Macromolecules, Vol. 37, No. 3, 2004
PC-PCL and Charged Phospholipid Analogues 957
organic phases with trace amounts of pyridine were
removed azeotropically by rotational evaporation at
ambient temperature. Yield: 90%. H NMR (CDCl3) δ
) 1.39 (m, 2H, -CH2-), 1.66 (m, 2H, -CH2-), 1.66 (m,
2H, -CH2-), 2.33 (t, 2H, -O(O)CCH2-), 4.09 (q, 2H,
-CH2OC(O)-), 4.22-4.41 (m, 4H, -CH2-CH2-), 5.08
(s, 2H, PhCH2-), 7.31 (m, 5H, ArH-). 31P NMR (CDCl3)
δ ) 18.1 (s).
-CH2OC(O)-), 5.08 (s, 2H, PhCH2-), 7.34 (m, 5H,
ArH-, R-end).
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2.3.9. Synthesis of R-Benzyl-ω-4-chloro-butanoyl-
Polycaprolactone (9). For the synthesis of 9, 2.0 g (0.44
mmol) of 1 and 87 µL (1.10 mmol) of pyridine were
added to a 50-mL predried two-necked round-bottom
flask that was equipped with a stir bar and purged with
nitrogen. The compounds were dissolved in 15 mL of
dry chloroform and a dropping funnel was attached and
the solution cooled to -10 °C. A funnel was charged with
92 µL (1.10 mmol) of 4-chlorobutyryl chloride to which
was added 5 mL of dry chloroform. This was slowly
added dropwise to the cooled solution over a 30-min
period. The solution was slowly allowed to reach ambi-
ent temperature and stirred for an additional 3 h. When
conversion was complete, the polymer was precipitated
in cold methanol, filtered, and dried until a constant
2.3.6. Synthesis of ([6-Benzyloxy-6-oxohexyl]oxy) Phos-
phatidyl Choline (Benzyl 6-Phosphatidyl Choline Hex-
anoate, 6). For the synthesis of 6, 0.2 g (0.61 mmol) of
5 was dissolved in 5 mL of dry acetonitrile and trans-
ferred into a 50-mL pressure tube that was equipped
with a stir bar and cooled to -20 °C. Approximately 113
µL (1.22 mmol) of trimethylamine(g) (Me3N) was care-
fully condensed into the pressure tube and properly
sealed. (Caution: Reaction under pressure!) The solu-
tion was heated and maintained at 60 °C for 45 h to
allow the reaction to complete. Following completion,
the product was filtered over a silica plug, eluting with
a 70/30 mixture of water and ethanol, according to a
1
weight was reached. Yield: 91%. H NMR (CDCl3) δ )
1.35 (m, 2H, -CH2-, poly), 1.65 (m, 2H, -CH2-, poly),
1.65 (m, 2H, -CH2-, poly), 2.05 (m, 2H, -CH2-, ω-end),
2.30 (t, 2H, -O(O)CCH2-, poly), 2.47 (t, 2H, -CH2-,
ω-end), 3.58 (t, 2H, -CH2-, ω-end), 4.04 (t, 2H, -CH2-
OC(O)-, poly), 5.10 (s, 2H, PhCH2-, R-end), 7.34 (m,
5H, ArH-, R-end).
1
published procedure.21 Yield: 80%. H NMR (CDCl3) δ
) 1.35 (m, 2H, -CH2-), 1.59 (m, 4H, -CH2-), 1.59 (m,
4H, -CH2-), 2.32 (t, 2H, -O(O)CCH2-), 3.33 (s, 9H,
-NCH3), 3.76 (m, 2H, -CH2-), 3.78 (m, 2H, -CH2-),
4.22 (m, 2H, -CH2-), 5.08 (s, 2H, PhCH2-), 7.31 (m,
5H, ArH-). 31P NMR (CDCl3) δ ) -0.9 (s).
2.3.10. Synthesis of R-Benzyl-ω-N,N,N-trimethyl-4-
oxobutan-1-aminium-Polycaprolactone (10). For the
synthesis of 10, 1.0 g (0.21 mmol) of 9 was weighed in
a 50-mL predried round-bottom flask and dissolved in
10 mL of dry acetonitrile. The solution was transferred
to a pressure tube with two stopcocks, purged with
nitrogen, sealed, and cooled to -10 °C. Approximately
2 equiv (39 µL, 0.42 mmol) of trimethylamine(g) to PCL
polymer were carefully condensed into the pressure tube
and slowly heated to 60 °C. (Caution: Reaction under
pressure!) The solution was stirred for 45 h and allowed
to cool to ambient temperature. The compound formed
was precipitated in cold methanol, and the precipitate
was collected and dried until it reached a constant
2.3.7. Synthesis of R-Benzyl-ω-4-oxobutanoic Acid-
Polycaprolactone (7). For the synthesis of 7, 2.0 g (0.44
mmol) of 1 and 88 mg (0.88 mmol) of succinic anhydride
was added to a 50-mL predried two-necked round-
bottom flask that was equipped with a stir bar and
purged with nitrogen. The compounds were dissolved
in 15 mL of dry chloroform, a dropping funnel was
attached, and the solution cooled to 0 °C. The funnel
was charged with 89 µL (0.88 mmol) of triethylamine
to which was added 5 mL of dry chloroform. This was
slowly added dropwise to the cooled solution over a 30-
min period. The solution was slowly allowed to reach
ambient temperature and stirred for an additional 3 h.
When conversion was complete, the polymer was pre-
cipitated in cold methanol, filtered, and dried until it
reached a constant weight. Yield: 97%. 1H NMR (CDCl3)
δ ) 1.35 (m, 2H, -CH2-, poly), 1.65 (m, 2H, -CH2-,
poly), 1.65 (m, 2H, -CH2-, poly), 2.30 (t, 2H, -O(O)-
CCH2-, poly), 2.62 (t, 2H, -CH2-, ω-end), 2.62 (t, 2H,
-CH2-, ω-end), 4.04 (t, 2H, -CH2OC(O)-, poly), 5.10
(s, 2H, PhCH2-, R-end), 7.34 (m, 5H, ArH-, R-end).
1
weight. Yield: 80%. H NMR (CDCl3) δ ) 1.35 (m, 2H,
-CH2-, poly), 1.65 (m, 2H, -CH2-, poly), 1.65 (m, 2H,
-CH2-, poly), 2.10 (m, 2H, -CH2-, ω-end), 2.30 (t, 2H,
-O(O)CCH2-, poly), 2.50 (t, 2H, -CH2-, ω-end), 3.43
(s, 9H, -NCH3, ω-end), 3.72 (t, 2H, -CH2-, ω-end), 4.04
(t, 2H, -CH2OC(O)-, poly), 5.10 (s, 2H, PhCH2-,
R-end), 7.34 (m, 5H, ArH-, R-end).
2.3.11. Synthesis of Benzyl 6-[(4-chlorobutanoyl) oxy]
Hexanoate (11). For the synthesis of 11, 0.2 g (0.9 mmol)
of 4 and 0.14 g (1.80 mmol) of pyridine were added to a
50-mL predried two-necked round-bottom flask that was
equipped with a stir bar and purged with nitrogen. The
compounds were dissolved in 5 mL of dry chloroform, a
dropping funnel was attached, and the solution was
cooled to -10 °C. A funnel was charged with 0.11 mL
(1.35 mmol) of 4-chlorobutyryl chloride, to which was
added 5 mL of dry chloroform. This was slowly added
dropwise to the cooled solution over a 30-min period.
The solution was allowed to reach ambient temperature
and stirred for an additional 5 h. TLC using a 1:1
mixture of hexane and ethyl acetate monitored the
conversion. The product was purified by flash chroma-
tography and eluted with the same system. Yield: 70%.
1H NMR (CDCl3) δ ) 1.38 (m, 2H, -CH2-), 1.65 (m,
2H, -CH2-), 1.65 (m, 2H, -CH2-), 2.05 (m, 2H, -CH2-
), 2.35 (t, 2H, -O(O)CCH2-), 2.47 (t, 2H, -CH2-), 3.58
(t, 2H, -CH2-), 4.07 (t, 2H, -CH2OC(O)-), 5.10 (s, 2H,
PhCH2-), 7.34 (m, 5H, ArH-).
2.3.8. Synthesis of 4-([6-(Benzyloxy)-6-oxohexyl]oxy)-
4-Oxobutanoic Acid (8). For the synthesis of 8, 0.2 g (0.9
mmol) of 4 and 0.135 g (1.35 mmol) of succinic anhydride
were added to a 50-mL predried two-necked round-
bottom flask that was equipped with a stir bar and
purged with nitrogen. The compounds were dissolved
in 5 mL of dry chloroform, with a dropping funnel
attached, and the solution cooled to 0 °C. The funnel
was charged with 0.17 mL (1.8 mmol) of triethylamine
to which was added 3 mL of dry chloroform. This
mixture was slowly added dropwise to the cooled solu-
tion over a 30-min period. The solution was slowly
allowed to reach ambient temperature, after which it
was stirred for an additional 3 h. The conversion was
monitored by TLC and eluted with a 1:1 mixture of
1
hexane/ethyl acetate. Yield (by NMR): 95%. H NMR
(CDCl3) δ ) 1.25 (m, 2H, -CH2-), 1.65 (m, 2H, -CH2-
), 1.65 (m, 2H, -CH2-), 2.32 (t, 2H, -O(O)CCH2-), 2.53
(t, 2H, -CH2-), 2.56 (t, 2H, -CH2C(O)OH), 4.00 (t, 2H,