Design, structure and anion recognition of larger-rim functionalized oxacalix[2]arene[2]triazine hosts

Article abstract of DOI:10.1016/j.tetlet.2014.04.007

Larger-rim functionalized tetraoxacalix[2]arene[2]triazine host molecules were efficiently synthesized through a fragment coupling followed by AlCl ₃-mediated deprotection/arylation protocol. Substituent effects, functions of counter cations on anion recognition in solution were systematically studied by means of fluorescence and NMR titrations.

Full text of DOI:10.1016/j.tetlet.2014.04.007

Tetrahedron Letters 55 (2014) 3172–3175
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Design, structure and anion recognition of larger-rim functionalized
oxacalix[2]arene[2]triazine hosts
⇑
Wei Liu, Qi-Qiang Wang, Zhi-Tang Huang, De-Xian 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
a r t i c l e i n f o
a b s t r a c t
Article history:
Larger-rim functionalized tetraoxacalix[2]arene[2]triazine host molecules were efficiently synthesized
through a fragment coupling followed by AlCl3-mediated deprotection/arylation protocol. Substituent
effects, functions of counter cations on anion recognition in solution were systematically studied by
means of fluorescence and NMR titrations.
Received 4 March 2014
Revised 27 March 2014
Accepted 3 April 2014
Available online 12 April 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Heteracalixaromatics
Anion recognition
Anion–p interaction
Host–guest chemistry
Owing to its importance in chemistry, biology and environmen-
tal science, anion recognition is one of the central themes in supra-
molecular chemistry.1 Since the beginning of this century, new
cooperative anion–
depending on the geometry of anions.4d–f Our continuous interests
on anion– interactions led us to carry out the current study.
p and lone-pair electron–p interactions,
p
motifs of non-covalent anion–
p
interactions, namely, interactions
Hence, one new type of tetraoxacalix[2]arene[2]triazine anion
receptors were designed with coupling p-tolyl groups on the lar-
ger-rim of the triazine rings, while varying different substitutes
on the larger-rim of the benzene rings. The including of the conju-
gated p-tolyl groups on the triazine rings would improve the spec-
troscopic performance of the host molecules. Their syntheses,
structure and anion recognition properties were herein reported.
We initiated the synthesis of 3 applying our previously devel-
oped AlCl3-mediated debenzylation reaction7,4r, taking the dichlo-
rinated macrocyclic compound 1 as the starting material. As shown
in Scheme 1, the benzyl groups were cleaved efficiently in toluene
at ambient temperature, concomitantly both the triazine rings
were also arylated by toluene via Friedel–Crafts reaction, produc-
ing compound 3 almost quantitatively. A similar condition was
then applied to synthesize compound 4 and the Friedel–Crafts
reaction enabled the arylation of the triazine rings of 2 by toluene
to give 4 in a high yield of 93%. The successful synthesis of 3 and 4
indicated that the AlCl3-mediated reaction could be used as a
deprotection–arylation or sole arylation procedure. The compound
5 was synthesized through the reaction of 3 and benzyl bromide in
the presence of K2CO3 with a high yield of 90%.
between anions and charge-neutral electron-deficient aromatic
rings, have attracted increasing attentions.2 In addition to the
extensively reported theoretical predictions,3 experimental evi-
dences for the interactions between anions and charge-neutral elec-
tron-deficient arenes, though still rare, have convincingly
demonstrated the existence of anion–
several groups including ourselves have demonstrated the crystal-
lographic observation of both non-covalent and weak anion–
interactions.4a–g,4i,4n,4r It is worth addressing that investigating
anion–
interactions in solution remains a challenging task.4h,4j–
In this context, most of the recognition models combined
anion– interactions with other non-covalent bond interactions
such as hydrogen bonding4h,4j,4o,4n,5c and halogen bonding.4q New
p
interactions.4 For example,
r
p
p
p,4r,5
p
host architectures are then in requirement for probing anion–
interactions in solution.
p
As a typical representative of heteracalixaromatics,6 tetraoxaca-
lix[2]arene[2]triazine, bearing an electron-deficient V-shaped cav-
ity formed with two triazine rings, has been demonstrated to be a
unique anion receptor based on anion–
solid states, the unique V-shaped electron-deficient cavities served
p
interactions.4d–f,4r,5 In
as a pair of tweezers to interact with the included anions through
The structures of the synthesized macrocyclic compounds 3, 4,
and 5 were established on the basis of spectroscopic data and ele-
mental analysis (Figs. S42–S47). To get the detailed structural infor-
mation in molecular level, single crystals of the three macrocyclic
⇑
Corresponding author. Tel.: +86 10 62565610; fax: +86 10 62564723.
E-mail address: dxwang@iccas.ac.cn (D.-X. Wang).
http://dx.doi.org/10.1016/j.tetlet.2014.04.007
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

W. Liu et al. / Tetrahedron Letters 55 (2014) 3172–3175
3173
R
R'
O
N
O
O
O
O
AlCl3, toluene
rt, 24 h
N
N
N
N
N
N
N
N
Cl
N
Cl
N
O
N
O
O
R
R'
1
2
, R = OBn
, R = H
3, R' = OH, yield 98%
4
, R' = H, yield 93%
Ph
Br
K2CO3, acetone
reflux
90%
OBn
O
N
O
O
N
O
N
N
N
N
OBn
5
Scheme 1. Synthesis of the larger-rim functionalized tetraoxacalix[2]arene[2]triazines 3, 4 and 5.
Figure 1. X-ray structure of 4 (A) top view, (B) side view, (C) stacked-badmintons-like self-assembly and (D) water channel. The ellipsoid probability is 25%. Hydrogen atoms
were omitted for clarity.
compounds were cultivated and crystallographic data of 3 and 4
were obtained. As shown in Figure 1 and Figures S1–S2, 3 and 4
adopt similar 1,3-alternate conformations.8 Each coupled p-tolyl
ring slightly twists with the triazine ring, with a dihedral angle of
16.15° and 5.19° for 3 and 4, respectively. Owing to the electron
deficient property of triazine rings, interesting interactions
between the host molecules and solvents were observed. For exam-
ple, in 4 a water molecule is included into the V-shaped cavity

3174
W. Liu et al. / Tetrahedron Letters 55 (2014) 3172–3175
formed with the two triazine rings, forming lone pair electron–
interactions with the triazine rings and weak hydrogen bonding
p
were calculated based on fluorescence titration curves using a
Hyperquad 2003 software,9 which are listed in Table 1. It is notice-
able from Table 1 that the host 4 shows decreased association con-
stants with anions compared to the parent dichloro-substituted
tetraoxacalix[2]arene[2]triazine 2,4d,4f probably due to the increas-
ing electron density on the triazine rings by the electron-donating
p-tolyl groups. The different substituents on the larger-rim of the
benzene rings slightly affect the association constants. For exam-
ple, the host 5, with a benzyloxy group attached on the benzene
rings, shows higher affinity towards the anions than 4. As the
bridge oxygen atoms tend to conjugate with the triazine rings
rather than benzene rings (Figs. S1–S2), the introduced benzyloxy
groups on the benzene rings are expected to barely affect the elec-
tronic density of the triazine rings. Then we speculated that the
electronic donating effect of the benzyloxy groups might increase
the electronic density of the benzene rings and hence facilitates
the counter cation association. To verify the hypothesis, we inves-
tigated the effect of cations on the association constants. As shown
in Table 1, while the different counter cations barely affected the
association constants for 4 and chloride, they resulted in increased
with the aryl hydrogen atoms (OÁ Á Á = 3.432 Å, OÁ Á ÁH–C = 3.375 Å,
p
Fig. 1A and B). Meanwhile, the other two sides of the water mole-
cule are also surrounded by another V-shaped cavity of two ben-
zene rings from the adjacent host molecule bearing short OÁ Á Á
p
distances (3.150 Å) and possible weak hydrogen bonding with the
two nitrogen atoms on the smaller rim of the triazine rings (O–
HÁ Á ÁN = 3.419 Å). The adjacent host molecules stack to each other
through
pÁ Á Áp interactions between the tolyl and triazine rings.
The multiple interactions eventually resulted in an interesting
stacked-badmintons-like self-assembly, in which a water channel
is formed (Fig. 1C and D). In the case of 3, an acetone molecule
was located above one of the triazine rings (Fig. S1B), approaching
the triazine ring through
r-type lone pair electron–p interaction,
which was indicated by the short O7acetoneÁ Á ÁC1triazine distance
(3.056 Å). In addition, the acetone molecule also forms a hydrogen
bond with one of the hydroxyl groups from the other host molecule
(OÁ Á ÁH–O = 2.710 Å). The coexistence of lone pair electron–
p
interactions and intermolecular hydrogen bonds hence led to a
ladder-like self-assembly motif in solid state (Fig. S1C).
association constants for
5 and chloride by an order of
We first examined the recognition properties of 3–5 towards
anions including ClÀ, BrÀ, SCNÀ, NOÀ3 , HSOÀ4 and H2POÀ4 by means
of spectroscopic titrations. Job’s plots indicated the formation of
1:1 complexes between the host molecules and the anions tested
(Fig. 2C and Fig. S3). As illustrated in Figure 2A and Figures
S4–S25, the addition of anions quenched the emission at 334 nm
and 463 nm for 3, 334 nm and 445 nm for 4, and 409 nm for 5,
respectively. The association constants (Ka(1:1)) of the complexes
Bu4N+(5ÁCl)À < Pro4N+(5ÁCl)À < Et4N+(5ÁCl)À < Me4N+(5ÁCl)À,
indi-
cating enhanced cation binding within the V-shaped cavity of the
two benzene rings by attaching the benzyloxy groups. With hydro-
xyl groups attached on the larger-rim of benzene rings, the host 3
gives the highest affinity towards the anions. While the cation
effects could not be excluded, the cooperative anion–p and hydro-
gen bonding interactions are probably the main contributions for
the enhanced binding.4r In addition, association constants listed
B
C
A
D
H3
O
H2
O
N
O
O
N
N
N
N
N
H1
O
OH
Figure 2. (A) Fluorescence titration curves of 3 (2.0 Â 10À4 M in 2 mL acetonitrile) upon the addition of Bu4NBr (0, 2.50, 4.99, 7.49, 9.99, 12.49, 14.98, 17.48, 19.98, 22.47,
24.97, 27.47, 29.96, 32.46, 34.96, 37.46 Â 10À4 M, respectively). The excitation wavelength is 300 nm. (B) The least-square nonlinear fitting (at 463 nm) with a Hyperquad
2003 program. (C) Job’s plot of the complex of 3 and Bu4NBr with a total concentration of 1.1 Â 10À2 M. (D) Partial 1H NMR spectra of 3 (1.06 Â 10À2 M in 0.5 mL of d6-
acetone) upon the addition of Bu4NBr.

W. Liu et al. / Tetrahedron Letters 55 (2014) 3172–3175
3175
Table 1
titration data) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2014.04.007.
Association constants (Ka(1:1)) of the host molecules with anions in acetonitrile
Ka(1:1) MÀ1
References and notes
3
4
5
Bu4NCl
Pro4NCl
Et4NCl
Me4NCl
Bu4NBr
Bu4NSCN
Bu4NNO3
Bu4NHSO4
Bu4NH2PO4
889 44
37
21
69
12
20
—
57
—
—
2
1
3
1
1
85
116
160
4
6
8
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results further supported the suspected cooperative anion–
p and
hydrogen bonding interactions in solution and were also consistent
with our previous observations.4r
In summary, one new type of larger-rim functionalized host
molecules have been synthesized through highly efficient AlCl3-
mediated deprotection/arylation protocol. The electron donating
nature of the p-tolyl groups coupling on the triazine rings weak-
ened the affinity of the host molecules towards anions. On the
other hand, the introduced benzyloxy and hydroxyl substituents
on the larger-rim of benzene rings enhanced the host-anion bind-
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Acknowledgments
We thank NNSFC (91127008, 21272239) and MOST
(2011CB932501, 2013CB834504) for financial support.
Supplementary data
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Supplementary data (experimental details, crystal structures,
1H and 13C NMR spectra of compounds, spectroscopic and NMR