9996 J. Am. Chem. Soc., Vol. 122, No. 41, 2000
He et al.
again removed in vacuo to ensure the removal of excess formic acid;
this was repeated twice. The residue was dissolved in hot acetone (3
mL), and then the solution was carefully added into Et2O (200 mL)
with stirring to afford a white precipitate, which was filtered and dried
in vacuo to give (95%) 7, as a white solid: 1.25 g; mp 166-168 °C;
1H NMR (DMSO-d6) δ 1.40-1.60 [br m, (CH2)3, 6H], 2.05-2.20 (br
m, CH2CH2CO2H, 12H), 3.34 (t, J ) 6.4 Hz, CH2NH, 2H), 4.17 (t, J
) 6.1 Hz, OCH2, 2H), 7.44 (m, 5,5′′-tpyH, 2H), 7.89-8.06 (br m, NH,
4,4′′,3′,5′-tpyH, 6H), 8.54 (d, J ) 7.8 Hz, 3,3′′-tpyH, 2H), 8.65 (d, J
) 5.0 Hz, 6,6′′-tpyH, 2H), 8.76-8.98 (m, ArH, 3H); 13C NMR (DMSO-
d6) δ 23.1 (CH2CH2CH2NH), 28.3, 28.4, (CH2CH2COOH), 28.8, 29.1
(CH2CH2CH2CH2NH), 40.5 (CH2NH), 58.1 (4°C), 67.9 (OCH2), 106.8
(5,5′′-tpyC), 121.0 (4,4′′-tpyC), 124.2 (d, 2,6-ArC), 124.5 (3,3′′-tpyC),
132.6, 136.1, 137.1 (4,3,5-ArC), 137.3 (3′,5′-tpyC), 147.7 (ArCNO2),
149.2 (6,6′′-tpyC), 155.0 (2,2′′-tpyC), 156.7 (2′,6′-tpyC), 163.8 (CON-
HC), 164.1 (CH2NHCO), 166.8 (4′-tpyC), 174.6 (CO2); IR (KBr) 3355,
3085, 2942, 1734, 1718, 1652, 1552, 1462, 1205, 792 cm-1; ESI-MS
m/z 757.8 (M + H)+. Anal. Calcd for C38H40N6O11: C, 60.31; H, 5.33;
N, 11.11. Found: C, 60.47; H, 5.37; N, 11.25.
631 mg; 1H NMR δ 1.30 (br s, CH3, 108H), 1.38-1.72 (br m,
CH2CH2CH2, 24H), 2.00-2.20 (br m, CH2CH2CO2, 48H), 2.43 (br s,
CH2CONH, 8H), 3.32 (br m, CH2CHCONH, CONHCH2, 16H), 3.55-
4.10 (br m, OCH2, 16H), 6.84 (s, NH, 4H), 7.21 (m, 5,5′′pyH, 8H),
7.30 (s, NH, 4H) 7.68-8.06 (br m, ArH, 4,4′′,3′,5′-tpyH, 28H), 8.45
(d, J ) 8.0 Hz, 3,3′′-tpyH, 8H), 8.55 (d, J ) 4.5 Hz, 6,6′′-tpyH, 8H),
9.16 (s, NH, 4H); 13C NMR δ 23.5 (CH2CH2CH2NH), 28.0 (CH3), 28.6,
29.2 (CH2CH2CH2CH2NH), 29.7,29.8 (CH2CH2CO2), 37.9 (CH2-
CONH), 40.1 (CONHCH2), 45.3 (4°C), 58.1 (4°C), 67.5, 67.9, 70.3 (all
OCH2), 80.6 (CMe3), 107.4 (5,5′′-tpyC), 120.4 (4-ArC), 121.3 (4,4′′-
tpyC), 123.8 (3,3′′-tpyC), 135.7, 136.1, (2,3,5,6-ArC), 136.8 (3′,5′-
tpyC), 139.2 (ArCNHCO), 148.9 (6,6′′-tpyC), 156.0 (2,2′′-tpyC), 157.0
(2′,6′-tpyC), 166.1, 166.8 (CONH, CH2NHCO), 167.1 (4′-tpyC), 170.8
(OCH2CH2CONH), 172.8 (CO2); IR (KBr) 3328, 3064, 2976, 2938,
2872, 1727, 1661, 1561, 1440, 1367, 1154, 840, 791, 741 cm-1; ESI-
MS m/z 1988.7 (M + 2Na)2+. Anal. Calcd for C217H284N24O44: C, 66.27;
H, 7.28; N, 8.54. Found: C, 65.93; H, 7.40; N, 8.40.
Second Tier Dendritic Core (12). To a stirred solution of the second
tier building block 9 (1.80 g, 938 µmol) and Et3N (142 mg, 1.41 mmol,
6 equiv.) in dry THF (40 mL) at -5 °C, was added dropwise a solution
of tetraacid chloride 10 (117 mg, 234 µmol) in THF (10 mL). Following
Method 3, the crude material was column chromatographed eluting
with a solution of hexane (25%) in EtOAc, followed by a solution of
MeOH (5%) in EtOAc to afford (24%) the pure 12, as a light yellow
Nitro Nonaester (8). To a solution of triacid 7 (800 mg, 1.06 mmol)
in dry DMF (10 mL) were added DCC (654 mg, 3.17 mmol) and
1-HOBT (428 mg, 3.17 mmol) at 25 °C. The mixture was stirred for
1 h, and then amine 2 (1.318 g, 3.17 mmol) was added. Following
Method 1, the crude product was column chromatographed eluting with
a solution of EtOAc (70%) in hexane to afford (90%) 8, as a white
1
solid: 452 mg; H NMR δ 1.30 (br s, CH3, 324H), 1.38-2.50 (br m,
1
CH2, 224H), 3.32 (br m, CH2O, CONHCH2, 16H), 3.55-4.10 (br m,
OCH2, 16H), 6.94 (s, NH, 4H), 7.20 (m, 5,5′′-tpyH, 8H), 7.30 (s, NH,
4H) 7.68-8.06 (br m, ArH, 4,4′′,3′,5′-tpyH, 28H), 8.45 (d, J ) 8.0
Hz, 3,3′′-tpyH, 8H), 8.60 (d, J ) 4.2 Hz, 6,6′′-tpyH, 8H), 9.16 (s, NH,
4H); 13C NMR δ 23.5 (CH2CH2CH2NH), 28.0 (CH3), 28.3, 28.8 (CH2-
CH2CH2CH2NH), 29.8,29.9 (CH2CH2CO2), 33.2, 33.2 (CH2CH2CONH),
38.6 (CH2CONH), 40.2 (CONHCH2), 45.6 (4°C), 57.3 (12 4°C), 58.6
(4 4°C), 68.0, 68.1, 69.7 (all OCH2), 80.3 (CMe3), 107.4 (5,5′′-tpyC),
120.4 (4-ArC), 121.2 (4,4′′-tpyC), 123.7 (3,3′′-tpyC), 135.8, 135.9,
(2,3,5,6-ArC), 136.6 (3′,5′-tpyC), 138.7 (ArCNHCO), 148.9 (6,6′′-
tpyC), 156.1 (2,2′′-tpyC), 156.9 (2′,6′-tpyC), 166.1, 166.5 (CONH, CH2-
NHCO), 167.2 (4′-tpyC), 170.7 (OCH2CH2CONH), 172.7 (CO2), 173.0
(CH2CONH); IR (KBr) 3361, 3063, 2976, 2936, 1729, 1652, 1558,
1453, 1370, 1150, 847 cm-1; MALDI-TOF-MS m/z 8075 (M + 2Na
-H)+, 2,5-dihyroxybenzoic acid (DHB) matrix. Anal. Calcd for
solid: 1.86 g; H NMR δ 1.33 (br s, CH3, 81H), 1.38-2.15 (br m,
CH2CH2CONH, CH2CH2CO2, CH2CH2CH2, 54H), 3.46 (br s, CH2NH,
2H), 4.16 (t, J ) 6.0 Hz, OCH2, 2H), 7.21 (m, 5,5′′-tpyH, 2H), 7.75
(td, J ) 7.2, 1.6 Hz, 4,4′′-tpyH, 2H), 7.91 (br m, NH, 3′,5′-tpyH, 4H),
8.51 (d, J ) 8.2 Hz, 3,3′′-tpyH, 2H), 8.58 (d, J ) 4.7 Hz, 6,6′′-tpyH,
2H), 8.83-8.98 (m, ArH, 3H); 13C NMR δ 23.4 (CH2CH2CH2NH),
28.0 (CH3), 28.3, 28.7 (CH2CH2CH2CH2NH), 29.5,29.8 (CH2CH2CO2),
31.8, 32.0 (CH2CH2CONH), 40.3 (CH2NH), 57.5 (3 4°C), 58.6 (4°C),
67.9 (OCH2), 80.5 (CMe3), 107.3 (5,5′′-tpyC), 121.2 (4,4′′-tpyC), 123.7
(3,3′′-tpyC), 124.4, 125.7, 130.3, 136.5, 136.6 (2,6,4,3,5-ArC), 136.7
(3′,5′-tpyC), 148.7 (ArCNO2), 148.9 (6,6′′-tpyC), 156.0 (2,2′′-tpyC),
157.0 (2′,6′-tpyC), 163.6 (CONHC), 164.5 (CH2NHCO), 167.1 (4′-
tpyC), 172.7 (CO2), 173.0 (CH2CONH); IR (KBr) 3365, 3058, 2976,
2937, 1726, 1655, 1556, 1452, 1370, 1151, 850 cm-1; ESI-MS m/z
1973.6 (M + Na)+. Anal. Calcd for C104H157N9O26: C, 64.07; H, 8.12;
N, 6.47. Found: C, 63.88; H, 8.10; N, 6.28.
C
433H656N36O104: C, 64.77; H, 8.23; N, 6.28. Found: C, 64.93; H, 8.43;
N, 6.40.
Dendritic Assembly (15). To a suspension of complex 13 (143 mg,
Second Tier Key Building Block (9). To a solution of 8 (2.45 g.
1.26 mmol) in MeOH (80 mL), was added 10% Pd/C (1.0 g). Following
Method 2, the crude material was column chromatographed eluting
with a solution of MeOH (5%) and hexane (20%) in EtOAc to give
153 µmol) in MeOH (20 mL), were added the first tier dendritic core
11 (150 mg, 38.1 µmol) and 4-ethylmorpholine (4 drops). Following
Method 4, complex 15 was isolated (97%) as a red solid: 311 mg; mp
1
(83%) 9, as a white solid: 2.01 g; H NMR δ 1.33-1.40 (br s, CH3,
1
> 152 °C (dec); H NMR (CD3CN) δ 1.20-1.40 (br d, CH3, 216H),
81H), 1.40-2.15 (br m, CH2CH2CONH, CH2CH2CO2, CH2CH2CH2,
54H), 3.42 (br s, CH2NH, 2H), 4.16 (t, J ) 6.0 Hz, OCH2, 2H), 6.25
(s, NH2, 2H), 7.21-7.52 (m, NH, ArH, 5,5′′-tpyH, 7H), 7.74 (td, J )
7.9, 1.4 Hz, 4,4′′-tpyH, 2H), 7.91 (s, 3′,5′-tpyH, 2H), 8.51 (d, J ) 7.9
Hz, 3,3′′-tpyH, 2H), 8.58 (d, J ) 4.0 Hz, 6,6′′-tpyH, 2H); 13C NMR δ
23.4 (CH2CH2CH2NH), 28.0 (CH3), 28.6, 29.0 (CH2CH2CH2CH2NH),
29.5,29.7 (CH2CH2CO2), 31.8, 32.3 (CH2CH2CONH), 39.9 (CH2NH),
57.3 (3 4°C), 58.2 (4°C), 67.9 (OCH2), 80.5 (CMe3), 107.3 (5,5′′-tpyC),
113.8, 116.1, 117.0 (4,3,5-ArC), 121.2 (4,4′′-tpyC), 123.7 (3,3′′-tpyC),
135.5, 135.8 (2,6-ArC), 136.6 (3′,5′-tpyC), 147.6 (ArCNH2), 148.9
(6,6′′-tpyC), 156.0 (2,2′′-tpyC), 156.9 (2′,6′-tpyC), 166.7, 167.1, 167.3
(CONHC, CH2NHCO, 4′-tpyC), 172.6 (COO), 173.0 (CH2CONH); IR
(KBr) 3359, 3063, 2976, 2947, 1732, 1655, 1567, 1452, 1370, 1151,
848, 790 cm-1; ESI-MS m/z 1942.8 (M + Na)+. Anal. Calcd for
1.50-2.50 (br m, CH2, 128H), 3.00-3.40 (br m, CH2, 24H), 4.40-
4.50 (br m, OCH2, 32H), 6.39 (br s, NH, 4H), 7.00-8.70 (br m, NH,
ArH, tpyH, 104H); 13C NMR (CD3CN) δ 24.4 (CH2CH2CH2NH), 25.3
(OCH2CH2CH2CONH), 28.4 (CH3), 28.6, 29.0 (CH2CH2CH2CH2NH),
30.8 (d, CH2CH2CO2), 33.0 (OCH2CH2CH2CONH), 37.9 (OCH2CH2-
CONH), 40.2 (CONHCH2), 45.2 (4°C), 58.8 (12 4°C), 59.6 (4 4°C), 66.0,
68.5, 70.7, 71.7 (all OCH2), 81.2, 81.3 (all CMe3), 112.6 (d, 5,5′′-
tpyC), 122.8 (4-ArC), 125.8 (d, 4,4′′-tpyC), 128.8 (d, 3,3′′-tpyC), 136.7,
137.2 (2,3,5,6-ArC), 139.1 (d, 3′,5′-tpyC), 140.9 (ArCNHCO), 153.7
(d, 6,6′′-tpyC), 157.7 (d, 2,2′′-tpyC), 159.7 (d, 2′,6′-tpyC), 167.2 (d,
4′-tpyC), 67.2, 167.6 (CONH, CH2NHCO), 171.8 (OCH2CH2CONH),
173.3 (OCH2CH2CH2CONH), 174.0 (d, CO2); IR (KBr) 3428, 3081,
2976, 2938, 1721, 1650, 1617, 1540, 1457, 1369, 1154, 846, 791, 758;
UV-vis λmax 242 (ꢀ ) 2.74 × 105), 268 (2.37 × 105), 306 (2.32 ×
105), 488 nm (6.67 × 104 dm3 mol-1 cm-1); MALDI-TOF-MS m/z
8283 (M - PF6)+, DHB matrix. Anal. Calcd for C381H508F48N40O76P8-
Ru4: C, 54.29; H, 6.08; N, 6.65. Found: C, 54.34; H, 6.13; N, 6.79.
Isomeric Metallodendrimer (16). To a solution of complex 14 (200
mg, 102 µmol) in MeOH (30 mL), were added the first tier dendritic
core 11 (100 mg, 25.4 µmol) and 4-ethylmorpholine (4 drops).
Following Method 4, complex 16 was generated (93%) as a red solid:
296 mg; mp > 152 °C (dec); 1H NMR (CD3CN) due to peaks
overlapping and broadening, the spectrum did not afford discernible
data; 13C NMR (CD3CN) δ 23.2 (CH2CH2CH2NH), 24.8 (OCH2CH2-
C
104H159N9O24; C, 65.08; H, 8.35; N, 6.57. Found: C, 64.93; H, 8.43;
N, 6.40.
First Tier Dendritic Core (11). To a stirred solution of first tier
building block 6 (800 mg, 894 µmol) and Et3N (135 mg, 1.34 mmol)
in dry THF (40 mL) at -5 °C, was added dropwise a solution of
tetraacid chloride38 10 (111 mg, 223 µmol) in THF (10 mL). Following
Method 3, crude material was column chromatographed eluting with a
solution of CHCl3 (30%) in EtOAc, followed by a mixture of MeOH
(5%) in EtOAc to afford (72%) the pure 11, as a light yellow solid:
(38) Newkome, G. R.; Lin, X. Macromolecules 1991, 24, 1443-1444.