Molecular recognition of polymethoxybenzenes by host molecule comprised of two pyromellitic diimides and two dialkoxynaphthalenes

Article abstract of DOI:10.1016/j.tet.2009.11.087

For the continuing study of the molecular recognition of the π-electron-poor host comprised of two pyromellitic diimides and two dialkoxynaphthalenes, its inclusion with π-electron-rich polymethoxybenzenes has been examined. The UV-vis titration studies indicated following order of the association constants (K_a's) as 1:1 complexes in CHCl₃: 1,3,5-trimethoxybenzene (31.3 M^-1)>1,3-dimethoxybenzene (9.2 M^-1)>1,2-dimethoxybenzene (6.5 M^-1)>1,4-dimethoxybenzenes (2.8 M^-1). The X-ray structural analysis of the complexes between the host and dimethoxybenzenes proved the intracavity 1:1 complexes and provided useful information on the structures of the complexes. Not only charge transfer interactions but also other weak interactions such as electrostatic, van der Waals, and the unique hydrogen bonds between the α-hydrogen atoms of the naphthalene and the methoxy oxygen atoms were considered to be responsible for the magnitude of the K_a's. Thus molecular recognition of polymethoxybenzenes has been accomplished by the neutral host using multipoint weak interactions in an organic solvent.

Full text of DOI:10.1016/j.tet.2009.11.087

Tetrahedron 66 (2010) 976–985
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Molecular recognition of polymethoxybenzenes by host molecule comprised
of two pyromellitic diimides and two dialkoxynaphthalenesq
,
,
,
,
Takeshi Nakagaki a b, Kato Shin-ichiro a b, Aya Harano a b, Teruo Shinmyozu a
*
a Institute for Materials Chemistry and Engineering (IMCE), Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
b Department of Chemistry, Graduate School of Sciences, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2009
Received in revised form 19 November 2009
Accepted 19 November 2009
Available online 23 November 2009
For the continuing study of the molecular recognition of the
pyromellitic diimides and two dialkoxynaphthalenes, its inclusion with
p
-electron-poor host comprised of two
-electron-rich poly-
p
methoxybenzenes has been examined. The UV–vis titration studies indicated following order of the
association constants (Ka’s) as 1:1 complexes in CHCl3: 1,3,5-trimethoxybenzene (31.3 Mꢀ1)>1,3-dime-
thoxybenzene (9.2 Mꢀ1)>1,2-dimethoxybenzene (6.5 Mꢀ1)>1,4-dimethoxybenzenes (2.8 Mꢀ1). The X-
ray structural analysis of the complexes between the host and dimethoxybenzenes proved the intracavity
1:1 complexes and provided useful information on the structures of the complexes. Not only charge
transfer interactions but also other weak interactions such as electrostatic, van der Waals, and the unique
Keywords:
Pyromellitic diimide
Macrocycle
Molecular recognition
Charge transfer interaction
hydrogen bonds between the
a-hydrogen atoms of the naphthalene and the methoxy oxygen atoms
were considered to be responsible for the magnitude of the Ka’s. Thus molecular recognition of poly-
methoxybenzenes has been accomplished by the neutral host using multipoint weak interactions in an
organic solvent.
Ó 2009 Published by Elsevier Ltd.
1. Introduction
the structural units. The molecular tubes constructed by the con-
nection of the structural units at the 3,6-positions of the pyro-
Pyromellitic diimide represents the smallest homolog of the
aromatic diimide and it has been used as important components in
supramolecular chemistry due to its p-accepting ability and flat p-
mellitic diimide should have an electron-deficient long cavity, in
which one-dimensional array of the -donating aromatic guests
may be formed. Therefore our molecular tubes may contribute to
p
plane.1 The electrochemical properties of pyromellitic diimide play
an important role in the functionality of the supramolecular ar-
chitectures such as [2]catenanes,2 [2]rotaxanes,3 and molecular
receptors.4 In our continuing efforts to synthesize organic molec-
ular tubes with the diameter of 1–5 nm for the inclusion of organic
guests, we have designed and synthesized the hosts 1, 2, and 3
comprised of pyromellitic diimide moieties with electron accepting
properties and intervening dialkoxybenzene or naphthalene
spacers as structural units of the tubes (Fig. 1).5 Their host cavities
the development of new cluster chemistry of the aromatic
nating molecules.
p-do-
Previously, we found that the host 3 with three pyromellitic
diimide moieties includes an electron-donating guest, [2.2.2]para-
cyclophane, via three-point CT interactions.5a The host 2 with the
two diimide moieties and benzene spacers interacts only outside of
the cavity with electron-donating naphthols to form supramolec-
ular assemblies via a combination of hydrogen bonds and CT in-
teractions because of its small cavity size.5b The homologous host 1
with naphthalene spacers includes an aniline in the cavity by CT
interaction. In addition, the amino group of this aniline further
interacts with anilines outside of the cavity to form a cyclic aniline
are
p-electron-poor and preferential inclusion of the p-donating
aromatic guests is expected via charge transfer (CT) interactions as
one of the driving force of the inclusion. Pyromellitic diimide is
a suitable skeleton of the structural unit because it has four con-
nection sites; two nitrogen atoms for the construction of the
structural units and the two carbon atoms at the 3,6-positions of
the benzene ring of the pyromellitic diimide for the connection of
trimer in a void space by N–H/N and N–H/p interaction in the
solid state.5c This unexpected structure of the inclusion complex
prompted us to study the inclusion phenomena of 1 in more detail
and we found that 1 can recognize polymethoxybenzenes in CHCl3.
In the past two decades, several recognition studies of poly-
methoxybenzenes by artificial macrocyclic hosts have been repor-
ted.6 Stoddart et al. reported the molecular recognition of the 1,2-,
1,3-, and 1,4-dimethoxybenzenes (Ka 8.1, 8.0, and 17 Mꢀ1) using
q
Molecular Tubes and Capsules, Part 5. For Part 1–4, see Refs. 5a–d.
* Corresponding author. Tel.: þ81 92 642 2720; fax: þ81 92 642 2735.
E-mail address: shinmyo@ms.ifoc.kyushu-u.ac.jp (T. Shinmyozu).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.11.087

T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
977
Figure 1. Three pyromellitic diimide-based macrocycles 1, 2, and 3 and their CPK presentations.
a tetracationic host, cyclobis(paraquat-p-phenylene), in CH3CN, and
elucidated the crystal structures of the inclusion complexes of the
1,4- and 1,2-dimethoxy-benzenes.6a,b Fujita et al. accomplished the
molecular recognition of 1,3,5-trimethoxybenzene (Ka 750) as well
diamine 8 was synthesized from 2,7-dihydroxynaphthalene 4 by
bromination7 and alkylation of the hydroxyl groups of 5 with hexyl
bromide,8 followed by replacement of the bromine atoms of 6 with
cyano groups and their reduction with DIBAL in toluene. The re-
sultant amine 8 was used for the next coupling reaction without
further purification. The amine 8 was reacted with the pyromellitic
dianhydride in THF at room temperature, and then the reaction
mixture was stirred at 50 ꢂC for 31 h. The resultant amic acids were
dehydrated with Ac2O and AcONa at 100 ꢂC and the crude products
were separated by silica gel column chromatography with CHCl3 to
give the macrocycles 1 (13%) and 9 (9%), respectively.5c
as 1,2-, 1,3-, and 1,4-dimethoxybenzenes (Ka 30, 580, and 330 Mꢀ1
)
by the macrocyclic polynuclear complex [(en)Pd(4,40-bpy)]4(NO3)8,
in water.6c Diederich et al. studied the inclusion phenomena of
octamethoxy-substituted tetraoxa[n.1.n.1]cyclophanes (n¼3 or 4)
and determined the Ka’s for 1,4-dimethoxybenznene in water (n¼4,
Ka 1.02ꢁ104 Mꢀ1; n¼3, Ka 3.7ꢁ102 Mꢀ1) and in MeOH (n¼4, Ka
8 Mꢀ1).6d These results suggested the importance of hydrophobic
interaction for the effective molecular recognition of di- and
trimethoxybenzenes.
2.2. Structural properties
In the present study, investigation of the inclusion properties of
the hosts as structural units of the molecular tubes is of primary
importance and we wish to report here the structural and the
electrochemical properties of the host 1, and its inclusion phe-
nomena of polymethoxybenzenes. We found that uncharged neu-
tral host 1 can recognize polymethoxybenzenes in nonpolar
organic solvent via multiple weak interactions such as CT, electro-
static, van der Waals, and C–H/O hydrogen bonding interactions.
We previously reported the molecular structure of the complex
1$(aniline)7 in the solid state,5c which showed that the trans-
annular pyromellitic diimide p-faces were located parallel to each
other with the average transannular distance of ca. 7.3 Å, and the
two naphthalene rings were coplanar and perpendicular to the
pyromellitic diimide p-faces (Fig. 2). In solution, the rotation of the
diimide moieties and the flipping of the naphthalene rings were
expected. The variable temperature (VT) 1H NMR spectra of 1 in
CD2Cl2 showed a gradual broadening of the signals assigned to the
diimide Ha protons, naphthalene Hb and Hc protons, and methylene
protons Hd as the temperature was lowered, but the coalescence of
these signals was not observed down to 193 K (Fig. 3), suggesting
the mobility of 1 even at 193 K as expected. MO calculations
2. Results and discussion
2.1. Synthesis
In the previous communication, we reported the coupling re-
action of pyromellitic dianhydride with 2,2-bis(aminomethyl)-3,6-
dihexyloxynaphthalene 8.5c We describe here the synthesis of the
diamine 8 and the coupling products 1 and 9 (Scheme 1). The
(B3LYP/6-31G ) suggested that the parallel-conformer is more sta-
*
ble than the syn-one by 1.71 kcal/mol (Fig. 4),9 whereas the possible
anti-one, in which two naphthalene rings are located in the

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T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
Scheme 1. Synthesis of pyromellitic diimide-based macrocycles 1 and 9.
opposite positions, is less stable than the syn-one and it is not the
stable conformer with a local minimum energy. Thus the parallel-
conformer was predicted to be the most stable and the conforma-
tions of 1 in the solid state were all parallel-ones.10 The crystal
packing force may also contribute to the stability of the parallel-
conformation to some extent.
2.3. Electrochemical properties
The cyclic voltammetric traces of 1 and 2 were recorded in a 1,2-
dichlorobenzene solution in the presence of n-Bu4NPF6 as the
supporting electrolyte (Fig. 5, Table 1). The host 2 with the trans-
annular distance of two diimide
p-faces being ca. 5.0 Å exhibited
the first two-electron reduction followed by the second two-
Figure 2. Crystal structure of the clathrate between 1 and aniline. The anilines outside
of the cavity of 1 were omitted for clarify.
Figure 3. The VT 1H NMR spectra of 1 in CD2Cl2 (5ꢁ10ꢀ3 M, 500 MHz).

T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
979
Figure 4. Two optimized structures of 10 based on MO calculation (Gaussian 03, B3LYP/6-31G
anti-conformer.
*
). The hexyloxy groups were converted to methoxy groups along with a sketch of the
Table 1
Potential (V vs Fc/Fcþ) for reduction processes of 1 and 2
redE1
redE2
redE3
redE4
1E1/2
1
2
ꢀ1.43
ꢀ1.42
ꢀ2.03
ꢀ2.25
ꢀ2.13
ꢀ2.41
ꢀ1.31
ꢀ1.29
ꢀ1.51
All electrochemical measurements were performed in o-dichlorobenzene solution
(5ꢁ10ꢀ4 M) containing 0.1 M tetra-n-butylammonium hexafluorophosphate at the
scan rate of 200 mV sꢀ1
.
electron reduction and each reduction process was split into two
waves (E1 ꢀ1.42; E2 ꢀ1.51 V and E3 ꢀ2.25; E4 ꢀ2.41 V vs Fc/Fcþ).
Although no splitting was observed in the first two-electron re-
duction in 1 (E1 and E2 1.43 V vs Fc/Fcþ) with the transannular
distance of two diimide p-faces being ca. 7.3 Å, the splitting of the
second two-electron reduction (E3 ꢀ2.03; E4 ꢀ2.13 V vs Fc/Fcþ)
was observed. Pyromellitic diimide shows two reversible one-
electron reductions and the first and second waves are ascribed to
the radical anion and dianion species, respectively.2f,3d,11 The
splitting of the first two-electron reduction in 2 indicated the
electronic repulsion between radical anion species and neutral
species, and the splitting of the second two-electron reduction in 1
and 2 indicated the presence of the electronic repulsion between
radical anion species and dianion species (Fig. 6). These repulsive
interactions may be more significant in 2 than in 1 as evidenced by
the splitting of the first two-electron reduction and the negative
shifts of the reduction potentials E2, E3, and E4 of 2 than the cor-
responding reduction potentials of 1 because of the shorter trans-
annular distance between the imide
p-faces in 2 than in 1. These
results indicated that the electronic repulsion between a neutral
and a radical anion species of the diimide moieties would exist
within ca. 5.0 Å, while that between a radical anion and a dianion
species of the diimide moieties would be more significant and the
interaction may exist even at ca. 7.3 Å. To the best of our knowledge,
this is the first report of the effective distances of electronic in-
teraction between a radical anion and a dianion species of trans-
annular pyromellitic diimide moieties. The first half-wave
potentials (1E1/2) of 1 and 2 were almost the same, indicating the
Figure 5. Cyclic voltammograms of 1 (blue line) and 2 (red line): (a) CV trace from
ꢀ0.5 to ꢀ3 (potential/V vs Fc/Fcþ), (b) CV trace from ꢀ0.5 to ꢀ2.0 (potential/V vs Fc/
Fcþ).

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T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
Figure 6. Proposed reduction processes of 1 and 2.
similar LUMO energy levels in 1 and 2; i.e., the
almost the same in 1 and 2.12
p
-accepting ability is
the similar experiment between 2 and 1,3-dimethoxybenzene, in
which only external binding was possible (Fig. 9b). A wide range of
the Ka values between 1 and the polymethoxybenzenes was
obtained (1.6–31.3 Mꢀ1) and 1,3,5-trimethoxybenzene showed the
largest Ka value (31.3 Mꢀ1), which was comparable to that obtained
by the 1H NMR titration in CDCl3 [32.1ꢃ5.15 Mꢀ1 (R¼0.999)] by
using nonlinear curve fitting with the 1/1 model (1: 1ꢁ10ꢀ3 M).
Although the internal and external bindings could not be distin-
guished by the UV–vis titration study, the Ka value of 0.3 Mꢀ1 for
the external binding between 2 and dimethoxy- and 1,3,5-trime-
thoxybenzenes suggested that the contribution of the external
binding to the Ka value was quite small.
2.4. Inclusion properties
In the 1H NMR titration study of 1 with 1,3-dimethoxybenzene
in CDCl3, the gradual upfield shift (Dd ꢀ0.23 ppm) of the aromatic
proton signal Ha of the diimide moieties and the corresponding
downfield shift (Dd 0.21 ppm) of the inner naphthalene proton
signal Hb were observed by addition of 10 M equiv of the guest,
while the outer naphthalene proton signal Hc remained intact
(Fig. 7). These complexation shifts suggested the internal binding of
the guest in a parallel fashion.
The p-donating abilities estimated by the wavelength of the CT
On the other hand, the negligible 1H NMR complexation shift of
the Ha’ proton signal of 2 (Dd ꢀ0.01 ppm) was ascribed to the ex-
ternal binding (Fig. 8). Previously we reported that the Ka value
obtained by the UV–vis titration method between 2 and 1,4-
dimethoxybenzene was 0.3 Mꢀ1 in CHCl3 and the small Ka value
was ascribed to the external binding because of the small cavity
size.5b The Ka values of 1 with other polymethoxybenzenes were
obtained by the UV–vis titration method since the 1H NMR com-
plexation shifts of polymethoxybenzenes were small except for
1,3,5-trimethoxy- and 1,3-dimethoxybenzenes. By employing the
CT band as a quantitative spectroscopic probe and then subjecting
the data to a Benesi–Hildebrand treatment, the 1:1 stoichiometry
was established and the Ka values were obtained in CHCl3 as is
summarized in Tables 2 and 4.13,14 As a typical example, the CT
spectral changes as an addition of the increasing amounts of 1,3-
dimethoxybenzene to 1 in CHCl3 was shown in Figure 9a along with
bands (lCT) and oxidation potentials (Eox) of dimethoxybenzenes
are in the order of 1,4-dimethoxybenzene>1,2-dimethox-
ybenzenez1,3-dimethoxybenznene (Table 3),15 whereas the Ka
values of 1 with dimethoxybenzenes in CHCl3 are in the following
order: 1,3-dimethoxybenzene (9.2 Mꢀ1)>1,2-dimethoxybenzene
(6.5 Mꢀ1)>1,4-dimethoxybenzene (2.8 Mꢀ1) (Table 4). This dis-
agreement between the order of the magnitude of the CT in-
teraction and that of the Ka values suggested the presence of other
weak interactions. In order to obtain more detailed information on
the structures of the complexes and elucidate the difference of the
Ka values in dimethoxybenzenes, crystal structures of the com-
plexes were investigated by the X-ray structural analysis.
The ORTEP drawings and space filling representations as well as
the top views of the structures of 1,2-dimethoxybenzene@1, 1,3-
dimethoxybenzene@1, and 1,4-dimethoxybenzene@1 are shown in
Figures 10 and 11. In all complexes, one guest molecule was
Figure 7. 1H NMR spectra (300 MHz) of 1 in CDCl3 at 5ꢁ10ꢀ3 M in the presence of 0–10 equiv of 1,3-dimethoxybenzene.

T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
981
Figure 8. 1H NMR spectra (300 MHz) of 2 in CDCl3 at 5ꢁ10ꢀ3 M in the presence of 0–10 equiv of 1,3-dimethoxybenzene.
Table 2
Association constants Ka’s between 1 or 2 and guest molecules in CHCl3 (298 K)
Table 3
The oxidation potentials of the guest molecules and the maximum absorption
wavelength of the CT bands of the CT complexes between 1 and the guest molecules
Guest compounds
Ka (Mꢀ1
)
Guest compound
Eox (V vs Fc/Fcþ)a
lCT (nm)b
1
2
1,2-Dimethoxybenzene
1,3-Dimethoxybenzene
1,4-Dimethoxybenzene
1.15
1.15
0.94
383
370–390 (br)
400
1,2-Dimethoxybenzene
1,3-Dimethoxybenzene
1,4-Dimethoxybenzene
6.5ꢃ0.2
0.3ꢃ0.07
0.3ꢃ0.04
0.3ꢃ0.03a
9.2ꢃ0.02
2.8ꢃ0.1
a
All electrochemical measurement was performed in CH2Cl2 solution (5ꢁ10ꢀ4 M)
a
The association constant was reported in Ref. 5b.
containing 0.1 M n-Bu4NPF6 at scan rate of 200 mV sꢀ1
.
b
All CT bands were measured in CHCl3.
Table 4
Association constants Ka’s between 1 or 2 and guest molecules in CHCl3 (298 K)
Entry
Guest compounds
Ka (Mꢀ1
)
1
2
1
2
3
1,3,5-Trimethoxybenzene
1,2,3-Trimethoxybenzene
1,2,3,5-Tetramethoxybenzene
31.3ꢃ2.9a
1.8ꢃ0.02
1.6ꢃ0.08
0.3ꢃ0.04
<0.1
<0.1
a
The association constant was calculated by nonlinear curve fitting with the 1/1
model using the UV–vis titration data of the charge transfer band, and determined to
be 3.1ꢃ0.29ꢁ10 Mꢀ1 (R¼0.996).
included between the pyromellitic diimide
p-faces in a parallel
fashion and the cavity size of the host 1 was ca. 7.0ꢁ7.8 Å. In ad-
dition, other guest molecules weakly interacted with the imide
moiety outside of the cavity (Fig. 10).
The electrostatic potential surfaces (EPSs) predicted that 1 has the
electron-deficient surface in the pyromellitic diimide moieties, while
the benzene rings of dimethoxybenzenes have the electron-rich
surfaces (Fig. 12). The surface of the carbonyl carbon atoms of
the diimide moieties is highly electron-deficient, while that of the
methoxy oxygen atoms of the guest is electron-rich. The fact that
the oxygen atoms of the methoxy groups are located just below the
carbonyl carbons of the diimide moieties at two positions in the 1,3-
dimethoxybenzene@1 in the solid state suggested the presence of
electrostatic interactions between them, while the overlap is present
in only one position in 1,4-dimethoxybenzene@1 and one complete
and one partial overlap were observed in 1,2-dimethoxybenzene@1
(Fig. 11). Thus the magnitude of the electrostatic interactions was
expected to be in the order of 1,3-dimethoxybenzene>1,2-
dimethoxybenzene>1,4-dimethoxybenznene.
Furthermore, the crystal data suggested the short contacts between
an oxygen atom of the methoxy group and a-hydrogen atoms of the
naphthalene ring (d1: 2.49 and d2: 2.58 Å as well as d3: 2.62 and d4:
2.57 Å) in 1,3-dimethoxybenzene@1 (Fig. 13), which are similar to or
within the sum of van der Waals radii of oxygen and hydrogen atoms
(2.61 Å). Similarly, a pair of C–H/O short (d1: 2.61 and d2: 2.59 Å) and
longer contacts (d3: 3.13 and d4: 2.87 Å) are present in 1,2-dimethox-
ybenzene@1, while only one pair of C–H/O short contacts exists (d1:
2.45 and d2: 2.50 Å) in 1,4-dimethoxybenzene@1. Bishop et al. pro-
posed the presence of the ether-1,3-peri aromatic hydrogen interaction
Figure 9. (a) Absorption spectra of 1 in CHCl3 (1ꢁ10ꢀ3 M) in the presence of 0–
500 equiv of 1,3-dimethoxybenzene. (b) Absorption spectra of 2 in CHCl3 (1ꢁ10ꢀ3 M)
in the presence of 0–1500 equiv of 1,3-dimethoxybenzene.

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T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
Figure 10. ORTEP drawing and space filling model of the crystal structures of host–guest complexes between 1 and 1,2-, 1,3- or 1,4-dimethoxybenzene. (a), (d) 1,2-Dimethox-
ybenzene@1, (b), (e) 1,3-dimethoxybenzene@1, (c), (f) 1,4-dimethoxybenzene@1. Hydrogen atoms and the guest molecules outside of the cavity of 1 are omitted for clarity.
as a stabilizing interaction of oxygenated diquinoline derivatives in the
crystal structures, in which the ether oxygen atom interacts with two
1,3-peri hydrogens of the quinoline ring of a second molecule with the
C–H/O distances being 2.57 and 2.66 Å.16
and these data fulfill the requirements of the optimum geometries
for the ether-1,3-peri aromatic hydrogen interaction. The magnitude of
this C–H/O interaction may be decreased in the following order: 1,3-
dimethoxybenzene>1,2-dimethoxybenzene>1,4-dimethoxybenznene,
and this order is the same as that of the electrostatic interaction. Thus
the molecular recognition of dimethoxybenzenes in 1 was ascribed to
the combination of the CT, electrostatic, C–H/O, and van der Waals
interactions.6,17
The optimum geometry for the ether-1,3-peri aromatic hydrogen
interaction requires two equal and short C–H/O distances, with the
aromatic and ether planes are orthogonal, and with the ether oxygen
atom lying in the aromatic plane. In the crystal structures of dime-
thoxybenzene@1, the naphthalene and ether planes are almost
orthogonal (1,3-dimethoxybenzene@1: 87.3 and 85.3ꢂ; 1,2-dime-
thoxybenzene@1: 85.0 and 87.9ꢂ; 1,4-dimethoxybenzene@1, 90.0ꢂ)
and the oxygen atoms are located in the plane of the naphthalene
ring (1,3-dimethoxybenzene@1: 0.38 and 1.93 Å; 1,2-dimethox-
ybenzene@1: 1.83 and 0.33 Å; 1,4-dimethoxybenzene@1, 0.42 Å),
Then inclusion behavior between 1 and polymethoxybenzenes
with more than three methoxy groups was examined and much
Figure 11. Top views of the crystal structures of the host–guest complexes. The guests
outside of the cavity and hydrogen atoms of 1 were omitted for clarity: (a) 1$1,2-di-
methoxybenzene, (b) 1$1,3-dimethoxybenzene, (c) 1$1,4-dimethoxybenzene.
Figure 12. Electrostatic potential surfaces: (a) 1 and (b) 1,2-, 1,3-, and 1,4-Dimethox-
ybenzene and 1,3,5-trimethoxybenzene (B3LYP/6-31G**//B3LYP/6-31G ).
*

T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
983
Figure 14. Optimized structure of 1,3,5-trimethoxybenzene@10 calculated by MO
18
calculation (Gaussian 09, M06/6-31G
*
,
The hexyloxy groups were replaced with
methoxy groups in 1.).
Table 5
The oxidation potentials of the guest molecules and the maximum absorption
wavelength of the CT bands of the CT complexes between 1 and the guest molecules
Guest compound
Eox (V vs Fc/Fcþ)a
lCT (nm)b
1,3,5-Trimethoxybenzene
1,2,3-Trimethoxybenzene
1,2,3,5-Tetramethoxybenzene
1.14
1.04
0.68
375
370–390 (br)
390–450 (br)
a
All electrochemical measurements were performed in dichloromethane solu-
tion (5ꢁ10ꢀ4 M) containing 0.1 M tetra-n-butylammonium hexafluorophosphate at
scan rate of 200 mV sꢀ1
.
b
All CT bands were measured in CHCl3.
a-hydrogen atoms of the naphthalene ring compared to the corre-
sponding interactions expected for 1,3-trimethoxybenzene@1. In ad-
dition, van der Waals interactions are expected to be more significant in
1,3,5-trimethoxybenzene@1 than 1,3-dimethoxybenzene@1. The
similar oxidation potentials and the wavelengths of the CT bands of
Figure 13. Top views of the crystal structure of host–guest complexes. The guests
outside of the cavity and hexyloxy groups of 1 were omitted for clarity. (a) 1,2-Di-
methoxybenzene@1: d1¼2.61 Å, d2¼2.59 Å, d3¼3.13 Å, and d4¼2.87 Å. (b) 1,3-Dime-
thoxybenzene@1: d1¼2.49 Å, d2¼2.58 Å, d3¼2.62 Å, and d4¼2.57 Å. (c) 1,4-
dimethoxybenzene@1: d1¼2.45 Å, d2¼2.50 Å.
smaller Ka values were obtained for 1,2,3-trimethoy- (1.8 Mꢀ1) and
1,2,3,5-tetramethoxy-benzene (1.6 Mꢀ1) compared to that of 1,3,5-
trimethoxybenzene (31.3 Mꢀ1) (Table 4).
18
The optimized structure (M06/6-31G
*
)
of 1,3,5-trimethox-
ybenzene@1 predicted the similar host–guest overlap to that of 1,3-
trimethoxybenzene@1, while the naphthalene ring of 1,3,5-trime-
thoxybenzene@1 was slightly deviated from planarity (Fig. 14). This
Figure 15. Optimized structures of 1,2,3-trimethoxybenzene by MO calculations
(Gaussian03, B3LYP/6-31G )
19. (a) Top view. (b) Side view. (c) Side view of the crystal
*
suggested the presence of the C–H/p interactions between the
structure of the CT complex between 1 and 1,3-dimethoxybenzene. Two pyromellitic
diimide moieties and the included 1,3-dimethoxybenzene were presented by the space
filling model. 1,3-Dimethoxybenzene outside of the cavity was omitted for clarity.
methoxy methyl groups and the naphthalene rings and more suitable
C–H/O interactions of the oxygen atom of the methoxy groups and

984
T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
1,3-dimethoxy- (1.15 V vs Fc/Fcþ; lmax 370–390 nm) and 1,3,5-trime-
thoxybenzenes (1.14 V vs Fc/Fcþ; lmax 375 nm) suggested their similar
magnitude of the CT interactions (Table 5). Thus the large Ka value of
1,3,5-trimethoxybenzene@1 may be attributable to the multipoint
1,3,5-trimethoxybenzene, and CV traces for guest molecules. CCDC
reference number 718293, 718294 and 724380. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2009.11.087.
interactions such as C–H/p, C–H/O, van der Waals, electrostatic in-
teractions along with CT interactions.
Based on the crystal structures of dimethoxybenzene@1, the
smaller Ka value of 1,2,3-trimethoxybenzene (1.8 Mꢀ1) may be as-
cribed to the fact that the 1,2,3-trimethoxybenzene cannot take
a suitable structure in the cavity of 1, which enables the CT, elec-
trostatic, and C–H/O interactions effective since the structure, in
which all the methoxy groups are located in the same plane of the
benzene ring, would be unfavorable due to the steric hindrance of
References and notes
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the three consecutive methoxy groups. The B3LYP/6-31G calcula-
*
tions19–23 most optimized the conformation with two coplanar
methoxy groups (Fig. 15). Deviation of a methoxy group from the
plane of the benzene ring would inhibit insertion of 1,2,3-trime-
thoxybenzene into the cavity of 1. Irrespective of the significantly
strong electron-donating ability of 1,2,3,5-tetramethoxybenzene,
the low Ka value (1.6 Mꢀ1) similar to that of 1,2,3-trimethox-
ybenzene was obtained probably due to similar steric reasons.
3. Conclusions
The parallel-conformation of 1 was observed in the crystal
structure of dimethoxybenzene@1 and this conformation was
expected to be the most stable one by MO calculations. In the
electrochemical study, the effective distance of the electronic re-
pulsive interactions between the radical anion and dianion was
expected to be ca. 7.3 Å, which is longer than those between the
radical anion and neutral species of the imide moieties (ca. 5.0 Å).
Although quantitative analysis of the responsible weak molecular
interactions is impossible at present, we found that 1 can recognize
polymethoxybenzenes by the multipoint interactions such as CT,
6. (a) Odell, B.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.;
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electrostatic, van der Waals, the C–H/O, and C–H/p interactions
in organic solvent. Thus molecular recognition of poly-
methoxybenzenes has been accomplished by the neutral host 1 in
nonpolar organic solvent, CHCl3. The synthesis of organic molecular
tubes by the stepwise connection of the functionalized host 1 is in
progress and the result will be reported elsewhere.
´
M.; Chou, A. J. Org. Chem. 1988, 53, 5595; (e) Ferrer, M.; Gutierrez, A.; Mounir,
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groups in 1, and sum of electronic and zero-point energies were calculated to
be ꢀ1863381.421 (parallel-10) and ꢀ1863379.711 (syn-10) kcal/mol,
respectively.
Acknowledgements
10. Even in solution, the parallel-conformer of 1 was expected to be a dominant
conformer by the comparison of the 1H NMR spectra of 1 and 9. The chemical
shifts of the proton signals of 1 and 9 are similar except for the inner naph-
thalene proton signals Hb, which showed the upfield shift in 1 (Dd¼0.41 ppm)
compared to that in 9. This upfield shift due to the ring current effect of the
pyromellitic diimide moieties was ascribed to the preferred parallel-confor-
mation of 1. While the optimized structure of 90 based on MO calculations
The computation was mainly carried out in the computer fa-
cilities at Research Institute for Information Technology, Kyushu
University. We thank Dr. Yoshihiro Watanabe (Kyushu University)
for the M.O. calculations. T.N. is grateful for the partial financial
support by the Front Researcher Development Program from the
Graduate School of Sciences, Kyushu University. We wish to thank
the Theme Project (Professor Tahsin J. Chow), Institute of Chemis-
try, Academia Sinica, Taiwan R.O.C., for the financial support of this
study. We also gratefully thank the financial support by a Grant-in-
Aid for Scientific Research on Innovative Areas (No. 21106015) from
the Ministry of Education, Culture, Sports, Science and Technology,
Japan.
(Gaussian 03, B3LYP/6-31G ) assumes a twisted conformation in which the Hb
*
protons are hardly influenced by the ring current effect of the pyromellitic
diimide moieties. In the MO calculations, the hexyloxy groups were replaced
with methoxy groups in 9.
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12. This is also supportedby MO calculations (B3LYP/6-31G ). The LUMO energy level
*
of 1 is ꢀ2.977 eV, which is similar to that of 2 reported in Ref. 5b (ꢀ3.004 eV). The
coordinate of the X-ray crystal analysis was used in these calculations.
13. (a) Benesi, H. A.; Hildebrand, J. H. J. Am. Chem. Soc. 1949, 71, 2703; (b) Person,
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Supplementary data
14. The Ka values of 1 with 1,2-, 1,3-, and 1,4-dimethoxybenzenes as well as 1,3,5-tri-
methoxybenzene obtained by the 1H NMR titration method in CDCl3 by using
nonlinear curve fitting with the 1/1 model were comparable to those obtained by
theUV–vistitrationmethod:Ka¼4.57ꢃ1.61 Mꢀ1, R¼0.998(1,2-dimethoxybenzene),
General experimental methods, 1H and 13C NMR spectra of 1, 7, 8,
and 9, UV–vis spectra 1 and 1 plus guest molecules, UV–vis spectra 2
and 2 plus guest molecules,1H NMRobservations of 1 and 2 recorded
in CDCl3 in the presence of guest molecules, structural data for the X-
ray analyses, calculated coordinate and total energies of optimized
structure of parallel-10, syn-10, 90, 1,2,3-trimethoxybenzene, and
1,3,5-trimethoxybenzene@10, calculated coordinate of 1,2-dime-
thoxybenzene, 1,3-dimethoxybenzene, 1,4-dimethoxybenzene, and
9.54ꢃ1.21 Mꢀ1
,
R¼0.999 (1,3-dimethoxybenzene), 3.36ꢃ2.03 Mꢀ1
R¼0.997
,
(1,4-dimethoxybenzene), and 32.1ꢃ5.15 Mꢀ1, R¼0.999 (1,3,5-trimethoxybenzene).
15. The electron-donating ability of the guests was estimated by the oxidation po-
tentials and the wavelengths of the CT bands obtained by the CV measurements
and UV–vis spectra, respectively. Based on these data, the electron-donating
ability of 1,4-dimethoxybenzene was the strongest in dimethoxybenzenes and
1,2,3- and 1,3,5-trimethoxybenzenes.

T. Nakagaki et al. / Tetrahedron 66 (2010) 976–985
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