Synthesis, structure, and conformation of terphenylene-derived azacalix[4]aromatics

Article abstract of DOI:10.1016/j.tet.2012.04.108

Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential nucleophilic aromatic substitution reactions of 5′-t-butyl-(1,1′:3′,1″-terphenyl)-3,3″-diamine 9 and 5′-t-butyl-(1,1′:3′,1″-terphenyl)- 4,4″-diamine 11

Full text of DOI:10.1016/j.tet.2012.04.108

Tetrahedron 68 (2012) 6071e6078
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Synthesis, structure, and conformation of terphenylene-derived azacalix[4]
aromatics
,
b
c
c
c
,
a,c,
*
Wen-Jing Hu a, Ming-Liang Ma a , Xiao-Li Zhao , Fang Guo , Xian-Qiang Mi , Biao Jiang , Ke Wen
*
*
a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China
b Shanghai Key Laboratory of Green Chemistry and Chemical Processes, 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
a r t i c l e i n f o
a b s t r a c t
Article history:
Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential
nucleophilic aromatic substitution reactions of 50-t-butyl-(1,10:30,100-terphenyl)-3,300-diamine 9 and 50-t-
butyl-(1,10:30,100-terphenyl)e 4,400-diamine 11 with 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride,
respectively. The bridging eNHe functions of the tetra-nitro substituted azacalix[2]arene[2]terphenylenes
1 and 2 have been transformed to the corresponding eN(CH3)e bridged azacalix[2]arene[2]terphenylenes
3 and 4 via N-alkylation. Single crystal X-ray analysis revealed that the terphenyl-3,300-diamine derived
azacalix[2]terphenylene[2]triazine 5 adopts a distorted chair conformation in the solid state, and the
terphenyl-4,400-diamine derived azacalix[2]terphenylene[2]triazine 6 was found to adopt a 1,3-alternate
conformation.
Received 11 February 2012
Received in revised form 21 April 2012
Accepted 28 April 2012
Available online 16 May 2012
Keywords:
Azacalixarenes
Terphenylene
Structure
Ó 2012 Elsevier Ltd. All rights reserved.
Conformation
1. Introduction
aromatic host could selectively bind ortho-salicylic acid in solution,
and incorporate
a
CH3CN molecule in the solid state.6 The
Calix[n]arenes and their derivatives,1 have received great re-
search interest because of their easy synthesis, well-defined con-
formational and cavity structures, and the abilities to act as host
molecules for wide variety of neutral or charged species. Recently,
heterocalix[n]aromatics,2 a class of structural analogous of calix[n]
arenes, in which the methylene bridges of conventional calix[n]
arenes are replaced by oxygen3 and nitrogen3c,4 atoms, respectively,
have attracted considerable interest due to their synthetic avail-
ability, tunable cavities, and potential applications in supramolec-
ular chemistry.5 However, the limited number of heterocalix[n]
aromatics available and the small cavity possessed by the hetero-
calix[4]aromatics family severely hampered their further use in
molecular recognition and guest encapsulation. In order to improve
the guest inclusion ability of the heterocalix[n]aromatics, two
strategies have been developed to expand their cavity spaces. One
was to construct heterocalix[4]aromatics with large aromatic com-
ponents to enlarge their cavity spaces. For instance, the introduction
of naphthyridine and naphthalene units into oxacalix[4]arene
scaffold resulted in heterocalix[4]aromatics with a well-defined
triptycene-containing heterocalix[4]aromatics developed by Chen
and co-workers7 were found to adopt fixed conformations with
enlarged cavity spaces, which could encapsulate a number of dif-
ferent guest species. The other strategy was to introduce more ar-
omatic rings into the heterocalix[4]aromatics scaffolds, and several
larger heterocalix[n]aromatics [n>4] have thus been con-
structed.3m,8 The guest complexation behaviour of some heterocalix
[n]aromatics [n>4] have been evaluated.
Due to its kinked shape, m-terphenylene has long been used as
a key strut of phenylene-based macrocycles9 and foldamers.10 Very
recently, we11 and others12 have employed terphenyl-4,400-diol in
the synthesis, structural and conformational studies of oxacalix[2]
terphenylene[2]aromatics. Due to the conformational flexibilities of
the m-terphenylene units, both 1,3-alternate and chair conforma-
tions have been adopted by the oxacalix[2]terphenylene[2]aro-
matics.11,12 A molecular cavity was formed by a chair conformational
oxacalix[2]terphenylene[2]pyrazine, which could trap a guest mol-
ecule of ethyl acetate in the solid state.11 However, terphenylene
units have not been found in the construction of azacalixaromatics.
Herein, we wish to report our recent results on the construction of
several 50-t-butyl-(1,10:30,100-terphenyl)- 3,300-diamine 9 and 50-t-
butyl-(1,10:30,100-terphenyl)-4,400-diamine 11 derived azacalix[2]ter-
phenylene[2]aromatics (Scheme 1). The t-butyl group on the
m-phenylene units serves to increase the solubility of the resulting
ꢀ
tweezers-like cavity separated by 7.0 A, such a heterocalix[4]
* Corresponding authors. Tel: þ86 21 62237102; fax: þ86 21 62601953; e-mail
addresses: mlma@brain.ecnu.edu.cn (M.-L. Ma), jiangb@sari.ac.cn (B. Jiang), wenk@
sari.ac.cn, kwen@brain.ecnu.edu.cn (K. Wen).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.108

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W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
macrocycles in organic solvents. The structural and conformational
properties of some resulting azacalix[2]terphenylene[2]aromatics
are discussed.
and mass spectra, which support their macrocyclic structural
features (Fig. 1). The 1H and 13C NMR spectra of 3 and 4 showed
only one set of proton and carbon signals, which indicate that the
H
H
H
H
H
N
N
N
N
N
N
N
N
N
N
NO2
NO2
N
N
NO2 O2N
NO2
NO2
O2N
O2N
O2N
1
2
3
O2N
NO2
O2N
H
H
H
H
H
H
H
N
N
N
N
N
N
N
O2N
O2N
NO2
Cl
NO2
N
N
N
N
N
N
N
N
Cl Cl
N
N
N
N
Cl
6
5
4
N
N
N
N
N
H
H
H
H
Scheme 1. The structures of the reported terphenylene-based azacalix[4]aromatics.
2. Results and discussion
structures of 3 and 4 are highly fluxional or different conforma-
tional structures, interchange rapidly in the NMR time scale (13C
NMR spectra of 3 and 4 see Supplementary data).
50-t-Butyl-(1,10:30,100-terphenyl)-3,300-diamine 9 and 50-t-butyl-
(1,10:30,100-terphenyl)-4,400-diamine 11 were prepared according to
a modified literature method (Scheme 2).13 Synthesis of the ter-
The terphenylediamine 9(11) reacted with cyanuric chloride
(2.2 equiv) in the presence of N(i-Pr)2(Et) in THF at 0ꢀ resulted in
linear trimer 14(15), which was further reacted with 9(11)
(1.0 equiv) in acetone under dilute condition in the presence of
N(i-Pr)2(Et) for 72 h afforded dichloronated eNHe bridged aza-
calix[2]terphenylene[2]triazines 5(6) as white solid(s) in the
overall yield(s) of 22% (43%), as shown in Scheme 4. Dichloronated
azacalix[2]terphenylene[2]triazine 5 and 6 were characterized by
1H, 13C NMR and mass spectroscopies, respectively. All these data
support the formation of dichloronated azacalix[2]terphenylene[2]
triazines 5 and 6. The broad peaks in the 1H and 13C NMR spectra
of 5 indicate that compound 5 might be in a restricted confor-
mation or different conformational structures, interchange slowly
in the NMR time scale (Supplementary data). However, only one
set of proton and carbon signals in the corresponding 1H and 13C
NMR spectra of 6 were observed, which indicate that compound 6
is highly fluxional in solution or different conformational struc-
tures, interchange rapidly in the NMR time scale (Supplementary
data).
phenylene-based
azacalix[4]aromatics
is
depicted
in
Schemes 3 and 4 (details see experimental section). Direct cyclo-
oligomerization of 9(11) with 1,5-difluoro-2,4-dinitrobenzene
provided tetra-nitro substituted azacalix[2]arene[2]terpheny-
lenes 1 and 2 in very low yields, thus, a sequential coupling
strategy is employed in their synthesis. The terphenyl-diamines
9(11) reacted with 1,5-difluoro-2,4-dinitrobenzene (0.5 equiv) in
reflux EtOH in the presence of N(i-Pr)2(Et) (DIPEA) for 24 h
resulted in the precipitation of linear product 12(13) as yellow
solid, which was used directly in the next step of the synthesis.
12(13) reacted with 1,5-difluoro-2,4-dinitrobenzene (1.0 equiv) in
reflux CH3CN in the presence of N(i-Pr)2(Et) for 48 h and afforded
eNHe bridged azacalix[2]arene[2]terphenylene 1(2) as yellow
solid(s). However, the solubility of 1 and 2 are extremely poor in
almost all organic solvents, which prevented their characteriza-
tion. To improve their solubility, methylation of the eNHe bridges
of 1 and 2 was carried out. The tetra-nitro substituted eN(CH3)-
bridged azacalix[2]arene[2]terphenylenes 3 and 4 were thus
obtained by the reaction of 1 and 2 with methyl iodide in the
presence of K2CO3, in the overall yields of 41% and 31%, re-
spectively, as shown in Scheme 3. No decent 1H and 13C NMR
spectra of 1 and 2 were obtained duo to their severely low solu-
bility. The tetra-nitro substituted eN(CH3)e bridged azacalix[2]
arene[2]terphenylenes 3 and 4 were characterized by 1H, 13C NMR
In order to analyze the structures and conformations of the
newly synthesized terphenylene-based azacalix[4]aromatics, X-ray
crystal structure analysis was carried out. Attempts to grow single
crystals of 1, 2, 3 and 4 with X-ray diffraction quality failed. How-
ever, single crystals of 5 and 6 suitable for X-ray diffraction studies
were obtained in the mixed solvent of DMSO and chloroform. The
X-ray result revealed that the terphenyl-3,300-diamine-based

W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
6073
bis(pinacolato)diboron
Pd(dppf)Cl2
O
O
B
B
DMF/KOAc
100oC
N2
O
O
Br
Br
7
NHBOC
Pd(PPh3)4/Ethanol
/Na2CO3(aq)
CF3COOH
CH2Cl2
+
tolune/N2
85oC
O
O
Br
B
O
B
O
NH2
NH2
NHBOC
NHBOC
9
7
8
NHBOC
Pd(PPh3)4/Ethanol
/Na2CO3(aq)
CF3COOH
+
tolune/N2
85oC
CH2Cl2
O
O
B
O
B
O
H2N
NH2
Br
COBHN
NHBOC
11
10
7
Scheme 2. Synthesis of 50-t-butyl-(1,10:30,100-terphenyl)-3,300-diamine 9 and 50-t-butyl-(1,10:30,100-terphenyl)-4,400-diamine 11.
O2N
NO2
N
N
H
H
12
NH2
NH2
NH2
NH2
O2N
NO2
9
DIPEA
+
Ethanol
F
F
O2N
NO2
N
N
H
H
H2N
NH2
H2N
NH2
11
13
O2N
F
NO2
CH3I
3
1
K2CO3
DMF
F
DIPEA
2
4
CH3CN
Scheme 3. Synthesis of tetra-nitro substituted azacalix[2]arene[2]terphenylenes 1, 2, 3 and 4.
azacalix[2]terphenylene[2]triazine 5 adopts a central symmetric,
twisted chair conformation in the solid state, different from the
conformational structures of most literature documented azacalix
[4]arenes2 and those of the terphenylene-derived oxacalixar-
omatics,11,12 as shown in Fig. 2. The pair of triazine rings is arranged
eclipsing and are pointing to opposite directions with the Cl.Cl
Due to the quality of the single crystal of 6, we were only
able to get a dataset that did not allow for high quality re-
finement, but could be used to confirm the basic structural
motif. As show in Fig. 3, a 1,3-alternate conformation for the
terphenyl-4,400-diamine-based azacalix[2]terphenylene[2]triazine
6 is observed, similar to the conformational structures of most
literature documented azacalix[4]arenes2 and terphenylene-
derived oxacalixaromatics.11,12 The terphenylene-based azacalix
[4]arene 6 adopts a ‘dimeric’ structure in the solid state, in which
one central benzene ring plane (including its t-butyl substituent)
of one monomer extended into the ‘void’ created by the two
terphenylene units of the other monomer (Fig. 3). The four
bridging nitrogen atoms are located in one plane. The pair of
triazine rings orients to form a wide opening with a dihedral
angle of 128.8ꢀ, resulting in a longer separation between the two
ꢀ
separation of 18.15 A. The pair of terphenylene units is highly
twisted. The four bridging nitrogen atoms in 5 are found located in
one plane (see Fig. 2c), and form a highly symmetrical rhomboid
ꢀ
ꢀ
with the two pairs of N.N distances of 4.67 A and 10.97 A, re-
spectively. The bridging nitrogen atoms were found to conjugate
ꢀ
with triazine rings (CeN bond length 1.35 A), and no conjugation
existing between the bridging nitrogen atoms and the connecting
ꢀ
phenyl rings (CeN bond length 1.41 A). In the crystal lattice, com-
pound 5 are arranged in layered fashion with the interlayer space
filled by solvent molecules of DMSO (Fig. 2d and e).
ꢀ
chlorine atoms (19.94 A). The central benzene ring planes of

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W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
1, DIPEA
Acetone
H
N
H
N
N
5
N
N
N
Cl
N
Cl
N
NH2
NH2
Cl
14
9
DIPEA
THF
Cl
Cl
N
N
+
N
Cl
Cl
H
H
2, DIPEA
Acetone
N
N
N
H2N
NH2
N
N
6
11
Cl
N
Cl
N
N
Cl
Cl
15
Scheme 4. Synthesis of dichloronated azacalix[2]terphenylene[2]triazines 5 and 6.
the two terphenylene units are arranged in
a
face-to-face
the crystal packing, and are filled with highly disordered
solvent molecules (DMSO). However, these solvent molecules
(DMSO) are hardly to be refined due to their highly disordered
nature.
manner with a dihedral angle of 72.5ꢀ, and a separation of
ꢀ
12.26 A between the quaternary carbon atoms of the two t-butyl
groups. In the solid state, large ‘empty’ spaces are created by
Fig. 1. 1H NMR spectra of compounds 3 (top) and 4 (bottom).

W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
6075
Fig. 2. Crystal structure of dichloronated azacalix[2]terphenylene[2]triazines 5 (a, top view; b, side view; c, schematic drawing of the plane formed by the four bridged nitrogen
atoms) and the molecular packing (layers) in the solid state (d and e). Colour codes: oxygen¼red, nitrogen¼blue, chlorine¼green, sulfur¼yellow, carbon¼gray, hydrogen¼light blue.
Fig. 3. Crystal structure of dichloronated azacalix[2]terphenylene[2]triazines 6 (a, top view; b, side view), the ‘dimeric’ structure of 6 (c) and the molecular packing in the solid state
(d). Colour codes: nitrogen¼blue, chlorine¼green, carbon¼gray, hydrogen¼light blue.

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W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
3. Conclusion
9/1) to afford di-tert-butyl (50-(tert-butyl)-[1,10:30,100-terphenyl]-
3,300-diyl)dicarbamate 8 as a white solid (4.74 g, 70.5%). 1H NMR
(CDCl3, 500 MHz, ppm):
AreH), 7.51 (s, 2H, AreH), 7.46 (s, 2H, AreH), 7.37 (dd, J1¼7.8 Hz,
J2¼7.9 Hz, 2H, AreH), 7.29 (d, J¼7.6 Hz, 2H, AreH), 6.59 (s, 2H, AreH),
1.53 (s, 18H, CH3eH), 1.40 (s, 9H, CH3eH); 13C NMR (CDCl3, 125 MHz,
In summary, we have synthesized several novel terphenylene-
based azacalix[4]aromatics by aromatic SN2 substitution reaction.
Crystal structure analyses revealed that the terphenyl-3,300-diamine
9 derived azacalixarene[2]terphenylene[2]- triazine 5 adopts a chair
conformation, while the terphenyl-4,400-diamine 11 derived azaca-
lixarene[2]terphenylene[2]triazine 6 adopts a 1,3-alternate confor-
mation in the solid state. No guest molecules were found to be
included in the cavity spaces formed by the macrocyclic compounds
5 and 6. Future research in this area should be focused in: (1) the
design and synthesis of a family of terphenylene-derived hetero-
calixaromatics with a well-defined, conformation fixed and large
cavity space, (2) molecular recognition and guest encapsulation
abilities of such host molecules. Studies in these aspects are cur-
rently ongoing in our laboratory; the results will be reported in due
course.
d
7.59 (d, J¼1.6 Hz, 1H, AreH), 7.55 (s, 2H,
ppm): d 152.76, 151.99, 142.66, 141.22, 138.71, 129.35, 123.62, 123.58,
122.24, 117.53, 34.95, 31.47, 28.35. HRMS (ESI): m/z calcd [MþNaþ]
C32H40N2O4Naþ: 539.2880; Found: 539.2881.
4.4. Synthesis of 50-(tert-butyl)-[1,10:30,100-terphenyl]-3,300-
diamine 9
Di-tert-butyl
(50-(tert-butyl)-[1,10:30,100-terphenyl]-3,300-diyl)
dicarbamate (1.044 g, 2.02 mmol) was dissolved in 100 mL
dichloromethane, trifluoroacetic acid (6 ml) was added in portions
at 0 ꢀC. After the addition complete, the temperature was raised to
rt and the reaction mixture was stirred for 24 h. The reaction
mixture was then washed with 100 ml 10% NaOH (aq), dried over
anhydrous Na2SO4. After removal of the solvent, the residue was
purified by column chromatography (petroleum ether/ethyl acetate
3/1) to afford 50-(tert-butyl)-[1,10:30,100-terphenyl]-3,300-diamine 9
as a yellow solid (560 mg, 89%). 1H NMR (CDCl3, 500 MHz, ppm):
4. Experimental
4.1. General
Commercially available chemicals were used without further
purification unless stated otherwise. 1H and 13C NMR spectra were
recorded on a Bruker Avance 500 or 400 spectrometer in CDCl3 or
DMSO-d6 with TMS as the reference. Mass spectra were recorded
on a microTOF QII mass spectrometer (Bruker Daltonics, Germany).
Single crystal X-ray diffraction data were collected on a Bruker
d
7.56 (d, J¼1.5 Hz, 3H, AreH), 7.24 (dd, J1¼7.9 Hz, J2¼7.8 Hz, 2H,
AreH), 7.04 (d, J¼7.7 Hz, 2H, AreH), 6.96 (d, J¼1.8 Hz, 2H, AreH),
6.70 (dd, J1¼1.5 Hz, J2¼2.1 Hz, 2H, AreH), 3.75 (s, 4H, NH2eH), 1.42
(s, 9H, CH3eH); 13C NMR (CDCl3, 125 MHz, ppm):
d 151.78, 146.67,
143.03, 141.51, 129.61, 123.43, 123.33, 117.87, 114.09, 114.03, 34.93,
31.47. HRMS (ESI): m/z calcd [MþNaþ] C22H24N2Naþ: 317.2012;
Found: 317.1993.
SMART APEX 2 X-ray diffractometer equipped with a normal focus
Mo-target X-ray tube (
ꢀ
l
¼0.71073 A).
4.2. Synthesis of 2,20-(5-(tert-butyl)-1,3-phenylene)-
bis(4,4,5,5-tetramethyl- 1,3,2-dioxaborolane) 7
4.5. Synthesis of di-tert-butyl(50-(tert-butyl)-[1,10:30,100-
terphenyl]-4,400-diyl) dicarbamate 10
Potassium acetate (10.1 g, 103.2 mmol) was added to a thor-
oughly degassed solution of 1,3-dibromo-5-(tert-butyl)benzene
(5.0 g, 17.2 mmol), bis(pinacolato)ediboron (10.5 g, 41.4 mmol),
and [1,10-bis(diphenylphosphino)eferrocene] palladium dichlor-
ide (1.56 g, 2.1 mmol) in 100 mL DMF. The reaction mixture was
heated at 100 ꢀC in the nitrogen protection for 4 h. After the
reaction was complete, the reaction mixture was cooled and
poured into water (300 mL), and extracted with ethyl acetate
(3ꢁ150 mL). The combined ethyl acetate layers were washed
with water (150 mL) and brine (150 mL), and dried over Na2SO4.
The solvent was removed under reduced pressure and the resi-
due was purified by flash chromatography (petroleum ether
100%) to give the title compound 7. 1H NMR (CDCl3, 500 MHz,
The product was obtained in a manner analogous to di-tert-
butyl(50-(tert-butyl)-[1,10:30,100-terphenyl]-3,300-diyl)dicarbamate,
by employing tert-butyl(4-bromophenyl)carbamate (3.82 g,
14.0 mmol) and 2,20-(5-(tert-butyl)-1,3-phenylene)bis(4,4,5,5-
tetramethyl-1,3,2-dioxaborolane) 10 (2.66 g, 6.9 mmol) in 82.4%
yield as a white solid. 1H NMR (DMSO-d6, 400 MHz, ppm):
d 9.44 (s,
2H, NHeH), 7.63 (d, J¼7.6 Hz, 4H, AreH), 7.56 (s, 3H, AreH), 7.53 (d,
J¼10.0 Hz, 4H, AreH), 1.49 (s, 18H, CH3eH), 1.38 (s, 9H, CH3eH); 13
C
NMR (DMSO-d6, 100 MHz, ppm):
d 153.31, 140.66, 139.43, 134.71,
127.39, 118.78, 79.52, 35.12, 31.57, 28.44. HRMS (ESI): m/z calcd
[MþNaþ] C32H40N2O4Naþ: 539.2880; Found: 539.2914.
4.6. Synthesis of 50-(tert-butyl)-[1,10:30,100-terphenyl]-4,400-
ppm):
d
8.11 (s, 1H, AreH), 7.92 (d, J¼0.9 Hz, 2H, AreH), 1.36 (s,
diamine 11
6H, CH3eH), 1.34 (s, 27H, CH3eH); 13C NMR (CDCl3, 125 MHz,
ppm):
d
149.26, 138.74, 134.46, 83.58, 34.66, 31.43, 24.86. HRMS
The product was obtained in a manner analogous to 9 using di-
tert-butyl (50-(tert-butyl)-[1,10:30,100-terphenyl]-4,400-diyl)dicarba-
mate 10 (2.1 g, 4.06 mmol) in 97% yield as a yellow solid. 1H NMR
(ESI): m/z calcd [MþNaþ] C22H36B2O4Naþ: 409.2670; Found:
409.2609.
(DMSO-d6, 400 MHz, ppm):
d
7.41 (d, J¼3.2 Hz, 3H, AreH), 7.37 (d,
4.3. Synthesis of di-tert-butyl(50-(tert-butyl)-[1,10:30,100-
J¼7.6 Hz, 4H, AreH), 6.65 (d, J¼11.2 Hz, 4H, AreH), 5.18 (s, 4H,
terphenyl]-3,300- diyl)dicarbamate 8
NH2eH), 1.36 (s, 9H, CH3eH); 13C NMR (DMSO-d6, 75 MHz, ppm):
d
151.74,148.68,141.39,128.59,128.06,126.45,120.60,114.66, 35.00,
To a tolune (217 mL) solution of tert-butyl (3-bromophenyl)car-
bamate (8.5 g, 31 mmol) and 2,20-(5-(tert-butyl)-1,3-phenylene)
bis(4,4,5,5-tetramethyl-1,3,2- dioxaborolane) 7 (5.0 g, 13.0 mmol)
was added sodium carbonate (21.2 g, 200 mmol) solution of water
and ethanol (1:1, 200 mL). After the mixture was degassed and
backfilled with nitrogen, Pd(PPh3)4 (1.4 g,1.24 mmol) was added. The
reaction mixture was refluxed for 30 h, and extracted with EtOAc
(3ꢁ150 mL). The organic extracts were washed with brine, dried over
anhydrous Na2SO4. After removal of the solvent, the residue was
purified by column chromatography (petroleum ether/ethyl acetate
31.75. HRMS (ESI): m/z calcd [MþNaþ] C22H24N2Naþ: 317.2012;
Found: 317.2090.
4.7. Synthesis of compound 3
To a EtOH (20 mL) solution of 50-t-butyl-(1,10:30,100-terphenyl)-
3,300-diamine 9 (100 mg, 0.316 mmol) and N(i-Pr)2Et (137
mL,
0.79 mmol), was added 1,5-difluoro-2,4-dinitrobenzene (32 mg,
0.158 mmol, 0.5 equiv) at rt. After stirring at reflux for 24 h, the
precipitate was isolated by filtration, followed by thorough washing

W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
6077
with hot water and EtOH, and dried in vacuum to afford a yellow
solid 12 (86 mg crude), which was used directly in the next step.
N(i-Pr)2Et (94 L, 0.54 mmol, equiv), 1,5-difluoro-2,4-di-
nitrobenzene (22 mg, 0.108 mmol, 1 equiv) and 12 (86 mg, crude)
were dissolved in 50 ml CH3CN. The resulting solution was refluxed
for 48 h, the precipitate was isolated by filtration, followed by
thorough washing with hot water, MeCN, and EtOH to afford
a yellow solid 1 (60 mg, crude). The yellow solid 1 (60 mg, crude)
was dissolved in 50 ml DMF, K2CO3 (149 mg, 0.624 mmol), methyl
4.11. Synthesis of compound 5
m
5
To an acetone (100 mL) solution of diisopropylethylamine
(106
L, 0.608 mmol) was added dropwise both solutions of 50-(tert-
m
butyl)-[1,10:30,100-terphenyl]-3,300-diamine 9 (80 mg, 0.253 mmol) in
acetone (50 mL) and compound 14 (155 mg, 0.253 mmol) in acetone
(50 mL) at room temperature over 4 h. After the addition, the
resulted mixture was stirred for another 72 h until the starting
materials were consumed. The solvent was removed, and the resi-
due was chromatographed on a silica gel column (petroleum ether/
ethyl acetate 7/3) to afford 5 as a white solid (87 mg, 40%). Single
crystals of 5 were obtained in DMSO-d6. 1H NMR (DMSO-d6,
iodide (31 mL, 0.5 mmol, large excess) were added in one portion.
The reaction mixture was kept at 80 ꢀC for 18 h. The mixture was
then cooled and poured into water (150 mL), extracted with ethyl
acetate (3ꢁ50 mL). The combined ethyl acetate layers were washed
with water (50 mL) and brine (50 mL), and dried over Na2SO4. The
solvent was removed under reduced pressure and the residue was
purified by flash chromatography (CH2Cl2/petroleum ether¼1/1) to
give the title compound 3 (65 mg, overall 41%). 1H NMR (CDCl3,
500 MHz, ppm):
d
10.35 (s, 4H, NHeH), 7.42 (d, J¼5.0 Hz, 14H,
AreH), 6.96 (d, 8H, J¼3.0 Hz, AreH), 1.38 (s, 18H, CH3eH); 13C NMR
(DMSO-d6, 125 MHz, ppm):
d 178.63, 167.94, 163.68, 151.55, 141.27,
140.55, 138.49, 128.52, 123.09, 122.71, 122.12, 119.27, 118.75, 34.58,
31.18. HRMS (ESI): m/z calcd [MþHþ] C50H45Cl2N10: 855.3240;
Found: 855.3148.
500 MHz, ppm):
d 8.53 (s, 2H, AreH), 7.50 (s, 4H, AreH), 7.38 (dd,
J1¼7.8 Hz, J2¼8.0 Hz, 4H, AreH), 7.28 (d, J¼7.3 Hz, 6H, AreH), 7.16
(s, 4H, AreH), 7.08 (dd, J1¼2.1 Hz, J2¼2.1 Hz, 4H, AreH), 6.93 (s, 2H,
AreH), 3.39 (s, 12H, CH3eH), 1.38 (s, 18H, CH3eH); 13C NMR (CDCl3,
4.12. Synthesis of compound 6
125 MHz, ppm):
d 152.37, 147.16, 146.91, 143.25, 140.90, 130.19,
The product 6 was obtained in a manner analogous to 5 by
employing 11, instead of 9, and 15 (196 mg, 0.62 mmol), to afford 6
in about 43% overall yield as a white powder. Single crystals of 6
were obtained in DMSO-d6 and CHCl3. 1H NMR (DMSO-d6,
127.34, 123.87, 123.56, 123.24, 119.88, 118.81, 41.46, 34.98, 31.42.
HRMS (ESI): m/z calcd [MþNaþ] C60H56N8O8Naþ: 1039.4113;
Found: 1039.3936.
500 MHz, ppm):
7.85 (d, J¼9.0 Hz, 8H, AreH), 7.53 (s, 4H, AreH), 1.35 (s, 18H,
CH3eH); 13C NMR (CDCl3 and DMSO-d6, 100 MHz, ppm):
167.98,
d
10.42 (s, 4H, NHeH), 7.90 (d, J¼9.0 Hz, 8H, AreH),
4.8. Synthesis of compound 4
d
163.83, 151.67, 140.34, 137.60, 136.14, 127.11, 122.30, 122.21, 120.79,
34.45, 31.01. HRMS (ESI): m/z calcd [MþNaþ] C50H44Cl2N10Na:
877.3020; Found: 877.2800.
Compound 4 was obtained in a manner analogous to 3 by
employing 50-t-butyl-(1,10:30,100-terphenyl)-4,400-diamine 11, in-
stead of 9, in 31% overall yield as a red powder. 1H NMR
(CDCl3, 500 MHz, ppm):
d 8.77 (s, 2H, AreH), 7.47 (d,
J¼8.5 Hz, 8H, AreH), 7.40 (s, 4H, AreH), 7.37 (s, 2H, AreH),
7.02 (d, J¼8.5 Hz, 8H, AreH), 6.70 (s, 2H, AreH), 3.22 (s, 12H,
AreH), 1.34 (s, 18H, CH3eH); 13C NMR (CDCl3 and DMSO-d6,
4.13. Crystallographic data for compound 5
[C31H40ClN5O3S3]; Mr¼662.31; monoclinic; space group P21/c;
a¼11.7290 ꢀ(4); b¼17.9527 (6); c¼17.7804 (6) A;
a
¼90ꢀ;
¼116.214
b
ꢀ
100 MHz, ppm):
d 151.51, 146.57, 144.55, 139.21, 136.36, 133.84,
3
(2)ꢀ;
g
¼90 ; V¼3358.90(19) A ; rcalcd¼1.310 gcmꢂ3; T¼173 (2) K;
ꢀ
128.24, 127.67, 125.41, 121.56, 120.69, 117.75, 34.29, 30.87.
HRMS (ESI): m/z calcd [MþHþ] C60H57N8O8:1017.4294; Found:
1017.4237.
38,228 independent measured reflections; F2 refinement;
R1¼0.0775; wR2¼0.2109. This data was deposited in the Cambridge
Crystallographic data centre, CCDC 862801.
4.9. Synthesis of compound 14
4.14. Crystallographic data for compound 6
To an ice-cooled THF (50 mL) solution of cyanuric chloride
(385 mg, 2.089 mmol) was added a THF (50 mL) solution of
diisopropyl(ethyl)amine (414
ꢁ
[C50H44Cl2N10]; Mr¼855.85; triclinic; space group Pı; a¼13.542
¼77.070 (6)ꢀ;
b
¼77.416 (7)ꢀ;
ꢀ
m
L, 2.373 mmol) and 50-(tert-bu-
(6); b¼15.944 (7); c¼17.494 (7) A;
a
3
ꢀ
ꢀ
tyl)-[1,10:30,100-terphenyl]-3,300-diamine 9 (300 mg, 0.949 mmol)
dropwise over 1 h. The resulting mixture was stirred for addi-
tional 5 h at room temperature. After removal of diisopropy-
l(ethyl)amine hydrochloride by filtration, the filtrate was
concentrated and chromatographed on a silica gel column (pe-
troleum ether/EtOAc: 9:1) to give 14 as a white solid (310 mg,
g
¼87.100 (6) ; V¼3593 (3) A ; rcalcd¼0.791 gcmꢂ3; T¼173 (2) K;
14,850 independent measured reflections; F2 refinement;
R1¼0.0883; wR2¼0.2316. This data was deposited in the Cambridge
Crystallographic data centre, CCDC 862802.
Acknowledgements
54%). 1H NMR (CDCl3, 400 MHz, ppm):
(s, 2H, AreH), 7.64 (s, 2H, AreH), 7.51 (d, J¼2.0 Hz, 5H), 1.45 (s,
9H, CH3eH); 13C NMR (CDCl3, 100 MHz, ppm):
164.22, 152.70,
d 7.93 (s, 2H, AreH), 7.80
The authors thank the National Natural Science Foundation of
China (21071053, 21002031, 61078071), Shanghai Commission for
Science and Technology (06Pj14034, 09ZR1422500, 10ZR1409700),
Shanghai education development foundation (2008CG31) for
financial support; support from ‘the FundamentalResearch Funds for
the Central Universities’ is also acknowledged.
d
142.76, 140.65, 136.27, 129.72, 124.66, 123.95, 123.44, 120.23,
120.03, 35.08, 31.45. HRMS (ESI): m/z calcd [MþNaþ]
C28H22Cl4N8Naþ: 635.0588; Found: 635.0614.
4.10. Synthesis of compound 15
Supplementary data
Compound 15 was obtained in a manner analogous to 14 by
employing 11, instead of 9, in about 82% yield as a white powder.
Due to the easy hydrolization of the product, no decent NMR
spectrum was obtained. The product was thus used directly in the
next step of the synthesis.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.04.108. These data
include MOL files and InChIKeys of the most important compounds
described in this article.

6078
W.-J. Hu et al. / Tetrahedron 68 (2012) 6071e6078
5. (a) Gong, H.-Y.; Zhang, X.-H.; Wang, D.-X.; Ma, H.-W.; Zheng, Q.-Y.; Wang,
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