Isophthalate Ester-Terminated Dendrimers
J. Am. Chem. Soc., Vol. 118, No. 37, 1996 8857
to yield a yellowish oil. The crude product was recrystallized twice
from 1200 mL of 3:1 THF/acetone and dried overnight in a vacuum
oven at 50 °C to afford 10 as a fine, white powder (184.1 g, 88.7%):
mp 132-133 °C; FT-IR (KBr) νmax cm-1 2982, 1723, 1595, 1446, 1369,
times to give the product 13 as a clear glass (4.49 g, 62.9%): FT-IR
(neat, NaCl) νmax cm-1 3420, 3060, 2991, 2938, 2907, 2875, 1722,
1596, 1447, 1369, 1324, 1238, 1203, 1163, 1115, 1029, 834, 758; H
NMR (CDCl3) δ 1.37 (t, 96 H, J ) 7.12 Hz, CH3), 4.36 (q, 64 H, J )
7.13 Hz, OCH2), 4.55 (s, 2 H, benzylic), 4.93-5.00 (s, 28 H, benzylic),
5.04-5.15 (s, 32 H, benzylic), 6.56-6.71 (m, 45 H, aromatic), 8.26-
8.29 (m, 32 H, aromatic), 8.60-8.62 (m, 16 H, aromatic); MALDI-
TOF MS, m/z calcd for C313H316O95 5621.0 (M + Na), found 5623.4
(M + Na). Anal. Calcd for C313H316O95: C, 67.16; H, 5.69. Found:
C, 66.96; H, 5.80.
1
1
1323, 1241, 1199, 1160, 1108, 1029, 831, 754; H NMR (CDCl3) δ
1.40 (t, 24 H, J ) 7.13 Hz, CH3), 4.37-4.44 (m, 18H, overlapping
OCH2 and focal point benzylic CH2), 4.99 (s, 4 H, benzylic), 5.12 (s,
8 H, benzylic), 6.54 (t, 1 H, J ) 2.20 Hz, aromatic), 6.60 (t, 2 H, J )
2.23 Hz, aromatic), 6.63 (d, 2 H, J ) 2.21 Hz, aromatic), 6.70 (d, 4 H,
J ) 2.23 Hz, aromatic), 8.29 (d, 8 H, J ) 1.58 Hz, aromatic), 8.63 (t,
4 H, J ) 1.62 Hz, aromatic); MALDI-TOF MS, m/z calcd for C73H75-
BrO22 1407.2 (M + Na), found 1407.7 (M + Na). Anal. Calcd for
C73H75BrO22: C, 63.34; H, 5.46. Found: C, 63.09; H, 5.31.
(K) (m-EtO2C)32-[G-4]-Br (14). (m-EtO2C)32-[G-4]-OH (13) (3.48
g, 6.21 × 10-4 mol) was dissolved in refluxing THF (10 mL) in a 50
mL round-bottomed flask equipped with a magnetic stirrer, reflux
condenser, and N2 inlet. CBr4 (0.62 g, 1.87 × 10-3 mol) and PPh3
(0.49 g, 1.87 × 10-3 mol) were added in rapid succession. Within 2
min, a white precipitate appeared and the reaction mixture turned bright
yellow. The reaction was then quenched with water and partitioned
between water and CH2Cl2. The organic layer was dried over MgSO4,
filtered, and concentrated. The crude product was purified by column
chromatography (1% Et2O in CH2Cl2 increasing slowly to 10%) to
afford the product 14 as a clear glass (2.70 g, 76.7%): FT-IR (KBr)
(H) (m-EtO2C)16-[G-3]-OH (11). (m-EtO2C)8-[G-2]-Br (10) (135.7.0
g, 9.8 × 10-2 mol) was combined with 3,5-dihydroxybenzyl alcohol
(6) (6.70 g, 4.78 × 10-2 mol), K2CO3 (27.02 g, 1.96 × 10-1 mol),
18-crown-6 (8.13 g, 3.10 × 10-2 mol), and THF (1.2) in a 2 L three-
necked round-bottomed flask equipped with a mechanical stirrer, reflux
condenser, heating mantle, and N2 inlet. The mixture was heated at
45-50 °C for 72 h, at which point the reaction was at >90% completion
by HPLC analysis (CH3CN, reverse phase). CH2Cl2 (500 mL) was
added, and the reaction mixture was filtered to remove insoluble
inorganic salts. The solvents were stripped on a rotary evaporator until
a final volume of 800 mL was reached, and the solution was placed in
a freezer overnight. The precipitates were recrystallized once from
2:1 THF/CH2Cl2 (700 mL) and again from 4:3 THF/CH2Cl2 (700 mL).
The product was dried overnight in a vacuum oven at 50 °C to afford
11 as a white powder (100.6 g, 76.7%): mp 113-115 °C; FT-IR (KBr)
ν
max cm-1 2981, 2937, 2906, 2875, 1721, 1595, 1447, 1369, 1325, 1238,
1196, 1157, 1108, 1049, 1028, 953, 928, 859, 832, 753; 1H NMR
(CDCl3) δ 1.36 (t, 96 H, J ) 7.13 Hz, CH3), 4.36 (q, 64 H, J ) 7.13
Hz, OCH2), 4.42 (s, 2 H, benzylic), 4.93-5.00 (s, 28 H, benzylic),
5.04-5.15 (s, 32 H, benzylic), 6.53-6.71 (m, 16 H, aromatic), 8.26-
8.29 (m, 16 H, aromatic), 8.60-8.62 (m, 8 H, aromatic); MALDI-
TOF MS, m/z calcd for C313H315BrO94 5683.8 (M + Na), found 5685.5
(M + Na). Anal. Calcd for C313H315BrO94: C, 66.41; H, 5.61.
Found: C, 66.21; H, 5.74.
ν
max cm-1 3522, 2982, 2938, 2905, 2874, 1723, 1596, 1447, 1369, 1324,
1
1242, 1199, 1159, 1108, 1029, 831, 754; H NMR (CDCl3) δ 1.39 (t,
48 H, J ) 7.12 Hz, CH3), 2.05 (t, 1 H, J ) 6.11 Hz, OH), 4.38 (q, 32
H, J ) 7.12 Hz, OCH2), 4.60 (d, 2 H, J ) 6.04 Hz, benzylic), 4.95 (s,
4 H, benzylic), 4.98 (s, 8 H, benzylic), 5.07-5.09 (m, 16 H, benzylic),
6.52-6.71 (m, 21 H, aromatic), 8.24-8.27 (m, 16 H, aromatic), 8.58-
8.61 (m, 8 H, aromatic); MALDI-TOF MS, m/z calcd for C153H156O47
2769.8 (M + Na), found 2769.6 (M + Na). Anal. Calcd for
(L) {(m-EtO2C)16-[G-3]}2-[C] (24). (m-EtO2C)16-[G-3]-Br (12)
(4.62 g, 1.64 × 10-3 mol) was combined with 4,4′-biphenol (0.15 g,
8.06 × 10-4 mol), K2CO3 (1.11 g, 8.03 × 10-3 mol), 18-crown-6 (0.204
g, 7.62 × 10-4 mol), and THF (45 mL) in a 100 mL round-bottomed
flask equipped with a magnetic stirrer, reflux condenser, and N2 inlet.
The mixture was heated at reflux for 24 h, at which point MALDI-
TOF analysis indicated the complete disappearance of the starting
material. The solvents were stripped in Vacuo, and the crude material
was loaded directly onto a silica gel column. Elution with 2% methanol
in CH2Cl2 followed by precipitation from THF into pentane afforded
24 as a fine powder (4.07 g, 89.5%): FT-IR (KBr) νmax cm-1 2952,
1725, 1596, 1498, 1455, 1374, 1324, 1237, 1192, 1048, 973, 830, 752;
1H NMR (CDCl3) δ 1.37 (t, 96 H, J ) 7.12 Hz, CH3), 4.37 (q, 64 H,
J ) 7.12 Hz, OCH2), 4.98 (s, 28 H, benzylic), 5.08 (s, 32 H, benzylic),
6.57 (m, 14 H, aromatic), 6.70 (m, 28 H, aromatic), 6.96 (d, 4 H, J )
9.00 Hz, aromatic), 7.40 (d, 4 H, J ) 8.77 Hz, aromatic), 8.26 (m, 32
H, aromatic), 8.60 (m, 16 H, aromatic); 13C NMR (CDCl3) δ 14.28,
61.40, 69.04, 69.82, 101.58, 106.53, 114.95, 127.62, 130.16, 131.26,
132.50, 133.57, 137.63, 139.22, 139.40, 139.48, 157.81, 159.76, 159.97,
160.05, 165.50; MALDI-TOF MS, m/z calcd for C318H318O94 5645.0
(M + H), found 5648.2 (M + H). Anal. Calcd for C318H318O94: C,
67.67; H, 5.68. Found: C, 67.77; H, 5.88.
C153H156O47: C, 66.90; H, 5.72. Found: C, 67.09; H, 5.59.
(I) (m-EtO2C)16-[G-3]-Br (12). (m-EtO2C)16-[G-3]-OH (11) (81.47
g, 2.97 × 10-2 mol) was combined with THF (160 mL) in a 1 L three-
necked round-bottomed flask equipped with a condenser, N2 inlet, and
mechanical stirrer. The mixture was heated to 60 °C, at which point
all of the solids were dissolved and the heating power was lowered.
CBr4 (10.33 g, 3.11 × 10-2 mol) and PPh3 (15.58 g, 5.94 × 10-2 mol)
were added all at once. After 10 min, a white precipitate formed and
the reaction mixture turned bright yellow. The reaction was quenched
with water (200 m), and then CH2Cl2 (200 mL) was added. The mixture
was poured into a separatory funnel, the organic layer was washed twice
with equal volumes of water and dried over magnesium sulfate, and
the solvents were stripped on a rotary evaporator to yield a yellowish
oil. The crude product was recrystallized twice from THF (700 mL)
and once from 5:3 THF/methanol (800 mL). The product was dried
overnight in a vacuum oven at 50 °C to afford 12 as a fine, white
powder (68.63 g, 82.2%): mp 110-111 °C; FT-IR (KBr) νmax cm-1
2982, 2939, 2906, 2874, 1723, 1596, 1447, 1369, 1324, 1238, 1198,
(M) {(m-EtO2C)32-[G-4]}2-[C] (25). (m-EtO2C)32-[G-4]-Br (14)
(1.40 g, 2.47 × 10-4 mol) was combined with 4,4′-biphenol (2.25 ×
10-2 g, 1.21 × 10-4 mol), K2CO3 (5.02 × 10-2 g, 3.63 × 10-4 mol),
18-crown-6 (1.60 × 10-2 g, 6.05 × 10-5 mol), and THF (10 mL) in a
25 mL round-bottomed flask equipped with a magnetic stirrer, reflux
condenser, and N2 inlet. The mixture was heated at reflux for 28 h, at
which point MALDI-TOF analysis indicated the complete disappearance
of the starting material. The solvents were stripped in Vacuo, and the
crude material was loaded directly onto a silica gel column. Elution
with a slow solvent gradient (10-13% Et2O in CH2Cl2) followed by
precipitation from THF to methanol afforded 25 as a fine powder, which
was dried overnight in a vacuum oven at 50 °C (1.29 g, 94.0%): FT-
IR (KBr) νmax cm-1 2982, 1723, 1596, 1447, 1369, 1324, 1237, 1198,
1
1160, 1108, 1029, 834, 754; H NMR (CDCl3) δ 1.39 (t, 48 H, J )
7.10 Hz, CH3), 4.38 (q, 32 H, J ) 7.13 Hz, OCH2), 4.42 (s, 2 H,
benzylic), 4.96 (s, 4 H, benzylic), 4.98 (s, 8 H, benzylic), 5.05-5.10
(m, 16 H, benzylic), 6.56-6.71 (m, 21 H, aromatic), 8.26-8.29 (m,
16 H, aromatic), 8.60-8.62 (m, 8 H, aromatic); MALDI-TOF MS, m/z
calcd for C153H155BrO46 2848.7 (M + K), found 2848.3 (M + K). Anal.
Calcd for C153H155BrO46: C, 65.41; H, 5.56. Found: C, 65.60; H, 5.69.
(J) (m-EtO2C)32-[G-4]-OH (13). (m-EtO2C)8-[G-3]-Br (12) (7.34
g, 2.61 × 10-3 mol) was combined with 3,5-dihydroxybenzyl alcohol
(0.18 g, 1.28 × 10-3 mol), K2CO3 (1.10 g, 8.02 × 10-3 mol), 18-
crown-6 (0.13 g, 5.10 × 10-4 mol), and THF (70 mL) in a 250 mL
round-bottomed flask equipped with a magnetic stirrer, reflux condenser,
heating mantle, and N2 inlet. The reaction was heated at 60 °C for
184 h, at which point the starting material was no longer evident by
TLC. The reaction mixture was partitioned between CH2Cl2 and water,
and the organic layer was washed three times with water and dried
over MgSO4. The solvent was then stripped on a rotary evaporator to
afford a yellowish oil. The crude product was purified by column
chromatography (1% Et2O in CH2Cl2 increasing slowly to 15%) three
1
1160, 1108, 1029, 833, 754, 719; H NMR (CDCl3) δ 1.34 (t, 192 H,
J ) 7.12 Hz, CH3), 4.33 (q, 128 H, J ) 7.11 Hz, OCH2), 4.92 and
5.03 (bs, 124 H, benzylic), 6.51-6.53 and 6.64-6.73 (m, 90 H,
aromatic), 6.93 (d, 4 H, J ) 8.56 Hz, aromatic), 7.36 (d, 4 H, J ) 8.57
Hz, aromatic), 8.21 (d, 64 H, J ) 1.50 Hz, aromatic), 8.55 (d, 32 H,
J ) 1.53 Hz, aromatic); 13C NMR (CDCl3) δ 14.19, 61.31, 68.86, 69.66,
96.84, 101.41, 106.28, 106.39, 114.76, 127.46, 129.99, 131.11, 132.35,
133.36, 137.57, 139.12, 139.16, 139.25, 139.40, 157.71, 159.63, 165.37;