The self-assembly of six-petal microflowers by hydrogen-bonded shape-persistent triangular aromatic hydrazide derivatives

Article abstract of DOI:10.1016/j.tetlet.2010.06.021

Six-petal microflowers have been self-assembled in methanol from C ₃-symmetric shape-persistent triangular aromatic hydrazide derivatives. Nine intramolecular hydrogen bonds are used to enhance the planarity of the aromatic backbone, while six 2-(2-(2-methoxyethoxy)ethoxy)- ethoxyl groups are appended to the rigid aromatic backbone. Scanning electron microscopy (SEM) images show that the molecules form unique six-petal flower-like aggregates in methanol. A self-assembling mechanism that is similar to the formation of snowflakes has been proposed.

Full text of DOI:10.1016/j.tetlet.2010.06.021

Tetrahedron Letters 51 (2010) 4221–4224
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The self-assembly of six-petal microflowers by hydrogen-bonded
shape-persistent triangular aromatic hydrazide derivatives
*
Jian-Bin Lin, Gui-Tao Wang, Xi-Kui Jiang, Zhan-Ting Li
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Six-petal microflowers have been self-assembled in methanol from C3-symmetric shape-persistent trian-
gular aromatic hydrazide derivatives. Nine intramolecular hydrogen bonds are used to enhance the pla-
narity of the aromatic backbone, while six 2-(2-(2-methoxyethoxy)ethoxy)-ethoxyl groups are appended
to the rigid aromatic backbone. Scanning electron microscopy (SEM) images show that the molecules
form unique six-petal flower-like aggregates in methanol. A self-assembling mechanism that is similar
to the formation of snowflakes has been proposed.
Received 14 April 2010
Revised 28 May 2010
Accepted 4 June 2010
Available online 9 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
The self-assembly of aromatic molecules into well-defined
supramolecular architectures has received considerable interest
in the past decades due to their fundamental and practical impor-
tance. In this context, the aggregation of several C3-symmetric aro-
matic systems has been extensively investigated, which lead to the
formation of supramolecular liquid crystals,1 vesicles,2 and organo-
gels,3 or the generation of supramolecular chirality.4 We have re-
cently utilized the intramolecular hydrogen bonding to induce
linear aromatic amide or hydrazide molecules to adopt folded or
extended conformations.5 The hydrazide-based shape-persistent
oligomers that bear amphiphilic or hydrophobic side chains may
stack to form vesicles or organogels.6 Herein, we report that two
hydrogen-bonded shape-persistent triangular aromatic hydrazide
derivatives can self-assemble into unique six-petal flower-like
architectures. To the best of our knowledge, this is the first
example that organic aromatic molecules stack to produce snow-
flake-styled aggregates, although several examples of six-petal
flower-shaped structures that are obtained from inorganic salts
have been reported.7
Triangular compounds 1a–c have been designed and prepared.
Nine six-membered N–HÁ Á ÁOR hydrogen bonds are introduced to
enhance the planarity of the aromatic backbones,8 whereas six 2-
(2-(2-methoxyethoxy)ethoxy)-ethoxyl groups are appended to
balance the amphiphilicity of the whole molecules. The synthesis
of these molecules is straightforward. The synthetic routes for 1a
and 1b are provided in Scheme 1.9 Thus, acid 26a was first coupled
with the related amines to give 3a and 3b, respectively, in high
yields. The two ester intermediates were then treated with an ex-
cess of hydrazine monohydrate in hot methanol to yield com-
pounds 4a and 4b, which were further reacted with trialdehyde
510 to produce 1a and 1b in high yields. 1H NMR spectra of the
crude products in CDCl3 showed that all the starting materials
were consumed and one set of signals was exhibited. Considering
the sensitivity of the 1H NMR technique, we proposed that the tri-
angular products should be formed in P95% yield. Instead of using
simple benzene-1,3,5-tricarbaldehyde, compound 5 was chosen for
the reactions because it could form three stable six-membered
O–HÁ Á ÁN intramolecular hydrogen bonds,11 which remarkably
rigidified and stabilized the core of the aromatic systems. The syn-
thesis of compound 1c is shown in Scheme 2. The key precursor 7
was first prepared by tolylation of ol 612 in chloroform. Then, com-
pound 8 was coupled with n-butylamine to give 9. The diol was
RO
OR
R'NH2, EDCI, DMAP
THF, r.t., 12 h
MeO2C
CO2H
2
RO
OR
CO2Me
NH2NH2, MeOH
50 ºC, 6 h
n-BuHNOC
3a (90%)
3b (81%)
CHO
HO
OHC
OH
CHO
5
RO
O
OR
O
OH
1a (90%)
1b (87%)
n-BuOH, reflux
12 h, 90%
NHBu-n NHNH2
4a: (90%)
4b: (85%)
R = (CH2CH2O)3Me,
3a, 4a: R' = Bu-n
3b, 4b: R' = ( )-CH(Me)CHMe2
R
* Corresponding author. Tel.: +86 21 54925122; fax: +86 21 64166128.
E-mail address: ztli@mail.sioc.ac.cn (Z.-T. Li).
Scheme 1. The synthesis of triangular compounds 1a and 1b.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.021

4222
J.-B. Lin et al. / Tetrahedron Letters 51 (2010) 4221–4224
TsCl, NEt3
CHCl3, r.t., 12 h, 75%
O
O
MeO
OH
6
MeO
OH
O
O
OTs
7
HO
n-BuNH2, DCC
THF, r.t., 24 h, 65%
MeO2C
CO2H
8
9
HO
OH
7, K2CO3, MeCN
reflux, 12 h, 70%
MeO2C
CONHBu-n
RO
OR
NH2NH2, MeOH
50 °C, 12 h, 85%
MeO2C
CONHBu-n
10
RO
OR
5, n-BuOH
1c
reflux, 12 h, 86%
R = S-CHCH(Me)O(CH2CH2O)2Me
Scheme 2. The synthesis of triangular compound 1c.
n-BuHNOC
CONHNH2
11
Figure 1. SEM images on mica surface: the samples of 1a after its MeOH solution
(1 mM) was evaporated in (a) 1 min, (b) 5 min, and (c) 30 min. (d) Fluorescence
micrograph of the sample for obtaining the second image. The samples of (e) 1b and
(f) 1c, after their MeOH solution (1 mM) was evaporated in 30 min.
further reacted with tosylate 7 to produce ester 10, which was
treated with an excess of hydrazine to afford benzohydrazide 11.
Finally, this precursor was reacted with 5 to produce 1c in 85%
yield.
be about 12
of the six-petal flowers ranged from 4
l
m (calculated from 30 platelets), while the diameter
m to 11 m. This difference
R"
N
H
l
l
R'
R'
O
O
implied that their formation followed different growth mecha-
nisms. The SEM images of compound 1b revealed that this triangu-
lar molecule did not generate any of the above ordered structures
(Fig. 1e), probably due to the steric effect of the larger 3-methylb-
utan-2-yl groups, which were close to the aromatic core and pre-
sumably weakened the stacking of the aromatic backbone.
Compound 1c formed the similar six-petal flowers (Fig. 1f). This
compound has six chiral side chains, but its assembled flowers
did not display an observable chiral bias. The SEM images also
showed that the samples obtained by evaporation of the mixture
solution of 1a and 1c within the molar ratio of 9:1–1:9 in methanol
all generated six-petal flower-shaped crystals, suggesting that
their aggregation might follow the identical mechanism. The intro-
duction of the chiral atom in 1b and 1c were originally used to test
if a chiral differentiation was induced for the flower-shaped aggre-
gates, which we did not observe from the SEM images.
O
H
O
H
N
N
O
R'
O
N
H O
H
N
H
N
R'
O
O
O
N
O
H
N
O
N
H
O
O
R"
R"
R'
H
O
R'
1a: R' = (CH2CH2O)3Me, R" = n-Bu
1b: R' = (CH2CH2O)3Me, R" =
The maximum absorbance wavelength of compound 1a in the
UV–vis spectra in methanol was shifted from 382 nm to 340 nm,
when the concentration was increased from 0.5 lM to 7 lM. The
1c: R' =
R" = n-Bu
O
O
OMe
large blue shifting indicated that it stacked in a H-aggregation
(face-to-face) form even in very dilute solution.13,14 Diluting the
solution of 1a in CD3OD from 5 mM to 0.2 mM caused the signal
of its H-5 proton of the peripheral benzene ring in the 1H NMR
spectra to shift downfield by 0.08 ppm. This result supported that
the molecule further stacked at higher concentrations. The X-ray
diffraction (XRD) of the dried samples of 1a obtained by evaporat-
ing its solution (1 mM) in methanol or the mixture of methanol
and water (1:1) revealed a broad peak at 0.40 nm and a strong,
sharp peak at 1.6 nm, respectively. The former peak might be
attributed to a less compact stacking of the aromatic backbone,15
while the latter peak was close to the size of the backbone
Scanning electron microscopy (SEM) images showed that com-
pound 1a formed dendrites that consisted of particles of nano
scales (Fig. 1a), when its solution in methanol was evaporated
quickly. With the evaporation rate being slowed down, hexagonal
platelets and then six-petal flower-shaped crystals were generated
selectively (Fig. 1b and c). The formation of the hexagonal platelets
was also confirmed by the fluorescent microscopy image (Fig. 1d).
The average diameter of the hexagonal platelets was estimated to

J.-B. Lin et al. / Tetrahedron Letters 51 (2010) 4221–4224
4223
(1.7 nm) and thus suggested a column-styled structure in the solid
state.
To get more insight into the formation mechanism of the un-
ique flower-shaped crystals, the effect of the media was also stud-
ied for compound 1a. Adding benzene to the solution of methanol
remarkably impeded the formation of the flowers. When the con-
tent of benzene was increased to 10% (v/v), no ordered structures
were observed on the SEM image. This result further supported
that stacking interaction played a key role for the formation of
the assembled flowers. The existence of benzene not only de-
creased the polarity of the medium, but also, presumably more
importantly, stacked with the aromatic systems of 1a and thus
weakened their own stacking.
The self-assembling behavior of compound 1a in the mixture of
methanol and water was also investigated by SEM. The results are
presented in Figure 2. Before the content of water was increased to
50%, six-petal flowers were always observed on the SEM images
(Fig. 2a–c). However, further increase of water resulted in the
selective formation of new leaf-like crystals (Fig. 2d). When the
content of water was increased to 90%, hexagonal rod-like crystals
were generated exclusively (Fig. 2e and f), although their average
size was considerably smaller that that formed by quickly evapo-
rating the solution of 1a in methanol (Fig. 1b). These results may
be rationalized by considering that, with the increase of the med-
ium polarity, the stacking of the aromatic systems was continually
enhanced and consequently the crystals grew more quickly from
the two ends of the small platelets. As a result, the growth from
the side was suppressed.
Figure 3. Possible mechanism for the formation of the six-petal flower-like
aggregates of compounds 1a and 1c. After the hexagonal plates are formed, they
grow more quickly from the corners than from the facets, like the process for the
formation of snow-flakes.
It is reasonable to propose that the crystal growth of the new
aromatic systems in the polar medium was a thermodynamically
and dynamically balanced process. For the formation of the six-pe-
tal flowers, the first step should be the nucleation of the stacked
aggregates into the hexagonal plates. These small crystals were al-
ways observed to co-exist together with the larger flower-shaped
structures, as shown in Figs. 1c and 2a. For the formation of the
hexagonal platelets, the triangular molecules might need to stack
in a dislocated manner (Fig. 3). Once the hexagonal crystal cores
were formed, they were grown more quickly from the corners than
from the smooth facets, as established for the formation of snow-
flakes,16 to produce the sectored flowers (Fig. 3). When the content
of water was high enough, the stacking interaction was enhanced.
Growth from the ends became overwhelming and the long prisms
were eventually formed.
In conclusion, we have demonstrated that hydrogen-bonded
shape-persistent triangular aromatic hydrazides can self-assemble
into six-petal flower-shaped crystals. The growth mechanism for
this kind of unique supramolecular architectures has been pro-
posed to resemble that for the formation of the snowflakes. The re-
sult illustrates that rationally designed rigid aromatic systems may
exhibit new self-assembling property that is usually displayed by
hard inorganic materials. In the future, we will investigate the
structural factors that affect the formation of the flower-shaped
crystals by designing new conjugated triangular molecules. The
formation of the micro-scaled hexagonal rods also bodes well for
future development of photo- and electro-active assembled struc-
tures. To realize this, large conjugated systems have to be designed.
Acknowledgments
We thank National Natural Science Foundation of China
(20921091, 20974118, 20872167, 20732007), Ministry of Science
and Technology of China (2007CB-808001), and Science and Tech-
nology Commission of Shanghai Municipality (09XD1405300) for
financial support.
References and notes
1. (a) Hennrich, G.; Omenat, A.; Asselberghs, I.; Foerier, S.; Clays, K.; Verbiest, T.;
Serrano, J. L. Angew. Chem., Int. Ed. 2006, 45, 4203–4206; (b) Feng, X.; Pisula, W.;
Kudernac, T.; Wu, D.; Zhi, L.; De Feyter, S.; Müllen, K. J. Am. Chem. Soc. 2009,
131, 4439–4448.
2. (a) Santacroce, P. V.; Okunola, O. A.; Zavalij, P. Y.; Davis, J. T. Chem. Commun.
2006, 3246–3248; (b) Seo, S. H.; Chang, J. Y.; Tew, G. N. Angew. Chem., Int. Ed.
Figure 2. SEM images on mica surface of the samples of 1a, after its solution in the
mixture of MeOH and water (1 mM) was evaporated in 30 min. The content (v/v) of
water is (a) 0%, (b) 30%, (c) 50%, (d) 70%, (e) and (f) 90%.

4224
J.-B. Lin et al. / Tetrahedron Letters 51 (2010) 4221–4224
2006, 45, 7526–7530; (c) Fernandez, G.; Garcia, F.; Sánchez, L. Chem. Commun.
2008, 6567–6569.
9. Compound 1a: A solution of compounds 4a (0.17 g, 0.30 mmol) and 5 (21 mg,
0.10 mmol) in butanol was heated under reflux for 12 h and then concentrated
with a rotavapor. The resulting slurry was recrystallized from ether to give 1a
as a pale yellow solid (0.16 g, 90%). 1H NMR (300 MHz, CDCl3) d: 13.36 (s, 3H),
11.06 (s, 3H), 8.67 (s, 3H), 8.43 (s, 3H), 7.62 (t, 3H), 5.97 (s, 3H), 4.44–3.28 (m,
96H), 1.60 (m, 6H), 1.41 (m, 6H), 0.98 (m, 9H). 13C NMR (75 MHz, CDCl3) d:
164.37, 161.62, 159.96, 159.90, 159.33, 144.29, 136.45, 114.00, 112.09, 99.21,
96.08, 75.34, 39.70, 31.72, 28.36, 28.33, 20.38, 19.71, 19.39, 13.78. MS (MALDI-
TOF): m/z 1857.4 [M+Na]+. HRMS (ESI): calcd for C87H135N9O33Na: 1856.9067.
Found: 1856.9055.
3. (a) de Loos, M.; van Esch, J. H.; Kellogg, R. M.; Feringa, B. L. Tetrahedron 2007, 63,
7285–7301; (b) Li, H.; Homan, E. A.; Lampkins, A. J.; Ghiviriga, I.; Castellano, R.
K. Org. Lett. 2005, 7, 443–446.
4. (a) Smulders, M. M. J.; Buffeteau, T.; Cavagnat, D.; Wolffs, M.; Schenning, A. P.
H. J.; Meijer, E. W. Chirality 2008, 20, 1016–1022; (b) Palmans, A. R. A.;
Vekemans, J. A. J. M.; Havinga, E. E.; Meijer, E. W. Angew. Chem., Int. Ed. 1997, 36,
2648–2651.
5. (a) Li, Z.-T.; Hou, J.-L.; Li, C.; Yi, H.-P. Chem. Asian J. 2006, 1, 766–778; (b) Li, Z.-
T.; Hou, J.-L.; Li, C. Acc. Chem. Res. 2008, 41, 1343–1353; (c) Zhao, X.; Li, Z.-T.
Chem. Commun. 2010, 46, 1601–1616.
10. Chong, J. H.; Sauer, M.; Patrick, B. O.; MacLachlan, M. J. Org. Lett. 2003, 5, 3823–
3836.
6. (a) Cai, W.; Wang, G.-T.; Xu, Y.-X.; Jiang, X.-K.; Li, Z.-T. J. Am. Chem. Soc. 2008,
130, 6936–6937; (b) You, L.-Y.; Jiang, X.-K.; Li, Z.-T. Tetrahedron 2009, 65, 9494–
9504; (c) Cai, W.; Wang, G.-T.; Du, P.; Wang, R.-X.; Jiang, X.-K.; Li, Z.-T. J. Am.
Chem. Soc. 2008, 130, 13450–13459.
11. Lin, J.-B.; Wu, J.; Jiang, X.-K.; Li, Z.-T. Chin. J. Chem. 2009, 27, 117–122.
12. Kim, H.-J.; Zin, W.-C.; Lee, M. J. Am. Chem. Soc. 2004, 126, 7009–7014.
13. Xiao, D.; Xi, L.; Yang, W.; Fu, H.; Shuai, Z.; Fang, Y.; Yao, J. J. Am. Chem. Soc. 2003,
125, 6740–6745.
7. (a) Ni, Y.; Liu, H.; Wang, F.; Liang, Y.; Hong, J.; Ma, X.; Xu, Z. Cryst. Res. Technol.
2004, 39, 200–206; (b) Liu, X.; Yi, R.; Wang, Y.; Qiu, G.; Zhang, N.; Li, X. J. Phys.
Chem. C 2007, 111, 163–167; (c) Zhang, J.; Sun, L.; Yin, J.; Su, H.; Liao, C.; Yan, C.
Chem. Mater. 2002, 14, 4172–4177.
14. Kasha, M.; Rawls, H. R.; Bl-Bayoumi, M. A. Pure Appl. Chem. 1965, 11, 371–392.
15. (a) Chen, Y.; Lü, Y.; Han, Y.; Zhu, B.; Zhang, F.; Bo, Z.; Liu, C.-Y. Langmuir 2009,
25, 8548–8555; (b) Xu, X.-N.; Wang, L.; Li, Z.-T. Chem. Commun. 2009, 6634–
6636.
8. Palmans, A. R. A.; Vekemans, J.; Fischer, H.; Hikmet, R. A.; Meijer, E. W. Chem.
Eur. J. 1997, 3, 300–307.
16. Libbrecht, K. G. Rep. Prog. Phys. 2005, 68, 855–895.