Quadruply hydrogen-bonded building block from hydrazide-quinolinone motif and gelation ability of its analogous oxalic monoester-monoamide derivative

Article abstract of DOI:10.1021/ol702194z

NMR and STM studies revealed that the hydrazide-quinolinone-based building block 5 exhibited a monomer-dimer-polymer equilibrium, while its acyclic analogue 6, due to conformational flexibility, exhibited a more complicated mode of aggregation and formed

Full text of DOI:10.1021/ol702194z

ORGANIC
LETTERS
2007
Vol. 9, No. 24
4991-4994
Quadruply Hydrogen-Bonded Building
Block from Hydrazide Quinolinone Motif
and Gelation Ability of Its Analogous
Oxalic Monoester Monoamide Derivative
−
−
Yong Yang, Hui-Juan Yan, Chuan-Feng Chen,* and Li-Jun Wan*
Beijing National Laboratory for Molecular Sciences, Center for Chemical Biology,
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China
cchen@iccas.ac.cn
Received September 6, 2007
ABSTRACT
NMR and STM studies revealed that the hydrazide−quinolinone-based building block 5 exhibited a monomer−dimer−polymer equilibrium,
while its acyclic analogue 6, due to conformational flexibility, exhibited a more complicated mode of aggregation and formed a gel in
dichloromethane/hexane.
Due to its directionality, specificity, and strength, hydrogen
bonding has been described as the “master key interaction
in supramolecular chemistry”.1 Multiple hydrogen-bonded
systems, especially quadruple hydrogen-bonded systems,
have gained great success in the construction of many
superstructures and applications in the fields of material
science, catalysis, and template synthesis.2 Inspired by the
hydrogen-bonding capability of nucleobases found in DNA
duplexes, quadruple hydrogen-bonded systems are mainly
based on functionalized nucleobases, especially urea deriva-
tives. Heterocycle-based quadruple hydrogen-bonded systems
developed by the groups of Meijer et al.3 and Zimmerman
et al.4 are examples of great success. However, the number
of quadruple hydrogen-bonded modules available for use in
supramolecular assembly is limited.5 There is a strong need
for the development of new quadruple hydrogen-bonded
systems to meet the demand of increasing applications.
Organogels are a new class of soft materials, composed
of a self-assembled superstructure of low-molecular-mass
organic gelators (LMOGs) through specific interactions and
a large volume of organic liquid immobilized therein.6
(3) (a) Beijer, F. H.; Kooijman, H.; Spek, A. L.; Sijbesma, R. P.; Meijer,
E. W. Angew. Chem., Int. Ed. 1998, 37, 75-78. (b) Sijbesma, R. P.; Beijer,
F. H.; Brunsveld, L.; Folmer, B. J. B.; Hirschberg, J. H. K. K.; Lange, R.
F. M.; Lowe, J. K. L.; Meijer, E. W. Science 1997, 278, 1601-1604.
(4) (a) Corbin, P. S.; Zimmerman, S. C. J. Am. Chem. Soc. 1998, 120,
9710-9711. (b) Park, T.; Zimmerman, S. C.; Nakashima, S. J. Am. Chem.
Soc. 2005, 127, 6520-6521.
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(2) Sijbesma, R. P.; Meijer, E. W. Chem. Commun. 2003, 5-16 and
references therein.
10.1021/ol702194z CCC: $37.00
© 2007 American Chemical Society
Published on Web 10/23/2007

Stimulated by the potential applications in sensors, molecular
electronics, and catalysts, great efforts have been paid to this
kind of new material. In hydrogen bond-mediated self-
assembly systems, little attention has been paid to the
hydrazide derivatives,7 considering their high density of
hydrogen-bonding sites (two acceptor sites and two donor
sites) and convenient fixation of conformation.
As stated above, most heterocycle-based quadruple hy-
drogen-bonded systems came from urea derivatives. Con-
tinuing our current interest in the hydrazide motif as an
excellent building block in self-assembly,8 we herein report
a new quadruple hydrogen-bonded motif based on hy-
drazide-quinolinone derivative. Its acyclic analogue oxalic
monoester-monoamide derivative gelates organic liquid to
form organogel. To increase the strength, in the design of
the target molecule 5 the following factors have been
considered (Scheme 1): (i) the rigid quinolinone framework
quadruple hydrogen-bonded homodimer; (ii) the aromatic
ring as a spacer reduces 2-fold repulsive electrostatic
interactions;10 (iii) the reservation of R-carbonyl vinyl motif
renders good proton donability of the NH group and
consequent high stability of the resulting homodimer. In the
case of its acyclic analogue 6, the self-assembly process may
be complicated by large conformational mobility.
2-(Octyloxy)-5-nitrobenzoic acid (1)11 was first converted
into its acyl chloride in refluxing thionyl chloride and then
coupled with acetylhydrazide to give compound 2 in
quantitative yield. The nitro functional group was reduced
under the catalytic hydrogenation conditions and then was
reacted with dimethyl acetylenedicarboxylate to give com-
pound 4 or was coupled with methyl oxalyl chloride to give
compound 6. Compound 4 further underwent thermal cy-
cloaddition reaction in reflux diphenyl ether to give com-
pound 5 in satisfying yield. As control, compounds 7,8a 8,12
and 913 were also synthesized (Scheme 2).
Scheme 1. Secondary Electrostatic Interaction Analysis of
Homodimer 5‚5 and Conformational Analysis of Acyclic 6
Scheme 2. Synthetic Route of 5 and 6, Chemical Structures
of Controls 7, 8, and 9
and introduction of an S(6)-type hydrogen-bonded ring9
confine the molecule to be planar and preorganize hydrogen-
bonding sites staying in register for the formation of a
(5) Selected examples: (a) Ducharme, Y.; Wuest, J. D. J. Org. Chem.
1988, 53, 5787-5789. (b) Lafitte, V. G. H.; Aliev, A. E.; Horton, P. N.;
Hursthouse, M. B.; Bala, K.; Golding, P.; Hailes, H. C. J. Am. Chem. Soc.
2006, 128, 6544-6545. (c) Martin, A. M.; Butler, R. S.; Ghiviriga, I.;
Giessert, R. E.; Abboud, K. A.; Castellano, R. K. Chem. Commun. 2006,
4413-4415. (d) Davis, A. P.; Draper, S. M.; Dunne, G.; Ashton, P. Chem.
Commun. 1999, 2265-2266. (e) Prabhakaran, P.; Puranik, V. G.; Sanjayan,
G. J. J. Org. Chem. 2005, 70, 10067-10072. (f) Lu¨ning, U.; Ku¨hl, C.
Tetrahedron Lett. 1998, 39, 5735-5738. (g) Gong, B. Polym. Int. 2007,
56, 436-443 and references therein.
(6) Weiss, R. G., Terech, P., Eds. Molecular Gels. Materials with Self-
Assembled Fibrillar Networks; Springer: Dordrecht, The Netherlands, 2005.
(7) (a) Nowick, J. S. Org. Biomol. Chem. 2006, 4, 3869-3885. (b) Zhao,
X.; Wang, X.-Z.; Jiang, X.-K.; Chen, Y.-Q.; Li, Z.-T.; Chen, G.-J. J. Am.
Chem. Soc. 2003, 125, 15128-15139. (c) Hou, J.-L.; Shao, X.-B.; Chen,
G.-J.; Zhou, Y.-X.; Jiang, X.-K.; Li, Z.-T. J. Am. Chem. Soc. 2004, 126,
12386-12394. (d) Li, C.; Wang, G.-T.; Yi, H.-P.;Jiang, X.-K.; Li, Z.-T.;
Wang, R.-X. Org. Lett. 2007, 9, 1797-1800.
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2006, 30, 140-142. (b) Yang, Y.; Hu, H.-Y., Chen, C.-F. Tetrahedron Lett.
2007, 48, 3505-3509. (c) Yang, Y.; Yang, Z.-Y; Yi, Y.-P.; Xiang, J.-F.;
Chen, C.-F.; Wan, L.-J.; Shuai, Z.-G. J. Org. Chem. 2007, 72, 4936-4946.
(d) Yang, Y.; Xiang, J.-F.; Chen, C.-F. Org. Lett. 2007, 9, 4355-4357.
(9) (a) Etter, M. C. Acc. Chem. Res. 1990, 23, 120-126. (b) Etter, M.
C.; Macdonald, J. C.; Bernstein, J. Acta Crystallogr., Sect. B. 1990, 46,
256-262. (c) Bernstein, J.; Davis, R. E.; Shimoni, L.; Chang, N.-L. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1555-1573.
1H NMR studies (Figure 1, each 5 mM) in CDCl3 revealed
significant downfield shifts of NH signals of 5 (11.64 ppm
for Hb, 10.45 ppm Ha, and 10.88 ppm for Hc) compared to
those of control compounds 7 (10.91 ppm for Hb, 9.03 ppm
Ha), and 8 (8.99 ppm for Hc), while minor downfield shifts
were observed for compound 6 (11.03 ppm for Hb, 9.42 ppm
for Ha, and 9.53 ppm for Hc) compared to controls 7 and 9
(10) (a) Jorgensen, W. L.; Pranata, J. J. Am. Chem. Soc. 1990, 112,
2008-2010. (b) Pranata, J.; Wierschke, S. G.; Jorgensen, W. L. J. Am.
Chem. Soc. 1991, 113, 2810-2819. (c) Murray, T. J.; Zimmerman, S. C.
J. Am. Chem. Soc. 1992, 114, 4010-4011.
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Soc. 2000, 122, 2635-2644.
(12) Jaen, J. C.; Laborde, E.; Bucsh, R. A.; Caprathe, B. W.; Sorenson,
R. J.; Fergus, J.; Spiege1, K.; Marks, J.; Dickerson, M. R.; Davis, R. E. J.
Med. Chem. 1995, 38, 4439-4445.
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Rosenthale, M. J. Med. Chem. 1975, 18, 926-933.
4992
Org. Lett., Vol. 9, No. 24, 2007

are much too long for any cross-peaks to be observed within
the same molecule of 5; the signals must correspond to
intermolecular contacts between the two constituent mol-
ecules of the homodimer. ESI-MS14 provided more evidence
for the formation of a homodimer; in additon to a signal
corresponding to monomer (432.4, [M + H]+, calcd: 432.2),
signals corresponding to the homodimer structure (885.7,
[2M + Na]+, calcd: 885.4; 863.7, [2M + H]+, calcd: 863.4)
were observed. Another important NOE contact between Hd
and Hg was also observed, which cannot be explained
intramolecularly based on a monomer or intermolecularly
based on a homodimer. There should exist an equilibrium
of monomer-homodimer-polymer as depicted in Figure 3.15
Figure 1. Stacked partial spectra of (a) 7, (b) 8, (c) 9, (d) 5, (e) 6,
each 5 mM in CDCl3, 298 K, 300 MHz.
(8.87 ppm for Hc). In addition to the different electrostatic
effects of the frameworks, different aggregation modes might
mainly account for these great differences.
Dilution 1H NMR experiments14 (298 K, 300 MHz,
CDCl3) on 5 revealed unique concentration dependency.
Within the concentration range investigated (from 100 mM
to 0.5 mM), almost all resonances of the protons of 5 shifted
downfield with the lowering of the concentration, especially
those for Hc (∆ ) 1.03 ppm) and He (∆ ) 1.12 ppm). This
phenomenon might suggest the existence of different ag-
gregation modes in CDCl3 solution. A 2D NOESY experi-
ment (Figure 2) further revealed important contacts between
Figure 3. Representation of a monomer-homodimer-polymer
equilibrium of 5, with important NOE contacts indicated by arrows.
1
Variable-temperature H NMR experiments14 (10 mM,
CDCl3, 600 MHz) further confirmed the above hypothesis.
With lowering the temperature, the spectra became unre-
solvable. This might come from slowing the above-
mentioned equilibrium, which complicated the picture of
NMR spectra. Scanning tunneling microscope (STM) tech-
nology provided other evidence. An STM image of 5 on high
oriented pyrolytic graphite (HOPG) is shown in Figure 4.
The image clearly shows the homodimer structure and the
zipperlike polymeric structure.
In the case of its acyclic analogue 6, because of flexible
comformation, there were great differences. First, dilution
1H NMR experiments (CDCl3, 300 MHz, 298 K)14 revealed
that below a concentration of 5 mM, it displayed a well-
Figure 2. 2D NOESY spectrum of 5, 100 mM, CDCl3, 298 K,
300 MHz, with important NOE contacts highlighted.
(15) At higher concentrations, the two hydrogen bond-linked polymer
might be favored, while the quadruple hydrogen-bonded homodimer might
be favored at lower concentrations. As a result, formation of quadruple
hydrogen bonds and the deshielding effects of the aromatic rings led to
downfield shifts of the protons. This unique phenomenon would need further
investigation. Because of the complicated picture of self-assembly, no
apparent association constant was provided.
Hh and Hg, Hh and Ha, Ha and Hc, and Hc and He. In addition
to Hc and He, distances between the above-mentioned protons
(14) See Supporting Information for details.
Org. Lett., Vol. 9, No. 24, 2007
4993

Figure 4. STM image of 5 on HOPG, showing homodimer
Figure 5. AFM image of a gel formed from 6 in CH2Cl2/hexane,
structure and zipperlike polymeric structure.
ca. 2% (w/w), with digital photography of the gel inserted.
resolved spectrum, while with increase of the concentration,
the spectrum became unresolvable. Lowering the temperature
also led to unresolvable spectra.14 These all suggested a more
complicated aggregation mode of 6 compared to those of 5.
Slow evaporation of a solution of 6 in CH2Cl2/hexane led to
an opaque gel at a concentration of ca. 2% (w/w). An AFM
image (Figure 5) on xerogel revealed fibrous structure. We
proposed that the single molecule of 6 first self-assembled
into a polymeric structure via hydrogen bonding, and then
the polymeric structures entangled with each other to form
a network. The nonpolar solvent was then immobilized
mainly through van der Waals interactions.
2% (w/w). We believe that the new building block we
presented here can find wide applications in the development
of new self-assemblies, material science, and construction
of various nanostructures.
Acknowledgment. We are very grateful to the National
Natural Science Foundation of China, National Basic Re-
search Program (2007CB808004), and the Chinese Academy
of Sciences for financial support. We also thank Dr. Jun-
Feng Xiang at Institute of Chemistry, Chinese Academy of
Sciences for assistance in NMR experiments.
In summary, we have presented a new hydrazidequinoli-
none-based quadruple hydrogen-bonded building block.
NMR and STM studies showed that there exists a monomer-
dimer-polymer equilibrium. Contrary to many heterocycle-
based systems, no isomerization in our system was observed.
While its acyclic analogue displayed a more complicated
aggregation mode due to its conformational flexibility. It
formed gel in dichloromethane/hexane at a concentration of
Supporting Information Available: Experimental pro-
cedure, characterization data, NMR spectra for new com-
1
pounds; VT and dilution H NMR spectra; ESI-MS of 5.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL702194Z
4994
Org. Lett., Vol. 9, No. 24, 2007