Synthesis of poly(benzyl ether) dendrimer containing tetra(ethyleneoxide) at core using click chemistry

Article abstract of DOI:10.1080/15421400802332842

The convergent synthetic strategy for the poly(benzyl ether) dendrimers having the tetraethyleneoxide at core via the copper-catalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide was described. Tetraethyleneglycol diazide, designed to serv

Full text of DOI:10.1080/15421400802332842

This article was downloaded by: [Chulalongkorn University]
On: 02 January 2015, At: 06:26
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Molecular Crystals and Liquid
Crystals
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gmcl20
Synthesis of Poly(benzyl
ether) Dendrimer Containing
Tetra(ethyleneoxide) at Core
Using Click Chemistry
Jae Wook Lee a , Hwa-Shin Kang a , Seung Choul Han
a , Sae Reum Sung a , Ji Hyeon Kim b , Jinho Oh c &
Sung-Ho Jin d
a Department of Chemistry and Department of
Medical Bioscience , Dong-A University , Busan ,
Korea
b Department of Chemical and Bio Engineering ,
Kyungwon University , Seongnam , Korea
c Institute for Gifted Students, Korea Advanced
Institute of Science and Technology , Daejeon ,
Korea
d Department of Chemistry Education and Center
for Plastic Information System , Pusan National
University , Busan , Korea
Published online: 31 Aug 2012.
To cite this article: Jae Wook Lee , Hwa-Shin Kang , Seung Choul Han , Sae Reum
Sung , Ji Hyeon Kim , Jinho Oh & Sung-Ho Jin (2008) Synthesis of Poly(benzyl
ether) Dendrimer Containing Tetra(ethyleneoxide) at Core Using Click Chemistry,
Molecular Crystals and Liquid Crystals, 492:1, 139/[503]-146/[510], DOI:
10.1080/15421400802332842
To link to this article: http://dx.doi.org/10.1080/15421400802332842

PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Mol. Cryst. Liq. Cryst., Vol. 492, pp. 139=[503]–146=[510], 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400802332842
Synthesis of Poly(benzyl ether) Dendrimer Containing
Tetra(ethyleneoxide) at Core Using Click Chemistry
Jae Wook Lee1, Hwa-Shin Kang1, Seung Choul Han1, Sae
Reum Sung1, Ji Hyeon Kim2, Jinho Oh3, and Sung-Ho Jin4
1Department of Chemistry and Department of Medical Bioscience,
Dong-A University, Busan, Korea
2Department of Chemical and Bio Engineering, Kyungwon University,
Seongnam, Korea
3Institute for Gifted Students, Korea Advanced Institute of Science
and Technology, Daejeon, Korea
4Department of Chemistry Education and Center for Plastic Information
System, Pusan National University, Busan, Korea
The convergent synthetic strategy for the poly(benzyl ether) dendrimers having
the tetraethyleneoxide at core via the copper-catalyzed 1,3-dipolar cycloaddition
reaction between alkyne and azide was described. Tetraethyleneglycol diazide,
designed to serve as the core in dendrimer, was stitched with the alkyne-functiona-
lized poly(benzyl ether) dendrons by the click chemistry leading to the formation of
triblock dendritic polymers in high yields. The absorption and emission of the
dendrimers were investigated. The structure of the dendrimers was characterized
with 1H NMR, 13C NMR, and IR spectroscopies, mass spectra, and gel-permeation
chromatography.
Keywords: 1,3-Dipolar cycloaddition; click chemistry; dendrimer; PEO
INTRODUCTION
Dendrimers are highly branched macromolecules, which are prepared
by repetition of a given set of reactions using either divergent or con-
vergent strategies [1]. Generally, the reactions employed are high
yielding without any side reactions. Well known processes, such as
This research was supported by the Dong-A University Research Fund.
Address correspondence to Jae Wook Lee, Department of Chemistry, Dong-A Univer-
sity, Busan 604-714, Korea. E-mail: jlee@donga.ac.kr and Sung-Ho Jin, Department of
Chemistry Education and Center for Plastic Information System, Pusan National
University, Busan 609-735, Korea. E-mail: shjin@pusan.ac.kr
139=[503]

140=[504]
J. W. Lee et al.
the Michael reaction, Williamson ether synthesis, amidations and
reductions have been used extensively [2]. Recent solid chemistry is
the click chemistry which is the copper-catalyzed 1,3-dipolar cycload-
dition reaction between alkyne and azide developed by Sharpless
and Tornøe [3]. This reaction is characterized by very high yields, mild
and simple reaction conditions, oxygen and water tolerance, and ease
of product isolation. It is highly chemoselective affording only the
desired 1,2,3-triazole even in the presence of a large variety of other
functional groups. This click chemistry is a modular approach that
uses the most practical and reliable chemical transformations and is
clearly a breakthrough in the synthesis of dendrimers and dendritic
and polymer materials [4]. We have developed the fusion and stitching
methods for the synthesis of symmetric and unsymmetric dendrimers
and diblock codendrimers using click chemistry between an alkyne
and an azide [5–7]. Overall, this method was found to be a straightfor-
ward strategy for the synthesis of triazole-based dendrimers. At this
time, we are intrigued to obtain the functional dendrimers containing
poly(ethyleneoxide) unit at core which could be utilized as solid-state
electrolyte for fuel cells and DSSCs, electrochemical sensors, electro-
chromic devices, and so on. The convergent methodology in the syn-
thesis of dendrimers installs the core in the final step and allows for
a large degree of chemical diversity such that functional groups can
be incorporated at nearly central position in the dendritic architec-
ture. Taking advantage of these facts, herein we report the general
´
and efficient strategy for the synthesis of Frechet-type poly(benzyl
ether) dendrimers having a tetra(ethyleneoxide) at core via click
reaction between azide and alkyne.
EXPERIMENTAL
General Methods
1H NMR spectra were recorded on a 500 MHz NMR spectrometer
using the residual proton resonance of the solvent as the internal
standard. Chemical shifts are reported in parts per million (ppm).
When peak multiplicities are given, the following abbreviations are
used: s, singlet; d, doublet; t, triplet; q, quartet; quin, quintet; d of d,
doublet of a doublet; m, multiplet; br, broad. 13C NMR spectra were
proton decoupled and recorded on a 75 MHz NMR spectrometer
using the carbon signal of the deuterated solvent as the internal
standard. FAB and MALDI mass spectra were obtained from Korea
Basic Science Institute (KBSI) in Daegu or Daejeon and POSTECH.
Flash chromatography was performed with 37–75 mm silica gel.

Poly(benzyl ether) Dendrimer Containing Tetra(ethyleneoxide)
141=[505]
Analytical thin layer chromatography was performed on silica
plates with F-254 indicator and the visualization was accomplished
by UV lamp or using an iodine chamber. Polydispersity (PDI) of den-
drimers was determined by gel permeation chromatography (GPC)
analysis relative to polystyrene calibration (Agilent 1100 series GPC,
Plgel 5 mm MIXED-C, refractive index detector) in THF solution. All
chemicals were obtained from commercial sources and used as
received.
General Procedure for the Synthesis of Dendrimers 3-Gm
A mixture of alkyne-functionalized poly(benzyl ether) dendrons
1-Dm (0.27 mmol) and tetraethylene glycol diazide 2 (0.12 mmol) in
DMF-H2O (4:1, 1.2 mL) in the presence of 10 mol% CuSO4 ꢀ 5H2O with
20 mol% sodium ascorbate was stirred at 50ꢁC for ꢂ 2.5 h. The reac-
tion mixture was poured into brine (30 mL) and the resulting solution
was extracted with EtOAc (30 mL ꢃ 3). The combined organic phase
was dried with sodium sulfate, concentrated, and purified by column
chromatography to afford the desired product 3-Gm.
Compound 3-G1. Rf0.1 (EtOAc); 95% yield. A yellowish oil; IR:
1
3005, 2940, 2870, 1597, 1462, 1204, 1153, 1096, 1053 cmꢄ1; H NMR
(500 MHz, CDCl3) d 3.54–3.55 (m, 8H), 3.77 (s, 12H), 3.82 (t, J ¼ 4.8 Hz,
4H), 4.50 (t, J ¼ 4.8 Hz, 4H), 4.53 (s, 4H), 4.66 (s, 4H), 6.37 (s, 2H), 6.50
(d, J ¼ 1.7 Hz, 4H), 7.70 (s, 2H); 13C NMR (75 MHz, CDCl3) d 50.6, 55.7,
64.1, 69.8, 70.8, 70.9, 72.8, 100.1, 106.0, 124.1, 140.7, 145.3, 161.3; MS
(FAB): m=z 657.0 [Mþ]; HRMS (FAB) Calcd for C32H44N6O9: 656.3170.
Found: 657.3248 [Mþ þ H]. PDI: 1.01.
Compound 3-G2. Rf0.15 (EtOAc); 96% yield; A yellowish oil; IR:
1
3009, 2940, 2839, 1597, 1458, 1204, 1153, 1092, 1053 cmꢄ1; H NMR
(500 MHz, CDCl3) d 3.50–3.54 (m, 8H), 3.77 (s, 24H), 3.81 (t, J ¼ 5.1 Hz,
4H), 4.48 (t, J ¼ 5.0 Hz, 4H), 4.52 (s, 4H), 4.64 (s, 4H), 4.95 (s, 8H), 6.40
(t, J ¼ 2.5 Hz, 4H), 6.52 (t, J ¼ 2.0 Hz, 2H), 6.56 (d, J ¼ 2.1 Hz, 8H), 6.60
(d, J ¼ 2.0 Hz, 4H), 7.68 (s, 2H); 13C NMR (75 MHz, CDCl3) d50.5, 55.8,
64.1, 69.8, 70.4, 70.8, 70.9 72.7, 100.3, 101.8, 105.7, 107.2, 124.1, 139.6,
140.8, 145.3, 160.4, 161.4; MS (FAB): m=z 1200.57 [Mþ]; HRMS (FAB)
Calcd for C64H76N6O17: 1200.5267 Found: 1201.5345 [Mþ þ H]. PDI:
1.01.
Compound 3-G3. Rf0.2 (EtOAc); 97% yield; A yellowish oil; IR
3013, 2940, 2839, 1597, 1458, 1204, 1153, 1053 cmꢄ1 1H NMR
;
(500 MHz, CDCl3) d 3.49–3.52 (m, 8H), 3.77 (s, 48H), 3.79 (t, J ¼ 5.8 Hz,
4H), 4.46 (t, J ¼ 5.0 Hz, 4H), 4.52 (s, 4H), 4.65 (s, 4H), 4.94 (s, 8H), 4.95
(s, 16H), 6.40 (t, J ¼ 2.0 Hz, 8H), 6.52 (s, 2H), 6.55 (t, J ¼ 2.1 Hz 4H),

142=[506]
J. W. Lee et al.
6.56 (d, J ¼ 2.1 Hz, 16H), 6.60 (d, J ¼ 1.6 Hz, 4H), 6.67(d, J ¼ 1.9 Hz,
8H), 7.67 (s, 2H); 13C NMR (75 MHz, CDCl3) d 50.5, 55.8, 64.1, 69.8,
70.4, 70.5, 70.8, 70.9, 72.7, 100.4, 101.8, 102.0, 105.7, 106.9, 107.2,
124.2, 139.6, 139.7, 140.9, 145.3, 160.4, 160.5, 161.4; MS (MALDI):
Calcd for C128H140N6O33: 2288.9461. Found: 2289.9343[Mþ þ H],
2311.9053[Mþ þ Na]. PDI: 1.01.
Compound 3-G4. Rf0.4 (EtOAc: dichloromethane ¼ 2:1); 93% yield;
A yellowish oil; IR 3013, 2940, 2839, 1593, 1458, 1204, 1150,
1049 cmꢄ1 1H NMR (500 MHz, CDCl3) d 3.47–3.49 (m, 8H), 3.75
;
(m, 100H), 4.42 (t, J ¼ 4.7 Hz, 4H), 4.50 (s, 4H), 4.63 (s, 4H), 4.93 (s,
56H), 6.39 (m, 16H), 6.54–6.55 (m, 46H), 6.60 (m, 4H), 6.65
(m, 24H), 7.65 (s, 2H); 13C NMR (75 MHz, CDCl3) d 50.0, 55.3, 63.6,
69.3, 69.92, 69.98, 70.3, 70.4, 72.2, 99.9, 101.2, 101.6, 105.2, 106.4,
106.7, 123.7, 139.1, 139.2, 139.3, 140.4, 144.8, 159.9, 160.0, 160.9;
MS (MALDI): Calcd for C256H268N6O65: 4465.7850. Found: 4488.8603
[Mþ þ Na]. PDI: 1.01.
RESULTS AND DISCUSSION
´
The synthetic strategy for Frechet-type poly(benzyl ether) dendrimers
having a tetra(ethyleneoxide) at core, linked by the triazole units, uti-
´
lized a convergent method using the alkyne-functionalized Frechet-
type poly(benzyl ether) dendrons 1-Dm and tetraethylene glycol
´
diazide 2 (Scheme 1). The propargyl-functionalized Frechet-type poly
(benzyl ether) dendrons 1-Dm (m ¼ 1 ꢂ 4: generation of dendron) were
synthesized by the propargylation of the corresponding dendritic ben-
zyl alcohols with propargyl bromide [5e]. Compound 2 was prepared
from the mesylation reaction of tetraethylene glycol with methanesul-
fonyl chloridein the presence of triethylamine and the subsequent
azidation with sodium azide. To efficiently connect the propargylfocal
´
point Frechet-type dendrons with tetraethylene glycol diazide 2,
the synthetic approach selected is based on the click condition using
Cu (I) species [3].
The efficiency of the click reaction between the alkyne-dendrons and
bis(azides) was evaluated by performing the model coupling reactions
between alkyne-dendron 1-D1 and compound 2. Click reaction was
carried out in a 4:1 solvent ratio of DMF to H2O using 5 mol%
CuSO4 ꢀ H2O with 10 mol% sodium ascorbate with respect to alkyne
as the in situ reducing agent to generate the active Cu(I) species. The
reaction of tetraethylene glycol diazide 2 and 2.2 equiv of alkyne-
dendron 1-D1 afforded the desired product 3-G1 in a yield of 94%
after 2.5 h at 50ꢁC which was separated by column chromatography.

Poly(benzyl ether) Dendrimer Containing Tetra(ethyleneoxide)
143=[507]
SCHEME 1 Synthesis of dendrimers via click reaction.
The disappearance of bis(azides) as well as generation and disappear-
ance of the mono-triazole derivative were monitored by TLC runs of the
reaction mixture. Given the success in the synthesis of first-generation
dendrimer, therefore we expanded this reaction to get higher-
generation dendrimers. The reactions of tetraethylene glycol diazide
2 and 2.2 equiv of alkyne-dendrons 1-D2 and 1-D3 afforded the dendri-
mers 3-G2 and 3-G3 in yields of 96 and 97%, respectively, after 1.5 h
FIGURE 1 1H-NMR spectra for (a) 3-G1, (b) 3-G2, (c) 3-G3, and (d) 3-G4.

144=[508]
J. W. Lee et al.
FIGURE 2 IR spectra for (a) 1-D1, (b) 2, and (c) 3-G1.
and 45 min at 50ꢁC. Finally, reaction of tetraethylene glycol diazide 2
and 2.2 equiv of alkyne-dendron 1-D4 gave the dendrimer 3-G4 in a
yield of 93% after 30 min at 50ꢁC. This result showed that the forma-
tion of triazole ring from an azide and an alkyne can be regarded as
a new connector to stitch a tetaethyleneoxide with the dendrons.
Therefore this approach may provide new methodological insight for
synthesis of triblock dendritic polymers [2b] and would greatly contrib-
ute to researches on the application side.
FIGURE 3 FAB mass spectrum of dendrimer 3-G2.

Poly(benzyl ether) Dendrimer Containing Tetra(ethyleneoxide)
145=[509]
FIGURE 4 GPC diagrams of dendrimers 3-Gm obtained from THF eluent.
The structures of the dendrimers 3-Gm were confirmed by 1H
NMR, 13C NMR, and IR spectroscopy. From the 1H NMR spectra
(CDCl3), the peaks of the triazole proton in dendrimers 3-Gm were
found at 7.70 ppm for 3-G1, 7.68 ppm for 3-G2, 7.67 ppm for 3-G3,
and 7.65 ppm for 3-G4, respectively (Fig. 1). The peaks of the methyl-
ene protons adjacent to the nitrogen of triazole in dendrimers 3-Gn
were found at 4.50 ppm for 3-G1, 4.48 ppm for 3-G2, 4.46 ppm for
3-G3, and 4.42 ppm for 3-G4, respectively. As the dendrimer gener-
ation increased, the peaks of the triazole proton and the methylene
protons adjacent to the nitrogen of triazole shifted gradually to up-
field which may be influenced by the dendritic microenvironment eff-
ect [8]. IR data also confirmed that neither alkyne (ꢂ 3285 cmꢄ1) nor
azide (ꢂ 2093 cmꢄ1) residues remain in the final dendrimer (Fig. 2).
Analysis of the dendrimers by FAB or MALDI-TOF mass spectrometry
as well as by gel-permeation chromatography (GPC) provides no signs
of products with defects that would arise from incomplete coupling.
Their FAB or MALDI mass spectrafor dendrimer exhibited very good
correlation with the calculated molecular masses (Fig. 3). Analysis of
the dendrimers by gel-permeation chromatography (GPC) shows very
low polydispersity values, PDI ¼ 1.01 for all dendrimers (Fig. 4).
CONCLUSION
We have successfully synthesized a series of triblock dendritic poly-
mers by copper-catalyzed 1,3-dipolar click chemistry between azide

146=[510]
J. W. Lee et al.
and alkyne. The tetraethyleneglycol diazide building block, designed
to serve as the core in dendrimer, was stitched together with the pro-
´
pargyl-functionalized Frechet-type poly(benzyl ether) dendrons lead-
´
ing to the formation of Frechet-type poly(benzyl ether) dendrimers
having the tetraethyleneoxide at corein high yields. Therefore, the
formation of regiospecific 1,4-disubstituted triazoles via copper(I)-
catalyzed [2 þ 3]-dipolar cycloaddition reaction between an alkyne
and an azide can be regarded as a new and efficient connector to con-
struct the diblock and=or triblock dendritic polymers from dendrons
and linear compound. This strategy may then provide an insight into
designing various amphiphilic dendritic materials. The synthesis and
applications of the block dendritic polymers with specific structures
and properties will now become part of the ongoing research efforts
in our laboratories.
REFERENCES
´
[1] Grayson, S. M. & Frechet, J. M. J. (2001). Chem. Rev., 101, 3819.
¨
[2] (a) Newkome, G. R., Moorefield, C. N., & Vogtle, F. (2001). Dendrimers and
´
Dendrons: Concepts, Synthesis, Applications, Wiley-VCH: Weinheim. (b) Frechet,
J. M. J. & Tomalia, D. A. (2001). Dendrimers and Other Dendritic Polymers, John
Wiely & Sons Ltd.
[3] (a) Rostovtsev, V. V., Green, L. G., Fokin, V. V., & Sharpless, K. B. (2002). Angew.
Chem. Int. Ed., 41, 2596. (b) Tornøe, C. W., Christensen, C., & Meldal, M. (2002).
J. Org. Chem., 67, 3057.
[4] (a) Lutz, J.-F. (2007). Angew. Chem. Int. Ed., 46, 1018. (b) Binder, W. H. &
Sachsenhofer, R. (2007). Macromol. Rapid Commun., 28, 15.
[5] (a) Lee, J. W. & Kim, B. K. (2005). Bull. Korean Chem. Soc., 26, 658. (b) Lee, J. W.,
Kim, B. K., & Jin, S. H. (2005). Bull. Korean Chem. Soc., 26, 833. (c) Lee, J. W., Kim,
B. K., Kim, J. H., Shin, W. S., & Jin, S. H. (2005). Bull. Korean Chem. Soc., 26, 1790.
(d) Lee, J. W. & Kim, B. K. (2006). Synthesis, 615. (e) Lee, J. W., Kim, J. H., Kim, B.
K., Shin, W. S., & Jin, S. H. (2006). Tetrahedron, 62, 894.
[6] (a) Lee, J. W., Kim, B. K., Kim, H. J., Han, S. C., Shin, W. S., & Jin, S. H. (2006).
Macromolecules, 39, 2418. (b) Lee, J. W., Kim, J. H., & Kim, B. K. (2006). Tetra-
hedron Lett., 47, 2683. (c) Lee, J. W., Kim, J. H., Kim, B. K., Kim, J. H., Shin, W.
S., & Jin, S. H. (2006). Tetrahedron, 62, 9193. (d) Lee, J. W., Kim, J. H., Kim, B.
K., Kim, J. H., Shin, W. S., Jin, S. H., & Kim, M. (2006). Bull. Korean Chem. Soc.,
27, 1795. (e) Lee, J. W., Kim, J. H., Kim, H. J., Han, S. C., Kim, J. H., Shin, W. S.,
& Jin, S. H. (2007). Bioconjugate Chem., 18, 579.
[7] (a) Lee, J. W., Kim, B. K., Kim, J. H., Shin, W. S., & Jin, S. H. (2006). J. Org. Chem.,
71, 4988.
[8] Wong, C.-H., Chow, H.-F., Hui, S.-K., & Sze, K.-H. (2006). Org. Lett., 8, 1811.