Published on the web October 16, 2010
1177
Synthesis and Solution Properties of a Novel Thermosensitive Poly(benzyl ether) Dendron
with Oligoethyleneoxy Chains at the Periphery
Li Xu, Lidong Shao, Lin Chen, Minqi Hu, and Yunmei Bi*
College of Chemistry and Engineering, Yunnan Normal University, Kunming, Yunnan 650092, P. R. China
(Received August 13, 2010; CL-100702; E-mail: biym@ynnu.edu.cn)
A novel thermosensitive second-generation poly(benzyl
O
ether) dendron with oligoethyleneoxy chains at the periphery
O
O
O
O
OH
O
was synthesized. Its cloud point (CP) decreased with an
increasing concentration over a range of concentrations from 9
to 60 wt %. Fluorescent spectroscopy and AFM studies revealed
that the dendron self-assembled into the spherical micelles,
about 50 nm in diameter, at concentration over its CMC in an
aqueous solution. This dendron has a potential as smart
thermosensitive materials.
O
O
HO
OH
b
a
O
O
O
O
OH
O
O
OTs
O
1
;
Z
2a: Z=CO
2b: Z=CH2OH
2c: Z=CH2Cl
2Me
c
d
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
O
HO
OH
O
In recent decades, there has been increased interest in
thermosensitive materials due to their promising applications in
many fields such as controlled drug release, cell culture, and
isolation of molecules.1-3 These materials exhibit a phase
transition from a soluble state to an insoluble state when the
temperature is above a lower critical solution temperature
(LCST). Because of tunable LCST behavior, poly(ethylene
glycol) (PEG)-based polymers have attracted great attention
in the last couple of years. Also, PEGs are nontoxic and
biocompatible.4 Short oligo(ethylene glycol) (OEG) groups have
been incorporated into not only linear but also dendritic
macromolecules.5 For example, water-soluble polyacrylates
and polystyrenics with short pendant OEG groups have been
reported.6 These polymers undergo phase transitions when the
temperature is above a critical point. A series of thermosensitive
OEG-based dendronized polymers and dendrimers were synthe-
sized.7 They exhibited sharp phase transitions and negligible
hysteresis. But to date, the most studied thermosensitive
materials have been polymers. To the best our knowledge,
reports of dendrons and small molecules exhibiting the LCST
phenomenon are very limited.8,9 It is generally accepted that an
appropriate combination of hydrophilic-hydrophobic balance in
the polymer chains is believed to be required for the phase
transition to occur.10 Just like certain thermosensitive amphi-
philic OEG-based dendrimers,5,9 the amphiphilic dendron with
the hydrophobic second-generation poly(benzyl ether) branch
unit and hydrophilic oligoethyleneoxy peripheries synthesized in
this study is potentially a responsive material to temperature
change. Indeed, we found that this amphiphilic dendron showed
LCST and critical micellization behavior. Here we report on the
synthesis and solution properties of this novel amphiphilic
dendron.
O
O
O
O
e
O
+
2c
O
O
O
O
O
O
O
CO2Me
3
Scheme 1. Synthesis of compounds 1, 2a, 2b, 2c, and 3.
Reagents and conditions: (a) 4-methylbenzenesulfonyl chloride,
KI, NaOH, THF, H2O, rt, 4 h; (b) K2CO3, KI, DMF, 80 °C, 48 h;
(c) LAH, THF, rt, 16 h; (d) SOCl2, DMF, DCM, rt, 2 h; (e)
K2CO3, DMF, 70 °C, 24 h.
adjusting the molar ratio of methyl gallate to compound 1 from
1:4 to 1:5 and prolonging the reaction time from 24 to 48 h. As
a consequence, 2a was obtained in sufficient purity only by
solvent extraction. Another improvement in this study in
comparison with the literature is prolongation of the reaction
time of 2a with LAH from 3 to 16 h. Also the molar ratio of
LAH to 2a was adjusted from 1.5:1 to 2:1. These conditions
furnished analytically pure 2b without column chromatography.
Chlorination of 2b with SOCl2 which is the most attractive
reagent for the chlorination of benzyl alcohols because of the
short reaction time, low temperature, and low price11 afforded
the corresponding chloride 2c. The alkylation of methyl gallate
with 2c by using K2CO3 as base in DMF generated the new
second-generation dendron 3. The purification of every com-
pound requires only solvent extraction. All these pure products
were obtained as oily liquids. The isolated yields were 92.3%,
90.0%, 93.4%, and 91.2% for 2a, 2b, 2c, and 3, respectively.
1H NMR spectra of 2a and 2b was consistent with the
literature.11b 2b and 3 were characterized by 1H NMR and
13C NMR spectra. The structure of 3 was further confirmed by IR
and ESI-MS (see the Supporting Information).16
The synthetic route of first- and second-generation dendrons
2a, 2b, 2c, and 3 are outlined in Scheme 1. The first-generation
dendron 2a was prepared by Williamson etherification of methyl
gallate with tosylated di(ethylene glycol) monomethyl ether 1.
2a was reduced with lithium aluminum hydride (LAH) to give
the first-generation dendron alcohol 2b. In an earlier paper,7b
purification of 2a and 2b required column chromatography.
In this study, the synthetic procedure of 2a was modified by
The new dendron 3 is water soluble at room temperature,
but a temperature-induced transition from a clear solution to a
turbid one was observed for 3 in an aqueous medium at a
concentration above the LCST. The effect of the dendron
concentration on the cloud point was investigated by turbidity
measurements using UV-vis spectrophotometry. As shown in
Chem. Lett. 2010, 39, 1177-1179
© 2010 The Chemical Society of Japan
Xu, Li
