Synthesis, structure and conformation of terphenylene-derived oxacalixaromatics

Article abstract of DOI:10.1002/ejoc.201101599

Oxacalix[4]aromatics comprised of terphenylene units have been synthesized by cyclooligomerization of 5′-tert-butyl-1,1′:3′,1″- terphenyl-4,4″-diol (1) and electron-deficient meta-dihalogenated benzene and heterocycles. Single-crystal X-ray analysis revealed that oxacalix[2]terphenylene[2]pyrazine 13 adopts a chair conformation, forming a molecular cavity to trap an ethyl acetate guest molecule in the solid state. 1,3-Alternate conformations are adopted by other oxacalix[2]terphenylene[2] aromatics (11, 12 and 15), which form a narrow tweezer-like molecular cavity that is incapable of encapsulating any guest molecules. Oxacalix[4]aromatics comprised of terphenylene units have been synthesized, andtheir structures and conformations have been elucidated. Copyright

Full text of DOI:10.1002/ejoc.201101599

FULL PAPER
DOI: 10.1002/ejoc.201101599
Synthesis, Structure and Conformation of Terphenylene-Derived
Oxacalixaromatics
Wen-Jing Hu,[a] Xiao-Li Zhao,[b] Ming-Liang Ma,*[a] Fang Guo,[c] Xian-Qiang Mi,[c]
Biao Jiang,*[c] and Ke Wen*[a,c]
Dedicated to Professor Wen-Qi Chen on the occasion of his 80th birthday
Keywords: Calixarenes / Aromatic substitution / Structure elucidation / Conformation analysis
Oxacalix[4]aromatics comprised of terphenylene units have
been synthesized by cyclooligomerization of 5Ј-tert-butyl-
1,1Ј:3Ј,1ЈЈ-terphenyl-4,4ЈЈ-diol (1) and electron-deficient
meta-dihalogenated benzene and heterocycles. Single-crys-
tal X-ray analysis revealed that oxacalix[2]terphenylene[2]-
pyrazine 13 adopts a chair conformation, forming a molecular
cavity to trap an ethyl acetate guest molecule in the solid
state. 1,3-Alternate conformations are adopted by other oxa-
calix[2]terphenylene[2]aromatics (11, 12 and 15), which form
a narrow tweezer-like molecular cavity that is incapable of
encapsulating any guest molecules.
tion and guest encapsulation. Two strategies have been de-
veloped to improve the guest encapsulation ability of the
heterocalix[n]aromatic family. In the first strategy, large aro-
matic components are employed in the construction of het-
erocalix[4]aromatic scaffolds to enlarge their cavity spaces.
For instance, Katz et al.[6] introduced naphthyridine and
naphthalene units into the oxacalix[4]arene scaffold and
found that the two naphthalene units separated by 7.0 Å
could form a defined tweezer-like cavity for selective bind-
ing of ortho-salicylic acid in solution and the incorporation
of a CH3CN molecule in the solid state. Chen and co-
workers introduced triptycene units into the heterocalix[4]-
aromatic system, which resulted in several new triptycene-
containing heterocalix[4]aromatics with enlarged cavities
and fixed conformations, and found that this class of heter-
ocalix[4]aromatic compounds could encapsulate a number
of different guest species.[7] In the second strategy, more
aromatic rings are introduced into the heterocalix[4]aro-
matic scaffolds. In this regard, several larger heterocalix[n]-
aromatics [n Ͼ 4] have been constructed[4m,8] and the guest
complexation behaviour of some larger heterocalix[n]aro-
matics [n Ͼ 4] have been evaluated.
Owing to its kinked shape, m-terphenylene is a key build-
ing block in phenylene-based macrocycles[9] and folda-
mers.[10] During the preparation of this manuscript, a new
report concerning the construction of oxacalix[2]m-terphen-
ylene[2]triazine was published.[11] In the work reported
herein, 5Ј-tert-butyl-1,1Ј:3Ј,1ЈЈ-terphenyl-4,4ЈЈ-diol (1) was
used as the nucleophilic partner in the synthesis of oxaca-
lix[4]arenes. The tert-butyl group on the m-phenylene unit
in 1 serves to increase the solubility of the resulting macro-
Introduction
Macrocyclic compounds have attracted great research
interest in the area of host–guest chemistry for a number
of decades.[1] [1n]Metacyclophanes (calix[n]arenes) and their
derivatives[2] are currently a focus of research because of
their easy synthesis, well-defined conformational and cavity
structures and their ability to act as host molecules for a
wide variety of neutral or charged species. Oxa- and aza[1n]-
metacyclophanes, a new class of heterocalix[n]aromatics in
which the methylene bridges in the calixarenes are replaced
by oxygen and nitrogen atoms, respectively, have attracted
considerable interest in recent years due to their synthetic
availability, tunable cavities and potential applications in
supramolecular chemistry.[3–5] However, the limited number
of heterocalix[n]aromatics available and their small molecu-
lar cavities severely hamper their use in molecular recogni-
[a] Shanghai Engineering Research Center of Molecular
Therapeutics and New Drug Development, East China Normal
University,
Shanghai 200062, China
Fax: +86-21-62621953
E-mail: mlma@brain.ecnu.edu.cn
kwen@brain.ecnu.edu.cn
[b] Shanghai Key Laboratory of Green Chemistry and Chemical
Processes and Department of Chemistry, East China Normal
University,
Shanghai 200062, China
[c] Center for Nanomedicine, Shanghai Advanced Research
Institute, Chinese Academy of Science,
Shanghai 201210, China
E-mail: jiangb@sari.ac.cn
wenk@sari.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101599.
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Terphenylene-Derived Oxacalixaromatics
cycles in organic solvents. The kinked shape of the m-ter- species, were observed, but they were difficult to separate
phenylene unit has led to several new oxacalix[2]terphen- from the reaction mixture. The introduction of electron-
ylene[2]aromatics with more conformational flexibility and withdrawing groups into the electrophile 2,6-dichloropyr-
larger molecular cavities than the known oxacalix[4]arenes idine (3), to give, for example, 2,6-dichloropyridine-3,5-di-
formed from resorcinol. The structures, conformations and carbonitrile (4) and 2,3,5,6-tetrachloropyridine (5), would
guest-trapping abilities of the novel oxacalix[2]terphenyl- greatly increase the electrophilicity of the resultant electro-
ene[2]aromatics in the solid state are discussed.
philes (4 and 5) and thus facilitate their aromatic substitu-
tion reactions with 1 under milder conditions. The reaction
of 1 with 2,6-dichloropyridine-3,5-dicarbonitrile (4) in the
presence of Cs2CO3 in DMSO at room temperature (0.5 h)
resulted in the formation of tetracarbonitrile-substituted
Results and Discussion
The synthesis of the terphenylene-based oxacalix[4]aro- oxacalix[2]terphenylene[2]pyridine 11 in a yield of 89.7%,
matics is depicted in Scheme 1. 5Ј-tert-Butyl-1,1Ј:3Ј,1ЈЈ-ter- whereas the condensation reaction of 1 with 2,3,5,6-tetra-
phenyl-4,4ЈЈ-diol (1) was prepared according to a modified chloropyridine (5) in the presence of Cs2CO3 in DMSO at
literature method (see the Exp. Sect. and the Supporting 120 °C (0.5 h) furnished tetrachlorinated oxacalix[2]ter-
Information).[12] The cyclooligomerization of 1 with 1,5-di- phenylene[2]pyridine 12 in 84.5% yield. Under the experi-
fluoro-2,4-dinitrobenzene (2) in the presence of Cs2CO3 in mental conditions, the product distributions were not affec-
DMSO at 50 °C for 3 h resulted in the formation of the ted by the temperature or concentration of the substrates,
expected terphenylene-based oxacalix[4]arene 9 in a yield of and therefore the cyclic tetramers are the thermodynami-
81.8%. No larger terphenylene-based oxacalix[n]arenes (n cally favoured products.
Ͼ 4) were detected.
The cyclooligomerization of 1 with meta-dichlorinated
The expected product was not obtained by heating the heterocycles that possess two or three aromatic nitrogen
reaction mixture with 2,6-dichloropyridine (3) in the tem- atoms, such as 2,6-dichloropyrazine (6), 4,6-dichloropyrim-
perature range of 50–200 °C due to its low reactivity. Fortu- idine (7) and cyanuric chloride (8), were also investigated.
nately, the expected oxacalix[2]terphenylene[2]pyridine 10 The reaction of 1 with 6 in the presence of Cs2CO3 in
was obtained in a yield of 40.5% by cyclocondensation of DMSO at 120 °C (3 h) furnished oxacalix[2]terphenylene-
1 and 2,6-dichloropyridine (3) in the presence of Cs2CO3 in [2]pyridine 13 in 44% yield. When 4,6-dichloropyrimidine
DMSO at 200 °C under microwave irradiation for 40 min. (7) was used as the electrophile, a mixture of inseparable
Byproducts, possibly larger cyclooligomers and polymeric products was generated by employing one-step and sequen-
Scheme 1. meta-Dihalogenated benzene and heterocycles 2–8 and the synthesis of oxacalix[2]terphenylene[2]aromatics 9–13 and 15.
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tial coupling strategies.[4h] The desired product, oxacalix[2]-
To analyse the structures and conformations of the newly
terphenylene[2]pyrimidine, was not isolated. This is possibly synthesized terphenylene-based oxacalix[4]aromatics, X-ray
a result of the unfavourable conformational preference of crystal structure analyses were carried out. Attempts to
the pyrimidine-derived linear ether intermediates in the fi- grow single crystals of 9 and 10 of X-ray diffraction quality
nal ring closure.[13] In the case of heterocycles that possess failed. Single crystals suitable for X-ray diffraction studies
three aromatic nitrogen atoms, such as cyanuric chloride were obtained for 11–13 and 15 in a variety of different
(8), direct cyclocondensation with 1 did not produce the solvents (see the Exp. Sect.). The X-ray data reveal that the
desired macrocyclic product. Fortunately, by employing a terphenylene-based oxacalix[4]aromatics 11, 12 and 15
fragment coupling strategy (Scheme 1), the reaction of 1 adopt a 1,3-alternate conformation in the solid state, similar
with 8 in a 1:2 ratio in THF in the presence of diisopropyl- to the conformational structures of most literature-docu-
ethylamine (DIPEA) at 0 °C afforded the linear terphenyl mented oxacalix[4]arenes.[4] In contrast, oxacalix[2]terphen-
14 in 63% yield, and the subsequent cyclocondensation re- ylene[2]pyrazine 13 was found to adopt a centrosymmetric
action between 1 and 14 was then accomplished in acetone chair conformation in the solid state. The structures of 11,
with DIPEA as base at room temperature to afford dichlor- 12 and 15 are shown in Figure 1. In 11, the four bridging
inated oxacalix[2]terphenylene[2]triazine 15 in 33.2% yield. oxygen atoms are located in one plane. The two pyridine
All the newly synthesized terphenylene-based oxacalix[4]- rings are eclipsed with a dihedral angle of 112.6° and a
1
aromatics (9–13 and 15) were studied by H and 13C NMR transannular N···N distance of 12.39 Å. The two terphenyl-
techniques. The results showed only one set of proton and ene units are highly twisted. In the crystal lattice, molecules
carbon signals in their corresponding 1H and 13C NMR of compound 11 are stacked in a tape-like arrangement
spectra, which indicates that the structures of these com- through π–π interactions (see the Supporting Information).
pounds are highly fluxional or that different conforma- Similar to 11, the four bridging oxygen atoms in 12 are also
tional structures interchange rapidly on the NMR timescle located in one plane, and the two pyridine rings in 12 are
(see the Supporting Information).
also eclipsed with a dihedral angle of 110.7° and a transan-
Figure 1. X-ray crystal structures of 11 (top left, top view; top right, side view), 12 (center left, top view; center right, side view) and 15
(bottom left, top view; bottom right, side view).
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Terphenylene-Derived Oxacalixaromatics
Figure 2. X-ray crystal structure of 13 revealing the encapsulation of a guest molecule of ethyl acetate in the solid state (left, top view,
right, side view).
nular N···N distance of 12.33 Å. In contrast to 11, the two
Conclusions
face-to-face oriented terphenylene units in 12 are parallel
We have synthesized six novel terphenylene-based oxa-
with centroid–centroid distances of 4.354, 4.466 and
calix[4]aromatics by aromatic SN2 substitution of 5Ј-tert-
butyl-1,1Ј:3Ј,1ЈЈ-terphenyl-4,4ЈЈ-diol (1) with electron-de-
ficient meta-dihalogenated benzene and heterocycles. Crys-
tal structure analyses revealed that 1,3-alternate and chair
conformations are adopted by these compounds in the solid
state. In the 1,3-alternate conformation adopted by the ter-
phenylene-based oxacalix[4]aromatics 11, 12 and 15, a clip-
like narrow space forms that eliminates the possibility of
4.354 Å between the three pairs of benzene rings in the two
terphenylene units. Similarly, tape-like arrays are formed by
12 in the crystal lattice driven by intermolecular C–H···Cl
and C–H···π interactions (see the Supporting Information).
In the case of 15, a distorted 1,3-alternate conformation is
adopted; the four bridging oxygen atoms are not located in
one plane. The two triazine rings are oriented to form a
wide opening with a dihedral angle of 116.4°. Thus, a
hosting any guest species, whereas the chair conformation
longer separation between the two chlorine atoms (19.61 Å)
adopted by the terphenylene-based oxacalix[4]aromatic 13
creates a molecular cavity that is large enough to encapsu-
and a shorter distance between the two lower-rim nitrogen
atoms (12.00 Å) in the two triazine rings are observed. The
late a guest molecule (for example, an ethyl acetate solvent
two terphenylene units are not parallel. The molecules stack
molecule). Studies on the synthesis, conformation fixation
together through intermolecular C–H···Cl and π–π stacking
and applications of the oxacalix[2]terphenylene[2]aromatics
interactions in the solid state (see the Supporting Infor-
family in host–guest chemistry are ongoing in our labora-
tory, and the results will be reported in due course.
mation). The crystal structures of 11, 12 and 15 show that
the 1,3-alternate conformation adopted by the terphenyl-
ene-based oxacalix[4]aromatics generally leaves no guest-ac-
cessible space between the rings, which limits their ability
to encapsulate guest molecules.
Experimental Section
General Methods: Commercially available chemicals were used
without further purification unless stated otherwise. 1H and 13C
NMR spectra were recorded with a Varian Mercury 500 (500 MHz)
or 300 (300 MHz) spectrometer in CDCl3 or [D6]DMSO with TMS
as the reference. Elemental analysis was performed for all new com-
pounds with an Elementar Vario EL (Germany) instrument. Mass
spectra were recorded with a microTOF QII mass spectrometer
(Bruker Daltonics, Germany).
As mentioned above, oxacalix[2]terphenylene[2]pyrazine
13 adopts a centrosymmetric, chair conformation in the so-
lid state, in contrast to 11, 12 and 15 as well as previously
reported oxacalix[4]aromatics.[4–6] Figure 2 shows that the
two pyrazine rings in 13 are planar, whereas the two ter-
phenylene units point in opposite directions. The two pe-
ripheral benzene ring planes are twisted by 33.3 and 41.2°
from the central m-phenylene spacer in the terphenylene
unit. This conformation adopted by 13 creates a molecular
cavity with a cross-section of 7.422ϫ12.016 Å, large
enough to trap small guest molecules, as is evidenced by the
inclusion of a solvated ethyl acetate in the solid state (due
to the vibrational nature of the included ethyl acetate, the
dataset did not allow its high-quality refinement).
Synthesis of 1,3-Bis(4-benzyloxyphenyl)-5-tert-butylbenzene: A solu-
tion of sodium carbonate (8.904 g, 84 mmol) in water (42 mL) and
ethanol (42 mL) was added to a mixture of 1,3-dibromo-5-tert-but-
ylbenzene (3.8 g, 13.0 mmol) and [4-(benzyloxy)phenyl]boronic
acid (6.5 g, 28.6 mmol) in toluene (84 mL). After degassing the
mixture and backfilling with nitrogen, [Pd(PPh3)4] (599 mg,
0.52 mmol) was added, and then the reaction mixture was heated
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at reflux for 30 h. The mixture was extracted with EtOAc, and the
organic extracts were washed with brine and dried with anhydrous
Na2SO4. After removal of the solvent, the residue was purified by
column chromatography (petroleum ether/ethyl acetate, 9:1) to af-
H), 7.21 (d, J = 8.4 Hz, 8 H, Ar-H), 6.88 (d, J = 7.9 Hz, 4 H, Ar-
H), 1.29 [s, 18 H, C(CH3)3] ppm. 13C NMR (CDCl3, 125 MHz): δ
= 162.46, 161.49, 153.213, 142.19, 140.97, 137.73, 127.72, 123.17,
122.60, 121.55, 104.87, 34.85, 31.41 ppm. HRMS (ESI): calcd.
C54H46N2O4Na [M + Na]+ 809.3350; found 809.3442. C54H46N2O4
ford 1,3-bis(4-benzyloxyphenyl)-5-tert-butylbenzene as a white so-
1
lid (5.54 g, 85.8%). H NMR ([D6]DMSO, 500 MHz): δ = 7.67 (d, (786.95): C 82.42, H 5.89, N 3.56; found C 82.24, H 6.14, N 3.58.
J = 8.7 Hz, 4 H, Ph-H), 7.57 (s, 1 H, Ar-H), 7.51 (d, J = 1.3 Hz, 2
Synthesis of Compound 11: A mixture of 1 (50 mg, 0.157 mmol),
H, Ar-H), 7.50 (d, J = 7.4 Hz, 4 H, Ar-H), 7.41 (dd, J1 = 7.30, J2
2,6-dichloropyridine-3,5-dicarbonitrile (4; 31 mg, 0.157 mmol) and
= 7.70 Hz, 4 H, Ar-H), 7.34 (d, J = 7.35 Hz, 2 H, Ar-H), 7.11 (d,
Cs2CO3 (113 mg, 0.346 mmol) in DMSO (50 mL) was stirred at
room temperature for 4 h. The reaction mixture was then poured
into ice/water (150 mL) and extracted with EtOAc (3ϫ50 mL). The
J = 8.7 Hz, 4 H, Ar-H), 5.16 (s, 4 H, CH2), 1.37 [s, 9 H, C(CH3)3]
ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 157.99, 151.83,
140.30, 137.13, 133.47, 128.50, 128.16, 127.87, 127.68, 121.89,
organic extracts were washed with brine and dried with anhydrous
121.85, 115.25, 69.29, 34.67, 31.24 ppm. HRMS (ESI): calcd. for
Na2SO4. After removal of the solvent, the residue was purified by
C36H34O2Na+ [M + Na]+ 521.2451; found 521.2324.
column chromatography (petroleum ether/ethyl acetate, 3:1) to af-
Synthesis of 5Ј-tert-Butyl-1,1Ј:3Ј,1ЈЈ-terphenyl-4,4ЈЈ-diol (1): 1,3- ford 11 as a white solid (62 mg, 89.7%). Crystals of 11 suitable for
Bis(4-benzyloxyphenyl)-5-tert-butylbenzene (1.890 g, 3.79 mmol)
was dissolved in ethyl acetate (30 mL), and a catalytic amount of
Pd(OH)2/C (10%) was added. The reaction mixture was degassed
and backfilled with hydrogen and then heated at 50 °C for 7 h. The
reaction mixture was filtered through diatomite, and the filtrate was
concentrated in a rotary evaporator. The residue was recrystallized
in EtOAc/petroleum ether (1:3) to give pure 1 as a white solid
(1.0 g, 83.0%). 1H NMR ([D6]DMSO, 500 MHz): δ = 9.50 (s, 2 H,
OH), 7.53 (d, J = 8.3 Hz, 4 H, Ar-H), 7.49 (s, 1 H, Ar-H), 7.45 (s,
2 H, Ar-H), 6.86 (d, J = 8.3 Hz, 4 H, Ar-H), 1.37 [s, 9 H,
C(CH3)3] ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 156.98,
151.55, 140.55, 131.67, 127.93, 121.33, 121.22, 115.62, 34.51,
31.18 ppm. HRMS (ESI): calcd. for C22H22O2Na [M + Na]+
341.1512; found 341.1480.
X-ray analysis were obtained from dichloromethane/ethyl acetate/
methanol (1:1:0.1) by slow concentration of the sample solution.
IR (KBr): ν = 3856.37, 3635.69, 3069.09, 2961.96, 2362.91,
˜
2235.35, 1606.03, 1558.95, 1430.16, 1335.09, 1288.51, 1245.67,
1212.15, 1160.30, 1117.12, 1015.09, 857.88, 823.54, 766.99, 704.63,
1
532.66, 446.77 cm–1. H NMR (CDCl3, 300 MHz ): δ = 9.14 (s, 2
H, Py-H), 7.77 (d, J = 8.7 Hz, 8 H, Ar-H), 7.72 (s, 2 H, Ar-H),
7.47 (s, 4 H, Ar-H), 7.33 (d, J = 8.7 Hz, 8 H, Ar-H), 1.28 [s, 18 H,
C(CH3)3] ppm. 13C NMR (CDCl3, 75 MHz): δ = 164.14, 151.68,
151.37, 150.78, 138.99, 137.81, 127.59, 122.53, 121.43, 121.10,
113.78, 90.55, 34.54, 31.01 ppm. HRMS (ESI): calcd.
C58H42N6O4Cl [M + Cl]– 921.2951; found 921.2153. C58H42N6O4
(886.99): C 78.54, H 4.77, N 9.47; found C 78.74, H 4.91, N 9.45.
Synthesis of Compound 12: A mixture of 1 (200 mg, 0.629 mmol),
2,3,5,6-tetrachloropyridine (5; 136 mg, 0.629 mmol) and Cs2CO3
(452 mg, 1.386 mmol) in DMSO (150 mL) was stirred at 120 °C for
0.5 h. The reaction solution was then poured into ice/water
Synthesis of Compound 9: A mixture of 5Ј-tert-butyl-1,1Ј:3Ј,1ЈЈ-ter-
phenyl-4,4ЈЈ-diol (1; 200 mg, 0.629 mmol), 1,5-difluoro-2,4-dinitro-
benzene (2; 128 mg, 0.629 mmol) and Cs2CO3 (452 mg,
1.386 mmol) in DMSO (100 mL) was stirred at 50 °C for 3 h. Then (200 mL) and extracted with EtOAc (3ϫ100 mL). The organic ex-
the solution was poured into ice/water (200 mL), extracted with
EtOAc (3ϫ50 mL) and washed with brine. The organic extracts
were dried with anhydrous Na2SO4. After removal of the solvent,
the residue was purified by column chromatography (petroleum
ether/CH2Cl2, 1:1) to afford 9 as a pale-yellow solid (248 mg,
tracts were washed with brine and dried with anhydrous Na2SO4.
After removal of the solvent, the residue was purified by column
chromatography (petroleum ether/ethyl acetate, 9:1) to afford 12 as
a white solid (245 mg, 84.5%). Crystals of 12 suitable for X-ray
analysis were obtained in chloroform. IR (KBr): ν = 2960.21,
˜
81.8%). IR (KBr): ν = 1617.11, 1505.22, 1478.97, 1347.24, 1293.21, 1577.12, 1506.54, 1387.58, 1308.65, 1265.47, 1162.41, 1093.55,
˜
1
1206.43, 1166.53, 830.22 cm–1. H NMR ([D6]DMSO, 500 MHz): 1014.20, 903.07, 858.26, 825.18, 729.24, 536.40 cm–1. 1H NMR
δ = 9.00 (s, 2 H, Ar-H), 7.83 (d, J = 8.6 Hz, 8 H, Ar-H), 7.66 (s, 2 (CDCl3, 500 MHz): δ = 7.84 (s, 2 H, Py-H), 7.41 (s, 6 H, Ar-H),
H, Ar-H), 7.52 (s, 4 H, Ar-H), 7.32 (d, J = 8.6 Hz, 8 H, Ar-H),
6.46 (s, 2 H, Ar-H), 1.30 [s, 18 H, C(CH3)3] ppm. 13C NMR ([D6]-
DMSO, 500 MHz): δ = 155.44, 152.42, 152.06, 138.80, 138.00,
132.85, 128.77, 125.54, 122.93, 121.34, 120.54, 105.94, 34.63,
31.01 ppm. HRMS (ESI): calcd. for C56H44N4O12Cl [M + Cl]–
999.2639; found 999.2769. C56H44N4O12 (964.97): C 69.70, H 4.60,
N 5.81; found C 69.76, H 4.00, N 5.66.
7.39 (d, J = 1.5 Hz, 8 H, Ar-H), 7.07 (d, J = 8.5 Hz, 8 H, Ar-H),
1.33 [s, 18 H, C(CH3)3] ppm. 13C NMR (CDCl3, 125 MHz): δ =
154.91, 152.54, 151.94, 141.37, 140.65, 138.55, 127.78, 123.21,
122.39, 121.78, 110.56, 34.84, 31.41 ppm. HRMS (ESI): calcd. for
C54H42Cl4N2O4Na [M
C54H42Cl4N2O4 (924.73): C 70.14, H 4.58, N 3.03; found C 69.98,
H 4.15, N 3.12.
+
Na]+ 947.1773; found 947.1983.
Synthesis of Compound 10: Compound 1 (50 mg, 0.158 mol), 2,6- Synthesis of Compound 13: A mixture of 1 (200 mg, 0.629 mmol),
dichloropyridine (3; 23 mg, 0.158 mmol) and Cs2CO3 (113 mg,
0.345 mmol) were added to DMSO (20 mL) in a glass tube with a
magnetic stirring bar and sealed with a plastic cap. The mixture
was heated at 200 °C under 50 W of microwave irradiation for
40 min. The resultant solution was poured into ice/water (100 mL)
and extracted with EtOAc (3ϫ20 mL). The organic extracts were
washed with brine and dried with anhydrous Na2SO4. After re-
moval of the solvent, the residue was purified by column
chromatography (petroleum ether, 100%) to afford 10 as a white
2,6-dichloropyrazine
6 (93.7 mg, 0.629 mmol) and Cs2CO3
(452 mg, 1.386 mmol) in DMSO (150 mL) was stirred at 120 °C for
0.5 h. The reaction solution was then poured into ice/water
(300 mL) and extracted with EtOAc (3ϫ100 mL). The organic ex-
tracts were washed with brine and dried with anhydrous Na2SO4.
After removal of the solvent, the residue was purified by column
chromatography (petroleum ether/ethyl acetate, 9:1) to afford 13 as
a white solid (108 mg, 44%). Crystals of 13 suitable for X-ray
analysis were obtained from dichloromethane/ethyl acetate (1:1).
solid (25 mg, 40.5%). IR (KBr): ν = 1598.65, 1578.18, 1506.65,
IR (KBr): ν = 2960.54, 1594.91, 1536.37, 1506.32, 1449.77,
˜
˜
1432.07, 1277.25, 1234.30, 1167.48, 1012.79, 838.19 cm–1. 1H NMR
([D6]DMSO, 500 MHz): δ = 7.97 (dd, J1 = 7.5, J2 = 8.0 Hz, 2 H,
Py-H), 7.66 (s, 8 H, Ar-H), 7.64 (s, 2 H, Ar-H), 7.46 (s, 4 H, Ar-
1403.45, 1253.32, 1206.33, 1172.69, 837.53 cm–1. 1H NMR (CDCl3,
500 MHz): δ = 8.21 (s, 4 H, Py-H), 7.47 (s, 6 H, Ar-H), 7.46 (d, J
= 1.8 Hz, 8 H, Ar-H), 7.18 (d, J = 8.55 Hz, 8 H, Ar-H), 1.36 [s, 18
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1448–1454

Terphenylene-Derived Oxacalixaromatics
H, C(CH3)3] ppm. 13C NMR (CDCl3, 125 MHz): δ = 157.22,
152.32, 152.17, 140.79, 138.35, 127.97, 127.73, 123.37, 121.31,
35.01, 31.39 ppm. HRMS (ESI): calcd. for C52H44N4O4Na [M +
Na]+ 811.3255; found 811.3263. C52H44N4O4 (788.93): C 79.16, H
5.62, N 7.10; found C 79.45, H 5.02, N 6.91.
dices (all data): R1 = 0.1007, wR2 = 0.2948, largest diff. peak and
hole: 1.310 and –0.696 e/Å3.
Single-Crystal Structure of 12: C54H42Cl4N2O4, Mr = 924.70, T =
296(2) K, orthorhombic, space group Pnma, a = 18.348(2), b =
26.829(3), c = 9.5215(11) Å, α = β = γ = 90°, V = 4687.1(9) Å3, Z
= 4, ρcalcd. = 1.310 g/cm3, crystal size = 0.15ϫ0.06ϫ0.06 mm, μ =
0.301 mm–1, reflections collected 28138, unique reflections 4459,
data/restraints/parameters 4459/0/307, GOF on F2 1.093, Rint for
independent data 0.0518, final R1 = 0.0493, wR2 = 0.1444, R in-
dices (all data): R1 = 0.0873, wR2 = 0.1742, largest diff. peak and
hole: 0.367 and –0.297 e/Å3.
Synthesis of Compound 14: A mixture of 1 (100 mg, 0.315 mmol)
and diisopropylethylamine (101 mg, 0.785 mmol) in THF (30 mL)
was added dropwise to an ice-cooled solution of cyanuric chloride
(8; 128 mg, 0.692 mmol) in THF (30 mL) over 1 h. The resulting
mixture was stirred for an additional 1 h. After removal of diiso-
propylethylamine hydrochloride by filtration, the filtrate was con-
centrated and purified by silica gel column chromatography with a
mixture of petroleum ether/EtOAc (100:7) as the mobile phase to
give pure 14 as a white solid (121 mg, 63%). 1H NMR (CDCl3,
500 MHz): δ = 7.72 (d, J = 8.65 Hz, 4 H, Ar-H), 7.62 (d, J =
1.45 Hz, 2 H, Ar-H), 7.61 (d, J = 1.5 Hz, 1 H, Ar-H), 7.27 (d, J =
6.6 Hz, 4 H, Ar-H), 1.44 [s, 9 H, C(CH3)3] ppm. 13C NMR (CDCl3,
125 MHz): δ = 173.14, 171.12, 152.55, 150.45, 140.46, 140.40,
128.81, 123.79, 123.55, 121.27, 35.03, 31.44 ppm. HRMS (ESI):
calcd. C29H25Cl4N6O3[M + CH3OH + H]+ 647.0711; found
647.5639.
Single-Crystal Structure of 13: C27.50H22N2O3, Mr = 428.47, T =
296(2) K, monoclinic, space group P21/c, a = 14.6532(18), b =
5.6133(7), c = 30.790(4) Å, α = γ = 90°, β = 94.273(4)°, V =
2525.5(5) Å3,
Z = 4, ρcalcd. = =
1.127 g/cm3, crystal size
0.45ϫ0.36ϫ0.32 mm, μ = 0.074 mm–1, reflections collected 27918,
unique reflections 4445, data/restraints/parameters 4445/54/340,
GOF on F2 0.973, Rint for independent data 0.0701, final R1
0.0911, wR2 = 0.2799, R indices (all data): R1 = 0.1368, wR2
0.3311, largest diff. peak and hole: 0.667 and –0.326 e/Å3.
=
=
Single-Crystal Structure of 15: C50H40Cl2N6O4, Mr = 859.78, T =
173(2) K, monoclinic, space group P21/c, a = 9.4309(5), b =
26.0246(15), c = 18.0086(10) Å, α = γ = 90°, β = 101.830(2)°, V =
Synthesis of Compound 15: Solutions of 1 (92 mg, 0.288 mmol) in
acetone (50 mL) and compound 14 (177 mg, 0.288 mmol) in acet-
one (90 mL) were both added dropwise to a solution of diiso-
propylethylamine (89 mg, 0.691 mmol) in acetone (100 mL) at
room temperature. After addition, the resulting mixture was stirred
for another 48 h until the starting materials had been consumed.
The solvent was removed, and the residue was purified by silica gel
column chromatography (petroleum ether/ethyl acetate, 100:7) to
afford 15 as a white solid (82 mg, 33.2%). Crystals of 15 suitable
for X-ray analysis were obtained in a mixed solvent of dichloro-
methane/ethyl acetate/methanol (1:1:0.1) by slow concentration of
4326.1(4) Å3,
Z = 4, ρcalcd. = =
1.320 g/cm3, crystal size
0.42ϫ0.36ϫ0.32 mm, μ = 0.204 mm–1, reflections collected 50080,
unique reflections 7619, data/restraints/parameters 7619/0/559,
GOF on F2 1.021, Rint for independent data 0.0490, final R1
0.0304, wR2 = 0.0805, R indices (all data): R1 = 0.0550, wR2
0.0906, largest diff. peak and hole: 0.232 and –0.241 e/Å3.
=
=
Supporting Information (see footnote on the first page of this arti-
1
cle): Detailed synthetic experimental procedures for 1, H and 13C
NMR spectra for all compounds, and Molecular packing of com-
pounds 11, 12, 13, 15.
the sample solution. IR (KBr): ν = 2924.51, 1492.89, 1410.39,
˜
1295.21, 1267.23, 1217.85, 1183.38 cm–1. 1H NMR (CDCl3,
500 MHz): δ = 7.47 (s, 4 H, Ar-H), 7.45 (d, J = 2.0 Hz, 8 H, Ar-
H), 7.43 (s, 2 H, Ar-H), 7.16 (d, J = 8.6 Hz, 8 H, Ar-H), 1.36 [s,
18 H, C(CH3)3] ppm. 13C NMR (CDCl3, 125 MHz): δ = 174.21,
171.88, 152.42, 150.75, 140.46, 139.61, 128.10, 123.64, 122.77,
121.16, 34.92, 31.36 ppm. HRMS (ESI): calcd. C50H40Cl2N6O4Na
[M + Na]+ 881.2380; found 881.2396. C50H40Cl2N6O4 (859.80): C
69.85, H 4.69, N 9.77; found C 70.23, H 5.03, N 9.88.
Acknowledgments
The authors thank the National Natural Science Foundation of
China (21071053, 21002031, 61078071), the Shanghai Commission
for Science and Technology (06Pj14034, 10ZR1409700) and the
Shanghai Education Development Foundation (2008CG31) for fin-
ancial support. Support from the Fundamental Research Funds for
the Central Universities is also acknowledged.
Crystal Structure Data Collection and Refinement: Intensity data
were collected at 173(2) K or room temperature (296 K) with a
Bruker SMART APEX 2 X-ray diffractometer equipped with a
nomal focus Mo-target X-ray tube (λ = 0.71073 Å). Data reduction
included absorption corrections by the multiscan method. The
structures were solved by direct methods and refined by full-matrix
least-squares using SHELXS-97.[14] All non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were included at their geo-
metrically ideal positions and refined isotropically. Experimental
data for 11–13 and 15 are shown below. CCDC-851880 (11),
-851881 (12), -851882 (13) and -851883 (15) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Published Online: January 17, 2012
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