Unsymmetrical N and/or O-bridged calixarene derivatives: Synthesis, structure and encapsulation of solvent molecules in the solid state

Article abstract of DOI:10.1016/j.tetlet.2011.12.099

Eight unsymmetrical N and/or O-bridged calixarene derivatives were obtained by 1 (naphthalene-2,7-diol), 2 (bis(4-hydroxyphenyl)methanone), 3 (4,4′-methylenedianiline), 4 (3,3′-methylenedianiline), 5 (4,4′-oxydianiline) and 6 (4,4′-(perfluoropropane-2,2-d

Full text of DOI:10.1016/j.tetlet.2011.12.099

Tetrahedron Letters 53 (2012) 1222–1226
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Unsymmetrical N and/or O-bridged calixarene derivatives: synthesis, structure
and encapsulation of solvent molecules in the solid state
⇑
Jingjing Yuan, Yanping Zhu, Mi Lian, Qinghe Gao, Meicai Liu, Fengcheng Jia, Anxin Wu
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Eight unsymmetrical N and/or O-bridged calixarene derivatives were obtained by 1 (naphthalene-2,7-
diol), 2 (bis(4-hydroxyphenyl)methanone), 3 (4,40-methylenedianiline), 4 (3,30-methylenedianiline), 5
(4,40-oxydianiline) and 6 (4,40-(perfluoropropane-2,2-diyl)dianiline) reacting with fragment a (4,40-bis(-
dichloro-s-triazinyloxy)propane-2,2-diyldibenzene) and b (N,N0-bis(dichloro-s-triazinyl)-4,40-methylene-
dianiline) under very mild reaction conditions via efficient fragment coupling strategy. We also obtained
the crystal structure of 1a (tetraoxocalix[2](propane-2,2-diyldibenzene,naphthalene)[2]triazine) which
can form a molecular capsule by two dimers with C–Hꢀ ꢀ ꢀN and C–Hꢀ ꢀ ꢀO quadruple hydrogen bonds,
and it has the encapsulation ability toward solvent molecules.
Received 1 November 2011
Revised 16 December 2011
Accepted 23 December 2011
Available online 30 December 2011
Keywords:
Fragment coupling strategy
Unsymmetrical
Ó 2011 Elsevier Ltd. All rights reserved.
Heterocalixaromatics
Proficiency in the art of design and synthesis of novel and func-
tional macrocyclic host molecules is a fundamental target of the
modern supramolecular chemistry. Along with the rapid develop-
ment of supramolecular chemistry, it is apparent that oxa-1 and
azacalixarenes2 have become the star molecules getting on the
stage of the macrocyclic host–guest chemistry due to their facile
synthesis and the interesting supramolecular properties that nitro-
gen and oxygen can bring to the host molecules. Hitherto, there is
much compelling work in this area, especially from groups such as
cyanuric chloride (5.54 g, 30 mmol) in the presence of diisopropyl-
ethylamine (DIPEA) (4.84 g, 37.5 mmol) using tetrahydrofuran
(THF) (100 ml) (Scheme 1). To avoid the production of di- or tri-
substitution chlorine, ice bath was used.6 Molecular fragment a
(4,40-bis(dichloro-s-triazinyloxy)propane-2,2-diyldibenzene) was
obtained in a 48% yield. The yield can be elevated slightly when
a large excess amount of cyanuric chloride was used.1b
With fragment a in hand, the synthesis of 1a was then attempted
under different conditions. As shown in Table 1, both the base and
the solvent were employed. When the reaction was conducted with
the base DIPEA, the use of 1,4-dioxane, DMF, and CH3CN all gave only
a trace amount of the desired product 1a (entries 3–5), and the use of
THF only gave 17% yield (entry 2), whereas acetone acted as an effec-
tive solvent to promote the formation of 1a in a 66% yield (entry 1).
And then, change of the base from inorganic base (Na2CO3 and
K2CO3) to organic base (Et3N), no expected product was observed
(entries 6–8). So the combination of DIPEA with acetone was the
optimization condition for the synthesis of 1a.
With the optimization condition, a series of diphenols and aro-
matic diamines were investigated for the synthesis of the unsym-
metrical heterocalixaromatic derivatives. In the beginning, as
illustrated in Scheme 2, naphthalene-2,7-diol (1) (160 mg, 1 mmol)
reacted with a (524 mg, 1 mmol) in acetone (80 ml), with the addi-
tion of DIPEA (322.5 mg, 2.5 mmol) as the acid scavenger to afford
1a in a 70% yield. As the result of the introduction of the naphtha-
lene with fluorescence effect and electron-rich conjugate surfaces
into the molecule, it was expected that the conformation of the
host molecule could demonstrate interesting effects.
Wang,1b–f,2c–g,3,5a–c
Chen,1m,n,2m,n,5e
Katz,1g,h,2l
Chambers,1a
Dehaen,1i,j and Siri.2i–k And preliminarily, heterocalixaromatics
have exhibited potential recognition to various guest species.3
In our previous work, we have developed a one-pot approach
toward cavity-size tunable oxacalixarene derivatives.4 However,
for the synthesis of unsymmetrical heterocalixaromatics,5 the frag-
ment coupling1b is more ideal than the one-pot approach due to
the appealing advantages in the straightforward introduction of
different heteroatoms and substituents into the bridging posi-
tions.2d In a continuation of our efforts, herein we reported a con-
venient fragment coupling strategy for the synthesis of novel
unsymmetrical N and/or O-bridged calixarene derivatives under
very mild conditions from simple and easily available starting
materials. We also obtained the crystal structure of 1a which can
form a molecular capsule by two dimers with C–Hꢀ ꢀ ꢀN and C–
Hꢀ ꢀ ꢀO quadruple hydrogen bonds, and it has the encapsulation
ability toward solvent molecules.
We began our investigation with 4,40-(propane-2,2-diyl) diphe-
nol (3.42 g, 15 mmol) as the nucleophilic reagent reacting with
In succession, treatment of bis(4-hydroxyphenyl)methanone
(2) (214 mg, 1 mmol) with molecular fragment a (524 mg, 1 mmol)
in the same conditions led to the formation of 2a in a 61% yield
⇑
Corresponding author. Tel.: +86 27 6786 7773.
E-mail address: chwuax@mail.ccnu.edu.cn (A. Wu).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.099

J. Yuan et al. / Tetrahedron Letters 53 (2012) 1222–1226
1223
Cl
O
N
O
N
°
N
N
DIPEA, THF, 0 C
N
N
N
N
+
Cl
Cl
HO
OH
Cl
N
Cl
Cl
Cl
a, 48%
Scheme 1. Synthesis of the molecular fragment a.
Table 1
Synthesis of tetraoxocalix[2](propane-2,2-diyldibenzene,naphthalene)[2]triazine 1aa
O
N
O
O
N
O
N
N
N
N
N
conditions
N
N
N
N
+
Cl
N
Cl
Cl
Cl
HO
OH
O
O
Cl
Cl
1
a
1a
Entry
Solvent
Base
Temp. (°C)
Time (h)
1a Yieldb
1
2
3
4
5
6
7
8
Acetone
THF
1,4-Dioxane
DMF
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
Na2CO3
K2CO3
Et3N
25
25
25
25
25
25
25
25
20
20
20
20
20
20
20
20
66%
17%
<10%
0
<10%
0
CH3CN
Acetone
Acetone
Acetone
0
0
a
Reaction was carried out with 1.0 equiv of fragment a, 1.0 equiv 1 (naphthalene-2,7-diol) and 2.5 equiv of base.
Isolated yields.
b
O
O
O
N
O
N
DIPEA
Acetone, 25 C
N
N
N
N
N
N
+
Cl
N
N
Cl
°
Cl
Cl
HO
OH
N
N
O
O
Cl
Cl
1
a
1a ,70%
Scheme 2. Synthesis of unsymmetrical O-bridged calixarene derivatives 1a via fragment coupling strategy.
(Scheme 3). With the carbonyl group linking the two benzenes, we
envision it may not only remodel the molecule, but also enlarge the
size of the cavity.
In order to obtain more molecules with tunable conformations
and cavities, a series of aromatic diamines (3–6) were also investi-
gated, under the prior condition. To our delight, 3a, 4a, 5a, 6a could
be obtained in 58%, 64%, 70% and 55% yields, respectively, and the
diverse aromatic diamines have little influence on the overall reac-
tion efficiency (Scheme 4).
Given the diversity of our research system and the orderliness
of the conformations of the macrocycles, fragment b (N,N0-bis(di-
chloro-s-triazinyl)-4,40-methylenedianiline) was obtained by con-
densation of 4,40-methylenedianiline (3) (1.98 g, 10 mmol) with
cyanuric chloride (3.69 g, 20 mmol) in the presence of DIPEA
(3.25 g, 25 mmol) using THF (100 ml) in an ice bath (Scheme 5).
Compounds 2b and 5b were prepared by the fragment b
(494 mg, 1 mmol) condensing with bis(4-hydroxyphenyl)metha-
none (2) (214 mg, 1 mmol) and 4,40-oxydianiline (5) (200 mg,
1 mmol) in the presence of DIPEA (322.5 mg, 2.5 mmol) in acetone
(100 ml) at room temperature (25 °C) (Scheme 6).
Fortunately, crystal of unsymmetrical O-bridged calixarene
derivatives 1a7 was obtained from slow evaporation of chloroform
solvent. The crystal structure of 1a adopts a twisted 1,3-alternate
conformation (Fig. 1). The cavity of 1a can be regarded as being
constructed by one naphthalene ring, propane-2,2-diyldibenzene
segments and two triazine rings.
X-ray structure analysis also showed that two molecules of 1a
can form a dimer by C–Hꢀ ꢀ ꢀN (dNꢀ ꢀ ꢀH = 2.645 Å, hC–Hꢀ ꢀ ꢀN = 165.72°)
and C–Hꢀ ꢀ ꢀO (dOꢀ ꢀ ꢀH = 2.664 Å, hC–Hꢀ ꢀ ꢀO = 154.81°) quadruple hydro-
gen bonds in the direction of face-to-face (Fig. 2). Subsequently, it

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J. Yuan et al. / Tetrahedron Letters 53 (2012) 1222–1226
O
O
N
O
O
N
O
N
N
N
N
O
N
O
N
DIPEA
Acetone, 25 C
Cl
Cl
N
N
N
N
+
°
Cl
Cl
HO
OH
Cl
Cl
a
2
2a, 61%
O
Scheme 3. Synthesis of unsymmetrical O-bridged calixarene derivatives 2a via fragment coupling strategy.
3
O
O
H2N
NH2
N
N
N
N
Cl
N
N
Cl
°
DIPEA, Acetone, 25 C
HN
NH
3a, 58%
4
O
O
N
N
N
NH2
NH2
Cl
N
Cl
°
DIPEA, Acetone, 25 C
N
N
HN
NH
O
O
4a, 64%
N
N
N
Cl
N
N
Cl
N
Cl
Cl
5
O
a
O
N
O
N
N
H2N
NH2
Cl
N
Cl
N
N
°
DIPEA, Acetone, 25 C
HN
NH
5a, 70%
O
F3C CF3
6
O
N
O
H2N
NH2
N
N
N
Cl
N
Cl
°
N
DIPEA, Acetone, 25 C
HN
NH
6a, 55%
F3C CF3
Scheme 4. Synthesis of unsymmetrical N, O-bridged calixarene derivatives 3a, 4a, 5a, 6a via fragment coupling strategy.
Cl
HN
N
NH
°
N
N
DIPEA, THF, 0 C
N
N
N
N
+
Cl
N
Cl
H2N
NH2
Cl
N
Cl
Cl
Cl
b, 66%
Scheme 5. Synthesis of the molecular fragment b.
is worth noting that a molecular capsule can be shaped by two di-
(dHꢀ ꢀ ꢀ = 2.866 Å, hC–Hꢀ ꢀ ꢀ = 32.73°). And one chloroform molecule
p p
mers through one pair of C–Hꢀ ꢀ ꢀO hydrogen bonds (dOꢀ ꢀ ꢀH = 2.526 Å,
was encapsulated in the cavity (Fig. 3). Finally, along the direction
of c-axis, an infinite molecular chain also can be viewed, which
hC–Hꢀ ꢀ ꢀO = 164.69°) and one pair of C–Hꢀ ꢀ ꢀ
p
interactions

J. Yuan et al. / Tetrahedron Letters 53 (2012) 1222–1226
1225
O
2
NH
N
HN
N
N
N
N
OH
HO
Cl
N
O
Cl
°
DIPEA ,Acetone, 25 C
O
NH
HN
2b, 70%
N
N
N
N
N
Cl
Cl
N
O
Cl
Cl
b
O
5
NH
N
HN
NH2
H2N
N
N
N
Cl
N
Cl
°
DIPEA ,Acetone, 25 C
N
NH
HN
5b, 72%
O
Scheme 6. Synthesis of unsymmetrical N, O-bridged calixarene derivatives 2b and 5b via fragment coupling strategy.
Figure 1. Crystal structure of unsymmetrical O-bridged calixarene derivatives 1a
(top view).
Figure 3. The molecular encapsule of 1a formed by two dimers and solvent
molecule CHCl3.
Figure 4. The infinite molecular chain formed by the molecular capsules of 1a
linking with each other along the direction of c-axis.
Figure 2. The structure of dimer formed by two 1a molecules.
ments of compounds 1a, 3a, 4a, 5a, and 6a in CDCl3 solution,
and found that no significant changes for compounds 1a, 3a, 5a,
and 6a at 298, 308, and 318 K. This indicated that these com-
pounds might have a rigid conformation at this temperature
range. However, significant spectral changes appeared for com-
pound 4a when temperature was changed from 298 to 318 K.
So we dissected these changes once again from 298 to 319 K for
every 3 K (Fig. 5).
was formed by the molecular capsules linking with each other
(Fig. 4). Furthermore, in the crystal structure, the solvent molecule
CHCl3 exists the phenomenon of symmetrical disorder. Due to the
unsymmetrical structure and the inclusion mechanics of 1a, we sup-
pose that these molecules will unfold engaging conformations and
develop to be the potential powerful host molecules with excellent
inclusion ability in supramolecular system.
In order to study conformation of the molecules in solution,
From the spectrum of 4a, we predicated the phenylene proton
signal Ha of 4a appeared as a singlet at d = 7.46 ppm in CDCl3
we further carried out the variable-temperature 1H NMR experi-

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J. Yuan et al. / Tetrahedron Letters 53 (2012) 1222–1226
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.12.099.
References and notes
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Figure 5. Variable-temperature 1H NMR experiments of compound 4a in CDCl3
solution.
solution at 298 K. When temperature was elevated from 298 to
319 K for every 3 K, the proton signal moved upfield gradually
and finally was enfolded into the neighboring doublet. This phe-
nomenon might attribute to the conformational conversion of
compound 4a in solution (See S10–S14 of Supplementary data
for details).
In summary, a number of unsymmetrical N and/or O-bridged
calixarene derivatives have been synthesized via general and
good-yield fragment coupling strategy. And we obtained the crys-
tal structure of 1a which can form a molecular capsule by two di-
mers with C–Hꢀ ꢀ ꢀN and C–Hꢀ ꢀ ꢀO quadruple hydrogen bonds. And it
has the inclusion ability toward solvent molecules. Variable-tem-
perature 1H NMR experiments of compound 4a in CDCl3 solution
have been carried out, and the chemical shift of phenylene proton
signal Ha of 4a might demonstrate the conformational conversion
of compound 4a in solution. Progress in the recognition ability of
these compounds is still underway. The work will be reported in
due course.
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Holm-Hansen, D. J. Am. Chem. Soc. 1951, 73, 2981–2983; (b) Blotny, G.
Tetrahedron Lett. 2006, 62, 9507–9522.
7. Crystal structure data for compound 1a: CCDC 850834.
chemical formula weight: 1342.23, tetragonal space group I4(1)cd, a = 28.8658
(2), b = 28.8658 (2), c = 14.754 (2) Å; = 90.000°, b = 90.000°, = 90.000°,
= 0.390 mmꢁ1
C63H41Cl7N12O8,
Acknowledgments
a
c
U = 12294(2) Å3, T = 298 (2) K, Z = 8, DC = 1.450 mg/m3,
l
,
k = 0.71073 Å, F(000) 5488, crystal size 0.20 ꢂ 0.20 ꢂ 0.10 mm3, 5374
independent reflections [R(int) = 0.1147], reflections collected 31488,
refinement method: full-matrix least-squares on F2: goodness-of-fit on F2
We would like to thank the National Natural Science Founda-
tion of China (Grant 20902035 and 201032001) for their generous
financial support and the research was supported in part by the
PCSIRT (No. IRT0953). We are also grateful to Xianggao Meng for
his help with X-ray diffraction analysis.
1.104, final R indices [I >2r(I)], R1 = 0.0647, wR2 = 0.1392, largest diff. peak and
hole 0.191 Åꢁ3 and ꢁ0.193 e Åꢁ3
.