Thiourea-Functionalized Poly(propylene imine) Dendrimers
J . Org. Chem., Vol. 66, No. 6, 2001 2143
downfield from TMS. NMR solvents, deuteriochloroform CDCl3,
and DMSO-d6 were purchased from Cambridge Isotope Labo-
ratories 1H NMR measurements: The NMR relaxation time
experiments and the 2D NMR 1H,1H NOESY experiments
were carried out on a Varian Inova 500 spectrometer operating
at 500.618 MHz and equipped with a 5 mm 500 SW/PFG probe
from Varian. Deuteriochloroform (>99.95 atomic % 2H) was
used as solvent, and 1H chemical shifts were referenced to
CDCl3 (δ 7.26). The spectra were obtained at 25 °C. One-
dimensional proton spectra were recorded with standard
parameters. The 2D NMR spectra were acquired using non-
spinning 5 mm samples with deuterium field-frequency lock-
C536H912N94S32: C, 66.36; H, 9.49; N, 13.57 Found: C, 64.81;
H, 9.43; N, 13.30.
DAB-den dr -(NHCSNH-Ad)64 (2e). DAB-dendr-(NH2)64 (0.93
g, 0.13 mmol) dissolved in chloroform (15 mL) was mixed with
adamantyl isothiocyanate (2.00 g, 10.35 mmol). Same proce-
dure as for compound 2a : yield 2.50 g (85%); Tg 115 °C; mp
1
159 °C; H NMR (500 MHz, CDCl3) δ (ppm) 1.40-1.80 (br s,
636H) 2.10-2.16 (m, 576H), 2.41-2.49 (br s, 372H), 3.52 (br
s, 128H), 6.39 (br s, 64H), 6.94 (br s, 64H); 13C NMR (75 MHz,
CDCl3) δ 26.7, 29.9, 36.5, 42.3, 52.3, 54.3, 180.3; IR (ATR) ν
(cm-1) 1245.8 (CdS), 2905.6 (C-H sat.), 3274.6 (N-H stretch);
MS (MALDI-TOF) calcd (C1080H1840N190S64) 19542.94, found
19584.52. Anal. Calcd for C1080H1840N190S64: C, 66.37; H, 9.51;
N, 13.62. Found: C, 65.16; H, 9.63; N, 13.27.
1
ing. For the H,1H-NOESY spectra, the following parameters
were used: spectral width, 5086 Hz (f2) and 5086 Hz (f1); 256
increments and 16 scans per increment in t1; calibrated mixing
time 0.1 s. Spin-lattice relaxation time (T1) measurements
were conducted using a standard 1H inversion-recovery
experiment supplied by Varian. Typical conditions: puls width
12.5 µs (calibrated), pulse delay >4T1, 20 s, 12 points per run,
16 accumulations per point. The concentrations of the host-
guest complexes were kept constant at 0.4 mM. The constancy
of the equilibrium signal intensity was always investigated
over the whole d2-array period.
Hexa d ecyl Isoth iocya n a te (3). DCC (35.00 g, 0.17 mol)
and carbon disulfide (71.00 mL, 1.19 mol) were dissolved in
stirred diethyl ether (400 mL). The mixture was cooled to -5
°C on an ice/ethanol bath, and hexadecylamine (40.00 g, 0.17
mol) was added in the cold. The mixture was stirred overnight,
allowing the mixture to warm to room temperature. The
precipitated dicyclohexylthiourea was filtered off, and solvent
and residual carbon disulfide were removed by evaporation.
The residue was distilled at 130-135 °C (0.01 mbar) yielding
31.00 g (65%) of the isothiocyanate as an oil: 1H NMR (500
MHz, CDCl3) δ (ppm) 0.90 (t, J 6.8 Hz, 3H), 1.25 (br s, 24H),
1.40 (qn, J 6.8 Hz, 2H), 1.69 (qn, J 6.8 Hz, 2H), 3.5 (t, J 6.8
Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 14.3, 22.9, 26.8,
29.1, 29.6-30.2, 32.2, 45.3, 129.9; IR (ATR) ν (cm-1) 2084.4
(NdCdS), 2921.3 (C-H sat.); LRMS calcd (C17H33NS) 283.6,
found 282; GC 100% purity.
DAB-d en d r -(NHCSNH-Ad )4 (2a ). DAB-dendr-(NH2)4 (0.12
g, 0.37 mmol) was dissolved in chloroform (3 mL). 1-Adamantyl
isothiocyanate (0.37 g, 1.90 mmol) was added and the mixture
stirred 48 h at room temperature. Precipitation during the
reaction occurred for the first-generation dendrimer. The
mixture was added dropwise into stirred diethyl ether (20 mL),
and the product was collected by filtration: yield 0.30 g (75%);
1
mp 156 °C; H NMR (500 MHz, CDCl3) δ (ppm) 1.46 (s, 4H)
DAB-d en d r -(NHCSNH-C16H33) (4a ). Compound 3 (1.63
4
1.68 (br s, 24H), 1.75 (br qn, 8H), 2.10 (br s, 36H), 2.40-2.49
(s + br t, 12H), 3.53 (br s, 8H), 5.90 (br s, 4H), 6.78 (br s, 4H);
13C NMR (75 MHz, CDCl3) δ 25.2, 27.1, 29.6, 36.3, 42.2, 44.0,
51.9, 54.2, 180.5; IR (ATR) ν (cm-1) 1227.9 (CdS), 2905.3 (C-H
g, 5.77 mmol) was dissolved in chloroform (5 mL) and added
to DAB-dendr-(NH2)4 (0.33 g, 1.03 mmol) in a round-bottomed
flask. The mixture was stirred for 48 h at room temperature
and added dropwise to stirred acetone (80 mL). The product
was collected by filtration and air-dried: yield 1.25 g (83%);
sat.), 3270.7 (N-H stretch); MS (MALDI-TOF) calcd (C60H100
-
1
N
10S4) 1089.94, found 1091.41. Anal. Calcd for C60H100N10S4:
mp 91-93 °C; H NMR (500 MHz, CDCl3) δ (ppm) 0.88 (br s,
C, 66.11; H, 9.27; N, 12.85. Found: C, 65.60; H, 10.07; N, 12.72.
DAB-d en d r -(NHCSNH-Ad )8 (2b). DAB-dendr-(NH2)8 (0.30
g, 0.40 mmol) dissolved in chloroform (8 mL) was mixed with
adamantyl isothiocyanate (0.68 g, 3.50 mmol). Same procedure
as for compound 2a : yield 0.840 g (90%); mp 161 °C; 1H NMR
(500 MHz, CDCl3) δ (ppm) 1.41 (s, 4H) 1.58 (s, 8H)1.70 (br s,
48H), 1.78 (qn, 16H), 2.13 (br s, 64H), 2.42-2.51 (m, 36H),
3.55 (br s, 16H), 6.00 (br s, 8H), 6.91 (br s, 8H); 13C NMR (75
MHz, CDCl3) δ 24.4, 25.2, 26.4, 29.8, 36.4, 42.3, 44.0, 52.3,
52.5, 54.3, 180.4; IR (ATR) ν (cm-1) 1215.5 (CdS), 2907.0 (C-H
12H), 1.25 (m, 104H), 1.52-1.58 (m, 12H), 1.75 (br s., 8H),
2.40-2.49 (m, 12 H), 3.48 (br s,16H), 6.28 (br s, 4H), 7.33 (br
s, 4H); 13C NMR (75 MHz, CDCl3) δ 14.2, 22.8, 27.1, 29.4, 29.5,
29.7, 29.8, 32.0, 43.6, 45.0, 52.8, 54.0, 181.1; IR (ATR) ν (cm-1
)
1214.8 (CdS), 2917.7 (C-H sat.), 3245.8 (N-H stretch); MS
(MALDI-TOF) calcd (C84H172N10S4) 1450.9, found 1453.04.
Anal. Calcd for C84H172N10S4: C, 69.53; H, 11.97; N, 9.66.
Found: C, 69.37; H, 12.18; N, 9.55.
DAB-d en d r -(NHCSNH-C16H33
) (4b). Compound 3 (1.57
8
g, 5.52 mmol) was dissolved in chloroform (5 mL) and added
to DAB-dendr-(NH2)8 (0.379 g, 0.49 mmol), same procedure
as for compound 4a : yield 1.25 g (83%); mp 70-73 °C; 1H NMR
(500 MHz, CDCl3) δ (ppm) 0.88 (br t, 24H), 1.25 (m, 208H),
1.57-1.74 (m, 44H), 2.39-2.49 (m, 36H), 3.47 (br s, 32H), 6.32
(br s, 8H), 7.35 (br s, 8H); 13C NMR (75 MHz, CDCl3) δ 14.3,
22.9, 26.8, 27.3, 29.6, 29.7, 29.9, 30.0, 32.2, 43.6, 45.3, 52.0,
52.3, 180.6; IR (ATR) ν (cm-1) 1214.8 (CdS), 2918.0 (C-H sat.),
3247.5 (N-H stretch); MS (MALDI-TOF) calcd (C176H360N22S8)
3042.06, found 3040.36. Anal. Calcd for (C176H360N22S8): C,
69.48; H, 11.95; N, 10.13. Found: C, 69.15; H, 11.95; N, 9.97.
sat.), 3273.6 (N-H stretch); MS (MALDI-TOF) calcd (C128H216
-
-
N
N
22S8) 2320.14, found 2361.83. Anal. Calcd for (C128H216
22S8): C, 66.26; H, 9.40; N, 13.28. Found: C, 64.82; H, 9.20;
N, 12.83.
DAB-den dr -(NHCSNH-Ad)16 (2c). DAB-dendr-(NH2)16 (0.14
g, 0.08 mmol) dissolved in chloroform (3 mL) was mixed with
adamantyl isothiocyanate (0.34 g, 1.75 mmol). Same procedure
as for compound 2a : yield 0.390 g (98%); Tg 127 °C; mp 158
1
°C; H NMR (500 MHz, CDCl3) δ (ppm)1.40 (s, 4H), 1.56 (m,
56H), 1.68-1.75 (m, 96H) 2.10 (br s, 192H), 2.41-2.48 (m,
84H), 3.53 (br s, 32H), 6.08 (br s, 16H), 6.89 (br s, 16H); 13C
NMR (75 MHz, CDCl3) δ 24.3, 26.5, 29.8, 36.5, 42.3, 43.9, 44.0,
52.3, 52.5, 52.8, 54.3, 180.5; IR (ATR) ν (cm-1) 1220.4 (CdS),
2906.0 (C-H sat.), 3271.0 (N-H stretch); MS (MALDI-TOF)
calcd (C264H448N36S16) 4780.54, found 4799.18. Anal. Calcd for
DAB-d en d r -(NHCSNH-C16H33
)
(4c). Compound 3 (1.53
16
g, 5.38 mmol) was dissolved in chloroform (5 mL) and added
to DAB-dendr-(NH2)16 (0.41 g, 0.24 mmol), same procedure as
1
for compound 4a : yield 1.30 g (87%); mp 67-69 °C; H NMR
(500 MHz, CDCl3) δ (ppm) 0.88 (br t, 48H), 1.25 (m, 416H),
1.57-1.74 (m, 92H), 2.39-2.49 (m, 84H), 3.49 (br s, 64H), 6.52
(br s, 16H), 7.34 (br s, 16H); 13C NMR (75 MHz, CDCl3) δ 14.3,
22.9, 26.8, 27.3, 29.0, 29.6, 29.7, 29.8, 29.9, 30.0, 30.2, 43.6,
45.3, 52.1, 52.3, 52.6, 52.8, 181.2; IR (ATR) ν (cm-1) 1214.7
(CdS), 2917.6 (C-H sat.), 3246.3 (N-H stretch); MS (MALDI-
TOF) calcd (C360H736N46S16) 6224.38, found 6243.00. Anal.
Calcd for C360H736N46S16: C, 69.46; H, 11.94; N, 10.35. Found:
C, 69.12; H, 12.13; N, 10.02.
C
264H448N36S16: C, 66.32; H, 9.47; N, 13.48. Found: C, 64.88;
H, 9.55; N, 13.23.
DAB-den dr -(NHCSNH-Ad)32 (2d). DAB-dendr-(NH2)32 (0.14
g, 0.04 mmol) dissolved in chloroform (3 mL) was mixed with
adamantyl isothiocyanate (0.33 g, 1.72 mmol). Same procedure
as for compound 2a : yield 0.39 g (98%); Tg 113 °C; mp 158 °C;
1H NMR (500 MHz, CDCl3) δ (ppm) 1.40 (s, 4H) 1.56 (br s,
120H), 1.68-1.75 (m, 192H) 2.10-2.13 (m, 288H), 2.41-2.48
(m, 180H), 3.53 (br s, 64H), 6.15 (br s, 32H), 6.94 (br s, 32H);
13C NMR (75 MHz, CDCl3) δ 24.2, 26.4, 29.7, 36.3, 42.2, 43.7,
43.8, 52.0, 52.2, 180.1; IR (ATR) ν (cm-1) 1228.0 (CdS), 2906.3
(C-H sat.), 3277.7 (N-H stretch); MS (MALDI-TOF) calcd
(C536H912N94S32) 9701.34, found 9700.80. Anal. Calcd for
DAB-d en d r -(NHCSNHC16H33
)
(4d ). Compound 3 (1.53
32
g, 5.38 mmol) was dissolved in chloroform (5 mL) and added
to DAB-dendr-(NH2)32 (0.42 g, 0.12 mmol), same procedure as
1
for compound 4a : yield 1.35 g (90%); mp 60-63 °C; H NMR
(500 MHz, CDCl3) δ (ppm) 0.88 (br t, 96H), 1.25 (m, 832H),