Hydrogen-bonding-induced oligoanthranilamide foldamers. Synthesis, characterization, and complexation for aliphatic ammonium ions

Article abstract of DOI:10.1016/j.tet.2005.06.042

The self-assembly of a novel series of intramolecular hydrogen bonding-driven foldamers have been described. Five linear aromatic amide oligomers 1-5, which bear two to six repeating benzoyl amide subunits, respectively, have been prepared by continuous amide-coupling reactions. The existence of three-centered hydrogen bonds in the oligomers and consequently, the folding conformation of the oligomers in the solid state and solution have been proved by the X-ray analysis (for 2) and the ¹H NMR and IR experiments. Molecular modeling reveals a planar and rigid conformation for the oligomers and a cavity of 0.86 nm in diameter for 6-mer 5. Fluorescent and ¹H NMR experiments have demonstrated that the new aromatic oligo-amide foldamers can bind primary and secondary alkyl ammonium ions in chloroform and the associated binding constants have been determined. It is revealed that 5-mer 4 exhibits the largest binding ability. A face-to-face binding mode has been proposed for the complexes.

Full text of DOI:10.1016/j.tet.2005.06.042

Tetrahedron 61 (2005) 7974–7980
Hydrogen-bonding-induced oligoanthranilamide foldamers.
Synthesis, characterization, and complexation for aliphatic
ammonium ions
*
Hui-Ping Yi, Chuang Li, Jun-Li Hou, Xi-Kui Jiang and Zhan-Ting Li
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 15 April 2005; revised 30 May 2005; accepted 6 June 2005
Available online 1 July 2005
Abstract—The self-assembly of a novel series of intramolecular hydrogen bonding-driven foldamers have been described. Five linear
aromatic amide oligomers 1–5, which bear two to six repeating benzoyl amide subunits, respectively, have been prepared by continuous
amide-coupling reactions. The existence of three-centered hydrogen bonds in the oligomers and consequently, the folding conformation of
the oligomers in the solid state and solution have been proved by the X-ray analysis (for 2) and the 1H NMR and IR experiments. Molecular
modeling reveals a planar and rigid conformation for the oligomers and a cavity of 0.86 nm in diameter for 6-mer 5. Fluorescent and 1H NMR
experiments have demonstrated that the new aromatic oligo-amide foldamers can bind primary and secondary alkyl ammonium ions in
chloroform and the associated binding constants have been determined. It is revealed that 5-mer 4 exhibits the largest binding ability. A face-
to-face binding mode has been proposed for the complexes.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Since, Perdesen’s discovery of the complexing affinity of
18-crown-6 and analogs for alkaline ions in 1967,1 a large
number of crown ethers, cryptands and related macrocycles
have been prepared for complexing discrete metal or
ammonium ions.2 Although early investigations have
revealed that flexible oligo(ethylene glycols) with two
terminal aromatic donors might also complex a cation by
wrapping themselves around the guest, the negative entropy
produced by the reduced conformational flexibility of the
linear molecules upon complexation usually greatly
decreases the binding ability of linear molecules.3,4
Covalent bonded rigid folding or crescent receptors
represent a new series of non-ring receptors for molecular
recognition.5 Nevertheless, the syntheses of these artificial
receptors are usually time-consuming and over-rigidified
shapes also make them generally lack the conformational
adaptability to meet the specific features of discrete guests.
In the last decade, there has been increasing interest in
utilizing hydrogen bonding to control the folding or helical
conformation of unnatural organic molecules.6 Recently, it
has been revealed that several hydrogen bonding and
hydrophobic interaction-driven folding molecules can
promote or even catalyze oxidation or alkylation reaction
of the pyridine nitrogen.7 Previously, we had reported that
intramolecular hydrogen bonding could be utilized to
facilitate the self-assembly of a new series of metallomacro-
cycles from rigid aromatic oligoamides.8 We also found
that hydrogen bonding-driven aromatic oligohydrazide
foldamers exhibit remarkably strong complexing ability
for saccharide derivatives in chloroform.9,10 The folding
architectures represent a new generation of non-ring
synthetic receptors, which possess recognizing ability
comparable to those of cyclophane receptors.11 In this
paper, we report the synthesis and characterization of a new
Keywords: Hydrogen bonding; Foldamer; Aromatic amide; Molecular
recognition; Alkyl ammonium ion.
*
Corresponding author. Tel.: C86 21 5492 5122; fax: C86 21 6416 6128;
e-mail: ztli@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.042

H.-P. Yi et al. / Tetrahedron 61 (2005) 7974–7980
7975
series of hydrogen bonded aromatic oligoamide foldamers
1–5 and their complexing behavior toward aliphatic
ammonium ions in chloroform.
formation of crescent or helical structures for the longer
oligomers.
The synthetic route for compounds 1–3 is shown in
Scheme 1. Compound 713 was first prepared from acid 6
in 95% yield in refluxing methanol catalyzed by sulfuric
acid, and then treated with concentrated nitric acid at room
temperature to afford compound 8 in 72% yield.14 The latter
was reacted with methyl iodide in acetone at room
temperature with potassium carbonate as base to produce
compound 9 in 80% yield. Palladium-catalyzed hydrogen-
ation of 9 in methanol gave rise to intermediate 10 in
quantitative yield, whereas its hydrolysis with sodium
hydroxide in aqueous methanol gave another intermediate
11 in 97% yield. Reaction of compound 12, obtained from
reaction of 11 with oxalyl chloride in the presence of N,N-
dimethyl formamide (DMF), with 10 in chloroform with
triethylamine as base produced 2-mer 1 in 98% yield.
Hydrogenation of 1 in THF gave 13 in 98% yield. The latter
was then reacted with 10 to produce 3-mer 2 in 85% yield.
By repeating the hydrogenation and coupling reactions, the
longer oligomers 3–5 could be conveniently prepared
starting from 2. The reaction conditions for the preparation
of 4 and 5 are presented in Scheme 2.
2. Results and discussion
Five aromatic oligoamides 1–5 have been designed, which
contain two to six benzene rings. Previous studies have
revealed that 2-methoxy-N-(2-methoxyphenyl)benzamide,
the repeating subunit of the present oligomers, adopts a rigid
and planar conformation as a result of the presence of two
intramolecular hydrogen bonds.8,12 It was envisioned that
this subunit in longer oligomers of the same skeleton should
also take up this conformation, which would led to the
Scheme 2.
Single crystals of 2-mer 1 were grown by slow evaporation
of the solution in chloroform at room temperature. The
crystal structure had been determined by the X-ray analysis
and is presented in Figure 1. As expected, the two benzene
rings and the central amide subunit share a perfectly
rigidified planar conformation because of the existence of
the three-centered hydrogen bonds.8,12 The NH/O distance
˚
is 1.98 and 2.17 A for the six-numbered and five-numbered
ring hydrogen bonds, respectively, whereas the NH/O
angle is 141.2 and 112.48, respectively, for both hydrogen
bonds. No single crystals of longer oligomers have been
obtained yet. Because the longer oligomers 2–5 are actually
elongation of the same backbone in 1, it is reasonable to
Scheme 1.

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H.-P. Yi et al. / Tetrahedron 61 (2005) 7974–7980
between the amide protons and the neighboring methoxyl
protons but not the neighboring benzene protons for all the
oligomers. This result obviously supports the hydrogen
bonded rigidified conformation but not a flexible, C–N
bond-freely rotatable conformation for the amide subunits.
The IR spectrum obtained in chloroform revealed the N–H
stretching frequency of less than 3350 cmK1 for all the
oligomers and the stretching frequency is independent on
the concentration (within the range of 0.5–5 mM), which is
also consistent with those of amides involved in intra-
molecular hydrogen bonds.15
Upon dilution from 35 to 0.5 mM, the signals of the NH and
aromatic protons in the 1H NMR spectrum of oligomers 1–5
in chloroform-d shift downfield only slightly. The largest
change of the chemical shift has been observed for 6-mer 5
(0.007 ppm for one of the amide protons). In principle, the
signals of hydrogen bonded amide protons would shift
upfield upon dilution of the solution due to the weakening of
the hydrogen bonding, this small downfield shifting should
reflect that very weak intermolecular aggregation or p–p
stacking exists at high concentration. Assuming a 1:1
binding mode for the intermolecular aggregation,9,16 self-
association constant of less than 8 MK1 was derived for
oligomers 3, 4, and 5, respectively, from the 1H NMR
dilution experiments.17 The UV–vis spectrum of all the
oligomers has similar shape with absorption maxima at
295 nm in chloroform. The shape of the spectrum of the
oligomers is not sensitive to its concentrations, and Beer’s
law was observed for all oligomers at %1.0!10K3 M as
judged from the changes of their absorbance as a function of
Figure 1. Crystal structure of 2-mer 1, which reveals a rigid planar
conformation due to the presence of two intramolecular hydrogen bonds.
assume that, without any important steric hindrance, similar
three-centered hydrogen bonds should exist in the longer
oligomers, which should make them take up a rigidified
folding conformation, as shown in Figure 3 with 5 as
example (vide infra).
Compounds 1–5 have been characterized by the 1H and 13
C
1
NMR and mass spectroscopy, and microanalysis. The H
NMR spectrum of the new oligomers in chloroform-d is
presented in Figure 2. It can be found that all the amide
protons of the oligomers are in the downfield area (10.35–
9.80 ppm), indicating that three-centered hydrogen bonds
also exist in these molecules in the solution. With the
elongation of the oligomers, the chemical shift of the amide
protons moves upfield. This is in accordance with the results
observed for the aromatic hydrazide-based foldamers,9
reflecting the decreased electron-donating ability of the
methoxyl oxygen atoms for the formation of two hydrogen
bonds simultaneously. The resolution of the spectrum of the
longest 6-mer 5 (Fig. 2e) is not reduced greatly compared to
that of the shorter oligomers, showing that no important
intra- or intermolecular stacking occurs in 5 (infra vide).
Additional evidence for the intramolecular hydrogen
1
their concentration. This is consistent with the above H
NMR result and suggests that the intermolecular association
can be ruled out in this concentration range.
Molecular modeling revealed that oligomers 2–5 adopt a
rigid crescent conformation as a result of the existence of
the intramolecular hydrogen bonds, which create a rigid
cavity with all the methoxyl groups located to the center of
the cavity. The distance between two cross-ring methoxyl
oxygen is approximately 0.86 nm for 6-mer 5 (Fig. 3). Such
a cavity size is comparable to that of the dibenzo[24]crown-8
ring,18 while the arrangement of its six methoxyl
oxygen atoms in the rigid conformation is similar to that
in an assumedly rigidified planar 18-crown-6 or Cram’s
spherands,19 with a difference of an increased spatial
separation of the neighboring oxygen atoms and sub-
sequently a larger cavity size in 5. Therefore, the complex-
ing behavior of this new series of folding oligomers towards
1
bonding came from 2D NOESY H NMR experiments in
chloroform-d, which revealed strong NOE connections
Figure 2. Partial 1H NMR spectrum (400 MHz, 3 mM) of oligomers 1 (a), 2
(b), 3 (c), 4 (d), and 5 (e) in chloroform-d at 25 8C, highlighting the
downfield chemical shift of the amide protons due to the existence of the
three-centered hydrogen bonds.
Figure 3. Hydrogen bonding-induced rigidified crescent conformation of
6-mer 5 and its energy-minimized structure.

H.-P. Yi et al. / Tetrahedron 61 (2005) 7974–7980
7977
alkylated ammonium ions 17$Cl and 18$Cl was investi-
gated in less polar chloroform.
calculated from the association constant using equation
DGZKRT ln Ka. The results are listed in Table 1. As an
example, Figure 4 presents the fluorescent spectra of 4 upon
addition of 17$Cl at different concentrations.
It can be found that, except 2-mer 1, all other longer
oligomers exhibit comparable complexing ability to the
ammonium, although 5-mer 4 gives rise to the largest
association constant for both ammonium ions. The existence
of the methyl groups in the cavity obviously reduces the
binding ability of the oligomers and, as a result, the binding
may occur in a face-to-face mode,22 in which the methyl
groups in the cavity are located away from the bound
ammonium ion. The association constant of the primary
ammonium 18$Cl is always larger than that of secondary
ammonium 17$Cl. This result may be rationalized by
considering that the former ion has one more proton for the
formation of more intermolecular hydrogen bonds and it
also imposes smaller steric hindrance. Compared to
oligomer 4, the longest oligomer 5 display a reduced
binding ability. This may reflect that the increase of the
steric hindrance with the increasing methyl groups in the
cavity may counteract the positive effect of the increased
methoxy oxygen number in the longer oligomers for
complexation with ammonium ion. Because all the
methoxyl oxygen atoms are involved in intramolecular
hydrogen bonding, the complexation of the foldaming
oligomers with ammonium may be driven by the inter-
molecular cation–p interaction, together with the inter-
molecular C]O/H–N and MeO/H–N hydrogen
bonding. The increase of the binding stability with the
Adding compounds 17$Cl or 18$Cl to the solution of
oligomers 1–5 in chloroform caused the fluorescent
emission of these oligomers to increase substantially. In
contrast, no obvious strengthening (!3%) was observed
when tetrabutylammonium chloride of the identical con-
centration was added under the same experimental
conditions, which ruled out the possibility of salt effect
and supported that complexes were formed between the
oligomers and the added ammonium ions in chloroform.
Upon addition of 1 equiv of the oligomers to the solution of
17$Cl or 18$Cl in chloroform-d, the signals of the NH signal
of the latter also shifted downfield (0.12 ppm for the case of
17$Cl and 5 at 5 mM) significantly. These observations also
indicate that the oligomers are able to bind the ammonium
ions. Job’s plot for the mixture of 5 and 17$Cl in
chloroform-d revealed the largest downfield shifting for
the NH proton signal at the 1:1 ratio,8c,20 which supports a
1:1 binding stroichiometry between the oligomer and the
ammonium guest. The association constants (Kassoc
)
between the oligomer and ammonium ion had been
determined by using an iterative least-square curve-fitting
method of the fluorescent and H NMR titration experi-
1
ments,9,21 and the corresponding free energy changes were
Table 1. Association constants (Kassoc, MK1) of the complexes between the folding oligomers and alkyl ammonium ions in CDCl3 at 25 8Ca
Complex
Kassoc (MK1
)
DG (kJ)
Complex
Kassoc (MK1
)
DG (kJ)
1$17$Cl
1$18$Cl
2$17$Cl
2$18$Cl
3$17$Cl
3$17$Cl
17
40
140
210
160
260
7.0
9.1
12.2
13.2
12.6
13.8
4$17$Cl
4$18$Cl
5$17$Cl
5$17$Clb
5$18$Cl
200
360
150
140
200
13.1
14.6
12.4
12.2
13.1
a With an error %20%.
1
b Obtained by H NMR dilution method with the NH signal of the salt as probe.
increase of the oligomer length may be caused by the
statistic effect. However, at the present stage, we are not
able to differentiate the discrete interactions.
3. Conclusion
In summary, we have reported the synthesis and character-
ization of a new series of aromatic amide oligomers, which
adopt folding conformation due to the existence of
intramolecular three-centered hydrogen bonds. The new
foldamers display modest binding affinity toward primary
and secondary alkyl ammonium ions in chloroform. A face-
to-face binding mode has been proposed for the resulting
complexes. In principle, one or two of the methoxyl groups
in the oligomers can be replaced with phenoxyl anion
without destroying the rigid folding conformation.23 The
resulting foldamers might display interesting binding ability
Figure 4. Partial fluorescent spectra of 4 (6.0!10K5 M, excitation
wavelengthZ345 nm) in chloroform at 25 8C, increased gradually with
the incremental addition of 17$Cl from 0 to 1.3 mM (inset: intensity change
of 4 with log[17$Cl]).

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H.-P. Yi et al. / Tetrahedron 61 (2005) 7974–7980
toward metal ions or ammonium ions due to increased
electrostatic interaction, which is being investigated.
sodium sulfate. Upon evaporation of the solvent under
reduced pressure, the crude product was purified by column
chromatography (petroleum ether/ethyl acetate 10:1) to give
compound 9 as a pale yellow solid (8.05 g, 80%). Mp 54–
1
4. Experimental
4.1. General methods
58 8C. H NMR (300 MHz, CDCl3): 7.84 (s, 1H), 7.73 (s,
1H), 3.97 (s, 6H), 2.41 (s, 3H). EI-MS: m/z 225 [M]C. Anal.
Calcd for C10H11NO5: C, 53.33; H, 4.92; N, 6.22. Found: C,
53.74; H, 5.04; N, 6.02.
Melting points are uncorrected. All reactions were
performed under an atmosphere of dry nitrogen. The H
1
4.1.4. Compound 10. A suspension of compound 9 (1.34 g,
5.96 mmol) and Pd–C (5%, 0.12 g) in methanol was stirred
under 1 atm of hydrogen gas at room temperature for 24 h.
The solid was filtered off over Celite and the filtrate
concentrated. The resulting residue was subjected to flash
chromatography (dichloromethane) to give the titled
compound as colorless oil (1.15 g, 99%). 1H NMR
(300 MHz, CDCl3): 7.01 (s, 1H), 6.73 (s, 1H), 3.90 (s,
3H), 3.82 (s, 3H), 2.24 (s, 3H). EI-MS: m/z 195 [M]C. Anal.
Calcd for C10H13NO3: C, 61.53; H, 6.71; N, 7.17. Found: C,
61.48; H, 6.86; N, 7.14.
NMR spectra were recorded on 400 or 300 MHz spec-
trometers in the indicated solvents. Chemical shifts are
expressed in parts per million (d) using residual solvent
protons as internal standards. Chloroform (d 7.26 ppm) was
used as an internal standard for chloroform-d. Elemental
analysis was carried out at the SIOC analytical center.
Unless otherwise indicated, all starting materials were
obtained from commercial suppliers and were used without
further purification. All solvents were dried before use
following standard procedures. The methods for the
determination of binding constants have been reported in
a previous paper.9
4.1.5. Compound 11. To a stirred solution of compound 9
(7.16 g, 31.8 mmol) in methanol (100 mL) and water
(50 mL) was added sodium hydroxide (2.67 g, 66.8 mmol)
at room temperature, the solution was then heated under
reflux for 3 h. Upon concentration under reduced pressure to
about 15 mL, the solution was neutralized with diluted
hydrochloric acid. The precipitate was formed, which was
filtered and washed with cold water to give compound 11 as
pale yellow powder (6.71 g, 97%). The product was further
recrystallized from ethanol for microanalysis. Mp 181–
183 8C. 1H NMR (300 MHz, CDCl3): 8.12 (s, 1H), 7.87 (s,
1H), 4.06 (s, 3H), 2.46 (s, 3H). EI-MS: m/z 211 [M]C. Anal.
Calcd for C9H9NO5: C, 51.19; H, 4.30; N, 6.63. Found: C,
51.43; H, 4.32; N, 6.52.
4.1.1. Compound 7. To a solution of 2-hydroxy-5-
methylbenzoic acid 6 (10.0 g, 65.8 mmol) in methanol
(150 mL) was added dropwise concentrated sulfuric acid
(2 mL), and the solution was heated under reflux for 24 h.
Upon removal of the solvent under reduced pressure, the
resulting residue was dissolved in ethyl acetate (100 mL)
and the solution was washed with saturated sodium
bicarbonate solution (25 mL!2), water (25 mL), brine
(25 mL), and dried over sodium sulfate. After the solvent
was evaporated in vacuo, the crude product was subjected to
flash column chromatography (dichloromethane/ethyl
acetate 10:1) to afford compound 7 as a colorless oil
(10.4 g, 95%).24 1H NMR (300 MHz, CDCl3): 10.56 (s, 1H),
7.63 (s, 1H), 7.26 (d, JZ8.1 Hz, 1H), 6.89 (d, JZ8.1 Hz,
1H), 3.94 (s, 3H), 2.28 (s, 3H). ESI-MS: m/z 167 [MCH]C.
4.1.6. Compound 1. To a solution of compound 11 (1.70 g,
8.06 mmol) in chloroform (25 mL) were added oxalyl
chloride (0.44 g, 5.80 mmol) and DMF (0.05 mL). The
solution was stirred at room temperature for 4 h and then
concentrated in vacuo to give compound 12 as yellow oil.
This crude product was dissolved in chloroform (20 mL)
and the solution was added to a solution of compound 10
(1.44 g, 7.38 mmol) and triethylamine (1.30 g, 1.30 mmol)
in chloroform (25 mL). The mixture was stirred at room
temperature for 5 h and then washed with dilute hydro-
chloric acid (1 N, 8 mL!2), aqueous sodium bicarbonate
solution (1 N, 10 mmol), water (15 mL), brine (15 mL), and
dried over sodium sulfate. The resulting residue was
subjected to column chromatography (chloroform/ethyl
acetate 20:1) to afford compound 1 as a yellow solid
(2.81 g, 98%). Mp 160–162 8C. 1H NMR (300 MHz,
CDCl3): 10.35 (s, 1H), 8.63 (s, 1H), 8.24 (s, 1H), 7.80 (s,
1H), 7.27 (s, 1H), 4.05 (s, 3H), 3.13 (s, 6H), 2.47 (s, 3H),
2.40 (s, 3H). 13C NMR (300 MHz, CDCl3): 166.1, 161.5,
149.3, 147.4, 144.1, 136.8, 135.3, 134.2, 132.4, 128.9, 128.7,
126.8, 125.3, 123.1, 64.4, 62.6, 52.3, 21.2, 20.7. IR (CHCl3): n
3320, 1710, 1676, 1531, 1471, 1251, 1198, 982 cmK1. EI-MS:
m/z 389 [MCH]C. Anal. Calcd for C19H20N2O7: C, 58.76; H,
5.19; N, 7.21. Found: C, 58.89; H, 5.32; N, 6.94.
4.1.2. Compound 8. A solution of compound 7 (10.3 g,
68.0 mmol) in water (110 mL) was cooled to 0 8C. To the
solution was added slowly concentrated nitric acid (70%,
110 mL) in 30 min. The solution was then stirred at room
temperature for 24 h and poured into ice water (250 mL).
The mixture was extracted with ether (100 mL!3) and the
combined organic phase was washed with aqueous sodium
carbonate (1 M, 50 mL), water (50 mL!2), brine (50 mL),
and dried over magnesium sulfate. After removal of the
solvent under reduced pressure, the resulting residue was
purified by column chromatography (petroleum ether/ethyl
acetate 30:1) to give compound 8 as a yellow solid (9.45 g,
72%). Mp 140–142 8C [142–144 8C]14. 1H NMR (300 MHz,
CDCl3): 11.78 (s, 1H), 7.98 (d, JZ4.8 Hz, 2H), 4.00 (s, 3H),
2.37 (s, 3H). ESI-MS: m/z 212 [MCH]C.
4.1.3. Compound 9. A suspension of compound 8 (9.44 g,
45.0 mmol), methyl iodide (12.8 g, 90.0 mmol), potassium
carbonate (19.9 g, 144 mmol), and 18-crown-6 (10 mg) in
acetone (250 mL) was stirred at room temperature for 36 h
and then the solvent was removed in vacuo. The resulting
residue was triturated with ether (200 mL) and the organic
phase was washed with diluted sodium bicarbonate (1 N,
50 mL!2), water (50 mL), brine (50 m) and dried over
4.1.7. Compound 13. A suspension of compound 1 (2.80 g,
7.82 mmol) and Pd–C (5%, 0.20 g) in tetrahydrofuran

H.-P. Yi et al. / Tetrahedron 61 (2005) 7974–7980
7979
(35 mL) was stirred at 50 8C under 1 atm of hydrogen gas
for 6 h. The solid was then filtered off over Celite. Upon
removal of the solvent under reduced pressure, the resulting
residue was subjected to flash chromatography (ethyl
acetate/dichloromethane 1:10) to give compound 13 as a
white powder (2.58 g, 98%). Mp 197–199 8C. 1H NMR
(300 MHz, CDCl3): 10.56 (s, 1H), 8.69 (s, 1H), 7.41 (s, 2H),
6.84 (s, 1H), 3.91 (s, 1H), 2.39 (s, 3H), 2.31 (s, 6H). EI-MS:
m/z 358 [M]C. Anal. Calcd for C19H22N2O5: C, 63.68; H,
6.19; N, 7.82. Found: C, 63.62; H, 6.23; N, 7.64.
145.3, 145.2, 145.2, 143.9, 136.9, 135.9, 135.8, 135.7,
135.6, 134.3, 132.8, 131.9, 131.8, 131.6, 129.0, 128.8,
126.9, 126.7, 126.6, 126.4, 126.3, 126.1, 126.0, 125.7,
125.5, 125.5, 125.4, 122.8, 64.4, 63.2, 63.0, 62.3, 52.1, 21.4,
21.4, 21.2, 20.2, 14.2. IR (CHCl3): n 3338, 2946, 1726,
1677, 1533, 1460, 1423, 1247, 981, 732 cmK1. MALDI-
TOF-HRMS: Required for C46H47N5O13Na: 900.3014.
Found: 900.3060.
4.1.13. Compound 5. Solvent for column chromatography:
dichloromethane/ethyl acetate (35:1), pale yellow powder in
1
81% yield. Mp 232–234 8C. H NMR (300 MHz, CDCl3):
4.1.8. Compounds 14, 15, and 16. These compounds were
prepared from the Pd–C-catalyzed hydrogenation of
compounds 2–4, respectively, by using the reaction
conditions described for 13. These compounds were
unstable in the air and used for the next step immediately
after purification.
10.23 (s, 1H), 10.12 (s, 1H), 10.10 (s, 1H), 10.08 (s, 1H),
9.81 (s, 1H), 8.68 (s, 1H), 8.66 (s, 1H), 8.65 (s, 1H), 8.62 (s,
2H), 8.13 (s, 1H), 7.73 (s, 2H), 7.71 (s, 1H), 7.67 (s, 2H),
7.31 (s, 1H), 4.04 (s, 3H), 3.99 (s, 3H), 3.96 (s, 6H), 3.92 (s,
3H), 3.78 (s, 3H), 3.75 (s, 3H), 2.47 (s, 9H), 2.41 (s, 3H),
2.39 (s, 3H), 2.07 (s, 3H). 13C NMR (100 MHz, CDCl3):
165.5, 163.5, 163.2, 163.1, 163.0, 161.5, 148.8, 147.0,
145.3, 145.2, 145.0, 143.8, 136.7, 136.0, 135.9, 135.8,
135.6, 134.2, 132.8, 132.0, 131.9, 131.7, 128.9, 128.6,
126.9, 126.8, 126.6, 126.4, 126.2, 126.2, 126.1, 125.9,
125.9, 125.8, 125.5, 125.4, 125.3, 122.6, 64.3, 63.2, 63.0,
62.9, 62.2, 52.1, 21.4, 21.3, 20.7. IR (CHCl3): n 3342, 2947,
1677, 1533, 1459, 1423, 1246, 979, 732 cmK1. MALDI-
TOF-MS: m/z 1064 [MCNa]C. Anal. Calcd for
C55H56N6O15: C, 63.45; H, 5.42; N, 8.07. Found: C,
62.96; H, 5.48; N, 7.97.
4.1.9. Compounds 2, 3, 4 and 5. These compounds were
prepared from the reaction of compound 11 and the
corresponding aniline 14–16 according to the experimental
procedure described for compound 1.
4.1.10. Compound 2. Solvent for column chromatography:
chloroform, white solid in 85% yield. Mp 211–213 8C. H
1
NMR (300 MHz, CDCl3): 10.23 (s, 1H), 8.68 (s, 1H), 8.60
(s, 1H), 8.26 (s, 1H), 8.25 (s, 1H), 7.83 (s, 1H), 7.71 (s, 1H),
7.43 (s, 1H), 4.08 (s, 3H), 3.94 (s, 3H), 3.93 (s, 3H), 3.91 (s,
3H), 2.48 (s, 3H), 2.45 (s, 3H), 2.40 (s, 3H). 13C NMR
(100 MHz, CDCl3): 166.1, 163.0, 161.5, 149.1, 147.2,
145.3, 144.0, 136.9, 135.7, 135.6, 134.3, 132.7, 131.7,
129.1, 128.6, 127.0, 126.4, 126.1, 125.2, 125.2, 123.0, 64.4,
63.2, 62.5, 52.3, 21.4, 21.3, 20.7. IR (CHCl3): n 3335, 1676,
1533, 1465, 1340, 1264, 1246, 1200, 988 cmK1. ESI-MS:
m/z 552 [MCH]C. Anal. Calcd for C28H29N3O9: C, 60.97;
H, 5.30; N, 7.62. Found: C, 60.82; H, 5.52; N, 7.67.
4.2. Molecular mechanics calculation
The folding patterns of the oligomers were constructed by
using the Builder program within the package HyperChem.
Then they were optimized by the conjugate gradient with
AccuModel software 2.1 using the MM3 force field. To
explore lower energy conformation, molecular dynamics
calculations were performed without constraints for the
oligomers.
4.1.11. Compound 3. Solvent for column chromatography:
dichloromethane, white solid in 82% yield. Mp 216–218 8C.
1H NMR (300 MHz, CDCl3): 10.20 (s, 1H), 10.09 (s, 1H),
10.01 (s, 1H), 8.68 (s, 1H), 8.64 (d, JZ1.5 Hz, 1H), 8.60 (s,
1H), 8.24 (d, JZ2.4 Hz, 1H), 7.85 (d, JZ2.7 Hz, 1H), 7.73
(s, 1H), 7.69 (s, 1H), 7.44 (s, 1H), 4.09 (s, 3H), 3.95 (s, 3H),
3.94 (s, 3H), 3.92 (s, 3H), 3.90 (s, 3H), 2.49 (s, 3H), 2.46 (s,
3H), 2.45 (s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz,
CDCl3): 165.1, 162.1, 162.1, 160.7, 148.1, 146.2, 144.2,
144.2, 143.2, 143.1, 135.8, 134.9, 134.7, 134.7, 133.3,
131.7, 130.9, 130.6, 128.1, 127.8, 126.0, 125.6, 125.2,
125.1, 124.5, 124.3, 124.3, 122.0, 63.4, 62.2, 62.1, 61.4,
51.3, 20.4, 20.2, 19.7. IR (CHCl3): n 3329, 1677, 1534,
1459, 1338, 1251, 980, 732 cmK1. ESI-MS: m/z 715 [MC
H]C. Anal. Calcd for C37H38N4O11: C, 62.18; H, 5.36; N,
7.84. Found: C, 62.46; H, 5.68; N, 7.65.
4.3. X-ray data
Empirical formula: C19H20N2O7. Space group Triclinic,
˚
˚
P-1, aZ7.5626(12) A, aZ107.155(3)8. bZ11.4681(17) A,
˚
bZ100.719(3)8. gZ11.7866(17) A, gZ100.902(3)8.
3
Volume 926.7(2) A . Crystal size 0.382!0.207!0.
˚
138 mm3.
Acknowledgements
This work was financially supported by the Ministry of
Science and Technology (G2000078101), the National
Natural Science Foundation and the Chinese Academy of
Sciences of China.
4.1.12. Compound 4. Solvent for column chromatography:
dichloromethane/ethyl acetate (40:1), white solid in 80%
yield. Mp 225–226.5 8C. 1H NMR (300 MHz, CDCl3):
10.20 (s, 1H), 10.10 (s, 1H), 9.94 (s, 1H), 9.80 (s, 1H), 8.74
(s, 1H), 8.68 (s, 1H), 8.65 (s, 1H), 8.62 (s, 1H), 8.23 (s, 1H),
7.81 (s, 1H), 7.70 (s, 3H), 7.43 (s, 1H), 4.08 (s, 3H), 3.97 (s,
3H), 3.96 (s, 3H), 3.91 (s, 3H), 3.86 (s, 3H), 3.84 (s, 3H),
2.47 (s, 9H), 2.45 (s, 3H), 2.39 (s, 3H). 13C NMR (100 MHz,
CDCl3): 165.8, 163.3, 163.3, 163.1, 161.7, 149.1, 147.2,
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