Macromolecules, Vol. 37, No. 18, 2004
Poly(2-isopropyl-2-oxazolines) 6787
Sch em e 1. Syn th esis of Me-P iP r Ox-NH2 by
F u n ction a liza tion of ω-Hyd r oxyl Ter m in a ls
(TOSOH HLC-8220) system equipped with two TSK gel
columns (G4000HHR and G3000HHR) and an internal refractive
index (RI) detector. Columns were eluted with DMF containing
lithium bromide (10 mM) and triethylamine (30 mM) with a
flow rate of 0.8 mL/min and at a temperature of 40 °C.
Molecular weights were calibrated with poly(ethylene glycol)
standards (Polymer Laboratories, Ltd., UK). Mass measure-
ments were performed on a MALDI-TOF mass spectrometer
(Bruker REFLEX III), operating at an acceleration voltage of
23 kV in the reflection mode. UV-vis spectra were obtained
with a V-550 UV/vis J ASCO spectrophotometer. The function-
ality of amino group was determined by using an ion-exchange
HPLC system equipped with TSK gel column (TOSOH SP-
5PW) and an internal refractive index (RI) detector. The
column was eluted with phosphate-buffered solution (2 mM
PBS (pH 6.5)) at a flow rate of 0.5 mL/min and at a temper-
ature of 30 °C.
Syn th esis of 3,3-Dieth oxy-1-p r op yl Tosyla te. A solution
of p-toluenesulfonyl chloride (9.61 g, 50.4 mmol, 1.5-fold molar
excess vs OH) in chloroform (50 mL) was added to a stirred
solution of 3,3-diethoxy-1-propanol (4.98 g, 33.60 mmol) and
triethylamine (23.5 mL, 168 mmol, 5-fold molar excess vs OH)
in anhydrous chloroform (150 mL) cooled to 0 °C and kept
under an argon atmosphere. At the end of the addition, the
reaction mixture was brought to room temperature and stirred
for 24 h. The mixture was filtered, and the filtrate was
concentrated under reduced pressure. The residue was purified
by chromatography on a silica gel column eluted with chloro-
form. Fractions containing the desired product were dried over
anhydrous sodium sulfate, filtered, and concentrated to dry-
ness. The product was stored at -20 °C under an argon
atmosphere (Figure S4).
Sch em e 2. Syn th esis of Heter otelech elic
Aceta l-P iP r Ox-OH
1H NMR (DMSO-d6, 400 MHz): δ (ppm) ) 1.10 (t, J ) 9.6
Hz, 3H, CH3CH2O), 2.80 (q, J ) 9.6 Hz, 2H, CH3CH2O), 4.50
(t, J ) 9.6 Hz, 1H, CHCH2CH2), 1.80 (q, J ) 9.6 Hz, 2H,
CHCH2CH2), 4.0 (t, J ) 9.6 Hz, 2H, CHCH2CH2), 7.50 (d, J )
8.5 Hz, 2H, C6H4CH3), 7.80 (d, J ) 8.5 Hz, 2H, C6H4CH3), 2.45
(s, J ) 8.5 Hz, 3H, C6H4CH3).
spectroscopy, MALDI-TOF mass spectrometry, and gel
permeation chromatography. Moreover, the tempera-
ture sensitivity of PiPrOx aqueous solutions was exam-
ined via turbidity measurements.
Syn th esis of P oly(2-isop r op yl-2-oxa zolin e) Ha vin g a n
Hyd r oxyl Gr ou p a t th e ω-Ter m in a l En d (Me-P iP r Ox-
OH). 2-Isopropyl-2-oxazoline (10 g, 88.4 mmol) was added via
a syringe to a solution of methyl p-tosylate (0.186 g, 1.0 mmol)
in acetonitrile (30 mL). The polymerization mixture was stirred
at 42 °C for ca. 506 h under an argon atmosphere. The mixture
was cooled to room temperature and treated with methanolic
NaOH (1 M) to quench the poly(2-isopropyl-2-oxazoline) ox-
azolinium living end groups. The solution was dialyzed for 2
days against distilled water to introduce an hydroxyl group
at one of the chain ends. Freeze-drying of the dialyzed solution
yielded a white colorless powder. In addition, eight samples
were collected in the course of the polymerization. They were
subjected to the same treatment and analyzed by GPC in order
to determine the conversion yield (total yields: 5.1 g, 51%).
Con ver sion of Ter m in a l Hyd r oxyl Gr ou p s in to P r i-
m a r y Am in o Gr ou p s via th e Mitsu n obu Rea ction (Me-
P iP r Ox-NH2) (Sch em e 1).18 Me-PiPrOx-OH (100 mg, 0.022
mmol) was added to a stirred solution of triphenylphosphine
(TPP) (57.7 mg, 0.22 mmol) and phthalimide (PI) (32.37 mg,
0.22 mmol) in THF (1 mL). Then, diethyl azodicarboxylate
(DEAD) (38.32 mg, 0.22 mmol) was added dropwise to the
mixture kept under an argon atmosphere. After being kept at
room temperature for 24 h, the mixture was dialyzed first
against ethanol and then against distilled water using a
Spectrapor dialysis membrane with a 1000 Mr molecular
weight cutoff value. The solution lyophilized for 2 days yielded
the phthalimide-activated polymer “Me-PiPrOx-PI”. The yield
was 90 mg and the conversion efficiency was ca. 70%,
Exp er im en ta l Section
Ma ter ia ls. 2-Isopropyl-2-oxaxoline was synthesized from
isobutyric acid (Wako Pure Chemical Industries, Ltd., Osaka,
J apan) and 2-aminoethanol (Wako Pure Chemical Industries,
Ltd., Osaka, J apan) as described previously (see Supporting
Information, Figures S1 and S2).16 Methyl p-tosylate (Tokyo
Kasei Kogyo Co., Ltd., Tokyo, J apan) was distilled from
calcium hydride under reduced pressure. 3,3-Diethoxy-1-
propanol (Aldrich Chemical Co. Ltd., Milwaukee, WI) and
p-toluenesulfonyl chloride (Wako Pure Chemical Industries,
Ltd., Osaka, J apan) were used as received. Acetonitrile (Wako
Pure Chemical Industries, Ltd., Osaka, J apan) was distilled
from calcium hydride. Tetrahydrofuran (THF) (Wako Pure
Chemical Industries, Ltd., Osaka, J apan) and chloroform
(Wako Pure Chemical Industries, Ltd., Osaka, J apan) were
purified by distillation following conventional procedures.17
Other chemicals, such as 1 N NaOH aqueous solution,
methanol, and ethanol, were purchased from Wako Pure
Chemical Industries, Ltd., Osaka, J apan, and used without
further purification. Triphenylphosphine (TPP) (Tokyo Kasei
Kogyo Co., Ltd., Tokyo, J apan), phthalimide (PI) (Wako Pure
Chemical Industries, Ltd., Osaka, J apan), diethyl azodicar-
boxylate (DEAD) (40 wt % in toluene; Tokyo Kasei Kogyo Co.,
Ltd., Tokyo, J apan), and hydrazine monohydrate (Wako Pure
Chemical Industries, Ltd., Osaka, J apan) were used as re-
ceived.
1
confirmed by comparing integral ratio obtained from H NMR
analysis. This material (50 mg, 0.011 mmol) was then dissolved
in ethanol (5 mL) and treated with hydrazine monohydrate
(5 mL). The mixture was kept at room temperature for 24 h.
After ethanol was evaporated, an aqueous sodium hydroxide
was added up to pH 9-10. The polymer was extracted with
methylene chloride and then purified by dialysis against
ethanol and distilled water using a Spectrapor dialysis mem-
Tech n iqu es. 1H NMR and 13C NMR spectra were recorded
on a J EOL EX 300 spectrometer (J EOL, Tokyo, J apan) at 400
MHz. Chemical shifts are reported in parts per million (ppm)
downfield from tetramethylsilane. Molecular weights and
molecular weight distributions were determined using a GPC