Intramolecular complex formation between flexible molecular tweezers and weak electron acceptor

Article abstract of DOI:10.3987/com-00-s(i)81

A flexible receptor having three aromatic chromophores can bind a weak electron acceptor which is linked covalently to the receptor with alkyl chain of an appropriate length. The receptor has tweezers type conformation when the acceptor was entrapped within the cavity. Sandwich type donnor-acceptor-acceptor arrangement was realized in solution.

Full text of DOI:10.3987/com-00-s(i)81

HETEROCYCLES, Vol. 54, No. 2, pp.849-864, Received 19th June, 2000
INTRAMOLECULAR COMPLEX FORMATION BETWEEN
FLEXIBLE MOLECULAR TWEEZERS AND WEAK
ELECTRON ACCEPTOR
Hirotaka Kurebayashi and Yoshimasa Fukazawa*
Department of Chemistry, Graduate School of Science, Hiroshima University,
Higashi-Hiroshima 739-8526, Japan
Abstract- A flexible receptor having three aromatic chromophores can bind a
weak electron acceptor which is linked covalently to the receptor with alkyl chain
of an appropriate length. The receptor has tweezers type conformation when the
acceptor was entrapped within the cavity. Sandwich type donnor-acceptor-acceptor
arrangement was realized in solution.
INTRODUCTION
Host-guest chemistry constitutes an important and rapidly growing research area.1 Many structurally
interesting hosts have been synthesized for studying the nature of the binding interactions between hosts
and guests. Molecular tweezers,2 containing two aromatic chromophores connected by spacer are suitable
receptors for planar guests since they can hold the guest with the two aromatic arms through π-stacking
interactions.3 The two aromatic arms of the host can bind the electron acceptor guests with charge transfer
interaction forming a sandwich type layered complexes.4 Although rigid tweezers,5 having a preorganized
face-to-face arrangement of the two aromatic chromophores are favorable for strong binding, flexible
tweezers6 have the adaptability for the variation of guests. In our previous papers, we reported that the
flexible tweezers (1 and 2) based on dioxa[2.2]orthocyclophane7 can bind strong p-electron deficient
guests to form the triple-decker type donor-acceptor-donor8 and donor-acceptor-acceptor9 arrangements in
the crystalline state. In a case of a relatively weak electron-accepting guest, however, no intermolecular
complex formation with host (2) was observed in solution. A large entropic cost10,11 prevented the
formation of the intermolecular complex of 2 and the weak electron acceptors in organic solvents. In
order to overcome the unfavorable entropic cost, we linked the guest to the host with an appropriate
methylene chain.12 In this paper, we report on the synthesis, intramolecular complex formation and
O
O
O
O
O
O
O
O
O
OMe
1
2

molecular structures of these tethered host-guest compounds
RESULT AND DISCUSSION
Synthesis
As the weak electron acceptor, 2,4,6-tribromoanisole, 4-nitroanisole, 2,4- and 2,5-dinitroanisole, N-
methylphthalimide, N-methyl-4-bromophthalimide, N-methyl-3- and 4-nitrophthalimide were selected.13
These weak electron acceptors were connected with ester linkage to host 2. Williamson type coupling of
carboxylic acid with corresponding ω-bromoalkyl derivative of weak electron acceptors in the presence of
K2CO3 in DMF gave the desired compounds (3a-3e, 4a-4e, 5, 6, 7, 8, 9, 10). Reference compounds (11,
12) were prepared to investigate the role of the phenanthrene ring in the formation of an intramolecular
complex. Compound (13) was also prepared to obtain the precise molecular dimension of the host moiety
by an X-ray crystallography. The synthetic route of 2 and 13 is shown in Scheme 1.
O
O
O
O
O
Ha
O (CH2)n Y
Hb
Hc
NO2
Hd
O
O
4a: n= 3
3a: n= 3
3b: n= 4
3c: n= 5
3d: n= 6
NO2
Hd
4b: n= 4
4c: n= 5
4d: n= 6
4e: n= 10
Y =
Y = N
N
O
O
3-Nitrophthalimido
4-Nitrophthalimido
3e: n= 10
O
O
NO2
5: n= 3, Y = 4-bromophthalimido
6: n= 3, Y = phthalimido
7: n= 3, Y = 2,5-dinitrophenoxy
8: n= 3, Y = 2,4-dinitrophenoxy
9: n= 3, Y = 4-nitrophenoxy
Br
Y =
N
N
O
Hd
O
O
O2N Hd
7
5
6
O2N
O
Br
10: n= 3, Y = 2,4,6-tribromophenoxy
NO2
Hd
O
NO2
O
Br
O
O
Hd
Br Hd
O (CH2)3
Y
8
10
9
O
Hc
O
O
O
NO2
11: Y = 4-nitrophthalimido
12: Y = 3-nitrophthalimido
O
13
Modeling study of host moiety
A modeling study of 2 as the host moiety was carried out to know the most probable binding structures in
solution. The calculation was carried out with AMBER* force field using GB/SA chloroform solvation
model14 in the program package of Macromodel V 6.0.15 Since the oxygen containing eight-membered

OH
OH
O
O
Br
Br
a)
b)
2 or 13
14
15
(a) 1,2,4,5-tetrakis(bromomethyl)benzene, Cs2CO3, acetone, 25%; (b) for 2:
methyl-3,4-dihydroxybenzene, Cs2CO3, acetone, 89%; for 4: 4-nitrocatecol,
Cs2CO3, acetone, 60%
Scheme 1
ring has three conformers,7a twist-boat (b), screw (s), and chair (c), 9 structures (bb, bs, bc, sb, ss, sc cb, cs,
and cc) are possible for the host moiety. For the effective binding of a planar p-guest, there should be at
least one perpendicular arrangement of the two neighboring aromatic rings in the host. Hence, 5
conformers having at least one twist-boat conformer were selected, within which bb, bc, and cb have each
two arrangements, syn and anti, of the two terminal chromophores. In the case of bb, they are boat-boat-
syn (bbs) and boat-boat-anti (bba), respectively. Altogether 8 conformers (bbs, bba, bs, bcs, bca, sb, cbs,
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
bba
10.12 kJ/mol
bbse
6.07
bbs
13.55
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
bca
12.75
bcs
7.28
bs
0.00
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
O
cba
17.75
cbs
21.50
sb
10.15
Figure 1. Structures of 2 with relative steric energies.

and cba) were taken into consideration and their relative steric energies were calculated. The calculation
disclosed that there are two conformers in bbs form which differs the arrangement of the two terminal
chromophores with respect to each other. One is skewed and the other is eclipsed. The former has skew
arrangement around the axis connecting the two centroids of the two oxygen carrying 6-membered
aromatic rings and the latter has eclipsed arrangement. The steric energy of the latter is smaller than the
former. The structures thus obtained are shown in Figure 1 together with their relative steric energies.
X-ray Study of host moiety
An X-ray crystallographic analysis of 13 was carried out
in order to know the structure of the host moiety. As can
be seen in ORTEP drawing, 13 does not have a
conformation of face-to-face syn arrangement of the two
terminal aromatic rings (Figure 2). The two terminal
chromophores are anti with each other to have bba form.
Two neighboring aromatic chromophores of the host have
roughly perpendicular arrangement. The dihedral angles
between each terminal aromatic ring and the central
durene ring are 88.4 ° for the benzoate and 73.3° for
phenanthrene, respectively. The two terminal
chromophores are not parallel to each other and have the
dihedral angle of 33.7 °. The perpendicular arrangement
Figure 2. ORTEP drawing of 13.
of the neighboring chromophores should be a prerequisite for an efficient binding of a planar guest. Both
the p-p stacking charge transfer interaction and CH-p type face-to-edge interactions16 should be effective
for guest binding.
NMR measurement
The nmr chemical shift differences of the aromatic protons in these tethered compounds with respect to
the references gave information of the extent of the intramolecular interaction between the host and guest
moieties in solution. The up-field shift of an aromatic proton from that of the reference compound should
be a good sign for the interaction such as p-p stacking as was found in [m.m]cyclophanes.17 In these
tethered compounds, there are roughly two conformers, open and closed forms. In the closed form as was
Figure 3. Open and closed forms in tethered compound.

shown in Figure 3, the aromatic proton of the guest should have large up-field shift because of the
influence of the ring current effect of the three aromatic chromophores of the host. It is obvious that the
entropy of the open form is far larger than closed one.18 The entropy changes are primarily a consequence
of losses of internal rotation of the tether moiety in the closed form. The equilibrium between the open
and closed forms should shift in favor of the latter when lowered the temperature, since the latter has
smaller entropy. Hence, the NMR measurements at lower temperature should give more prominent shift
changes because of the increase of the population of the smaller entropy conformers.
The temperature dependent changes of the
ppm
chemical shift of 3a are shown in Figure 4.
Ha
● ●
●
● ●
●
● ● ●
●
The up-field shifts of Ha, Hc, and Hd are
clearly seen when lowered the temperature.
The gradient of Hd is largest of the three. On
the other hand, Hb moved to the down-field.
Table 1 shows the changes of the chemical
shift of the aromatic protons in the tethered
compounds together with the chemical shift
values of the reference compounds. The
largest up-field shift was observed at Hd
● ●
8.00
◆
Hb
◆
●
● ● ●
● ● ● ●
◆
● ● ●
●
●
7.00
6.00
◆
◆
Hd
◆
●
●
●
◆
●
Hc
●
●
●
●
5.00
-80 -60 -40 -20
Figure 4. Temperature dependent chemical shift of 3a.
0
20 40
℃
proton of 3a at –60 °C. Up-field shift of Hd was also observed in compounds (4a) and (5). Up-field
shift of both Ha and Hc and down-field shift of Hb were commonly observed in compounds (3a, 4a, 5,
and 6). The shift difference of Ha is largest in 3a and decreases in the order of 3a>4a>5>6. The same
trend was observed also in Hc and Hd. This order is consistent with the electron accepting ability of the
guests as was indicated by the LUMO energy levels.13 The down field-shift of Hb of these compounds
was also consistent to this order. It was thus clear that the stronger the electron accepting ability of the
guest the larger contribution of the closed form in the dynamic equilibrium of the close/open forms in
solution.
In order to know a role of the phenanthrene ring in the intramolecular complex formation, tethered
compounds (11) and (12) were prepared and their chemical shift behaviors toward the temperature change
were examined. Hd protons of both 11 and 12 did not change at all even at –60 °C (Table 1). This means
that the phenanthrene ring is requisite for the formation of closed form. The π-π stacking interaction
between the phenenthrene and the electron-accepting guests is thus essential for the intramolecular
complex formation. The phthalimide functionality is efficient for the formation of the closed form,
however, phenols are not effective even in the dinitro derivatives whose LUMO energy levels are lower
than that of N-methyl-3-bromophthalimide. No large chemical shift change was observed even in the
aromatic proton of the guest moiety of 7, 8, 9, and 10. In these compounds, the chemical shift of the

aromatic protons of the host moiety (Ha, Hb, and Hc) did not change also from the reference compound
even at the low temperature. The behavior of the chemical shift changes in these compounds suggested a
negligible contribution of the closed form to the dynamic equilibrium. The chemical shift change might
be explained due to the change of relative population within the open form, since there should be a
significant amount of conformers in the open than and their populations are temperature dependent.
Modeling study of closed form of 6
In order to know the structure of the closed form in solution, the modeling study of 6 was carried out. The
low mode search algorithm19 was selected to generate all the possible structures. The 3000 initial
structures were generated and then optimized with AMBER* force field. The structures are shown in
Figure 5.
The structure of the host moiety of the most stable structure (c1) has tweezers type conformation with
face-to-face syn arrangement of the two terminal aromatic rings. The two terminal chromophores lie
parallel and have skewed arrangement to each other (bbs-skew). The guest was suitably accommodated in
this cleft. Both the p-p stacking and face-to-edge interactions are operative in binding the guest. In this
Table 1. Selected Chemical Shift Changes in Tethered Compounds and Chemical
Shifts of Reference Compounds
Ha
Hb
Hc
Hc
Hd
Hd
Hd Hd
Hd Hd
(11,12) (3a, 11)(4a, 12) (5) (8)
(9) (10)
Reference 25˚C 8.58 7.17 6.89
6.85 8.58
8.08 7.86 8.46 8.08 7.58
-0.14* 0.05 -0.33
-0.69
-2.12
25˚C
3a
-60˚C
0.21 -0.89
25˚C -0.08 0.03 -0.22
-0.14 0.14 -0.63
-0.39
-0.50
-1.10
-0.46
4a
5
-60˚C
25˚C -0.04 0.00 -0.12
-0.09 0.06 -0.28
-0.61
-60˚C
25˚C -0.03 -0.01 -0.09
-0.04 0.03 -0.13
6
-60˚C
25˚C -0.01 0.00 0.00
0.01 0.05 0.01
25˚C -0.02 0.00 0.00
0.00 0.04 0.00
25˚C -0.01 -0.02 0.01
0.01 0.02 0.02
25˚C 0.00 -0.02 0.01
7
-60˚C
-0.08
-0.05
0.08
0.13
0.06
0.10
8
9
-60˚C
-60˚C
10
11
0.00 0.02 0.03
-60˚C
25˚C
-60˚C
25˚C
0.01 -0.09
0.02 -0.04
0.01
0.03
0.01
0.02
12
-60˚C
*) - sign denotes up-field shift

structure, the guest lied on the phenanthrene to have maximum overlap with it. This π−π stacking
interaction should be the major contributor to the formation of the closed form in solution.
Quite similar triple-decker stacking interaction was observed in the second structure (c2). Its energy
difference form c1 is 2.0 kJ/mol. Again, the maximum overlap between the guest and phenanthrene was
observed in the structure. In c2, the host moiety has bbs-eclipsed conformation and the two oxygen
carrying 6-membered rings of the two terminal chromophores are superimposed when viewed along the
perpendicular direction of one of the two terminal arenes of the host. Other structures of the closed form
having the host conformation other than bbs-skew or bbs-eclipse are c3 and c4. They have bs or bcs
conformer in the host moiety. In these structures π−π stacking interaction between the guest and
phenanthrene was observed. However, they are less stable by 15.5 and 19.8 kJ/mol from c1, respectively.
The instability of these structures may come from the lesser contact area between the host and guest
moieties. In both structures the mean squares plane of the guest is almost perpendicular to that of the
benzoate ring and has poor overlap with durene ring of the host moiety. There are quite many structures
in between c2 and c3. They have either bbs-skew or bbs-eclipse form of the host moiety but have
different orientations of ester functionality,different chain conformations, and different orientations of
the guest with respect to the host phenanthrene.
Structure of closed form in solution
The temperature-dependent chemical shift movements of the aromatic protons gave a good clue for the
O
O
O
O
O
O
O
O
N
O
O
O
N
O
O
O
O
O
O
c1
c2
O
O
O
O
N
O
N
O
O
O
O
O
O
O
O
O
O
c4
Figure 5. Structures of closed form for 6.
c3

structure elucidation. The chemical shift simulation20 is also the method of choice. If the precise
arrangement of the interacting two aromatic rings is known, the resulting induced chemical shift change
of the aromatic protons can be easily estimated by the influence of the ring current effect21 of the
interacting counterpart.
The up-field shift of the guest proton should be largest in c1 because of the shielding effects due to the
surrounding three aromatic rings. Both Ha and Hc have to show up-field shifts of similar amount to each
other. The chemical shift of Hb, however, should have down-field movement because Hb is placed in the
deshielding region of the guest aromatic ring. The characteristic feature of these chemical shift
movements of c1 should be observed also in c2. Both Hd and Ha should have up-field shift movements in
c3 and c4 because of the stacking arrangement of the guest and phenanthrene, however, both Hb and Hc
have to be shifted to the lower field because they are placed within the deshielding cone of the guest
benzene ring.
The observed behavior of the chemical shift movements in 3a, 4a, 5, and 6 is consistent with the
theoretical shift movements in c1 and c2 but not compatible to those of c3 and c4. Thus, the chemical
shift movements of all the aromatic protons can be clearly explained by the formation of the
intramolecular complex with the triple-decker sandwich arrangement of the three aromatic rings as in c1
and c2. In other words, the guest moiety was entrapped within the tweezers shaped host in the closed
form. Of course, the observed shift values reflect the population of the closed form in the equilibrium.
The bigger the contribution of the closed form the larger the shift values in solution.
Chain length effect
The formation of the closed form is related to a ring formation by an intramolecular cyclization.22 It is
known that the yield of the cyclization is dependent on the chain length. In many instances, the formation
of medium size rings (8- to 11-membered) is the most difficult.23 In order to understand the effect of the
chain length on the ease of the formation of the closed form in the equilibrium, we prepared series of
compounds (3a–3e, 4a–4e) having the host and guest moieties linked with different chain length.
Intuitively, the probability of the two chromophores coming closer enough for the formation of the closed
form should decrease as the chain gets longer. In terms of entropy, this implies the negative contribution
of ΔS owing to reduction of freedom of internal rotation of the chain when disordered open-chain
converted into the closed form.
The NMR chemical shift differences of the aromatic protons at –60 °C in the series of 3a–3e with respect
to the references are given in Figure 6. Protons Ha, Hc, and Hd show up-field shift. The shift difference
of Hd is largest in 3a and decreases with the number of the methylene in the chain. It is rather surprising
that shift in 3c (n=5) is larger than that of 3b (n=4) and the graph shows a zigzag line. The same trends
are shown in both Ha and Hc and also in Hb though the shift magnitudes are negative. It is known that
n=3 (trimethylene chain) is the special number24 to have the largest interaction between the two

chromophores linked by an appropriate methylene chain. Since the magnitude of the chemical shift
difference corresponds to the population of the closed form, 3c has larger population of the closed form
t han 3b though the entropy change in closed/open forms in 3c should be more negative than in s3b. The
same chemical shift behavior including zigzag lines with respect to the chain length was observed in the
series of compounds (4a-4e), though the magnitudes of the shift differences are smaller.
∆δ (ppm)
◆
2
Hd
1
Hc
●
●
◆
Ha
Hb
◆
●
●
●
◆
●
●
◆
●
●
●
0
●
●
●
-1
3a
3b
3c
3d
3e
Figure 6. Chain length dependence of chemical shift difference in 3a-3e.
CONCLUSION
This paper presents the synthesis of the flexible molecular tweezers having the covalently linked weak
electron accepting guest and the formation of the intramolecular triple-decker complex of donor-acceptor-
acceptor arrangement. The behavior of the temperature-dependent chemical shift movement of the
aromatic protons was consistent to the formation of the intramolecular complexes whose structures were
predicted by molecular mechanics calculations. Efficiency of the intramolecular complex formation is
dependent both on the electron accepting ability of the guest and chain length which links the host and
guest moieties.
EXPERIMENTAL
Preparation of the tethered compounds
A mixture of 2 and 10 eq of lithium hydroxide monohydrate in MeOH/THF/H2O = 1/3/1 was refluxed for
3 h and treated with 1N-HCl. The mixture was extracted with ethylacetate, and the organic layer was
washed with brine, and dried (Na2SO4). The solvent was removed under reduced pressure to afford
carboxylic acid (95%). 1H-NMR (300 MHz CDCl3) δ 8.59-8.57 (m, 2H), 8.26-8.23 (m, 2H), 7.74 (d, 1H,
J= 1.5 Hz), 7.62-7.57 (m, 5H), 7.16 (s, 1H), 7.00 (s, 1H), 6.92 (d, 1H, J=8.5 Hz), 5.66 (s, 2H), 5.62 (s,
2H), 5.49 (s, 2H), 5.34 (s, 2H); IR 3300-2800, 1692, 1254 cm-1. MS M+ m/z 490; HRMS for C31H22O6:
m/z (calcd) M+=490.1416; m/z (obsd) =490.1422.
A mixture of carboxylic derivative and 1 eq of corresponding bromoalkyl derivatives of weak electron
acceptor and 1.5 eq of K2CO3 in 30 mL of DMF was stirred one day at 80℃. The reaction mixture was
poured into 50 mL of ethyl acetate. The organic layer was washed with 1N-HCl, saturated NaHSO4 and
brine, dried (Na2SO4). The solvent was removed under reduced pressure, residue was purified by silica
gel column chromatography (CHCl3) and then by GPC (CHCl3) to afford tethered derivatives.
Tethered compound (3a) (n=3)
75% yield. yellow powder, mp 216-219℃; 1H-NMR (300 MHz CDCl3) δ 8.42-8.36 (m, 3H), 8.21-8.16
(m, 2H), 7.82 (dd, 1H, J=1.5, 8.5 Hz), 7.81-7.43 (m, 5H), 7.20 (s, 1H), 7.19-7.16 (m, 2H), 7.08 (s, 1H),

6.52 (d, 1H, J=8.5 Hz), 5.70 (s, 2H), 5.68 (s, 2H), 5.45 (s, 2H), 5.33 (s, 2H), 4.32 (t, 2H, J=6.0 Hz),
3.89 (t, 2H, J= 6.5 Hz), 2.16 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.993, 165.811, 165.268, 153.647,
151.044, 147.464, 140.155, 139.369, 136.717, 136.526, 135.848, 134.497, 132.883, 131.413, 129.098,
128.605, 128.477, 128.320, 127.953, 127.718, 126.880, 126.702, 125.963, 125.520, 125.472, 124.785,
124.368, 123.726, 122.327, 122.270, 122.034, 121.744, 120.738, 118.107, 75.981, 74.805, 74.102,
72.768, 62.899, 36.400, 26.978; IR 1718, 1539, 1344 cm-1. MS M+ m/z 722; HRMS for C42H30N2O10: m/z
(calcd) M+=722.1900; m/z (obsd) =722.1904.
Tethered compound (3b) (n=4)
78% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.47-8.42 (m, 2H), 8.31-8.27 (m, 2H), 8.21-8.15 (m,
2H), 7.61-7.49 (m, 6H), 7.41 (dd, 1H, J=2.1, 8.4 Hz), 7.16 (s, 1H), 7.04 (s, 1H), 6.73 (d, 1H J=8.4, Hz),
5.68 (s, 2H), 5.62 (s, 2H), 5.45 (s, 2H), 5.33 (s, 2H), 4.24 (t, 2H, J=6.3 Hz), 3.75 (t, 2H, J=6.6 Hz),
1.82 (m, 4H); 13C-NMR (75 MHz CDCl3) δ 163.066, 162.792, 162.471, 150.858, 148.264, 144.777,
136,948, 136.834, 133.614, 133.568, 133.232, 133.018, 131.439, 129.989, 128.394, 125.907, 125.434,
125.373, 124.824, 124.778, 123.816, 123.641, 123.229, 122.550, 122.489, 121.710, 121.665, 120.947,
119.368, 118.849, 118.819, 118.094, 115.240, 72.892, 71.580, 71.480, 70.000 60.890, 35.206, 22.990,
21.800; IR 1716, 1538, 1343 cm-1. MS M+ m/z 736; HRMS for C43H32 N2O10: m/z (calcd) M+=736.2059;
m/z (obsd) =736.2024.
Tethered compound (3c) (n=5)
66% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.46-8.43 (m, 2H), 8.36 (d, 1H, J=1.8 Hz), 8.25-8.16
(m, 3H), 7.61-7.49 (m, 6H), 7.39 (dd, 1H, J=1.8, 8.4 Hz), 7.19 (s, 1H), 7.04 (s, 1H), 6.75 (d, 1H, J=8.4
Hz), 5.67 (s, 2H), 5.63 (s, 2H), 5.47 (s, 2H), 5.33 (s, 2H), 4.21 (t, 2H, J=6.0 Hz), 3.70 (t, 2H, J=7.2 Hz),
1.74 (m, 4H), 1.42 (br m, 2H); 13C-NMR (75 MHz CDCl3) δ 166.069, 165.840, 165.558, 153.717,
151.191, 147.735, 139.930, 139.792, 136.756, 136.588, 136.161, 135.978, 134.452, 132.987, 131.560,
128.867, 128.745, 128.386, 127.791, 126.791, 126.669, 126.189, 125.563, 125.423, 124.856, 124.617,
123.862, 122.351, 121.855, 121.039, 118.231, 75.932, 74.566, 74.490, 72.929, 63.999, 38.287, 28.033,
27.613, 22.860; IR 1716, 1539, 1343 cm-1. MS M+ m/z 750; HRMS for C44H34N2O10: m/z (calcd)
M+=750.2213; m/z (obsd) =750.2244.
Tethered compound (3d) (n=6)
70% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.51-8.48 (m, 2H), 8.45 (d, 1H, J=1.8 Hz), 8.39 (dd,
1H, J=1.8, 6.3 Hz), 8.23-8.18 (m, 2H), 7.77 (d, 1H, J=6.3 Hz), 7.63 (d, 1H, J=1.2 Hz), 7.61-7.50 (m, 5H),
7.15 (s, 1H), 7.00 (s, 1H), 6.85 (d, 1H, J=8.7 Hz), 5.65 (s, 2H), 5.61 (s, 2H), 5.45 (s, 2H), 5.31 (s, 2H),
4.21 (t, 2H, J=6.6 Hz), 3.70 (t, 2H, J=7.2 Hz), 1.71 (br m, 4H), 1.41 (br t, 4H); 13C-NMR (75 MHz
CDCl3) δ 166.130, 165.863, 165.680, 153.762, 151.374, 147.949, 140.227, 139.899, 136.763, 136.458,
136.199, 136.039, 134.490, 133.170, 131.400, 128.974, 128.592,128.439, 128.394, 127.860, 127.799,
126.753, 126.723, 126.227, 125.578, 125.464, 125.060, 124.541, 124.052, 122.381, 121.908, 121.794,
121.161, 118.361,75.848, 74.787, 74.528, 73.155, 64.648, 38.485, 28.445, 28.170, 26.324, 25.622; IR
1716, 1539, 1343 cm-1. MS M+ m/z 764; HRMS for C45H36 N2O10: m/z (calcd) M+=764.2370; m/z (obsd)
=764.2369.
Tethered compound (3e) (n=10)
56% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.58 (d, 1H, J=1.8 Hz), 8.56-8.53 (m, 2H), 8.50 (dd,
1H, J=1.8, 8.1 Hz), 8.27-8.21 (m, 2H), 7.93 (d, 1H, J=8.1 Hz), 7.70 (d, 1H, J=2.1 Hz), 7.69-7.52 (m, 5H),
7.14 (s, 1H), 7.00 (s, 1H), 6.90 (d, 1H, J=8.7 Hz), 5.64 (s, 2H), 5.61 (s, 2H), 5.45 (s, 2H), 5.32 (s, 2H),
4.23 (t, 2H, J=6.6 Hz), 3.70 (t, 2H, J=7.5 Hz), 1.68 (br m, 4H), 1.29 (br s, 12H); 13C-NMR (75 MHz
CDCl3) δ 163.204, 162.921, 162.838, 150.797, 148.546, 145.120, 137.368, 137.238, 133.698, 133.415,
133.163, 131.592, 130.394, 128.143, 126.052, 125.625, 125.480, 124.915, 124.877, 123.771, 123.244,
122.580, 122.534, 122.328, 121.558, 121,214, 119.444, 118.910, 118.849, 118.208, 115.4921, 72.846,
71.854, 71.747, 70.305, 61.981, 35.702, 26.294, 26.309, 26.149, 26.012, 25.653, 25.386, 23.738, 22.937;
IR 1717, 1539, 1343 cm-1. MS M+ m/z 820; HRMS for C49H44N2O10: m/z (calcd) M+=820.2996; m/z
(obsd) =820.2993.
Tethered compound (4a) (n=3)
77% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.49-8.45 (m, 2H), 8.24-8.19 (m, 2H), 7.68 (dd, 1H,

J=1.0, 8.0 Hz), 7.62-7.48 (m, 6H), 7.36-7.33 (m, 2H), 7.17 (s, 1H), 7.04 (s, 1H), 6.67 (d, 1H, J=8.5 Hz),
5.68 (s, 2H), 5.65 (s, 2H), 5.46 (s, 2H), 5.32 (s, 2H), 4.31 (t, 2H, J=6.0 Hz), 3.88 (t, 2H, J=7.0 Hz), 2.16
(m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.650, 165.342, 162.788, 153.671, 147.696, 144.708, 140.017,
139.899, 136.785, 136.771, 136.273, 134.861, 134.89, 133.717, 131.449, 128.694, 128.459, 128.441,
128.103, 127.972, 127.928, 126.800, 126.764, 126.509, 126.111, 125.572, 125.522, 124.804, 124.494,
123.455, 122.441, 122.78, 121.890, 121.830, 120.967, 76.003, 74.604, 74.549, 72.902, 62.622, 36.315,
27.078; IR 1718, 1541, 1354 cm-1. MS M+ m/z 722; HRMS for C42H30N2O10: m/z (calcd) M+=722.1900;
m/z (obsd) =722.1893.
Tethered compound (4b) (n=4)
77% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.56-8.52 (m, 2H), 8.25-8.20 (m, 2H), 8.10 (dd, 1H,
J=1.2, 8.4 Hz), 7.91 (dd, 1H, J=1.2, 7.5 Hz), 7.76 (dd, 1H, J=7.5,8.4Hz), 7.67 (d, 1H, J=2.1 Hz), 7.61-
7.53 (m, 5H), 7.13 (s, 1H), 7.00 (s, 1H), 6.86 (d, 1H, J=8.4 Hz), 5.64 (s, 2H), 5.61 (s, 2H), 5.59 (s, 2H),
5.32 (s, 2H), 4.27 (t, 2H, J=6.0 Hz), 3.76 (t, 2H, J=6.9 Hz), 1.80 (m, 4H); 13C-NMR (75 MHz CDCl3)
δ 165.471, 165.619, 162.857, 153.892, 147.964, 140.235, 140.174, 136.687, 136.519, 136.130, 135.154,
134.459, 133.895, 133.216, 131.240, 128.615, 128.462, 128.386, 127.913, 127.875, 126.822, 126.761,
126.349, 125.555, 125.517, 124.838, 124.693, 122.450, 121.878, 121.847, 121.184, 75.917, 74.764,
74.703, 73.116, 63.976, 38.287, 26.072, 24.966; IR 1718, 1541, 1352 cm-1. MS M+ m/z 736; HRMS for
C43H32N2O10: m/z (calcd) M+=736.2059; m/z (obsd) =736.2014.
Tethered compound (4c) (n=5)
69% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.54-8.51 (m, 2H), 8.25-8.20 (m, 2H), 7.93 (dd, 1H,
J=1.2, 7.8 Hz), 7.87 (dd, 1H, J=1.2, 7.8 Hz), 7.70-7.51 (m, 7H), 7.14 (s, 1H), 7.00 (s, 1H), 6.85 (d, 1H,
J=8.7 Hz), 5.65 (s, 2H), 5.62 (s, 2H), 5.44 (s, 2H), 5.31 (s, 2H), 4.23 (t, 2H, J=6.3 Hz), 3.71 (t, 2H,
J=7.2 Hz), 1.74 (m, 4H), 1.45 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.756, 165.672, 162.865, 153.801,
147.994, 144.866, 140.174, 140.067, 136.702, 136.519, 136.115, 135.039, 134.528, 133.879, 131.232,
128.615, 128.447, 128.294, 127.913, 127.867, 126.753, 126.257, 125.563, 125.510, 125.029, 124.594,
123.633, 122.427, 121.870, 121.840, 121.145, 75.901, 74.734, 74.635, 73.162, 64.312, 38.417, 28.132,
27.827, 23.188; IR 1718, 1541, 1357 cm-1. MS M+ m/z 750; HRMS for C44H34N2O10: m/z (calcd)
M+=750.2213; m/z (obsd) =750.2221.
Tethered compound (4d) (n=6)
74% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.56-8.53 (m, 2H), 8.25-8.20 (m, 2H), 8.01 (dd, 1H,
J=0.9, 6.6 Hz), 7.98 (dd, 1H, J=0.9, 6.6 Hz), 7.78 (t, 1H, J=6.6 Hz), 7.67 (d, 1H, J=2.1 Hz), 7.62-7.52 (m,
5H), 7.13 (s, 1H), 6.99 (s, 1H), 6.89 (d, 1H, J=8.7 Hz), 5.64 (s, 2H), 5.60 (s, 2H), 5.44 (s, 2H), 5.31 (s,
2H), 4.22 (t, 2H, J= 6.6Hz), 3.70 (t, 2H, J= 6.9Hz), 1.70 (m, 4H), 1.41 (m, 4H); 13C-NMR (75 MHz
CDCl3) δ 165.794, 165.756, 162.888, 153.808, 148.063, 144.943, 140.311, 140.166, 136.687, 136.458,
136.100, 135.100, 134.536, 134.009, 131.179, 128.569, 128.470, 128.356, 127.921, 127.875, 126.822,
126.753, 126.273, 125.563, 125.517, 125.166, 124.579, 123.717, 122.443, 121.901, 121.840, 121.580,
121.184, 75.871, 74.826, 74.696, 73.223, 64.701, 38.577, 28.498, 28.170, 26.423, 25.591; IR 1718, 1541,
1354 cm-1. MS M+ m/z 764; HRMS for C45H36N2O10: m/z (calcd) M+=764.2370; m/z (obsd) =764.2374.
Tethered compound (4e) (n=10)
62% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.56-8.53 (m, 2H), 8.26-8.21 (m, 2H), 8.04-8.01 (m,
2H), 7.80 (t, 1H, J=7.8 Hz), 7.69 (d, 1H, J=2.4 Hz), 7.62-7.53 (m, 5H), 7.12 (s, 1H), 6.98 (s, 1H), 6.90 (d,
1H, J=8.4 Hz), 5.64 (s, 2H), 5.60 (s, 2H), 5.43 (s, 2H), 5.30 (s, 2H), 4.23 (t, 2H, J=6.9 Hz), 3.68 (t, 2H,
J=7.5 Hz), 1.67 (m, 4H), 1.29 (m, 12H); 13C-NMR (75MHz CDCl3) δ 165.817, 162.872, 153.785,
148.124, 144.943, 140.334, 140.212, 136.657, 136.413, 136.070, 135.070, 134.574, 134.085, 131.095,
128.577, 128.478, 128.317, 127.921, 127.875, 126.807, 126.753, 126.234, 125.563, 125.517, 125.334,
124.541, 123.755, 122.443, 121.893, 121.840, 121.519, 121.184, 75.833, 74.833, 74.726, 73.284, 64.991,
38.737, 29.330, 29.284, 29.162, 29.002, 28.658, 28.277, 26.728, 25.590; IR 1718, 1541, 1357 cm-1. MS
M+ m/z 820; HRMS for C49H44N2O10: m/z (calcd) M+=820.2996; m/z (obsd) =820.2990.
Tethered compound (5)
60% yield. colorless oil; 1H-NMR (300 MHz CDCl3) δ 8.55-8.52 (m, 2H), 8.25-8.22 (m, 2H), 7.85 (s, 1H),
7.62-7.45 (m, 6H), 7.47 (d, 1H, J=7.6 Hz), 7.44 (dd, 1H, J=1.5, 7.6 Hz), 7.15 (s, 1H), 7.02 (s, 1H), 6.78 (d,

1H, J=8.5 Hz), 5.66 (s, 2H), 5.64 (s, 2H), 5.45 (s, 2H), 5.32 (s, 2H), 4.30 (t, 2H, J=6.0 Hz), 3.85 (t, 2H,
J=6.5 Hz), 2.13 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 167.387, 166.876, 165.478, 153.921, 147.979,
140.268, 140.140, 136.790, 136.676, 136.579, 136.287, 134.549, 133.535, 131.228, 130.420, 128.791,
128.701, 128.538, 128.492, 127.982, 127.963, 126.783, 126.742, 126.477, 126.210, 125.560, 125.531,
124.693, 124.668, 124.430, 122.482, 122.438, 121.915, 121.882, 121.083, 75.958, 74.796, 74.694,
73.165, 62.461, 35.634, 27.444; IR 1714 cm-1. MS M-1+, M+1+ m/z 755, 757; HRMS for C42H30NO8Br:
m/z (calcd) M-1+=755.1155, M+1+=757.1144; m/z (obsd) M-1+=755.1147, M+1+=757.1103.
Tethered compound (6)
60% yield. colorless oil; 1H-NMR (300 MHz CDCl3) δ 8.56-8.53 (m, 2H), 8.27-8.21 (m, 2H), 7.76-7.73
(m, 2H), 7.67 (d, 1H, J=2.7 Hz), 7.63-7.49 (m, 7H), 7.14 (s, 1H), 7.00 (s, 1H), 6.80 (d, 1H, J=8.4 Hz),
5.65 (s, 2H), 5.62 (s, 2H), 5.44 (s, 2H), 5.31 (s, 2H), 4.31 (t, 2H, J=6.0 Hz), 3.85 (t, 2H, J=6.6 Hz),
2.14 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 168.221, 165.543, 153.862, 147.929, 140.204, 140.174,
136.657, 136.527, 136123, 134.459, 133.841, 131.911, 131.217, 128.539, 128.478, 127.936, 127.905,
126.738, 126.280, 125.533, 125.502, 124.731, 123.129, 122.450, 122.435, 121.870, 121.062, 75.924,
74.749, 74.703, 73.101, 62.328, 35.204, 27.628; IR 1710 cm-1. MS M+ m/z 677; HRMS for C42H31NO8:
m/z (calcd) M+=677.2050; m/z (obsd) =677.2010.
Tethered compound (7)
83% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.67 (d, 1H, J=3.0 Hz), 8.52-8.51 (m, 2H), 8.25 (dd,
1H, J=2.5, 9.5 Hz), 8.23-8.19 (m, 2H), 7.65 (d, 1H, J=2.0 Hz), 7.60-7.52 (m, 5H), 7.10 (s, 1H), 7.02 (d,
1H, J=9.0 Hz), 6.95 (s, 1H), 6.87 (d, 1H, J=9.0 Hz), 5.61 (s, 2H), 5.56 (s, 2H), 5.41 (s, 2H), 5.28 (s,
2H), 4.46 (t, 2H, J=6.0 Hz), 4.24 (t, 2H, J=6.0 Hz), 2.28 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.497,
156.403, 154.082, 148.160, 140.266, 140.170, 140.021, 138.680, 136.708, 136.295, 136.212, 134.504,
131.109, 128.944, 128.603, 128.439, 128.434, 127.911, 127.881, 126.781, 126.253, 125.559, 125.564,
124.633, 124.628, 122.439, 121.869, 121.856, 121.812, 121.343, 114.097, 75.815, 74.750, 74.678,
73.287, 67.248, 60.821, 28.388; IR 1711, 1526, 1342 cm-1. MS M+ m/z 714; HRMS for C40H30N2O11: m/z
(calcd) M+=714.1850; m/z (obsd) =714.1866.
Tethered compound (8)
69% yield. yellow oil; 1H-NMR (300 MHz CDCl3) δ 8.53-8.51 (m, 2H), 8.23-8.20 (m, 2H), 7.86-7.78 (m,
3H), 7.66 (d, 1H, J=1.5 Hz), 7.60-7.52 (m, 5H), 7.09 (s, 1H), 6.95 (s, 1H), 6.88 (d, 1H, J=8.5 Hz), 5.61 (s,
2H), 5.57 (s, 2H), 5.41 (s, 2H), 5.28 (s, 2H), 4.45 (t, 2H, J=6.0 Hz), 4.28 (t, 2H, J=6.0 Hz), 2.28 (m,
2H); 13C-NMR (75 MHz CDCl3) δ 165.506, 154.062, 152.156, 150.143, 148.131, 140.305, 140.172,
136.714, 136.348, 136.158, 134.480, 131.146, 128.561, 128.460, 128.455, 127.923, 127.879, 126.771,
126.759, 126,314, 126.035, 125.580, 125.534, 124.657, 124.645, 122.432, 121.887, 121.825, 121.313,
115.331, 109.599, 75.845, 74.789, 74.675, 73.239, 67.037, 60.838, 28.344; IR 1712, 1544, 1346 cm-1. MS
M+ m/z 714; HRMS for C40H30N2O11: m/z (calcd) M+=714.1850; m/z (obsd) =714.1871.
Tethered compound (9)
61% yield. colorless powder, mp 148-149℃; 1H-NMR (300 MHz CDCl3) δ 8.57-8.54 (m, 2H), 8.25-8.21
(m, 2H), 8.16 (d, 2H, J=7.2 Hz), 7.68 (d, 1H, J=1.8 Hz), 7.63-7.52 (m, 5H), 7.12 (s, 1H), 6.96 (s, 1H),
6.90 (d, 3H, J=7.2 Hz), 5.63 (s, 2H), 5.59 (s, 2H), 5.43 (s, 2H), 5.30 (s, 2H), 4.45 (t, 2H, J=6.0 Hz),
4.16 (t, 2H, J=6.0 Hz), 2.25 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.619, 163.673, 154.060, 148.178,
141.509, 140.380, 140.273, 136.725, 136.725, 136.283, 136.222, 134.490, 131.117, 128.569, 128.470,
127.936, 127.905, 126.776, 126.288, 125.876, 125.594, 125.555, 124.754, 124.640, 122.465, 121.893,
121.832, 121.344, 114.355, 75.871, 74.833, 74.749, 73.315, 65.304, 61.260, 28.513; IR 1701, 1593, 1340
cm-1. MS M+ m/z 669; HRMS for C40H31NO9: m/z (calcd) M+=699.1999; m/z (obsd) =699.1957.
Tethered compound (10)
54% yield. colorless powder, mp 152-153℃; 1H-NMR (300 MHz CDCl3) δ 8.58-8.55 (m, 2H), 8.27-8.22
(m, 2H), 7.72 (d, 1H, J=2.1 Hz), 7.63 (s, 2H), 7.61-7.54 (m, 5H), 7.13 (s, 1H), 6.98 (s, 1H), 6.89 (d, 1H,
J=8.7 Hz), 5.63 (s, 2H), 5.59 (s, 2H), 5.43 (s, 2H), 5.30 (s, 2H), 4.45 (t, 2H, J=6.0 Hz), 4.16 (t, 2H, J=6.0
Hz), 2.25 (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.657, 153.976, 152.526, 148.124, 141.509, 140.403,
136.710, 136.405, 136.161, 135.016, 134.497, 131.186, 128.501, 127.951, 127.913, 126.769, 126.357,

125.578, 125.540, 125.006, 124.701, 122.473, 121.908, 121.855, 121.252, 118.994, 117.491, 75.871,
74.833, 74.749, 73.315, 65.304, 61.260, 28.513; IR 1711 cm-1. MS M-3+, M-1+, M+1+, M+3+m/z 858, 860,
862, 864; HRMS for C40H29O7Br3: m/z (calcd) MS M-3+=857.9463, M-1+=859.9446, M+1+=861.9431,
M+3+=863.9425; m/z (obsd) M-3+=857.9460, M-1+=859.9471, M+1+=861.9458, M+3+=863.9431.
Preparation of tethered compounds (11) and (12)
A mixture of 1,2-bis(bromomethyl)benzene (1.6 g, 6.1 mmol) and methylprotocatechuate (1.3 g, 6.5
mmol) in 30 mL of acetone was added dropwise to a suspension of cesium carbonate (5.0 g, 15 mmol) in
30 mL of acetone at refluxed temperature. The reaction mixture was refluxed for 2 h and was filtered. The
solvent was removed under reduced pressure, residue was purified by silica gel column chromatography
(50% Hexane/CHCl3) to afford 1.3 g (81%) of cyclophane methyl ester; colorless powder, mp 112-113℃;
1H-NMR (300 MHz CDCl3) δ 7.74 (d, 1H, J=1.8 Hz), 7.62 (dd, 1H, J=1.8, 8.4 Hz), 7.30-7.26 (m, 3H),
7.13 (br t, 1H), 6.94 (d, 1H, J=8.4 Hz); 13C-NMR (75 MHz CDCl3) δ 166.344, 154.258, 136.153, 134.406,
130.461, 128.951, 128.523, 128.050, 126.204, 124.937, 124.670, 121.245, 76.420, 73.986, 51.92; IR
1716, 1304 cm-1. MS M+ m/z 270; HRMS for C16H14O4: m/z (calcd) M+=270.0892; m/z (obsd) =280.0872.
A mixture of cyclophane methyl ester (500 mg, 1.8 mmol) and lithium hydroxide monohydrate (780 mg,
18 mmol) in 7 mL of MeOH/THF/H2O = 3/3/1 was refluxed for 1 h. The reaction mixture was poured
into 150 mL of ethyl acetate. The organic layer was washed with 1N-HCl and brine, and then dried
(Na2SO4). The solvent was removed under reduced pressure to afford 470 mg (99%) of carboxylic acid.
colorless powder; 1H-NMR (300 MHz CDCl3) δ 7.80 (d, 1H, J=2.4 Hz), 7.68 (dd, 1H, J=2.4, 8.1 Hz),
7.29-7.26 (m, 3H), 7.14 (br s, 1H), 6.96 (d, 1H J=8.1 Hz); 13C-NMR (75 MHz CDCl3) δ 155.067, 148.414,
136.161, 134.215, 130.622, 129.027, 128.546, 127.959, 127.020, 125.433, 123.648, 121.344, 73.902; IR
2917, 1687 cm-1. MS M+ m/z 256; HRMS for C15H12O4: m/z (calcd) M+=256.0736; m/z (obsd) =256.0771.
A mixture of carboxylic acid (50 mg, 0.19 mmol) and 1 eq of corresponding w-bromoalkylphthalimides
and 1.5 eq of K2CO3 in 30 mL of DMF was stirred for one day at 80℃. The reaction mixture was poured
into 50 mL of ethyl acetate. The organic layer was washed with 1N-HCl, saturated NaHSO4 and brine,
and then dried (Na2SO4). The solvent was removed under reduced pressure, residue was purified by silica
gel column chromatography (CHCl3) and then by GPC (CHCl3) to afford tethered compounds.
Tethered compound (11)
73% yield. colorless powder, mp 153-154℃;1H-NMR (300 MHz CDCl3) δ 8.61 (d, 1H, J=2.1 Hz), 8.48
(dd, 1H, J=2.1, 8.4 Hz), 7.91 (d, 1H, J=8.4 Hz), 7.56 (d, 1H, J=2.4 Hz), 7.49 (dd, 1H, J=2.4, 8.4 Hz),
7.31-7.26 (m, 3H), 7.13 (br t, 1H), 6.82 (d, 1H, J=8.4 Hz), 4.34, (t, 2H, J=6.0 Hz), 3.93, (t, 2H, J=6.6 Hz),
2.19, (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.489, 154.258, 136.374, 136.069, 134.337, 133.414,
130.522, 129.134, 128.989, 128.584, 128.073, 126.097, 124.510, 124.312, 118.620, 76.374, 73.948,
62.481, 36.273, 27.543; IR 1721, 1536, 1342 cm-1. MS M+ m/z 488; HRMS for C15H12O4: m/z (calcd)
M+=488.1220; m/z (obsd) =488.1214.
Tethered compound (12)
69% yield. colorless oil;1H-NMR (300 MHz CDCl3) δ 8.04-7.99 (m, 2H), 7.82 (t, 1H, J =7.5 Hz), 7.65
(d, 1H, J=2.1 Hz), 7.50 (dd, 1H, J=2.1, 8.7 Hz), 7.31-7.26 (m, 3H), 7.14 (br t, 1H), 6.83 (d, 1H, J=8.7 Hz)
4.33, (t, 2H, J=6.6 Hz), 3.91, (t, 2H, J=6.6 Hz), 2.18, (m, 2H); 13C-NMR (75 MHz CDCl3) δ 165.680,
165.505, 154.228, 148.300, 136.222, 135.207, 134.430, 134.085, 130.530, 129.012, 128.516, 128.439,
128.088, 126.868, 126.097, 124.670, 124.586, 123.770, 121.145, 76.413, 73.902, 62.381, 36.250, 27.534;
IR 1719, 1541, 1356 cm-1. MS M+ m/z 488; HRMS for C15H12O4: m/z (calcd) M+=488.1220; m/z (obsd)
=488.1216.
Preparation of dioxa[2.2]orthocyclophane derivatives (2) and (13)
A mixture of phenanthrenequinone (50 mg, 0.24 mmol) and a catalytic amount of 10% palladium-carbon
in 5 mL of THF was stirred under H2 for one day at rt. The reaction mixture was filtered under Ar and the
filtrate was added dropwise to a mixture of 1,2,4,5-tetrakis(bromomethyl)benzene (320 mg, 0.71 mmol)
and cesium carbonate (188 mg, 0.58 mmol) in 50 mL of acetone at reflux temperature. The reaction
mixture was refluxed for 1 h and was filtrated. The solvent was removed under reduced pressure and the
residual oil was chromatographed on silica gel (3% Ethyl acetate/Hexane) to afford 30mg (25%) yield of

15; colorless powder, mp 201~204℃. 1H-NMR (300 MHz CDCl3) δ 8.61-8.57 (m, 2H), 8.29-8.25 (m,
2H), 7.65-7.57 (m, 4H), 7.25 (s, 2H), 5.64 (s, 4H), 4.59 (s, 4H); 13C-NMR (75 MHz CDCl3) δ 140.662,
137.336, 136.557, 131.484, 128.485, 127.959, 126.822, 125.632, 122.504, 121.916; IR 1209, 1109 cm-1.
MS M-2+, M+, M-2+,m/z 496, 498, 500; HRMS for C24H18O2Br2: m/z (calcd) M-2+ =495.9669, M+
=497.9765, M-2+ =499.9639; m/z (obsd) M-2+ =495.9687, M+ =497.9763, M-2+ =499.9632.
A mixture of 15 and 1.1 eq of related catecol in acetone was added dropwise to a suspension of cesium
carbonate (2.5 eq) in acetone at reflux temperature. The reaction mixture was refluxed for 2 h and was
filtrated. The solvent was removed under reduced pressure and the residual oil was chromatographed on
silica gel (12.5% Ethyl acetate/Hexane) to afford dioxa[2.2]orthocyclophane derivatives (2) and (13);
Dioxa[2.2]orthocyclophane derivative (13)
60% yield colorless powder; mp 228~230℃. 1H-NMR (300 MHz CDCl3) δ 8.59-8.57 (m, 2H), 8.26-8.22
(m, 2H), 7.92 (d, 1H, J=2.4 Hz), 7.81(dd, 1H, J= 2.4, 9.0 Hz), 7.62-7.56 (m, 4H), 7.17 (s, 1H), 7.01 (s,
1H), 6.94 (d, 1H, J=9.0 Hz), 5.66 (s, 2H), 5.62 (s, 2H), 5.52 (s, 2H), 5.37 (s, 2H); 13C-NMR (75 MHz
CDCl3) δ 155.678, 147.910, 142.707, 140.395, 140.281, 137.198, 136.596, 135.978, 133.864, 131.560,
128.577, 128.462, 127.997, 127.936, 126.830, 126.791, 125.624, 122.488, 121.901, 121.840, 121.542,
120.688, 119.436, 76.313, 74.810, 74.696, 73.315; IR 1522, 1334, 1265 cm-1. MS M+ m/z 491; HRMS for
C30H21NO6: m/z (calcd) M+=491.1369; m/z (obsd) =491.1365.
Dioxa[2.2]orthocyclophane derivative (2)
89% yield; colorless powder;mp 94~96℃.1H-NMR (300 MHz CDCl3) δ 8.58-8.57 (m, 2H), 8.26-8.23
(m, 2H), 7.70 (d, 1H J=1.2Hz), 7.62-7.56 (m, 5H), 7.14 (s, 1H), 7.00 (s, 1H), 6.90 (d, 1H, J=8.5 Hz), 5.65
(s, 2H), 5.62 (s, 2H), 5.46 (s, 2H), 5.33 (s, 2H); 13C-NMR (75 MHz CDCl3) δ 166.291,
153.987, 148.186, 140.447, 140.324, 136.776, 136.496, 136.228, 134.592, 131.201, 128.564, 128.556,
128.024, 127.983, 126.784, 126.771, 126.363, 125.593 125.552, 124.995, 124.711, 122.490, 121.946,
121.885, 121.246, 75.949, 74.907, 74.800, 73.287, 51.968; IR 1715, 1289, 1249 cm-1. MS M+ m/z 504;
HRMS for C32H24O6: m/z (calcd) M+=504.1573; m/z (obsd) =504.1572.
X-Ray Diffraction Analysis of 13
The crystal data for 13 are follows; Monoclinic space group P21/a with a = 14.4750 (4), b = 14.0470 (8),
c = 14.926 (8) Å, b = 107.436 (3)˚, V =2295.4 (2) Å3, and Z = 4. The experimental formula is C30H21NO10,
molecular weight is 491.14 and calculated density is 1.42g･cm-3. The three-dimensional X-Ray data were
collected by the use of graphite-monochromated Mo-Ka radiation (λ= 0.71073 Å) on Mac Science
DIP2030 diffractometer. Of 4251 total unique reflections, 3195 were considered observed at the level of
|Fo| > 3.0 σ|Fo|. The structure was solved by the direct method (Sir97). All non-hydrogen atoms were
located on the initial E synthesis. The location of hydrogen atoms were calculated and included in the
further calculations Full matrix least square refinements with anisotropic 37 non-hydrogen atoms and 21
isotropic hydrogen converted to a conventional R factor of 0.097.
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