Quinoxaline-based U-shaped septuple-bridged [7,7]orthocyclophanes: synthesis, solid-state structure, and self-assembly

Article abstract of DOI:10.1016/j.tet.2009.09.078

We report a three-step synthesis of 12 septuple-bridged [7,7]orthocyclophanes 11 comprising (i) two quinoxaline-based sidewalls and (ii) a linker built-in with a succinimide ring that carries phenyl, p-methoxyphenyl, p-hydroxyphenyl, or p-methoxybenzyl ap

Full text of DOI:10.1016/j.tet.2009.09.078

Tetrahedron 65 (2009) 10243–10257
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Quinoxaline-based U-shaped septuple-bridged [7,7]orthocyclophanes: synthesis,
solid-state structure, and self-assembly
,
b
,
b
b
Teh-Chang Chou a , Kuen-Cheng Lin , Cheng-An Wu
*
a Department of Applied Chemistry, Chaoyang University of Technology, Wufong, Taichung 41369, Taiwan
b Department of Chemistry and Biochemistry, National Chung Cheng University, Minsyong, Chiayi 621, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
We report a three-step synthesis of 12 septuple-bridged [7,7]orthocyclophanes 11 comprising (i) two
quinoxaline-based sidewalls and (ii) a linker built-in with a succinimide ring that carries phenyl,
p-methoxyphenyl, p-hydroxyphenyl, or p-methoxybenzyl appendants. The synthesis began from the Diels–
Alder adduct of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene (1) and succinimide ring-fused
dioxatetracyclodecadiene 9, followed by ruthenium-promoted oxidation of dichloroetheno-bridges in the
Received 10 August 2009
Received in revised form
13 September 2009
Accepted 18 September 2009
Available online 30 September 2009
adduct to generate a bis-a-diketone, which was then condensed with an arene-1,2-diamine to construct
sidewalls (phane parts), furnishing U-shaped septuple-bridged [7,7]orthocyclophanes 11 embedding quin-
oxaline, dimethylquinoxaline, or benzoquinoxaline rings. Concentration-variant 1H NMR spectra of N-p-
methoxybenzyl substituted orthocyclophanes (11zd, 11xd, and 11yd) and single-crystal structures of four
orthocyclophanes (11xa, 11yd, 11zb, and 11zd) revealed that the U-shaped septuple-bridged [7,7]ortho-
cyclophanes 11 have a tendency of self-assembly, forming V-shaped dimeric entities driven chiefly by
Keywords:
Orthocyclophanes
Self-assembly
p–p stacking interaction
Quinoxaline
intermolecular
p–p
stacking interaction in both solid state and solution of high concentration.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
a rigid U-shape framework like a clip or a tweezer having concave-
convex topology. Notable examples are systems derived from
Troger’s base,3 Kagan’s ether,4 glycoluril,5 ‘byobuene’,6 and others
that are linked by a rigid polycyclic spacer.7 With the attachment of
specially designed functional groups or fluorophores to the aro-
matic rings, they afford opportunity to demonstrate the formation
of host–guest complex8,9 and self-assembled dimeric entity10 via
the processes manipulated by weak but specific noncovalent
intermolecular interactions, to explore potential application as
sensing systems,11 and for investigating intramolecular long-range
electron/energy transfer phenomena between the electronically
coupled donor and acceptor chromophores.12
[n,n0]Orthocyclophanes are polycyclic molecules consisting of
aromatic units (typically benzene rings) connected between the
ortho positions of the aromatic rings by aliphatic chains of n- and n0-
atom length. Compared with the various meta,meta- and para,para-
[n,n0]cyclophanes,1 they are less strained and have the possibility of
existing in two different conformations, in which the aromatic units
are in antiparallel (anti-periplanar, A) or parallel fashion (syn-peri-
planar, A0).2 The aromatic rings could be forced to align face-to-face
in proximity by means of bridge(s) across the aliphatic chains. The
bridged [n,n0]orthocyclophanes (B) thereby structured acquire
C
n'
C
n'
C
n'
C
n
n
C
n
C
n
A
A'
B
Recently, we developed an efficient three-step synthetic approach
to the U-shaped multi-bridged [n,n0]orthocyclophanes containing
various quinoxaline rings with the generic structure E, via the process
illustrated in Scheme 1.13 This process consists of three fundamental
operations: (1) the Diels–Alder reaction of 1,2,3,4-tetrachloro-5,5-
dimethoxycyclopentadiene (TDCp, 1)14 with a bis-dienophile to
* Corresponding author. Tel.: þ886 4 2332 3000x4309; fax: þ886 4 2374 2341.
E-mail address: tcchou@cyut.edu.tw (T.-C. Chou).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.078

10244
T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
MeO
OMe
Cl
Cl
MeO OMe
i
Cl
Cl
MeO
Cl
OMe
+
Cl
Cl
Cl
Cl
Diels-Alder reaction
Cl
Cl
Cl
Cl
bis-dienophile
C
TDCp (1)
NH2
H2N
OMe
MeO
Cl
Cl
MeO
OMe
Cl
Cl
OMe
MeO
Cl
iii
ii
(ADA)
MeO
Cl
OMe
N
N
N
N
Cl
Condensation with
arene-1,2-diamines
O
O
Ru-promoted
oxidation
O
O
D
E
MeO
OMe
MeO
Cl
OMe
Cl
Cl
Cl
MeO
Cl
OMe
MeO
Cl
OMe
Cl
Cl
N
N
N
N
N
N
N
N
7.87 Å
4.69 Å
10.56 Å
3.86 Å
2
3
Scheme 1. Synthetic strategy for the construction of U-shaped multi-bridged orthocyclophanes.
construct bis-adduct C as the central scaffold, (2) the conversion of
dichloroetheno-bridges in C by ruthenium-promoted oxidation using
aligned quinoxaline rings and N-arylsuccinimide group on the
opposite side of the molecular framework platform, using dioxa-
tetracyclic bis-alkene anhydride 417 as an entry point. We envis-
aged that the cycloaddition of TDCp (1) onto 4 should follow the
same stereoselectivity exhibited by that of cyclopentadiene and 7-
oxanorbornenes,17 and is predictable based on the consideration of
steric hindrance put forth by the anhydride moiety of 4. In a sense,
the double Diels–Alder adduct thus formed is structurally ex-
traordinary. Both sides of the molecular framework carry functional
groups suitable for further elaboration. One side (top) is suitable for
effecting the imidization of dicarboxylic anhydride moiety with
primary amines to furnish dicarboximides, and the other side
(bottom) for transforming the dihaloetheno-bridges to the corre-
Khan’s protocol15 to generate bis-
a-diketone D, followed by (3) the
construction of sidewalls (phane parts) by the condensation of bis-
a-
diketone D with an arene-1,2-diamine (ADA) to produce the U-shaped
[n,n0]orthocyclophanes E embedding quinoxaline-based aromatic
rings. The practicality and efficacy of the synthetic strategy illustrated
in Scheme 1was demonstrated by the syntheticimplementation of the
U-shaped quadruple-bridged [5,5]orthocyclophanes 2, [6,6]orthocy-
clophane 3, and theirderivatives from the Diels–Alder adducts of TDCp
with 1,4-cyclohexadiene and 1,5-cyclooctadiene, respectively.13,16
As revealed by the X-ray single-crystal structure, the pair of face-
to-face quinoxaline rings in 2 stretches out from the boat cyclo-
hexane-intercalated scaffold in an inward (converging) fashion with
transannular distances (dNN¼4.69 Å, dCC¼3.86 Å), permissible for
significant intramolecular excimer interaction between quinoxalinyl
chromophores.13 On the other hand, the molecular structure of 3
exhibits two quinoxaline rings facing each other and suspending
from the boatlike cyclooctane-intercalated scaffold in an outward
(diverging) style with distances (dNN¼7.87 Å, dCC¼10.56 Å) between
quinoxalinyl chromophores, too far apart to interact with each other
and inappropriate to develop stable host–guest complexes.
sponding
a-dioxoetheno-bridges by ruthenium-promoted oxida-
tion15 (Scheme 1) to lay a concrete way toward the U-shaped
septuple-bridged [7,7]orthocyclophanes F of our interest. Molecu-
lar modeling predicted that [7,7]orthocyclophanes F thereby con-
structed by the condensation of derived bis-a-diketones with
various arene-1,2-diamines could have the sidewalls aligned in
parallel fashion with transannular distance of about 7.7 Å, more apt
for the formation of host–guest complexes by clipping via arene–
arene interactions.18 This paper describes the synthesis and self-
assembly of the U-shaped septuple-bridged [7,7]orthocyclophanes
We were then prompted to alter the linker (bis-dienophile)
and worked on the synthesis of the septuple-bridged [7,7]ortho-
cyclophanes with generic formula F that contains face-to-face
driven chiefly by
p–
p
stacking interaction involving quinoxaline-
based aromatic rings.
ArCH2 NH2
O
O
ArCH2
O
N
OMe
Cl
O
MeO
Cl
MeO
O
OMe
Cl
N
Cl
OMe
MeO
Cl
Cl
H2N
MeO
Cl
OMe
Cl
Cl
Cl
1
Cl
NH2
O
Cl
O
1
N
O
O
(Scheme 1)
NH2
4
N
N
H2N
F

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10245
R
R
O
O
O
7a or 7b or 7c or 7d
OH
N
NH
O
O
Ac2O, NaOAc
60 °C, 2 d
O
n-BuLi/THF
O
-5 °C, 1 h
rt, 12 h
O
O
O
O
O
O
4
9a: R = -Ph
9b: R = -PhOMe
9c: R = -PhOAc
(40%)
(80%)
(70%)
8a ( ----)
8b (60%)
8c (57%)
8d (80%)
9d: R= -CH2PhOMe (55%)
OMe
Cl
MeO
Cl
OMe
OMe
OH
heat
1
tolune,
110 °C, 48 h
Cl
Cl
1
NH2
NH2
NH2
NH2
7a
7d
7b
7c
R
O
O
O
N
O
OMe
OMe
MeO
Cl
O
Cl
OMe
OMe
MeO
Cl
Cl
MeO
Cl
Cl
MeO
Cl
Cl
Cl
Cl
Cl
O
O
Cl
Cl
O
O
Cl
Cl
Cl
5a (90%)
5b (90%)
5c (92%)
5o (neat, 80 °C, 2 h, 65%)
.
RuCl3 3H2O (0.1 eq),
NaIO4 (2.5 eq)
CHCl3:CH3CN:H2O =
3:3:1, 0 °C
5d (neat, 80 °C, 4-6 h, 96%)
R
O
O
O
N
O
O
OMe
OMe
OMe
OMe
MeO
MeO
Cl
Cl
Cl
Cl
MeO
Cl
MeO
Cl
Cl
Cl
O
O
O
O
O
O
O
O
O
O
O
O
6o (24 h, 96%)
6a (24 h, 85%)
6b (12 h, 92%)
6c (12 h, 90%)
6d (12 h, 98%)
Scheme 2. Synthesis of syn-bis-a-diketonic platform molecules 6.
2. Results and discussion
2.1. Synthesis
of n-BuLi and cyclization of the resultant amic acid 8 with sodium
acetate in acetic anhydride at 60 ꢀC.17 Regrettably, the overall yields
of succinimides 9 from 4 were rather low (40–50%), probably due to
the propensity of amic acids 8 to undergo retro-Diels–Alder frag-
mentation. The reaction of 4 with 4-aminophenol (7c) gave N-p-
acetoxyphenylsuccinimide 9c resulting from acetylation of phenolic
hydroxyl group. The succinimide 9a–d thereby obtained were
subjected to the Diels–Alder reaction with TDCp affording bis-ad-
ducts 5a–d in the yields of 90–96%. As expected, the cycloaddition
The dioxatetracyclic bis-alkene anhydride 4 was prepared from
the corresponding bis-adduct of furan and acetylene dicarboxylic
acid19 by treatment with oxalyl chloride in refluxing CH2Cl2.17 As
shown in Scheme 2, heating anhydride 4 with TDCp (1) under neat
condition at 80 ꢀC for 2 h afforded bis-adduct 5o in 65% yield, which
was converted to bis-
a
-diketone 6o in almost quantitative yield
of TDCp onto the p-bonds of 9a–d occurred in high yield and ster-
(96%) by following essentially the ruthenium-promoted oxidation
procedure reported by Khan et al. [RuCl3$3H2O (0.1 equiv), NaIO4
(2.5 equiv), CHCl3/CH3CN/H2O¼3:3:1, 0 ꢀC, 12 h].15 The bis-adduct
5o was found to be inert to the condensation with primary amines
to give the corresponding N-substituted succinimides, even under
forcing conditions. Apparently, the anhydride moiety in 5o is
shielded by the hydrogen atoms at ring junctions. Consequently,
the synthesis of succinimide series of septuple-bridged
[7,7]orthocyclophanes required recourse to the conversion of an-
hydride 4 to the succinimides 9 prior to performing the Diels–Alder
reaction with TDCp.
eoselectivity to furnish the U-shaped cavity molecules 5a–d, which
were then oxidized by using Khan’s procedure to deliver the
corresponding bis-a-diketones 6a–d in yields of 85–98%.
We have previously demonstrated that quinoxaline sidewalls
could be installed cleanly in high yields by performing the reaction
of bis-a-diketone with arene-1,2-diamines (ADA) in PhCl at
refluxing temperature and in the presence of Zn(OAc)2 as a cata-
lyst.13 As shown in Scheme 3, applying the same procedure to the
condensation reactions of bis-a-diketone 6o with ADA [benzene-
1,2-diamine (10x), 4,5-dimethylbenzene-1,2-diamine (10y), and
naphthalene-2,3-diamine (10z)], the corresponding septuple-
bridged [7,7]orthocyclophanes containing quinoxaline (11xo),
dimethylquinoxaline (11yo), and benzoquinoxaline rings (11zo)
The conversion was achieved in two steps by reaction with pri-
mary amine [aniline (7a), 4-methoxybenzenamine (7b), 4-amino-
phenol (7c), or p-methoxybenzylamine (7d)] in THF in the presence
were realized in yields of 60–78%. When bis-a-diketones 6a–d were

10246
T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
O
X
O
OMe
OMe
MeO
Cl
Cl
6o: X = O
6a: X =
N
OH
MeO
Cl
6c: X =
6d: X =
N
N
Cl
O
N
O
O
O
O
O
OMe
OMe
6b: X =
6
arene-1,2-diamine
(10x, 10y, or 10z)
(2.20 eq),
PhCl (0.04 M),
Zn(OAc)2 (0.10 eq),
reflux
H2N
NH2
H2N
NH2
H2N
NH2
10x
10y
10z
O
O
O
O
X
X
X
O
O
O
OMe
OMe
MeO
OMe
Cl
MeO
Cl
MeO
Cl
Cl
Cl
N
Cl
MeO
MeO
Cl
OMe MeO
Cl
OMe
OMe
Cl
Cl
Cl
Cl
N
N
N
N
N
O
O
O
O
O
N
N
N
N
N
N
11xo (48 h, 60%)
11xa (30 h, 78%)*
11xb (36 h, 82%)
11xc (36 h, 88%)
11xd (48 h, 74%)
11yo (48 h, 68%)
11ya (48 h, 78%)*
11yb (24 h, 83%)
11yc (36 h, 85%)
11yd (48 h, 60%)
11zo (48 h, 78%)
11za (72 h, 65%)*
11zb (24 h, 83%)
11zc (36 h, 90%)
11zd (48 h, 72%)
*Using TFA as catalyst, with 0.4 nm molecular sieve
Scheme 3. Synthesis of U-shaped septuple-bridged [7,7]orthocyclophanes 11 from syn-bis-a-diketones 6.
allowed to react with ADA (10x, 10y, and 10z) in refluxing PhCl in
the presence of catalytic amount of Zn(OAc)2 for 1–2 days, the
desired septuple-bridged [7,7]orthocyclophanes 11’s were also
shift toward higher magnetic field, up to a total of about 1.05,
0.95, and 0.52 ppm, respectively. Particularly, the protons located
closer to the nitrogen atoms of benzoquinoxaline ring showed
larger shift (He>Hf>Hg). Whereas the methine protons(Hb), and
protons of N-p-methoxybenzyl appendant (Hc and Hd) remained
essentially unchanged, a downfield movement was observed for
the oxa-bridgehead methine Ha (0.33 ppm). This observation
implied the occurrence of the concentration-dependent mole-
cular self-assembly and prompted us to perform the same ex-
periment on 11xd and 11yd (Fig. 1b and c, respectively). Similarly,
upfield shifts of the quinoxaline ring protons (He/Hf) and down-
field shift of the oxa-bridgehead methine proton (Ha) were ob-
served for 11xd, albeit in much less magnitude (0.18/0.16 ppm
and 0.06 ppm, respectively), in the concentration range of
5.0ꢁ10ꢂ4 M to 3.0ꢁ10ꢂ2. Similar phenomenon was observed for
obtained in good yields (60–90%). In the case of bis-a-diketone 6a,
the condensation reactions were also performed by using TFA as
catalyst and molecular sieve (0.4 nm) as water scavenger to furnish
the corresponding orthocyclophanes 11xa, 11ya, and 11za in good
yields. The acetyl group at 6c inherent from 9c was lost during the
Zn(OAc)2-catalyzed condensation reactions, producing N-p-
hydroxyphenyl orthocyclophanes 11xc, 11yc, and 11zc, which were
converted to the corresponding acetates for supplementary struc-
tural characterization. All the U-shaped septuple-bridged
[7,7]orthocyclophanes and their respective precursor molecules
gave satisfactory elemental analyses or HRMS data and were
properly characterized by their 1H/13C NMR, IR, and MS spectral
analyses (Experimental section).
11yd in the concentration range of 3.0ꢁ10ꢂ4 M to 3.0ꢁ10ꢂ2
,
which showed upfield shifts of the aromatic He (0.28 ppm) and
methyl Hf (0.23 ppm) at quinoxaline ring and downfield shift of
the oxa-bridgehead Ha (0.11 ppm).20
2.2. 1H NMR spectral study
The U-shaped septuple-bridged [7,7]orthocyclophanes 11 ex-
hibit conformational rigidity and C2v symmetry-reflected 1H NMR
spectra. The assignments of the absorption signals for the pro-
tons were made using intensity, chemical shift, and splitting
pattern, and in some cases further supported by COSY and HMQC
experiments. At the onset we recorded the room-temperature 1H
NMR spectra of 11zd at various concentrations in CDCl3. As
shown in Figure 1a, when the concentration was gradually in-
creasing from 5.0ꢁ10ꢂ4 M to 1.0ꢁ10ꢂ1 M, the absorption signals
of He, Hf, and Hg at the benzoquinoxaline ring displayed steady
The intermolecular p–p stacking interaction plays a fundamen-
tal role in stabilizing the self-assembled supramolecular structures
of aromatic ring-containing compounds.18 For the U-shaped
orthocyclophanes, intermolecular
p
–p
stacking interaction
could conceivably lead to the formation of dimeric entities by
simultaneous penetration of the aromatic sidewalls of two ortho-
cyclophane molecules into the opposing U-shaped cleft (i.e.,
reciprocal clipping) by the type of either orthogonal (G) or anti-
parallel (H) manner, as shown schematically in Figure 2. As an al-
ternative, they can assemble in line-up fashion without reciprocal

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10247
(a)
π-π stacking interaction
He Hf Hg Hd
HcHa
Hb
*
5×10-4
1×10-3
2×10-3
4×10-3
M
M
M
M
*
*
*
*
*
reciprocal
clipping
*
H
d
H
G
c
MeO
O
H
N
O
H
OMe
MeO Cl
MeO
Cl
N
b
orthogonal
antiparallel
OMe
Cl
Cl
O
N
O H
a
N
N
H
e
6×10-3
8×10-3
M
M
H
H
line-up
(without clipping)
f
g
11zd
1×10-2
2×10-2
5×10-2
1×10-1
M
M
M
M
*
H
H
H
H
-1.05 ppm
*
e
f
g
a
J
I
-0.95 ppm
-0.52 ppm
+0.33 ppm
Figure 2. Schematic representations of the possible ways for the U-shaped orthocy-
clophanes to form dimers driven by stacking interaction.
p–p
2.3. X-ray crystal structural study
9
8
7
6
5
4
3
Among the septuple-bridged [7,7]orthocyclophanes 11 synthe-
sized, we were able to obtain single crystals of 11xa, 11yd, 11zb, and
11zd that were suitable for room-temperature X-ray crystal struc-
ture determination by recrystallization from solvent system of
ethanol–chloroform.22 The ORTEP plots of their X-ray crystal
structures are depicted in Figure 3 and the tables for crystal data/
structure refinement are provided in Table 1. Table 2 lists some
selected parameters from the X-ray crystal structures of 11xa, 11yd,
11zb, and 11zd, which describe the structure and packing motifs.
Probably due to steric constrain resulting from reciprocal clipping
to form dimeric entity in the crystal packing, two conformations
with different mean interplanar distances were noted for the
crystal structure of 11yd, 11zb, and 11zd. Unlike the crystal struc-
tures of 2 and 3,13 the pair of heteroaromatic rings are stretching
out from the rigid intercalator scaffold in almost parallel (syn-
periplanar) manner (Fig. 3), as indicated by the mean interatomic
distances between nitrogen atoms (dNN) and end carbon atoms
(dCC), which are nearly equal (<0.5 Å). On the other hand, 11xa
exists in one conformation and displays two quinoxaline rings
stretching out in a slightly diverging style (dCC–dNN¼w1.08 Å) in
the crystal structure. In the rotation-constrained solid state, the
phenyl-substituted succinimides 11xa and 11zb displayed dihedral
angles between the planes of phenyl and imide rings (CAr–CAr–N–
CC]O) by 72.9ꢀ and 51.9ꢀ/66.5ꢀ, respectively (Table 2). As shown in
Figure 3, the p-methoxyphenyl ring in succinimides 11yd and 11zd
is inclined alongside, rather than vertically, to the molecular
framework. This alignment probably benefits from the intra-
(b)
He Hf Hd
Hc Ha
Hb
5×10-4
M
1×10-3
2×10-3
M
M
H
d
H
c
O
N
MeO
MeO
O
H
OMe
Cl
N
Cl
b
MeO
Cl
OMe
4×10-3
M
Cl
O
N
O H
a
N
N
H
e
6×10-3
8×10-3
M
M
H
f
11xd
-0.28 ppm
-0.23 ppm
+0.11 ppm
1×10-2
2×10-2
3×10-2
M
M
M
H
H
H
e
f
a
ppm 9
8
7
6
5
4
3
(c)
He Hd
Hc Ha
Hb Hf
3.0×10-4
6.0×10-4
1.2×10-3
2.4×10-3
M
M
M
M
M
M
d
H
H
c
MeO
MeO
O
N
O
H
OMe
Cl
Cl
N
b
MeO
Cl
OMe
3.6×10-3
4.8×10-3
Cl
O
N
O H
a
N
N
H
e
6.0×10-3
1.2×10-2
M
M
H
f
11yd
1.8×10-2
2.4×10-2
3.0×10-2
ppm 9
M
M
M
molecular CH–
p
interactions23 of phenyl ring with the polarized
C–H bonds of methoxy group at the acetal carbon atom, indicated
by short OCH3/Cph distances (Table 2).
H
H
H
-0.18 ppm
-0.16 ppm
+0.06 ppm
e
f
a
All the orthocyclophanes (11xa, 11yd, 11zb, and 11zd) existed as
self-assembly dimeric structures in the crystal. As shown in Fig-
ure 4, the first salient feature is that the dimeric structure is
resulted from simultaneous penetration of the aromatic sidewalls
of two orthocyclophane molecules into the opposing U-shaped
cleft (i.e., reciprocal clipping) by the type resembling G depicted in
Figure 2. The molecular skeletons of orthocyclophane in the di-
meric structure of 11xa, 11zb, 11yd, and 11zd are oriented in
V-shape by a clipping angle of about 45ꢀ, 85ꢀ, 81ꢀ, and 75ꢀ, re-
spectively (Fig. 4, side-view). The mean planes of their hetero-
aromatic rings are separated by 3.68/5.05 Å, 3.82/3.56 Å, 3.95/
4.06 Å, and 3.70/3.50 Å, respectively (Fig. 4, face-view, Table 2),
indicating that these aromatic rings benefit from the direct face-to-
8
7
6
5
4
3
2
Figure 1. Concentration-variant 1H NMR spectra in CDCl3. (a) 11zd (500 MHz), (b)
11xd (400 MHz), (c) 11yd (400 MHz).
clipping to form dimeric (I/J) and polymeric entities. The observed
concentration-dependent chemical shifts behavior shown in
Figure 1 implied that in solution the U-shaped orthocyclophanes 11
could self-assemble to form dimeric entities and coexist in equi-
librium with their respective monomers, when the concentration
was increasing. The changing trend of chemical shifts suggested
that they were more likely to assemble by reciprocal clipping in
orthogonal (G) or antiparallel (H) manner.13,21 The speculation was
supported by examination of the crystal structures of [7,7]ortho-
cyclophanes 11xa, 11yd, 11zb, and 11zd described in the next
section.
face
p–p p,p
stacking interactions in the crystal.18,24 The
interaction appears to be most efficient for orthocyclophanes 11zb
and 11zd, in which the estimated mutual cover area of benzoqui-
noxaline rings is about 70% (Fig. 4b and d, side-view). The
p,p

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T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
Figure 3. The ORTEP plots of X-ray crystal structures. (a) 11xa, (b) 11yd, (c) 11zb, and (d) 11zd. Color coding: C, black; H, cyan; N, blue; O, red; Cl, green.
interaction in dimeric 11xa is expected to be much weaker, because
the quinoxaline rings are aligned in an offset parallel geometry
(Fig. 4a). In the case of 11yd, the quinoxaline rings have mutual
events observed in solution for N-p-methoxybenzylsuccinimides
11xd, 11yd, and 11zd shown in Figure 1. As clearly revealed by the
side-view drawings of the dimeric structures shown in Figure 4, the
heteroaryl rings are face-to-face juxtaposed to reciprocally exert
anisotropic shielding effects on the aryl ring (He, Hf, and Hg) and
dimethyl protons (in 11yd) that are positioned on top of the aro-
matic ring. On the other hand, the oxa-bridgehead methine protons
(Ha) are located in-plane with the internal sandwiched aromatic
ring and thus are deshielded to show upfield shifts.27
Next we describe the additional noncovalent interactions that
control the packing of dimeric entities into two- and three-di-
mensional structures in the crystal. Examination of the crystal
packing revealed that the dimeric entities of 11yd, 11zb, and 11zd
cover area of about 50% for
p,p interaction (Fig. 4c, side-view),
which is apparently assisted by the van der Waals interaction of
dimethyl substituents to provide additional driving force for
effective self-assembly.18,25 Further examination of the packing
motifs in the dimeric structures of 11xa, 11zb, 11yd, and 11zd
interestingly revealed that nitrogen atom of the sandwiched het-
eroaromatic ring is located close to the hydrogen atoms at two
oxa-bridgeheads with H/N distances in the range of 2.65–3.68 Å
and H/N/H angles of 56.7–71.5ꢀ (Table 2) to exert double O–H/
N
Ar/H–O hydrogen bonding interactions.26 The dimeric structures
of 11yd, 11zb, and 11zd are additionally stabilized by C–H/N in-
teractions using nitrogen atom of the external heteroaromatic rings
and the polarized C–H bonds of one methoxy group of the inter-
calator, as suggested by short OCH3/NAr distances (2.71–3.36 Å,
Table 2).26 We attribute the preference of forming dimeric structure
by the type of V-shaped arrangement shown in Figure 4 to these
extra intradimeric interactions (see also Fig. 5).
are mainly driven by
mensional arrays of dimeric aggregate (Fig. 5). The
separation distances between dimers are 3.49 Å, 3.45 Å, and 3.56 Å,
respectively (Table 2). This interdimeric stacking interaction is
absent in the association of dimeric entities of 11xa. As shown in
Figure 5a, the external dimethylquinoxaline walls of one dimeric
11yd pack against the identical walls of the neighbors in an anti-
parallel manner, like the type I depicted in Figure 2. In this packing
motif, the methyl groups are concomitantly close to the nitrogen
atoms of quinoxaline ring (dN/H¼2.76/3.06 Å; 2.90/3.17 Å) and the
p
–
p
stacking interaction to form two-di-
p–p
mean plan
p–p
The fact that the U-shaped orthocyclophanes 11 could undergo
dimerization in the crystal driven most significantly by
p–p
stacking interactions evidently echoes with the 1H NMR spectral

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10249
Table 1
Crystal data and structure refinement for compounds 11xa, 11zb, 11yd, and 11zd
Identification code
11xa
11zb
11yd
11zd
Empirical formula
Formula weight
Crystal size [mm]
Temperature [K]
Wavelength [Å]
Crystal system,
space group
C44H33Cl4N5O8
901.55
(C53H39Cl4N5O9)2(CHCl3)
2182.75
(C50H45Cl4N5O9)2(C2H5OH)
2049.49
(C54H41Cl4 N5O9)2
2091.44
0.20ꢁ0.13ꢁ0.13
0.12ꢁ0.06ꢁ0.05
0.32ꢁ0.31ꢁ0.30
0.19ꢁ0.11ꢁ0.03
298
298
298
298
0.71073
Tetragonal, I-42d
0.71073
Triclinic, P-1
0.71073
Triclinic, P-1
0.71073
Triclinic, P-1
Unit cell dimensions
a¼30.8823(17) Å,
b¼30.8823(17) Å,
c¼21.3738(17) Å
a¼12.7563(19) Å,
b¼15.381(2) Å,
c¼29.160(5) Å,
a¼11.855(2) Å,
b¼17.704(3) Å,
c¼25.195(4) Å,
a¼14.784(2) Å,
b¼16.376(3) Å,
c¼23.988(4) Å,
a
g
¼75.987(3)ꢀ,
b
¼80.798(3)ꢀ,
a
b
¼83.623(3)ꢀ,
a
b
¼105.364(2)ꢀ,
¼73.191(3)ꢀ
¼76.920(3)ꢀ,
¼90.004(2)ꢀ,
g
¼79.775(3)ꢀ
g
¼110.558(2)ꢀ
Volume [Å3]
Z
20,385(2)
16
1.175
0.282
7424
5288.9(14)
2
1.371
0.360
2244
5055.2(15)
2
5215.4(15)
2
Density (calcd) [mg/m3]
Absorption coefficient [mmꢂ1
F(000)
1.346
10.296
2132
1.332
0.288
2160
]
q
range for data
collection [ꢀ]
1.76–28.36
1.41–25.35
1.17–28.43
1.38–25.68
Index ranges
ꢂ37&h&39, ꢂ41&k&29,
ꢂ19&l&28
ꢂ15&h&15, ꢂ18&k&18,
ꢂ35&l&35
ꢂ15&h&15, ꢂ23&k&23,
ꢂ33&l&33
ꢂ18&h&18, ꢂ19&k&19,
ꢂ29&l&29
Reflections collected
64,717
52,926
59,070
52,193
Independent reflections
12,385 [Rint¼0.0923]
19,338 [Rint¼0.1730]
23,753 [Rint¼0.0909]
19,710 [Rint¼0.0946]
Completeness to
q¼25.35
98.5%
99.7%
93.4%
99.5%
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
0.9650 and 0.9454
12,385/0/555
1.051
0.9839 and 0.9596
19,338/0/1325
0.782
0.9176 and 0.9124
23,753/0/1273
0.947
0.9909 and 0.9469
19,710/0/1308
0.941
Final R indices [I>2
R indices (all data)
Drmax
s
(I)]
R1¼0.0919, wR2¼0.2290
R1¼0.1526, wR2¼0.2635
0.944, ꢂ0.504
R1¼0.0852, wR2¼0.1749
R1¼0.2966, wR2¼0.2382
0.500, ꢂ0.324
R1¼0.0905, wR2¼0.1996
R1¼0.2188, wR2¼0.2410
0.617, ꢂ0.356
R1¼0.0976, wR2¼0.2275
R1¼0.2267, wR2¼0.2722
1.085, ꢂ0.514
, ]
Drmin [e Åꢂ3
R¼
S
wR2¼
jjFojꢂjFcjj/ jFoj.
S
[S
w(F2oꢂF2c)2/
S .
[w(F2o)2]1/2
oxygen atom of methoxy group at the acetal carbon atom (dO/H
¼
c. In addition to the p–p stacking interaction as the major driving
2.63/2.76 Å), suggestive of benefit from CH/X (X¼N, O) close
contacts.26 Differently from that of 11yd, the interdimeric packing
motifs of 11zb and 11zd assume a V-shaped arrangement like the
type J depicted in Figure 2, as, respectively, shown in Figure 5b and
force for dimeric aggregation of 11zb and 11zd, the association of
dimeric structures is further reinforced by packing motif based on
OCH3/OCH3 interactions26 using the polarized C–H bonds of
methoxy groups of intercalators (dO/H: 11zb 2.51/2.62 Å; 11zd
Table 2
Selected parameters of the X-ray crystal structures of 11xa, 11yd, 11zb, and 11zd
11xa
11yd
11zb
11zd
Monomera
dNN (Å)
dCC (Å)
OCH3/CPh (Å)
CAr–CAr–N–CC]O (ꢀ)
8.41
9.49
d
7.74/7.72
7.45/7.43
3.02/3.11
d
7.89/7.91
8.00 /8.39
d
7.70/7.65
7.48/7.13
3.01/3.49
d
72.9
51.9/66.5
Intradimeric interactions
Molecular clipping
angle (ꢀ)
45
81
85
75
p
–
p
mean
3.68; 5.05
3.56; 3.82
3.95; 4.06
3.50; 3.70
plan separation (Å)
O–H/NAr hydrogen bond
H/N/H distances (Å) [angle (ꢀ)]
2.65; 2.82 [64.2]
2.87;3.24 [71.5], 3.19;
3.36 [62.6]
2.75; 2.81 [62.3], 3.15;
3.68 [56.7]
2.77; 3.05 [58.2], 3.09;
3.13 [64.3]
OCH3/NAr contact (Å)
d
2.71; 3.36
3.25
2.90; 2.94
Interdimeric interactions
p
–
p
mean
d
3.49
3.45
3.56
plan separation (Å)
CH3/NAr (Å)
d
2.76/3.06; 2.90/3.17
d
d
CH3/OCH3 (Å)
OCH3/OCH3 (Å)
OCH3/NAr (Å)
OCH3/O]C–N (Å)
CH3/O]C–N (Å)
d
2.63;2.76
d
d
d
2.83
2.64
d
2.51/2.62
3.05
2.75; 3.08
d
2.63; 2.73/2.77
2.82
2.57/3.30
d
d
2.78
d
2.73/2.82, 2.84/2.86
EtOHb
CHCl3
d
c
Solvate
d
a
Except 11xa, two conformations were noted for the crystal structure of 11yd, 11zb, and 11zd.
EtOH is distorted.
d(Cl3CH/N)¼2.39 Å.
b
c

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T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
Figure 4. The packing motifs observed for the dimer in crystal using space-filling and stick representations: (a) 11xa, (b) 11zb, (c) 11yd, and (d) 11zd. Color coding: C, gray; H, white;
N, blue; O, red; Cl, green.
2.63/2.73/2.77 Å, Table 2). Additionally, the OCH3/NAr close con-
tact between the nitrogen atom in benzoquinoxaline ring and
hydrogen atom at the nearby methoxy group of intercalator is also
manifestly supportive (dN/H: 11zb 3.05 Å; 11zd 2.82 Å).
tail’), are held together by the OC–H3/O]C–N interactions between
polarized C–H bond of OCH3 group and electron-enriched carbonyl
oxygen of succinimide group (dN/H¼2.75/3.08 Å, Fig. 7a, Table
2).10e,26 To unit V-shaped dimeric 11zb to form the two-dimensional
sheetlikethequadruplet showninFigure 7a, theN-p-methoxyphenyl
rings are used as shown in Figure 7b. The anti-periplanar display of
p-methoxyphenyl rings (parallel-displaced geometry),18,24 which are
spaced out by an intercentroid distance of 6.10 Å with shortest
interatomic distance of 4.43 Å between meta-carbon atoms, are evi-
Without
succinimide 11xa makes use of the appended N-phenyl ring to knit
dimeric structures, via CH– interactions (indicated by Ph–H/N
p–p stacking interaction between dimers, N-phenyl-
p
close contact), into a circular molecular column consisted of four
arrays of dimeric aggregate as illustrated in Figure 6a. Each of the
four dimeric structures is concurrently one of the building blocks of
the neighboring circular molecular column, resulting in the for-
mation of interlaced molecular columns. It is interesting to note
that the N-phenyl and quinoxaline rings involving in the PhH/N
close contacts assemble into a four-component configuration
(Fig. 6b), in which each N-phenyl group binds one quinoxaline ring
by the ‘edge-to-face’ geometry28 with a distance of 4.35 Å between
the centroids and a shortest interatomic distance of dN/H¼3.26 Å
(m-CH/N). Each N-phenyl group further connects to another qui-
noxaline ring of neighboring dimer by similar arrangement, but
larger spaced out, with centroid-to-centroid distance of 6.50 Å and
a shortest interatomic distance of dN/H¼3.13 Å (p-C–H/N). The
N-phenyl groups themselves also adopt the ‘edge-to-face’ geome-
dently resulted from
p–p stacking interactions. Each of the
p-methoxyphenyl ring then employs its oxygen atoms in CH3O and
O]C–N groups to grip neighboring benzoquinoxaline rings through
H3C–O/H–CAr and N–C]O/H–CAr close contacts (dO/H¼2.59/
2.65 Å, Fig. 7b).10f,26 The alliance is further stabilized by the packing
motif based on the interactions between the polarized C–H bonds of
OCH3 in p-methoxyphenyl ring and the nitrogen atom in benzoquin-
oxaline ring (dN/H¼2.86 Å).26
Although carrying different N-substituents in succinimide
moiety, the crystal packing of N-p-methoxybenzyl 11yd is very
similar to that of N-p-methoxyphenyl 11zb. The quadruplet shown
in Figure 8a discloses that 11yd chiefly employs electron-enriched
carbonyl oxygen of succinimide moiety to stitch together the
V-shaped molecular arrays of dimers by means of close contacts
with aromatic ortho-hydrogen and polarized C–H bond of OCH3
group at linker (ArCH3/O]C–N, dO/H¼2.73/2.82 and 2.84/2.86 Å;
OC–H3/O]C–N, dO/H¼2.78 Å, Table 2). The carbonyl oxygen of
succinimide moiety further contacts closely with the ortho-hydro-
gen atom of appended N-p-methoxybenzyl group to apply ArH/
O]C–N interaction (dO/H¼2.56 Å), which works together with the
ArH/NAr contact (dN/H¼2.95, Fig. 8a Å), grasps the neighboring
p-disubstituted benzene rings to line up in parallel-displaced
geometry18,24 as shown in Figure 8b. An intercentroid distance of
5.19 Å with shortest interatomic distance of 5.18 Å between meta-
try28 with a distance of 6.24 Å between the
p-ring centroids and
a shortest p-C–H/p-C a distance of 2.99 Å. The circular molecular
column is additionally stabilized by interdimeric packing motifs
based on OCH3/OCH3 and OCH3/NAr interactions26 using the
polarized C–H bonds of methoxy groups (dO/H¼2.83 Å, dN/H
¼
2.64 Å, Table 2) as shown in Figure 6a.
Figure 7a shows part of the crystal packing of V-shaped dimers of
N-p-methoxyphenyl succinimide 11zb displayed on the ac-plane that
composed of four dimeric units reiterating along the crystallographic
b-axis to form four molecular arrays, in which molecules of solvating
CHCl3 are grasped in position to fill the voids by hydrogen bonding to
the nitrogen atom of benzoquinoxaline ring (Cl3CH/N, dN/H
¼
and CH2-attached carbon atoms evidently benefits the p–p stack-
ing interaction, and thus stabilize the interdimeric packing of 11yd
dimers.
2.39 Å).26 In this quadruplet arrangement, the two V-shaped
molecular arrays, which are aligned in different direction (‘head-to-

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10251
Figure 6. The packing motifs observed for crystal 11xa. (a) Showing a circular mo-
lecular column formed by dimeric structures viewed along the c-axis on the ab-plane
and the OCH3/NAr (ꢃ) andOCH3/OCH3 (,) close contacts between dimeric struc-
tures. (b) Illustrating the center-to-center distances between N-phenyl (cyan colored)
and quinoxaline rings and their roles in the interdimeric connection by m-CH/N and
p-C–H/N interactions. The N-phenyl groups adopt the ‘edge-to-face’ geometry with
a distance of 6.24 Å between the p-ring centroids and a shortest p-C–H/p-C a distance
of 2.99 Å. Distances are in Å unit. For clarity, the irrelevant hydrogen atoms are
omitted.
Figure 5. Intradimeric and interdimeric packing motifs observed for the dimer in
crystal using space-filling and stick representations: (a) 11yd along the c-axis, (b) 11zb
along the b-axis, and (c) 11zd along the a-axis. Packing-motif icon: -, OCH3/CPh
contact; B, intradimeric OCH3/NAr contact; ꢃ, interdimeric OCH3/NAr contact; :,
OH/NAr hydrogen bond; A, CH3/NAr contact; >, CH3/OCH3 contact; ,, OCH3/
OCH3 contact. For clarity, the distorted solvate EtOH in 11yd and some hydrogen atoms
are omitted. Color coding: C, gray; H, white; N, blue; O, red; Cl, green; benzene ring,
cyan.
3.57 Å)28 and ArH/OCH3 contacts (dO/H¼3.16 Å). The external
N-p-methoxybenzyl groups of adjacent paired dimers, which are
anti-periplanar aligned and far apart, employ Ar–OCH3/O]C–N
contacts to connect the nearby paired dimers (dO/H¼3.30 Å,
Fig. 9a).
An examination of the crystal packing of 11zd reveals that the
appended N-p-methoxybenzyl group plays a major role of uniting
V-shaped dimers of 11zd. The noteworthy feature is that the paired
dimers reciprocally insert one of their two N-p-methoxybenzyl
groups into each other, such that the methoxy hydrogen and imide
oxygen atoms are in close contact to fasten the paired dimers
through Ar–OCH3/O]C–N interactions (dO/H¼2.57/3.31 Å,
Fig. 9a). As shown in Figure 9b, these two ‘internal’ N-p-methoxy-
benzyl groups are anti-periplanar aligned and displaced by an
intercentroid distance of 7.04 Å with shortest interatomic distance
of 4.13 Å between ortho carbon and hydrogen atoms. This geo-
3. Conclusion
In summary, 12 [7,7]orthocyclophanes (Scheme 3) comprising
two sidewalls (phane parts) made of quinoxaline, dimethylqui-
noxaline, or benzoquinoxaline rings and a septuple-bridged linker
incorporated with succinimide moiety that carries phenyl,
p-methoxyphenyl, p-hydroxyphenyl, or p-methoxybenzyl appen-
dants were synthesized via a three-step synthetic route (Scheme 1).
The tendency of these U-shaped [7,7]orthocyclophanes to self-as-
semble and form reciprocally clipped V-shaped dimeric entities has
been studied and supported by concentration-variant 1H NMR
spectroscopy and X-ray crystal structural analysis. Examination of
metrical alignment is secured by Ar–H/O]C–N contact (dO/H
¼
2.60 Å). Within the paired dimeric structures, the phenyl rings of
internal and external N-p-methoxybenzyl groups adopt face-titled-
T structure18,28a with dihedral angle of about 60ꢀ and shortest C–C
the crystal packing revealed that the
p–p stacking interaction is the
distance of 4.34 Å, appropriate for CH–
p
interaction (dp-C/m-H
¼
key driving force for self-assembly to form dimeric entity and

10252
T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
Figure 7. The packing motifs observed for crystal 11zb. (a) Viewed along the b-axis
showing the assembly of four V-shaped molecular arrays of dimeric 11zb, the OCH3/
O]C–N (;) close contacts, and the interaction of solvating CHCl3 with benzoqui-
noxaline ring (dN/H¼2.39 Å). (b) Illustrating the parallel-displaced geometry of
N-methoxyphenyl rings (cyan colored) and their role in uniting V-shaped dimeric 11zb
by (i) H3C–O/H–CAr (2.59 Å), (ii) OCH3/NAr (2.86 Å), and (iii) N–C]O/H–CAr (2.65 Å)
close contacts.
two-dimensional arrays of dimeric aggregate. Additional non-
covalent interactions involving nitrogen atom in hetroaromatic
ring, the polar groups (OCH3 and N–C]O) of intercalator, and
particularly the N-appended aryl ring, which are attributed co-
operatively to the formation of three-dimensional crystalline ar-
chitectures in the crystals, were also disclosed. In combination,
these results suggest that design and synthesis of quinoxaline-
based multi-bridged orthocyclophanes that have potential of
building up complex crystalline architectures via self-assembly and
cross-assembly with guest molecules could be realized by synthetic
strategy shown in Scheme 1.
Figure 8. The packing motifs observed for crystal 11yd. (a) Showing the knitting of V-
shaped molecular arrays of dimeric 11yd by four kinds of close contacts. (b) Illustrating
the parallel-displaced geometry of N-p-methoxybenzylic rings with intercentroid
distance of 5.19 Å and shortest interplanar distance of 5.18 Å (C1–m-C). For clarity, the
irrelevant hydrogen atoms are omitted.
s (C), d (CH), t (CH2), and q (CH3). The assignment of proton and
carbon NMR peaks for some compounds was supported by 1H–1H
COSY and HMQC spectra. Mass (MS) spectra were obtained on
a Finnigan/Thermo Quest MAT 95XL instrument by the FAB mode
with 3-nitrobenzyl alcohol (3-NBA) as the matrix. Ultraviolet/visible
(UV/vis) absorption spectra were measured with HP 8453 UV–Vis-
ible Photodiode Array spectrophotometer. Fluorescence emission
spectra were obtained using a Varian Cary-Eclipse fluorescence
spectrometer. Spectrometric grade solvent and quartz cell
(1ꢁ1 cm2) were used. The X-ray crystallographic data were recorded
with a Bruker AXS SMART APEX CCD X-ray diffractometer. Graphite
4. Experimental
4.1. General experimental
Melting points were determined in capillaries on a Bu¨chi Melting
Point B-540 apparatus, and were uncorrected. Infrared (IR) spectra
were recorded on a JASCO FT/IR-460 spectrophotometer as a solid
suspended in a KBr disk. 1H and 13C NMR spectra were collected on
a Bruker DPX-400 or Varian-Unity INOVA-500 spectrometer using
CDCl3 as solvent (unless otherwise specified). Coupling constants
are reported in hertz. The number of attached hydrogen on the
carbon atom was determined by the DEPT analysis and is denoted as
monochromatized Mo K
a
radiation [
l
¼0.71073 Å] and temperature
of 298(2) K were used. The CCD data were processed with SAINTand
the structures were solved by direct method (SHELXS-97) and re-
fined on F2 by full-matrix least-squares techniques (SHELXL-97).
Analytical thin-layer chromatography (TLC) was performed on
E. Merck silica gel 60 F254 plate (0.20 mm). Flash chromatography

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10253
(100 MHz, CDCl3)
d
166.1 (s), 127.3 (s), 112.8 (s), 80.2 (d), 75.1 (s), 74.8
(s), 53.5 (d), 52.8 (q), 51.9 (q); MS (FABþ) m/z (%) 760 (Mþþ4, 9), 758
(Mþþ2, 6), 756 (Mþ, 3), 728 (15), 726 (25), 724 (27); HRMS (FABþ)
Calcd for C26H21Cl8O9 (MþþH): 756.8688. Found: 756.8705; Anal.
Calcd for C26H20Cl8O9: C, 41.09; H, 2.65; O, 18.95. Found: C, 41.53; H,
2.94; O, 18.65.
4.2.2. Preparation of N-substituted succinimides 9a–d. The N-sub-
understituted succinimides 9a–d were prepared in two steps by
following essentially the reported procedure.17 The dioxatetracyclic
bis-alkene anhydride 4 was subjected to the reaction with aniline
(7a), 4-methoxybenzenamine (7b), 4-aminophenol (7c), or
p-methoxybenzylamine (7d) in THF promoted by n-BuLi at ꢂ78 ꢀC
to rt, and the resultant amic acid 8, without isolation, was treated
with sodium acetate in acetic anhydride and stirred at 60 ꢀC for 2
days to provide N-substituted succinimides 9a, 9b, 9c, and 9d17 in
40%, 48%, 40%, and 44% overall yield, respectively.
4.2.2.1. N-Phenyl-11,12-dioxatetracyclo[6.2.1.13,6.02,7]dodeca-4,9-
dien-2,7-carboximide (9a). Mp 264 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.38–7.43 (m, 3H), 7.01–7.03 (m, 2H), 6.77 (s, 4H), 5.36 (s, 4H); 13
C
NMR (100 MHz, CDCl3) d 173.2 (s), 139.2 (d), 131.1 (s), 129.2 (d), 129.0
(d), 126.0 (d), 81.6 (d), 69.1 (s); MS (FABþ) m/z (%) 307 (Mþ, 31), 289
(27), 281 (20), 136 (98), 109 (82), 95 (97), 73 (58), 69 (100); HRMS
(FABþ) Calcd for C18H13NO4 (Mþ): 307.0845. Found: 307.0847.
4.2.2.2. N-(4-Methoxyphenyl)-11,12-dioxatetracyclo[6.2.1.13,6.02,7]-
dodeca-4,9-dien-2,7-carboximide (9b). Mp 284–285 ꢀC (acetone);
IR (KBr, cmꢂ1) 1717 (s), 1607 (w), 1513 (m), 1185 cmꢂ1 (m); 1H NMR
(400 MHz, CDCl3):
d
6.92 (s, 4H), 6.75 (s, 4H), 5.35 (s, 4H), 3.80 (s,
173.5 (s), 159.8 (s), 139.2 (d), 127.3
3H); 13C NMR (100 MHz, CDCl3)
d
(d), 123.7 (d), 114.5 (d), 81.6 (d), 69.0 (s), 55.5 (q); MS (FABþ) m/z (%)
337 (Mþ, 20), 307 (28), 289 (31), 263 (20), 237 (22); HRMS (FABþ)
Calcd for C19H15NO5 (Mþ): 337.0950. Found: 337.0956; Anal. Calcd
for C19H15NO5: C, 67.65; H, 4.48; N, 4.15; O, 23.72. Found: C, 67.33;
H, 4.33; N, 4.11; O, 23.68.
4.2.2.3. N-(4-Acetoxyphenyl)-11,12-dioxatetracyclo[6.2.1.13,6.02,7]-
dodeca-4,9-dien-2,7-carboximide (9c). Mp 259–260 ꢀC (acetone);
IR (KBr, cmꢂ1) 1708 (s), 1512 (m), 1210 (s), 1126 (m); 1H NMR
(400 MHz, CDCl3)
6.75 (s, 4H), 5.35 (s, 4H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3)
173.0 (s),168.9 (s), 150. 5 (s), 139.2 (d),128.4 (s),127.0 (d), 122.4 (d),
d
7.15 (d, 2H, J¼8.8 Hz), 7.05 (d, 2H, J¼8.8 Hz),
Figure 9. The packing motifs observed for crystal 11zd. (a) Showing the connection of
V-shaped molecular arrays of dimeric 11zd by ArOCH3/O]C–N contacts with dH/
d
¼i: 2.57 Å, ii: 3.31 Å, iii: 3.30 Å; (b) showing two anti-periplanar aligned N-p-me-
O
81.6 (d), 69.1 (s), 21.1 (q); MS (FABþ) m/z (%) 366 (MþþH, 16), 339
(12), 307 (85), 289 (64), 137 (100), 77 (95); HRMS (FABþ) Calcd for
C20H16NO6 (MþþH): 366.0972. Found: 366.0985; Anal. Calcd for
C20H15NO6: C, 65.75; H, 4.14; N, 3.83; O, 26.28. Found: C, 65.39; H,
3.72; N, 4.42; O, 26.12.
thoxybenzyl groups that are displaced by an intercentroid distance of 7.04 Å with
shortest interatomic distance of 4.13 Å between o-C and o-H atoms and held by ArH/
O]C–N contacts (iv: dH/O¼2.60 Å), and two paired N-p-methoxybenzyl groups that
are face-titled-T structured by a dihedral angle of about 60ꢀ with shortest m-C–p-C
distance of 4.34 Å (dp-C/m-H¼3.57 Å) and ArH/OCH3 contacts (v: dO/H¼3.16 Å). Hy-
drogen atoms at the intercalators and aromatic rings except N-methoxybenzyl rings
are omitted for clarity.
4.2.3. Diels–Alder reactions of TDCp and N-substituted succinimides
9a–d. Preparation of syn-bis-DA-adducts 5a–d. A mixture of
N-substituted succinimide 9a, 9b, 9c, or 9d (1 mmol) and TDCp
(1, 2.2 mmol) without solvent or in toluene was heated with stirring
at reflux temperature for 2 days. After cooling solvent was removed
at vacuum and the resultant white solid was filtered, washed with
small amount of ether, and dried to give syn-bis-DA-adduct 5a
(90%), 5b (90%), 5c (92%), or 5d (96%) as white solid, pure enough
for the next step.
was performed on E. Merck silica gel (230–400 mesh). All solvents
used were either reagent grade or were distilled prior to use.
4.2. Syntheses
4.2.1. 5,6,7,8,14,15,16,17-Octachloro-21,21,22,22-tetramethoxy-19,20-
dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11.04,9.013,18]docosa-6,15-dien-2,11-
dicarboxylic anhydride (5o). A mixture of dioxatetracyclic bis-alkene
anhydride 417 (0.20 g, 0.86 mmol) and 1,2,3,4-tetrachloro-5,5-dime-
thoxycyclopentadine (1, 0.50 g, 1.89 mmol) was heated with stirring
at 90 ꢀC for 2 h. After cooling, the resultant white solid was filtered,
collected, rinsed with ether, and dried to give syn-bis-DA-adduct 5o
(0.43 g, 65%) as a white solid, which was pure enough and was used
without purification for the next step: mp 348–349 ꢀC (decomp.); IR
(KBr, cmꢂ1) 1786 (s), 1192 (s), 922 (s); 1H NMR (400 MHz, CDCl3)
4.2.3.1. N-Phenyl-5,6,7,8,14,15,16,17-octachloro-21,21,22,22-tetra-
methoxy-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11.04,9.013,18]do-
cosa-6,15-dien-2,11-dicarboximide (5a). Mp 315–316 ꢀC; 1H NMR
(400 MHz, CDCl3)
4H), 3.56 (s, 6H), 3.49 (s, 6H), 2.92 (s, 4H); 13C NMR (100 MHz,
CDCl3) 171.7 (s), 130.7 (s), 130.0 (s), 129.9 (d), 127.2 (d), 126.4 (d),
112.9 (s), 79.9 (d), 75.2 (s), 72.1 (s), 53.8 (d), 52.8 (q), 51.7 (q); MS
d 7.55–7.59 (m, 3H), 7.19–7.20 (m, 2H), 4.91 (s,
d
d
4.88 (s, 4H), 3.56 (s, 6H), 3.50 (s, 6H), 2.90 (s, 4H); 13C NMR

10254
T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
(FABþ) m/z (%) 838 (24), 836 (33), 834 (26), 802 (18), 800 (26), 798
(25), 460 (25), 307 (100), 289 (97), 71 (86); HRMS (FABþ) Calcd for
C32H26Cl8NO8 (MþþH): 831.9161. Found: 831.9175.
(400 MHz, CDCl3)
d
4.81 (s, 4H), 3.68 (s, 6H), 3.50 (s, 6H), 3.12 (s,
186.9 (s), 166.0 (s), 103.3 (s),
4H); 13C NMR (100 MHz, CD3COCD3)
d
82.0 (d), 77.9 (s), 72.3 (s), 55.6 (d), 53.5 (q), 53.4 (q); MS (FABþ) m/z
(%) 685 (MþþHþ4, 40), 683 (MþþHþ2, 46), 681 (MþþH, 24), 597
(33), 595 (61), 593 (50), 229 (48), 187 (82), 149 (100); HRMS (FABþ)
Calcd for C26H21Cl4O13 (MþþH): 680.9731. Found: 680.9742; Anal.
Calcd for C26H20Cl4O13: C, 45.77; H, 2.95; O, 30.49. Found: C, 46.15;
H, 3.38; O, 30.26.
4.2.3.2. N-(4-Methoxyphenyl)-5,6,7,8,14,15,16,17-octachloro-21,21,
22,22-tetramethoxy-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11
.
0
4,9.013,18]docosa-6,15-dien-2,11-dicarboximide (5b). Mp 348–
349 ꢀC (CHCl3/hexane); IR (KBr, cmꢂ1) 1718 (s), 1512 (m), 1185 (s);
1H NMR (400 MHz, CDCl3):
7.11 (d, 2H, J¼9.1 Hz), 7.06 (d, 2H,
J¼9.1 Hz), 4.91 (s, 4H), 3.87 (s, 3H), 3.58 (s, 6H), 3.52 (s, 6H), 2.92
(s, 4H); 13C NMR (100 MHz, CDCl3):
171.7 (s), 160.2 (s), 127.3 (d),
d
4.2.4.2. N-Phenyl-5,8,14,17-tetrachloro-21,21,22,22-tetramethoxy-6,
d
7,15,16-tetraoxo-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11.04,9
.
126.9 (s), 122.9 (s), 114.9 (d), 112.6 (s), 79.6 (d), 74.9 (s), 71.7 (s),
55.3 (q), 53.5 (d), 52.5 (q), 51.4 (q); MS (FABþ) m/z (%) 866
(MþþHþ4, 7), 864 (MþþHþ2, 6), 862 (MþþH, 2), 830 (10), 828 (9),
307 (20), 253 (22), 136 (74); HRMS (FABþ) Calcd for C33H28Cl8NO9
(MþþH): 861.9267. Found: 861.9280; Anal. Calcd for
C33H27Cl8NO9: C, 45.81; H, 3.15; N, 1.62; O, 16.45. Found: C, 45.87;
H, 3.08; N, 2.01; O, 16.64.
0
13,18]docosa-2,11-dicarboximide (6a). Reaction time 24 h; Yield
85%; mp>400 ꢀC (decomp.); 1H NMR (400 MHz, CDCl3)
d 7.57–
7.63 (m, 3H), 7.18–7.20 (m, 2H), 4.88 (s, 4H), 3.67 (s, 6H), 3.50 (s,
6H), 3.12 (s, 4H); MS (FABþ) m/z (%) 758 (MþþHþ2, 12), 756
(MþþH, 10), 329 (28), 307 (99), 289 (90), 176 (70), 77 (94); HRMS
(FABþ) Calcd for C32H26Cl4NO12 (MþþH): 756.0204. Found:
756.0201; Anal. Calcd for C32H25Cl4NO12: C, 50.75; H, 3.33; N,
1.85; O, 25.35. Found: C, 50.33; H, 3.48; N, 1.68; O, 25.29.
4.2.3.3. N-(4-Acetoxyphenyl)-5,6,7,8,14,15,16,17-octachloro-21,21,22,
22-tetramethoxy-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11.04,9
.
4.2.4.3. N-(4-Methoxyphenyl)-5,8,14,17-tetrachloro-21,21,22,22-tet-
0
13,18]docosa-6,15-dien-2,11-dicarboximide (5c). Mp 354–355 ꢀC
(CHCl3/hexane); IR (KBr, cmꢂ1) 1717 (s), 1608 (w), 1505 (m), 1368
(m), 1212 (s); 1H NMR (400 MHz, CDCl3)
7.31 (d, 2H, J¼8.8 Hz),
7.23 (d, 2H, J¼8.8 Hz), 4.92 (s, 4H), 3.56 (s, 6H), 3.50 (s, 6H), 2.34 (s,
3H), 2.90 (s, 4H); 13C NMR (100 MHz, CDCl3)
171.6 (s), 168.8 (s),
ramethoxy-6,7,15,16-tetraoxo-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17
.
0
2,11.04,9.013,18]docosa-2,11-dicarboximide (6b). Reaction time 12 h;
d
Yield 92%; mp 299 ꢀC (decomp.); IR (KBr, cmꢂ1) 1778 (s), 1720 (s),
1511 (m), 1256 (m), 1195 (m), 1124 (m); 1H NMR (400 MHz, CDCl3)
d
d
7.10 (s, 4H), 4.83 (s, 4H), 3.88 (s, 3H), 3.68 (s, 6H), 3.50 (s, 6H), 3.10 (s,
151.5 (s), 128.0 (s), 127.4 (s), 127.2 (d), 123.1 (d), 112.9 (s), 79.9 (d),
75.2 (s), 72.1 (s), 53.8 (q), 52.8 (d), 51.7 (q), 21.0 (q); MS (FABþ) m/z
(%) 892 (MþþHþ2, 15), 890 (MþþH, 17), 858 (27), 856 (30), 854
(15), 664 (28), 307 (80), 253 (72); HRMS (FABþ) Calcd for
C34H28Cl8NO10 (MþþH): 889.9216. Found: 889.9227; Anal. Calcd
for C34H27Cl8NO10: C, 45.72; H, 3.05; N, 1.57; O, 17.91. Found: C,
45.60; H, 3.04; N, 1.74; O, 17.51.
4H); 13C NMR (100 MHz, CDCl3)
d
185.2 (s), 170.3 (s), 156.0 (s), 127.2
(d), 122.3 (s), 115.3 (d), 102.0 (s), 80.5 (d), 76.0 (s), 68.4 (s), 55.7 (q),
54.5 (d), 52.9 (q), 52.3 (q); MS (FABþ) m/z (%) 788 (MþþHþ2, 45), 786
(MþþH, 35), 785 (Mþ, 11), 752 (15), 370 (27), 289 (28), 136 (98), 77
(82); HRMS (FABþ) Calcd for C33H28Cl4NO13 (MþþH): 786.0309.
Found: 786.0309; Anal. Calcd for C33H27Cl4NO13: C, 50.34; H, 3.46; N,
1.78; O, 26.42. Found: C, 49.85; H, 3.61; N, 1.74; O, 26.37.
4.2.3.4. N-(4-Methoxybenzyl)-5,6,7,8,14,15,16,17-octachloro-21,21,
4.2.4.4. N-(4-Acetoxyphenyl)-5,8,14,17-tetrachloro-21,21,22,22-tet-
22,22-tetramethoxy-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11
0
.
ramethoxy-6,7,15,16-tetraoxo-19,20-dioxaoctacyclo[10.6.1.13,10.15,8
.
1
4,9.013,18]docosa-6,15-dien-2,11-dicarboximide (5d). Mp 299–
301 ꢀC; IR (KBr, cmꢂ1) 1708 (s), 1188 (s); 1H NMR (400 MHz,
CDCl3)
7.44 (d, J¼8.6 Hz, 2H), 6.92 (d, J¼8.6 Hz, 2H), 4.79 (s, 4H),
4.59 (s, 2H), 3.81 (s, 3H), 3.43 (s, 6H), 3.25 (s, 6H), 2.54 (s, 4H); 13C
NMR (100 MHz, CDCl3) 172.2 (s), 159.6 (s), 130.8 (d), 127.2 (s),
14,17.02,11.04,9.013,18]docosa-2,11-dicarboximide
(6c). Reaction
time 12 h; Yield 90%; mp 312 ꢀC (decomp.); IR (KBr, cmꢂ1) 1778
d
(s), 1726 (s), 1507 (w), 1372 (w), 1197 (s), 1125 (m); 1H NMR
(400 MHz, CDCl3)
4.84 (s, 4H), 3.67 (s, 6H), 3.50 (s, 6H), 3.09 (s, 4H), 2.36 (s, 3H); 13C
NMR (100 MHz, CDCl3) 185.2 (s), 169.9 (s), 168.9 (s), 151.5 (s),
d
7.35 (d, 2H, J¼8.8 Hz), 7.22 (d, 2H, J¼8.8 Hz),
d
126.8 (s), 114.5 (d), 112.7 (s), 79.8 (d), 75.2 (s), 71.9 (s), 55.3 (q),
53.3 (d), 52.6 (q), 51.4 (q), 42.4 (t); MS (FABþ) m/z (%) 880 (Mþþ6,
14), 878 (Mþþ4, 14), 876 (Mþþ2, 8), 846 (22), 844 (27), 842 (27),
257 (33), 255 (58), 253 (63), 207 (30), 135 (99), 121 (100); HRMS
(FABþ) Calcd for C34H30Cl8NO9 (MþþH): 875.9429; Found:
875.9435; Anal. Calcd for C34H29Cl8NO9: C, 46.45; H, 3.32; N, 1.59.
Found: C, 46.88; H, 3.54; N, 1.35.
d
127.2 (s), 126.9 (d), 123.4 (d), 102.0 (s), 80.5 (d), 76.0 (s), 68.4 (s),
54.5 (d), 52.8 (q), 52.3 (q), 21.1 (q); MS (FABþ) m/z (%) 818
(MþþHþ4, 50), 816 (MþþHþ2, 80), 814 (MþþH, 74), 728 (25), 391
(34), 370 (94), 289 (90), 138 (100), 77 (97); HRMS (FABþ) Calcd for
C34H28Cl4NO14 (MþþH): 814.0258. Found: 814.0254; Anal. Calcd
for C34H27Cl4NO14: C, 50.08; H, 3.34; N, 1.72; O, 27.47. Found: C,
49.80; H, 3.33; N, 1.68; O, 27.52.
4.2.4. General procedure for the preparation of bis-a-ketones. A
suspension of NaIO4 (2.50 mmol) and RuCl3$3H2O (0.11 mmol) in
water (3 mL) was added in portions to an ice-cooled suspension of
syn-bis-DA-adduct 5o, 5a, 5b, 5c, or 5d (1.0 mmol) in CHCl3 (10 mL)
and CH3CN (10 mL). The resulting dark orange colored mixture was
stirred at 0–5 ꢀC for a period of 12–24 h, monitored by TLC and 1H
NMR. After completion of reaction, the mixturewas then added with
water (50 mL) and extracted with CH2Cl2 or CHCl3 (2ꢁ15 mL). The
combined organic phase was washed with water (2ꢁ20 mL), dried
over MgSO4, filtered by suction through a pad of silica gel to remove
any ruthenium derived residue, and evaporated. Purification by
4.2.4.5. N-(4-Methoxybenzyl)-5,8,14,17-tetrachloro-21,21,22,22-tet-
ramethoxy-6,7,15,16-tetraoxo-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17
0
.
2,11.04,9.013,18]docosa-2,11-dicarboximide (6d). Reaction time 12 h;
Yield 98%; mp 354–361 ꢀC (decomp.); IR (KBr, cmꢂ1) 1778 (s), 1708
(s), 1199 (s), 667 (s); 1H NMR (400 MHz, CDCl3)
7.41 (d, J¼8.7 Hz,
2H), 6.95 (d, J¼8.7 Hz, 2H), 4.69 (s, 4H), 4.62 (s, 2H), 3.82 (s, 3H), 3.44
(s, 6H), 3.43 (s, 6H), 2.68 (s, 4H); 13C NMR (100 MHz, CDCl3)
185.2
d
d
(s), 170.4 (s), 159.9 (d), 130.7 (s), 126.2 (s), 114.7 (d), 101.8 (s), 80.5 (d),
76.0 (s), 68.4 (s), 55.3 (q), 54.1 (d), 52.6 (q), 52.1 (q), 42.7 (t); MS
(FABþ) m/z (%) 802 (MþþHþ2, 7), 800 (MþþH, 6), 799 (Mþ, 6); HRMS
(FABþ) Calcd for C34H30Cl4NO13 (MþþH): 800.0466. Found:
800.0480; Anal. Calcd for C34H29Cl4NO13: C, 50.96; H, 3.65; N, 1.75.
Found: C, 51.03; H, 3.59; N, 1.76.
recrystallization afforded pale yellow platelets of bis-a-diketone 6.
4.2.4.1. 5,8,14,17-Tetrachloro-21,21,22,22-tetramethoxy-6,7,15,16-
tetraoxo-19,20-dioxaoctacyclo[10.6.1.13,10.15,8.114,17.02,11.04,9.013,18]do-
cosa-2,11-dicarboxylic anhydride (6o). Reaction time 24 h; Yield
96%; mp>400 ꢀC (decomp.); IR (KBr, cmꢂ1) 1786 (s); 1H NMR
4.2.5. General procedure for the preparation of quinoxaline-based
septuple-bridged [7,7]orthocyclophanes 11. o-Phenylenediamine

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10255
(10x), 4,5-dimethylbenzene-1,2-diamine (10y), or naphthalene-
2,3-diamine (10z) (1.10 mmol) was added to a solution of bis-
4.2.5.5. N-Phenyl-7,14,24,31-tetraaza-5,16,22,33-tetrachloro-
37,37,38,38-tetramethoxy-10,11,27,28-tetramethyl-35,36-dioxadode-
a
-
diketone 6o, 6a, 6b, 6c, or 6d (0.50 mmol) in chlorobenzene
(12.5 mL) containing a catalytic amount of zinc acetate (0.1 equiv)
or trifluoroacetic acid (a few drops) and 0.4 nm molecular sieve (for
the case of 10x). The reaction mixture was heated under reflux for
hours, monitored by TLC and 1H NMR. The reaction mixture was
filtered to remove salt and the filtrate was concentrated. The resi-
due was purified via recrystallization to afford pure compound 11.
cacyclo[18.14.1.13,18.15,16.122,33.02,19.04,17.06,15.08,13.021,34.022,33.025,30
]
octatriaconta-6(15),7,9,11,13,23(33),25,27,29,30-decaene-2,19-di-
carboximide (11ya). Reaction time 48 h; Yield 78%; mp 355–358 ꢀC
(EtOH/CHCl3); 1H NMR (400 MHz, CDCl3)
d 7.76 (s, 4H), 7.64–7.67
(m, 2H), 7.57–7.63 (m, 1H), 7.30–7.32 (m, 2H), 4.45 (s, 4H), 3.74 (s,
6H), 3.39 (s, 6H), 3.27 (s, 4H), 2.33 (s, 12H); 13C NMR (100 MHz,
CDCl3)
d 171.5 (s), 150.2 (s), 141.3 (s), 139.8 (s), 130.8 (s), 130.0 (d),
128.6 (d), 126.4 (d), 112.6 (s), 79.6 (d), 72.1 (d), 71.1 (d), 54.2 (d), 52.4
(q), 52.1 (q), 20.0 (q); MS (FABþ) m/z (%) 960 (MþþHþ4, 13), 958
(MþþHþ2, 21), 956 (MþþH, 13), 663 (11), 460 (21), 289 (94), 71
(84); HRMS (FABþ) Calcd for C48H42Cl4N5O8 (MþþH): 956.1782.
Found: 956.1782.
4.2.5.1. 7,14,24,31-Tetraaza-5,16,22,33-tetrachloro-37,37,38,38-tet-
ramethoxy-35,36-dioxadodecacyclo[18.14.1.13,18.15,16.122,33.02,19.04,17.06,15
0
.
8,13.021,34.022,33.025,30]octatriaconta-6(15),7,9,11,13,23(33),25,27,29,30-
decaene-2,19-dicarboxylic anhydride (11xo). Reaction time 48 h; Yield
60%; mp>400 ꢀC (CHCl3); IR (KBr, cmꢂ1) 1790 (s), 1516 (s); 1H NMR
(400 MHz, CDCl3)
J1¼6.3 Hz, J2¼3.5 Hz, 4H), 4.49 (s, 4H), 3.73 (s, 6H), 3.33 (s, 6H), 3.27 (s,
4H); 13C NMR (100 MHz, CDCl3)
165.9 (s), 151.0 (s), 142.3 (s), 129.4
d
7.95 (dd, J1¼6.3 Hz, J2¼3.5 Hz, 4H), 7.56 (dd,
4.2.5.6. N-Phenyl-7,18,28,39-tetraaza-5,20,26,41-tetrachloro-45,45,
46,46-tetramethoxy-43,44-dioxatetradecacyclo[ 22.18.1.13,22.15,20.126,41
.
d
0
2,23.04,21.06,19.08,17.010,15.025,42.027,40.029,38.031,36]hexatetraconta-
(d), 128.9 (d), 112.3 (s), 79.8 (d), 73.6 (s), 72.0 (s), 53.9 (d), 52.5 (q), 52.3
(q); MS (FABþ) m/z (%) 830 (Mþþ6, 57), 829 (Mþþ4þH, 100), 828
(Mþþ4, 92), 827 (Mþþ2þH, 95); HRMS (FABþ) Calcd for
C38H29Cl4N4O9 (MþþH): 825.0683. Found: 825.0687.
6(19),7,9,11,13,15,17,27(40),28,30,32,34,36,38-tetradecaene-2,23-di-
carboximide (11za). Reaction time 72 h; Yield 65%; mp 383–384 ꢀC
(EtOH/CHCl3); 1H NMR (400 MHz, CDCl3)
d 8.40 (s, 4H), 7.79–7.82 (m,
4H), 7.66–7.68 (m, 2H), 7.38–7.41 (m, 4H), 7.32–7.34 (m, 2H), 4.59 (s,
4H), 3.76 (s, 6H), 3.39 (s, 6H), 3.31 (s, 4H); 13C NMR (100 MHz, CDCl3)
4.2.5.2. 7,14,24,31-Tetraaza-5,16,22,33-tetrachloro-37,37,38,38-
tetramethoxy-10,11,27,28-tetramethyl-35,36-dioxadodecacyclo[18.14.
1.13,18.15,16.122,33.02,19.04,17.06,15.08,13.021,34.022,33.025,30]octatriaconta-
6(15),7,9,11,13,23(33),25,27,29,30-decaene-2,19-dicarboxylic anhy-
dride (11yo). Reaction time 48 h; Yield 68%; mp>400 ꢀC (CHCl3);
IR (KBr, cmꢂ1) 1790 (s), 1406 (s), 1197 (s), 1115 (s); 1H NMR
d 171.4 (s), 151.8 (s), 138.4 (s), 132.4 (s), 130.8 (s), 130.0 (d), 127.8 (d),
127.1 (d), 126.4 (d), 126.2 (d), 111.2 (s), 79.6 (d), 72.2 (d), 70.8 (d), 54.2
(d), 52.5 (q), 52.1 (q); MS (FABþ) m/z (%) 1004 (MþþHþ4, 8), 1002
(MþþHþ2, 11), 1000 (MþþH, 10), 899 (10), 337 (65), 323 (43), 77
(85); HRMS (FABþ) Calcd for C52H38Cl4N5O8 (MþþH): 1000.1469.
Found: 1000.1472.
(400 MHz, CDCl3)
d
7.57 (s, 4H), 4.46 (s, 4H), 3.72 (s, 6H), 3.35 (s,
166.0
6H), 3.21 (s, 4H), 2.23 (s, 12H); 13C NMR (100 MHz, CDCl3)
d
4.2.5.7. N-(4-Methoxyphenyl)-7,14,24,31-tetraaza-5,16,22,33-tet-
rachloro-37,37,38,38-tetramethoxy-35,36-dioxadodecacyclo[18.14.1.
1
6(15),7,9,11,13,23(33),25,27,29,30-decaene-2,19-dicarboximide
(11xb). Reaction time 36 h; Yield 82%; mp>410 ꢀC (CHCl3/EtOH);
IR (KBr, cmꢂ1) 1718 (s), 1519 (m), 1193 (m); 1H NMR (400 MHz,
(s), 150.0 (s), 141.2 (s), 139.6 (s), 128.3 (d), 112.3 (s), 79.8 (d), 73.5 (s),
72.0 (s), 53.8 (d), 52.4 (q), 52.2 (q), 19.9 (q); MS (FABþ) m/z (%) 885
(MþþHþ4, 14), 883 (MþþHþ2, 23), 881 (MþþH, 18), 315 (100), 301
(49), 242 (31); HRMS (FABþ) Calcd for C42H37Cl4N4O9 (MþþH):
881.1315. Found: 881.1322.
3,18.15,16.122,33.02,19.04,17.06,15.08,13.021,34.022,33.025,30]octatriaconta-
CDCl3)
d
8.04 (dd, 4H, J1¼6.3 Hz, J2¼3.5 Hz), 7.62 (dd, 4H,
4.2.5.3. 7,18,28,39-Tetraaza-5,20,26,41-tetrachloro-45,45,46,46-
J1¼6.3 Hz, J2¼3.5 Hz), 7.24 (d, 2H, J¼8.8 Hz), 7.16 (d, 2H, J¼8.8 Hz),
tetramethoxy-43,44-dioxatetradecacyclo[22.18.1.13,22.15,20.126,41.02,23
0
.
4.52 (s, 4H), 3.92 (s, 3H), 3.75 (s, 6H), 3.34 (s, 6H), 3.30 (s, 4H); 13C
4,21.06,19.08,17.010,15.025,42.027,40.029,38.031,36]hexatetraconta-
NMR (100 MHz, CDCl3) d 171.7 (s), 160.5 (s), 151.1 (s), 142.5 (s),
6(19),7,9,11,13,15,17,27(40),28,30,32,34,36,38-tetradecaene-2,19-
dicarboxylic anhydride (11zo). Reaction time 48 h; Yield 78%;
mp>400 ꢀC (CHCl3); IR (KBr, cmꢂ1) 1790 (s), 1403 (s), 1197 (s); 1H
129.5 (d), 129.2 (d), 127.5 (d), 123.0 (s), 115.2 (d), 112.5 (s), 79.5 (d),
72.0 (s), 70.9 (s), 55.6 (q), 54.2 (d), 52.3 (q), 52.0 (q); MS (FABþ) m/z
(%) 933 (Mþþ4, 6), 932 (Mþþ3, 7), 930 (MþþH, 5); HRMS (FABþ)
Calcd for C45H36Cl4N5O9 (MþþH): 930.1262. Found: 930.1263.
Anal. Calcd for C45H35Cl4N5O9: C, 58.02; H, 3.79; N, 7.52; O, 15.46.
Found: C, 57.90; H, 3.75; N, 7.58; O, 15.41.
NMR (400 MHz, CDCl3)
J2¼3.0 Hz, 4H), 7.34 (dd, J1¼6.4 Hz, J2¼3.0 Hz, 4H), 4.57 (s, 4H), 3.75
(s, 6H), 3.39 (s, 6H), 3.27 (s, 4H); 13C NMR (100 MHz, CDCl3)
165.9
d
8.26 (s, 4H), 7.68 (dd, J1¼6.4 Hz,
d
(s), 151.7 (s), 138.4 (s), 132.6 (s), 127.9 (d), 127.1 (d), 126.4 (d), 111.1
(s), 80.0 (d), 73.4 (s), 72.1 (s), 53.9 (d), 52.5 (q), 52.3 (q); MS (FABþ)
m/z (%) 927 (MþþHþ4, 19), 926 (MþþHþ2, 16), 925 (MþþH, 13);
HRMS (FABþ) Calcd for C46H33Cl4N4O9 (MþþH): 925.1002. Found:
925.1009.
4.2.5.8. N-(4-Methoxyphenyl)-7,14,24,31-tetraaza-5,16,22,33-tet-
rachloro-37,37,38,38-tetramethoxy-10,11,27,28-tetramethyl-35,36-
dioxadodecacyclo[18.14.1.13,18.15,16.122,33.02,19.04,17.06,15.08,13.021,34
.022,33.025,30]octatriaconta-6(15),7,9,11,13,23(33),25,27,29,30-deca-
ene-2,19-dicarboximide (11yb). Reaction time 24 h; Yield 83%;
mp>410 ꢀC (CHCl3/EtOH); IR (KBr, cmꢂ1) 1722 (s), 1503 (s), 1208 (s),
4.2.5.4. N-Phenyl-7,14,24,31-tetraaza-5,16,22,33-tetrachloro-37,37,
38,38-tetramethoxy-35,36-dioxadodecacyclo[18.14.1.13,18.15,16.122,33
0
.
1117(s); 1H NMR (400 MHz, CDCl3)
d 7.82 (s, 4H), 7.28 (d, 2H,
2 ,19 . 04 ,17 . 06 ,15 . 08 ,13 . 021, 3 4 . 02 2 , 3 3 . 02 5 , 3 0 ]octatriaconta-
J¼8.0 Hz), 7.16 (d, 2H, J¼8.0 Hz), 4.42 (s, 4H), 4.01 (s, 3H), 3.76 (s, 6H),
6(15),7,9,11,13,23(33),25,27,29,30-decaene-2,19-dicarboximide
3.34 (s, 6H), 3.21 (s, 4H), 2.38 (s, 12H); 13C NMR (100 MHz, CDCl3)
(11xa). Reaction time 30 h; Yield 78%; mp 355–356 ꢀC (EtOH/
d 171.8 (s), 160.6 (s), 150.2 (s), 141.3 (s), 140.0 (s), 128.6 (d), 127.6 (d),
CHCl3); IR (KBr, cmꢂ1) (s); 1H NMR (400 MHz, CDCl3)
d
8.00–8.02
123.2 (s), 115.3 (d), 112.6 (s), 79.5 (d), 72.1 (s), 70.9 (s), 55.7 (q), 54.2
(d), 52.4 (q), 52.1 (q), 20.0 (q); MS (FABþ) m/z (%) 988 (MþþHþ2, 30),
987 (Mþþ2, 19), 986 (MþþH, 22), 985 (Mþ, 19), 930 (12), 315 (32),
136 (100); HRMS (FABþ) Calcd for C49H44O9N5Cl4 (MþþH):
986.1888. Found: 986.1889; Anal. Calcd for C49H43N5O9Cl4: C, 59.58;
H, 4.39; N, 7.09; O, 14.58. Found: C, 60.08; H, 4.22; N, 7.20; O, 14.92.
(m, 4H), 7.65–7.69 (m, 2H), 7.59–7.62 (m, 5H), 7.31–7.33 (m, 2H),
4.54 (s, 4H), 3.72 (s, 6H), 3.35 (s, 6H), 3.32 (s, 4H); 13C NMR
(100 MHz, CDCl3) d 171.5 (s), 151.2 (s), 142.6 (s), 130.7 (s), 130.1 (d),
130.0 (d), 129.6 (d), 129.3 (d), 126.4 (d), 112.6 (s), 79.6 (d), 72.1 (s),
71.1 (s), 54.3 (d), 52.4 (q), 52.1 (q); MS (FABþ) m/z (%) 904
(MþþHþ4, 23), 902 (MþþHþ2, 30), 900 (MþþH, 22), 663 (22), 460
(60), 307 (100), 273 (51), 165 (88); HRMS (FABþ) Calcd for
C44H34Cl4N5O8 (MþþH): 900.1156. Found: 900.1163.
4.2.5.9. N-(4-Methoxyphenyl)-7,18,28,39-tetraaza-5,20,26,41-tet-
rachloro-45,45,46,46-tetramethoxy-43,44-dioxatetradecacyclo[22.18.1.

10256
T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
13,22.15,20.126,41.02,23.04,21.06,19.08,17.010,15.025,42.027,40.029,38.031,36]hex-
atetraconta-6(19),7,9,11,13,15,17,27(40),28,30,32,34,36,38-tetrade-
caene-2,23-dicarboximide (11zb). Reaction time 24 h; Yield 83%;
mp>410 ꢀC (CHCl3/EtOH); IR (KBr, cmꢂ1) 1722 (s), 1195 (s), 1105
138.6 (s), 132.7 (s), 127.9 (d), 127.4 (d), 127.3 (d), 126.4 (d), 123.2
(d), 111.3 (s), 109.8 (s), 79.6 (d), 72.1 (s), 70.8 (s), 54.2 (q), 52.5 (q),
51.2 (q), 21.2 (q); MS (FABþ) m/z (%) 1059 (MþþHþ1, 8), 1058
(MþþH, 8); HRMS (FABþ) Calcd for C54H40Cl4N5O10 (MþþH):
1058.1524. Found: 1058.1548.
(s); 1H NMR (400 MHz, CDCl3)
d 8.36 (s, 4H), 7.81 (dd, 4H,
J1¼6.4 Hz, J2¼3.2 Hz), 7.34 (dd, 4H, J1¼6.4 Hz, J2¼3.2 Hz), 7.29 (d,
2H, J¼8.0 Hz), 7.12 (d, 2H, J¼8.0 Hz), 4.59 (s, 4H), 3.92 (s, 3H),
3.79 (s, 6H), 3.39 (s, 6H), 3.28 (s, 4H); 13C NMR (100 MHz,
4.2.5.13. N-(4-Methoxybenzyl)-7,14,24,31-tetraaza-5,16,22,33-tet-
rachloro-37,37,38,38-tetramethoxy-35,36-dioxadodecacyclo[18.14.1.
CDCl3)
d
171.7 (s), 160.6 (s), 152.0 (s), 138.8 (s), 133.0 (s), 127.6
1
3,18.15,16.122,33.02,19.04,17.06,15.08,13.021,34.022,33.025,30]octatriaconta-
(d), 127.5 (d), 126.6 (d), 123.2 (s), 115.3 (d), 111.4 (s), 79.6 (d),
72.1 (s), 70.8 (s), 55.7 (q), 54.3 (d), 52.5 (q), 52.2 (q); MS (FABþ)
m/z (%) 1032 (MþþHþ2, 20), 1030 (MþþH, 16), 664 (40), 663
(45), 307 (60); HRMS (FABþ) Calcd for C53H40Cl4N5O9 (MþþH):
1030.1575. Found: 1030.1593; Anal. Calcd for C53H39Cl4N5O9: C,
61.70; H, 3.81; N, 6.79; O, 13.96. Found: C, 61.47; H, 3.51; N,
6.75; O, 14.05.
6(15),7,9,11,13,23(33),25,27,29,30-decaene-2,19-dicarboximide
(11xd). Reaction time 48 h; Yield 74%; mp>400 ꢀC (CHCl3); IR
(KBr, cmꢂ1) 1708 (s), 1196 (s); 1H NMR (400 MHz, CDCl3)
d 7.97
(dd, J1¼6.3 Hz, J2¼3.5 Hz, 4H), 7.57 (dd, J1¼6.3 Hz, J2¼3.5 Hz,
4H), 7.53 (d, J¼8.7 Hz, 2H), 7.00 (d, J¼8.7 Hz, 2H), 4.71 (s, 2H),
4.40 (s, 4H), 3.85 (s, 3H), 3.44 (s, 6H), 3.26 (s, 6H), 2.90 (s, 4H);
13C NMR (100 MHz, CDCl3)
d 171.9 (s), 159.7 (s), 151.4 (s), 142.3
(s), 130.8 (d), 129.1 (d), 128.8 (d), 126.8 (s), 114.6 (d), 112.1 (s),
79.4 (d), 72.1 (s), 70.8 (s), 55.3 (q), 53.7 (d), 52.2 (q), 51.9 (q),
42.4 (t); MS (FABþ) m/z (%) 946 (MþþHþ2, 30), 945 (Mþþ2, 14),
944 (MþþH, 26); HRMS (FABþ) Calcd for C46H38Cl4N5O9
(MþþH): 944.1418. Found: 944.1446; Anal. Calcd for
C46H37Cl4N5O9: C, 58.23; H, 3.94; N, 7.41; O, 15.23. Found: 57.92;
H, 3.85; N, 7.49; O, 15.30.
4.2.5.10. N-(4-Hydroxyphenyl)-7,14,24,31-tetraaza-5,16,22,33-
tetrachloro-37,37,38,38-tetramethoxy-35,36-dioxadodecacyclo[18.14.
1.13,18.15,16.122,33.02,19.04,17.06,15.08,13.021,34.022,33.025,30]octatriaconta-
6(15),7,9,11,13,23(33),25,27,29,30-decaene-2,19-dicarboximide
(11xc). Reaction time 36 h; Yield 88%; mp>410 ꢀC (CHCl3/hex-
ane); IR (KBr, cmꢂ1) 3423 (br), 1718 (s), 1193 (s), 1119 (s); 1H NMR
(400 MHz, CDCl3)
d
8.04 (dd, 4H, J1¼6.3 Hz, J2¼3.4 Hz), 7.63 (dd,
4H, J1¼6.3 Hz, J2¼3.4 Hz), 7.18 (d, 2H, J¼8.7 Hz), 7.09 (d, 2H,
4.2.5.14. N-(4-Methoxybenzyl)-7,14,24,31-tetraaza-5,16,22,33-
tetrachloro-37,37,38,38-tetramethoxy-10,11,27,28-tetramethyl-
J¼8.7 Hz), 6.72 (s, 1H), 4.52 (s, 4H), 3.74 (s, 6H), 3.34 (s, 6H), 3.29
(s, 4H); 13C NMR (100 MHz, CDCl3)
d
171.8 (s), 157.1 (s), 151.2 (s),
35,36-dioxadodecacyclo[18.14.1.13,18.15,16.122,33.02,19.04,17.06,15.08,13
.
142.6 (s), 129.6 (d), 129.2 (d), 127.8 (d), 123.1 (s), 116.8 (d), 112.6
(s), 79.6 (d), 72.1 (s), 71.0 (s), 54.3 (d), 52.5 (q), 52.2 (q); MS
(FABþ) m/z (%) 918 (MþþHþ2, 1), 916 (MþþH, 1), 307 (10), 77
(27); HRMS (FABþ) Calcd for C44H34Cl4N5O9 (MþþH): 916.1105.
Found: 916.1107.
0
21,34.022,33.025,30]octatriaconta-6(15),7,9,11,13,23(33),25,27,29,30-
decaene-2,19-dicarboximide (11yd). Reaction time 48 h; Yield
60%; mp>400 ꢀC (CHCl3); IR (KBr, cmꢂ1) 1709 (s), 1196 (s); 1H
NMR (400 MHz, CDCl3)
d
7.65 (s, 4H), 7.52 (d, J¼8.7 Hz, 2H),
6.99 (d, J¼8.7 Hz, 2H), 4.68 (s, 2H), 4.32 (s, 4H), 3.84 (s, 3H),
3.44 (s, 6H), 3.27 (s, 6H), 2.84 (s, 4H), 2.25 (s, 12H); 13C NMR
4.2.5.11. N-(4-Hydroxyphenyl)-7,14,24,31-tetraaza-5,16,22,33-
tetrachloro-37,37,38,38-tetramethoxy-10,11,27,28-tetramethyl-
(100 MHz, CDCl3) d 172.0 (s), 159.6 (s), 150.5 (s), 141.1 (s), 139.5
(s), 130.8 (d), 128.4 (d), 126.8 (s), 114.6 (d), 112.2 (s), 79.4 (d),
72.1 (s), 70.8 (s), 55.3 (q), 53.6 (d), 52.2 (q), 51.9 (q), 42.4 (t);
MS (FABþ) m/z (%) 1004 (MþþHþ4, 22), 1002 (MþþHþ2, 36),
1000 (MþþH, 26), 999 (Mþ, 5), 663 (12), 315 (47), 307 (31), 289
(24), 154 (100); HRMS (FABþ) Calcd for C50H46Cl4N5O9 (MþþH):
1000.2044. Found: 1000.2048; Anal. Calcd for C50H45Cl4N5O9:
C, 59.95; H, 4.53; N, 6.99; O, 14.37. Found: C, 59.84; H, 4.26; N,
7.17; O, 14.07.
35,36-dioxadodecacyclo[18.14.1.13,18.15,16.122,33.02,19.04,17.06,15.08,13
.
0
21,34.022,33.025,30]octatriaconta-6(15),7,9,11,13,23(33),25,27,29,30-
decaene-2,19-dicarboximide (11yc). Reaction time 36 h; Yield 85%.
Mp>400 ꢀC (CHCl3/hexane); IR (KBr, cmꢂ1) 3478 (br), 1770 (m),
1720 (s), 1506 (s), 1196 (s), 1114 (s); MS (FABþ) m/z (%) 975
(MþþHþ2, 32), 973 (MþþH, 28), 315 (100), 301 (56), 77 (45);
compound 11yc was characterized by the corresponding acetate
derivative obtained by treatment with acetic anhydride. 1H
NMR (400 MHz, CDCl3)
d
7.68 (s, 4H), 7.37 (d, 2H, J¼8.4 Hz), 7.31
4.2.5.15. N-(4-Methoxybenzyl)-7,18,28,39-tetraaza-5,20,26,41-
tetrachloro-45,45,46,46-tetramethoxy-43,44-dioxatetradecacyclo[22.
18.1.13,22.15,20.126,41.02,23.04,21.06,19.08,17.010,15.025,42.027,40.029,38.031,36]-
hexatetraconta-6(19),7,9,11,13,15,17,27(40),28,30,32,34,36,38-tetra-
decaene-2,23-dicarboximide (11zd). Reaction time 48 h; Yield
72%; mp>400 ꢀC (CHCl3); IR (KBr, cmꢂ1) 1708 (s), 1516 (s); 1H
(d, 2H, J¼8.4 Hz), 4.47 (s, 4H), 3.71 (s, 6H), 3.35 (s, 6H), 3.21 (s,
4H), 2.37 (s, 3H), 2.27 (s, 12H); 13C NMR (100 MHz, CDCl3)
d
171.3 (s), 168.8 (s), 151.4 (s), 150.1 (s), 141.2 (s), 139.6 (s), 127.9
(d), 128.3 (d), 128.0 (s), 127.4 (d), 123.2 (d), 112.4 (s), 79.5 (q),
72.0 (s), 70.9 (s), 54.1 (d), 52.4 (q), 52.0 (q), 21.1 (q), 19.9 (q); MS
(FABþ) m/z (%) 1015 (MþþHþ1, 40), 1014 (MþþH, 44); HRMS
(FABþ) Calcd for C50H44Cl4N5O10 (MþþH): 1014.1837. Found:
1014.1845.
NMR (400 MHz, CDCl3)
d
7.89 (s, 4H), 7.55 (d, J¼8.7 Hz, 2H), 7.35
(dd, J1¼6.1 Hz, J2¼3.0 Hz, 4H), 7.14 (dd, J1¼6.1 Hz, J2¼3.0 Hz, 4H),
7.02 (d, J¼8.7 Hz, 2H), 4.72 (s, 2H), 4.60 (s, 4H), 3.86 (s, 3H), 3.49
(s, 6H), 3.35 (s, 6H), 2.89 (s, 4H); 13C NMR (100 MHz, CDCl3)
4.2.5.12. N-(4-Hydroxyphenyl)-7,18,28,39-tetraaza-5,20,26,41-tet-
rachloro-45,45,46,46-tetramethoxy-43,44-dioxatetradecacyclo[22.18.1.
1
d 171.8 (s), 159.7 (s), 152.1 (s), 138.3 (s), 132.4 (s), 130.8 (d), 127.8
(d), 127.0 (d), 126.9 (s), 126.1 (d), 114.6 (d), 110.9 (s), 79.5 (d), 72.2
(s), 70.7 (s), 55.3 (q), 53.8 (d), 52.3 (q), 52.0 (q), 42.5 (t); MS
(FABþ) m/z (%) 1046 (MþþHþ2, 100), 1045 (Mþþ2, 55), 1044
(MþþH, 73); HRMS (FABþ) Calcd for C54H42Cl4N5O9 (MþþH):
1044.1731. Found: 1044.1727; Anal. Calcd for C54H41Cl4N5O9: C,
62.02; H, 3.95; N, 6.70; O, 13.77. Found: C, 61.57; H, 4.17; N, 6.93;
O, 13.43.
3,22.15,20.126,41.02,23.04,21.06,19.08,17.010,15.025,42.027,40.029,38.031,36]hex-
atetraconta-6(19),7,9,11,13,15,17,27(40),28,30,32,34,36,38-tetrade-
caene-2,23-dicarboximide (11zc). Reaction time 36 h; Yield 90%;
mp>400 ꢀC; IR (KBr, cmꢂ1) 3478 (br), 1720 (s), 1196 (s). MS
(FABþ) m/z (%) 1018 (MþþHþ2, 4), 289 (10); compound 11zc was
characterized by the corresponding acetate derivative obtained
by treatment with acetic anhydride. IR (KBr, cmꢂ1) 1770 (w), 1720
(s), 1645 (m), 1507 (s), 1196 (s); 1H NMR (400 MHz, CDCl3)
d
8.18
Acknowledgements
(s, 4H), 7.58–7.59 (m, 4H), 7.34–7.40 (m, 4H), 7.26–7.29 (m. 4H),
4.66 (s, 4H), 3.75 (s, 6H), 3.40 (s, 6H), 3.27 (s, 4H), 2.39 (s, 3H); 13C
The financial support from the National Science Council of Tai-
wan is gratefully acknowledged.
NMR (100 MHz, CDCl3)
d 171.2 (s), 168.9 (s), 151.9 (s), 151.4 (s),

T.-C. Chou et al. / Tetrahedron 65 (2009) 10243–10257
10257
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