5776 Glauser et al.
Macromolecules, Vol. 35, No. 15, 2002
liquid. No further purification was necessary, and the product
(4) was used directly for subsequent reactions.
10.1 mmol) and DPTS (0.94 g, 3.02 mmol) were added and
stirred for 18 h at 35 °C. The solution was filtered, diluted
with CH2Cl2, and washed three times with 50 mL of saturated
NH4Cl solution. The organic phase was dried over MgSO4, and
the solvents were distilled off. The viscous oil was redissolved
in ethyl acetate, cooled in liquid nitrogen, and cold filtered.
Evaporation of the organic solvent yielded 5.3 g of a trans-
parent, slightly yellow oil. The crude product was purified by
column chromatography on silica gel with ethyl acetate/hexane
(1:1). The column was neutralized with 10% triethylamine/
hexane in order to prevent the cleavage of the acetonide
protective group. 1.3 g (0.6 mmol, 27% yield) of 12 was obtained
as a clear oil.
1H NMR (CDCl3): δ 0.00 (s, 6H, -SiCH3), 0.71 (s, 3H,
-CH3), 0.82 (s, 9H, -SiC(CH3)3), 2.28-2.35 (m, 2H, -OH), 3.41
and 3.53 (s, 2H, -CH2O-), 3.47-3.66 (m, 4H, -CH2OH). 13C
NMR (CDCl3): δ -5.7, 16.8, 18.1, 25.8, 41.0, 67.9, 68.8.
3-(2-Br om oisob u t yr a t e )-2-(t er t -b u t yld im e t h ylsila n -
yloxym eth yl)-2-m eth yl-p r op a n -1-ol, 6. Compound 4 (30.5
g, 130 mmol) was dissolved in dry triethylamine (40 mL, 286
g, 2.2 equiv) and cooled to 0 °C. 2-Bromoisobutyryl bromide
(16.07 mL, 130 mmol, 1 equiv) was added dropwise. The
reaction mixture was stirred for 4 h at room temperature. After
dilution with 500 mL of CH2Cl2, the mixture was extracted
three times with 50 mL of a saturated solution of sodium
bicarbonate. The organic phase was dried over magnesium
sulfate. The solution was concentrated, and the crude product
was purified by column chromatography on silica gel with ethyl
acetate/hexane (1:10) to give 38.7 g (100.9 mmol, 78% yield)
of product 6.
1H NMR: δ 1.08 (s, 18H, -CH3), 1.17 (s, 9H, -CH3), 1.27
(s, 9H, -CH3), 1.30 (s, 18H, (-OCH2)2C(CH3)2), 1.35 (s, 18H,
(-OCH2)2C(CH3)2), 1.89 (s, 18H, -C(CH3)2Br), 3.56 (d, 12H,
-COCH2-, J ) 11.8 Hz), 4.09 (d, 12H, -COCH2-, J ) 11.9
Hz), 4.18 (s, 6H, -CCH2OOC-), 4.20 (s, 6H, -CCH2OOC-),
4.32 (s, 18H, -CCH2OOC-), 8.77 (s, 3H, -Ph-).
1H NMR (CDCl3): δ 0.00 (s, 6H, -SiCH3), 0.81 (s, 3H, -SiC-
(CH3)3), 0.83 (s, 9H, -SiCH2(CH3)3), 1.87 (s, 6H, -C(CH3)2-
Br), 2.28-2.35 (m, H, -OH), 3.50 and 3.53 (s, 4H, -CH2O-),
4.13 (s, 2H, -CH2OH). 13C NMR (CDCl3): δ -5.7, 8.5, 16.6,
18.1, 25.8, 30.8, 41.0, 45.2, 55.8, 67.5, 67.7, 128.4, 129.5, 171.8.
Ben zen e-1,3,5-tr ica r boxylic Acid 1,3,5-Tr is-[3-(2-br o-
m oisobu tyr a te)-2-(ter t-bu tyld im eth ylsila n yloxym eth yl)-
2-m eth ylp r op yl] Ester , 8. Compound 6 (34.51 g, 99 mmol,
3.3 equiv) was dissolved in 100 mL of CH2Cl2 and triethyl-
amine (13.8 mL, 99 mmol, 3.3 equiv) at room temperature.
The solution was stirred for 30 min, followed by the dropwise
addition of 1,3,5-benzenetricarbonyl trichloride (7) (7.96 g, 30
mmol). The reaction mixture was stirred for 3 h, and 20 mL
of ammonium chloride solution was added. After dilution with
200 mL of CH2Cl2, the mixture was extracted three times with
50 mL of a saturated solution of ammonium chloride. The
water phase was reextracted with CH2Cl2, and the combined
organic phases were dried over magnesium sulfate. The
solution was concentrated, and the crude product was purified
by column chromatography on silica gel with ethyl acetate/
hexane (1:9) to give 26.5 g (20.29 mmol, 68% yield) of 8.
1H NMR: δ 0.00 (s, 18H, -SiCH3), 0.84 (s, 27H, -CH3), 1.08
(s, 9H, -SiC(CH3)3), 1.89 (s, 18H, -C(CH3)2Br), 3.58 (s, 6H,
-SiOCH2-), 4.16 (s, 6H, -CCH2OOC-), 4.30 (s, 6H, -CCH2-
OOCPh), 8.79 (s, 3H, -Ph). 13C NMR: δ -5.6, 16.9, 18.2, 25.8,
30.8, 40.7, 55.6, 64.9, 67.1, 74.6, 131.5, 134.4, 164.8, 171.3.
Ben zen e-1,3,5-tr ica r boxylic Acid 1,3,5-Tr is(3-(2-br om o-
isobu tyr a te)-2-h yd r oxym eth yl-2-m eth ylp r op yl) Ester , 9.
Compound 8 (11.1 g, 8.50 mmol) was dissolved in 200 mL of
dichloromethane, and Et2O‚BF3 (4.81 mL, 38.23 mmol, 4.5
equiv) was added dropwise and stirred at room temperature
for 3.5 h. A saturated solution of ammonium chloride was
added, and the mixture was diluted with 200 mL of chloroform
and washed three times with 200 mL of a sodium bicarbonate
solution and twice with 200 mL of water. The water phase
was extracted with 50 mL of chloroform, and the combined
organic phases were dried over magnesium sulfate and
concentrated. The crude product was purified by column
chromatography over silica gel with ethyl acetate/hexane
(1:1) to give 6.13 g (6.36 mmol, 75% yield) of product 9.
1H NMR: δ 1.11 (s, 9H, -CH3), 1.92 (s, 18H, -C(CH3)2Br),
2.20-2.50 (bs, 3H, -OH), 3.60 (s, 6H, -CCH2OH), 4.23 (s, 6H,
-CCH2OOC-), 4.36 (d, 6H, -CCH2OOCPh-), 8.81 (s, 3H,
-Ph-). 13C NMR: δ 16.9, 30.7, 40.8, 55.6, 64.9, 67.2, 67.5,
131.2, 134.7, 164.7, 171.9.
13C NMR (CDCl3): δ 17.7, 18.5, 22.1, 25.1, 30.6, 39.5, 42.0,
47.0, 55.4, 65.0, 66.0, 66.5, 98.1, 131.1, 134.6, 164.1, 171.0,
172.1, 173.5.
P olym er iza tion of MMA (DP ) 11) fr om a Tr iin itia tor
(12), 14, a n d a Gen er a l P r oced u r e for th e P olym er iza tion
of Meth a cr yla tes by ATRP . The initiator 12 (0.37 g, 0.16
mmol) was dissolved in 15 mL of THF and degassed by freeze-
thaw (3×). Before the last thaw, CuBr (23.0 mg, 0.16 mmol)
and dNbPy (131.0 mg, 0.33 mmol) were added under argon.
Once the THF removed, freshly distilled and degassed MMA
(1.03 mL, 9.6 mmol) was added to the flask. The reaction
proceeded for 16 h at 95 °C, resulting in a polymer with a high
viscosity (solid in the case of higher molecular weights). The
polymer was dissolved in THF and precipitated in methanol.
1.00 g (73% yield) of 14 was obtained as a white powder. The
degree of polymerization per arm (DP/arm) was evaluated by
scaling a peak of the MMA (1H NMR δ 3.53 (s, 3H/monomer,
-COOCH3)) to the protons of the aromatic core (1H NMR δ
8.77 (s, 3H, -Ph-)). Many of the other peaks overlap in the
1H NMR spectrum.
The same procedure was used for the polymerization of
BMA, producing yields around 65%. The DP/arm was obtained
by scaling a BMA peak (1H NMR: δ 4.82 (s, 2H/monomer,
-COOCH2Ph)) to the protons of the aromatic core (1H NMR:
δ 8.77 (s, 3H, -Ph-)).
Ma cr om olecu le w ith 3 Hyd r op h ilic Den d r on s (g-2)
a n d 3 Hyd r op h obic Ta ils (MMA, DP ) 11), 21, a n d a
Gen er a l P r oced u r e for th e Dep r otection of th e Den -
d r on s. Dowex 50WX8-200 ion-exchange resin (0.4 g) was
added to 14 (0.5 g) dissolved in 10 mL of a THF/methanol
mixture (1:1). The reaction mixture was stirred at 50 °C for
48 h to effect the deprotection reaction. The mixture was
cooled, filtered to remove the Dowex, and concentrated (0.48
g, 95% yield). No further purification was necessary. The
disappearance of the acetonide peak (13C NMR (CDCl3) δ 98.1)
indicated that the deprotection was complete. The amphiphilic
nature and the polydispersity of the polymer did not allow for
a well-resolved 1H NMR spectrum.
Ma cr om olecu le w ith 3 Hyd r op h obic Den d r on s ((g-2)p )
a n d 3 Hyd r op h ilic Ta ils (MAA, DP ) 17), 23, a n d a
Gen er a l P r oced u r e for th e Rem ova l of th e Ben zyl
Gr ou p . The macromolecule 20 (0.82 g, 0.07 mmol) was
dissolved in 100 mL of a THF/tert-BuOH (50:50) solvent
mixture. The dendron’s acetonide protecting group did not get
cleaved using tert-BuOH. Under nitrogen, 1.0 g of Pd/C (10
wt %) was added into the reaction flask. The apparatus for
catalytic hydrogenolysis was filled with H2(g) at 30 psi, and
the reaction mixture was shaken for 24 h. The Pd/C was
removed by filtration (0.2 µm Teflon filters), and the solvents
were evaporated to yield 23 (0.40 g, 49% yield) as a clear,
brittle resin. No further purification was necessary. Depro-
tection was monitored by the disappearance of the peak of the
benzyl ether (1H NMR δ 4.82 (s, 2H/mer (???), -COOCH2Ph)).
The presence of the acetonide was verified by NMR (1H NMR:
δ 1.30 (s, 18H, (-OCH2)2C(CH3)2), 1.35 (s, 18H, (-OCH2)2C-
(CH3)2); 13C NMR: (CDCl3) δ 98.1).
Den d r on Syn th esis. Synthesis of generation 2 ((g-2)p, 10)
and generation 3 ((g-3)p, 11) acetonide protected dendrons
based on 2,2′-bis(hydroxymethyl)propionic acid (bis-MPA) was
performed according to the literature.14 The subscript “p”
indicates that the terminal hydroxyls of the dendrons are
protected with acetonide groups.
Tr i-ATRP In itia tor w ith Th r ee P r otected Secon d
Gen er a tion Den d r on s, 12, a n d a Gen er a l P r oced u r e for
DCC/DP TS Cou p lin g. The core 9 (2.16 g, 2.2 mmol) and the
(g-2)p dendrons 10 (4.5 g, 10.1 mmol) were dissolved in 100
mL of CH2Cl2. 1,3-Dicyclohexylcarbodiimide (DCC) (2.08 g,