1995, 107, 752–754; Angew. Chem. Int.
Ed. Engl. 1995, 34, 661–662; c) M. Yoshida, M. Goto, F. Nakanishi,
Organometallics 1999, 18, 1465–1470; d) N. Avarvari, N. Mezailles,
L. Ricard, P. Le Floch, F. Mathey, Science 1998, 280, 1587–1589;
e) N. Avarvari, N. Maigrot, L. Ricard, F. Mathey, P. Le Floch, Chem.
Eur. J. 1999, 5, 2109–2118.
[11] D.-X. Wang, Q.-Y. Zheng, Q.-Q. Wang, M.-X. Wang, Angew. Chem.
2008, 120, 7595–7598; Angew. Chem. Int. Ed. 2008, 47, 7485–7488.
[12] B.-Y. Hou, D.-X. Wang, H.-B. Yang, Q.-Y. Zheng, M.-X. Wang, J.
Org. Chem. 2007, 72, 5218–5226.
[13] W. Maes, W. V. Rossom, K. V. Hecke, L. V. Meervelt, W. Dehaen,
Org. Lett. 2006, 8, 4161–4164.
[14] a) H. Kꢄmmerer, G. Happel, V. Bçhmer, D. Rathay, Monatsh.
Chem. 1978, 109, 767–773; b) C. D. Gutsche, J. A. Levine, J. Am.
Chem. Soc. 1982, 104, 2652–2653.
[15] C. Schalley, Analytical Methods in Supramolecular Chemistry, Wiley-
VCH, Weinheim, 2007, p. 193.
[16] a) P. Gans, A. Sabatini, A. Vacca, Talanta 1996, 43, 1739–1753;
b) Hyperquad 2003 software, Protonic Software, http://www.hyper-
quad.co.uk.
[9] For a review on thiacalixarenes, see: N. Morohashi, F. Narumi, N.
Iki, T. Hattori, S. Miyano, Chem. Rev. 2006, 106, 5291–5316.
Received: January 4, 2010
Published online: May 12, 2010
Chem. Eur. J. 2010, 16, 7265 – 7275
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7275