Second-Generation Supramolecular Dendrimer
FULL PAPER
(
150 MHz, CDCl
C), 109.0 (d, Ar-2,6-C), 107.5 (d, Ar-4-C), 68.0 (t, OCH
CH CH), 30.5 (t, CHCH CH ), 28.9 (t, CH CH CH ), 23.8 (t,
CH CH ), 14.0 (q, CH CH CH ), 11.0 ppm (q,
); MS (EI): m/z (%): 266 (10) [M] C, 154 (100)
3
): d=167.3 (s, CO), 156.9 (s, Ar-3,5-C), 132.2 (s, Ar-1-
N-(4-Methoxycarbonyl-2-pyridyl)-N’-(2-pyridyl)urea (17): Diphenylphos-
phoryl azide (1.17 mL, 5.43 mmol) was added to a suspension of 16
(835 mg, 5.48 mmol), pyridine-2-carboxylic acid (668 mg, 2.56 mmol), and
anhydrous triethylamine (751 mL, 5.39 mmol) in anhydrous benzene
(24 mL). The mixture was stirred at reflux for 24 h and then filtered. The
residue 17 was washed with chloroform (935 mg, 62%). M.p. 205–2088C;
2
), 38.8 (d,
2
2
2
2
2
3
CHCH
CHCH
2
CH
3
3
), 22.9 (t, CH
2
2
3
2
2
3
+
2
CH
+
+
[
[
2
MꢀC
M+H] , 155 (100) [MꢀC
928, 2860 (aliph. CꢀH), 1688 (C=O), 1599, 1508 (arom.), 1452 (aliph.
8
H
17+H] C, 137 (59) [MꢀC
8
H17O] ; MS (CI): m/z (%): 267 (10)
17+2H] C; IR (ATR): n˜ =3352 (OꢀH), 2959,
1
+
+
H NMR (300 MHz, DMSO): d=10.9 (brs, 1H; NH), 10.2 (brs, 1H;
8
H
3
1
1
NH), 8.49 (d, J=5.1 Hz, 1H; Py -6-H), 8.38 (brs, 1H; Py -3-H), 8.31
3
4
5
2
3
ꢀ1
(ddd, J=5.0 Hz, J=1.9 Hz, J=0.9 Hz, 1H; Py -6-H), 7.79 (ddd, J=
.4 Hz, J=7.2 Hz, J=1.9 Hz, 1H; Py -4-H), 7.66 (brs, 1H; Py -3-H),
.49 (dd, J=5.1 Hz, J=1.4 Hz, 1H; Py -5-H), 7.07 (ddd, J=7.2 Hz, J=
.0 Hz, J=0.9 Hz, 1H; Py -5-H), 3.91 ppm (s, 3H; CH
125 MHz, DMSO): d=165.5 (s, COCH
Py -2-C), 152.3 (s, NHCONH), 149.3 (d, Py -6-C), 147.7 (d, Py -6-C),
39.4 (s, Py -4-C), 139.1 (d, Py -4-C), 118.7 (d, Py -5-C), 117.5 (d, Py -5-
C), 112.9 (d, Py -3-C), 112.1 (d, Py -3-C), 53.3 ppm (q, CH
CꢀC), 1242, 1154 cm (CꢀOꢀC); elemental analysis calcd (%) for
(266.33): C 67.64, H 8.33; C15 ·0.5H O (275.34): C 65.43, H
.42; found: C 65.48, H 8.53.
,5-Bis(4-bromobutoxy)benzoic acid 2-ethylhexyl ester (24): 1,4-Dibro-
3
4
2
2
8
7
5
C
8
15
H
22
O
4
H
22
O
4
2
3
4
1
3
3
4
2
13
3
); C NMR
), 153.8 (s, Py -2-C), 152.8 (s,
3
1
(
3
mobutane (28.1 g, 130 mmol) and 23 (3.50 g, 13.0 mmol) were dissolved
in anhydrous acetone (50 mL). Potassium carbonate (5.40 g, 39.1 mmol)
was added and the mixture was stirred for 24 h at 608C. The mixture was
filtered and the solvent removed under reduced pressure. Excess 1,4-di-
2
1
2
1
2
2
1
1
2
1
3
); IR (KBr):
n˜ =3500, 3300–3021 (NꢀH, arom. CꢀH), 1734, 1707 (C=O), 1576, 1560,
bromobutane was removed with
a
rotary evaporator connected to
ꢀ1
+
1
[
[
522 cm (arom.); MS (EI, 70 eV): m/z (%): 272 (11) [M] C, 241 (4)
+ + +
a rotary vane pump (0.1 mbar) to yield a yellow oil. The crude product
was dissolved in cyclohexane (100 mL) and filtered through a short
column (20 cm) of silica gel. The column was flushed with cyclohexane
MꢀOCH
3
] , 179 (31) [MꢀHN’Py] , 152 (100) [MꢀOCNPy] , 121 (51)
+
+
MꢀOCNPyꢀOCH
3
] ; MS (CI, isobutane): m/z (%): 273 (100) [M+H] ,
+ +
1
79 (62) [MꢀHN’Py] , 153 (80) [MꢀOCNPy] , 121 (73) [MꢀOCN-
+
(
200 mL) to remove remains of 1,4-dibromobutane. Afterwards, the prod-
PyꢀOCH
3 12 4 3
] ; HRMS: calcd for C13H N O : 272.09094; found: 272.09070
(D=0.9 ppm); calcd for C CH N O : 273.09430; found: 273.09400
12 12 4 3
1
3
uct was eluted by using cyclohexane/ethyl acetate (9:1, R
was obtained as a yellow oil (6.06 g, 87%). H NMR (500 MHz, CDCl
d=7.15 (d, J=2.4 Hz, 2H; Ar-2,6-H), 6.62 (t, J=2.4 Hz, 1H; Ar-4-H),
f
=0.40) and 24
):
1
3
(D=1.1 ppm).
4
4
N-{4-[N-(8-Amino-3,6-dioxaoctyl)aminocarbonyl]-2-pyridyl}-N’-(2-pyridy-
l)urea (18): A suspension of 17 (1.02 g, 3.77 mmol) and 1,8-diamino-3,6-
dioxaoctane (11.7 mL, 80.0 mmol) in anhydrous THF was heated at
reflux until a transparent liquid formed. Afterwards, the solution was
stirred at 608C for 24 h. The solvent was removed under reduced pres-
sure and the residue was dissolved in chloroform (100 mL) and washed
twice with water (100 mL). After extraction of the aqueous layer with
chloroform, the combined organic layers were dried with magnesium sul-
fate. The solvent was removed under reduced pressure and the residue
3
4
.22 (m
c
, 2H; OCH
2
CH), 4.02 (t, J=6.6 Hz, 4H; Ar-O-CH
2
), 3.49 (t,
, 4H; Ar-
3
J=6.4 Hz, 4H; CH
2
-Br), 2.07 (m
c
, 4H; BrCH
), 1.72 (sept., J=6.1 Hz, 1H; OCH
), 0.94 (t, J=7.4 Hz, 3H; CHCH
2 3 3
CH CH ); C NMR (125 MHz, CDCl ): d=166.4 (s, C=O), 159.9 (s,
2
CH
2
), 1.96 (m
c
3
OCH
CH
CH
2
CH
2
2
CH), 1.50–1.28 (m, 8H; 4
3
3
2
2
CH
3
), 0.90 ppm (t, J=7.0 Hz, 6H;
1
3
2
Ar-3,5-C), 132.5 (s, Ar-1-C), 107.8 (d, Ar-2,6-C), 106.2 (d, Ar-4-C), 67.6
(
(
(
t, COOCH
t, CH CH CH
ArOCH CH ), 24.1 (t, CHCH
CH CH CH ), 11.1 ppm (q, CHCH
2
), 67.2 (t, ArOCH
CH ), 29.4 (t, BrCH
CH
2
), 38.9 (d, CH
CH ), 28.9 (t, CH
), 22.9 (t, CH CH
2
CH), 33.3 (t, BrCH
CH CH CH
CH CH ), 14.0 (q,
2
), 30.6
2
2
2
3
2
2
2
2
2
3
), 27.8
2
2
2
3
2
2
2
3
was stirred with diethyl ether (10 mL). After filtration, 18 was obtained
1
CH
2
+
2
2
3
2
CH
H
3
); MS (EI): m/z (%): 536 (5)
17O] , 135 (100) [C
as a yellow solid (1.24 g, 85%). H NMR (500 MHz, [D
6
]DMSO): d=
+
+
+
3
[
M] C, 455 (1) [MꢀBr] , 405 (8) [MꢀC
8
4
H
8
Br] ;
10.34 (brs, 2H; NHCONH), 8.80 (t, J=5.7 Hz, 1H; CONH), 8.40 (dd,
J=5.2 Hz, J=0.7 Hz, 1H; Py -6-H), 8.30 (ddd, J=5.0 Hz, J=1.9 Hz,
J=0.9 Hz, 1H; Py -6-H), 8.16 (brs, 1H; Py -3-H), 7.79 (ddd, J=8.4 Hz,
J=7.2 Hz, J=1.9 Hz, 1H; Py -4-H), 7.67 (br. d, J=8.4 Hz, 1H; Py -3-
+
+
3
5
3
5
1
3
4
MS (CI): m/z (%): 537 (76) [M+H] , 425 (100) [MꢀC
8
H
15] , 135 (46)
+
2
1
3
[
C
4
H
8
Br] ; IR (ATR): n˜ =2957, 2927, 2872 (aliph. CꢀH), 1715 (C=O),
ꢀ
1
4
2
3
2
1
594 (arom.), 1445 (aliph. CꢀC), 1226, 1160 (CꢀOꢀC), 560 cm (CꢀBr);
(536.34): C 51.51, H 6.77;
12 (561.59): C 53.04, H 7.11; found: C 53.17, H 7.03.
,5-Bis[4-(2,4,6-trioxo-1,3,5-triazinan-1-yl)butoxy]benzoic acid 2-ethyl-
hexyl ester (25): Isocyanuric acid (1.93 g, 14.9 mmol) and 24 (2.00 g,
.73 mmol) were dissolved in anhydrous DMF (25 mL). 1,8-Diazabicyclo-
[5.4.0]undec-7-ene (1.14 g, 1.12 mL, 7.46 mmol) was added dropwise and
3
4
1
3
elemental analysis calcd (%) for C23
·0.3C
H
36Br
2
O
4
H), 7.39 (dd, J=5.2 Hz, J=1.5 Hz, 1H; Py -5-H), 7.06 (ddd, J=7.2 Hz,
3
4
2
J=5.0 Hz,
CH OCH CH
J=1.0 Hz,
OCH ), 3.35 ppm (t, J=5.8 Hz, 2H; CH
): d= 168.4 (s, Py-CONH), 154.5 (s, NHCONH), 154.3
1H;
Py -5-H),
3.50–3.47
(m,
); C NMR
8H;
C
23
H
36Br
2
O
4
6
H
3
13
2
2
2
2
2
NH
2
3
(
(
1
125 MHz, CDCl
3
1
2
1
2
s, Py -2-C), 153.9 (s, Py -2-C), 149.2 (d, Py -6-C), 147.9 (d, Py -6-C),
45.9 (s, Py -4-C), 140.1 (d, Py -4-C), 119.6 (d, Py -5-C), 117.1 (d, Py -3-
3
1
2
2
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
1
1
C), 114.0 (d, Py -5-C), 112.2 (d, Py -3-C), 71.4 (t, CH
CONHCH CH ), 68.1 (t, OCH CH O), 40.9 (t, CH CH
t, CONHCH CH
); IR (ATR): n˜ =3436 (NꢀH), 1691, 1651 (C=O), 1541,
2
CH
2
2
NH ), 70.5 (t,
the mixture was stirred for 24 h at 708C. Water (100 mL) and tert-butyl
methyl ether (100 mL) were added and the organic layer was separated.
Excess isocyanuric acid was removed by filtration, the solvent was re-
moved, and the crude product was purified by column chromatography
(
(
7
(
(
2
2
2
2
2
2
NH
2
), 40.8 ppm
(
1
[
2
ꢀ1
2
+
474, 1417 cm (arom.); MS (ESI): m/z: 411 (5) [M+Na] , 389 (100)
+
M+H] ; elemental analysis calcd (%) for C18
H
24
N
6
O
2
(388.4): C 55.66,
silica gel, dichloromethane/methanol, 10:1, R
f
=0.24) to yield 480 mg
H 6.23, N 21.64; C18H N O ·CH OH·0.3CHCl : C 49.61, H 6.62, N 17.07;
24 6 2 3 3
1
21%) of 25. H NMR (600 MHz, [D
.01 (d, J=2.2 Hz, 2H; Ar-2,6-H), 6.76 (t, J=2.2 Hz, 1H; Ar-4-H), 4.18
6
]DMSO): d=11.39 (brs, 4H; NH),
found: C 49.54, H 6.71, N 17.44.
4
4
5
-Benzoyloxy-N,N’-bis(8-{[2-(2-pyridylaminocarbonylamino)-4-pyridyl]-
3
3
d, J=5.7 Hz, 2H; OCH
2
CH), 4.00 (t, J=6.0 Hz, 4H; Ar-OCH
2
), 3.69
2
CH ,
carbonylamino}-3,6-dioxaoctyl)isophthalic acid diamide (19): Anhydrous
triethylamine (50 mL) and 18 (500 mg, 1.28 mmol) were dissolved in an-
hydrous THF (50 mL). After the dropwise addition of 13 (207 mg,
3
t, J=6.9 Hz, 4H; CH
2
N), 1.80–1.60 (m, 9H; CH CH CH
2
2
2
3
CHCH
CHCH
2
), 1.38 (quint., J=7.4 Hz, 2H; CHCH
2
CH
3
), 1.35–1.23 (m, 6H;
3
3
2
CH
2
CH
2
), 0.90 (t, J=7.4 Hz, 3H; CHCH
2
CH
3
), 0.87 ppm (t, J=
6
44 mmol) dissolved in anhydrous THF (6 mL), the mixture was stirred at
1
3
7
.0 Hz, 6H; CH
COO), 159.8 (s, Ar-3,5-C), 149.9 (s, CH
31.7 (s, Ar-1-C), 107.2 (d, Ar-2,6-C), 105.9 (d, Ar-4-C), 67.6 (t,
ArOCH ), 66.9 (t, COOCH ), 40.1 (t, CH N), 38.2 (d, CH CH), 30.0 (t,
CH CH CH CH ), 24.1 (t, NCH CH ), 28.4 (t, CH CH CH CH ), 25.9
Ar-OCH CH ), 23.5 (t, CHCH CH ), 22.4 (t, CH CH CH CH ), 13.8 (q,
CH CH CH CH ), 10.1 ppm (q, CHCH CH ); MS (MALDI-TOF, Cl-
CCA): m/z: 633.13 [M+H] , 655.26 [M+Na] , 671.28 [M+K] ; MS
2
CH
2
CH
3
); C NMR (150 MHz, [D
6
]DMSO): d=165.4 (s,
RT for 24 h. The newly formed solid was filtered off and discarded. The
solvent was removed under reduced pressure and the residue was puri-
fied by column chromatography (silica gel, chloroform/methanol, 97:3, to
2
NCO), 148.67 (s, NHCONH),
1
2
2
2
2
remove the starting material 18, then 3:1) to yield 19 as a white solid
1
2
2
2
3
2
2
2
2
2
3
(
2
206 mg, 31%). M.p. 1348C; H NMR (500 MHz, DMSO): d=10.81 (brs,
(
2
2
2
3
2
2
2
3
3
H; NHCONH), 10.35 (brs, 2H; NHCONH), 8.76 (t, J=5.5 Hz, 2H;
PyCONH), 8.71 (t, J=5.5 Hz, 2H; Ar CONH), 8.39 (d, J=5.2 Hz, 2H;
Py -6-H), 8.31–8.29 (m, 3H; Py -6-H, Ar -2-H), 8.17–8.15 (m, 4H; Py -3-
H, Ar -2,6-H), 7.92 (d, J=1.4 Hz, 2H; Ar -4,6-H), 7.79–7.75 (m, 3H;
Py -4-H, Ar -4-H), 7.69–7.65 (brs, 2H; Py -3-H), 7.63 (m , 2H; Ar -3,5-
c
H), 7.38 (dd, J=5.2 Hz, J=1.4 Hz, 2H; Py -5-H), 7.05 (ddd, J=7.2 Hz,
2
J=6.2 Hz, J=0.9 Hz, 2H; Py -5-H), 3.58–3.54 (m, 16H; CH O),
3
1
3
2
2
2
3
2
3
+
+
+
1
2
1
1
+
2
4
1
(
2
1
ESI): m/z: 655.27 [M+Na] ; IR (ATR): n˜ =3208, 3075 (NH, OH), 2960,
2
2
2
2
930, 2872 (aliph. CꢀH), 1675 (CONH), 1595 (arom.), 1453 (aliph. CꢀC),
ꢀ
1
3
4
1
3
226, 1165 cm (CꢀOꢀC); elemental analysis calcd (%) for C29
H
N
6
O
40
10
3
4
2
(
632.664): C 55.05, H 6.37, N 13.28; found: C 55.03, H 6.49, N 13.32.
Chem. Eur. J. 2012, 18, 8498 – 8507
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8505