Macromolecules
ARTICLE
Table 1. Characterization Data for Small-Molecule Model Reactions
trimer
31P (ppm)
1H (ppm)
m/z
2
18.5a
4.20 (2H, q, gly), 3.42 (2H, t, gly), 2.60 (2H, t, toco), 2.17 (9H, t, toco), 1.78 (2H, m, toco), 1.54 (3H, m, toco),
1.39 (4H, m, toco), 1.26 (13H, m, toco), 1.15 (4H,m, toco and 3H, gly), 0.85 (12H, m, toco)
4.02 (2H, q, ethoxy), 2.60 (2H, t, toco), 2.17 (9H, t, toco), 1.78 (2H, m, toco), 1.54 (3H, m, toco),
1.39 (4H, m, toco), 1.26 (13H, m, toco and 3H, d, ethoxy), 1.15 (4H,m, toco), 0.85 (12H, m, toco)
7.6 (1H, d, NHCCHCH), 7.0 (1H, t, CCHCHCH), 6.4 (2H, t,
1729c
3
4
14.3a
3.61a
1558c
1120.6c
CCHCHCHCH), 4.10 (2H, t, CH2CH3), 1.1 (3H, d, CH2CH3)
5a
5b
17.67a
17.01b
7.91 (s, 1H, NCHC), 4.78 (s, 2H, CHCCH2OH), 4.73 (s, 2H, CCH2OC) 2.40 (s, 3, CCH3), 1.45 (s, 6H, CH(CH3)2)
1383c
1144d
7.91 (s, 1H, NCHC), 5.12 (s, 2H, CHCCH2OH), 4.80 (s, 2H, CCH2OC), 2.58 (s, 3, CCH3)
a NMR spectra was measured in CDCl3. b NMR spectra were in D2O. c Mass spectra for solution in 50% MeOH/50% DCM. d Mass spectra for solution
in 100% MeOH.
and triethylamine (19.2 mL, 138.0 mmol) were then added to the
hexachlorocyclophosphazene solution. The mixture was stirred for 4 h at
room temperature, then dimethylaminopyridine (0.703 g, 5.75 mmol) was
added, and the solution was refluxed for 96 h followed by removal of all the
solvent. The oily residue was dissolved in dichloromethane, and the excess
starting material was removed by flash chromatography. The dichloro-
methane solution was extracted with deionized water and subsequently
dried over magnesium sulfate, filtered, and dried under vacuum for 1 week.
A red/orange oil was obtained with 62% yield based on the amount of
hexachlorocyclotriphosphazene. Physical and structural characterization
data are presented in Table 1.
Table 2. Deprotection Conditions for Polymers 11a and 12a
polymer
amount of acid
temp (°C)
time (h)
% removed
11a
12a
4.27 g; 74.2 mmol
3.22 g; 69.9 mmol
25
25
50
50
95
95
for 24 h and added to the polymer solution by filter addition. The resultant
solution was refluxed for 48 h, then dimethylaminopyridine (2.10 g, 17.3
mmol) was added, and the solution was refluxed for an additional 72 h, at
which point 31P NMR spectra were consistent with complete chlorine
replacement. The reaction mixture was cooled to room temperature,
filtered, concentrated, and dialyzed versus THF/methanol (75/25) for 3
days. A brown solid was obtained in a 73% yield. Physical and structural
characterization data are shown in Table 3.
Synthesis of Poly[((DL-R-tocopherol)0.94(ethoxy)1.06)phosphazene]
(8). Poly(dichlorophosphazene) (2.00 g, 17.3 mmol) was dissolved in
dry THF (200 mL). DL-R-Tocopherol (8.18 g, 18.9 mmol) was dissolved
in dry THF (75 mL) and was added to a suspension of sodium hydride
(0.687 g, 17.3 mmol) in THF (50 mL). After 24 h the reactant solution
was added dropwise to the polymer solution. After refluxing for 48 h,
sodium ethoxide (2.64 g, 38.8 mmol) was added, and the solution was
refluxed for an additional 168 h. The reaction mixture was concentrated,
precipitated into methanol (3 times), and dried under vacuum for 5 days.
A light brown solid was obtained, and the yield was 85.9%. Physical and
structural characterization data are given in Table 3.
Synthesis of Poly[bis(ethyl-2-aminobenzoate)phosphazene] (9).
Poly(dichlorophosphazene) (3.00 g, 25.8 mmol) in dry THF (300 mL)
was treated with ethyl 2-aminobenzoate (13.39 g, 90.6 mmol) and
triethylamine (39.7 mL, 285 mmol). The reaction mixture was refluxed
for 120 h and was subsequently cooled to room temperature, filtered, and
dialyzed versus dichloromethane/methanol (50/50) for 3 days. The
resultant polymer was dried under vacuum for 5 days to give an off-white
solid in a 43% yield. Physical and structural characterization data are
presented in Table 3.
Synthesis of Poly[bis(3,4’-O-isopropylidene)phosphazene] (10a). Poly-
(dichlorophosphazene) (1.00 g, 8.63 mmol) was dissolved in dry THF
(100 mL). 3,40-O-Isopropylidene (5.95 g, 28.4 mmol) in dry THF (25
mL) was added to a suspension of sodium hydride (1.10 g, 27.6 mmol)
in THF (100 mL). This solution was allowed to react for 24 h at room
temperature, at which point the sodium salt precipitated from solution.
The polymer solution was then added dropwise to the suspension over a
period of an hour. This mixture was refluxed for 72 h, concentrated, and
dialyzed versus methanol for 3 days. After dialysis, the polymer solution
was concentrated and washed with triethylamine for 3 h. The resultant
solution was dried, dissolved in dichloromethane, and extracted with
water to remove the triethylamine hydrochloride salts. A brown solid
was obtained in 64% yield. Physical and structural characterization data
are listed in Table 3.
Synthesis of Hexa(3,40-O-isopropylidene)cyclotriphosphazene (5a).
3,40-O-Isopropylidene (4.49 g, 23.0 mmol) was dissolved in dry THF
(400 mL) and added to a suspension of sodium hydride (0.909 g, 22.7
mmol) in THF (50 mL). The resultant solution was stirred at room
temperature for 24 h, at which point the sodium salt precipitated from
solution. Hexachlorocyclotriphosphazene (1.00 g, 28.8 mmol) dissolved
in THF (10 mL) was added dropwise to the salt solution over a period of
2 h, during which the sodium salt dissolved. The resulting solution was
then refluxed for 24 h followed by removal of the solvent under reduced
pressure. The oily residue was dissolved in dichloromethane, extracted
with deionized water, and subsequently dried over magnesium sulfate,
filtered, and dried under vacuum for 1 week. An orange solid was
obtained. The yield was 75.4% based on the amount of hexachlorocy-
clotriphophazene. Physical and structural characterization data are
shown in Table 1.
Deprotection of Hexa(3,40-O-isopropylidene)cyclotriphosphazene
(5a) To Form Hexa(pyridoxine)cyclotriphosphazene (5b). Hexa(3,40-
O-isopropylidene)cyclotriphosphazene (5) (0.50 g, 0.360 mmol) was
dissolved in methanol (2 mL). To this was added 80% trifluoroacetic
acid (2 mL, 53.0 mmol) in methanol, and the mixture was stirred at
50 °C. After 48 h the solvent was removed under reduced pressure, and
the oily residue was redissolved in dichloromethane and extracted with
deionized water. The water layer was concentrated and purified by size
exclusion column chromatography using Sephadex G-25. The product
was dried under vacuum for 1 week to give a yellow oil in 40% yield.
Physical and structural characterization data are given in Table 1.
Polymer Syntheses (7-12). The syntheses followed a similar
pattern, and the differences are emphasized in the following descriptions.
Synthesis of Poly[((DL-R-tocopherol)0.66(ethylglycinato)1.34)phosp-
hazene] (7). Poly(dichlorophosphazene) (2.00 g, 17.3 mmol) was dis-
solved in dry THF (200 mL). DL-R-Tocopherol (8.18 g, 18.9 mmol) was
dissolved in dry THF (75 mL) and was added to a suspension of sodium
hydride (0.687 g, 17.3 mmol) in THF (50 mL). The reaction was
allowed to proceed for 24 h, and the mixture was then added dropwise to
the polymer solution. After 24 h at room temperature and 72 h refluxing,
a suspension of glycine ethyl ester hydrochloride (4.82 g, 34.5 mmol)
and triethylamine (12.0 mL, 86.3 mmol) in THF (50 mL) was refluxed
1357
dx.doi.org/10.1021/ma1027406 |Macromolecules 2011, 44, 1355–1364