Solvophobically driven self-association of a butadiyne-bridged pyridine macrocycle

Article abstract of DOI:10.1016/j.tet.2008.08.058

A butadiyne-bridged square-shaped pyridinophane 2b having ester groups derived from triethylene glycol monomethyl ether was prepared and its self-assembling properties were investigated to assess the repulsive dipole-dipole interaction in less polar solvent and solvophobic driving force in polar solvents. Concentration-dependent ¹H NMR spectra showed that whereas 2b did not self-assemble in chloroform-d, it did in polar solvents consisting of chloroform-d and methanol-d₄ (4:6 to 6:4) with increasing association constants with the increasing methanol-d₄ composition. Comparison of the free energies of association with those of the previously reported benzene macrocycle 1b indicates that solvophobically induced self-association of 2b is more promoted than 1b. The reasons for this difference are discussed from both enthalpy and entropy points of view.

Full text of DOI:10.1016/j.tet.2008.08.058

Tetrahedron 64 (2008) 11490–11494
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Solvophobically driven self-association of a butadiyne-bridged
pyridine macrocycle
*
Motohiro Sonoda, Yui Yamaguchi, Kazukuni Tahara, Keiji Hirose, Yoshito Tobe
Division of Frontier Materials Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka 560-8531, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 June 2008
Received in revised form 21 July 2008
Accepted 20 August 2008
Available online 26 August 2008
A butadiyne-bridged square-shaped pyridinophane 2b having ester groups derived from triethylene
glycol monomethyl ether was prepared and its self-assembling properties were investigated to assess the
repulsive dipole–dipole interaction in less polar solvent and solvophobic driving force in polar solvents.
Concentration-dependent 1H NMR spectra showed that whereas 2b did not self-assemble in chloroform-d,
it did in polar solvents consisting of chloroform-d and methanol-d4 (4:6 to 6:4) with increasing asso-
ciation constants with the increasing methanol-d4 composition. Comparison of the free energies of as-
sociation with those of the previously reported benzene macrocycle 1b indicates that solvophobically
induced self-association of 2b is more promoted than 1b. The reasons for this difference are discussed
from both enthalpy and entropy points of view.
This work is dedicated to Professor Reginald
H. Mitchell on the occasion of his 65th
birthday.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Macrocycles
Self-assembly
Solvophobic effect
Butadiynes
Shape-persistent molecules
1. Introduction
Inouye reported that acyclic pyridinylene–enthynylene oligomers
and polymers having polar oligoethylene glycol side chains adopt in
Macrocyclic metaphenylene–ethynylene, metaphenylene–buta-
diynylene, and their hybrid oligomers constitute a central class of
shape-persistent molecules,1 which have been attracting much in-
terest because of their self-assembling properties in solution,2 solid,3
and liquid crystalline phases,4 as well as at interfaces or on surfa-
polar solvents a helical conformation.7 It should be pointed out that
the polymers adopt the stacking geometry even though they possess
substituents of electron-donating nature, which generally inhibit
aromatic stacking even in polar media.2c,8 The thus formed one-di-
mensionalcavitywasusedtobindsaccharidederivativesbyhydrogen
bonding interaction. It is, therefore, expected that, for a pyridine-
containing macrocycle, solvophobic interaction would overcome the
repulsive dipole–dipole interaction to promote self-association in
polar solvents if it is soluble in such media. To provide an answer to
this question and to obtain a rough estimate of the relative energies of
the attractive and repulsive interactions, we investigated self-asso-
ciation behavior of square-shaped pyridinylene–butadiynylene
macrocycle 2b in polar solvents.
ces.2g,3d,4d,5 In solution aggregation is driven by
p–p stacking in-
teraction, mainly in less polar solvents such as chloroform, and/or
solvophobic interaction in polar solvents. Self-assembly due to
stacking of macrocycles containing pyridine rings in solution,3c,d,6
however, wasnot reportedexcept for the followingexamples because
of electrostatic repulsion owing to dipole–dipole interaction of the
pyridine rings. Association was observed only when other driving
force was provided as in the size-selective heteroassociation of pyr-
idinylene–butadiynylene macrocycles with the corresponding ben-
zene macrocycles due to electrostatic interaction,6a solvophobically
driven aggregation of a macrocycle containing pyridine substituents
by a nonpolar solvent (cyclohexane),6b dimerization of a macrocycle
possessing positively charged interior pyridinium ion moieties,6b and
the formation of a dimeric metal complex of a macrocycle having
exterior nitrogen atoms for coordination.6e By contrast, Abe and
* Corresponding author. Tel.: þ81 6 6850 6225; fax: þ81 6 6850 6229.
E-mail address: tobe@chem.es.osaka-u.ac.jp (Y. Tobe).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.058

M. Sonoda et al. / Tetrahedron 64 (2008) 11490–11494
11491
Previously, we synthesized and investigated self-association of
octyl ester-substituted square macrocycle 1a in chloroform. Since 1a
was not soluble in polar solvents consisting of chloroform and
methanol, we prepared the corresponding ester 1b of triethylene
glycol monomethyl ether (TEG). Extrapolation of the free energies of
association of 1b in chloroform/methanol (8:2 to 3:7) mixtures to
pure chloroform and methanol, assuming infinite association with
with TEG followed by palladium-catalyzed cross coupling with
(trimethylsilyl)acetylene. Oxidative coupling of 3a gave dimer 4a,
the protecting groups of which were exhaustively removed to
give 4c. Oxidative coupling of 4c under the usual Eglington
coupling conditions gave the desired cyclic tetramer in a poor
yield of 4%. Alternatively, partial deprotection of 4a gave mono-
protected dimer 4b, the oxidative coupling of which gave linear
tetramer 5a. After deprotection of 5a, intramolecular coupling of 5b
under high dilution conditions afforded 2b in 24% yield (overall 5%
from 4a).
equal association constants, yielded a rough estimate of
D
G of ꢀ7.2
and ꢀ31.2 kJ molꢀ1, respectively.2f These results suggest that if the
contributing driving forces of self-association can be divided into
aromatic
p
–
p
stacking interaction of dispersive and electrostatic
Self-association of 2b was investigated on the basis of concen-
tration-dependent 1H NMR chemical shifts in chloroform-d/meth-
anol-d4 mixtures (4:6 to 6:4). The upfield shift (0.1–0.3 ppm) of the
pyridine ring proton of 2b was observed as its concentration in-
creased, indicating solvophobically induced aggregation. However,
because of the limited solubility of 2b in methanol-enriched sol-
vents and the small chemical shift change in chloroform-enriched
solvents, the dilution experiments were carried out within a rela-
tively narrow range of solvent composition. The chemical shift
change was analyzed with the infinite association model of equal
association constants (KE),2b,c,f,13 because oligomeric aggregation
of shape-persistent macrocycles is most likely to occur in polar
media.2 Table 1 shows KE and the corresponding free energies of
natures9 and solvophobic intereaction,1d,8,10 though they are gener-
ally collective and difficult to separate, it may be possible to estimate
the relative magnitude in polar and less polar solvents. Assuming
that, for example, the magnitude of
p–p stacking interaction is
constant in chloroform and methanol11 and that the solvophobic
interaction is absent in pure chloroform,12 we can assess the sol-
vophobic contribution to
significantly larger compared to p–p stacking force in chloroform. In
D
G of ꢀ24.2 kJ molꢀ1 in methanol, which is
contrast to 1a, the corresponding pyridine analog 2a did not self-
assemble in chloroform presumably owing to the dipole–dipole
repulsion.6a While 2a was not soluble in polar solvents, its TEG ester
derivative 2b would be soluble in polar solvents and thus would
provide an estimate of dipole–dipole repulsion on the basis of the
above assumptions. In this connection, we prepared 2b and exam-
ined its self-association behavior in polar solvents.
Table 1
Association constants and the corresponding free energies for self-aggregation of
square-shaped pyridine macrocycle 2b in polar solvents at 303 Ka
2. Results and discussion
Solvent
KE (Mꢀ1
)
D )
G (kJ molꢀ1
The synthesis of 2b was carried out by oxidative dimerization of
the dimer unit 4c or intramolecular cyclization of linear tetramer
5b as shown in Scheme 1. The unsymmetrically protected mono-
mer unit 3b was obtained by partial deprotection of 3a, which was
obtained from dichloropyridinecarboxylic acid by esterification
CDCl3/CD3OD¼6:4
CDCl3/CD3OD¼5:5
CDCl3/CD3OD¼4:6
15ꢁ1
85ꢁ9
ꢀ6.8ꢁ0.2
ꢀ11.2ꢁ0.3
ꢀ14.6ꢁ0.6
327ꢁ64
a
Determined on the basis of the infinite association model of equal association
constants.
CO2TEG
N
CO2TEG
CO2TEG
Cu(OAc)2-H2O
Pyridine
N
N
R2
R1
R1
R2
4a R1=R2=TMS
4b R1=H, R2=TMS
4c R1=R2=H
3a R1=R2=TMS
3b R1=H, R2=TMS
3c R1=R2=H
TBAF
H2O, THF
TBAF
H2O, THF
CuCl, TMEDA
O2, acetone
Cu(OAc)2-H2O
Pyridine
TEGO2C
CO2TEG
N
N
Cu(OAc)2-H2O
Pyridine
2b
TEGO2C
TBAF
CO2TEG
N
N
R1
R2
TEG=(OCH2CH2)3OCH3
5a R1=R2=TMS
5b R1=R2=H
H2O, THF
Scheme 1. Synthesis of macrocycle 2b.

11492
M. Sonoda et al. / Tetrahedron 64 (2008) 11490–11494
40
30
20
10
0
reduction of repulsive dipole–dipole interaction between the
pyridine rings and increased electrostatic interaction both
through weak hydrogen bonding with the solvent. These results
provide additional aspects in self-assembly of shape-persistent
macrocycles particularly with those containing heterocyclic
components.
3. Experimental section
3.1. Synthesis of 3a
-10
-20
-30
To an ice-cooled solution of 2,6-dichloropyridine-4-carboxylic
acid (989 mg, 5.15 mmol), 4-(dimethylamino)pyridine (105 mg,
0.859 mmol), triethylene glycol monomethyl ether (1.05 g,
6.37 mmol) in 45 mL of 1,2-dichloroethane was slowly added
a suspension of 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide
hydrochloride (1.22 g, 6.37 mmol) in 15 mL of 1,2-dichloroethane.
The mixture was stirred at room temperature for 70 h. CHCl3 and
water were added to the mixture. The mixture was acidified with
0.5 N HCl, the organic layer was washed with saturated NaHCO3
solution and saturated NaCl solution, and dried over MgSO4. After
removal of the solvent, the product was purified by chromatogra-
phy on silica gel to give 1.50 g (86%) of TEG ester of 2,6-dichloro-
pyridine-4-carboxylic acid as a pale yellow oil. 1H NMR (400 MHz,
0
20
40
60
volume % of CD OD in CDCl
80
100
3
3
Figure 1. Relationship between ꢀ
DG of aggregation of macrocycles 1b and 2b and the
composition of CD3OD in CDCl3; solid circle: 1b (Ref. 2f), solid square: 2b.
association. The free energies (ꢀ
DG) were plotted against the sol-
vent composition as shown in Figure 1, from which we estimate
that the association in pure chloroform is endoergonic by
8.52 kJ molꢀ1, being consistent with the absence of aggregation in
this solvent. Figure 1 also indicates that the free energy of associ-
ation in pure methanol would be ꢀ30.22 kJ molꢀ1; the difference
CDCl3)
3.57 (m, 6H), 3.49–3.46 (m, 2H), 3.31 (s, 3H); 13C NMR (75 MHz,
CDCl3) 162.3, 151.0, 142.2, 122.4, 71.7, 70.5, 70.42, 70.39, 68.5, 65.3,
D 7.76 (s, 2H), 4.48–4.45 (m, 2H), 3.80–3.77 (m, 2H), 3.67–
d
58.8; IR (neat) 3086, 2876, 2822, 1736, 1583, 1548, 1455, 1415, 1359,
1283, 1156, 1110, 1028, 893, 816, 765, 738 cmꢀ1; HRMS (FAB) found:
338.0566 (Mþþ1), Calcd for C13H18NO5Cl2: 338.0562.
between the
D
Gs in two solvents of 2b (ca. 39.2 kJ molꢀ1) is sig-
nificantly larger than that of 1b (24.2 kJ molꢀ1). In other words, the
aggregation of 2b is more sensitive to the solvent polarity than
that of 1b, indicating that there must be additional stabilizing
forces for aggregation of 2b in polar solvents in addition to the
solvophobic force. From the enthalpy aspect, because the pyridine
unit of 2b would be better solvated than the benzene unit of 1b in
polar solvents, the observed trend is contradictory to the expecta-
tion. However, the dipole–dipole repulsion must be reduced with
increasing solvent polarity. Moreover, hydrogen bonding between
the solvent and the nitrogen atom of the pyridine ring would
promote self-association by electrostatic interaction. Indeed, as an
extreme case, protonation of the pyridine rings of pyridinylene–
ethynylene polymers with trifluoroacetic acid was shown to
promote helix formation by favorable electrostatic interaction.14
Hence, the difference between the response to the solvent polarity
of 1b and 2b can be attributed to the reduction of repulsive dipole–
dipole interaction and the increase of attractive electrostatic
interaction between the pyridine rings of 2b in polar solvents. On
the other hand, from the viewpoint of entropy, the formation of
hydrogen bonding network of the polar solvent (methanol) around
the benzene moieties of 1b would be entropically more unfavorable
than that for the pyridine rings of 2b. To minimize such network
formation, aggregation of benzene macrocycle 1b should be
more strongly promoted than that of pyridine macrocycle 1b,
contrary to the observed tendency. Accordingly, the enhanced self-
association tendency of 2b in polar solvents is mostly likely of
enthalpic origin.
A solution of the above ester (14.8 g, 43.9 mmol), PPh3, (1.11 g,
4.23 mmol), (trimethylsilyl)acetylene (12.3 g, 125 mmol), CuI
(193 mg,1.01 mmol), and Pd2(dba)3$CHCl3 (298 mg, 0.351 mmol) in
200 mL of triethylamine was degassed by bubbling of Ar. The
mixture was then heated at 74 ꢂC for 46.5 h. After cooling, the
mixture was filtered and the filtrate was washed with ether. The
filtrate was concentrated and the residue was chromatographed on
silica gel (hexane/AcOEt¼9:1 to 0:1 as eluent) to give 16.8 g of 3a
(83%) as a yellow oil. 1H NMR (270 MHz, CDCl3)
d
7.91 (s, 2H), 4.53–
4.49 (m, 2H), 3.86–3.82 (m, 2H), 3.73–3.63 (m, 6H), 3.55–3.52 (m,
2H), 3.37 (s, 3H), 0.27 (s, 18H); 13C NMR (75 MHz, CDCl3)
163.3,
d
143.7, 137.7, 125.4, 102.2, 96.4, 71.6, 70.3, 70.2, 68.5, 64.7, 58.6, ꢀ0.6;
IR (neat) 3075, 2959, 2898, 2819, 2162, 1735, 1590, 1549, 1454, 1397,
1330, 1251, 1224, 1190, 1110, 1030, 992, 847, 762 cmꢀ1; HRMS (EI)
found: 461.2048, calcd for C23H35NO5Si2: 461.2054.
3.2. Synthesis of 3b
To a solution of 3a (7.88 g, 17.1 mmol) in 100 mL of water and
300 mL of THF was added slowly over 30 min a solution of TBAF
prepared by diluting a 13 mL of commercially available 1 M THF
solution of TBAF with 87 mL of THF. After addition of 1 N HCl aq, the
mixture was extracted with ether. The extract was washed with
saturated NaCl solution and dried over MgSO4. After evaporation of
the solvents, the product was purified by chromatography on silica
gel (hexane/AcOEt¼19:1 to 1:3 as eluent) to give 1.76 g of 3b (30%)
as a yellow oil together with 1.93 g (25%) of unreacted 3a. 1H NMR
In conclusion, we prepared butadiyne-bridged square-shaped
pyridinophane 2b having ester groups derived from triethylene
glycol monomethyl ether and investigated its self-assembling
properties to assess the repulsive dipole–dipole interaction in less
polar solvent (chloroform-d) and solvophobic driving force in
polar solvent (methanol-d4). Comparison of the free energies of
association with those of the previously reported benzene mac-
rocycle 1b indicates that solvophobically induced self-association
of 2b is more promoted than 1b. The increased self-association
driving force of 2b compared to 1b can be ascribed to the
(300 MHz, CDCl3)
d
7.95 (d, J¼1.4 Hz, 1H), 7.94 (d, J¼1.4 Hz, 1H),
4.53–4.50 (m, 2H), 3.85–3.82 (m, 2H), 3.73–3.63 (m, 6H), 3.55–3.52
(m, 2H), 3.37 (s, 3H), 3.21(s, 1H), 0.28 (s, 9H); 13C NMR (75 MHz,
CDCl3) d 163.7, 144.3, 143.3, 138.2, 126.2, 125.8, 102.3, 97.1, 81.7, 78.6,
71.9, 70.70, 70.66, 70.6, 68.9, 65.2, 59.0, ꢀ0.3; IR (neat) 3232, 3074,
2960, 2876, 2165, 2112, 1733, 1592, 1551, 1454, 1397, 1324, 1249,
1223, 1187, 1109, 1029, 987, 970, 904, 847, 767 cmꢀ1; HRMS (EI)
found: 389.1661; calcd for C20H27NO5Si: 389.1659.

M. Sonoda et al. / Tetrahedron 64 (2008) 11490–11494
11493
3.3. Synthesis of 4a
silica gel column (elution with CHCl3) to remove inorganic salts.
The product was purified by chromatography on silica gel followed
A solution of 3b (2.38 g, 6.12 mmol) in 50 mL of acetone was
bubbled with O2. To this solution was added a solution prepared by
diluting a 4-mL solution of Hay catalyst, prepared from CuI
(265 mg, 2.68 mmol) and TMEDA (114 mg, 0.981 mmol) in 20 mL of
acetone, with 6 mL of acetone, and the mixture was bubbled with
O2. After stirring for 40 h, the mixture was diluted with 1 N HCl and
ether. The organic layer was separated, washed with water and
brine, and dried over MgSO4. The solvent was removed in vacuo,
and the residue was chromatographed on silica gel (hexane/
AcOEt¼9:1 to 1:9 as eluent) to afford 1.91 g (80%) of 4a as a white
solid together with unreacted 3b (0.20 g, 8%). Mp 97–98 ꢂC; 1H
by recycling GPC to afford 4 mg (4%) of 2b as a yellow solid. Mp
1
167 ꢂC (decomposed); H NMR (400 MHz, CDCl3, 30 ꢂC)
d 7.95 (s,
8H), 4.54–4.52 (m, 8H), 3.86–3.84 (m, 8H), 3.74–3.65 (m, 24H),
13
3.57–3.54 (m, 8H), 3.39 (s,12H); C NMR (68 MHz, CDCl3, 30 ꢂC)
d
163.3, 143.5, 138.9, 125.1, 82.3, 74.8, 72.0, 70.8, 70.72, 70.69, 68.9,
65.4, 59.0; IR (KBr) 3077, 2873, 2225, 2152, 1731, 1591, 1542, 1419,
1391, 1350, 1259, 1117, 1026, 945, 848, 767 cmꢀ1; HRMS (FAB)
found: 1261.4498; calcd for C68H69N4O20: 1261.4505.
3.6. Synthesis of 5a
NMR (300 MHz, CDCl3)
d
7.99 (d, J¼1.4 Hz, 2H), 7.98 (d, J¼1.4 Hz,
Hay coupling of 4b (1.93 g, 2.74 mmol) was carried as described
for the preparation of 4a to give 1.58 g (82%) of 5a as a white solid.
2H), 4.54–4.51 (m, 4H), 3.86–3.83 (m, 4H), 3.74–3.64 (m, 12H),
3.56–3.53 (m, 4H), 3.37 (s, 6H), 0.29 (s, 18H); 13C NMR (75 MHz,
Mp 100–101 ꢂC; 1H NMR (270 MHz, CDCl3)
d
8.07 (d, J¼1.3 Hz, 2H),
CDCl3) d 163.4, 144.5, 142.6, 138.2, 126.6, 102.0, 97.5, 80.4, 74.1, 71.9,
8.06 (d, J¼1.3 Hz, 2H), 8.01 (d, J¼1.5 Hz, 2H), 7.99 (d, J¼1.5 Hz, 2H),
4.56–4.51 (m, 8H), 3.87–3.83 (m, 8H), 3.75–3.62 (m, 24H), 3.59–
3.53 (m, 8H), 3.38 (s, 6H), 3. 37 (s, 6H), 0.29 (s, 18H); 13C NMR
70.7, 70.61, 70.57, 68.8, 65.2, 59.0, ꢀ0.4; IR (KBr) 3070, 2969, 2933,
2875, 2824, 2155, 1733, 1590, 1547, 1452, 1396, 1323, 1245, 1225,
1190, 1101, 1023, 976, 950, 932, 904, 849, 767 cmꢀ1; HRMS (FAB)
found: 777.3225; calcd for C40H53N2O10Si2: 777.3239. Anal. Calcd
for C40H53N2O10Si2: C, 61.83; H, 6.75; N, 3.61. Found: C, 61.74; H,
6.73; N, 3.57.
(68 MHz, CDCl3)
d 163.3, 162.9, 144.5, 143.1, 142.9, 142.4, 138.4,
138.2, 127.44, 127.39, 126.6, 126.5, 101.9, 97.5, 80.6, 80.2, 79.9, 74.4,
74.2, 73.8, 71.8, 70.59, 70.56, 70.51, 70.48, 68.7, 68.6, 65.3, 65.1,
58.9, ꢀ0.4; IR (KBr) 3075, 2956, 2874, 2825, 2157, 1732, 1544, 1394,
1322,1225,1111, 854, 768 cmꢀ1; MS (FAB) m/z 1407.3 (MþH)þ. Anal.
Calcd for C74H86N4O20Si2: C, 63.14; H, 6.16; N, 3.98. Found: C, 63.07;
H, 6.23; N, 3.88.
3.4. Synthesis of 4b and 4c
Exhaustive deprotection of 4a (1.91 g, 2.46 mmol) was done by
carrying out the reaction as described for the preparation of 3b for
12 h to give 1.58 g of 4c as a brown solid, which was used without
purification for the preparation of 2b. Analytically pure sample of
4c was obtained in a separate run to prepare 4b.
3.7. Synthesis of 5b
Deprotection of 5a (206 mg, 0.146 mmol) was carried as de-
scribed for the preparation of 4b to give 162 mg (88%) of 5c as
a yellowish brown solid. Mp 119–120 ꢂC; 1H NMR (400 MHz, CDCl3)
When the deprotection was terminated after 1.5 h, mono pro-
tected 4b (828 mg, 31%) was obtained as a white solid, together
with 4c (106 mg, 4%, white solid) and unreacted 4a (1.01 g, 35%).
d
8.07 (two d, J¼1.5 Hz, 4H), 8.05 (d, J¼1.2 Hz, 2H), 8.01 (d, J¼1.2 Hz,
2H), 4.55–4.52 (m, 8H), 3.86–3.83 (m, 8H), 3.72–3.64 (m, 24H),
Compound 4b: mp 78–79 ꢂC; 1H NMR (270 MHz, CDCl3)
d 8.04 (d,
3.56–3.53 (m, 8H), 3.375 (s, 6H), 3.371 (s, 6H), 3.26 (s, 2H); 13C NMR
J¼1.3 Hz, 1H), 8.01 (d, J¼1.3 Hz, 1H), 8.00 (d, J¼1.4 Hz, 1H), 7.98 (d,
J¼1.4 Hz, 1H), 4.55–4.51 (m, 4H), 3.87–3.83 (m, 4H), 3.74–3.64 (m,
12H), 3.56–3.53 (m, 4H), 3.37 (s, 6H), 3.26 (s, 1H), 0.29 (s, 9H); 13C
(100 MHz, CDCl3)
d 163.3, 163.2, 143.9, 143.2, 143.1, 142.7, 138.6,
138.5, 127.62, 127.60, 127.2, 126.8, 81.4, 80.5, 80.3, 80.1, 79.2, 74.5,
74.4, 74.1, 71.9, 70.73, 70.71, 70.66, 70.6, 68.80, 68.78, 65.4, 65.3,
59.1; IR (KBr) 3220, 3073, 2876, 2824, 2155, 2109, 1734, 1589, 1544,
1451, 1394, 1319, 1225, 1187, 1112, 1029, 948, 849, 768 cmꢀ1; HRMS
(FAB) found: 1263.4691; calcd for C68H71N4O20: 1263.4662. Anal.
Calcd for C68H70N4O20$H2O: C, 63.74; H, 5.66; N, 4.37. Found: C,
63.88; H, 5.82; N, 4.23.
NMR (68 MHz, CDCl3) d 163.3, 163.2, 144.5, 143.8, 142.7, 142.5, 138.3,
138.2, 127.0, 126.6, 126.5, 102.0, 97.5, 81.3, 80.4, 80.1, 79.1, 74.1, 73.9,
71.8, 70.61, 70.59, 70.54, 70.52, 68.72, 68.69, 65.23, 65.15, 58.9,
ꢀ0.4; IR (KBr) 3231, 3075, 2955, 2877, 2820, 2152, 2111, 1732, 1590,
1548, 1453, 1396, 1322, 1224, 1189, 1113, 1029, 945, 848, 768 cmꢀ1
;
HRMS (FAB) found: 705.2857; calcd for C37H45N2O10Si: 705.2843;
Anal. Calcd for C37H45N2O10Si: C, 63.05; H, 6.29; N, 3.97. Found: C,
62.89; H, 6.33; N, 3.93. Compound 4c: mp 94–95 ꢂC; 1H NMR
3.8. Synthesis of 2b by intramolecular oxidative
coupling of 5b
(400 MHz, CDCl3)
d
8.05 (d, J¼1.5 Hz, 2H), 8.01 (d, J¼1.5 Hz, 2H),
4.54–4.52 (m, 4H), 3.86–3.84 (m, 4H), 3.73–3.65 (m, 12H), 3.56–
3.54 (m, 4H), 3.38 (s, 6H), 3.26 (s, 2H); 13C NMR (100 MHz, CDCl3)
Intramolecular Eglinton coupling of 5b (189 mg, 0.15 mmol) was
carried out as described for the oxidative dimerization of 4c, except
that pure pyridine was used as the solvent, to give 46 mg (24%) of
2b as a yellow solid.
d
163.4, 143.9, 142.8, 138.5, 127.1, 126.7, 81.4, 80.3, 79.2, 74.2, 71.9,
70.7, 70.65, 70.63, 68.8, 65.3, 59.0; IR (KBr) 3218, 3067, 2987, 2874,
2829, 2162, 2109, 1729, 1590, 1552, 1445, 1396, 1355, 1319, 1228,
1186, 1138, 1111, 1026, 953, 932, 904, 862, 829, 769, 730 cmꢀ1
;
HRMS (FAB) found: 633.2464; calcd for C34H37N2O10: 633.2448.
Anal. Calcd for C34H37N2O10: C, 64.55; H, 5.74; N, 4.43. Found: C,
64.85; H, 5.83; N, 4.42.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan.
3.5. Synthesis of 2b by oxidative dimerization of 4c
To a solution of Cu(OAc)2$H2O (308 mg, 1.70 mmol) in 100 mL of
a mixture of pyridine and benzene (3:2¼v/v) was added a solution
of 4c (95 mg, 0.15 mmol) in 100 mL of the same solvent mixture
through a Hershberg dropping funnel over a 18 h period. The funnel
was rinsed with 40 mL of the solvent mixture and the reaction
mixture was further stirred for 4 h. After most of the solvent was
removed in vacuo, the residue was passed through a short plug of
References and notes
1. For reviews: (a) Moore, J. S. Acc. Chem. Res. 1997, 30, 402–413; (b) Ho¨ger, S.
J. Polym. Sci., Part A 1999, 37, 2685–2698; (c) Grave, C.; Schlu¨ter, A. D. Eur.
J. Org. Chem. 2002, 3075–3098; (d) Zhao, D.; Moore, J. S. Chem. Commun. 2003,
807–818; (e) Ho¨ger, S. Chem.dEur. J. 2004, 10, 1320–1329; (f) Ho¨ger, S. In Acet-
ylene Chemistry; Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; Wiley-VCH:
Weinheim, 2005; pp 427–452.

11494
M. Sonoda et al. / Tetrahedron 64 (2008) 11490–11494
2. (a) Zhang, J.; Moore, J. S. J. Am. Chem. Soc. 1992, 114, 9701–9702; (b) Shetty, A. S.;
Zhang, J.; Moore, J. S. J. Am. Chem. Soc. 1996, 118, 1019–1027; (c) Lahiri, S.;
Thompson, J. L.; Moore, J. S. J. Am. Chem. Soc. 2000, 122, 11315–11319; (d) Tobe,
Y.; Utsumi, N.; Kawabata, K.; Naemura, K. Tetrahedron Lett. 1996, 37, 9325–9328;
(e) Tobe, Y.; Utsumi, N.; Nagano, A.; Naemura, K. Angew. Chem., Int. Ed. 1998, 38,
1285–1287; (f) Tobe, Y.; Utsumi, N.; Kawabata, K.; Nagano, A.; Adachi, K.; Araki,
S.; Sonoda, M.; Hirose, K.; Naemura, K. J. Am. Chem. Soc. 2002, 124, 5350–5364;
(g) Tobe, Y.; Nagai, T.; Araki, S.; Ichikawa, T.; Nomoto, A.; Sonoda, M.; Hirose, K.
Adv. Funct. Mater. 2006, 16, 1549–1554; (h) Ho¨ger, S.; Bonrad, K.; Mourran, A.;
Beginn, U.; Mo¨ller, M. J. Am. Chem. Soc. 2001, 123, 5651–5659; (i) Rosselli, S.;
Ramminger, A.-D.; Wagner, T.; Silier, B.; Wiegand, S.; Ha¨ußler; Lieser, G.;
Scheumann, V.; Ho¨ger, S. Angew. Chem., Int. Ed. 2001, 40, 3138–3141; (j) Rosselli,
S.; Ramminger, A.-D.; Wagner, T.; Lieser, G.; Ho¨ger, S. Chem.dEur. J. 2003, 9,
3481–3491; (k) Nakamura, K.; Okubo, H.; Yamaguchi, M. Org. Lett. 2001, 3,
1097–1099; (l) Saiki, Y.; Sugiura, H.; Nakamura, K.; Yamaguchi, M.; Hoshi, T.;
Anzai, J. J. Am. Chem. Soc. 2003, 125, 9268–9269; (m) Saiki, Y.; Nakamura, K.;
Nigorikawa, Y.; Yamaguchi, M. Angew. Chem., Int. Ed. 2003, 42, 5190–5192; (n)
Lin, C.-H.; Tour, J. J. Org. Chem. 2002, 67, 7761–7768.
Heiney, P. A.; Nelson, J. C.; Moore, J. S. Langmuir 1999, 15, 6897–6900; (c)
Tahara, K.; Lei, S.; Mamdouh, W.; Yamaguchi, Y.; Ichikawa, T.; Uji-i, H.; Sonoda,
M.; Hirose, K.; De Schryver, F. C.; De Feyter, S.; Tobe, Y. J. Am. Chem. Soc. 2008,
130, 6666–6667; (d) Pan, G.-B.; Cheng, X.-H.; Ho¨ger, S.; Freyland, W. J. Am.
Chem. Soc. 2006, 128, 4218–4219.
6. (a) Tobe, Y.; Nagano, A.; Kawabata, K.; Sonoda, M.; Naemura, K. Org. Lett. 2000, 2,
3265–3268; (b) Klyatskaya, S.; Dingenouts, N.; Rosenauer, C.; Mu¨ ller, B.; Ho¨ger,
S. J. Am. Chem. Soc. 2006, 128, 3150–3153; (c) Campbell, K.; McDonald, R.;
Branda, N. R.; Tykwinski, R. R. Org. Lett. 2001, 3, 1045–1048; (d) Campbell, K.;
McDonald, R.; Tykwinski, R. R. J. Org. Chem. 2002, 67, 1133–1140; (e) Campbell,
K.; Kuehl, C. J.; Ferguson, M. J.; Stang, P. J.; Tykwinski, R. R. J. Am. Chem. Soc. 2002,
124, 7266–7267; (f) Sun, S.-S.; Lees, A. J. Organometallics 2001, 20, 2353–2358.
7. (a) Waki, M.; Abe, H.; Inouye, M. Chem.dEur. J. 2006, 12, 7839–7847; (b) Waki,
M.; Abe, H.; Inouye, M. Angew. Chem., Int. Ed. 2007, 46, 3059–3061.
8. Cubberley, M. S.; Iverson, B. L. J. Am. Chem. Soc. 2001, 123, 7560–7563.
9. (a) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112, 5525–5534; (b)
Cozzi, F.; Siegel, J. S. Pure Appl. Chem. 1995, 67, 683–689; (c) Hunter, C. A.;
Lawson, K. R.; Perkins, J.; Urch, C. J. J. Chem. Soc., Perkin Trans. 2 2001, 651–669.
10. (a) Smithrud, D. B.; Diederich, F. J. Am. Chem. Soc. 1990, 112, 339–343; (b) Hill,
D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem. Rev. 2001, 101,
3893–4011.
3. (a) Venkataraman, D.; Lee, S.; Zhang, J.; Moore, J. S. Nature 1994, 371, 591–593;
(b) Ho¨ger, S.; Morrison, D. L.; Enkelmann, V. J. Am. Chem. Soc. 2002, 124, 6734–
6736; (c) Henze, O.; Lentz, D.; Scha¨fer, A.; Franke, P.; Schlu¨ ter, A. D. Chem.dEur.
J. 2002, 8, 357–365; (d) Grave, C.; Lentz, D.; Scha¨fer, A.; Samori, P.; Rabe, J. P.;
Franke, P.; Schlu¨ter, A. D. J. Am. Chem. Soc. 2003, 125, 6907–6918.
11. We are not aware of reports regarding solvent effect on
interaction of dispersive and electrostatic natures.
p–p stacking
4. (a) Zhang, J.; Moore, J. S. J. Am. Chem. Soc.1994,116, 2655–2656; (b) Mindyuk, O. Y.;
Stetzer, M. R.; Heiney, P. A.; Nelson, J. C.; Moore, J. S. Adv. Mater. 1998, 10, 1363–
1366; (c) Ho¨ger, S.; Enkelmann, F.; Bonrad, K.; Tschieske, C. Angew. Chem., Int. Ed.
2000, 39, 2268–2270; (d) Fischer, M.; Lieser, G.; Rapp, A.; Schnell, I.; Mamdouh,
W.; De Feyter, S.; De Schryver, F. C.; Ho¨ger, S. J. Am. Chem. Soc. 2004, 126, 214–222.
5. (a) Shetty, A. S.; Fischer, P. R.; Stork, K. F.; Bohn, P. W.; Moore, J. S. J. Am. Chem.
Soc. 1996, 118, 9409–9414; (b) Mindyuk, O. Y.; Stetzer, M. R.; Gidalevitz, D.;
12. For shape-persistent macrocycles of phenylene–ethynylene and phenylene–
butadiynylene types, chloroform is believed to best solvate the macrocyclic
backbone. Both polar (such as methanol and acetonitrile) and apolar (cyclo-
hexane) solvents are nonsolvents.2
13. Martin, B. B. Chem. Rev. 1996, 96, 3043–3064.
14. Abe, H.; Masuda, N.; Waki, M.; Inouye, M. J. Am. Chem. Soc. 2005, 127, 16189–
16196.