7592
A. Arduini et al. / Tetrahedron 59 (2003) 7587–7594
reagents were of reagent grade quality as obtained
from commercial suppliers and were used without
further purification. Column chromatography were per-
formed on silica gel 63–200 mesh. NMR spectra were
recorded in CDCl3 at 300 K unless otherwise
indicated. Mass spectra were determined in the CI
mode (CH4) as appropriate. Melting point are uncorrected.
N-hydroxymethyl-N0-phenylurea,36 calix[4]arenes 2,37 437
and 1138 were synthesized according to literature
procedures.
acetate (100 mL). The reaction was then quenched by
treatment with a 10% HCl solution (50 mL, CAUTION!).
The organic layer was separated, washed with a saturated
solution of Na2CO3 (100 mL), dried (Na2SO4), and
evaporated to dryness. Purification of the residue by
crystallization with hexane, gave 0.6 g (75%) of 7: mp
146–1488C. 1H NMR (300 MHz) d: 0.63 (t, 6H, J¼7.2 Hz);
1.5–1.7 (m, 4H); 3.05 and 3.15 (2d, 4H, J¼13.5 Hz); 3.7–
3.9 (m, 4H); 4.41 and 4.44 (2d, 4H, J¼13.4 Hz); 4.77 and
4.82 (2s, 4H); 6.21 (d, 2H, J¼7.5 Hz); 6.44 (s, 2H); 6.50 (t,
1H, J¼7.8 Hz); 6.92 (t, 2H, J¼7.3 Hz); 6.98 and 7.07 (2dd,
4H, J1¼7.3 Hz, J2¼1.7 Hz); 7.3–7.5 (m, 10H). 13C NMR
(75 MHz) d: 9.4, 22.8, 30.8, 31.0, 76.5, 105.9, 119.5, 122.3,
122.5, 127.6, 127.8, 128.2, 128.25, 128.3, 128.5, 128.7,
129.5, 130.0, 131.6, 133.5, 135.4, 135.9, 136.6, 136.9,
137.7, 154.6, 157.5. MS-CI(þ) m/z: 714 [MHþ]; Anal.
Calcd for C49H47NO4: C, 82.44; H, 6.64, N, 1.96. Found: C,
82.62; H, 6.70 N, 1.90.
4.1.1. 5-Bromo-25,27-dipropoxycalix[4]arene (5). To a
solution of 4 (2.0 g, 3.9 mmol) in methyl ethyl ketone
(200 mL), NBS was added (0.6 g, 3.5 mmol). After stirring
at rt for 4 h, the solution was diluted with CH2Cl2 (100 mL)
and then treated with a saturated aqueous solution of
Na2SO3 (100 mL). The organic layer was separated, washed
with brine (2£100 mL), dried (Na2SO4), and the solvent was
completely evaporated under reduce pressure. Purification
of the residue by chromatography (hexane/CH2Cl2, 60:40)
gave 0.9 g (45%) of 5 as a pale yellow solid: mp 180–1818C
(dec.). 1H NMR (300 MHz) d: 1.31 (t, 6H, J¼7.4 Hz); 2.0–
2.1 (m, 4H); 3.32, 3.38 (2d, 4H, J¼13 Hz); 3.97 (t, 4H,
J¼6 Hz); 4.28, 4.31 (2d, 4H, J¼13 Hz); 6.66 (t, 1H,
J¼7.5 Hz); 6.76 (t, 2H, J¼7.5 Hz); 6.8–6.9 (m, 4H); 7.12
(d, 2H, J¼7.5 Hz); 7.17 (s, 2H); 8.4 and 8.2 (2s, 2H). 13C
NMR (75 MHz) d: 10.8, 23.4, 29.6, 31.1, 31.3, 78.4, 110.2,
118.9, 125.3, 127.9, 128.4, 129.2, 130.1, 130.6, 132.5,
133.5, 151.8, 152.5, 153.2. MS-CI(þ) m/z: 587 [MHþ];
Anal. Calcd for C34H35BrO4: C, 69.50; H, 6.00. Found: C,
69.32; H, 6.05.
4.1.4. 5-Aminomethyl-26,28-dibenzyloxy-25,27-diprop-
oxycalix[4]arene (8). To
a solution of 7 (0.6 g,
0.84 mmol) in dry THF (30 mL), B2H6 (1 M solution in
THF, 8.4 mL) was added. The resulting mixture was
refluxed for 24 h under argon atmosphere, cooled, treated
with methanol (20 mL, CAUTION!), and then refluxed for
an additional 30 min. The solvent was then completely
evaporated under reduced pressure and the residue taken up
with CH2Cl2 (50 mL) and a saturated solution of Na2CO3
(50 mL). The organic layer was separated, washed with
brine (2£100 mL), dried (Na2SO4), and the solvent was
completely evaporated. Purification of the solid residue by
chromatography (CH2Cl2/CH3OH, 95:5) gave 0.33 g (55%)
of 8 as a white solid: mp 200–2018C (dec.). 1H NMR
(300 MHz) d: 0.65 (t, 6H, J¼7.4 Hz); 1.33 (bs, 2H); 1.7–1.8
(m, 4H); 3.14, 3.15 (2d, 4H, J¼13.3 Hz); 3.30 (s, 2H); 3.8–
3.9 (m, 4H); 4.47, 4.48 (2d, 4H, J¼13.2 Hz); 4.82 (s, 4H);
6.20 (s, 2H); 6.36 (bs, 3H); 6.88 (t, 2H, J¼7.5 Hz); 7.0 (d,
4H, J¼7.5 Hz); 7.3–7.5 (2m, 10H). 13C NMR (75 MHz) d:
9.5, 22.8, 31.0, 31.1, 45.8, 76.5, 77.4, 121.9, 126.4, 127.6,
127.8, 127.83, 128.1, 128.6, 128.7, 128.9, 129.0, 134.0,
136.3, 137.6, 137.8, 153.4, 154.9, 157.5. MS-CI(þ) m/z:
717 [MHþ]; Anal. Calcd for C49H51NO4: C, 81.98; H, 7.16,
N, 1.95. Found: C, 82.12; H, 7.20; N, 1.90.
4.1.2. 5-Cyano-25,27-dipropoxycalix[4]arene (6). To a
solution of 5 (2.0 g, 3.4 mmol) in DMF (100 mL), CuCN
(0.90 g, 10.2 mmol) was added. The resulting hetero-
geneous mixture was poured into a thick wall glass
autoclave and then heated at 2008C for 48 h under vigorous
stirring. After cooling, the solvent was completely evapor-
ated under reduced pressure. The resulting sticky residue
was extracted twice with hot ethyl acetate (2£50 mL). The
combined organic phases were then washed twice with brine
(2£100 mL), dried (Na2SO4), and the solvent was com-
pletely evaporated to dryness (the separated water phase
was carefully treated with a solution of sodium hypochlorite
to destroy the residuals cyanide ions). Purification of the
solid residue by chromatography (hexane/CH2Cl2, 50:50)
afforded 1.8 g (90%) of 6 as a white solid: mp 200–2018C
(dec.). 1H NMR (300 MHz) d: 1.31 (t, 6H, J¼7.4 Hz); 2.0–
2.1 (m, 4H); 3.37, 3.39 (2d, 4H, J¼13.1 Hz); 3.9–4.0 (m,
4H); 4.28, 4.30 (2d, 4H, J¼13 Hz); 6.6–6.7, 6.7–6.8, 6.9–
7.0, 7.0–7.1, (4m, 9H); 7.37 (s, 2H); 8.19 and 9.19 (2s, 2H).
13C NMR (75 MHz) d: 10.8, 23.4, 31.1, 31.3, 78.4, 118.9,
119.0, 125.4, 127.7, 128.3, 128.4, 128.7, 128.8, 129.2,
129.5, 131.8, 132.4, 133.6, 151.7, 153.2. MS-CI(þ) m/z:
534 [MHþ]; Anal. Calcd for C35H35NO4: C, 78.77; H, 6.61;
N, 2.62. Found: C, 78.99; H, 6.67; N, 2.53.
4.1.5. 5-(N-Phenylureido)methyl-26,28-dibenzyloxy-
25,27-dipropoxycalix[4]arene (9). To a solution of 8
(0.3 g, 0.42 mmol) in dry CH2Cl2 (25 mL), phenyl iso-
cyanate (0.05 g, 0.42 mmol) was added. After 3 h under
stirring, the mixture was poured into water (50 mL) and
diluted with CH2Cl2 (50 mL). The organic layer was
separated, washed with water (2£100 mL), dried
(Na2SO4), and the solvent was completely evaporated.
Crystallization with diethyl ether afforded 0.27 g (90%) of 9
as pure white solid: mp 116–1188C. 1H NMR (300 MHz) d:
0.62 (t, 6H, J¼7.4 Hz); 1.6–1.7 (m, 4H); 3.07, 3.11 (2d, 4H,
J¼13 Hz); 3.7–3.8 (m, 4H); 3.89 (d, 2H, J¼5.3 Hz); 4.31
(bt var, 1H); 4.40 and 4.43 (2d, 4H, J¼13.2 Hz); 4.78, 4.79
(2s, 4H); 6.03 (bs var, 1H); 6.16 (s, 2H); 6.2–6.3 (m, 3H);
6.78 (t, 2H, J¼7.4 Hz); 6.9–7.0 (m, 4H); 7.0–7.1, 7.2–7.3
(2m, 5H); 7.3–7.5 (m, 10H). 13C NMR (75 MHz) d: 10.3,
22.8, 29.5, 31.1, 32.7, 42.4, 44.1, 75.5, 120.3, 121.3, 121.96,
122.65, 124.7, 126.94, 127.3, 127.86, 128.8, 129.0, 129.4,
129.98, 131.8, 134.2, 136.2, 137.6, 154.4, 155.3, 157.4. MS-
4.1.3. 5-Cyano-26,28-dibenzyloxy-25,27-dipropoxy-
calix[4]arene (7). To a solution of 6 (0.80 g, 1.5 mmol) in
DMF (60 mL), NaH (0.22 g, 9.2 mmol) was added. The
resulting heterogeneous mixture was stirred for 30 min, then
benzyl bromide (0.65 g, 3.8 mmol) was added. The mixture
was heated at 658C for 3 h, cooled and diluted with ethyl