M. von Delius, F. Hauke, A. Hirsch
FULL PAPER
7.1 Hz, 2 H), 2.45 (s, 3 H), 1.21 (t, 3J = 7.1 Hz, 3 H) ppm. 13C
NMR (CDCl3, 100.5 MHz): δ = 144.76, 132.97, 129.79, 127.98,
70.73, 70.68, 70.50, 69.77, 69.22, 68.65, 66.61, 21.63, 15.14 ppm.
350 g of SiO2, EtOAc/hexanes, 4:1). Clear, colorless oil. Yield:
1.67 g (85%). 1H NMR (CDCl3, 400 MHz): δ = 7.13 (m, 2 H), 6.88
3
4
3
(td, J = 7.4, J = 1.1 Hz, 1 H), 6.83 (d, J = 8.1 Hz, 1 H), 4.12 (t,
3
IR (neat): ν = 2976, 2872, 1598, 1451, 1355, 1293, 1247, 1177, 1096,
3J = 5.2 Hz, 2 H), 3.88 (t, J = 5.2 Hz, 2 H), 3.75 (m, 2 H), 3.70–
˜
1015, 919, 815, 772, 663 cm–1. MS (FAB, NBA): m/z = 333 [M]+.
3.57 (m, 8 H), 3.53 (q, 3J = 6.9 Hz, 2 H), 2.61 (t, 3J = 8.1 Hz, 2
H), 1.80 (s, 1 H), 1.58 (m, 4 H), 1.38 (m, 4 H), 1.21 (t, 3J = 6.9 Hz,
3 H) ppm. 13C NMR (CDCl3, 100.5 MHz): δ = 156, 131.44 (1 C,
14), 129.85 (1 C, 13), 126.76 (1 C, 11), 120.54 (1 C, 12), 111.34,
70.75, 70.62, 69.84, 69.73, 67.49, 66.56, 62.77, 32.56, 30.00, 29.63,
29.11, 25.41, 14.98 ppm. MS (FAB, NBA): m/z = 355 [M]+. IR
1-{2-[2-(2-Ethoxyethoxy)ethoxy]ethoxy}-2-iodobenzene (23): In a
dry 250 mL round-bottomed flask with nitrogen inlet, 2-iodo-
phenol (10.0 g, 45.5 mmol, 1.0 equiv.) and 22 (15.1 g, 45.5 mmol,
1.0 equiv.) were dissolved in DMF (120 mL, extra dry). Following
the addition of potassium carbonate (37.7 g, 69.83 mmol,
6.0 equiv.), the suspension was stirred at room temperature for
48 h. The solvent was then evaporated, and water (50 mL) was
added. The mixture was neutralized with HCl (1 , pH = 5) and
extracted three times with dichloromethane (80 mL). The combined
organic phases were washed with water, dried with MgSO4 and
filtered, and the solvents were removed under reduced pressure.
The crude product was purified by flash column chromatography
(8ϫ24 cm, 400 g of SiO2, DCM/EtOAc, 95:5). Clear, light yellow
oil. Yield: 14.78 g (85%). 1H NMR (CDCl3, 400 MHz): δ = 7.77
(neat): ν = 3435, 2930, 2860, 1602, 1494, 1451, 1351, 1243, 1108,
˜
1054, 934, 845, 753 cm–1. C20H34O5 (354.49): calcd. C 67.76, H
9.67, O 22.57; found C 67.51, H 9.68.
1-[4Ј-{2-[2-(2-Ethoxyethoxy)ethoxy]ethoxy}-3Ј-(6-hydroxyhexyl)-
phenyl]hydroazafullerene (26): In a dry 100 mL round-bottomed
flask with nitrogen inlet and reflux condenser, the bi(azafullerenyl)
2 obtained from C60-N-MEM-oxo-lactam 7 (120 mg, 140.4 µmol,
1.0 equiv.) was dissolved in ODCB (80 mL). Compound 25
(248 mg, 0.7 mmol, 5.0 equiv.) and p-TsOH (538 mg, 2.8 mmol,
20 equiv.) were added to this solution, which was stirred at 150 °C
for 20 min, while a slow stream of oxygen was passed over the
reaction mixture. The progress of the reaction was monitored by
analytical HPLC (Cosmosil, toluene, 1.0 mLmin–1) or TLC (tolu-
ene/MeOH, 9:1, Rf = 0.3). After the mixture had cooled to room
temperature, the product was obtained by flash column chromatog-
raphy (4ϫ15 cm, 60 g of SiO2, toluene, toluene/MeOH, 9:1). For
further purification, the black solid was dissolved in a minimum
amount of CS2, precipitated from n-pentane, washed five times
with n-pentane and dried in high vacuum. To avoid solubility prob-
lems, however, purification of the material by means of preparative
HPLC, rather than by reprecipitation, was carried out. Brown,
amorphous solid. Yield: 21 mg (18% corresponding to 7). HPLC
(Nucleosil, toluene/MeOH, 98:2, 1.0 mLmin–1): tR = 5.5 min. 1H
NMR (C2D2Cl4, 400 MHz): δ = 8.61 (m, 2 H), 7.32 (d, 3J = 8.6 Hz,
3
4
3
(dd, J = 7.7, J = 1.7 Hz, 1 H), 7.28 (m, 1 H), 6.84 (dd, J = 8.0,
4J = 1.3 Hz, 1 H), 6.71 (td, J = 7.7, J = 1.3 Hz, 1 H), 4.17 (t, J
3
4
3
3
= 5.2 Hz, 2 H), 3.93 (t, J = 5.2 Hz, 2 H), 3.82 (m, 2 H), 3.69 (m,
4 H), 3.60 (m, 2 H), 3.53 (q, 3J = 7.1 Hz, 2 H), 1.21 (t, 3J = 7.1 Hz,
3 H) ppm. 13C NMR (CDCl3, 100.5 MHz): δ = 157.55, 139.51,
129.46, 122.74, 112.45, 86.65, 71.18, 70.71, 70.66, 69.79, 69.46,
68.95, 66.58, 15.06 ppm. IR (neat): ν = 2972, 2868, 1583, 1475,
˜
1440, 1374, 1351, 1278, 1247, 1108, 1054, 1019, 930, 845, 749,
706 cm–1. MS (FAB, NBA): m/z = 381 [M + H]+.
6-(2-{2-[2-(2-Ethoxyethoxy)ethoxy]ethoxy}phenyl)hex-5-yn-1-ol
(24): In a dry 100 mL round-bottomed flask with nitrogen inlet, 23
(8.72 g, 22.9 mmol, 0.9 equiv.), copper(I) iodide (243 mg,
1.27 mmol, 0.05 equiv.) and bis(triphenylphosphane)palladium(II)
chloride (536 mg, 0.76 mmol, 0.03 equiv.) were dissolved in dieth-
ylamine (10 mL, 102 mmol, 4.0 equiv.) and dry THF (50 mL). The
solution was cooled to 0 °C and stirred for 10 min, after which hex-
5-yn-1-ol (2.88 mL, 25.5 mmol, 1.0 equiv.) was added. The reaction
mixture was stirred at room temperature for 24 h and quenched
with aqueous NH4Cl (20 mL). Extraction with Et2O (3ϫ60 mL),
washing with brine, drying with MgSO4, filtration and evaporation
of the solvent gave a yellow crude product, which was purified by
repeated flash column chromatography (8ϫ35 cm, 400 g of SiO2,
DCM/EtOAc, 1:1, 11ϫ25 cm, 550 g of SiO2, EtOAc/hexanes, 8:2).
Clear, colorless oil. Yield: 2.30 g (29%). 1H NMR (CDCl3,
3
1 H), 4.37 (t, 3J = 4.7 Hz, 1 H), 4.01 (t, J = 4.7 Hz, 2 H), 3.82 (m,
3
3
2 H), 3.71–3.59 (m, 8 H), 3.52 (q, J = 7.1 Hz, 2 H), 2.94 (t, J =
7.8 Hz, 2 H), 1.85 (m, 2 H), 1.65–1.46 (m, 6 H), 1.22 (t, 3J = 7.1 Hz,
3 H) ppm. 13C NMR (C2D2Cl4, 100.5 MHz): δ = 157.68, 154.48,
149.15, 147.79, 147.60, 147.58, 147.30, 147.15, 146.57, 146.34,
146.16, 145.83, 145.60, 144.98, 144.96, 144.44, 144.22, 143.95,
143.05, 142.66, 141.98, 141.73, 141.51, 141.30, 140.88, 140.80,
139.65, 137.56, 133.25, 133.15, 132.91, 128.65, 125.93, 124.04,
112.21, 82.62, 70.63, 70.33, 70.29, 69.54, 69.45, 67.75, 66.34, 62.71,
32.54, 30.63, 29.68, 29.30, 25.37, 15.03 ppm. IR (neat): ν = 3258,
˜
3
4
3
300 MHz): δ = 7.36 (dd, J = 7.6, J = 1.6 Hz, 1 H), 7.22 (td, J =
2910, 2868, 2806, 1725, 1687, 1559, 1509, 1444, 1420, 1393, 1370,
1278, 1251, 1231, 1197, 1073, 1046, 1023, 992, 938, 919, 838, 803,
764, 741, 706, 679 cm–1. UV/Vis (toluene): λmax = 285, 324, 443 nm.
MS (FAB, NBA): m/z = 722 [C59N]+, 1076 [M]+, 1092 [M + O]+.
7.9, 4J = 1.6 Hz, 1 H), 6.87 (m, 2 H), 4.18 (t, 3J = 5.2 Hz, 2 H),
3
3.94 (t, J = 5.2 Hz, 2 H), 3.80 (m, 2 H), 3.72–3.63 (m, 6 H), 3.58
(m, 2 H), 3.52 (q, 3J = 7.0 Hz, 2 H), 2.50 (t, 3J = 6.6 Hz, 2 H),
3
2.01 (s, 1 H), 1.83–1.65 (m, 4 H), 1.21 (t, J = 7.0 Hz, 3 H) ppm.
1-{3Ј-[6-(Azidomethoxy)hexyl]-4Ј-(2-[2-(2-ethoxyethoxy)ethoxy]-
ethoxy)phenyl}hydroazafullerene (27) and One-Pot Experiments Di-
rected Towards C58N2: In a dry 2 mL flask with nitrogen inlet, 26
(21 mg, 24.9 µmol, 1.0 equiv.) was dissolved under nitrogen in tet-
rachloroethane (0.5 mL), and trimethylsilyl chloride (7.9 µL,
62.3 µmol, 2.5 equiv.) and paraformaldehyde (0.8 mg, 27.4 µmol,
13C NMR (CDCl3, 100.5 MHz): δ = 159.36, 133.34, 128.84, 120.72,
113.81, 112.21, 94.12, 70.91, 70.74, 70.70, 69.82, 69.69, 68.33,
66.63, 62.35, 31.92, 24.88, 19.47, 15.12 ppm. IR (neat): ν = 3343,
˜
2934, 2872, 1725, 1598, 1494, 1447, 1262, 1100, 1058, 938,
753 cm–1. MS (FAB, NBA): m/z = 351 [M]+.
6-(2-{2-[2-(2-Ethoxyethoxy)ethoxy]ethoxy}phenyl)hexan-1-ol (25): 1.1 equiv.) were added at room temperature. The solution was
In a 50 mL round-bottomed flask with nitrogen cap, 24 (1.94 g,
5.53 mmol, 1.0 equiv.) was dissolved in EtOH (15 mL). Palladium/
charcoal catalyst (10%, 194 mg, 0.18 mmol, 0.033 equiv.) was
added, and the suspension was stirred under hydrogen under stan-
dard conditions for 18 h. The reaction mixture was filtered through
Celite (30 g, 535 coarse), and the filter cake was thoroughly rinsed
with ethanol. Evaporation of the solvents gave the crude product,
which was purified by flash column chromatography (8ϫ25 cm,
stirred at room temperature for 2 h, during which the insoluble
paraformaldehyde was successively consumed. The excess trimeth-
ylsilyl chloride was removed under reduced pressure (appr.
100 mbar). Because of the high reactivity, as well as toxicity (!),[22]
of the chloromethyl ether, the crude material was used without fur-
ther purification. Under nitrogen, sodium azide (594 mg, µmol,
3.0 equiv.) and 18-crown-6 (40 mg, 0.15 µmol, 0.05 equiv.) were
added to the crude chloromethyl ether, and the reaction mixture
4118
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4109–4119