A highly stable double helix of aromatic oligoamide comprised of fused ring aromatic units

Article abstract of DOI:10.1016/j.tet.2011.11.081

Aromatic oligoamides of 2,6-diaminofluorobenzene and 1,8- diazafluoroanthrancene-2,7-diacid have been synthesized by a convergent method. The heptameric oligoamide can not only fold into a single helix but also hybridize into a highly stable double helix through intensive intermolecular aromatic stackings, which has been extensively characterized in the solid state by single crystal X-ray diffractions and in solution by ¹H NMR, NOESY, and UV/vis spectra. The K_dim values of the heptamer are over 10⁷ L mol^-1 in various solutions at rt. The extensive interstrand interactions, enlarged diameter (5.4 ?), and lower torsion angles (13°) render heptamer 1 readily to hybridize into a highly stable double helix based on spring-like extension mechanism.

Full text of DOI:10.1016/j.tet.2011.11.081

Tetrahedron 68 (2012) 4479e4484
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A highly stable double helix of aromatic oligoamide comprised of fused ring
aromatic units
,
,
,
,
,
Quan Gan a c, Jie Shang a c, Brice Kauffmann b, Ying Wang a c, Fusheng Bie a c, Hua Jiang a
*
a Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, PO Box 62 No. 2.
Zhongguancun No., Haidian District, Beijing 100190, China
b
ꢀ
ꢀ
Institut Europeen de Chimie et Biologie, Universite de BordeauxdCNRS UMS3033, 2 rue Robert Escarpit, F-33607 Pessac, France
c Graduate School of Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Aromatic oligoamides of 2,6-diaminofluorobenzene and 1,8-diazafluoroanthrancene-2,7-diacid have
been synthesized by a convergent method. The heptameric oligoamide can not only fold into a single
helix but also hybridize into a highly stable double helix through intensive intermolecular aromatic
stackings, which has been extensively characterized in the solid state by single crystal X-ray diffractions
and in solution by 1H NMR, NOESY, and UV/vis spectra. The Kdim values of the heptamer are over
Received 30 September 2011
Received in revised form 16 November 2011
Accepted 24 November 2011
Available online 1 December 2011
107 L molꢀ1 in various solutions at rt. The extensive interstrand interactions, enlarged diameter (5.4 A),
ꢁ
Keywords:
Double helices
Foldamers
Hybridization
Hydrogen bonds
and lower torsion angles (13ꢁ) render heptamer 1 readily to hybridize into a highly stable double helix
based on spring-like extension mechanism.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
by hydrogen bond and aromatic pep stacking. Although many ar-
omatic oligoamides have been found to display well-defined helical
structures, only limited systems show tendency to aggregate into
double, triple, and quadruple helices.5,6 Other examples include
oligoresorcinols,7 ethynylhelicene oligomers,8 m-terphenyl back-
bone oligomers exploiting amidiniumecarboxylate salt bridges,9
alternate sequences of aromatic hydrogen bond donors and ac-
ceptors.10 However, much attention has been focused on the
characterization of helical structures. Detailed understanding of the
ability of foldamers to hybridize into double helices, a fundamental
issue to the research of double helices, is still scarce. In this regard,
oligoamides of 2,6-diaminopyridine and 2,6-pyridinedicarboxylic
acid described by Huc and co-workers represent a significant
advance.5
Several strategies including extending strand lengths, enlarging
helical diameters or changing substituents5,7 have been used to
increase the stability of double helices. For instance, Huc demon-
strated that oligoamides of 2,6-diaminopyridine and 2,6-
pyridinedicarboxylic acid not only adopt a stable single helical
conformation in solution as seen in other aromatic oligoamides
foldamers, but also hybridize into double helical duplex. The di-
merization constants of double helices increase on increasing the
length of strands while the solution was equilibrated well.5 The
mechanism proposed for this hybridization involved a screw-like
slippage in which the intrastrand interaction in single helix was
destroyed in company with the simultaneous formation of
Helical structures as observed in biomacromolecules, such as
proteins and DNA are ubiquitous, but play vital roles in their ex-
quisite biological functions. For example, double helical structure of
DNA is a key to genetic information storage, replication, and tran-
scription. Inspired by such sophisticated structures and remarkable
efficient hybridization of biomacromolecules, chemists have been
engaged in developing a large number of artificial molecules with
well-defined folded structures driven by noncovalent forces over
the last decade.1 Synthetic oligomers able to intertwine into mul-
tiple helices are of great interest because they might provide arti-
ficial molecular platforms to mimic folded structures and biological
functions, for instance, double helical structure, information stor-
age, and duplication in DNA, and also might have potential appli-
cation in material sciences. Different types of multiple helical
structures have been constructed so far by metal coordination,
hydrogen bond, aromatic
pep
stacking or salt bridge.1,2 Metal co-
ordination has proved effective for building helicates that were
comprised of metal cations and organic ligands.3 As for metal-free
helix,4 aromatic oligoamides represent one of most intensively
studied foldamers, helical structures of which were usually driven
* Corresponding author. Tel./fax: þ86 10 82612075; e-mail address: hjiang@
iccas.ac.cn (H. Jiang).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.081

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Q. Gan et al. / Tetrahedron 68 (2012) 4479e4484
interstrand interaction in double helices.11 As a result of hybrid-
ization, a global and maximized intermolecular interaction in par-
diazafluoroanthrancene-2,7-dicarboxylic acid 8 with quantitative
yield. Afterward, the activation of diacid 8 was carried out in the
presence of Ghosez reagent to generate diacid chloride that was
directly coupled with monoamine 6 to generate trimer 3. How-
ever, if a small amount of methanol was added into the reaction
solution to quench the acid chloride after the coupling reaction
proceeded for a certain time, dimer 2 and trimer 3 could be pre-
pared in one pot with acceptable yields. At the meantime, a small
part of starting materials diester 7 generated from the coupling
could also be recycled. This approach thus directly provided two
main short oligomers in one reaction and avoided nasty mono-
hydrolysis of diester 7. The desired heptamer 1 was successfully
achieved in moderate yield by the coupling reaction between
trimeric diamine and dimeric acid chloride.
ticular aromatic
pep stacking was achieved in double helices in
comparison with in single helix. Although the hybridization was
governed by many intrinsic factors, such as length of sequence and
substituent of strand as well as extrinsic factors like solvent polarity
and temperature, the formation of double helices is a highly co-
operative process that is strictly controlled by the enthalpic gain
and entropic loss during the hybridization.
We recently found that tetrameric and octameric amides of 7-
amino-8-fluoro-2-quinolinecarboxylic acid with a large helical di-
ameter exhibited a remarkable aggregation behavior.6 That is, tet-
ramer is able to adopt a helical conformation with a large pitch that
allows the formation of an unprecedented quadruple helix and
octamer dimerizes as a stable anti-parallel double helix. With the
aim of investigating the formation of multiple helices of aromatic
oligoamides, we became interested in the aromatic oligoamides
sequences with more fused ring aromatic monomers. We antici-
pated that the large surface and size of the fused ring aromatic
monomers render aromatic oligoamides to readily form stable
double helices in view of the spring-like hybridization mechanism.
Herein, we reported the design, synthesis, and hybridized behavior
of a new series of oligoamide strands alternately consisting of 2,6-
2.2. Solid state studies
Single crystal X-ray diffraction provided detailed information
about the double helical structures of heptamer 1 (Fig. 1 and S1).
Yellow crystals of heptamer 1 suitable for crystallographic analysis
were obtained upon diffusion of hexane into C2H4Cl2 and chloro-
benzene solution, respectively. Both crystal structures displayed
a very similar double helical architecture (Section 4.3), which is
unexpectedly different from that of oligoamides of pyridine, whose
double helical structure possesses a C2-symmetry axis.5 In the
present double helices, each strand is shifted by one aromatic ring,
leading to that the diazaanthracene units in one strand and the
fluorobenzene units in the other alternately stack onto each other.
That is, each diazaanthracene unit in one strand was sandwiched
between the two fluorobenzene units in the other strand and vice
diaminofluorobenzene
and
1,8-diazafluoroanthrancene-2,7-
dicarboxylic acid; we notably showed that heptameric amide hy-
bridized into a highly stable double helix in the solid phase and in
solution via extensive intermolecular
p-p stacking with di-
merization constant Kdim over 107 L molꢀ1 in various solvents at rt.
2. Results and discussion
versa (Fig. 1). The global and extensive interstrand aromatic
pep
2.1. Design and synthesis
stackings have been achieved as a result of such a slippage. This
stacking pattern is likely due to the strong interactions between the
electron-rich aminobenzene moiety and the electron-deficient
diazaanthracence unit and partly due to the large surface of the
fused aromatic units. All the fluorine atoms, amide protons, and
diazaanthracene nitrogen atoms of the sequences point to the he-
lical hollow cavity, and participate in the formation of a strong
three-center F/HN and N/HN hydrogen bonding, which are one
of main driven forces inducing the strand to adopt a helical struc-
The structures of the aromatic oligoamides and their synthetic
procedures were listed in Scheme 1. We chose a three fused aro-
matic ring for the present study because the fused ring aromatic
monomer not only provides a large surface that is favorable for
aromatic pep stacking during the formation of double helices, but
also possesses a large helical diameter in comparison with a single
aromatic ring so as to lower the enthalpic cost of spring-like ex-
tension.5,6 Moreover, foldamers containing a few units of fused
aromatic ring have been less studied.5,12 Initially, we have
designed a series of the oligoamides comprised of only fused ring
aromatic units, i.e., the oligoamides of 1,8-diazafluoro-anthran-
cene-2,7-dicarboxylic acid and 1,8-diazafluoroanthrancene-2,7-
diamine. It turned out that the syntheses of such arylamides
were very efficient for short strands like trimer but became very
difficult for long strands like pentamer and heptamer, presumably
due to the strong aromatic stacking in methylene chloride solution
that hinders the effective elongation of the strand. To overcome
this synthetic hindrance, we used 2,6-diaminofluorobenzene
instead of 1,8-diazafluoro-anthrancene-2,7-diamine to reduce ar-
omatic interaction and designed new oligoamide strands alter-
nately consisting of 2,6-diaminofluorobenzene and 1,8-diazafluo-
roanthrancene-2,7-dicarboxylic acid. Moreover, the fluorine atom
in fluorobenzene provides a hydrogen bond acceptor so that the
protons of amides can readily form a three center hydrogen bond
that also contributes to the stability of helix. As expected, the
synthesis of heptamer 1 via a convergent approach as shown in
Scheme 1 was smooth. Although diester 7 was easily prepared
according to the procedure reported by us,13 mono-saponification
of diester 7 was found to produce monoacid in a very low yield due
to the poor solubility in most common organic solvents (MeOH,
THF, DMF). This situation renders it infeasible to prepare dimer 2
through the coupling of monoacid and monoamine 6. Fortunately,
we found that diester 7 could be easily hydrolyzed to generate 1,8-
ꢁ
ture. The double helical pitch is 7 A, which is identical to that of all
other double helices, and nearly four monomeric units are needed
for one turn. However, the diameter of the double helices and
arylamide torsions angles differ essentially. The inner diameter of
ꢁ
the helix (1)2 is about 5.4 A, which is obviously larger than that of
pyridine carboxamide oligomers. The tilt angle of the strand in the
double helix (1)2 is about 13ꢁ (Fig. S2), which is significantly smaller
than that of the pyridine carboxamide oligomers (43ꢁ) and the
pyridine carboxamide oligomers with a large unit in the middle of
sequence (28ꢁ).5 Hence, extensive interstrand interactions, en-
larged diameter, and lower torsion angles render heptamer 1
readily to hybridize into a highly stable double helix based on
spring-like extension mechanism.
2.3. Solution studies
The double helical structure of oligomer 1 was further con-
firmed by 1H NMR, NOESY, and UV/vis spectra in solution. The 1H
NMR spectra of dimer and trimer in CDCl3 show the sharp signal
peaks of amide protons at low field (signals at 10e12 ppm) (Fig. 2
(a) and (b)), suggestive of the formation of intramolecular hydro-
gen bonding. However, the chemical shifts of amide and aromatic
proton of heptamer 1 displays an obvious upfield shift compared to
those of dimer and trimer (Fig. 2 (c)), in particular, the chemical
shift of NHBoc shows about a shift of 1.2 ppm from 6.8 ppm to
5.6 ppm. The data imply that signals of heptamer were significantly

Q. Gan et al. / Tetrahedron 68 (2012) 4479e4484
4481
Scheme 1. Reagents and conditions: (a) di-tert-butyl-dicarbonate, dioxane, 80 ꢁC,
4 days; (b) H2, Pd/C, EtOAc, 8 h; (c) NaOH, THF/water, rt, 2 h; (d) 1-chloro-N,N,2-
trimethylpropenylamine, DCM, rt, 10 h; (e) DIEA, DCM, rt, 6 h, then methanol; (f) NaOH, THF/water, rt, 4 h, then 1-chloro-N,N,2-trimethylpropenylamine, DCM, rt, 2 h; (g) TFA/
DCM, rt, 2 h. (h) DIEA, DCM, rt, 10 h.
shielded by aromatic
pep stacking either from single helix or
double helix. Moreover, one set of signals observed for heptamer 1
hints at the existence of only one species in solution. By combining
with the crystal data, we therefore can conclude that heptamer 1
prevails as a double helical conformation in solution.
The ROESY experiment was carried out to provide additional
evidence to support the formation of the double helices. As shown
in Fig. 3, the ROESY correlations observed between fluorobenzene
and the isobutyl groups of the fused ring aromatic units reveal that
fluorobenzene rings overlap with the 1,7-diazaanthracene rings, in
agreement with crystal data. Furthermore, cross peaks were also
found between amide protons of Boc groups and isobutyl groups.
These contracts sufficiently confirm that the heptamer presents
double helical conformation in solution. Given that 1 adopts a sin-
gle helical structure, fluorobenzene rings would only overlap with
other benzene units in the sequence but never with the 1,7-
diazaanthracene moieties (Fig. S3). Finally, the formation of dou-
ble helix in solution was also supported by ESI-MS that displays
a doubly charged species [2Mþ2H]þ2 (Fig. S4).
Fig. 1. Side view and top view of the crystal structures of heptamer 1 (crystals grown
from C2H2Cl4/hexane). The benzene and 1,7-diazaanthrancence moieties are labeled in
deep blue and green, respectively. Isobutoxy side chains, hydrogen atoms, and solvent
molecules are removed for clarity.
In order to determine the dimerization constant Kdim of 1, we
performed 1H NMR experiments in different solvents including the
apolar solvents CDCl3 and C2D2Cl4 and polar solvent pyridine-d5,
a known solvent able to strongly weaken the hybridization of these
oligomers. In all solvents, only one set of signals was detected at the
concentration of 1 mM so we are unable to extract the dimerization
constant from these NMR data (Fig. S5). Hence, to quantify Kdim
,
double helices must be dissociated to some extent so as to produce
measurable parameters. Dilution and heating are two efficient
approaches to dissociate double helices.11 The UV/vis variable
concentration experiments were carried out in CHCl3 and pyridine
(Fig. S6 and S7). The data showed that LamberteBeer law was
complied strictly even when the concentration was decreased to
0.5 mm. Neither hypochromism nor bathochromic shift was ob-
served, suggesting that the double helical structure is rather robust
with the Kdim value over 107 L molꢀ1 in chloroform and pyridine at
rt, respectively. This phenomenon is sharply different from the case
1
Fig. 2. The part of H NMR spectra (400 MHz, CDCl3, 1 mM, 20 ꢁC) of (a) dimer 2, (b)
trimer 3, (c) heptamer 1.

4482
Q. Gan et al. / Tetrahedron 68 (2012) 4479e4484
a few of fused ring aromatic units in the sequences. Such en-
hancement mainly originates from the unique properties of the
fused ring aromatic unit including large surface and size that lower
the enthalpic cost of spring-like extension during the hybridization.
It was expected that arylamide comprised of more or full fused ring
aromatic units would display more stable double helices that is of
great interest in constructing supramolecular polymers with highly
stable helical structures by hybridization.
4. Experimental section
4.1. General procedure and materials
All coupling reactions were carried out under a dry nitrogen
atmosphere. Materials were obtained from commercial suppliers
and used without further purification unless otherwise specified.
Dry dichloromethane (DCM), chloroform (CHCl3), and diisopropy-
lethylamine (DIPEA) were distilled from calcium hydride (CaH2)
prior to use. NMR spectra were recorded on Bruker AVANCE 600
(600 MHz), Bruker AVANCE 400 (400 MHz), and Bruker DMX 300
(300 MHz) spectrometers. Chemical shifts are expressed in parts
per million (ppm,
standards (chloroform:
DMSO: 2.50 ppm; pyridine:
MALDI-TOF were obtained on GCT, LC-MS 2010, Bruker Apex IV
FTMS, and Autotlex III spectrometers, respectively.
d
) using residual solvent protons as internal
7.26 ppm; tetrachloroethane: 6.00 ppm;
8.74 ppm). EI, ESI mass spectra and
d
d
Fig. 3. Partial ROESY spectrum (600 MHz, CDCl3, 1 mM, 20 ꢁC) of heptamer 1. Corre-
lations observed between protons of the isobutyl groups and fluorobenzene and amide
protons of Boc groups are labeled in ellipse and rectangle, respectively.
d
d
4.2. Synthesis
of pyridine carboxamide heptamer with an anthracene in the
center, whose dimerization constant Kdim is 6.5ꢂ105 L molꢀ1 in
pyridine at 25 ꢁC.5 Upon heating the solution of 1 (1 mM) in C2D2Cl4
from 20 to 100 ꢁC, the 1H NMR spectrum revealed the emergence of
a second set of signals at lower field (Fig. 4) indicative of the
presence of the single helix of heptamer 1. The proportions be-
tween these two sets of signals varied with temperatures, but no
coalescence was observed. Integrating the two proportions of sig-
nals allowed us to estimate the dimerization constant
Kdim¼1.7ꢂ104 L molꢀ1 at 80 ꢁC and 7.9ꢂ103 L molꢀ1 at 100 ꢁC in
C2D2Cl4, respectively.
4.2.1. tert-Butyl (2-fluoro-3-nitrophenyl)carbamate (5). A solution
of 2-fluoro-3-nitroaniline14 (0.24 g, 1.5 mmol) in dioxane (10 mL)
containing di-tert-butyl-dicarbonate (1.0 g, 4.6 mmol) was heated
at 60 ꢁC for 3 days. The solvent was removed in vacuo, and the
residue was purified by flash chromatography (SiO2) eluting with
hexane/CH2Cl2 from 100:10 to 100:50 vol/vol to afford the pure
product (0.31 g, 80%). 1H NMR (CDCl3, 400 MHz):
1H), 7.69e7.63 (m, 1H), 7.52 (t, J¼2.4 Hz, 1H), 6.86 (br, 1H), 1.54 (s,
9H). 13C NMR (CDCl3, 100 MHz):
152.1, 146.6, 144.0, 137.4, 137.4,
d
8.48 (t, J¼9.6 Hz,
d
129.5, 129.5, 125.1, 124.3, 124.3, 118.6, 118.5, 82.2, 28.3. MS (ESI):
279.1 [MþNa]þ (calcd for C11H13FN2O4Na, 279.08).
4.2.2. tert-Butyl (3-amino-2-fluorophenyl)carbamate (6). Compound
5 (0.24 g, 0.94 mmol) was dissolved in EtOAc (20 mL), and of 10% Pd/
C (25 mg) was added. The reaction mixture was stirred for 6 h under
hydrogen at atmospheric pressure. After filtration through Celite and
concentration, the residual oil was purified by flash chromatography
(SiO2) eluting with CH2Cl2 to obtain product 6 as white solid (0.18 g,
85% yield). 1H NMR (CDCl3, 400 MHz):
6.89e6.85 (m,1H), 6.64 (br,1H), 6.48e6.43 (m,1H), 3.41 (br,1H),1.52
(s, 9H). 13C NMR (CDCl3, 100 MHz):
152.5, 143.4, 140.2, 134.3, 134.1,
d
7.45 (t, J¼6.4 Hz, 1H),
d
127.2, 127.1, 124.3, 124.3, 111.0, 109.7, 80.9, 28.4. MS (ESI): 249.2
[MþNa]þ (calcd for C11H15FN2O2Na, 249.10).
4.2.3. Dimer (2) and trimer (3). Diacid 8 (0.86 g, 2.0 mmol) was
suspended in anhydrous CHCl3 (10 mL). 1-Chloro-N,N,2-
trimethylpropenylamine (0.53 mL, 2.0 equiv) was added and the
reaction was allowed to stir at rt for 3 h. The reaction mixture re-
mains a suspension, but the reaction does work under these con-
ditions. The solvent and excess reagents were removed under
vacuum and the residue was dried under vacuum for at least 2 h to
yield acid chloride as a yellow-orange solid. To a solution of the
freshly prepared diacid chloride in CHCl3 (10 mL) was added
dropwise a mixture solution of monoamine 6 (0.22 g, 1.0 mmol)
and distilled DIPEA (0.68 mL, 4.0 mmol) in dry CHCl3 (10 mL) at rt.
Then, 1 mL MeOH was added. After 1 h stirring, the solution mix-
ture was evaporated and the product was purified by flash
Fig. 4. Part of the 300 MHz 1H NMR spectra in 1 mM C2D2Cl4 solution showing amide
resonances of heptamer 1 upon changing temperature: (a) 20 ꢁC; (b) 80 ꢁC; (c) 100 ꢁC.
Increasing the temperature leads to the onset of a new species in slow exchange on the
NMR timescale. Signals belonging to the single and double helix are, respectively,
marked with white and black circles.
3. Conclusion
We demonstrated that the stability of the double helices of
aromatic oligoamides could be significantly enhanced by using

Q. Gan et al. / Tetrahedron 68 (2012) 4479e4484
4483
chromatography (SiO2) eluting with CH2Cl2/EtOAc from 100:1 to
100:10 vol/vol to obtain 2 as a yellowish solid (0.39 g, 36% yield),
and 3 as a yellowish solid (0.34 g, 32% yield). Meantime, starting
materials 7 could be recycled (0.13 g, 12% yield). Dimer 2: 1H NMR
Kappa goniometer and the osmic mirrors VarimaxÒ HF optics.
The system is driven by the CrystalClear15 suite, which was also
used for the unit cells determinations, the integration, scaling, and
absorption correction of the raw data. All the structures have been
solved by direct methods with SHELXD and refined by full-matrix
least-squares methods using SHELXL.16 The WinGX software was
used for modeling.17 It has to be noticed that all the crystals de-
scribed below contain a large percentage of disordered solvent
molecules and very few of them could be modeled in the Fourier
difference density maps. High flux X-ray beams on small crystals
with high solvent contents can explain the modest quality of the
refinement statistics reported in this study.
(CDCl3, 400 MHz):
d
10.65 (s, 1H), 9.01 (s, 1H), 8.19 (t, J¼6.4 Hz, 1H),
7.89 (s, 1H), 7.74 (s, 1H), 7.55 (s, 1H), 7.19 (t, J¼6.4 Hz, 1H), 6.79 (s,
1H), 4.21 (d, J¼6.4 Hz, 2H), 4.17 (d, J¼6.4 Hz, 2H), 4.13 (s, 3H),
2.41e2.35 (m, 2H), 1.56 (s, 9H), 1.21e1.19 (m, 12H). 13C NMR (CDCl3,
100 MHz):
d 166.0, 163.7, 163.3, 161.8, 155.0, 152.8, 152.4, 152.3,
151.4, 144.1, 141.7, 136.2, 136.1, 135.1, 135.0, 127.1, 127.0, 126.0, 125.9,
124.5, 124.5, 122.4, 122.0, 115.3, 114.8, 111.1, 111.0, 99.6, 97.3, 81.3,
75.7, 75.5, 53.8, 28.4, 28.5, 28.3, 19.2. MS (MALDI-TOF): 653.2
[MþH]þ (calcd for C34H39F2N4O7, 653.28); 675.2 [MþNa]þ (calcd for
C34H38F2N4O7Na, 675.26). Trimer 3: 1H NMR (CDCl3, 400 MHz):
Information concerning the crystallographic data collection and
structure refinement of 1: (a) crystallization solvent: hexane/
1,2-dichloroethane, formula C118H137Cl12F7N14O16, Mw¼2565.82,
crystal size 0.2ꢂ0.2ꢂ0.2 mm3, T¼113(2) K, triclinic, space
d
10.54 (s, 2H), 8.67 (s,1H), 8.21 (t, J¼6.4 Hz, 2H), 7.85 (s, 2H), 7.51 (s,
2H), 7.17 (t, J¼6.4 Hz, 2H), 6.83 (s, 2H), 4.05 (d, J¼6.4 Hz, 4H),
2.35e2.28 (m, 2H), 1.57 (s, 18H), 1.18 (d, J¼6.6 Hz, 12H). 13C NMR
group Pꢀ1, a¼22.924(5) A, b¼23.927(5) A, c¼27.624(6) A,
ꢁ
ꢁ
ꢁ
3
(CDCl3, 100 MHz):
d
163.6, 161.6, 152.6, 152.5, 144.1, 141.7, 134.9,
a
¼111.57(3)ꢁ,
b
¼91.20(3)ꢁ,
g
¼111.53(3)ꢁ,
V¼12,893(4) A ,
ꢁ
134.8, 127.0, 127.0, 126.2, 126.1, 124.6, 124.6, 121.9, 115.4, 114.5, 111.0,
110.9, 96.9, 81.3, 75.5, 28.4, 28.3, 19.2. MS (MALDI-TOF): 847.3
[MþH]þ (calcd for C44H50F3N6O8, 847.36); 869.3 [MþNa]þ (calcd for
C44H49F3N6O8Na, 869.35).
Z¼8, rcalcd¼1.322 g cmꢀ3
;
m
¼0.333 mmꢀ1, unique data 46,843, pa-
rameters 2972, GOF¼1.296, R1¼0.1669, wR2¼0.3041 for data
(I>2
s (I)), CCDC 846724; (b) crystallization solvent: hexane/
chlorobenzene, formula C124H120Cl4F7N14O16
,
Mw¼2333.76,
crystal size 0.3ꢂ0.1ꢂ0.2 mm3, T¼113(2) K, triclinic, space
ꢁ
ꢁ
ꢁ
4.2.4. Heptamer (1). Trimer 3 (0.42 g 0.5 mmol) was dissolved in
CH2Cl2 (10 mL), and excess TFA (5 mL) was added. The mixture was
stirred at rt for 3 h. The solvent was evaporated and the residue was
dissolved in CH2Cl2 (20 mL), washed with saturated NaHCO3, dried
over Na2SO4, and then evaporated to give trimer diamine as a yel-
low solid. It was dried in vacuo, and used without further purifi-
cation. Separately, dimer 2 (0.65 g, 1.0 mmol) was dissolved in
a mixture of THF (50 mL) and H2O (5 mL). NaOH (0.1 g, 2.5 mmol)
was added, and the solution was stirred at rt for 5 h. The solution
was neutralized with 1 N HCl to pH¼4e5, then concentrated under
reduced pressure to remove THF. H2O (30 mL) was added to the
residue. The aqueous phase was extracted with CH2Cl2 (3ꢂ50 mL).
The combined organic phases were dried over Na2SO4 and then
evaporated to give the corresponding dimer acid as a yellowish
solid. It was dried in vacuo, and then dissolved in CH2Cl2 (10 mL). To
this solution was added 1-chloro-N,N,2-trimethylpropenylamine
(0.26 g, 2.0 mmol). The reaction mixture was stirred at rt for 2 h
resulting in a homogeneous solution, then evaporated to provide
the corresponding dimer acid chloride. To a solution of the trimer
diamine in CH2Cl2 (20 mL) containing DIPEA (0.7 mL, 4.0 mmol)
was added a solution of dimer acid chloride in CH2Cl2 (10 mL) via
cannula. The reaction mixture was stirred at rt overnight. The so-
lution was evaporated and the product was purified by flash
chromatography (SiO2) eluting with CH2Cl2/EtOAc from 100:5 to
100:20 vol/vol to obtain 1 as a yellowish solid (0.77 g, 82% yield). 1H
group Pꢀ1, a¼21.404(4) A, b¼21.827(4) A, c¼31.385(6) A,
3
ꢁ
ꢁ
a
¼94.18(3)ꢁ,
b
¼108.49(3)ꢁ,
g
¼111.08(3) , V¼12,682(4) A , Z¼4,
rcalcd¼1.136 g cmꢀ3
;
m
¼0.165 mmꢀ1, unique data 45,801, parame-
ters 2678, GOF¼1.071, R1¼0.1795, wR2¼0.3138 for data (I>2
s (I)),
CCDC 846725.
Acknowledgements
We thank the NNSF of China (20972164) and the National Basic
Research Program of China (Grant No. 2009CB930802), the CAS
‘Hundred talents program’ for financial support.
Supplementary data
Supplementary data include experimental procedures, UV/vis,
X-ray crystallography tables, high resolution ESI mass spectrum,
and NMR spectra. Supplementary data associate with this article
can be found at doi:10.1016/j.tet.2011.11.081.
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