O. Hudecek et al. / Tetrahedron 67 (2011) 5213e5218
5217
(150 ml). The precipitate was filtered off, washed with methanol
and air dried to give 400 mg (75%) of product 6 as a slightly brown
powder, mp: 270 ꢃC (decomp.). 1H NMR (300 MHz; (CD3)2SO): dH
9.86 (2H, s, AreCHO), 8.52e8.49 (4H, m, AreH (Nos)), 8.14e8.11
(4H, m, AreH (Nos)), 7.80 (4H, s, AreH), 6.51 (2H, t, J¼7.6 Hz, AreH),
6.29 (4H, d, J¼7.6 Hz, AreH), 3.92 (4H, d, J¼13.5 Hz, AreCH2eAr ax),
3.76 (4H, t, J¼8.3 Hz, 2ꢂ OCH2), 3.16 (4H, d, J¼14.7 Hz, AreCH2eAr
eq), 1.74e1.67 (4H, m, 2ꢂ OCH2CH2), 0.73 (6H, t, J¼7.3 Hz, 2ꢂ CH3).
574.2 (100) [MþNaꢀ2H]ꢀ. EA calcd for C34H35NO6, C, 73.76; H, 6.37;
N, 2.53%. Found C, 73.42; H, 6.31; N, 2.39%.
4.7.3. Synthesis of 5,17-dibromo-26,28-dipropoxycalix[4]arene-25,27-
diol (cone) 9. General procedure was applied to 100 mg of calixar-
ene 6, KOH (270 mg) in 20 ml of ethanol and 20 ml of
dichloromethane. No further purification was needed, and product 9
was obtained in 97% yield (62 mg) as a white powder, mp:
214e216 ꢃC. 1H NMR (300 MHz; CDCl3, Me4Si): dH 8.22 (2H, s,
AreOH), 7.08 (4H, s, AreH), 7.04 (4H, d, J¼7.3 Hz, AreH), 6.66 (2H, t,
J¼7.5 Hz, AreH) 4.26 (4H, d, J¼12.9 Hz, AreCH2eAr ax), 3.95 (4H, t,
J¼6.2 Hz, 2ꢂ OCH2), 3.35 (4H, d, J¼13.2 Hz, AreCH2eAr eq), 2.11e2.00
(4H, m, 2ꢂ OCH2CH2), 1.31 (6H, t, J¼7.5 Hz, 2ꢂ CH3). 13C NMR
13C NMR (75 MHz; CD2Cl2):
d 191.2, 162.9, 151.4, 144.4, 141.5, 136.9,
133.6, 131.8, 131.2, 130.2, 128.9, 126.2, 124.8, 77.2, 31.9, 23.4, 9.8. TOF
MS (ESþ) m/z (%): for C48H42N2O14S2 (935.00) found: 957.6 (100)
[MþNa]þ. EA calcd for C48H42N2O14S2, C, 61.66; H, 4.53; N, 3.00; S,
6.86%. Found C, 61.52; H, 4.40; N, 2.89; S, 6.62%.
(75 MHz; CDCl3, Me4Si): d 153.5,151.4, 135.9, 132.2, 129.0,127.4, 119.7,
4.7. Deprotection of (p-nitrobenzenesulfonyl) groupdgeneral
procedure
117.9, 78.8, 31.6, 23.7, 11.1. TOF MS (ESꢀ) m/z (%): for C34H34Br2O4
(666.46) found. 665.2 (100) [MꢀH]ꢀ. EA calcd for C34H34Br2O4, C,
61.28; H, 5.14; Br, 23.98%. Found C, 61.02; H, 5.02; Br, 23.73%.
The corresponding calixarenes 4e6 were dissolved in a mix-
ture of dichloromethane and ethanol (1:1, v/v) and 50 equiv of
powdered potassium hydroxide was added. The reaction mixture
was allowed to stir at room temperature for 24 h, then acidified
with 1 M hydrochloric acid and extracted with CH2Cl2. The
combined organic layers were washed with brine and dried over
MgSO4, and the organic solvent was evaporated under reduced
pressure.
4.7.4. Synthesis of 5,17-diamino-26,28-dipropoxycalix[4]arene-25,27-
diol (cone) 10. A catalytic amount (10 mg) of Raney nickel was
added to the solution of calix[4]arene 7 (400 mg, 0.67 mmol) and
hydrazine monohydrate (1.5 ml) in methanol (100 ml), and resulting
mixture was heated to reflux. After 7 h the same amount of hydra-
zine monohydrate (1.5 ml) and Raney nickel was added once again
and the mixture was refluxed for further 15 h. After cooling to room
temperature, the resulting suspension was filtered through the short
column of Celite, the column was washed by additional 50 ml of
MeOH, and the solvent was removed under reduced pressure. The
solid residue was dissolved in 100 ml of CH2Cl2, washed with water,
brine and dried over MgSO4. The evaporation of solvent gave 262 mg
of product 10 (73%) as a brown powder, mp: 313e315 ꢃC. 1H NMR
(300 MHz; CDCl3, Me4Si): dH 8.43 (2H, s, AreOH), 7.01 (4H, d,
J¼7.3 Hz, AreH), 6.63 (2H, t, J¼7.3 Hz, AreH), 6.22 (4H, s, AreH), 4.24
(4H, d, J¼12.6 Hz, AreCH2eAr ax), 3.91 (4H, t, J¼6.3 Hz, 2ꢂ OCH2),
3.24 (4H, d, J¼12.9 Hz, AreCH2eAr eq), 3.16 (4H, br s, AreNH2),
4.7.1. Synthesis of 5,17-dinitro-26,28-dipropoxycalix[4]arene-25,27-
diol (cone) 7. General procedure was applied to 3.28 g of calixar-
ene 3, KOH (9.50 g) in 500 ml of ethanol, 500 ml of DCM and 3.5 ml
of water.13 The residue after evaporation was dissolved in 2 ml of
dichloromethane and precipitated by addition of methanol
(100 ml). The precipitate was filtered off to give 1.86 g (92%) of
product 7 as an orange powder, mp: 224e227 ꢃC. 1H NMR
(300 MHz; CDCl3, Me4Si): dH 7.96 (2H, s, AreOH), 7.85 (4H, s, AreH),
7.15 (4H, d, J¼7.6 Hz, AreH), 6.74 (2H, t, J¼7.6 Hz, AreH) 4.35 (4H, d,
J¼12.9 Hz, AreCH2eAr ax), 4.04 (4H, t, J¼6.2 Hz, 2ꢂ OCH2), 3.50
(4H, d, J¼13.2 Hz, AreCH2eAr eq), 2.17e2.06 (4H, m, 2ꢂ OCH2CH2),
1.34 (6H, t, J¼7.5 Hz, 2ꢂ CH3). 13C NMR (75 MHz; CDCl3, Me4Si):
2.07e1.96 (4H, m, 2ꢂ OCH2CH2), 1.29 (6H, t, J¼7.5 Hz, 2ꢂ CH3). 13
C
NMR (75 MHz; CDCl3, Me4Si): d 153.8, 145.0, 143.1, 134.2, 128.6, 128.4,
118.9, 116.2, 78.5, 31.8, 23.7, 11.2. MS ESIꢀ m/z (%): for C34H38N2O4
(538.30) found: 537.2 (100) [MꢀH]ꢀ. EA calcd for C34H38N2O4, C,
75.86; H, 7.12; N, 5.20%. Found C, 75.53; H, 7.10; N, 5.13%.
d
157.4, 153.3, 145.0, 135.3, 129.4, 126.8, 124.9, 120.3, 79.4, 31.7, 23.7,
11.1. TOF MS (ESꢀ) m/z (%): for C34H34N2O8 (598.66) found: 619.2
(100) [MþNaꢀ2H]ꢀ. EA calcd for C34H34N2O8, C, 68.22; H, 5.72; N,
4.68%. Found C, 67.99; H, 5.60; N, 4.49%.
4.7.5. Synthesis of 5,17-bis(N0-phenylureido)-26,28-dipropoxycalix[4]
arene-25,27-diol (cone) 11. Phenyl isocyanate (110 mg, 0.92 mmol)
was added to a solution of calix[4]arene 10 (100 mg, 0.18 mmol) in
30 ml of dry CH2Cl2 under nitrogen atmosphere. The mixture was
stirred for 3 days at room temperature. Then,10 ml of MeOH was added
to quench the reaction, and solutionwas stirred for further 2 h. Solvents
were removed under reduced pressure and the residue was purified by
column chromatography (Al2O3, eluent CH2Cl2/MeOH¼100:1) to give
115 mg of product 11 (79%), Rf¼0.7, as a slightly brown solid, mp:
224e226 ꢃC. 1H NMR (300 MHz; DMSO-d6): dH 8.55 (2H, s, AreOH),
8.43 (2H, s, NH), 8.29 (2H, s, NH), 7.33 (4H, d, J¼9.7 Hz, AreH), 7.19 (4H, t,
J¼8.1 Hz, AreH), 7.11e7.09 (8H, m, AreH), 6.89 (2H, t, J¼7.3 Hz, AreH),
6.57 (2H, t, J¼7.5 Hz, AreH), 4.15 (4H, d, J¼12.9 Hz, AreCH2eArax), 3.91
(4H, t, J¼5.71 Hz, 2ꢂ OCH2), 3.40 (4H, d, J¼12.9 Hz, AreCH2eAr eq),
2.02e1.91 (4H, m, 2ꢂ OCH2CH2),1.30 (6H, t, J¼7.3 Hz, 2ꢂ CH3).13C NMR
1H NMR spectrum12 (300 K, CDCl3, Me4Si) of isomer 7a for
comparison: dH (ppm): 9.44 (s, 2H, eOH), 8.05 (4H, s, AreH), 7.00
(4H, d, J¼7.7 Hz, AreH), 6.85 (2H, t, J¼7.7 Hz, AreH), 4.30 (4H, d,
J¼13.2 Hz, AreCH2eAr ax), 4.02 (4H, t, J¼6.0 Hz, eOeCH2CH2), 3.51
(4H, d, J¼13.2 Hz, AreCH2eAr eq), 2.27e2.03 (4H, m, eOCH2CH2e),
1.33 (6H, t, J¼7.1 Hz, eCH3).
4.7.2. Synthesis of 5-mononitro-26,28-dipropoxycalix[4]arene-25,27-
diol (cone) 8. General procedurewas applied to 663 mgof calixarene
4, KOH (2.00 g) in 100 ml of ethanol and 100 ml of dichloromethane.
The residue after evaporation was dissolved in 1 ml of dichloro-
methane and precipitated by addition of methanol (50 ml), and the
precipitate was filtered off to give 231 mg (58%) of product 8 as
yellow powder, mp: 223e226 ꢃC. 1H NMR (300 MHz; CDCl3, Me4Si):
dH 8.05 (2H, s, AreH), 7.80 (2H, s, AreOH), 7.12e7.08 (4H, m, AreH),
6.92 (2H, d, J¼7.6 Hz, AreH), 6.74 (1H, t, J¼7.5 Hz, AreH), 6.70 (2H, t,
J¼7.5 Hz, AreH) 4.39 (2H, d, J¼13.2 Hz, AreCH2eAr ax), 4.28 (2H, d,
J¼12.9 Hz, AreCH2eAr ax), 4.03 (2H, t, J¼6.3 Hz,1ꢂ OCH2), 4.00 (2H,
t, J¼6.3 Hz, 1ꢂ OCH2), 3.46 (2H, d, J¼14.1 Hz, AreCH2eAr eq), 3.41
(2H, d, J¼13.5 Hz, AreCH2eAr eq), 2.16e2.02 (4H, m, 2ꢂ OCH2CH2),
1.33 (3H, t, J¼7.5 Hz, 1ꢂ CH3), 1.32 (3H, t, J¼7.5 Hz,1ꢂ CH3). 13C NMR
(75 MHz; CDCl3:DMSO-d6 4:1, v/v):
d 152.2, 151.8, 146.0, 138.5, 135.0,
321.8,127.6,127.4,126.8,120.8,118.4,117.9,117.3, 77.2, 30.2, 22.2, 9.8. MS
ESIþ m/z (%): for C48H48N4O6 (776.94) found: 815.4 (100) [MþK]þ,
799.8 (80) [MþNa]þ, 777.26 (100) [M]þ. EA calcd for C48H48N4O6, C,
74.21; H, 6.23; N, 7.21%. Found C, 74.10; H, 6.15; N, 7.20%.
Acknowledgements
(75 MHz; CDCl3, Me4Si):
d 157.9, 153.5, 151.9, 144.8, 135.4, 133.4,
129.3, 128.3, 128.2, 126.9, 125.8, 124.9, 119.8, 79.2, 78.7, 31.7, 31.6,
This research was partly supported by the Czech Science
Foundation (203/09/0691) and the Grant Agency of the Academy of
23.7, 11.2, 11.1. TOF MS (ESꢀ) m/z (%): for C34H35NO6 (553.66) found: